Proton therapy versus photon radiation therapy for the management of a recurrent desmoid tumor of the right flank: a case report
© Kil et al.; licensee BioMed Central Ltd. 2012
Received: 3 August 2012
Accepted: 19 October 2012
Published: 26 October 2012
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.
KeywordsProton therapy Intensity-modulated radiotherapy Benign tumors Case report
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%[1–3]. Several studies have suggested lower LR rates when adjuvant radiation therapy (RT) is employed[4–6]. Previously, our institution reported improved local-regional control in patients with DT receiving a total radiation dose ≥ 55 Gy after surgical resection. 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.
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.
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 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).
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%. Proton therapy has been demonstrated to reduce gastrointestinal exposure compared to photon-based radiotherapy in the treatment of abdominal malignancies[8, 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[10–21], 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.
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.
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.
Organs at risk
Cobalt Gray equivalent
Clinical target volume
Intensity-modulated radiation therapy
Magnetic resonance imaging
Target or organ volume receiving ≥ 18 Gy
Target or organ volume receiving ≥ 30 Gy
Target or organ volume receiving ≥ 4 Gy.
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.
- Ballo MT, Zagars GK, Pollack A, Pisters PW, Pollack RA: Desmoid tumor: prognostic factors and outcome after surgery, radiation therapy, or combined surgery and radiation therapy. J Clin Oncol 1999, 17: 158-167.PubMed
- Merchant NB, Lewis JJ, Woodruff JM, Leung DH, Brennan MF: Extremity and trunk desmoid tumors: a multifactorial analysis of outcome. Cancer 1999, 86: 2045-2052. 10.1002/(SICI)1097-0142(19991115)86:10<2045::AID-CNCR23>3.0.CO;2-FView ArticlePubMed
- Nuyttens JJ, Rust PF, Thomas CR Jr, 3rd Turrisi AT: Surgery versus radiation therapy for patients with aggressive fibromatosis or desmoid tumors: A comparative review of 22 articles. Cancer 2000, 88: 1517-1523. 10.1002/(SICI)1097-0142(20000401)88:7<1517::AID-CNCR3>3.0.CO;2-9View ArticlePubMed
- Zlotecki RA, Scarborough MT, Morris CG, Berrey BH, Lind DS, Enneking WF, Marcus RB Jr: External beam radiotherapy for primary and adjuvant management of aggressive fibromatosis. Int J Radiat Oncol Biol Phys 2002, 54: 177-181.View ArticlePubMed
- Kamath SS, Parsons JT, Marcus RB, Zlotecki RA, Scarborough MT: Radiotherapy for local control of aggressive fibromatosis. Int J Radiat Oncol Biol Phys 1996, 36: 325-328.View ArticlePubMed
- Guadagnolo BA, Zagars GK, Ballo MT: Long-term outcomes for desmoid tumors treated with radiation therapy. Int J Radiat Oncol Biol Phys 2008, 71: 441-447. 10.1016/j.ijrobp.2007.10.013View ArticlePubMed
- Rutenberg MS, Indelicato DJ, Knapik JA, Lagmay JP, Morris C, Zlotecki RA, Scarborough MT, Gibbs CP, Marcus RB: External-beam radiotherapy for pediatric and young adult desmoid tumors. Pediatr Blood Cancer 2011, 57: 435-442. 10.1002/pbc.22916View ArticlePubMed
- Nichols RC Jr, Huh SN, Prado KL, Yi BY, Sharma NK, Ho MW, Hoppe BS, Mendenhall NP, Li Z, Regine WF: Protons offer reduced normal-tissue exposure for patients receiving postoperative radiotherapy for resected pancreatic head cancer. Int J Radiat Oncol Biol Phys 2012,83(1):158-163. 10.1016/j.ijrobp.2011.05.045View ArticlePubMed
- Milby AB, Both S, Ingram M, Lin LL: Dosimetric comparison of combined intensity-modulated radiotherapy (IMRT) and proton therapy versus IMRT alone for pelvic and para-aortic radiotherapy in gynecologic malignancies. Int J Radiat Oncol Biol Phys 2012, 82: e477-e484. 10.1016/j.ijrobp.2011.07.012View ArticlePubMed
- Kry SF, Salehpour M, Followill DS, Stovall M, Kuban DA, White RA, Rosen II: The calculated risk of fatal secondary malignancies from intensity-modulated radiation therapy. Int J Radiat Oncol Biol Phys 2005, 62: 1195-1203. 10.1016/j.ijrobp.2005.03.053View ArticlePubMed
- Tukenova M, Guibout C, Oberlin O, Doyon F, Mousannif A, Haddy N, Guerin S, Pacquement H, Aouba A, Hawkins M, et al.: Role of cancer treatment in long-term overall and cardiovascular mortality after childhood cancer. J Clin Oncol 2010, 28: 1308-1315. 10.1200/JCO.2008.20.2267View ArticlePubMed
- Haddy N, Mousannif A, Tukenova M, Guibout C, Grill J, Dhermain F, Pacquement H, Oberlin O, El-Fayech C, Rubino C, et al.: Relationship between the brain radiation dose for the treatment of childhood cancer and the risk of long-term cerebrovascular mortality. Brain 2011, 134: 1362-1372. 10.1093/brain/awr071View ArticlePubMed
- Travis LB, Ng AK, Allan JM, Pui CH, Kennedy AR, Xu XG, Purdy JA, Applegate K, Yahalom J, Constine LS, et al.: Second malignant neoplasms and cardiovascular disease following radiotherapy. J Natl Cancer Inst 2012, 104: 357-370. 10.1093/jnci/djr533PubMed CentralView ArticlePubMed
- Hall EJ, Wuu CS: Radiation-induced second cancers: the impact of 3D-CRT and IMRT. Int J Radiat Oncol Biol Phys 2003, 56: 83-88. 10.1016/S0360-3016(03)00073-7View ArticlePubMed
- Dorr W, Herrmann T: Second primary tumors after radiotherapy for malignancies. Treatment-related parameters. Strahlenther Onkol 2002, 178: 357-362. 10.1007/s00066-002-0951-6View ArticlePubMed
- Boice JD Jr, Day NE, Andersen A, Brinton LA, Brown R, Choi NW, Clarke EA, Coleman MP, Curtis RE, Flannery JT, et al.: Second cancers following radiation treatment for cervical cancer. An international collaboration among cancer registries. J Natl Cancer Inst 1985, 74: 955-975.PubMed
- Book Non-Targeted and Delayed Effects of Exposure to Ionizing Radiation In Non-Targeted and Delayed Effects of Exposure to Ionizing Radiation. City: UNSCEAR; 2009.
- Xu XG, Bednarz B, Paganetti H: A review of dosimetry studies on external-beam radiation treatment with respect to second cancer induction. Phys Med Biol 2008, 53: R193-R241. 10.1088/0031-9155/53/13/R01PubMed CentralView ArticlePubMed
- Shore RE: Issues and epidemiological evidence regarding radiation-induced thyroid cancer. Radiat Res 1992, 131: 98-111. 10.2307/3578322View ArticlePubMed
- Followill D, Geis P, Boyer A: Estimates of whole-body dose equivalent produced by beam intensity modulated conformal therapy. Int J Radiat Oncol Biol Phys 1997, 38: 667-672. 10.1016/S0360-3016(97)00012-6View ArticlePubMed
- Brenner DJ, Curtis RE, Hall EJ, Ron E: Second malignancies in prostate carcinoma patients after radiotherapy compared with surgery. Cancer 2000, 88: 398-406. 10.1002/(SICI)1097-0142(20000115)88:2<398::AID-CNCR22>3.0.CO;2-VView ArticlePubMed
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.