Proton therapy versus photon radiation therapy for the management of a recurrent desmoid tumor of the right flank: a cas...

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Title:
Proton therapy versus photon radiation therapy for the management of a recurrent desmoid tumor of the right flank: a case report
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English
Creator:
Kil, Whoon Jong
Nichols Jr., R Charles
Kilkenny, John W.
Huh, Soon Y.
Ho, Meng Wei
Gupta, Pratibha
Marcus, Robert B.
Indelicato, Daniel J.
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Abstract:
Desmoid tumors are benign mesenchymal tumors with a strong tendency for local recurrence after surgery. Radiotherapy improves local control following incomplete resection, but nearby organs at risk may limit the dose to the target volume. The patient in this report presented with a recurrent desmoid tumor of the right flank and underwent surgery with microscopically positive margins. Particular problems presented in this case included that the tumor bed was situated in close proximity to the liver and the right kidney and that the right kidney was responsible for 65% of the patient’s renal function. Intensity-modulated radiation therapy plans delivering 54 Gy necessarily exposed the right kidney to a V18 of 98% and the liver to a V30 of 55%. Proton therapy plans significantly reduced the right kidney V18 to 32% and the liver V30 to 28%. In light of this, the proton plan was utilized for treatment of this patient. Proton therapy was tolerated without gastrointestinal discomfort or other complaints. Twenty-four months after initiation of proton therapy, the patient is without clinical or radiographic evidence of disease recurrence. In this setting, the improved dose distribution associated with proton therapy allowed for curative treatment of a patient who arguably could not have been safely treated with intensity-modulated radiation therapy or other methods of conventional radiotherapy. Keywords: Proton therapy, Intensity-modulated radiotherapy, Benign tumors, Case report
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Publication of this article was funded in part by the University of Florida Open-Access publishing Fund. In addition, requestors receiving funding through the UFOAP project are expected to submit a post-review, final draft of the article to UF's institutional repository, IR@UF, (www.uflib.ufl.edu/UFir) at the time of funding. The institutional Repository at the University of Florida community, with research, news, outreach, and educational materials.
General Note:
Kil et al. Radiation Oncology 2012, 7:178 http://www.ro-journal.com/content/7/1/178; Pages 1-6
General Note:
doi:10.1186/1748-717X-7-178 Cite this article as: Kil et al.: Proton therapy versus photon radiation therapy for the management of a recurrent desmoid tumor of the right flank: a case report. Radiation Oncology 2012 7:178.

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au id A1 snm Kilmnm Jongfnm Whooninsr iid I1 email wkil@floridaproton.org
A2 ca yes NicholsCharlesRsuf Jrrnichols@floridaproton.org
A3 Kilkennymi WJohnI2 john.kilkenny@jax.ufl.edu
A4 HuhYSoonshuh@floridaproton.org
A5 HoWeiMengmho@floridaproton.org
A6 GuptaPratibhaI3 pratibha.gupta@jax.ufl.edu
A7 MarcusBRobertrmarcus@floridaproton.org
A8 IndelicatoJDanieldindelicato@floridaproton.org
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ins University of Florida Proton Therapy Institute, Jacksonville, FL, USA
Department of Surgery University of Florida Shands Hospital, Jacksonville, FL, USA
Department of Radiology University of Florida Shands Hospital, Jacksonville, FL, USA
source Radiation Oncology
issn 1748-717X
pubdate 2012
volume 7
issue 1
fpage 178
url http://www.ro-journal.com/content/7/1/178
xrefbib pubidlist pubid idtype doi 10.1186/1748-717X-7-178pmpid 23098082
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http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
kwdg
kwd Proton therapy
Intensity-modulated radiotherapy
Benign tumors
Case report
abs
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Abstract
Desmoid tumors are benign mesenchymal tumors with a strong tendency for local recurrence after surgery. Radiotherapy improves local control following incomplete resection, but nearby organs at risk may limit the dose to the target volume. The patient in this report presented with a recurrent desmoid tumor of the right flank and underwent surgery with microscopically positive margins. Particular problems presented in this case included that the tumor bed was situated in close proximity to the liver and the right kidney and that the right kidney was responsible for 65% of the patient’s renal function. Intensity-modulated radiation therapy plans delivering 54 Gy necessarily exposed the right kidney to a Vsub 18 of 98% and the liver to a V30 of 55%. Proton therapy plans significantly reduced the right kidney V18 to 32% and the liver V30 to 28%. In light of this, the proton plan was utilized for treatment of this patient. Proton therapy was tolerated without gastrointestinal discomfort or other complaints. Twenty-four months after initiation of proton therapy, the patient is without clinical or radiographic evidence of disease recurrence. In this setting, the improved dose distribution associated with proton therapy allowed for curative treatment of a patient who arguably could not have been safely treated with intensity-modulated radiation therapy or other methods of conventional radiotherapy.
bdy
Background
Desmoid tumor (DT) is a deep-seated fibroblastic neoplasm that arises from musculoaponeurotic stromal tissue. It exhibits slow growth with a strong tendency for local recurrence (LR) and a low metastatic potential. DTs can arise anywhere in the body, but commonly occur in the proximal extremities, trunk, and abdominal wall. Surgery remains the primary treatment for DT with a goal of gross total resection with wide surgical margins. Because of the infiltrative growth pattern of DT, surgical resection alone is associated with a significant LR rate of 24% to 77%
abbrgrp
abbr bid B1 1
B2 2
B3 3
. Several studies have suggested lower LR rates when adjuvant radiation therapy (RT) is employed
B4 4
B5 5
B6 6
. Previously, our institution reported improved local-regional control in patients with DT receiving a total radiation dose ≥ 55 Gy after surgical resection
B7 7
. While delivering doses in the range of 55 Gy to extremity lesions can be achieved with 3-dimensioanl conformal RT (3DCRT) or intensity-modulated RT (IMRT) using x-rays since the targets are generally located away from critical radiosensitive tissues delivering such doses to truncal targets is more difficult due to the proximity of highly radiosensitive organs, such as the lungs, spinal cord, intestines, liver and kidneys.
Proton therapy (PT) has the potential to improve the therapeutic index in such a setting compared to conventional x-ray-based therapy. While x-rays pass through the patient and leave a track of exposure from the entrance surface to the exit surface of the patient, protons (which are particles with mass) can be accelerated to penetrate into tissue only to the depth of the target. When patients are treated with proton-based radiotherapy most of the radiation energy is discharged at a discrete and predictable depth called the Bragg peak. A "spread-out Bragg peak" can be created to match the exact depth and thickness of the target. The case we present here demonstrates a situation where the improved therapeutic index associated with PT allowed for the potentially curative treatment of a patient who arguably could not have been safely treated with x-rays.
Case presentation
A 36-year-old white female self-detected a mass in the right flank. Magnetic resonance imaging (MRI) demonstrated a 7.3 × 4-cm lobulated mass along the right posterior-lateral abdominal wall at the level of the right kidney (Figure 
figr fid F1 1A). Incisional biopsy was performed followed by surgical resection. Final resection margins were microscopically negative. Postoperative MRI of the abdomen demonstrated no residual mass in the right flank (Figure 
1B). No adjuvant treatment was recommended.
fig Figure 1caption Serial magnetic resonance imaging (MRI) scanstext
b Serial magnetic resonance imaging (MRI) scans. (A) Taken at the initial diagnosis. The red arrow indicates 7.3 × 4-cm mass on the right posterior-lateral abdominal wall at the level of the flank and right kidney. (B) Taken after the initial surgery, showing no evidence of disease. (C) Taken 12 months after the initial surgery. The red arrow indicates 6.5 × 2.8-cm recurrent mass on the previous surgical bed. (D) Taken at 24 months after completing proton therapy. No evidence of re-recurrence of the tumor.
graphic file 1748-717X-7-178-1
Approximately 12 months after the surgical resection, the patient noticed a palpable lump in the surgical bed. MRI of the abdomen revealed a 6.5 × 2.8-cm mass involving the right flank with an associated abdominal wall hernia (Figure 
1C). Salvage surgery was performed to remove the recurrent mass and repair the hernia. Final histopathology again revealed a benign DT. The microscopic surgical margin was focally positive. The patient’s case was presented at a multidisciplinary tumor board with the recommendation that she receive adjuvant radiotherapy based on the tumor’s recurrent nature and the presence of positive margins.
At her initial radiation oncology consultation, the patient demonstrated a long, horizontal incision in the right posterolateral aspect of the abdominal wall that was healing. No suspicious palpable abnormality was appreciated. Given the proximity of the tumor bed to the right kidney, split renal function studies were ordered. Laboratory data showed that blood urea nitrogen and creatinine levels to be within normal ranges (8.0 mg/dL and 0.49 mg/dL, respectively) as well as a glomerular filtration rate of > 60 mL per minute. A nuclear renal scan using Tc-99m MAG3 demonstrated decreased flow and uptake within the left kidney compared to the right kidney (Figure 
F2 2). The right kidney was the dominant kidney, comprising 65% of the patient’s renal function. The risks and benefits of adjuvant external-beam RT in this context were discussed with the patient who elected to pursue adjuvant radiotherapy.
Figure 2A nuclear renal scan after intravenous injection of 11.085 mCi of Tc-99m MAG3
A nuclear renal scan after intravenous injection of 11.085 mCi of Tc-99m MAG3. There is decreased flow and uptake within the left kidney compared to the right. Differential renal function is 35% for the left kidney and 65% for the right kidney. There is prompt bilateral excretion with a transit time of three minutes. No evidence of obstruction.
1748-717X-7-178-2
For the RT, an optimized IMRT plan was generated to deliver a dose of 54 Gy (1.8 Gy per fraction) to the tumor bed (Figure 
F3 3A). The planning target volume (PTV) consisted of the initial tumor bed plus the recurrent tumor bed with an approximately 6-cm margin on the abdominal wall (but not extending into the abdominal cavity). Ninety-five percent of the PTV volume received 100% of the prescribed target dose and 100% of the PTV volume received 95% of the target dose. Normal-tissue goals of particular interest were as follows: right kidney V18 (volume receiving ≥ 18 Gy) to < 70%; left kidney V18 to < 30%; liver V30 Gy to < 50%; and spinal cord maximum to < 46 Gy. IMRT plans delivering 54 Gy to the PTV, however, necessarily exposed the 98% of the right kidney to ≥ 18 Gy and 55% of the liver to ≥ 30 Gy. Minimizing the right kidney dose was necessarily prioritized because the right kidney was the dominant kidney and responsible for 65% of the patient’s renal function.
Figure 3Colorwash comparisons of the intensity-modulated radiotherapy (IMRT) and proton plans to deliver 59.40 Gy or 598.40 Cobalt Gray Equivalent (CGE) to the planning target volume (PTV)
Colorwash comparisons of the intensity-modulated radiotherapy (IMRT) and proton plans to deliver 59.40 Gy or 59.40 Cobalt Gray Equivalent (CGE) to the planning target volume (PTV). Dose-volume histograms (DVH) for these plans are shown in Figure 
F4 4.
1748-717X-7-178-3
To deliver a high dose of radiation to the PTV without compromising the function of the right kidney, PT plans were then generated. The clinical target volume (CTV) and PTV were identical. The proton plan utilized two fields that included posterior-anterior and right posterior-oblique fields. The CTV and PTV coverages were identical. Dose was prescribed in cobalt Gy equivalent (CGE) by use of a relative biological effectiveness of 1.1. The proton plan reduced the right kidney V18 to 32% and the liver V30 to 28% without adversely affecting other critical organs or compromising target coverage (Figure 
3B). Additional benefits from the PT plan compared to the photon IMRT plan included sparing the left kidney from any radiation exposure and lowering the integral dose to the body. In light of these advantages, the PT plan was recommended.
The initial PT plan was to deliver 54 CGE (1.8 CGE per fraction) to the PTV. The patient, however, had a family emergency, resulting in a 2-week treatment delay after delivery of 5.4 CGE. Therefore, the final PTV dose was increased to 59.4 CGE over 33 fractions. Normal-tissue exposures for the PT plan compared to the photon IMRT plan were as follows (with hypothetical optimized IMRT exposures in parentheses): mean liver dose, 17.6 CGE (versus 36.1 Gy); mean right kidney dose, 18.9 CGE (versus 38.8 Gy); mean spinal cord dose, 0.1 CGE (versus 18.9 Gy) (Figure 
4). The integral dose to the body was lower with protons, particularly in the low dose range, with greater than a 5-fold reduction in the volume of uninvolved normal tissues receiving a dose of 10 Gy (Figure 
F5 5).
Figure 4Dose-volume histogram (DVH) data for the proton plan (delivered) and the corresponding optimized intensity-modulated radiotherapy (IMRT) plan shown in Figure 3
Dose-volume histogram (DVH) data for the proton plan (delivered) and the corresponding optimized intensity-modulated radiotherapy (IMRT) plan shown in Figure3. The planning target volume (PTV) dose was 59.40 Gy for the IMRT plan and 59.40 CGE for the proton plan. Normal-tissue exposures for the proton plan were 32% for the right kidney V18 CGE and 28% for the liver V30 CGE 28%. Normal-tissue exposures for the IMRT plan were 98% for the right kidney V18 Gy and 55% for the liver V30 Gy.
1748-717X-7-178-4
Figure 5DVH demonstrates reduced total body dose with protons, notably in the low-dose range
DVH demonstrates reduced total body dose with protons, notably in the low-dose range.
1748-717X-7-178-5
The patient tolerated the treatment uneventfully without nausea or other gastrointestinal discomfort. Her only measurable toxicity was grade 1 skin erythema without desquamation in the treated field. Her blood urea nitrogen and creatinine levels were 10.0 mg/dL and 0.7 mg/dL, respectively, with a glomerular filtration rate of greater than 101.2 mL per minute at the completion of PT. Her most recent physical examination 24 months after treatment demonstrates no palpable mass and no skin toxicity. She is without any gastrointestinal toxicity and is working full-time. MRI of the abdomen at 24 months after initiation of PT demonstrates no evidence of recurrent disease (Figure 
1D).
Discussion
DTs are benign tumors with locally aggressive growth and a high rate of recurrence after surgical resection. Adjuvant postoperative RT is regularly utilized at our institution to reduce recurrence risk. A previous study published by the University of Florida evaluating the local-regional control of DTs in an adult cohort showed a 5-year local-regional control rate of 83%
7
. Proton therapy has been demonstrated to reduce gastrointestinal exposure compared to photon-based radiotherapy in the treatment of abdominal malignancies
B8 8
B9 9
. The same principles described in the aforementioned studies allowed for significant normal-tissue sparing in this case. In addition to allowing for the delivery of a radiation dose adequate to secure disease control while avoiding renal and gastrointestinal toxicity, PT also was associated with a significant reduction in total-body radiation exposure compared to the exposure associated with IMRT. Since the correlation between radiation exposure and radiation-induced second malignancies is well established
B10 10
B11 11
B12 12
B13 13
B14 14
B15 15
B16 16
B17 17
B18 18
B19 19
B20 20
B21 21
, and a survival time of 10 years or longer is not uncommon for patients with DTs, reducing the body volume receiving low-dose radiation may be of particular importance in patients for whom a high rate of disease control and long-term survival is expected.
Conclusion
Proton therepy in this case allowed for the delivery of a radiation dose adequate to achieve local control without exposing the patient to renal or gastrointestinal toxicity. Our pretreatment dosimetry indicated that such a favorable outcome could not have been achieved with IMRT. PT in this case was also associated with a lower integral total body dose than would have been associated with IMRT. The latter finding might be particularly relevant in reducing the risk of late iatrogenic malignancy in a young patient.
Consent
Written informed consent was obtained from the patient for publication in this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.
Abbreviations
OARs: Organs at risk; CGE: Cobalt Gray equivalent; CTV: Clinical target volume; DT: Desmoid tumor; Gy: Gray; IMRT: Intensity-modulated radiation therapy; MRI: Magnetic resonance imaging; PT: Proton therapy; RT: Radiation therapy; V18: Target or organ volume receiving ≥ 18 Gy; V30: Target or organ volume receiving ≥ 30 Gy; V4: Target or organ volume receiving ≥ 4 Gy.
Competing interests
The authors declare that they have no competing interests.
Authors’ contributions
WJK analyzed the treatments and drafted the manuscript. RCN planned and analyzed the treatments and contributed to the final draft of the manuscript. JWK performed the surgeries and contributed to the final draft of the manuscript. SYH planned the treatments, assisted with analysis, and contributed to the manuscript. MWH planned the treatments, assisted with analysis, and contributed to the manuscript. PG reviewed the imaging and contributed to the manuscript. RBM assisted with planning and analyzing the treatments and contributed to the manuscript. DJI assisted with planning and analyzing the treatments and contributed to the manuscript. All authors read and approved the final manuscript.
bm
ack
Acknowledgements
We would like to thank Jessica Kirwan and the editorial staff at the University of Florida Department of Radiation Oncology for helping edit and prepare the manuscript for publication.
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Desmoid tumors are benign mesenchymal tumors with a strong tendency for local recurrence after surgery. Radiotherapy improves local control following incomplete resection, but nearby organs at risk may limit the dose to the target volume. The patient in this report presented with a recurrent desmoid tumor of the right flank and underwent surgery with microscopically positive margins. Particular problems presented in this case included that the tumor bed was situated in close proximity to the liver and the right kidney and that the right kidney was responsible for 65% of the patient’s renal function. Intensity-modulated radiation therapy plans delivering 54 Gy necessarily exposed the right kidney to a V18 of 98% and the liver to a V30 of 55%. Proton therapy plans significantly reduced the right kidney V18 to 32% and the liver V30 to 28%. In light of this, the proton plan was utilized for treatment of this patient. Proton therapy was tolerated without gastrointestinal discomfort or other complaints. Twenty-four months after initiation of proton therapy, the patient is without clinical or radiographic evidence of disease recurrence. In this setting, the improved dose distribution associated with proton therapy allowed for curative treatment of a patient who arguably could not have been safely treated with intensity-modulated radiation therapy or other methods of conventional radiotherapy.
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CASEREPORTOpenAccessProtontherapyversusphotonradiationtherapy forthemanagementofarecurrentdesmoid tumoroftherightflank:acasereportWhoonJongKil1,RCharlesNicholsJr1*,JohnWKilkenny2,SoonYHuh1,MengWeiHo1,PratibhaGupta3, RobertBMarcus1andDanielJIndelicato1AbstractDesmoidtumorsarebenignmesenchymaltumorswithastrongtendencyforlocalrecurrenceaftersurgery. Radiotherapyimproveslocalcontrolfollowingincompleteresection,butnearbyorgansatriskmaylimitthedoseto thetargetvolume.Thepatientinthisreportpresentedwitharecurrentdesmoidtumoroftherightflankand underwentsurgerywithmicroscopicallypositivemargins.Particularproblemspresentedinthiscaseincludedthat thetumorbedwassituatedincloseproximitytotheliverandtherightkidneyandthattherightkidneywas responsiblefor65%ofthepatient ’ srenalfunction.Intensity-modulatedradiationtherapyplansdelivering54Gy necessarilyexposedtherightkidneytoaV18of98%andthelivertoaV30of55%.Protontherapyplanssignificantly reducedtherightkidneyV18to32%andtheliverV30to28%.Inlightofthis,theprotonplanwasutilizedfor treatmentofthispatient.Protontherapywastoleratedwithoutgastrointestinaldiscomfortorothercomplaints. Twenty-fourmonthsafterinitiationofprotontherapy,thepatientiswithoutclinicalorradiographicevidenceof diseaserecurrence.Inthissetting,theimproveddosedistributionassociatedwithprotontherapyallowedfor curativetreatmentofapatientwhoarguablycouldnothavebeensafelytreatedwithintensity-modulatedradiation therapyorothermethodsofconventionalradiotherapy. Keywords: Protontherapy,Intensity-modulatedradiotherapy,Benigntumors,CasereportBackgroundDesmoidtumor(DT)isadeep-seatedfibroblasticneoplasmthatarisesfrommusculoaponeuroticstromaltissue.Itexhibitsslowgrowthwithastrongtendencyfor localrecurrence(LR)andalowmetastaticpotential.DTs canariseanywhereinthebody,butcommonlyoccurin theproximalextremities,trunk,andabdominalwall.SurgeryremainstheprimarytreatmentforDTwithagoalof grosstotalresectionwithwidesurgicalmargins.Because oftheinfiltrativegrowthpatternofDT,surgicalresection aloneisassociatedwithasignificantLRrateof24%to 77%[1-3].SeveralstudieshavesuggestedlowerLRrates whenadjuvantradiationtherapy(RT)isemployed[4-6]. Previously,ourinstitutionreportedimprovedlocalregionalcontrolinpatientswithDTreceivingatotal radiationdose 55Gyaftersurgicalresection[7].While deliveringdosesintherangeof55Gytoextremitylesions canbeachievedwith3-dimensioanlconformalRT (3DCRT)orintensity-modulatedRT(IMRT)usingx-rays -sincethetargetsaregenerallylocatedawayfromcritical radiosensitivetissues-deliveringsuchdosestotruncal targetsismoredifficultduetotheproximityofhighly radiosensitiveorgans,suchasthelungs,spinalcord, intestines,liverandkidneys. Protontherapy(PT)hasthepotentialtoimprovethe therapeuticindexinsuchasettingcomparedtoconventionalx-ray-basedtherapy.Whilex-rayspassthrough thepatientandleaveatrackofexposurefromtheentrancesurfacetotheexitsurfaceofthepatient,protons (whichareparticleswithmass)canbeacceleratedto penetrateintotissueonlytothedepthofthetarget. Whenpatientsaretreatedwithproton-basedradiotherapymostoftheradiationenergyisdischargedata discreteandpredictabledepthcalledtheBraggpeak.A "spread-outBraggpeak"canbecreatedtomatchthe *Correspondence: rnichols@floridaproton.org1UniversityofFloridaProtonTherapyInstitute,Jacksonville,FL,USA Fulllistofauthorinformationisavailableattheendofthearticle 2012Kiletal.;licenseeBioMedCentralLtd.ThisisanOpenAccessarticledistributedunderthetermsoftheCreative CommonsAttributionLicense(http://creativecommons.org/licenses/by/2.0),whichpermitsunrestricteduse,distribution,and reproductioninanymedium,providedtheoriginalworkisproperlycited.Kil etal.RadiationOncology 2012, 7 :178 http://www.ro-journal.com/content/7/1/178

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exactdepthandthicknessofthetarget.Thecasewe presentheredemonstratesasituationwherethe improvedtherapeuticindexassociatedwithPTallowed forthepotentiallycurativetreatmentofapatientwho arguablycouldnothavebeensafelytreatedwithx-rays.CasepresentationA36-year-oldwhitefemaleself-detectedamassin therightflank.Magneticresonanceimaging(MRI) demonstrateda7.34-cmlobulatedmassalongthe rightposterior-lateralabdominalwallatthelevelof therightkidney(Figure1A).Incisionalbiopsywasperformedfollowedbysurgicalresection.Finalresection marginsweremicroscopicallynegative.Postoperative MRIoftheabdomendemonstratednoresidualmassin therightflank(Figure1B).Noadjuvanttreatmentwas recommended. Approximately12monthsafterthesurgicalresection, thepatientnoticedapalpablelumpinthesurgicalbed. MRIoftheabdomenrevealeda6.52.8-cmmass involvingtherightflankwithanassociatedabdominal wallhernia(Figure1C).Salvagesurgerywasperformed toremovetherecurrentmassandrepairthehernia. FinalhistopathologyagainrevealedabenignDT.The microscopicsurgicalmarginwasfocallypositive.The patient ’ scasewaspresentedatamultidisciplinarytumor boardwiththerecommendationthatshereceive adjuvantradiotherapybasedonthetumor ’ srecurrent natureandthepresenceofpositivemargins. Atherinitialradiationoncologyconsultation,the patientdemonstratedalong,horizontalincisioninthe rightposterolateralaspectoftheabdominalwallthatwas healing.Nosuspiciouspalpableabnormalitywasappreciated.Giventheproximityofthetumorbedtotheright kidney,splitrenalfunctionstudieswereordered.Laboratorydatashowedthatbloodureanitrogenandcreatinine levelstobewithinnormalranges(8.0mg/dLand0.49 mg/dL,respectively)aswellasaglomerularfiltrationrate of>60mLperminute.AnuclearrenalscanusingTc99mMAG3demonstrateddecreasedflowanduptake withintheleftkidneycomparedtotherightkidney (Figure2).Therightkidneywasthedominantkidney, comprising65%ofthepatient ’ srenalfunction.Therisks andbenefitsofadjuvantexternal-beamRTinthiscontext werediscussedwiththepatientwhoelectedtopursue adjuvantradiotherapy. FortheRT,anoptimizedIMRTplanwasgeneratedto deliveradoseof54Gy(1.8Gyperfraction)tothe tumorbed(Figure3A).Theplanningtargetvolume (PTV)consistedoftheinitialtumorbedplustherecurrenttumorbedwithanapproximately6-cmmarginon theabdominalwall(butnotextendingintotheabdominalcavity).Ninety-fivepercentofthePTVvolume received100%oftheprescribedtargetdoseand100%of Figure1 Serialmagneticresonanceimaging(MRI)scans. ( A )Takenattheinitialdiagnosis.Theredarrowindicates7.34-cmmassonthe rightposterior-lateralabdominalwallattheleveloftheflankandrightkidney.( B )Takenaftertheinitialsurgery,showingnoevidenceofdisease. ( C )Taken12monthsaftertheinitialsurgery.Theredarrowindicates6.52.8-cmrecurrentmassontheprevioussurgicalbed.( D )Takenat24 monthsaftercompletingprotontherapy.Noevidenceofre-recurrenceofthetumor. Kil etal.RadiationOncology 2012, 7 :178 Page2of6 http://www.ro-journal.com/content/7/1/178

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Figure2 Anuclearrenalscanafterintravenousinjectionof11.085mCiofTc-99mMAG3. Thereisdecreasedflowanduptakewithinthe leftkidneycomparedtotheright.Differentialrenalfunctionis35%fortheleftkidneyand65%fortherightkidney.Thereispromptbilateral excretionwithatransittimeofthreeminutes.Noevidenceofobstruction. Figure3 Colorwashcomparisonsoftheintensity-modulatedradiotherapy(IMRT)andprotonplanstodeliver59.40Gyor59.40Cobalt GrayEquivalent(CGE)totheplanningtargetvolume(PTV). Dose-volumehistograms(DVH)fortheseplansareshowninFigure4. Kil etal.RadiationOncology 2012, 7 :178 Page3of6 http://www.ro-journal.com/content/7/1/178

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thePTVvolumereceived95%ofthetargetdose. Normal-tissuegoalsofparticularinterestwereasfollows: rightkidneyV18(volumereceiving 18Gy)to<70%; leftkidneyV18to<30%;liverV30Gyto<50%;and spinalcordmaximumto<46Gy.IMRTplansdelivering 54GytothePTV,however,necessarilyexposedthe98% oftherightkidneyto 18Gyand55%oftheliverto 30Gy.Minimizingtherightkidneydosewasnecessarilyprioritizedbecausetherightkidneywasthe dominantkidneyandresponsiblefor65%ofthe patient ’ srenalfunction. TodeliverahighdoseofradiationtothePTVwithout compromisingthefunctionoftherightkidney,PTplans werethengenerated.Theclinicaltargetvolume(CTV) andPTVwereidentical.Theprotonplanutilizedtwo fieldsthatincludedposterioranteriorandrightposteriorobliquefields.TheCTVandPTVcoverageswereidentical.DosewasprescribedincobaltGyequivalent (CGE)byuseofarelativebiologicaleffectivenessof1.1. TheprotonplanreducedtherightkidneyV18to32% andtheliverV30to28%withoutadverselyaffecting othercriticalorgansorcompromisingtargetcoverage (Figure3B).AdditionalbenefitsfromthePTplancomparedtothephotonIMRTplanincludedsparingthe leftkidneyfromanyradiati onexposureandlowering theintegraldosetothebody.Inlightoftheseadvantages,thePTplanwasrecommended. TheinitialPTplanwastodeliver54CGE(1.8CGE perfraction)tothePTV.Thepatient,however,hada familyemergency,resultingina2-weektreatmentdelay afterdeliveryof5.4CGE.Therefore,thefinalPTVdose wasincreasedto59.4CGEover33fractions.NormaltissueexposuresforthePTplancomparedtothe photonIMRTplanwereasfollows(withhypothetical optimizedIMRTexposuresinparentheses):meanliver dose,17.6CGE(versus36.1Gy);meanrightkidney dose,18.9CGE(versus38.8Gy);meanspinalcorddose, 0.1CGE(versus18.9Gy)(Figure4).Theintegraldose tothebodywaslowerwithprotons,particularlyinthe lowdoserange,withgreaterthana5-foldreductionin thevolumeofuninvolvednormaltissuesreceivinga doseof10Gy(Figure5). Figure4 Dose-volumehistogram(DVH)datafortheprotonplan(delivered)andthecorrespondingoptimizedintensity-modulated radiotherapy(IMRT)planshowninFigure3. Theplanningtargetvolume(PTV)dosewas59.40GyfortheIMRTplanand59.40CGEforthe protonplan.Normal-tissueexposuresfortheprotonplanwere32%fortherightkidneyV18CGEand28%fortheliverV30CGE28%.NormaltissueexposuresfortheIMRTplanwere98%fortherightkidneyV18Gyand55%fortheliverV30Gy. Kil etal.RadiationOncology 2012, 7 :178 Page4of6 http://www.ro-journal.com/content/7/1/178

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Thepatienttoleratedthetreatmentuneventfullywithoutnauseaorothergastrointestinaldiscomfort.Heronly measurabletoxicitywasgrade1skinerythemawithout desquamationinthetreatedfield.Herbloodureanitrogenandcreatininelevelswere10.0mg/dLand0.7mg/ dL,respectively,withaglomerularfiltrationrateof greaterthan101.2mLperminuteatthecompletionof PT.Hermostrecentphysicalexamination24months aftertreatmentdemonstratesnopalpablemassandno skintoxicity.Sheiswithoutanygastrointestinaltoxicity andisworkingfull-time.MRIoftheabdomenat24 monthsafterinitiationofPTdemonstratesnoevidence ofrecurrentdisease(Figure1D).DiscussionDTsarebenigntumorswithlocallyaggressivegrowth andahighrateofrecurrenceaftersurgicalresection. AdjuvantpostoperativeRTisregularlyutilizedatourinstitutiontoreducerecurrencerisk.Apreviousstudy publishedbytheUniversityofFloridaevaluatingthe local-regionalcontrolofDTsinanadultcohortshowed a5-yearlocal-regionalcontrolrateof83%[7].Proton therapyhasbeendemonstratedtoreducegastrointestinalexposurecomparedtophoton-basedradiotherapy inthetreatmentofabdominalmalignancies[8,9].The sameprinciplesdescribedintheaforementionedstudies allowedforsignificantnormal-tissuesparinginthiscase. Inadditiontoallowingforthedeliveryofaradiation doseadequatetosecurediseasecontrolwhileavoiding renalandgastrointestinaltoxicity,PTalsowasassociated withasignificantreductionintotal-bodyradiationexposurecomparedtotheexposureassociatedwithIMRT. Sincethecorrelationbetweenradiationexposureand radiation-inducedsecondmalignanciesiswellestablished[10-21],andasurvivaltimeof10yearsorlonger isnotuncommonforpatientswithDTs,reducingthe bodyvolumereceivinglow-doseradiationmaybeofparticularimportanceinpatientsforwhomahighrateof diseasecontrolandlong-termsurvivalisexpected.ConclusionProtontherepyinthiscaseallowedforthedeliveryofa radiationdoseadequatetoachievelocalcontrolwithout exposingthepatienttorenalorgastrointestinaltoxicity. OurpretreatmentdosimetryindicatedthatsuchafavorableoutcomecouldnothavebeenachievedwithIMRT. PTinthiscasewasalsoassociatedwithalowerintegral totalbodydosethanwouldhavebeenassociatedwith Figure5 DVHdemonstratesreducedtotalbodydosewithprotons,notablyinthelow-doserange. Kil etal.RadiationOncology 2012, 7 :178 Page5of6 http://www.ro-journal.com/content/7/1/178

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IMRT.Thelatterfindingmightbeparticularlyrelevant inreducingtheriskoflateiatrogenicmalignancyina youngpatient.ConsentWritteninformedconsentwasobtainedfromthepatient forpublicationinthiscasereportandanyaccompanying images.Acopyofthewrittenconsentisavailablefor reviewbytheEditor-in-Chiefofthisjournal.Abbreviations OARs:Organsatrisk;CGE:CobaltGrayequivalent;CTV:Clinicaltarget volume;DT:Desmoidtumor;Gy:Gray;IMRT:Intensity-modulatedradiation therapy;MRI:Magneticresonanceimaging;PT:Protontherapy;RT:Radiation therapy;V18:Targetororganvolumereceiving 18Gy;V30:Targetororgan volumereceiving 30Gy;V4:Targetororganvolumereceiving 4Gy. Competinginterests Theauthorsdeclarethattheyhavenocompetinginterests. Authors ’ contributions WJKanalyzedthetreatmentsanddraftedthemanuscript.RCNplannedand analyzedthetreatmentsandcontributedtothefinaldraftofthemanuscript. JWKperformedthesurgeriesandcontributedtothefinaldraftofthe manuscript.SYHplannedthetreatments,assistedwithanalysis,and contributedtothemanuscript.MWHplannedthetreatments,assistedwith analysis,andcontributedtothemanuscript.PGreviewedtheimagingand contributedtothemanuscript.RBMassistedwithplanningandanalyzing thetreatmentsandcontributedtothemanuscript.DJIassistedwith planningandanalyzingthetreatmentsandcontributedtothemanuscript. Allauthorsreadandapprovedthefinalmanuscript. Acknowledgements WewouldliketothankJessicaKirwanandtheeditorialstaffattheUniversity ofFloridaDepartmentofRadiationOncologyforhelpingeditandprepare themanuscriptforpublication. Authordetails1UniversityofFloridaProtonTherapyInstitute,Jacksonville,FL,USA.2DepartmentofSurgeryUniversityofFloridaShandsHospital,Jacksonville, FL,USA.3DepartmentofRadiologyUniversityofFloridaShandsHospital, Jacksonville,FL,USA. 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Submit your next manuscript to BioMed Central and take full advantage of: € Convenient online submission € Thorough peer review € No space constraints or color “gure charges € Immediate publication on acceptance € Inclusion in PubMed, CAS, Scopus and Google Scholar € Research which is freely available for redistribution Submit your manuscript at www.biomedcentral.com/submit Kil etal.RadiationOncology 2012, 7 :178 Page6of6 http://www.ro-journal.com/content/7/1/178