A PROSPECTIVE BIOPSYCHOSOCIAL INVESTIGATION INTO HEAD AND NECK CANCER CAREGIVING By CHANDYLEN NIGHTINGALE A DISSERTATION PRESENTED TO THE GRADUATE SCHOOL OF THE UNIVERSITY OF FLORIDA IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF DOCTOR OF PHILOSOPHY UNIVERSITY OF FLORIDA 2014
Â© 2014 Chandylen Nightingale
To my loving family
4 ACKNOWLEDGMENTS I owe a great deal of gratitude to many people in my life who have supported me during my academic journey. First and foremost, I want to thank my husband who has been a tremendous contributor to my success in achieving my PhD . He has been incredibly patient and selfless while I continued to stay in school to achieve my degree . Graduate s chool has been a demanding experience but his love and support has helped carry me through the years. In my moments of weaknes s, his words provided balance that calm ed my anxiety. Anytime I doubted my ability to overcome a challenge during my graduate degree , he was there to assure me that in the end, everything would work out. He was always right. Equally signi ficant, my mother has been a vit al contributor to my accomplishments. My mother has always encouraged me to set high goals and she never doubted my ability to achieve them. Her constant reinforcement and unconditional love gave me the courage to pursue a PhD. To this day, m y mother wil l put her needs aside to help fulfill my dreams , and I cannot imagine accomplishing my degree without her support . I am also thankful for the support that my grandfather provided over the course of my life. He worked hard to ensure that I woul d have opportunities and his diligence was an important resource to me achieving my PhD . Although he is no longer with us, I know that he is still cheering me on. I am also appreciative for the love and support I have received from other family members as w ell as my friends and colleagues. I am thankful to my advisor and mentor, Dr. Giselle Carnaby. Dr. Carnaby took of life research. For the past five years, she has helped me develop a line of research
5 that I grateful for the countless hours of support and substantial enthusiasm she provided for my dissertation and numerous other academic endeavors of mine. Throughout my degree, s he consistently encouraged me to seek opportunities to advance my skills and achie vement and I thrived off of these challenge s . I am also grateful for the valuable input I have received from my other committee members. Dr. Barbara Curbo w has also served a s a mentor for me and she has worked hard to guide me toward a successful career. I am thankful for the time she has given me to discuss this dissertation research and her genuine feedback during my academic job search . She also played an instrumental role in assisting me with obtaining the funding that was needed to carry out this research. In addition, Dr. Deidre Pereira has taught me a great deal about the field of psychoneuroimmunology and assisted significantly with the cortisol component of this disse rtation research . Her expertise in this area was essential for the development and data analysis stages of this project. I am also grateful for the valuable input from Dr. John Wingard. A s an oncolo gy physician with considerable experience in psychosocial oncology research, his insightful feedback was balanced with a practical, yet methodological perspective. I also want to thank Dr. William Mendenhall and Dr. Robert Amdur for allowing me to recruit patients under their care. In addition, I would like to t hank Mr. Paul Deutsch for his significant financial contribution for this dissertation research through the Paul Deutsch Doctoral Research Award . Lastly, I am grateful to the participants who completed this study during the ir arduous treatment experience.
6 TABLE OF CONTENTS page ACKNOWLEDGMENTS ................................ ................................ ............................ 4 LIST OF TABLES ................................ ................................ ................................ ...... 9 LIST OF FIGURES ................................ ................................ ................................ .. 10 LIST OF ABBREVIATIONS ................................ ................................ ..................... 11 ABSTRACT ................................ ................................ ................................ ............. 13 CHAPTER 1 INTRODUCTION ................................ ................................ .............................. 15 Overview ................................ ................................ ................................ ........... 15 Head and Neck Cancer ................................ ................................ ..................... 15 Caregiving in the United States ................................ ................................ ........ 19 Psychosocial Functioning in Caregivers ................................ ........................... 20 Caregiving and Health Outcomes ................................ ................................ ..... 20 Concepts and Definitions ................................ ................................ .................. 25 Informal Caregiver ................................ ................................ ...................... 25 Quality of Life ................................ ................................ ............................. 26 Caregiver Burden ................................ ................................ ....................... 26 Social Support ................................ ................................ ............................ 27 Cortisol ................................ ................................ ................................ ....... 27 Conclusion ................................ ................................ ................................ ........ 28 Overview of Chapters ................................ ................................ ....................... 29 2 THE IM PACT OF CAREGIVING ON HEAD AND NECK CANCER CAREGIVERS: A LITERATURE REVIEW ................................ ........................ 31 Background ................................ ................................ ................................ ....... 31 Synthesis of Findings ................................ ................................ ........................ 32 Caregiver Burden ................................ ................................ ....................... 32 Quality of Life ................................ ................................ ............................. 35 Social Support ................................ ................................ ............................ 37 Pertinent Theoretical Approaches and Models ................................ ................. 39 Emotional Contagion Theory ................................ ................................ ...... 40 Caregiver Well being Implications ................................ .............................. 41 Caregiving Stress Process Model ................................ .............................. 41 Adapted Pittsburgh Mind Body Center Model ................................ ............. 42 Theory of the Social Car e System ................................ .............................. 43 Working Model ................................ ................................ ................................ .. 44 Chapter Conclusion ................................ ................................ .......................... 46
7 3 CAREGIVER BURDEN, QUALITY OF LIFE, AND SOCIAL SUPPORT IN CAREGIVERS OF PAT IENTS WITH HEAD AND NECK CANCER ................. 51 Background ................................ ................................ ................................ ....... 51 Methods ................................ ................................ ................................ ............ 54 Participants ................................ ................................ ................................ . 54 Procedure ................................ ................................ ................................ ... 55 Measures ................................ ................................ ................................ .... 55 Caregiver burden ................................ ................................ ................. 55 Caregiver quality of life ................................ ................................ ........ 55 Caregiver social support ................................ ................................ ...... 56 Data Analysis ................................ ................................ ............................. 56 Results ................................ ................................ ................................ .............. 57 Participants ................................ ................................ ................................ . 57 Aim 1 ................................ ................................ ................................ .......... 58 Aim 2a ................................ ................................ ................................ ........ 59 Aim 2b ................................ ................................ ................................ ........ 60 Discussion ................................ ................................ ................................ ........ 61 4 DIURNAL CORTISOL RHYTHM IN HEAD AND NECK CANCER CAREGIVERS OVER THE RADIATION/CHEMORADIATION TREATMENT PERIOD ................................ ................................ ................................ ............ 76 Background ................................ ................................ ................................ ....... 76 Methods ................................ ................................ ................................ ............ 78 Participants ................................ ................................ ................................ . 78 Procedure ................................ ................................ ................................ ... 79 Caregiver Assessment ................................ ................................ ............... 80 Caregiver salivary cortisol ................................ ................................ .... 80 Caregiver burden ................................ ................................ ................. 81 Caregiver qu ality of life ................................ ................................ ........ 81 Caregiver social support ................................ ................................ ...... 82 Care recipient Assessment ................................ ................................ ........ 82 Quality of life ................................ ................................ ........................ 82 Social support ................................ ................................ ...................... 83 Swallowing fun ction ................................ ................................ ............. 83 Data Analysis ................................ ................................ ............................. 83 Results ................................ ................................ ................................ .............. 85 Participants ................................ ................................ ................................ . 85 Aim 1 ................................ ................................ ................................ .......... 86 Aim 2 ................................ ................................ ................................ .......... 86 Discussion ................................ ................................ ................................ ........ 87 5 HEAD AND NECK CANCER CAREGIVING: A DISCUSSION OF FINDINGS . 98 Dissertation Findings ................................ ................................ ........................ 98 Chapter 2 Findings ................................ ................................ ..................... 98
8 Chapter 3 Findings ................................ ................................ ................... 100 Chapter 4 Findings ................................ ................................ ................... 102 Biopsychosocial Model of Caregiving ................................ ............................. 103 Strengths ................................ ................................ ................................ ........ 106 Limitations ................................ ................................ ................................ ....... 108 Future Research ................................ ................................ ............................. 110 Clinical and Policy Implications ................................ ................................ ....... 112 Conclusion ................................ ................................ ................................ ...... 115 APPENDIX A ADDITIONAL DETAILS FOR METHODS ................................ ....................... 119 B SALIVA JOURNAL ................................ ................................ ......................... 125 LIST OF REFERENCES ................................ ................................ ....................... 128 BIOGRAPHICAL SKETCH ................................ ................................ .................... 139
9 LIST OF TABLES Table page 2 1 Review of studies ................................ ................................ ......................... 47 3 1 Participant characteristics at study entry (n=34) ................................ ........... 68 3 2 Caregiver burden and QOL ................................ ................................ .......... 69 3 3 Correlations for social support and burden (n = 32) ................................ ..... 70 3 4 Most common preferences for sources of support ................................ ........ 71 4 1 Caregiver characteristics at study entry (n=32) ................................ ............ 92 4 2 Care recipient characteristics at study entry (n=32) ................................ ..... 93 A 1 Power calculations ................................ ................................ ...................... 120
10 LIST OF FIGURES Figure page 2 1 Biopsychosocial Model of Caregiving using a head and neck cancer context ................................ ................................ ................................ .......... 50 3 1 Recruitment flow chart for caregivers ................................ ........................... 72 3 2 Caregiver Esteem, as measured by the CRA ................................ ............... 73 3 3 Caregiver Impact on Health, as measured by the CRA ................................ 7 4 3 4 Caregiver Disruptiveness, as measured by the CQOL C instrument ............. 75 4 1 Caregiver diurnal cortisol rhythm at T1 and T2 ................................ ............. 94 4 2 .................... 95 4 3 and diurnal cortisol rhythm at T2 .................. 96 4 4 Care T2 ................................ ................................ ................................ ................. 97 5 1 Supported Relationships in the Biopsychosocial Model of Caregiving ....... 117 A 1 Recruitment diagram ................................ ................................ .................. 120
11 LIST OF ABBREVIATIONS ACTH ANOVA BI CAR CQOLC CRA CRH DSM EAT 10 FACT HN FOIS GED HADS HNC HPA HPV IRB ISSB MOS PI QOL A drenocorticotropic hormone Analysis of variance Burden Interview Cortisol awakening r esponse Caregiver Quality of Life Index Cancer Caregiver Reaction Assessment Corticotropin releasing h ormone Diagnostic Statistical Manual Eating Assessment Tool Functional Assessment of Cancer Therapy Head and Neck Functional Oral Intake Scale General Education Diploma Hospital Anxiety and Depression Scale Head and Neck Cancer Hypothalamic p ituitary a d renal Human Papilloma Virus Institutional Review Board Inventory of Socially Supportive Behavior Medical Outcomes Study Principal Investigator Quality of life SAM SEM S ympathetic adrenomedullary Structural equation modeling
12 SF 20 SPSS US Short form 20 Statistical Package for the Social Sciences United States WHOQOL BREF World Health Organization Quality of Life BREF
13 Abstract of Dissertation Presented to the Graduate School of the University of Florida in Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy A PROSPECTIVE BIOPSYCHOSOCIAL INVESTIGATION INTO HEAD AND NECK CANCER CAREGIVING By Chandylen Nightingale August 2014 Chair: Giselle Carnaby Major: Public Health Social and Behavioral Sciences Head and neck cancer (HNC) is a leading cause of cancer related morbidity, death, and disfigurement, presenting patients and caregivers with profound challenges. Evaluation of psychosocial functioni ng among H NC patients has been increasing, albeit modestly, yet relatively little attention has been focused on their caregivers. This dissertation aimed to evaluate the biopsychosocial impact of the caregiving experience on caregivers of patients with HNC. A prospe ctive parallel arm design was followed in which caregivers and care recipients were evaluated simultaneously at the initiation of radiation/chemoradiation (T1), five weeks into treatment (T2), and approximately one month following the conclusion of treatme nt (T3). Caregivers completed burden and QOL instruments at all three time points and perceived social support and preferences for sources of support at T2 only . HNC care recipients completed QOL and perceived social support instruments at the same time po ints. In addition, salivary cortisol was collected in caregivers at T1 and T2. Burden results demonstrated that caregivers experienced significantly lower esteem at T2 and a significantly greater impact on health at T3. QOL results demonstrated that disru ptiveness became significantly worse at T2. Higher social support was typically associated with less burden and better QOL in
14 caregivers. most common first preference for source of support was a spouse or partner for various types of social sup port. Finally, greater caregiver schedule burden at T1 was associated with a more abnormal cortisol slope at T1, when controlling for age and gender. In addition, lower care recipient functional QOL and lower overall caregiver QOL at T1 were each separatel y associated with a more abnormal cortisol slope at T2 . Overall, findings have confirmed increased burden and reduced QOL in caregivers , substantiated by a physiological response (neuroendocrine). These data further the concept of a true shared treatment p henomenon between care recipient and caregiver. It is recommended that future studies employ a larger sample size and evaluate additional biomarkers of stress such as alpha amylase and pro inflammatory cytokines among HNC caregivers. In addition, the resul ts of this dissertation call for a concerted effort to provide interventional resources for HNC caregivers, especially those providing care during and shortly after radiation/chemoradiation treatment.
15 CHAPTER 1 INTRODUCTION Overview Head and Neck Cancer (HNC) is a leading cause of cancer related morb idity, death, and disfigurement [ 1 ] . Patients and families must deal with considerable functional impairments and psychosocial ramifications from this disease and its associated ablative treatments [ 2 ] . HNC patients typically receive significant informal care from family members who are confronted with tasks related to the unique and significant burden of this disea se [ 2 ] , yet research focused on HNC caregivers is sparse. Whil e it is understood that cancer caregivers in general may suffer from burden and impaired QOL [ 3 ] , little research confirms this phenomena in the HNC caregiver population. The multidimensional effects of caregiving can extend beyond pure psychosocial outcomes and impact health status as well. The processes by which this occurs are less understood, although it has been suggested that a biological response may mediate psychosocial and health outcomes. However, no resea rch to date has evaluated biological responses in HNC caregivers and few studies have explored these domains in the broader caregiving literature [ 4 ] . As such, the impact of providing care for a patient with HNC on psychosocial and physiological outcomes needs elucidat ion. This introductory chapter outline s the background and context of the problem, definitions for key constructs which were evaluated in this dissertation, and the research purpose and study aims. Head and Neck Cancer Cancer is a major public health problem in the United States (US) and the second leading cause of death [ 5 ] . It is estimated that approximately 1,665,540
16 individuals will be diagnosed with cancer in 2014 [ 6 ] . Not surprising then, the nation ha s deemed the reduction of cancer incidence as a health care priority [ 7 ] . Concordantly it is estimated that more than 55,000 people will be diagnos ed with HNC in the US in 2014 alone, accounting for approximately 3% of all cancers [ 1 , 8 ] . While incidence rates for most cancers have decreased, an evaluation of data from 1973 2004 indicated that incidence rates for HPV related HNC cases have increased cons iderably [ 9 ] . Moreover, while advancement in oncologic treatment has resulted in a n improved five year survival rate, recurrence remains high for HNC [ 1 , 10 ] . Unfortunately, more than one half of all new cases of oral cancer are diagnosed at an advanced stage. This of ten necessitates treatment with a combination of interventions [ 11 ] . Consequently, patients patients of other cancer diagnoses [ 12 ] . These statistics indicate that while the overall incidence of HNC is less tha n other cancers (e.g., breast, colorectal, lung), HNC presents a major burden (personally and financially) for the US in terms of disabled survivorship [ 11 ] . The result of these trends is a cadre of patients that are younger and living longer with significant dysfunction. Cancer of the head and neck most often develops in the outer layers of the skin , or squamous cells , and includes the skin covering the larynx, nasal cavity, sinuses, lip, salivary glands, mouth, or throat [ 13 ] . The typical patient is male and greater than 50 years of age, however, recently the incidence ra te among young adults is increasing due to HPV related oropharyngeal cases [ 1 , 14 , 15 ] . Although HPV is now an established etiological factor for HNC, alc ohol and tobacco still account for approximately 75% of cases [ 16 18 ] . Other less common risk factors include diet [ 19 ] ,
17 oral health [ 20 ] , and Epstein Barr virus infection [ 21 ] . Regardless of cause, the overwhelming consequence of recent trends in HNC is an increasingly younger patient profil e, combined with an improved survival rate, resulting in a HNC population surviving longer with the long term effects of the disease and treatment. Similar to other cancer diagnoses, treatment options for HNC typically include surgery, radiation therapy, chemotherapy, targeted therapy, or a combination of these options. Treatment options also vary based on additional clinical factors such as tumor location and stage of disease, as well as patient factors including overall health and age [ 13 ] . Overwhelmingly the ablative tre atments used to control HNC in most patients result in associated toxicity. In locally advanced cancers treatment toxicity is significant, and long term effects of the disease and treatment have been described as life altering [ 22 ] . I ndeed, a recent systematic review demonstrated a significant decrease in QOL following radiation or combined chemoradiation (radiation/chemoradiation) for HNC [ 23 ] . In addition to generic cancer symptoms (e.g., pain, fatigue), patients with HNC also report problems specific to the disease [ 22 ] . One of the most detrimental and common disease spe cific impairments in HNC is dysphagia (i.e., difficulty swallowing) with over 75% of patients experiencing some form of swallowing difficulty during or after oncologic treatment [ 24 , 25 ] . The functional ramifications of dysphagia often result in complicated feeding (including non oral feeding) and coughing or choking upon swallowing [ 2 , 22 ] . Similarly, patients may also experience changes in saliva, taste, chewing, and sense of smell. In some cases , patients may also experience difficulty
18 breathing and speaking [ 22 ] . Collectively, these symptoms significantly impede core aspects of daily life for HNC patients. As well as the physical impact of HNC, psychosocial difficulties among these pat ients have also been well substantiated in the literature. Many patients suffer from facial disfigurement [ 26 ] , which may give rise to body image issues [ 27 ] and increased likelihood of stigmatization [ 28 ] . Moreover, psychological effects include a high incidence of anxiety [ 29 ] , fear of recurrence [ 30 , 31 ] , and depression [ 32 ] . Further, psychosocial problems can also impact intimate relationships. For example, research has noted evidence of decreased marital and sexual functioning among patien ts with HNC [ 33 ] . Correspondingly other detrimental impacts from HNC can i nclude financ ial and occupational sequelae. Research has demonstrated that among survivors of more than twelve different types of cancer, HNC was among the top three cancer diagnoses ( including survivors of central nervous system and stage IV blood and lym ph malignancies) at greatest risk of abandoning their occupation [ 34 ] . This may be especially problematic for HNC patients who are typically already of a lower socio economic status [ 35 ] . Qualitative studies have also highlighted common psychosocial issues reported by patients with HNC [ 36 ] . For example , a recent meta synthesis of studies reported that HNC patients showed significant disruptions in their daily lives, social and existential changes, feelings of a loss of self and their future, and in some cases, limited support following treatment. These findings further underscore the widespread extent of the HNC experience. In addition, compared to other cancer diagnoses including prostate, large bowel, and melanoma, post surgical oral cancer patients report higher
19 levels of care needs [ 37 ] . Taken together, it is not surprising that HNC patients suffer from psychological distress that surpasses that of breast, colon, prostate, and gynecologic cancers [ 38 ] . Caregiving in the United States Over the last decade, p atient care has increasingly shifted from the hospital to the home, resulting in a greater number of family members providing informal care. Currently, there are approximately 4.6 million Americans providing informal care for someone with cancer [ 39 ] . Consequently, caregivers represent a significant source of cancer related care in the US. Informal caregivers have been defined as anyone providing un paid assistance for a person needing help [ 40 ] . The most recent report available indicates that unpaid caregiving services saves the US healthcare system an estimated $450 billion annually [ 41 ] . While these uncompensated services reduc e the burden on the health care system, they come at an extraordinary cost to the individual well being of the caregivers. P atient care is in part well being. However, family members are often thrown into a caregiver r ole unexpectedly, and have little time to prepare for the multifaceted demands they are confronted with [ 42 ] . Caregiving t asks may range from providing emotional support, navigating the complex healthcare system, to providing hands on complex medical care to the care recipient with a lack of training in these areas [ 42 , 43 ] . These unpaid informal services are therefore critical to achieving optimal patient outcomes, including survival [ 44 ] . However, c ollectively, these responsibilities can be overwhelming for informal caregivers.
20 Psychosocial Functioning in Caregivers T he negative impact of caregiving in general is well documented in the literature [ 45 ] . Although some caregivers report the caregiving experience to be rewarding, it has been demonstrated that providing ca re for others can be demanding across mul tiple dimensions of their lives [ 43 , 46 ] . Moreover, c aregivers have been reported to experience a range of emotional distress including anger, depression, and anxiety [ 47 ] , and many caregivers of cancer patients in parti cular demonstrate emotional symptoms that meet Diagnostic Statistical Manual (DSM) criteria for psychiatric pathology [ 48 ] . C aregivers may also face challenges and distress related to financial stability and employment. For example, the majority of caregivers (70 %) experience transitions in their place of employment and/or barriers to financial advancement (e.g., are unable to accept a promotion) as a result of their caregiving role [ 39 ] . Moreover, caregivers are frequently faced with re duced hours or termination at their place of employment as a result of the caregiving demands [ 49 , 50 ] . It has also been reported that in comparison to men, women are more likely to suffer from certain occupational hardships such as losing benefits [ 39 ] . Correspondingly e mployment hardships may be further complicated by the out of pocket expenses that caregivers pay associated with providing care [ 39 ] . Collectively these data suggest that caregivi ng experience may impose wide reaching penalties that impede the health and well being of both the caregiver and patient. Caregiving and Health Outcomes Although caregiving research is saturated with the emotional and social ramifications of their caregivi ng role, studies have also begun to demonstrate specific health consequences as well. Research indicates that caregivers often neglect their own health care needs, with 17% perceiving a decline in their health as a consequence
21 of their caregiving role [ 43 , 51 , 52 ] . Kurtz et al. [ 51 ] found an association between caregiver burden and risk for mor bidity among cancer caregivers. Likewise, Lee et al [ 53 ] found that spouse caregiving was an independent risk factor related to cardiovascular disease. Furthermore, immunological research has demonstrated that providing informal care can reduce immune system functioning [ 54 ] . Correspondingly and most concerning is that ca regiving has also been shown to increase the likelihood of mortality [ 55 ] . The cause of t hese negative outcomes is currently unknown, as longer term r esearch exploring relationships amo ng caregivers is sparse. However, suggested contributory factors may includ e stress induced mind body interaction s [ 56 ] . Recently, s tress and broader psychosocial ramifications of the caregiving experience have been proposed to have interrelated negative health consequences that are mediated by an array of physiological processes (e.g. alteration in diurnal cortisol pattern ) [ 56 ] . One of the proposed mechanisms underlying these phenomena includ es th e ability to regulate response to environmental challenges [ 57 ] . The p hysiological stress response primes the body to cope with threat by accessing energy reserves, increasing blood supply , and suppressing nonessential functions [ 57 ] . Stress responses primarily involve the activation of two nervous system pathways: the hypothalamic pituitary adrenocortical (HPA) axis and the sympathetic adrenomedullary (SAM) system [ 57 ] . The S AM system of the stress response acts to increase cardiovascular arousal, regulate secretion of c irculating catecholamines (adrenaline, noradrenaline), and reduce non essential body functions [ 57 ] . The HPA axis includes the hypothalamus, the pituitary gland, an d the adrenal cortex and regulates the production and release of cortisol [ 57 ] .
22 Cortisol is a steroid hormone or glucocorticoid and is a biomarker of stress [ 57 ] . When stress is encountered (e.g. due to psychosocial problems) the hypothalamus i s stimulated to secrete corticotropin releasing hormone (CRH) [ 57 ] . CRH then stimulates the pituitary to release adrenocorticotropic hormone (ACTH) into the bloodstream. In turn, this causes the adrenal cortex to release gluc ocorticoids, including cortisol . Cortisol has been implicated in negative health outcomes [ 58 ] . For example, stress and cortisol have been linked t o suppressed immune system functioning , tumor initiation and growth , and metabolic syndrome [ 59 61 ] . In addition, e xaggerated or prolonged exposure to cortisol has been associated with increased risk of cardiovascular di sease, infectious diseases, and the development of other chronic illness es [ 62 ] . Although initial stress responses are thought to be adaptive, prolonged, pronounced or repeated exposure has been shown to contribute (over time) to significant illness. Applying these findings to a seemingly stressful caregiving experience suggests that the stress and broader psychosocial ramifications that result from informal caregiving may have negative health consequences that are mediated by physiological processes (e.g., dysregulation in daily cortisol rhythm ). Few studies have assessed the physio logical stress response of caregivers using the HPA axis. No study has evaluated salivary cortisol in the HNC caregiver population and limited studies have assessed cortisol in the broader c aregiving population [ 63 65 ] . Rohleder et al. [ 64 ] assessed diurnal cortisol rhythm in eighteen family caregivers of brain cancer patients and nin eteen matched controls at four time points (pre radiation, post radiation, 6 weeks, and 4 months later). Their findings demonstrated no significant difference between groups in cortisol output or diurnal cortisol rhythm in caregivers
23 versus matched control s at any of the time point. However, authors did not report change in cortisol output or diurnal rhythm over time in the caregiver group alone, nor did they assess cortisol during radiation treatment, when the stress response maybe heightened. Likewise Ve dhara et al. [ 65 ] assessed salivary cortisol output in 41 caregivers and 62 controls. Caregivers consisted of spouses of patients with multiple sclerosis who had been providing care for a min imum of three years. Cortisol was collected longitudinally at two different time points (approximately 28 days apart). Although both groups showed a normal diurnal rhythm characterized by a negative slope, the non caregivers demonstrated higher cortisol le vels in comparison to the caregivers. However, because all caregivers had been providing care for at least three years, it is possible that the caregivers had successfully adjusted to their caregiving role and its associated burden. Indeed, the authors rep only moderately high with modest levels of associated distress. Although these results suggest a normal salivary cortisol response in caregivers, the results may differ for HNC caregivers who are exposed to sign ificant challenges during the acute radiation/chemoradiation period. In contrast, Miller and colleagues [ 63 ] evaluated cortisol slope in 25 parents of children with cancer and a control group of 25 parents of healthy children. Parents of the children with cancer demonstrated significantly flatter slopes and greater psychological distress in comparison to the parents of the healthy children. However, the authors did not assess change in cortisol rhythm at different assessment points, so these findings only provide information at one point in time. Moreover, it is possible that
24 distress and its associated physiologic response may be different when caring for children as opposed to caring for an adult. More research should evaluate cortisol response acros s time in caregivers of adults with cancer. Current studies demonstrate heterogeneity in the measurement of cortisol responses in caregivers in comparison to non caregivers. For example, the studies evaluated cortisol respons e in family caregivers [ 64 ] , spouses [ 65 ] , and parents [ 63 ] . They also differed in the freque ncy of cortisol collection in one day, frequency of days, and frequency of assessment points. R esearch is needed that utilizes similar groups and collection methods to determine how cortisol rhythm changes over the treatment experience as well as what fact ors may predict diurnal cortisol rhythm in caregivers of patients with HNC. Such consistency in information could be used to develop and refine psychosocial and health interventions that utilize mind body techniques for the HNC caregiver population. Undou btedly, the detrimental effects of caregiving are pervasive in the literature. While the general caregiving literature, (including that of cancer caregiving), has been a burgeoning area of research in recent years, caregivers of patients with HNC remain a relatively forgotten population. Although findings from the broader caregiving literature may extrapolate to the HNC caregiver population, the unique nature of the disease will necessitate additional caregiving tasks that would not otherwise be present in a general cancer group (e.g., cleaning a tracheostomy tube). In addition, as stated above, compared to many other cancer diagnoses, oral cancer patients perceived greater care needs and HNC patients in general, were found to have greater psychological dist ress [ 37 , 38 ] . Consequently, an alternate profile of burden and QOL may be present for HNC
25 caregivers. Moreover, the relationship physiological outcomes , such as cortisol pattern, is largely unknown. The provision of information on the specific burden characteristics of HNC caregivers may aid in the development of targeted psychosocial services to mitigate the negative impact on the caregiver. The ability to reduce burden and negative physiological outcomes and promote QOL in HNC caregivers may in turn help optimize informal patient care and reduce burden on the health care system. This study, therefore, prospectively evaluate d biopsychosocial outcomes in informal caregivers of patients with HNC during and shortly after the acute radiation /chemoradiation treatment period . Key concepts in the caregiving literature, including burden and QO L were assessed over the radiation /chemoradiation treatment period and social support was evaluated toward the end of treatment. Change in and predictors of diurnal cortisol rhythm were also evaluated over radiation /chemoradiation treatment. In the followi ng section, definitions of important concepts and variables evaluated in this study are discussed. Concepts and Definitions Informal Caregiver Inform al caregivers have typically been defined as a person providing unpaid care [ 40 ] . Although informal caregivers often include a family member, they may also include a significant other or friend [ 66 ] . defined as anyone who is providing unpaid care by helping a patient with HNC during the radiation /chemoradiation treatment period. Three primary variables of interest in this study are QOL, caregiver burden, and social support. QOL and caregiver burden have received a lot of attention in the broader
26 caregiving literature and social support has been pervasive in the social and behavioral science literature. The specific operatio nal definitions for these concepts to be utilized in this study are outlined below . Quality of Life Quality of life (QOL) is a multidimensional construct that typically includes the domain s of physical, emotional, social, and spiritual/existential well bei ng, although exact definitions can vary within the literature [ 67 ] . The incons istency in definitions is also reflected in differences among QOL instruments [ 67 ] . QOL is sometimes differentiated from health related quality of life ( HR QOL ), a measure of QOL that is typically used in a health context [ 68 ] . However, these terms are often used interchangeably with the argument that differentiating between the two is meaningless. In this study, the distinction between QOL and HR QOL is not recognized; rather, the term QOL is used as an umbrella concept including a health context as well. Further , the full spectrum of QOL was measured using a multidimensional QOL instrument rather than an instrument that assesse d a single dimension of QOL or a composite of such instruments. A multidimensional measurement approach was chosen to allow for comprehensive assessment of the overall QOL , as well as information on the specific dimensions of QOL. Additionally, the assessment of QOL in this project is primarily focused on caregivers of p atients with HNC, although the care was also measured to evaluate a potential relationship between patient and caregiver outcomes. Caregiver Burden Similar to QOL, the definition of caregiver burden also lacks uniformity within the literatu re. Some studies distinguish between objective and subjective caregiver burden, while other studies do not. Objective burden pertains to characteristics of the actual
27 care provided such as number of hours. In contrast, subjective burden pertains to the eff (p.119) [ 69 ] . Caregiver as sessment in this dissertation research caregiving experience as a subjective measure of burden. Social Support rel (p.187) [ 70 ] . Similar to QOL and caregiver burden, there are multiple domains of social support. These domains typically include emotional (e.g., showing empathy), instrumental (e.g., tangible aid and services), informational (e.g., advice), and appraisal support (co nstructive feedback), or a similar variation of these terms [ 71 ] . Social support may be measured by the support one actually receives or support one perceives. This distinction is important because research has demonstrated that perceived adequacy of support is more important than the availability of support [ 72 ] . Consequently, the actual amount of soci al support may be less important than the amount of support a person perceives. Correspondingly, i n this study the assessment of social support focuses upon the caregiver perce ive d level of social support as well as their preferences for sources of suppo rt. Cortisol Cortisol collection and method of evaluation can vary. Although cortisol can be collected through various specim ens, salivary cortisol is a popular method of collection due to its ease of collection [ 58 ] . Diurnal cortisol measures vary but common approaches include total cortisol (area under the curve), the cortisol awakening
28 response (CAR), and diurnal cortisol r hythm [ 73 ] . Within this study, cortisol slope (also referred to as the diurnal cortisol rhythm) was evaluated in HNC caregivers. Psychoneuroendocrinology literature indicates that under normal circumstances, cortisol secretion is highest in the morning and lowest in the evening, demonstrat ing a negative diurnal pattern [ 58 ] . Encountering acute stress results in high cortisol levels thro ughout the day and chronic stress can result in a blunted slope. Consequently, lower values (reflecting more rapid declines) indicate a normal response whereas higher slope values (as they approach 0) reflect flat diurnal rhythms and have been reported to reflect dysregulation of the HPA axis [ 58 ] . This study evaluate s diurnal cortisol rhythm in caregivers of patients with HNC . Delineation of the constructs discussed above is critical to the focus of this dissertation. The above mentioned constructs have, in the past, been ill defined or defined with great variability, which can yield discrepant findings across the literature. Further, providing these definitions support s interpretation and replication of the study findings, facilitating planning for future related research. The exact operationalization of these constructs is also discussed in Chapter 3 and Chapter 4 where they were evaluated . Conclusion HNC is a complex disease whose course and treatment can result in significant and long lasting toxicities. Many of these adverse outcomes extend and complicate the care process. Informal caregivers are an integral part of the H NC care team, but they are often overwhelmed by the experience. While patient treatment and survival is understandably the priority, informal caregivers may become neglected. In order to
29 effectively address the needs of HNC caregivers, mor e information reg arding the biopsychosocial impact of the caregiving experience is needed. Overview of Chapters Psychosocial functioning of HNC caregivers was first explored through a literature review in Chapter 2 . Specifically, the chapter reviews quantitative studies t hat have evaluated burden, QOL, and social support in care givers of HNC patients in or post treatment . In addition, this chapter includes a review of caregiver models and theories and concludes with a proposed model of caregiving, using HNC as an exemplar. Chapter 3 presents an evaluation of burden, QOL, and social support in caregivers of patients with HNC. Level and change in burden and QOL during radiation/chemoradiation and out to one month following treatment were assessed. In addition, level of perceived social support, preferences for sources of support, as well as the relationship between social support with burden and QOL were evaluated during radiation/chemoradiation in this chapter. The aims of this chapter were to: (1) describe and compare levels of burden and QOL in HNC caregivers from the initiation of treatment toward the conclusion of their care and shortly following treatment, (2 a ) assess the relationship between perceived social support with burden and QOL , and (2b) identify pref erences for sources of support among HNC caregivers. The biological impact of caregiving was explored in Chapter 4 . Specifically, this chapter includes an evaluation of change in diurnal cortisol rhythm from the initiation o f radiation/chemoradiation treatment toward the conclusion of treatment in caregivers of patients with HNC. In addition, predictors of diurnal cortisol rhythm (at the initiation of
30 treatment and toward the conclusion of treatment) were identified in this c hapter. The aims for Chapter 4 are to: (1) d escribe and compare diurnal cortisol rhythm in HNC radiation/chemoradiation treatment , and (2) i dentify the demographic, psychosocial, and treatment and disease related predictors of diurnal cortisol rhythm in HNC caregivers. Finally, C hapter 5 synthesizes the findings of this dissertation and discusses the implications for future research in this area. In addition, clinica l implications for working with caregivers of patients with HNC are discussed. Collectively, the findings from this dissertation provide greater insight into the biopsychosocial functioning of HNC caregivers, a population that has received very little atte ntion. In addition to augmenting the HNC caregiver literature, the findings of this dissertation may be useful for evaluating other cancer caregivers or the broader caregiving population. As our population continues to age, informal caregivers will remain a vital element of care delivery in the US.
31 CHAPTER 2 THE IMPACT OF CAREGIVING ON HEAD AND NECK CANCER CAREGIVERS : A LITERATURE REVIEW Background Informal cancer caregiving is prevalent in the United States, with an estimated 4.6 million Americans caring for someone with cancer [ 39 ] . The service s provided by informal caregivers are estimated to save the United States health (US) care system $450 billio n each year , but this number does not reflect the potential health care costs that may arise due to the associated psychological and health impact on the caregiver [ 41 ] . This problem is further complicated by the fact that informal caregivers are typically un paid for the services they p rovide [ 40 ] and therefore may be ill equipp ed to appropriately address their own needs to maintain an optimal quality of life (QOL). Given that informal caregivers have a significant role in patient care, the being may influence the quality of care provided to the patient. However , research has demonstrated a multitude of negative psycho social outcomes for caregivers [ 45 ] . For example, emotional distress [ 47 ] and psychiatric pathology has been noted [ 48 ] . In addition, many caregivers are often faced with employment challenges such as reduced hours or termination as a result of the caregiving demands [ 49 , 50 ] . While awareness regarding the psychosocial ramifications of informal caregiving has improved due to increasing research in this area, caregiv ers of patients with head and neck cancer ( HNC ) have received little research acknowledgement. Although findings from the broader caregiving literature may provide some insight into HNC caregiving, it is unknown at this time if an alternate profile of burd en and QOL occur for HNC caregivers. However, given that HNC is a leading cause of cancer related
32 morbidity, death, and disfigurement, the disease may necessitate profound caregiving demands distinct from other caregiving experiences. For example, patients with HNC have been found to suffer from greater psychological distress when compared to breast, colon, prostate, and gynecologic cancer patients [ 38 ] which may result in a more challenging experience for caregivers who are typical ly responsible for providing emotional support [ 42 ] . In addition, to further exacerbate this issue, research has demonstrated that oral cancer patients perceive higher levels of care needs in comparison to prostate, large bowel, and melanoma cancer patients [ 37 ] . A synthesis of the literature pertaining to HNC caregiving may highlight the need for furt her research in this area and prompt investigators to evaluate this relatively forgotten population. Therefore, t he purpose of this chapter was to review quantitative studies that have evaluated psychosocial functioning in caregivers of patients or survivo rs of HNC. Specifically, studies that have assessed burden, QOL, and social support in HNC caregivers were reviewed. In addition , this chapter also review ed theories and models that are relevant to these constructs and conclude s with a working model using HNC as an exemplar. Synthesis of Findings Caregiver Burden Research demonstrates that caregiver burden is associated with greater patient functional disability, depression, and cognitive impairment [ 74 76 ] . Caregiver burden has also been found to increase over the treatment period and is associated with increased hours of care per day [ 77 , 78 ] . Correspondingly , patients with HNC receiving radiation/ chemoradiation experience a multitude of negative side effects tha t worsen as
33 the treatment progresses. T his may culminate in increased burden for caregivers of HNC over the course of the radiation/ chemoradiation period. Only four published studies have assessed caregiver burden in caregivers of patients with HNC [ 37 , 7 9 81 ] ( see Table 2 1 ). Chen et al. [ 37 ] assessed burden in 122 family caregivers of hospitalized newly diagnosed oral ca ncer patients 10 to 14 days post tumor excision surgery. The authors reported that HNC caregivers demonstrated moderate levels of perceived burden on the Caregiver Reaction Assessment (CRA). Unfortunately the a uthors incorrectly report ed that the highest l caregiving, specifically, self worth attributed to the caregiving role rather than burden [ 82 ] . Their reported statistics indicate d that the greatest burden was in the disrupted needs including physical/daily living, health system/ information, and psychological. Furthermore, the a uthors also provide d a total score for burden and i ndicate d that the prime predictor of overall burden was caregiver social support. However, instrument developers of the CRA report that each subscale is distinct and unidimensional, which means the instrument, cannot provide a cumulative burden score [ 82 ] . Although informative for the descriptive subscale findings, this study demonstrated major flaws in raising questions regarding the integrity of the reported findings. Moreover, the cross sectional nature of the study only provid e d scores at one time point, preventing authors from ascertaining potential fluctuations in burden and pred ictors of burden over time. Similarly, another cross sectional study was conducted by Verdonck de Leeuw et al. [ 80 ] , usin g 41 spouse caregivers of HNC patients that
34 presented during follow up to curative treatment ( surgery , radiation , parotidectomy with radiation, surgery combined with radiation, or chemoradiation ) . In this study burden was assessed using the CRA, but the au thors reported only the percentage of caregivers The a uthors did not explain what each percentage represent ed ( because there are multiple items to each subscale and ), nor d id they provide descriptive results for burden subscales. The a uthors however, report ed a positive moderate correlation between the CRA and the Hospital Anxiety and Depression Scale (HADS). Consequently, the methodologic al errors in this study reduce the value of any informative evidence regarding burden in caregivers of HNC patients. Blood et al. [ 79 ] conducted a longitudinal study evaluating HNC caregivers. This study used a repeated measures cross sectional design with 75 spouse caregivers of laryngeal cancer whose care recipient had received a laryngectomy. Caregivers were categorized into groups by time since diagnosis (i.e., 1 = 2 6 months , 2 = 7 12 months, 3 = 13 18 months, 4 = 19 24 months, 5 = 25 36 months, and 6 = 36 48 months). The authors found that caregiver burden decreased as time since diagnosis increased, although burden scores were only significantly different in early diagnosis groups (groups 1 and 2). Caregivers of newly diagnosed patients (groups 1 & 2) demonstrated mild to moderate burden while the remaining groups demonstrated little or no burden. Thus burden was most pronounced in the first 12 months of surgical recovery. O verall, burden scores varied greatly from no burden to a severe degree of burden. It was reported that male caregivers showed significantly less burden than female caregivers. The longitudinal nature of Blood and study [ 79 ] offers data on how caregiver
35 burden might change over time. However, the study only provided this information for post surgical patients and did not include an assessment of those in active cancer treatment (e.g., during radiation treatment) when a care recipients needs may be more extensive. Moreover, the burden instrument used (Burden Interview) in this study was developed for dementia caregivers , and may not be sensitive enough to detect the unique burden profile associated with caring for a patient with HNC. A more recent pilot study [ 81 ] evaluated burden in ten caregivers of patients with HNC using the Burden Interview (BI) . Caregivers were assessed at the beginning of radiation/ chemoradiation, toward the middle of radiation/ chemora diation, and at the end of radiation/ chemoradiation. Findings demonstrated that burden increased across time, with a significant increase from the first to second time point. The a uthors also reported minimal to moderate burden in caregivers. However, simi lar to Blood and study [ 79 ] , the results may not accurately reflect true burden in this population due to the instrument choice (i.e., BI). Moreover, Nightingale et al. [ 81 ] emphasize that more research w as needed with a larger sample size. Collectively, the evidence to date on burden in HNC caregivers is sparse. Two of the four studies present limited data due to weaknesses [ 37 ] or a lack of information [ 80 ] . The remaining studies [ 79 , 81 ] both utilized a prospective design and demonstrated that burden increased over time, yet these studies relied on an instrument developed for dementia caregivers. More longitudinal research is needed with a burden instrument that can provide a valid measur e of burden in HNC caregivers. Quality of Life Only four studies have evaluated QOL quantitatively using a multidimensional scale in HNC caregivers [ 79 , 83 85 ] (see Table 2 1) . In Blood and [ 79 ]
36 longitudinal study (discussed above ), authors also evaluated QOL but did not provide specific scores for the QOL instrument (i.e., Medical Outcomes Study Short Form 20) because their primary focus was on burden. The authors , did however, report that the SF 20 was not significantly correlated with caregiver strain, burden, or stress. Although the SF 20 is often used as a measure of QOL, the instrument is intended to provide a measure of health status and is not a sufficient measure of QOL alone [ 67 ] . Consequently, reported results can only be taken to demonstrate that caregiver strain, burden, and stress were not associated with caregiver health status in this study sample . Drabe et al. [ 83 ] also conducted a cross sectional study in which they assessed QOL in 31 HNC wives of patients who were o n average, 3.7 years post treatment. QOL was measured using the World Health Organization Quality of Life BREF (WHOQOL BREF). The ir findings indicated that QOL scores were high (indicative of good QOL) and similar to the referenced healthy norms . However, this QOL scale may not detect QOL impairment specific to cancer caregivers. Similarly, Ross et al. [ 85 ] measured QOL among caregivers of HNC survivors who were on average of 19 months post diagnosis. QOL in this study was assessed with the Caregiver Quality of Life Index Cancer (CQOLC). The authors reported that the CQOLC scores were much higher (i.e. better) than those reported in a prior study [ 86 ] using the same scale among caregivers of various cancer diagnoses. Unfortunately, t hese studies only provide information regarding caregiver QOL well after treatment has ended , when caregiving tasks and their associated ramifications may be attenuated.
37 Only one study [ 84 ] has prospectively a ssessed QOL in caregivers of HNC patients over the radiation/chemoradiation time period . Patterson and colleagues [ 84 ] assessed QOL using the CQOLC instrument at three different times: (1) pre treatment, (2) th ree months post treatment, and (3) twelve months post treatment. In this study caregivers reported a significant increase in QOL between three months and twelve months post treatment , but no significant change was found between pre treatment and the three month time point. Although this study demonstrated increased QOL after treatment, it did not provide any information regarding QOL during the critical acute treatment period. T he literature to date presents an incomplete picture of caregiver QOL. It lacks characterization of how caregiver QOL may be affected during acute treatment, and does not delineate how it might change over the radiation/ chemoradiation period. Moreover, many of the studies did not use QOL instruments specific to cancer caregivers. Thes e issues underscore the need for more target ed research focused upon HNC caregivers and the effects on caregiver QOL during critical care transitions. Social Support Social support is associated with critical health outcomes [ 87 ] . For example, social support has been found to influence disease incidence and mortality rates [ 88 ] . Moreover, social support has been associated with emotional well being and coping during stressful life experiences [ 88 ] . Not s urprisi ngly, social support has also been an area of neglected investigation in the HNC caregiver population. To date , o nly t hree published studies have addressed this concept in HNC caregivers [ 37 , 89 , 90 ] (see Table 2 1) . Chen and colleagues [ 37 ] assessed social support in caregivers of patients with HNC using the Inventory of Socially Supportive Behavior (ISSB). The authors
38 reported that when caregivers lacked social support, they perceived their caregiving experiences to be negative. In addition, social support was reported to be the major predictor of burden in this study. T he authors did not , however, report the actual scores for social support or indicate how the scores compared to other caregiver groups . Nevertheless , Chen and colleagues [ 37 ] findings suggest that social support has xperience and warrant further investigation regarding the impact of burden perception. Baghi et al. [ 89 ] also assessed the characteristics of social support in HNC relatives in a cross sectional study. Seventy eight relatives of HNC survivors (6 48 months post treatment) were assessed using a non validat ed instrument developed for the study. The a uthors reported descriptive results demonstrating that almost 80% of relatives considered it necessary to maintain social contact with friends, family, etc., yet only 57% were able to do so. Almost 23% indicated they were overextended in maintaining social relationships with their contacts. Relatives in this study were also asked which source provided maximal support. Approximately 51% indicated their friends, 22% reported the cancer care recipients themselves, 17 % indicated family, and approximately 10% reported others, or did not specify a source. About 33% indicated that they never called for help when faced with excessive caregiving demands and approximately 13% reported that they continuously asked for help wh en experiencing excessive demands. A pproximately 19% of relatives responded that they had a difficult time accepting help from others. However, similar to many other HNC caregiver studies, this evaluation only included caregivers of survivors who were post treatment. Consequently, it is possible that preferences for sources of social support and
39 willingness to ask for and accept social support may differ or alter when confronted with acute radiation/ chemoradiation treatment experiences. More research is nee ded that explores this concept in caregivers of HNC patients undergoing radiation/ chemoradiat i on. In a more recent study, Chen et al. [ 90 ] used a cross sectional design to assess social support in caregivers of oral cancer patients post surgery. This study utilized a Taiwanese version of the Social Support Scale, which measures social support received from family and healthcare professionals. The authors reported that caregivers perceived greater social support with family than healthcare professionals. Moreover, lower levels of social support were associated with greater overall unmet supportive care need by caregivers. Cumulatively , these findings suggest that social support is an important dim ension in HNC caregiving and more research is needed to explore this concept in caregivers of HNC patients undergoing radiation/ chemoradiation. . Pertinent Theoretical Approaches and Models In addition to limited psychosocial evaluation s that have be en conducted among HNC caregivers, studies have overwhelmingly lacked a theoretical foundation or model to guide investigation. Kerlinger [ 91 ] s et of interrelated concepts, definitions, and propositions that present a systematic view of events or situations by specifying relations among variables in order to explain and predict the ev ents or (p.9). A more thorough and less abstract explanation of constructs can be demonstrated in a theoretical model. A number of theoretical approaches have been proposed within the various domains of burden , QOL , and social support that may help elucidate the caregiving
40 experience in HNC. While several theories have been postulated to explain the process of caregiving and the relationship between caregiver and care recipient, the majority of studies within the HNC caregiver literature do not include a theoretical foundation. Conversely, most caregiver models were not conceptualized specifically in a HNC context. Emotional Contagion Theory It has been proposed that people unconsciously adopt the emotional states of a person with whom they have a relationship. This theory has been referred to as the Emotional Contagion Theory [ 92 ] . According to Hatfield and colleagues [ 92 ] , individuals will unconsciously mimic nonverbal behaviors of another person and this generates a sim ilar emotional experience between the observer and actor. Emotional contagion is more likely to occur when there is familiarity and a shared common threat between individuals in a relationship. The Emotional contagion theory, therefore, may help explain wh y HNC caregivers struggle emotionally with the caregiving experience and in turn, may explain why promoting caregiver well being may promote positive outcomes for HNC patients. The Emotional C ontagion T heory has been explored in prostate cancer patient ca regiver dyads, with the idea that emotional contagion would foster dyadic interdependence [ 93 ] . In addition, meta analytic evidence from 46 studies has demonstrated a correlation in emotional distress between cancer survivors a nd spouses [ 94 ] . Currently, only one published study [ 84 ] has explored the interdependence between HNC patient and caregiver dyads. Findings from this study indicated that at twelve months post treatment, patient QOL accounted for 52% of the variation in
41 caregiver QOL. Unfortunately this relationship was not explored during the acute treatment period, when patient and caregiver challenges may be extensive. Caregiver Well being Implications Longacre et al. [ 95 ] also proposed a model that depicts the implications of caregiver well being on the caregiver, care recipient, and healthcare utilization. This model was proposed w ithin a published review of psychological functioning of HNC caregivers, although the model itself does not specifically address HNC. Caregiver well being is defined as having limited/ reduced distress. Effects of caregiver well being on the caregiver incl ude improved QOL, better physical health, and ability to provide care. This subsequently results in enhanced outcomes such as physical and emotional well being for the HNC patient. Likewise, within the health care systems this (including hospitals, insurance, Medicare, and Medicaid) equates to fewer discharge delays and fewer delayed placement s to nursing homes. This model underscores the need to support caregivers throughout their experience to promote caregiver well being and positive outcomes for the caregiver, care recipient, and health care system. Although caregiver well being, it does not articulate the processes that result in caregiver outcom es. Caregiving Stress Process Model Pearlin and colleagues [ 96 ] a process. This model was partially conceptualized from disease patients. The model includes the following four domains: (1) the background and context of stress, (2) primary and secondary stressors, (3) the mediators of stress, and (4) outcomes of stress [ 96 ] . Background and context pertains to the
42 socioeconomic status, caregiving history, composition of family and networks, and availability of community based formal programs. Primary stressors pertain to the care rast, secondary stressors result from the primary stressors, and include role strains (e.g., family conflict, economic problems) and intrapsychic strains (e.g., self esteem, loss of self). Within the model, coping and social support mediate or moderate the stress process at different points. The outcomes of the model include well being, mental and physical health, and the ability to sustain various social roles [ 96 ] . Pearlin and colleagues [ 9 6 ] suggested that future studies could build upon their model. In line with this recommendation, Weitzner, Haley, and Chen [ 97 ] adapted the Pearli n model f or cancer caregivers . Their model includes primary and secondary stressors, several mediators and moderators (stress appraisal, coping, social support, distress appraisal, personality variables, and relationship variables), and caregiver well being as the outcome. Fletcher and colleagues [ 98 ] later adapted this model, again for cancer caregivers. However, in addition to the stress process (i.e., primary and secondary stressors, appraisal, and cognitive behavioral responses) a nd contextual factors (personal, sociocultural, economic, and health care), their model also included the cancer trajectory as an additional element. None of these aforementioned models, however, considered the biopsychosocial experience of caregiving as a critical feature or modulator of the caregiving process. Adapted Pittsburgh Mind Body Center Model The only caregiving model that has considered the mind body interactions that occur during caregiving, is one proposed by Sherwood and colleagues [ 56 ] and applied to caregivers of brain cancer patients. This biobehavioral model considers both patient
43 and caregiver variables that ultimately affect caregiver overall health. Patient factors pertain to characteristics of the disease and these factors are believed to affect the behavioral responses. Similarly, personal characteristics of the behavioral responses. The behavioral responses then lead to biologic responses, which impact the main model outcome, caregiver health. Theory of the Social Care System Cantor [ 99 , 100 ] proposed a system of social care , acting as a hierarchical compensatory model of social support. This system is a network of family, friends, and formal support services. Formal support service s may include community/government agencies, hospitals, and homecare services. According to this theory, there are five levels of sources of support, with the closest sources to the individual being in level one and the farthest sources being in level 5. A ccording to Cantor, older adults will prefer support from those classified in level one (those who are closest to them). The levels include the following: (1) biological family members and spouses, (2) friends and neighbor. The third level includes, (3) th ose who provide professional services (e.g., clergy), (4) organizations/providers in the community who provide formal services, and (5) governmental agencies with the power to make policy decisions. Cantor posited that when individuals do not have the opti on to receive support from their preferred source, they seek support in the next subsequent level. For example, if family members are not available (level one), an individual may seek support from a neighbor (level two). In reviewing the data published in the HNC population , Baghi and colleagues [ 89 ] ( results discussed earlier ) suggest opposition to this theory because caregivers reported that the source in which they received the most support was their friends, not
44 family. However, it is unclear if the source caregivers received the most support from ( i.e., friends) was also their preferred source. The limited data available on HNC es not provide a satisfactory profile of their perceived support or preferred sources of support . Given that social support has been shown to be related to positive health outcomes and may offer a buffer against negative experiences [ 101 ] a profile of social support in the HNC caregiver population is urgently needed. Moreover, additional information regarding the relationship between caregiver social support and other key areas of psychosocial functioning (burden and QOL) is warranted. Working Model The u s e of a theoretical model helps guide sci entific investigation by specifying relationships among variables and constructs. Public health and other health care professionals can use models to design interventions to promote health and reduce suffering. To date, no models have been developed specif ically for HNC caregivers. Among the current broader caregiving models, Sherwood et al. (2008) proposed the only model that takes into consideration the interplay between psychological and biological response to stress. Although the model acknowledges the influence of care recipient factors on caregiver functioning, the model does not consider pertinent indicators of care recipient well being (e.g., QOL) or the interdependence between such patient indicators and caregiver well being . Consequently, building upon the work of Sherwood and others reviewed above, t he model proposed for this dissertation is informed by their work [ 56 , 92 , 95 , 96 ] and collectively shown in F igu re 2 1 . The model proposed in this study depicts the interconnectivity between care recipient , caregiver, and clinical factors on caregiver outcomes (burden, QOL,
45 psych o neuro endocrine/physiological outcomes, physical health) and care recipient QOL. Althou gh a comprehensive assessment of this model in its entirety is beyond the scope of this dissertation, the proposed model (represented below) is presented to support the aims of this study and to support conceptualization . As depicted in Figure 2 1, the bl ue boxes represent the care recipient variables. This section of the model demonstrates that care recipient demographics and symptom severity and morbidity interconnect to impact care recipient QOL. It also demonstrates that the relationship between care r ecipient disease and treatment factors and care recipient QOL is mediated by care recipient symptoms and morbidity. For example, patient s receiving more aggressive ablative treatment for HNC (i.e., combined chemoradia tion) and consequently developing signi ficant morbidity (e.g., dysphagia), may ultimately demonstrate greater impairment in QOL. In contrast, the gray colored boxes represent the caregiver variables . This section depicts that similar to care recipient s, caregiver demographics are interconnected to caregiver outcomes (i.e., QOL and burden). In addition, caregiver burden may impact QOL and psycho neuro endocrine /physiological functioning and this relationship is moderated by perceived social support. Careg iver burden and health outcomes are mediated by psycho neuro endocrine /physiological functioning. Moreover, overall physical health may impact QOL. Lastly, the yellow lines represent the interdependence between care recipient and caregiver functioning. Speci fically, caregiver burden can be affected by patient disease and treatment factors as well as patient symptoms, morbidity, and QOL. In addition, patient QOL and caregiver QOL
46 demonstrate a reciprocal relationship , with caregiver QOL mediating the relations hip between patient QOL and caregiver psychoneuroendocrine/physiological functioning. This proposed model helps inform current literature pertaining to caregivers of patients with HNC. The model takes into consideration caregiver psychosocial functioning and cortisol response, a s well as the interdependence between care recipient and caregiver QOL. Future research should evaluate this model in HNC patient caregiver dyads to determine if the hypothesized relationships can be supported . In addition, althoug h the model was developed using a HNC exemplar, future research should explore if the model can be extrapolated to other caregiving populations. Chapter Conclusion HNC requires complex treatment with significant and deleterious side effects. Informal careg ivers are intimately involved in the treatment experience and suffer many negative consequences as well. The majority of the literature that currently exists lacks a theoretical foundation . This review has provided an overview of the current literature in HNC caregiver functioning and has highlighted the need for further research in this area. Specifically, future studies should employ prospective designs to ascertain the biopsychosocial effects associated with HNC caregiving over the radiation/chemoradiati on treatment period. We recommend using the proposed working model to guide future research investigation among HNC caregivers.
47 Table 2 1. Review of s tudies Study Sample Treatment Time post treatment Design Main Findings Baghi et al. (2007) [ 89 ] Relative caregivers (N = 78), spouses = 20% S urgery with or without chemoradiation, > 6 months, median = 24, range = 6 48 months Cross sectional Approximately 44% wished to have psychological care for themselves. Approximately 80% considered maintenan ce of social contacts to friends , family, etc. ne cessary but only 57% were able to do so. Approximately 23% were overextended in maintaining their social contacts. Blood et al. (1994) [ 79 ] Patients & their spouses (N = 75) Surgery (Laryngectomy) 2 48 months post surger y Repeated cross sectional Strain and burden decreased as time from diagnosis increased. Strain was highest in the first 6 months of rehabilitation. Although strain decreased, it was not a significant difference in subgroups. Burden was the highest in sub groups 1 & 2. Male caregivers reported significantly less strain and burden than female caregivers. Present stress did not appear to be correlated to the two burden scales. Chen et al. (2009) [ 37 ] Patients & caregivers (N = 122 dyads) Not stated NA Cross sectional Caregivers h ad moderate levels of caregiving experience domains. Factors significantly related to those burdens across 5 domains of support, patie psychological needs.
48 Table 2 1. c o n tinued Study Sample Treatment Time post treatment Design Main Findings Chen et al. (2014) [ 90 ] Caregivers Surgery 7 49 days Cross sectional Caregivers perceived greater social support from family than healthcare professionals. Moreover, lower levels of social support were associated with greater overall unmet supportive care needs by caregivers. Drabe et al. (2008) [ 83 ] Female spouse caregivers Surgery, radiation/ chemoradiation M = 3.7 years Cross sectional QOL scores were high (indicative of good QOL) and similar to the referenced healthy norms. Nightingale et al. ( 2014 ) [ 81 ] Caregivers Radiation/ Chemoradiation NA Longitudinal Minimal to moderate levels of burden which increased significantly from the beginning of treatment to the middle of treatment.
49 Table 2 1. c o n tinued Study Sample Treatment Time post treatment Design Main Findings Patterson et al. (2012) Ross et al. (2010) [ 85 ] Patients & caregivers Family caregivers Radiation with or without chemoth erapy Not stated Baseline assessment = pre treatment; Final assessment = 12 months post treatment 6 24 months Longitudinal Cross sectional QOL did not change from pre treatment to 3 months but increased significantly between 3 and 12 months. and swallowing problems had a significant Moderate high distress was noted in 38% of caregivers. QOL scores were better than the scores reported in initial evaluation. Studies on caregivers of patients undergoing active cancer treatment. Greater time spent caregiving was associated with worse psychological well being, but also more positive adaptation to caregiving. Thirty nine percent reported that their practical & informational needs were met. Verdonck de Leeuw et al. (2007) [ 80 ] Spouses & patients (N = 41 dyads) Variation 3 120 months Cross sectional A clinical level of distress was noted in 20% of spouses and 27% of patients. Distress in spouses was related to presence of feeding tube, passive coping, less vitality, and disrupted daily life schedule resulting from caregiving.
50 Figure 2 1. Biopsychosoci al Model of Caregiving using a head and neck cancer c ontext
51 CHAPTER 3 CAREGIVER BURDEN, QUALITY OF LIFE, AND SOCIAL SUPPORT IN CAREGIVERS OF PATIENTS WITH HEAD AND NECK CANCER Background More than 55,000 people will be diagnosed with head and neck cancer (HNC) in the United States in 2014 alone [ 1 ] . Patients with HNC are at risk for disease specific impairments (e.g., di fficulty swallowing) as well as a host of psychosocial ramifications such as stigmatization, psychological distress, and body image issues [ 24 , 25 , 27 29 , 32 ] . Collectively, the negative impact of HNC on the patient can result in a difficult care experience for informal caregivers [ 2 , 95 ] . Currently, there are approximately 4.6 million Americans providing informal care for someone with cancer [ 39 ] . Although the negative effects of informal caregiving are well substantiated in the literature, investigation into HNC caregiving remains sparse. For example, caregiver burden, QOL, and social support have been well evaluated in cancer caregivers, but hav e been given little research attention among HNC caregivers. Only four published studies have assessed burden in caregivers of patients with HNC [ 37 , 79 , 80 ] . Chen et al. [ 37 ] reported moderate levels of burden in 122 family caregivers of hospitalized newl y diagnosed oral cancer patients 10 to 14 days post surgery; however, the authors reported a total burden score using the Caregiver Reaction Assessment (CRA), which is only intended to measure multiple dimensions of burden separately, not collectively. Mor eover, the cross sectional nature of the study only provides a snapshot of burden at one time point, rather than an understanding of burden across an arduous treatment period such as radiation/chemoradiation. Similarly, Verdonck de Leeuw et al. [ 80 ] also evaluated burden in HNC caregivers but did not report descriptive findings for the scale nor state the intensity of burden reported.
52 The limited prospective evaluation of burden in HNC caregivers has demonstrated that among caregivers of patients who are post treatment, burden decreases as time since diagnosis increases and burden is predominantly moderate in level at most [ 79 ] . Similarly, among caregivers of patients during the acute radiation/chemoradiation period, burden increased across the treatment trajectory, with the most notable increase from the initiation to the middle of treatment with levels characterized as moderate. Collectively, these studies suggest that burden increase s during radiation/chemoradiation and decrease thereafter. Moreover, intensity of burden is moderate at both time points . However, these studies relied on measurement by an instrument developed for dementia caregivers. More prospective research is needed w ith larger samples to evaluate its validity as a cancer specific caregiver burden measure. Similar to the evaluation of HNC caregiver burden, only a handful of studies have assessed quality of life (QOL) in caregivers of patients with HNC. Drabe et al. [ 83 ] and Ross and colleagues [ 85 ] reported that QOL levels were consistent with the normal population and higher than scores reported for a previous cancer caregiver study, respectively. However, their HNC patients were an average of 19 months [ 85 ] and 3.7 years post treatment [ 83 ] , when toxicity and associated morbidity is likely attenuated. Alternatively other p rospective studies have demonstrated that QOL was not correlated with caregiver strain, burden, or stress in caregivers of HNC patients post treatment [ 79 ] and QOL increases during the post treatment phase [ 84 ] . Moreo ver, Nightingale et al. [ 81 ] reported a decrease in QOL from the initiation to the middle of
53 radiation/chemoradiation, yet QOL scores were for the most part similar to or above population norms. Although social support has been associated with emotional well being and health outcomes [ 87 , 88 ] , limited studies have eva luated it in HNC caregivers, including the relationship it may have with burden and QOL. Chen et al. [ 37 ] reported that social support, in combination with other factors, predicted burden associated with disrupted schedule and that caregivers who lacked social support perceived their caregiving experien ce to be more negative. Chen et al. [ 90 ] also reported that caregivers perceived more support from family members in comparison to health professionals and less support was associated with caregiv Another study that reported on social support focused on the characteristics of social support of HNC patients 6 48 months post treatment [ 89 ] . The authors of this study reported that almost 80% of caregivers believed that it was necessary to maintain soci al contact, although only 57% were able to accomplish this. Most concerning, approximately 33% of caregivers indicated that they never call for help when faced with excessive caregiving demands. Collectively, these findings indicate that social support may have strong implications for the HNC caregiving experience and clearly warrant s further investigation. Current evidence regarding the psychosocial functioning of HNC caregivers is sparse and is restricted to a few prospective evaluations, the use of non c ancer caregiver specific measures, with a predominate focus on caregivers of patients post treatment rather than during the acute radiation/chemoradiation period [ 95 ] . Radiation/chemoradiation is an arduous treatment experience , which may necessitate
54 greater caregiving demands. Consequently, the purpose of this study was to evaluate psychosocial functioning in caregivers of HNC patients receiving radiation/chemoradiation. To do so, this study aim ed to: (1) describe and compare levels of burden and QOL in HNC caregivers from the initiation of treatment toward the conclusion of their care radiation/ chemoradiation, and shortly following treatment, and (2 a ) assess the relationship between perceived social support with burden and QOL . It was hypothesized that burd en would be come greater and QOL lower during the radiation/chemoradiation period and improve following treatment. In addition, it was hypothesized that greater social support would be associated with lower burden and better (higher) QOL. An additional exploratory aim for this study was to : (2b) identify pref erences for sources of support among HN C caregivers. Methods Participants Caregivers of patients with HNC were recruited from the U niversity of F lorida month period. Patients with HNC referred for radiation with or without chemotherapy (radiation/chemora diation) treatment were identified by the attending radiation oncologist and subsequently approached by a clinical researcher. All eligible patients were asked to identify an informal caregiver. The study researcher obtained informed consent from caregiver s who were; (1) providing care for a HNC patient with planned external beam radiotherapy with or without chemotherapy with a curative intent, and (2) at least 21 years of age. Conversely, caregivers were excluded if they; (1) had a current cancer diagnosi s, (2) were above 90 years of age, and (3) unable to read and c ommunicate in English language (See Figure 3 1) .
55 Procedure Caregiver socio demographic, patient disease, and treatment related variables including treatment type (radiation or combined chemora diation ), tumor stage, and tumor location were recorded at the commencement of radiation treatment through a standardized intake interview and medical chart review. Additionally, caregivers completed burden and QOL instruments at the beginning of radiation treatment (T1), five weeks into radiation treatment (T2), and one month following conclusion of treatment (T3). In addition, caregivers completed two social support instruments at T2. The study was approved by the local Institutional Review Board. More in formation regarding the methods employed for this chapter are included in Appendix A. Measures Caregiver b urden The Caregiver Reaction Assessment (CRA) [ 82 ] was used to assess caregiver burden at all three time points. This instrument evaluates both positive and negative aspects of caregiving including esteem, lack of family support, finances, schedule, and health subscales. The instrument has 24 items that pa rticipants indicate their degree of agreement using a 5 point Likert scale (strongly disagree to strongly agree). The CRA was initially tested in a variety of caregiver types, including cancer caregivers. The instrument has established construct validity a nd internal reliability and is recommended to assess burden in caregivers [ 102 ] . Caregiver quality of l ife The Caregiver Quality of Life Index Cancer scale ( CQOLC ) [ 86 ] was used to measure QOL at all three time points (T1, T2, T3). The CQOLC assesses burden, disruptiveness, adaptation, and financial concerns. The instrument has 35 items and
56 uses a 5 point Likert scale (i.e. , not at all, a little bit, somewhat, quite a bit, very much) to measure intensity of response. It was developed and tested in cancer caregivers, and has demonstrated construct validity, internal consistency, and test retest reliability. It has been strong ly recommended as a QOL assessment for cancer caregivers [ 102 ] . Caregiver social s upport The Medical Outcomes Study (MOS) Social Support Survey [ 103 ] was used to assess perceived availability of social support at T2 only. This 19 item instrument evaluates emotional, informational, tangible, positive social interaction, and affectionate support. The MOS uses a Likert scale from 1 5 in which respondents indicate intensity of response from none of the time to all of the time. Higher reported scores are interpreted as greater perceived social support. The MOS Social Support Survey can be evaluated as a single scale or as separate domains, although the autho rs recommend evaluating each subscale separately. This scale has been used in caregiver populations and has demonstrated good internal reliability, test retest reliability, and convergent and discriminant validity [ 103 ] . Caregivers also completed a modified measure of support preferences [ 104 ] . This questionnaire assesses who respondents prefer to receive support from in nine different situations. Specifically, caregivers indicated their first and second choice for each of the situations. Data Analysis Descriptive statistics (mean, stan dard deviation, and standard error) and graphic analyses were used to understand the distribution, assumptions, and potential outliers for burden and QOL, at all three time points. If outliers were confirmed to be correct, they were not excluded from analy ses. Burden, QOL , and perceived social support were treated as continuous variables. All hypothesis testing was performed at the two sided
57 0.05 level. Repeated measures ANOVA or the equivalent non parametric Friedman analysis (for variables not normally di stributed) was used to assess for difference across time points for burden and QOL. Pairwise comparisons were selected to identify which time points were significantly different. The most common first and second preferences for sources of support were ide ntified by obtaining p ercentages for each source of support for the various types of support . Relationships between social support with burden and social support with QOL were evaluated using bivariate Pearson correlations or the equivalent non parametric Spearman correlation . All analyses were performed using SPSS, version 21.0. Results Participants Thirty four caregivers completed T1 assessments, 32 completed T2 assessments, and 28 completed T3 assessments. Study loss ( approximately 18 %) was due to caregivers feeling overwhelmed (n = 3), the care recipient being medically unable to finish radiation/ chemoradiation treatment (n = 1), and care recipient death (n = 2) (See Figure 3 1) . Caregivers were an average of 56.94 years of age ( SD = 2.46), predominantly female (85%), mostly white (88%) and non Hispanic/Latino (94%). The majority of the caregivers were a spouse or partner to the care recipient (7 4 %). Approximately 68% of caregivers completed a college, technical, or graduate/ profes sional degree. Approximately 29% of caregivers reported a n annual household income of > 29,999, 29% reported $30,000 59,999, and 35 % reported > $60,000 and approximately . Slightly more than half o f the caregiver sample ( 53% ) was not employed. Presence of caregiver disease was reported in 38% of caregivers at T1 . The majority of care -
58 recipients were receiving combined chemoradiation (6 8 %). Stage of disease varied, although stage II was most common (32%). Five care recipients were being treated for a recurr ent HNC diagnosis (See Table 3 1 ). Aim 1 Descriptive statistics (see Table 3 2 ) indicated that all burden subscales , with the exception of finances , became worse from T1 to T2, with family support and impact on health continuing to become worse at T3. Alt hough impact on schedule and esteem showed an improvement at T3, values remained worse than T1 values. In contrast, the impact on finances subscale improved at T2, but became worse again at T3. There was a significant time effect for the esteem subscale ( F (2, 26) = 3.82 , p p 2 = .23) (See Figure 3 2 ) . Follow up comparisons indicated that esteem was significantly worse at T2 in comparison to T1 ( p < .03 , d = 0.47 ). Impact on health also demonstrated a significant time effect ( F (2, 26) = 7.66 , p p 2 =.37) with follow up comparisons demonstrating that impact on health was significantly worse at T3 in comparison to T2 ( p = .02 , d = 0.15 ) (See Figure 3 3) . Descriptive statistics demonstrated that caregivers who reported having a disease at baseline (n = 13) had a greater impact on health across time points. In contrast to burden, descriptive statistics demonstrated that overall QOL and all subscales with the exception of the disruptiveness subscale, improved at T2, with the financial subsca le continuing to improve at T3. However, overall QOL and positive adaptation became worse at T3, decreasing below T1 values. The disruptiveness subscale demonstrated a significant time effect ( X 2 (2) = 7.58, p = .02) (See Figure 3 4 ) . Follow up comparisons indicated that disruptiveness became significantly worse at T2 ( p = .02 , d = 0.34 ) and improved at T3, but stayed below baseline values . Descriptive
59 statistics demonstrated that spouses had worse overall QOL and greater burden at all three time points. A im 2 a Caregivers reported the highest level of perceived social support in the affectionate domain ( M = 4.07, SD = 1.11) followed by the positive social domain ( M = 3.75, SD = 1.12), the emotional/informational domain ( M = 3.70, SD = 1.05), and the tangibl e domain ( M = 3.52, SD = 1.14) . Correlational analyses (see Table 3 3) demonstrated significant relationships between burden scales and social support scales. Most relationships indicated that greater burden was associated with less social support . Greater (i.e., better) esteem was associated with greater affectionate ( r s = .35, p = .05) and positive social ( r s = .36, p = .04) support. Greater burden on the family support subscale was associated with lower emotional/informational ( r = .57 , p = .001) and tangible ( r = .60, p = .001) support and greater affectionate ( r s = .35, p = .05) and positive social ( r s = .36, p = .04) support. Greater burden on the impact on finances subscale was associated with less emotional/information al ( r = .38, p = .03), tang ible ( r = .41, p = .02), affectionate ( r s = .43, p = .01), and positive social ( r s = .46, p = .01) support. Finally, greater burden on the impact of health subscale was associated with less emotional /informational ( r = .44, p = .01), tangible ( r = .4 6, p = .01), affectionate ( r s = .52, p = .002), and positive social ( r s = .53, p = .002) support. Similarly, correlational analyses revealed significant relationships between QOL scales a nd social support (see Table 3 3 ). The majority of these relationships indicated that better QOL was associated with more social support. Overall QOL was positively associated with more emotional/information al ( r = . 53 , p = . 002 ) , tangible ( r = . 55 , p =
60 . 001 ) , affectionate ( r s = .60, p < .001), and positive soci al ( r s = .53, p = .002) support. Greater QOL on the disruptiveness subscale was associated with more emotional/information al ( r = . 43 , p = . 01 ) , tangible ( r = . 55 , p = . 001 ) , and positive social ( r s = .60, p = .001) support and less affectionate support ( r s = .43, p = .02). Greater QOL on the positive adaptation scale was associated with higher emotional/informational ( r = . 44 , p = . 01 ) , tangible ( r = . 40 , p = . 02 ) , affectionate ( r s = .60, p < .001), and positive social ( r s = .53, p = .002) support. Lastly, greater QOL on the financial scale was positively associated with higher emotional/informational ( r s = . 48 , p = . 0 1 ) , tangible ( r s = . 46 , p = . 009 ) , affectionate ( r s = .50, p = .002), and positive social ( r s = .53, p = .002) suppo rt. Aim 2b Spouses and partners were the most common source of support identified as the first preference for eac h type of support (See Table 3 4 ). Specifically, caregivers indicated they would ask their spouses/partners for help if they suddenly felt ill (73%), needed to borrow money (43%), needed help with house or child care (53.3%), were lonely and wanted to talk (76.7%), needed someone to listen (73%), wanted encouragement (6 7 %), needed help filling out a form (4 7 %), wanted medical advice (40%), an d needed assistance with legal decisions (4 7 %). In contrast, caregivers did not uniformly identify the same source of support when asked to identify their second preference (e.g., if their first preference was unavailable). e most common second preference selected for borrowing money (32%), house or child care (2 7 %), filling out a form (29%), and assistance with legal decisions (2 7 preference selected for suddenly feeling ill (29%) , encouragement (38%), and medical
61 advice (2 7 %). Lastly, a friend was the most common second preference identified by caregivers for feeling lonely and wanting to talk (44%) and needing someone to listen (38%). Discussion This study evaluated burden and Q OL over the radiation/chemoradiation treatment period and social support toward the end of treatment in caregivers of patients with HNC. The hypotheses in this study were partially supported. Our findings indicated that burden typically became worse from t he beginning of treatment (T1) to five weeks into treatment (T2) , as expected, although many QOL subscales demonstrated improvement at this time. In contrast to our expectations, many of the burden subscales reflected increased burden from T2 to T3 while many of the QOL subscales reflected decreased QOL from T2 to T3. Given that many of the subscales reflected a non significant change , these results should be interpreted with cauti on. Interestingly, however, close to 32% of caregivers scored in the lower range for QOL at this final time point. However, despite similar patterns within many of the burden subscales, the only subscales that changed significantly over the assessment peri od were the esteem and impact on health subscales . Specifically , caregivers reported significantly poorer esteem at T2 time point in comparison to T1 , with time point accounting for 23% of the variance. In addition, there was a significantly greater impact on health at T3 time point in comparison to T2 , with time point accounting for 37% of the variance. Impact on schedule burden was consistently greater than all other burden subscales at all three time points. In addition, approximately 25% of caregivers s till had high schedule burden at study conclusion ( T3 ) . Collectively, the burden results suggest that HNC caregivers
62 experienced the most burden associated with the impact on their schedule and the greatest increase in burden occurring toward the conclusio n of radiation/chemoradiation treatment (esteem subscale ) and approximately one month following treatment (impact on health subscale ). minimal improvement at study conclusion ( T3 ) , these burden score s remained below T1 scores. These findings can be understood when taking into consideration the HNC caregiving experience over the radiation/chemoradiation and short term survivorship period s . Caregivers t m ay be associated with a decline in patient functional ability and increased care demands. For example, the majority of patients in this study experienced dysphagia toward the conclusion of treatment, which has been found to be associated with caregiver distress [ 80 ] and QOL [ 84 ] . While caregivers may enter the experience greatly valuing their care role, these feelings may attenuate as patient s deteriorate and caregivers struggle to provide the necessary care and support for patient s . Similarly, the reported i ncreased impact on health shortly following treatment may be a consequence of the stress and burden associated with the caregiving experience. Likewise, a greater impact on health shortly following treatment may also be associated with the care neglect of their own health needs during the treatment experience . In total, 38% of caregivers reported the occurrence of a comorbid disease at study entry and these participants reported a greater impa ct on health at each time point in comparison to caregivers without a disease at study enrollment.
63 E may be an artifact of the time commitment and change of environment associated with the caregiving role. For example, p atients typically had a myriad of medical appointments (radiation, chemoradiation, swallowing therapy, nutrition counseling, etc.) and often times the caregiver provided transportation and attended the appointments as well . Moreover, the majority of care r ecipients were from out of town and had to relocate during the treatment period. O nce care recipients return ed to their normal environment, the increased caregiving role likely continued during patient recovery . Collectively, these circumstances may be lik ely to have In addition to caregivers experiencing schedule burden, the only QOL subscale that changed significantl y over time was disruptiveness. C aregivers experienced significantly greater disruptiv ene ss in their daily schedule toward the end of treatment ( T2 ) in comparison to T1. These results suggest that an increase in caregiving related time demands is associated with attenuated QOL for caregiver s. These findings are consistent with prior burden and QOL findings reported among cancer caregivers. For example, the T1 caregiver burden scores in our study are similar to that reported by Chen et al. [ 37 ] among caregivers of oral cancer patients who had recently completed surgery. However, caregivers in our study reported much higher esteem in compariso n to Chen and [ 37 ] study. In contrast, caregivers in our study reported higher burden scores in com parison to caregivers of advanced cancer patients (predominately prostate and breast) in another study [ 105 ] . De spite the greater burden in our sample of HNC caregivers, our participants reported greater esteem at all
64 three time points in comparison to the caregivers of advanced cancer patients noted above [ 105 ] . As expected, higher perceived social support was typically associated with lower burden and higher QOL at T2. In addition, the most common first preference for so urce of support was a spouse/partner for each of the nine types of support. In contrast, there was variability in the most common second choice for source of support across the different types of support. However, a concerning finding is that caregivers in dicated that when tasked to select their second preference for source of support, caregivers indicated that they would not seek help from others for four of the nine types of support (borrowing money, house or child care, filling out a form, and assistance with legal decisions). the Theory of the Social Care System [ 99 , 100 ] . This theory posits that individuals will seek support from biological family members and spouses first. Similarly, the most common first prefere nce for all nine types of support was a spouse or partner. However, the theory also posits that when family and spouses are not available, caregivers will seek support from friends (including neighbors). Our findings suggest that in the absence of a spouse or partner, caregivers are more likely to avoid seeking support from any source and instead rely on themselves only. This finding is similar to a report from a previous study which indicated that 33% of HNC caregivers never call for help when faced with e xcessive caregiving demands [ 89 ] . However, caregiv ers in Baghi and colleagues [ 89 ] study were more likely to receive support from friends whereas in our study, caregivers preferred to seek support from a spouse or partner. This discrepancy,
65 [ 89 ] were spouses to the care recipient. Caregivers in the present study w ere predominantly (74%) a spouse or partner to the care recipient. The present study has several strengths and limitations. This study evaluated change in burden and QOL across three different time points that had not previously been evaluated in HNC careg ivers. Moreover, the QOL and burden instruments utilized are specific to cancer caregiving. As noted previously in this paper, the majority of studies that have evaluated HNC caregivers used cross sectional designs, non cancer specific instruments, and wer e focused predominantly on caregivers of patients who were farther out from treatment. One inherent problem to evaluating burden in caregivers is the potential for attrition due to the level of caregiver burden. Although three caregivers withdrew due to fe eling overwhe lmed, this only accounted for about an 8 % loss. Related to this, the overall study loss was only approximately 1 8 %. This study was limited by the small sample size. However, the distribution for each variable was evaluated and non parametric s tatistics were utilized where appropriate. Future research should include a larger sample size. In addition, caregivers were recruited at the beginning of their care and evaluating caregivers from diagnosis through survivorship would provide a more complete assessment of burden and QOL along the cancer trajectory and is therefore recommended for future studies. Lastly perceived social support and preferences for sources of support were only evaluat ed at T2. Consequently, our results pertaining to those outcomes only represent a snapshot in time, rather than an idea of how social support and sources of support
66 may change over the treatment experience. Future research should prospectively evaluate the se outcomes to determine if they change during or after the radiation/chemoradiation treatment period, especially given the noted increased burden and impaired QOL that was demonstrated in this study. In addition to addressing the limitations of this stud y, it is also recommended that future research further explore differences in psychosocial functioning among caregivers with various relationships to the care recipient. Our descriptive results demonstrated that spouses/partners had lower overall QOL and g reater burden (measured by the CQOLC instrument) at all three time points in comparison to other types of caregivers. However, the majority of our sample was comprised of spouses/partners so future research should evaluate this relationship among a larger more heterogeneous sample. Likewise, a larger sample would allow for the identification of different factors associated with burden and QOL in caregivers such as indicators of intensity of care (e.g., hours of daily care provided), care recipient disease and treatment characteristics, patient disfigurement, as well as personal attributes of the caregiver (e.g., coping mechanisms, spirituality) . Moreover, it is recommended that future studies employ a mixed methods design for a more in depth evaluation of burden in HNC caregivers over the treatment period. At times, participants anecdotally expressed significant burden that was not always reflected in thei r survey responses. In fact, many caregivers expressed difficulty with completing some of the items on the CRA and CQOLC instrument s (e.g., ). A mixed methods evaluation may point to a d iscrepancy in qualitative and quantitative responses
67 associated with level of burden and QOL experienced. As such, a future mixed methods evaluation may demonstrate the need for the development of HNC specific instrument s to measure caregiver burden and QO L . Lastly, although burden and QOL are defined as separate constructs, the CQOLC instrument also that is distinct from the caregiver burden instrument (CRA). However, fut ure research may want to confirm the independent constr ucts within these two scales using factor analysis . Similarly, the CRA and CQOLC instruments have similarities among some of their domains (e.g., schedule burden in the CRA instrument and disruptiveness in the CQOLC instrument). As such, factor analysis co uld also be utilized to determine the relationship among the domains included in the CRA and CQOLC instruments to ascertain any degree of overlap. Our findings suggest that caregivers of patients with HNC experience the greatest increase in burden at five weeks into treatment in comparison to the beginning of treatment or post treatment. In addition, while QOL tends to improve five weeks into treatme nt, it typically decreases post treatment. Moreover, greater perceived social support is associated with less burden and greater QOL among HNC caregivers. Finally, the majority of HNC caregivers prefer to seek support from a spouse/partner when needing a v ariety of different types of support. Clearly, these findings underscore the difficult nature of caring for a patient with HNC and call for intervention to mitigate the negative impact on caregivers.
68 Table 3 1. Participant characteristics at study e ntry (n=34) Age(years) M = 56.94 SD = 2.46 Variable n % Relationship to care recipient Spouse/ partner 25 7 4 % Gender Female 29 85% Race White 30 88% Other 4 1 2 % Ethnicity Not Hispanic/Latino 32 94% Education < High School Degree 1 3 % High School/GED 10 29% College/Tech. Degree 17 50% Graduate School 6 1 8 % Income < 29,999 10 29% 30,000 59,999 10 29% > 60,000 1 3 3 8 % Not reported 1 3% Employment Not Employed 18 5 3 % Presence of Disease Yes 13 38% Treatment Radiation only 11 32 % Combined chemoradiation 23 6 8 % Prior surgery 13 38 % AJCC Stage 0 2 6 % I 4 1 2 % II 11 32 % III 4 1 2 % IV 9 26 % No t Stage d 4 1 2 % Recurrence Yes 5 1 5 %
69 Table 3 2. Caregiver burden and QOL Scale T1 M SD range T2 M SD range T3 M SD range (n = 34) (n = 32) (n = 28) CRA Instrument Esteem 4.47 0.42 3.57 5.00 4.23 0.54 3.29 5.00 4.37 0.48 3.29 5.00 Family Support 1.98 0.62 1.00 3.00 2.20 0.90 1.00 4.80 2.14 1.00 1.00 5.00 Finances 2.79 1.13 1.00 5.00 2.70 1.17 1.00 4.67 2.68 1.27 1.00 5.00 Schedule 3.15 0.83 1.60 4.80 3.26 0.93 1.00 4.60 3.19 0.91 1.20 5.00 Health 2.07 0.81 1.00 4.00 2.23 0.88 1.00 4.25 2.51 0.93 1.00 4.75 CQOLC Instrument QOL Total 92.14 18.43 44.69 124.00 92.94 19.12 55.00 128.00 89.51 24.42 44.00 128.00 Burden 23.21 7.93 5.00 35.00 25.38 7.51 12.00 40.00 24.54 8.72 7.00 37.00 Disruptiveness 22.15 4.45 13.00 28.00 20.72 4.67 12.00 28.00 20.75 6.00 5.00 28.00 Positive Adaptation 17.47 4.99 8.00 25.00 17.03 5.43 2.00 26.00 16.82 6.20 6.00 27.00 Financial 8.35 3.06 1.00 12.00 8.63 3.21 3.00 12.00 8.93 3.40 0.00 12.00
70 Table 3 3. Correlations for social support and burden (n = 32) Scales Affectionate Support Positive Social Support Emotional/ Informational Support Tangible Support CRA Instrument Esteem r s = .35, p = .05 r s = .36, p = .04 NS NS Lack of Family Support r s = .35, p = .05 r s = .36, p = .04 r = .57, p = .001 r = .60, p < .001 Impact on Finances r = .41, p = .02 r s = .46, p = .01 r = .38, p = .03 r = .41, p = .02 Impact on Health r s = .52, p = .002 r s = .53, p = .002 r = .44, p = .01 r = .46, p = .01 Impact on Schedule NS NS NS NS CQOLC Instrument Overall QOL r s = 60, p < .001 r s = .53, p = .002 r = .53, p = .002 r = .55, p = .001 Disruptiveness r s = .43, p = .02 r s = .60, p < .001 r = .43, p = .01 r = .55, p = .001 Positive Adaptation r s = .60, p < .001 r s = .53, p = .002 r = .44, p = .01 r = .40, p = .02 Financial r s = .50, p = .002 r s = .53, p = .002 r s = .48, p = .006 r s = .46, p = .01
71 Table 3 4. Most common preferences for sources of s upport Support Type First Choice Count (%) Second Choice Count (%) Suddenly feel ill Spouse/Partner 22 (73%) Other family 10 (29%) Borrow Money Spouse/Partner 13 (43%) No one/myself 11 (32%) House/child care Spouse/Partner 16 (53%) No one/myself 9 (2 7 %) Lonely and want to talk Spouse/Partner 23 (7 7 %) Friend 15 (44%) Need someone to listen Spouse/Partner 22 (73%) Friend 13 (38%) Encouragement Spouse/Partner 20 (6 7 %) Other family 13 (38%) Need help filling out form Spouse/Partner 14 (4 7 ) No one/myself 10 (29%) Medical advice Spouse/Partner 12 (40%) Other family 9 (2 7 %) Assistance with legal decisions Spouse/Partner 14 (4 7 %) No one/myself 9 (2 7 %)
72 Figure 3 1. Recruitment flow chart for caregivers
73 Figure 3 2 . Caregiver Esteem, as measured by the CRA 1 1 Caregiver Esteem changed significantly over the treatment period ( F (2, 26) = 3.82 , p p 2 = .23).
74 Figure 3 3 . Caregiver Impact on Health , as measured by the CRA 2 2 Caregiver Impact on Health changed significantly over the treatment period ( F (2, 26) = 7.66 , p = .002, p 2 =.37).
75 Figure 3 4 . Caregiver D isruptiv eness, as measured by the CQOL C instrument 3 3 Caregiver disruptiveness changed significantly over the treatment period ( X 2 (2) = 7.58, p = .02).
76 CHAPTER 4 DIURNAL CORTISOL RHYTHM IN H EAD AND N ECK C ANCER CAREGIVERS OVER THE RADIATION/CHEMORADIATION TREATMENT PERIOD Background Cortisol, a steroid hormone or glucocorticoid, is a biomarker of stress that is released from the hypothalamic pituitary adrenal (HPA) axis [ 57 ] . The HPA axis includes the hypothalamus, the pituitary gland, and the adrenal cortex [ 57 ] . Specifical ly, stressful stimuli trigger the hypothalamus to secrete corticotro pin releasing hormone (CRH) which then stimulates the pituitary to release adrenocorticotropic hormone (ACTH) into the bloodstream. In turn, this causes the adrenal cortex to release gluco corticoids, including cortisol [ 57 ] . Activation of the HPA axis is adaptive when experienced short term; however, pro longed or extreme activation of the HPA axis has been implicated in negative health outcomes [ 58 ] . For example, abnormal cortisol response has been associated with mortality among breast cancer patients [ 106 ] , immunolo gic decline [ 60 ] , met abolic syndrome [ 61 ] , and risk for cardiovascular disease [ 62 ] . Psychoneuroendocrinology literature indicates that under normal circumstances, cortisol secretion is highest in the morning at approximately 30 45 minutes post awakening (i.e., the cortisol awakening response or CAR) and lowest in the evening, demonstrating a negative diurnal pattern [ 58 ] . Encountering acute stress results in high cortisol levels throughout the day and chronic stress can result in a blunted slope. Consequently, lower slope values reflect a more rapid decline and indicate a normal r esponse . In contrast, higher slope values reflect flat diurnal rhythms as they approach 0 and have been reported to reflect dysregulation of the HPA axis [ 58 ] . Research into diurnal cortisol rhythm among various populations that encounter stressful stimuli has increased in recent years but has been mostly neglected among
77 informal caregivers. Research h as demonstrated that informal caregivers experience a range of emotional distress including anger, depression, and anxiety [ 47 ] , and many caregivers of cancer patients in particul ar demonstrate emotional symptoms that meet Diagnostic Statistical Manual (DSM) criteria for psychiatric pathology [ 48 ] . However, little is known about how the body physiologically responds to the informal caregiving experience, especially among cancer caregivers. Few studies have evaluated diurnal cortisol rhythm in informal caregivers and among those that have, findings have been inconsistent. For example, Rohleder et al. [ 64 ] reported similar cortisol rhythm in eighteen family caregivers of brain cancer patients and nineteen matched controls . Likewise Vedhara et al. [ 65 ] reported a normal cortisol rhythm in spouse caregivers of patie nts with multiple sclerosis . I n contrast, Miller and colleagues [ 63 ] found that parents of children with cancer demonstrated significantly flatter slopes in comparison to the parents of healthy children. Although the studies did not consistently demonstrate a different cortisol response in caregivers in comparison to non caregivers , there was great heterogeneity across these studies. For example, the studies evaluated cortisol response in family caregivers [ 64 ] , spouses [ 65 ] , and parents [ 63 ] . They also differed in the frequency of cortisol collection in one day, frequency of days, and frequency of assessment points. More research is needed to determine how cortisol rhythm changes over the treatment experience as well as what factors may predict diurnal cortisol rhythm in caregivers of patients with head and neck cancer ( HNC ) . This information could be used to develop and refine psy chosocial and health interventions that utilize mind body techniques for the HNC caregiver population .
78 The purpose of this study was to prospectively evaluate diurnal cortisol rhythm in caregivers of patients with HNC undergoing radiation/chemoradia t i on. The study aims were to: (1) describe and compare diurnal cortisol rhythm in HNC caregivers from the initiation of radiation/chemoradiation treatment toward the conclusion of their care treatment , and (2) identify the demographic, psychosocial, and treatment and disease related predictors of diurnal cortisol rhythm in HNC caregivers. It was hypothesized that diurnal cortisol rhythm would become significantly flatter toward the conclusion of treatment. It was also hypothesized that greater burden and lower care recipient and caregiver QOL would predict a more abnormal cortisol slope among HNC caregivers. In addition, we expected that older age, more aggressive treatment (combined chemoradiation), difficulty swallowing, and a more advanced disease s tage would be associated with a more abnormal cortisol slope. Methods Participants Patient plus caregiver combinations (dyads) were recruited from the University of Florida Oncology service over a six month period. Care recipients were identified by the treating radiation oncologist as appropriate for inclusion in this study and informal caregivers were subsequently identifi ed by the care recipient. Each d yad was approached by the study researcher, who reviewed study procedures, and obtained informed con Inclusion criteria for care recipients was as follows: (1) HNC, confirmed by clinical history and exam, with positive cross sectional study and histopathological biopsy excluding other pathology, (2) planned external beam radiotherapy (with or without chemotherapy), and (3) at least 21 years of age. Patients were excluded from the study
79 if they: (1) were receiving palliative treatment with a non curative intent, (2) above 90 years of age , and (3) were unable to read and communicate in English language. Caregivers meeting the following inclusion criteria were eligible: (1) providing care for a patient with HNC meeting the inclusion criteria above, and (2) at least 21 years of age. Convers ely, caregivers were excluded if they: (1) had a current cancer diagnosis, (2) were above 90 years of age, and (3) unable to read and communicate in English language. Procedure This study utilized a prospective parallel arm design. Caregivers and care re cipients received a standard intake interview at baseline to collect socio demographic characteristics and information regarding the relationship between care recipient and caregiver. Care recipient disease and treatment related variables including treatme nt type (radiation or combined chemoradiation ), tumor stage, and tumor location were obtained via medical chart review. Assessments were conducted at both of the following time points: (a) the beginning of the care (b) five weeks following the onset of the care recip . All instruments were completed at the cancer center clinic or in a patient preferred location and returned to the study researcher in person at the clinic or by mail. All procedures were implemented after approval from the local Institutional Review Board. More information regarding the methods employed for this chapter are included in Appendix A.
80 Caregiver Assessment Caregiver salivary c ortisol Caregivers completed salivary cortisol collections two times a day (on waking and at 21:00 hou rs) for three consecutive days following the T1 and T2 assessment s . This frequency of saliva ry cortisol collection (i.e., two times per day for three days) has been determined to be a n accurate measure of diurnal cortisol slope pattern [ 107 ] . Moreover, salivary cortisol has been determined to be a reliable measure of free circulating cortisol in the body [ 108 ] . The cortisol collection procedure entailed the participant placing a cotton role in their mouth for approximately two minutes and then storing the sample in a salivette (plastic tube). Caregiver participants were instructed to refrain from eating, drinking, smoking, brushing their teeth, or using mouthwash for 30 minutes prior to any saliva collection. Caregivers were also provided w ith a journal to record compliance with the above mentioned behaviors as well as the date and time of saliva collection (See Appendix B for saliva journal ) . Caregivers were asked to store their samples in a freezer until they were returned to the study res earcher in an insulated cooler that was provided to them. They were also given the opportunity to return saliva samples via mail (1 3 day delivery) with pre paid postage provided. Saliva is considered bio exempt and can safely be mailed without special pre cautions. Moreover, research indicates that saliva samples can be maintained at room temperature for extended periods without freezing [ 109 ] . After saliva samples were returned to the study researcher, samples were stored at 80 C until shipped on dry ice via overnight priority shipping to Salimetrics Inc. (State College, PA) for as saying. Caregivers were also asked to return their study behavior journals with the saliva cortisol samples.
81 Saliva samples were assayed in singulate to determine cortisol levels using a highly sensitive enzyme immunoassay (Salimetrics, State College, PA). The test uses assay coefficient of variation of 3.5% , and an average inter assay coefficient of variation of 5.1%. Method accuracy determined by spike and recovery averaged 100.8% and linearity determined by serial dilution averaged 91.7%. Caregiver burden Caregiver burden was assessed at both time points (T1, T2) using the Caregiver Reaction Asses sment (CRA) [ 82 ] . The CRA assesses the positive and negative aspects of caregiving with five subscales including esteem, family support, finances, schedule, and health. The instrument has 24 items and uses a 5 point Likert scale (i.e., strongly disagree, disagree, neithe r agree n or disagree, agree, strongly agree). The CRA was initially tested in a range of caregivers, including cancer caregivers. The instrument has demonstrated construct validity and internal reliability and has been recommended as an instrument to measu re caregiver burden [ 102 ] . Caregiver quality of life QOL was measured at both time points using the Caregiver Quality of Life Index Cancer scale ( CQOLC ) [ 86 ] . The CQOLC was originally developed and tested in caregivers of patients with lung, breast, and prostate cancers. The instrument assesses burden, disruptiveness, positive adaptation, and financial concerns. The CQOLC ha s 35 items and uses a 5 point Likert scale (i.e., not at all, a little bit, somewhat, quite a bit, very much). It has demonstrated construct validity , internal consistency, and test retest
82 reliability and has been strongly recommended as a QOL instrument f or cancer caregivers [ 102 ] . Caregiver s ocial support Social support was assessed in caregivers only at a single time point (T2) using the Medical Outcomes Study (MOS) Social Support Surve y [ 103 ] . This instrument assesses the perceived availability of several types of social support including emotional, informational, tangible, positive social interaction, an d affection. The instrument has 19 items and uses a Likert scale from 1 5 to measure intensity of response. The scale ranges from none of the time to all of the time. Higher rankings indicate greater social support. The instrument can be scored using a tot al summed score (for the 19 items) as an overall index, although authors recommend evaluating each dimension separately due to demonstrated independence among subscales. This tool has been used in caregiver populations [ 103 , 110 ] . It has demonstrated good internal reliability , test retest reliability, and convergent and discriminant validity [ 103 ] . Care recipient Assessment Quality of life QOL was measured at both time points in care recipients using the Functional Assessment of Cancer Therapy Head and Neck (FACT HN) instrument [ 111 , 112 ] . The FACT HN is a 27 item instrument and measures intensity of response through a 4 point Likert scale (i.e., not at all to very much). This instrument h as five subscales consisting of physical, social/family, emotional, functional, and additional concerns related to HNC. Scores are calculated for each subscale as well as summed for total performance on the instrument. The FACT HN has demonstrated internal consistency [ 113 ] and constr uct validity [ 112 , 114 ] .
83 Social support Care recipient social support was assessed at T2 using the MOS Social Support Survey [ 103 ] , which is described above. Swallowing function Swallowing ability was assessed at both time points using the Eating Assessment Tool (EAT 10) [ 115 ] and the Functional Oral Intake Scale (FOIS) [ 116 ] . The Eat 10 is a validated self swallowing ability. The EAT 10 has 10 items and uses a Likert scale ranging from 0 (no problem) to 4 (severe problem) to measure intensity of perception. A score of 3 or greater is indicative of dysphagia. The FOIS is a 7 point ordinal scale that is completed by the study researcher. It describes the functional oral intake of food and liquid with con sideration for alternate food sources, modifications in food/liquid, and required maneuvers or compensations used by the patients to sustain a particular level of intake. A score of 5 or greater is indicative of dysphagia. This scale has demonstrated stron g concurrent and content validity compared to disability and clinical swallowing measures and inter rater reliability across time points. Data Analysis Initially descriptive statistics and graphic analyses were used to understand the distribution of the d ata, assess assumptions , and search for outliers. Outliers for all data excluding cortisol , were checked for errors and if their values were correct, they were used. Cortisol data were log transformed to control for skewness and subsequently reviewed for t ime and concentration value outliers. Values were considered outliers if they were fo u r standard deviations above the mean. However, outliers were re tained if within normal concentration values for the participant s age and gender and there were
84 no additional behavioral compliance issues (e.g., smoked a cigarette) or medication s known to interfere with cortisol concentration values that were reported in the . All hypothesis testing was performed at the two sided 0.05 level. F or both a im s , analysis was conducted to review the relationship between cortisol slope s on collection time s . Unstandardized beta coefficients were calculated for cortisol slope at T1 and T2 by regressing r aw cortisol concentration values on collection time s , consistent with Sephton and colleagues [ 106 ] and Vedhara and colleagues [ 117 ] . C orrelation analyses and descriptive statistics were used to determine whether potential demographic variables , treatment and disease related variables, and psychosocial variables were associated with cortisol slope . Demographic variables included age, gender, and socioeconomic status (educat ion and income). Treatment and disease related variables included stage of disease, type of treatment (radiation or chemoradiat i on), and swallowing ability (dysphagia or no dysphagia). Lastly, psychosocial variables included caregiver burden, caregiver and care recipient QOL , and caregiver and care recipient social support . For aim one, a paired samples t test was used to evaluate change in cortisol slope as a continuous variable from T1 to T2. For aim two, variables that were significantly associated wit h the dependent variable (diurnal corti sol rhythm) were entered into separate linear regression analyse s as predictor variables while controlling for age and gender . Age and gender have demonstrated a relationship with diurnal cortisol and are commonly use d as covariates in cortisol analyses [ 73 ] . All analyses were performed using version 21.0 of SPSS.
85 Results Participants Thirty two care givers completed T1 assessments and 29 completed T2 assessments . Participant loss ( 9 %) was at tributed to caregivers feeling overwhelmed (n = 1 ), the care recipient being medically unable to finish radiation/ chemoradiation treatment (n = 1), and care recipient death (n = 1 ). Caregivers were an average of 57.41 years of age ( SD = 14.60), predominant ly female (84%), mostly white (9 1 %) and non Hispanic/Latino (9 4 %) (See Table 4 1) . The majority of the caregivers were a spouse or p artner to the care recipient (7 2 %). Many caregivers (6 9 %) completed a college, technical, or graduate/ professional degree. Annual household Income varied greatly with 28% reporting less than 29,999, 28% reporting 30,000 59,999, and 4 1 % reporting greater than or equal to 60,000. In addition, a little more than half ( 53% ) of the caregivers were not employed. Presence of care gi ver disease was reported in 39 % of caregivers at T1. Care recipients were an average of 60.59 years of age ( SD = 14.99 ). The typical care recipient was male ( 75 %), white ( 8 8 %), and non Hi s pa nic/Latino ( 9 7 %). Approximately half of the sample (50%) had a college/technical, or graduate/professional degree. The majority of care recipients were recei ving combined chemoradiation (6 6 %). Stage of d isease varied, although stage II was most common (35 %). Five care recip ients (16%) were being treated for a recurrent HNC diagnosis (See Table 4 2 ).
86 Aim 1 A paired samples t test revealed a significant a significantly flatter diurnal cortisol slope at T2 ( M = .03, SD = .03) in comparison to T1 ( M = .04, SD = .04) ( t (28) = 2.56, p = .02 , d = 0.60 ) (See Figure 4 1) . Aim 2 T1 diurnal cortisol slope was positively correlated with caregiver schedule burden at T1 ( r = .34, p = .05). A l inear regression analysis indicated that w hen controlling for age and gender, caregiver schedule burden at T1 was significantly associated with cortisol slope at T1 ( = .35, p = .05), accounting for 18.0% of the variance. (See Figure 4 2) . These results indicate for every one standard deviation increase in caregiver schedule burden at T1, th ere was a .35 increase in diurnal cortisol rhythm. In contrast , T2 diurnal cortisol slope was negatively correlated with the r = .37, p = .05), care recipient r = .40, p = .05) , care recipient emotio nal QOL at T1 ( r = .39, p = .05), and care recipient functional QOL at T1 ( r = .42, p = .04) . Separate linear regression analys e s were used to predict cortisol slope at T2 from each of the four correlated predictor variables individually. When T1 was significantly associated with diurnal cortisol rhythm at T2 ( = .3 9, p = .04) , accounting for 17.0% of the variance (See Figure 4 3 ) . For every one standard deviation increase in caregiver In addition, w hen controlling for age and gender, care recipient functional QOL at T1 was significantly associated with diurnal cortisol slope at T2 ( = .41, p = .05), which accounted for 19.0 % of the variance (See Figure 4 4 ) . For every one standard deviation
87 increase in care recipient diurnal cortisol slope . Discussion This study first aimed to evaluate change in diurnal cortisol rhyt hm over the radiation/chemoradiation treatment period in caregivers of patients with HNC. Consistent with the hypothesis , o ur results demonstrated that cortisol rhythm became flatter (became more abnormal) from the initiation of treatment (T1) toward the conclusion of treatment ( five weeks post treatment initiation) (T2) , indicating overstimulation of the HPA axis . Moreover, the change in diurnal cortisol slope represented a moderate to large effect size. Secondary burden analyses also demonstrated that ca a greater impact on their health and schedule , as well as a lack of family support at T2 in comparison to T1. In addition, QOL results demonstrated that disruptiveness and positive adaptation became worse at T2. Our findings of a flatter slope at T2, may be associated with our secondary results indicating a more impaired profile of burden and QOL, also at T2. Our findings demonstrate a flatter slope at both T1 and T2 in comparison to slope values reported in a previous study of cancer car egivers [ 63 ] . However, these findings may in part be attributed to differences in participants (e.g., parents/caregivers of children versus caregivers of adult patients) as well as methodolo gical differences in salivary cortisol collection (e.g., number of days collected, frequency of collection per day) [ 63 ] . The second aim of this study was to identify predictors of diurnal cortisol rhythm in caregivers of patients with HNC. R esult s indicated that caregivers cortisol slope at T1 was predicted by caregiver schedule burden at T1, when adjusting for age and ge nder. Specifically, the more schedule burden a caregiver reported, the flatter (more
88 blunted, abnormal) their cortisol slope was. In addition to identifying a predictive relationship with cortisol slope at T1, results also demonstrated relationship s with c ortisol slope at T2. When controlling for age and gender, caregivers overall QOL at T1 as well as care recipient s functional QOL at T1 each individually predicted cortisol slope at T2. In other words, higher (better) caregiver overall QOL and care recipi ent functional QOL were each associated with a steeper (mor e normal) cortisol slope at T2 when controlling for age and gender. In contrast to our hypothesis, n o relationship was found between cortisol slope and demographic characteristics , swallowing abili ty, or disease or treatment related variables. In addition, care recipient and caregiver social support was not associated with cortisol slope. Moreover, although care hese relationships did not remain with in the regression analyses. These findings support the idea of a mind body interaction associated with the HNC caregiving experience. Collectively, these findings suggest neuroendocrine system respond s more negatively toward the conclusion of the radiation/chemoradiation treatment experience as opposed to the initiation of the treatment, specifically by demonstrating a more dysregulated diurnal cortisol rhythm. In addition, these findings also suggest that caregiver schedule burden , caregiver QOL , and care recipient functional QOL each neuroendocrine response to the subjective caregiving experience. There were several strengths to this study. This study was the first to evaluate diurnal cortisol rhythm in HNC caregivers and one of onl y a few that have evaluated it in the broader cancer caregiving literature [ 63 , 64 , 118 ] . The limited investigation into HNC
89 caregiving has mostly been restricted to psychosocial outcomes only and neglected to explore how the body physiologically respond s to the HNC caregiving experience [ 95 ] . S tudies that have evaluated diurnal cortisol rhythm in the broader cancer caregiving literature have mostly utilized a cross sectional design and failed to consider how cortisol slope changes acros s time points [ 63 , 64 ] . In contrast, this study prospectively evaluated cortisol rhythm and demonstrated that the pattern changes over the radiation/chemoradiation treatment experience among HNC caregivers. Another strength of the present study was the evaluation of both caregiver and care recipient demonstrated interdependence among HNC patient and caregiver psychos ocial factors [ 84 ] . This study augments that literature by also demonstrating a relationship between the care recipient This is not surprising because secondary anal yses indicated that care recipient and caregiver QOL w ere positively correlated within and across both time points. A noted limitation in the present study is the small sample size, which may have resulted in inadequate power to identify additional relationships within our data. However, despite the small sample size, this study still yielded significant results . Moreover, the sample size was an improvement from previous studies that have evaluated cortisol in cancer caregivers [ 63 , 64 , 118 ] . Another limita tion in the presen t study is the small amount of variance that was accounted for in the regression analyses, diurnal cortisol rhythm during radiation/chemoradiation treat ment. However, this is the first study to identify burden and QOL predictors of dysregulated diurnal cortisol rhythm
90 in HNC caregivers and consequently, provide s valuable information to augment the limited literature. Finally, this study was limited by the lack of a control or comparison group. The inclusion of a control or comparison group would have helped to identify if the findings were specific to HNC caregivers, as opposed to non caregivers or other types of caregivers. However, given that a primary a im in this study was to determine the potential predictive relationship between caregiver burden (among other variables) with cortisol slope, the evaluation of a non caregiver population would not be pertinent to focus of this study . Moreover, a comparison group would have been limited to other types of cancer caregivers, given the use of cancer specific burden and QOL instruments in this study. M ore research regarding cortisol responses among HNC caregivers is needed. Future research should include a larger sample size and evaluate additional factors that d their neuroendocrine response. Additionally, other confounders may want to be evaluated health care needs, which could ultimately affect their cortisol response. Furthe r investigation into cortisol, specifically, may want to evaluate additional diurnal slope measures (e.g., the cortisol awakening response, or CAR). In addition, t his study was focused on evaluation over the radiation/chemoradiation period; however, f uture studies may also want to evaluate cortisol response in HNC caregivers across the cancer care continuum from diagnosis through survivorship to determine pattern s of change. Moreover, although this study was concerned with cortisol response, future studies may
91 want to consider additional biomarkers of stress such as alpha amylase and pro inflammatory cytokines [ 119 ] . In addition, in line with the limitations of this study addressed above, future research may want to emplo y a larger sample size and potentially a control or comparison group. Moving forward, clinicians should be aware of the potential negative impact of the caregiving experience on HNC caregivers, including psychosocial impairment and dysregulation in diurna l cortisol rhythm during the radiation/chemoradiation treatment period. Intervention s aimed at reducing burden and increasing both care recipient and caregiver QOL may be beneficial in reducing or preventing abnormal cortisol response in HNC caregivers. Th e ability to reduce or prevent abnormal cortisol response is important because of its relationship with other negative health outcomes such as increased mortality among breast cancer patients, immunologic decline, cardiovascular disease, and metabolic syndrome [ 59 62 ] .
92 Table 4 1. Caregiver characteristics at study e ntry (n=32) Age(years) M = 57.41 SD = 14.60 Variable n % Relationship to care recipient Spouse/ partner 23 7 2 % Gender Female 27 84% Race White 29 9 1 % Other 3 9% Ethnicity Not Hispanic/Latino 30 9 4% Education < High School 1 3% High School/GED 9 28% College/Tech. Degree 16 50% Graduate School 5 1 9 % Income < 29,999 9 28% 30,000 59,999 9 28% > 60,000 13 4 1% Not reported 1 3% Employment Not Employed 17 53% Presence of Disease Yes 11 39%
93 Table 4 2. Care recipient characteristics at study entry (n=32) Age(years) M = 60.59 SD = 14.99 Variabl e n % Gender Male 24 75% Race White 28 8 8 % Other 4 1 2 % Ethnicity Not Hispanic/Latino 31 9 7 % Education < High School 4 1 3 % High School/GED 12 37% College/Tech. Degree 10 31% Graduate School 6 1 9 % Treatment Radiation only 11 34% Combined chemoradiation 21 6 6 % Prior surgery 12 3 8 % AJCC Stage 0 3 9% I 4 1 3 % II 11 3 5 % III 3 9% IV 8 25% No t Stage d 3 9% Recurrence Yes 5 1 6 % Treatment Combined c hemoradiation 21 6 6 %
94 Figure 4 1. Caregiver diurna l cortisol rhythm at T1 and T2 4 4 Caregiver diurnal cortisol rhythm became significantly flatter at T2 in comparison to T1 ( t (28) = 2.56, p = .02, d = 0.60).
95 Figure 4 2 . C aregiver schedule burden and diurnal cortisol rhythm at T1 5 5 Controlling for age and gender, caregiver schedule burden at T1 was significantly associated with cortisol slope at T1 ( = .35, p = .05), accounting for 18.0% of the variance
96 Figure 4 3. overall QOL at T1 and diurnal cortisol rhythm at T2 6 6 significantly associated with diurnal cortisol rhythm at T2 ( = .39, p = .04), accounting for 17.0% of the variance
97 Figure 4 4. Care functional QOL at T1 diurnal cortisol slope at T2 7 7 Controlling for age and gender, care diurnal cortisol slope at T2 ( = .41, p = .05), accounting for 19.0% of the variance.
98 CHAPTER 5 HEAD AND NECK CANCER CAREGIVING : A DISCUSSION OF FINDINGS Informal caregivers are a vital source of cancer related care in the U nited S tates (US) . While the cancer caregiving experience has the potential to be rewarding for some, adverse consequences have increasingly become apparent in the literature. The nat ure of the multifaceted demands often nec essitate that the caregiving role become the priority above t he caregiver being. Consequently, the caregiving population typically experiences negative outcomes that impact their overall quality o f life (QOL) , including their health. This dissertation focused on head and neck cancer (HNC) caregivers, a population that has received little attention in the cancer caregiving literature. Dissertation Findings Chapter 2 Findings Chapter 2 of this dissertation reviewed quantitative studies that have evaluated burden, QOL, and social support in HNC caregivers. Our review of burden indicated that there are only four published studies that have evaluated this construct in HNC caregivers [ 3 7 , 79 81 ] . Two of the studies did not contribute a clear picture of burden in this p opulation due to statistical flaws or a lack of information provided in the manuscript [ 37 , 80 ] . The remaining two studies demonstrated that burden increased over time ; however , these studies utilized an instrument that was developed for dementia caregivers [ 79 , 81 ] . A cancer caregiver burden scale (e.g., Caregiver Reaction Assessment [ 82 ] ) may provide a more accurate representation of burden in HNC caregivers.
99 Similar to burden, there are only four published studies that have evaluated QOL in HNC caregivers [ 79 , 83 85 ] . These studies, however, did not provide any information pertaining to QOL during the acute radiation/chemoradiation period and how it change d during this ti me period. In addition, the QOL instruments that were utilized were not specific to cancer caregivers. A cancer caregiver QOL instrument (Caregiver Quality of Life Index Cancer [ 86 ] ) may ha ve been more successful in providing a valid representation of QOL among HNC caregivers. Our review in Chapter 2 also demonstrated that social support among HNC caregivers has only been evaluated in three published studies [ 37 , 89 , 90 ] . Findings in these studies indicated that a lack of social s upport was related to a negative caregiving experience and was a predictor of burden [ 37 ] . It was also found that caregivers received more social support from family in c omparison to health care professionals and that lower social support was associated with greater overall unmet supportive care needs [ 90 ] . In addition, it was found that almost 80% of relatives co nsidered it necessary to maintain contact with various sources of support, yet almost 60% were not able to do so [ 89 ] . Moreover, the most common source of support reported was friends [ 89 ] . Chapter 2 also reviewed different theories and models that could be applied to informal caregiving. Findings demonstrated that models failed to take into consideration the impact of both patient and caregiver variables on patient psychosocial functioning and caregiver psychosocial, biological, and health outcomes. Moreover, models were not developed specifically for HNC. Consequently, a biopsychosocial mode l of informal caregiving was proposed using HNC as an exemplar.
100 Collectively, the findings of the review conducted in Chapter 2 warrant ed further investigation into the psychosocial and physiological stress effects associated with informal caregiving among HNC caregivers. Specifically, the review highlighted the need for more prospective studies during the acute radiation/chemoradi ation period and emphasized the need for cancer caregiving specific instruments . In addition, the review of theories and models highlighted the need to develop and test a broader biopsychosocial model that could be applied to HNC patient caregiver dyads. This dissertation addressed these gaps in Chapter 3 and Chapter 4 and served to augment the limited information existed regarding HNC caregivers. Chapter 3 Findings Chapter 3 evaluated burden and QOL over the radiation/chemoradiation treatment period and social support toward the end of treatment in HNC caregivers. Results demonstrate d that burden subscales typically reflected greater burden from the initiation of treatment (T1) to five weeks into treatment (T2) , with the esteem subscale demonstrating significantly greater burden at T2 and the impact on health subscale demonstrating si gnificantly greater burden at T3 . In other words, caregivers had less esteem associated with the caregiving role toward the conclusion of treatment and experienced a greater impact on their health approximately one month following treatment. Specifically, 23% of the variance in esteem was accounted for by time point , demonstrating a moderate effect size. In addition, 37% of the variance in impact on health was accounted for by time point , demonstrating a large effect size . These findings may be attributed to the fact that the radiation/chemoradiation treatment effects increase over the duration of treatment, which may subsequently necessitate greater caregiving demands. As a consequence, when the caregiving experience become s
101 more chal lenging, caregivers may have less of a desire to provide care for the patient . In addition, the increased caregiving demands may lead to a greater impact on health /or energy limitations. Many of the burden subscales also becam e worse at the last assessment, approximately one month post treatment (T3) , although the change was not significant . In contrast to burden , QOL typically showed a small (and insignificant) im provement at T2, with many subscales subsequently decreasing at T3 . The disruptiveness subscale became significantly worse at T2 , despite a small (and insignificant) improvement in other subscales at this time. It is not surprising that caregivers had g rea ter disruptiveness in the ir schedule at T2 because they typically accompanied care recipients to their daily treatment appointments . Moreover, approximately 94% of dyads lived outside of the city where treatment took place. Of those who lived outside of th e city where treatment took place, the majority of the dyads were forced to temporarily relocate during the treatment period while others had a lengthy daily commute to and from treatment. The necessity of relocating or making a long daily commute likely c ontributed to the disruptive schedule experienced by caregivers. These findings were also supported by a high level of caregiver schedule burden in comparison to other subscales across all three time points. Although the burden and QOL subscales demonstrat ed change across time, many of these subscales demonstrated descriptive change s only and thus should be interpreted with some caution.
102 Social support findings indicated that greater social support was associated with less burden and greater QOL at T2. A p revious study [ 37 ] also found a r elationship between social support and burden among HNC caregivers. Specifically, the authors noted that social support predicted level of burden in caregivers [ 37 ] . The implications of social support have received a lot of attention in the psycho oncology and broader health literature [ 87 , 88 ] and our findings support the idea that higher levels of perceived social support are associated with more optimal outcomes . In addition to the evaluation of relationships between social support with burden and QOL , Chapter 3 also evaluated preferences for sources of support. HNC caregivers preferred to seek support from a spouse/partner when needing a variety of different types of support. These findings support the Theory of the Social Care System which posits that individuals are more likely to seek support from biological family members and partners first. However, the theory also posits that second to family, individuals prefer to seek support from friends. In contrast, we found when the spouse or partner was not available, caregivers reported that they preferred to only rely on themselves, rather than seek support from others. Similarly, 33% of HNC caregivers in a previous stud y reported that they never call for help when faced with excessive caregiving demands [ 89 ] . It is possible, however, that caregivers felt this way because the majority were temporarily relocated during the treatment experience and therefore lacked contact with friends or other family members who may resid e in their hometown. Chapter 4 Findings Chapter 4 was the first study to evaluate diurnal cortisol rhythm in HNC caregivers. As expected, cortisol slope became significantly flatter at T2 in comparison to T1 , which represented a moderate to high effect si ze ( d = 0.60) . As stated above,
103 this is also the time at which burden tended to be the worst in caregivers yet surprisingly, QOL was the highest. It was also demonstrated in Chapter 4 that caregiver burden and care recipient and caregiver QOL were both re lated to caregiver cortisol slope. Specifically, after adjusting for age and gender, greater caregiver schedule burden at T1 was associated with more abnormal cortisol slope at T1. In addition, care recipient QOL at T1 each separately predicted cortisol slope at T2 when controlling for age and gender. Although this evaluation did not include a control group of caregivers such as previous studies, it was the first study to prospectively evaluate the relationship between caregiver diurnal cortisol slope with caregiver demographic variables, care recipient disease and treatment related variables, and care recipient and caregiver psychosocial v ariables (burden, QOL, social support) . The findings in this dissertation support previous studies that have reported a negative effect of the caregiving experience on informal caregivers of cancer patients [ 45 , 120 ] . More specifically, the f indings from this dissertation provide a more holistic assessment of the impact of the caregiving experience on HNC caregivers, a population which previously received little attention. In addition to evaluating psychosocial constructs including burden, QOL , and social support, this dissertation also evaluated an established biomar ker of stress, cortisol. Moreover, important relationships between caregiver cortisol response with caregiver burden and care recipient and caregiver QOL were identified. Biopsych osocial Model of Caregiving A review of relevant caregiving models was conducted in Chapter 2 of this dissertation. The Pittsburgh Mind Body Center Model proposed by Sherwood and
104 colleagues [ 56 ] was adapted to caregivers of brain cancer patients and inform ed the model proposed in this dissertation. Sherwood and model [ 56 ] is the only caregiving model that includes the interplay between psychological and biological responses t o stress. While the model acknowledges a relationship between s , it does not take into consideration how care recipient factors such as overall QOL influence the caregiver . Taking this into consid eration, as well as the review of other caregiving models, a working model was proposed in Chapter 2 to help understand the potential relationships between care recipient variables and caregiver psychosocial and physiological responses to st ress (e.g., cor tisol response) . The model proposed in this study depicts the interconnectivity between care recipient , caregive r, and clinical factors on caregiver outcomes (burden, QOL, psych o n euroen docrine/physiological outcomes, physical health) and care recipient QO L. Briefly, the model demonstrates that patient demographics and clinical variables interconnect to impact care recipient QOL. Similar ly, caregiver demographics and patient clinical variables are also interconnected to caregiver outcomes (i.e., QOL and burden). Caregiver burden impact s QOL and psycho neuro endocrine/ph ysiological functioning and these relationship s are moderated by perceived social support. The model also demonstrates that the relationship between c aregive r burden and health outcomes is me diated by psycho neuro endocrine/physiological functioning. Moreover, overall physical health impact s their QOL. Lastly, care recipient QOL and caregiver QOL demonstrate a reciprocal relationship.
105 Although t his dissertation did not intend to test the model in its entirety, the findings have demonstrated relationships among some of the constructs (See Figure 5 1) . Specifically, with burden and QOL was assessed in Chapt er 3 (aim 2) using Pears on correlation analyses. Results demonstrated that higher perceived social support was associated with lower burden and higher QOL for almost all subscales in the three instruments . The findings from this study suggest that social support may not moderate the relationship between caregiver burden and QOL, as previously hypothesized in the model. However, given the association between social support with caregiver burden and QOL, f uture research should evaluat e if social support mediates this relat ionship. In the previously presented model, social support was also depicted to moderate the relationship between caregiver burden and psychoneuroendocrine/ physiological response. The relationship between social support and diurnal cortisol slope was eval uated in Chapter 4 of this dissertation (aim 2). Pearson correlational analyses did not demonstrate an association between social support and diurnal cortisol slope . However, the aims of this dissertation research were not to evaluate the impact of social support as a moderator to the relationship between caregiver burden and diurnal cortisol slope. Consequently, this relationship cannot be su pported nor refuted based on the findings. Future research should evaluate the potential impact of social support as a moderator to the relationship between caregiver burden and psychoneuroendocrine/physiological response . In addition, predictors of dysregulated cortisol response in HNC caregivers were identified in Chapter 4 (aim 2) . As expected, caregiver burden was associated with
106 dysregulated cortisol slope. Specifically, when controlling for age and gender, higher caregiver schedule burden predicted a more dysregulated cortisol slope. However, it is noteworthy to mention that while caregiver schedule burden was ass ociated with cortisol slope, the remaining burden subscales were not. In addition, lower care recipient and caregiver QOL each separately predicted a more dysregulated cortisol slope when controlling for age and gender. Moreover, although it was not a prim ary aim of this dissertation, secondary analyses demonstrated a positive correlation between care recipient and caregiver overall QOL within and across the three time points. This finding supports the reciprocal relationship between care recipient and care giver QOL depicted in the model, and is consistent with the Emotional Contagion Theory discussed in Chapter 2 [ 92 ] . Although caregiver QOL was not evaluated as a mediator to the relationship between care recipient QOL and caregiver physiological response as depicted in the model, the findings of this research do not refute this relationship either. Future research should evaluate this relationship. Collectively, t hese findings warranted a minor re conceptualization of the model (See Figure 5 2). The revised model was developed based on the findings in this dissertation research as well as well as hypothesized relationships that should be evaluated in future research. The only change to the model is the inclusion of social support as a mediator (as opposed to a moderator) to caregiver burden and QOL. Although patient functional QOL was associated with diurnal cortisol slope in caregivers, this relationship is expected to be med iated by caregiver QOL, as depicted in the model. Strengths There were several strengths of this dissertation research. In Chapter 3 , change in burden and QOL among HNC caregivers was evaluated across three different time
107 points . Specifically, the study described in Chapter 3 provided information on pattern of change in burden and QOL among HNC caregivers from the initiation of treatment, to five weeks into treatment, and again at approximately one month following treatment. Prior studies that evaluated b urden or QOL in HNC caregivers neglected these time points in the cancer trajectory and tended to focus on patients much further out from treatment [ 79 , 80 , 85 , 89 ] . We also utilized QOL and burden instruments that ar e specific to cancer caregiving whereas previous studies often utilized non cancer specific instruments, which may be challenging when attempting to detect outcomes specific to the cancer caregiving experience . C hapter 4 described the first study to evaluate diurnal cortisol rhythm in HNC caregivers and one of only a few that have evaluated it in the broader cancer caregiving liter ature [ 63 , 64 , 118 ] . Previous studies were mostly restricted to psychosoc ial outcomes only and neglected to explore physiological responses to the HNC caregiving experience , such as cortisol response [ 95 ] . In addition, the study in C hapter 4 demonstrated that both caregiver and care recipient factor s contribute cortisol response. This finding builds upon previous research that has demonstrated a relationship between care recipient and caregiver quality of life [ 93 ] by demonstrating that care recipient s QOL can als o In addition, many of the previous studies that pertained to psychosocial functioning among HNC caregivers or cortisol response among caregivers in general, utilized a cross sectional assessment [ 95 ] . In contrast, the stu dies in this dissertation research evaluated change across time. In addition, the loss of study subjects was relatively low despite the increased burden noted in caregivers . T here was about an
108 18% loss of participants in the study described in Chapter 3 an d a 9% loss of participants in the study described in Chapter 4 . Limitations Limitations were apparent in this dissertation research. Clearly this study is limited by the small sample size. A portion of the study described in Chapter 3 began with a sample size of 34 participants, with 28 completing all three assessment points. Concordantly, the study in Chapter 4 had 32 participants complete the first assessment with 29 completing both assessments. However, given the limited r esearch in this area, this dissertation research still adds valuable information to the caregiving psycho oncology literature. In addition, the sample size in Chapter 4 was larger than many of the previous caregiving studies that evaluated cortisol diurnal rhythm [ 63 , 64 , 118 ] . Moreover, non parametric statistics were utilized when appropriate. Despite the small sample size , results still indicated significant findings. However, it is possible that the study was under powered to detect other relationships that were explored in the data. In addition, characteristics (e.g., demographic, treatment related) for non consenting participants were not recorded for this dissertation research. Consequently, the sample evaluated in this research may not be fully representative of the population . However, a retrospective review of sample characteristics in previously published US studies demonstrated that the reported sample characteristics from this study are comparable [ 81 , 84 ] . The study in described in Chapter 3 provided pertinent information on change in burden and QOL over time . However, many of the patients received surgery prior to radiation/chemoradiation , which likely necessitated caregiving tasks at that time as well. This dissertation research did not evaluate caregivers immediately following surgery,
109 which may have provided more information on how burden and QOL change over the HNC caregiving experience . In addition, at approximately one month following treatment (T3), caregivers did not demonstrate a noticeable improvement in burden or QOL and in some cases, these outcomes became worse. It may have been more advantageous to evaluate caregivers further o ut from treatment in order to see improvement in psychosocial functioning. Chapter 3 also evaluated perceived social support as well as preferences for sources of support; however, this evaluation was completed toward the conclusion of treatment rather than across time. P articipants at this time reported moderate to high social support . While initially counter intuitive, this support may have been in part attributed to the environment of the treatment facility. Patients and caregivers have access to a c omprehensive health care team (e.g., radiation oncologist, hematologist, swallow/speech therapist, nutritionist, social worker) at the treatment facility that provide s support during the treatment period. In addition, many participants anecdotally noted th at they received significant support from others at the local facility including free lodging. to non local families undergoing treatment. Participants commented on how comforting it was to befriend others and discuss a shared treatment experience. However, when the patient caregiver dyad returns home to their normal environment following treatment, they are su ddenly faced with managing increasing treatment effects virtually on their own. Although the result s in Chapter 4 identified associations between caregiver cortisol slope with caregiver schedule burden, care recipient functional QOL, and caregiver overall QOL, re sults demonstrated that there was still a lot of variance
110 unaccounted for in our analyses. The small sample size of the study limited the amount of predictor variables that could be entered into regression analyses. However, this is the first study to demonstrate these relationships with caregiver cortisol and underscore the need for more research in this area. Lastly, an additional limitation of the study described in Chapter 4 was the lack of a comparison or control group, which would have been be neficial for confirming that our findings were specific to HNC caregivers. Future Research Moving forward, future studies should address the limitations presented in this dissertation research and build upon our findings . Specifically, a larger sampl e si ze should be employed to ensure adequate power for detecting significant relationships. Likewise , when recruiting a larger sample, another recommendation would be to include participants from a variety of demographic backgrounds to determine if these facto rs are associated with caregiver outcomes. The caregiver sample in this study was predominantly white (non Hispanic/Latino) and female , which consequently prevented analyses to explore disparities among outcomes. Likewise, descriptive results indicated tha t spouses/partners had more impaired overall QOL and burden (as measured by the CQOLC instrument). However, these findings should be interpreted with caution given the small sample size which included mostly spouse/partner caregivers (74%). Future research using a larger sample size with a more heterogeneous group of caregiver s may corroborate these results. In addition, in line with increasing the sample size, the inclusion of a control or comparison group would also be beneficial, as mentioned above. Thi s dissertation research was in part concerned with change in burden, QOL , and diurnal cortisol slope over the treatment period. However, future research should
111 consider following the patient caregiver dyad sooner (e.g., i mmediately following surgery) through a later time point in the survivorship period (e.g., three six months post treatment). Although some research suggests an improvement in burden and QOL following treatment for HNC caregivers [ 79 , 84 ] , more research is needed to substantiate these findings. In addition, future research should evaluate potential factors associated with burden and QOL such as intensity of care (e.g., hours of da ily care provided), treatment and disease characteristics, patient disfigurement, as well as caregiver personal characteristics (e.g., coping mechanism, spirituality , personality disposition ). tisol response should be evaluated such as coping mechanisms, sleep quality, and adherence or Moreover, a prospective evaluation of social support would provide useful information to ascertain if and when inte rventions need to address methods to increase or sustain optimal levels of support for the HNC patient caregiver dyad. O ur results also highlight the need for a mixed methods evaluation in which caregivers can explain or elaborate on their experience using their own words. Some caregivers expressed difficulty when completing the burden and QOL instruments because they either felt the need to justify their responses or they were unsure of how to answer an item (e.g., O thers have dumped caring for ___ onto m , ). It is possible that caregivers underreported their level of burden and/or over reported their level of QOL due to feelings of guilt associated with any negative feelings they may have regarding their caregiving role. It is also possible that some caregivers had lowered awareness of their
112 feelings or may have adopted avoidant coping strategies. A mixed methods evaluation may identify any discrepancy between quantitative and qualitative findings, suggesting a need for future instrument development particular to HNC caregiver burden and QOL. It is also recommended that future studies further evaluation the relationship between the burden and QOL subscales in the CRA and CQOLC instruments. For example, the CQOLC includes a burden subscale, yet the items in this domain appear to be distinct from the domains included in the CRA instrument. Future research may evaluate the relationship between these items using factor analysis. Moreover, it is also recommended that future studies evaluate the relationship between the other domains across the two instruments as well (e.g., caregiver schedule burden and disruptiveness QOL). Lastly, future research should evaluate the model proposed in this disse rtation in HNC caregiver populations or other cancer caregivers. To do so, a larger sample should be utilized so that the model can be explored using path analysis or structural equation modeling (SEM). The dissertation research did not aim to evaluate the various mediating and moderating relationships among the model parameters . Consequently, future research should explore these relationships as well as build upon this working model by considering additional factors that are important to the caregiving exp erience yet not included in the present proposed model. Clinical and Policy Implications The results of this dissertation call for a concerted effort to provide interventional resources for HNC caregivers, especially those providing care during and shortly after the radiation/chemoradiation treatment period. Researchers and health care professionals should collaborate to develop and implement services that address the
113 care psychosocial functioning , in an effort to prevent negative health consequences (e.g., dysregulated cortisol response) . Likewise, it is critical that policy makers also recognize the importance of supporting the well being of informal caregivers by addressing their needs . In 1993, the Family Leave Act was passed i n the United States (US) ; This Act allows informal caregivers to take leave, although th e time is un paid [ 121 ] . While other countries (e.g., Canada) have begun to place a greater emphasis on supporting informal caregiver s, the US continues to remain primarily focused on the care recipient only [ 122 ] . For example, there has been a rec ent effort to th screenings among cancer patients [ 123 ] . However, the findings of this dissertation research demonstrate the negative impact of the cancer experience on the caregiver as well. Moreover previous research has demonstrat ed moderate to high distress in 38% of HNC caregivers [ 85 ] and a desire for psychological care in 44% of HNC caregivers. Collectively, these findings underscore the importance of having regular psychological distress screenings for HNC caregivers as well. Concordantly, our findings demonstrating a flattened cortisol slope over treatment suggest that regular health screening should also be impl emented for informal caregivers as well . Although this dissertation research did not investigate additional health implications associated with the cortisol response , previous research has demonstrated negative health consequences for informal caregivers [ 43 , 53 ] , further supporting the need for regular health screenings among informal caregivers. is well over due, research has begun to develop successful interventions for cancer caregivers. A
114 meta analysis of interventions for cancer caregivers found 29 studies that aimed to improve outcomes for the care giver and/or care recipient [ 124 ] . This review identified three types of caregiver interventions that included psychoeducational, skills training, and therapeutic counseling interventions . Re sults indicated that the interventions demonstrated significant improvement in caregiver burden and QOL, among other outcomes assessed. Unfortunately, interventions developed specifically for HNC caregivers are sparse. One study [ 125 ] evaluated level of inter est and barriers in participation in a family group intervention for family members of HNC survivors. The authors reported that only 19% of the invited families participated in the intervention. Moving forward, it will be important to develop interventions that not only appeal to caregivers , but are feasible for caregivers to participate in. Although caregivers in this study reported moderate to high levels of social support, they also indicated their first preference of support was their spouse/partner, w hich was the care recipient for 74% of the participants. In addition, in the absence of a spouse/partner, many caregivers reported that would rely on themselves rather than seek support elsewhere. In light of these findings, interventions may want to consi der implementing resources in addition to the health care team where caregivers may seek support. For example, many caregivers in this study anecdotally expressed comfort in talking about the caregiving experience with other HNC caregivers they met during the treatment experience. Specifically, other caregivers provided emotional and informational support which participants valued because of the shared treatment experience. Taking this into consideration, it may be fruitful to consider an intervention appro ach that focuses on training prior HNC caregivers to serve as peer navigators for
115 caregivers who are about to embark on the caregiving experience during the treatment and short term survivorship periods. Psychosocial interventions have been evaluated for HNC patients [ 126 ] but have not demonstrated promising outcomes. For example, a recent systematic review and meta analysis identified seven studies meeting their inclusion criteria that evaluated psychosocial interventions for HNC patients. However, the results of the revie w demonstrated no evidence of improved outcomes including improved QOL, anxiety, or depression among patients. The findings of the review indicated that only one s tudy included caregivers, and the inclusion of the caregiver was at the discretion of the pat ient. The results of this dissertation as well as previous research demonstrating interdependence between patient and caregiver well being [ 81 , 84 , 94 ] suggest that researchers and clinicians may want to consider the benefits and drawbacks of dyad based interventions in which the patient and caregiver are targeted as one unit. Conclusion This dissertation research identified change in caregiver burden and QOL among HNC caregivers at various time points including the initiatio n of radiation/chemoradiation, five weeks into treatment, and approximately one month following the conclusion of treatment. In addition, relationships between caregiver social support with burden and QOL upport were evaluated five weeks into the radiation/c hemoradiation treatment period. Further research into psychosocial and physiological functioning among HNC caregivers is warranted. In addition, evidenced based interventions should be applied to HNC car egivers to mitigate the biopsychosocial impact of the caregiving experience . Finally, health care providers and policy makers should recognize the critical role that informal
116 caregivers have in cancer related care in the US and find ways to support their c aregiving roles.
117 Figure 5 1 . Supported Relationships in the Biopsychosocial Model of Caregiving
118 Figure 5 2 . Revised Biopsychosocial Model of Caregiving using a Head and Neck Cancer C ontext
119 APPENDIX A ADDITIONAL DETAILS FOR METHODS Recruitment Care recipients were identified by the treating radiation oncologist as appropriate for inclusion in this study and informal caregivers were subsequently identified by the care recipient. The study researcher used Epic to confirm that each referred care recipient is between the ages of 21 and 90 years and is not receiving palliative radiation (unless this information is already communicated by the radiation oncologist). Each eligible parti cipant was greeted by the study researcher and asked if they would be willing to learn about their potential participation in a study that was aiming to evaluate caregiver well being for those who provide informal care for patients with head and neck cance r. The University IRB 01 approved informed consent form was reviewed with each eligible participant who was interested in study participation. Participants were given the opportunity to ask questions as well as take a blank copy home with them to review pr the study researcher. Those who consented to participating were provided with a signed copy of their informed consent (See Figure A 1 below) . Characteristics regarding those who declined to participate were not recorded.
120 F igure A 1. Recruitment diagram Power Analysis and Sample Size Feasibility Table A 1 displays power and sample size options to detect this difference. Sample size and power calculations are based on a t test, with level of significance set at 0.05. Assuming at least 20% attrition rate for this population, N= 30 is an adequate sample size. Analysis is based on pilot data collected using the Zarit Burden Interview at baseline and 6 weeks. Table A 1 . Power calculations Power Effect Size N .80 .68 19 .90 .68 25 .95 .68 30 P rocedures to Enhance F ollow up Dyads received reminder telephone calls and/ or text messages for each follow up and all assessment points were managed in tracking system. Moreover, participants were allowed to complete their surveys away from the clinic or by telephone. This
121 allowed par ticipants to complete assessments at their own convenience and preferred location within each allocated assessment time point. In addition, each dyad was provided with a $25 gas card at the last assessment point to prevent missed data attributed to cost of transportation. Missed appointments were followed up promptly with a telephone call and/or text message to re schedule. Efforts to Prevent Attrition A 5 10% attrition rate was anticipated because of previous attrition rates in trials with the HNC patient population as well as pilot data with HNC caregivers. All participants were given an additional window of 3 days from the T1 and T2 target assessment point and an additional window of 2 weeks from their third target assessment point (1 m o th) to complete the measures (for C hapter 4 only) . If the HNC care recipient withdrew from the study at any time, the caregiver was still able to participate. Procedures to enhance follow up discussed above also aided in decreasing attrition rates. Survey Completion All instruments were completed at the radiation clinic or in a patient preferred location overnight and returned to the study researcher at the radiation clinic or by mail. he time point was highlighted. If participants chose to complete instruments away from the clinic, instruments were first reviewed with the participant either at the clinic or over the telephone. Participants who completed their instruments away from the c linic were each provided with a white security envelope with a seal at the top. Participants were instructed to not put any additional information on the surveys or envelope (e.g., name).
122 Salivary Cortisol Assessment Participants were provided with a sma ll insulated cooler which included two ice packs as well as six salivettes (plastic tubes) and six cotton roles. Salivettes were Collection time was specified with the day (i.e ., day 1 = 1, day 2 = 2, day 3 = 3) as well were instructed to place the cotto n role under their tongue for approximately 1 2 minutes or until saturated and subsequently place in salivette. They were provided with a picture to illustrate process of putting the cotton role in the salivette. Participants were also instructed to stor e the ice packs and completed assessments in a freezer if possible, until transporting back to the study researcher. If necessary, they were also provided with pre paid postage to mail samples back (using 1 3 delivery day method). Cortisol N oncompliance Noncompliance with cortisol collection can provide an inaccurate measure of cortisol diurnal secretion. Noncompliance has been noted in 26% of participants collecting saliva cortisol samples [ 127 ] . Participants were provided with a journal to record the exact time in which their saliva was collected as well as compliance with behavioral instructions. Self reported compliance tends to overestimate actual compliance [ 128 ] . This issue was addressed by thoroughly explaining to participants that it is important they record the accurate time of collection, regardless of what time the collection actually took place. Moreover, cortisol was collected at the minimal ti me
123 points that have been recommended to estimate daily cortisol slope in an effort to reduce burden to participants. Data Collection and Management The study researcher collected all data from participants. To ensure participant confidentially, data was entered into a database in a central computer system. Participants were identified only by participant ID. Investigators had password access to this d atabase. The primary study researcher and a trained research assistant conducted all data entry and management. The study researcher conducted all statistical analyses, under the supervision of her PhD advisor and dissertation committee chair . The study re searcher ensured completeness of data, standardized data entry, coded, cleaned, and reviewed at regular (weekly) intervals. Routine monitoring, maintenance, and quality control of the d atabase was provided by the study researcher . Missing Data A set of pr ocedures were followed to account for missing data. First, w hen participants returned surveys, the study researcher reviewed the surveys to ensure completeness of data. Second, a ny unanswered items were addressed with the participant at that time , if possi ble . Unanswered items were left blank if: (1) participants indicated that they purposely chose to not answer an item (e.g., did not feel comfortable answering an item) (2) participant s were unavailable to discuss an un answered item, or (3) the instrument had been completed more than two days prior to returning to the study researcher . Third , w hen calculating scores for the instruments that result in scale data (i.e., CRA, CQOLC, FACT HN, EAT 10, MOS Social Support Survey) , missing data were accounted for b y pro rat ing the scale or subscale score u sing the following
124 calculation: ((Sum Total/ Number of items in (sub)scale) * Number of items answered) ) . However, if more than half of the items were unanswered, the score was not calculated and was instead record ed as missing data. M issing data among instruments that only reflect percentages ( i.e., Preferences for sources of support), were not adjusted for; rather, they were recorded as missing data.
125 APPENDIX B SALIVA JOURNAL Instructions Please read all instructions and contact the Principal Investigator (PI) Chandylen Nightingale at (352) 262 4450 with any questions. Please read all instructions prior to beginning. When to collect your saliva 1. You will need to collect your saliva when you wake up and again at 9:00pm . 2. If you forget to collect your saliva, collect it as soon as you remember. 3. If you missed a day, please contact the PI for instructions on how to proceed (352 262 4450). Guidelines for collecting saliva 1. Please d o not do the following 30 minutes prior to collecting your saliva: a. Eat b. Drink liquids c. Brush your teeth d. Smoke or use tobacco products e. Use mouthwash **However, if you do, please indicate this in your saliva journal by answering the questions. 2. Please do not drink alcohol during the three days in which you collect saliva or for 10 hours prior to your Day 1, Time 1 collection. However, if you do, continue to collect your saliva and indicate your alcohol use in your saliva journal. PROCEED TO THE NEXT PAGE FOR FURTHER INSTRUCTIONS
126 How to use the oral swab 1. Remove oral swab from outer packaging and place under the tongue. 2. Keep oral swab in place (do not move around in mouth) for 1 2 minutes to ensure that it is saturated. 3. Place the oral swab into the upper portion of the tube (as demonstrated below in #2. Each tube has a separate label which corresponds to the time of your collection. Please store your oral swabs in the tubes as labeled below. If you accidentally store y our swab in the wrong tube, please make a note of this and inform us when you return your samples: AT THE BEGINNING OF RADIAITON TREATMENT Day of collection Time of collection Corresponding Tube Day 1 Upon waking up Day 1 At 9pm Day 2 Upon waking up Day 2 At 9pm Day 3 Upon waking up Day 3 At 9pm 5 WEEKS Day of collection Time of collection Corresponding Tube Day 1 Upon waking up Day 1 At 9pm Day 2 Upon waking up Day 2 At 9pm Day 3 Upon waking up Day 3 At 9pm
127 4. Replace cap and snap securely onto tube (as demonstrated below in #3) After you collect your saliva 1. Store your saliva in a freezer and keep indoors as much as possible, unless it is being transported. 2. Complete your salivary journal each time you collect saliva. 3. Please bring your samples back to the radiation clinic at the time discussed with you. If samples will need to be returned by mail, please discuss this with the PI (352 262 4450).
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139 BIOGRAPHICAL SKETCH Chandylen Nightingale was born in Saint Augustine, Florida in 1983. As a first generation college student, she earned her B.S. degree in p sychology and graduated with Cum L aude hon ors in 2006 from the University of Florida (UF). Shortly after graduating , she return ed to UF to e arn her m degree in p ublic h ealth with a concentration in the Social and Behavioral Sciences (SBS). During this time, she became interested in psycho o ncology research . She began conducting research under Dr. Giselle Carnaby and completed a study on quality of life outcomes for patients with head and neck cancer , for which she received the Yul Brenne r Head and Neck Cancer Award . Wanting to pursue this li ne of research more, Mrs. Nightingale decided to further her degree to complete her PhD in public health . During her PhD, Mrs. Nightingale continued her quality of life rese arch in head and neck cancer, expanding her focus to include informal caregivers of patients with head and neck cancer as well. This pilot study was funded through a joint fellowship through the Centers for Disease Control and the Society for Public Health Education. After completing her pilot project an d watching her mother provide informal care for her grandfather, her interest in informal caregiving increased. Consequently, she decided to complete her dissertation research in this area, building upon her work with head and neck cancer patients and care givers. Mrs. Nightingale hopes to continue conducting research pertaining to patients with cancer and their informal caregivers . Eventually, she plans to develop interventions to promote quality of life outcomes for patients with cancer and their informal caregivers.