IntroductionIntensity-modulated radiation therapy (IMRT) and proton beam therapy (PBT) are increasingly being employed to treat rectal cancer in the preoperative setting.1Reyngold M Niland J Ter Veer A Bekaii-Saab T Lai L Meyer JE Nurkin SJ Schrag D Skibber JM Benson AB Weiser MR Crane CH Goodman KA Trends in intensity modulated radiation therapy use for locally advanced rectal cancer at National Comprehensive Cancer Network centers.,2Proton beam radiotherapy for anal and rectal cancers. Although the Radiation Therapy Oncology Group (RTOG) trial 0822 did not demonstrate a benefit in toxicity profile to IMRT when compared to 3D conformal radiation therapy (3DCRT), the use of concurrent oxaliplatin on that trial may have masked the marginal benefit of IMRT.3Hong TS Moughan J Garofalo MC Bendell J Berger AC Oldenburg NB Anne PR Perera F Lee RJ Jabbour SK Nowlan A DeNittis A Crane C. NRG Oncology Radiation Therapy Oncology Group 0822: A Phase 2 Study of Preoperative Chemoradiation Therapy Using Intensity Modulated Radiation Therapy in Combination With Capecitabine and Oxaliplatin for Patients With Locally Advanced Rectal Cancer. Accordingly, increasingly conformal treatment with IMRT and even PBT may be appropriate when dose constraints, particularly the small bowel, cannot be met with 3DCRT. PBT also has a role in the setting of reirradiation and in treating younger patients4Berman AT Both S Sharkoski T Goldrath K Tochner Z Apisarnthanarax S Metz JM Plastaras JP. Proton Reirradiation of Recurrent Rectal Cancer: Dosimetric Comparison, Toxicities, and Preliminary Outcomes.,5Rectal cancer in young patients: incidence and outcome disparities.. In younger patients, the lower integral dose afforded by PBT may lead to a lower incidence of radiation-induced second malignancies, though this effect may be muted in part if using short-course irradiation.Rectal distention with air or fecal matter is a major concern with radiation therapy planning because it may cause positional changes in target volumes and affect the amount of normal tissue subject to irradiation. In prostate cancer, multiple studies have demonstrated an increased risk of biochemical failure in patients simulated with a distended rectum.6de Crevoisier R Tucker SL Dong L Mohan R Cheung R Cox JD Kuban DA. Increased risk of biochemical and local failure in patients with distended rectum on the planning CT for prostate cancer radiotherapy., 7Engels B Soete G Verellen D Storme G. Conformal arc radiotherapy for prostate cancer: increased biochemical failure in patients with distended rectum on the planning computed tomogram despite image guidance by implanted markers., 8Heemsbergen WD Hoogeman MS Witte MG Peeters ST Incrocci L Lebesque JV. Increased risk of biochemical and clinical failure for prostate patients with a large rectum at radiotherapy planning: results from the Dutch trial of 68 GY versus 78 Gy. Although rectal cancer patients are not typically treated with definitive irradiation as with prostate cancer, these studies underscore the fact that variations in rectal distension may be clinically meaningful. When treating rectal cancer with PBT, the penetration depth of the beam depends on the stopping powers of the various regions through which it passes.9SU-E-T-481: Dosimetric Effects of Tissue Heterogeneity in Proton Therapy: Monte Carlo Simulation and Experimental Study Using Animal Tissue Phantoms. Thus, tissue heterogeneity, such as rectal distension with air, has the potential to dramatically affect the distal range of the treatment beam, potentially compromising target coverage and delivering large amounts of dose into anterior normal tissues. As a result, the most appropriate proton beam arrangement to account for varying tissue homogeneity within the rectal contour is not well-defined.Historically, a single PA beam was employed in this setting, with the assumption that the rectal air content will “average out” with fractionation.10Tatsuzaki H Urie MM Willett CG. 3-D comparative study of proton vs. x-ray radiation therapy for rectal cancer. More recently, combinations of a posteroanterior (PA), opposed lateral, right posterior oblique (RPO), and/or left posterior oblique (LPO) beams have all been published.10Tatsuzaki H Urie MM Willett CG. 3-D comparative study of proton vs. x-ray radiation therapy for rectal cancer., 11Isacsson U Montelius A Jung B Glimelius B. Comparative treatment planning between proton and X-ray therapy in locally advanced rectal cancer., 12Colaco RJ Nichols RC Huh S Getman N Ho MW Li Z Morris CG Mendenhall WM Mendenhall NP Hoppe BS. Protons offer reduced bone marrow, small bowel, and urinary bladder exposure for patients receiving neoadjuvant radiotherapy for resectable rectal cancer., 13Wolff HA Wagner DM Conradi LC Hennies S Ghadimi M Hess CF Christiansen H. Irradiation with protons for the individualized treatment of patients with locally advanced rectal cancer: a planning study with clinical implications., 14Radu C Norrlid O Braendengen M Hansson K Isacsson U Glimelius B. Integrated peripheral boost in preoperative radiotherapy for the locally most advanced non-resectable rectal cancer patients. A University of Florida study compared 3DCRT, IMRT, and PBT neoadjuvant therapy plans using a PA and opposed lateral arrangement of uniform scanning/passive scattering beams and demonstrated improved small bowel, urinary bladder, and pelvic bone marrow dosimetry with PBT.12Colaco RJ Nichols RC Huh S Getman N Ho MW Li Z Morris CG Mendenhall WM Mendenhall NP Hoppe BS. Protons offer reduced bone marrow, small bowel, and urinary bladder exposure for patients receiving neoadjuvant radiotherapy for resectable rectal cancer. Another report employed PA, LPO, and RPO beams using spot scanning PBT/IMPT, similarly demonstrating improved dosimetry to the small bowel, testes, and urinary bladder in patients undergoing neoadjuvant therapy.13Wolff HA Wagner DM Conradi LC Hennies S Ghadimi M Hess CF Christiansen H. Irradiation with protons for the individualized treatment of patients with locally advanced rectal cancer: a planning study with clinical implications. Additional studies from Sweden and the Mayo Clinic utilized LPO/RPO beam arrangements and demonstrated dosimetric superiority with PBT.14Radu C Norrlid O Braendengen M Hansson K Isacsson U Glimelius B. Integrated peripheral boost in preoperative radiotherapy for the locally most advanced non-resectable rectal cancer patients.,15Jeans EB Jethwa KR Harmsen WS Neben-Wittich M Ashman JB Merrell KW Giffey B Ito S Kazemba B Beltran C Haddock MG Hallemeier CL. Clinical Implementation of Preoperative Short-Course Pencil Beam Scanning Proton Therapy for Patients With Rectal Cancer. While collectively these studies supported the use of PBT from a dosimetric standpoint, they all employed different field designs.

Given the heterogeneity with previous work, the present study was conceived to more comprehensively explore the optimal beam arrangement in the treatment of rectal cancer with PBT by accounting for variations in intestinal dilation. Using pencil beam scanning technique, we simulated and compared proton beam arrangements for a wide variety of intestinal gas scenarios to determine which proton beam arrangement would be the most robust. We hypothesized that a single PA beam would be ill-advised and that an RPO/LPO arrangement would provide comparable coverage to 3-beam (PA and opposed laterals) or 5-beam (PA, RPO, LPO, and opposed laterals) arrangements.

Methods and Materials

A rectal cancer patient with a clinical stage IIIB (cT3, cN1b, cM0) moderately differentiated adenocarcinoma without anatomical variants or artificial hardware was selected for plan optimization and evaluation. The patient's lesion was 6 cm from the external anal verge. The patient underwent three-dimensional computed tomography (CT) simulation with a helical CT scanner (Brilliance Big Bore, Philips Healthcare System, Cleveland, OH). An alpha cradle was used for simulation in the supine position. Intravenous iodinated contrast was used for accurate delineation of the nodal basins, though a non-contrast CT was used for proton treatment planning.

Contouring of the target volumes was per Radiation Therapy Oncology Group (RTOG) atlas guidelines.16Myerson RJ Garofalo MC El Naqa I Abrams RA Apte A Bosch WR Das P Gunderson LL Hong TS Kim JJ Willett CG Kachnic LA. Elective clinical target volumes for conformal therapy in anorectal cancer: a radiation therapy oncology group consensus panel contouring atlas. The primary gross tumor volume (GTV-P) encompassed the gross disease by physical examination, colonoscopy report, and magnetic resonance imaging (MRI) of the pelvis. The nodal gross tumor volume (GTV-N) encompassed any positive lymph nodes by MRI pelvis or diagnostic CT scan. The high-risk clinical target volume (CTV-HR) included the GTV with a 2 cm superior and inferior margin, as well as the mesorectum and presacral space at involved levels. The standard-risk CTV (CTV-SR) included the CTV-HR, the presacral space, obturator lymph nodes, internal iliac lymph nodes, entire mesorectum, and rectum. The CTV-SR was prescribed 45 Gray equivalents (GyE) in 25 fractions with the CTV-HR receiving 50 GyE via a simultaneous integrated boost (SIB). The entire rectum was contoured and observed to have a maximal diameter of approximately 2 cm in short axis. To simulate rectal contraction, the rectal contour was isotropically reduced in size by 0.5 cm to generate a contour with a maximal diameter of approximately 1 cm. The rectal contour was then isotropically expanded in size by 0.5 cm, 1 cm, and 1.5 cm to generate contours with diameters of 3 cm, 4 cm, and 5 cm, respectively. Care was taken so that the artificial contours did not extend into rigid structures, such as the piriformis muscle or bone. The contours also did not extend into the ischiorectal fossa or otherwise outside the mesorectum. Normal structures were contoured as per RTOG guidelines.17Gay HA Barthold HJ O'Meara E Bosch WR El Naqa I Al-Lozi R Rosenthal SA Lawton C Lee WR Sandler H Zietman A Myerson R Dawson LA Willett C Kachnic LA Jhingran A Portelance L Ryu J Small Jr., W Gaffney D Viswanathan AN Michalski JM Pelvic normal tissue contouring guidelines for radiation therapy: a Radiation Therapy Oncology Group consensus panel atlas. Of note, individual loops of small bowel were contoured as opposed to a bowel bag. The internal genitalia contour comprised of the penile bulb and the base of the penis, with all else denoted external genitalia. All contours were completed by a physician specializing in gastrointestinal radiation oncology.Single field uniform dose (SFUD) plan was generated if single beam was used. Multi-field uniform dose (MFUD) plans using SFUD technique were generated otherwise, based on pencil beam scanning (PBS) technique. Multifield optimization (MFO) was avoided due to lack of robustness to anatomical uncertainties. Planning was completed with RayStation version 6 (RaySearch Laboratories AB, Stockholm, Sweden). Monte Carlo dose calculations were performed with robust optimization parameters: 3.5% for range uncertainty and 5 mm isotropically for setup uncertainties. All evaluations in this analysis were done with nominal planning. To improve plan robustness, intestinal air was overridden as water to create a “overshooting at worst-case scenario” condition in the planning CT scan. Clinical goals and dose constraints were institutional but based on RTOG 0822 (Table 1). Plans were optimized such that the volume receiving 100% of the prescribed dose (V100%) > 97% for CTVs. For plan evaluation, V100%o) and left posterior oblique (LPO, 220o), (c) PA and opposed lateral beams, and (d) PA, RPO, LPO, and opposed lateral beams. For multibeam plans, the extent of beam overlap was minimized to reduce possible skin toxicity. To assess how an overdistended rectum could perturb dose distribution, the plans were then evaluated on the 1 cm, 2 cm, 3 cm, 4 cm, and 5 cm rectal contours assigning air medium to the rectal contour. Thus, there were a total of 20 plan evaluations for the above different setups. Subsequently, plans were generated and optimized for all four beam arrangements based on a 5 cm rectal contour. Evaluations were then run on 4 cm, 3 cm, 2 cm, and 1 cm rectal contours with air medium as well as the planning CT scan to assess the effect of an under-distended rectum on the dose distribution. This afforded an additional 20 plan evaluations for the different beam setups. Finally, plans were optimized based on the 4 cm and 3 cm rectal contours and then run on the other rectal contours as well as the planning CT for the 2- and 3-beam arrangements. This generated an additional 20 plan evaluations. In total, 60 plan evaluations were run and evaluated. Dosimetric parameters for the target volumes, small bowel, bladder, external genitalia, internal genitalia, and femoral heads were evaluated and compared.

Table 1Institutional clinical goals/dose constraints based on RTOG 0822.

Abbreviations: CTV45, clinical target volume prescribed 45 GyE; CTV50, clinical target volume prescribed 50 GyE.

ResultsDosimetric parameters are presented in Table 2 for the plans optimized to the planning CT scan and then evaluated based on rectal diameters of 1 cm, 2 cm, 3 cm, 4 cm, and 5 cm for each of the 4 beam arrangements. In addition, the percentage volume receiving 30 Gy (V30Gy) and V20Gy were evaluated for external genitalia and V45Gy, V40Gy, and V30Gy were evaluated for the femoral heads for each of the plan evaluations. In all cases, these values were less than 2% and so are not displayed for conciseness. With a single PA beam arrangement, V100% > 90% to the CTV-HR prescribed 50 Gy (CTV50Gy) was lost with a relatively small rectal distension of ≥3 cm (for 3 cm, V100% = 88.8%). In addition, dose constraints to the bladder (V30Gy40Gy30Gy = 61.4% and V40Gy = 50.4%) and to the internal genitalia with ≥2 cm (V30Gy). The 2-beam, 3-beam, and 5-beam arrangements maintained CTV50Gy V100% > 95% even with 5 cm rectal distension. Relative to the 2-beam arrangement, the 3-beam and 5-beam arrangements had modest increases in small bowel parameters which exceeded dose constraints. In particular, for small bowel the 3-beam and 5-beam arrangements had V40Gy > 70 cm3, whereas the 2-beam arrangement had V40Gy3. Despite the opposed lateral configuration included in the 3-beam and 5-beam arrangements, dose constraints to the femoral heads were not exceeded. Figure 1 represents representative slices of plans for (A) 1-beam, (B) 2-beam, (C) 3-beam, and (D) 5-beam arrangements based on the planning CT (above) and with maximal rectal distension to 5 cm (below), demonstrating the characteristic altered dose distributions with increased air medium with a single PA beam arrangement. On the other hand, differences in the target coverage between 2-beam, 3-beam, and 5-beam arrangements are not overt when looking at this dose distribution.

Table 2Dosimetric parameters for the 4 beam arrangements optimized to the planning CT and iterated across rectal diameter sizes.

Values highlighted in red did not meet institutional dose constraints.

Abbreviations: CTV45, clinical target volume prescribed 45 GyE; CTV50, clinical target volume prescribed 50 GyE; PA, posteroanterior; RPO, right posterior oblique; LPO, left posterior oblique.

Figure 1Plan comparison for (A) PA field arrangement, (B) RPO/LPO, (C) PA/opposed lateral, and (D) RPO/LPO/PA/opposed lateral on plan CT (above) and with 5 cm rectal distension (below). With PA field arrangement, there was high-dose region extending anteriorly to bladder with maximal rectal distension. On the other hand, with maximal rectal distension target coverage perturbations in dose distributions were much more modest for the other beam arrangements.

Next, plans were generated and optimized to the rectal contour of 5 cm and were then evaluated based on rectal diameters of 4 cm, 3 cm, 2 cm, 1 cm, and planning CT for each of the 4 beam arrangements (Table 3). Again, all external genitalia and femoral head values did not approach institutional constraints and are not included in the table. In addition, there were minor violations of V40Gy to the small bowel for the 3-beam and 5-beam arrangements (77.2% and 77.1%, respectively). With rectal contraction to 3 cm, V100% >90% was lost to the CTV50Gy for the 1-beam (87.5%), 3-beam (84.8%), and 5-beam arrangements (85.7%), but upheld for the 2-beam arrangement (94.2%). Nonetheless, with further rectal contraction to 2 cm, V100% > 90% to the CTV50Gy was lost for the 2-beam arrangement as well (81.3%).

Table 3Dosimetric parameters for the 4 beam arrangements optimized to the 5 cm rectal diameter and iterated across rectal diameter sizes including plan CT.

Values highlighted in red did not meet institutional dose constraints.

Abbreviations: CTV45, clinical target volume prescribed 45 GyE; CTV50, clinical target volume prescribed 50 GyE; PA, posteroanterior; RPO, right posterior oblique; LPO, left posterior oblique.

Finally, plans optimized to the rectal contours of 4 cm and 3 cm were then evaluated based on all other rectal diameters and the planning CT for the 2-beam and 3-beam arrangements (Table 4). This evaluation was completed based on the observation that with the plans optimized based on a 5 cm contour, plan degradation was observed with modest rectal contraction. With the 4 cm plans, V100% > 90% to the CTV50Gy was met for the 2-beam arrangement with rectal contraction to 2 cm (92.4%), whereas it was 89.4% for the 3-beam arrangement. With the 3 cm plans, V100% > 90% was met with both the 2-beam and 3-beam arrangements with rectal contraction all the way to 1 cm (93.1% and 91.6%, respectively), simulating a patient with no rectal gas.

Table 4Dosimetric parameters for the 2 and 3 beam arrangements optimized to the 4 cm rectal diameter and 3 cm rectal diameter iterated across rectal diameter sizes including plan CT.

Values highlighted in red did not meet institutional dose constraints.

Abbreviations: CTV45, clinical target volume prescribed 45 GyE; CTV50, clinical target volume prescribed 50 GyE; PA, posteroanterior; RPO, right posterior oblique; LPO, left posterior oblique.

Discussion

To our knowledge, this is the first study evaluating the optimal proton therapy field design in the treatment of patients with rectal cancer. Based on a total of 60 plan evaluations, our analysis suggests that a single PA beam arrangement should be avoided. In addition, both RPO/LPO and PA/opposed lateral beam arrangements appear to be reasonable choices, though the RPO/LPO approach intuitively offers less integral dose and avoids beams that traverse the femoral heads. The addition of RPO/LPO beams to the PA/opposed lateral arrangement does not appear to afford any marginal benefit and is not indicated. Finally, patients with maximal rectal diameter in short axis >3 cm on planning CT should either be re-simulated or noninvasive measures to reduce intestinal gas should be pursued prior to treatment based on the possibility of rectal contraction severely compromising target coverage with subsequent treatments. Non-invasive gas-reducing measures may include prophylactic bowel regimen, daily enema, or rectal catheters.

Previous preclinical planning studies evaluating the dosimetric benefits of proton beam therapy in patients with rectal cancer have generally acknowledged but not accounted for perturbations in intestinal gas. Colaco et al. compared plans generated with 3DCRT, IMRT, and PBT in 8 patients undergoing preoperative therapy.12Colaco RJ Nichols RC Huh S Getman N Ho MW Li Z Morris CG Mendenhall WM Mendenhall NP Hoppe BS. Protons offer reduced bone marrow, small bowel, and urinary bladder exposure for patients receiving neoadjuvant radiotherapy for resectable rectal cancer. PBT plans were generated with uniform scanning/passive scattering and a 3-beam arrangement of PA and opposed lateral beams, with heavier weight of the PA beam (3.1 to 1). To account for rectal distension with air, the Hounsfield units were overridden for the air-filled portion of the rectum. Wolff et al. generated proton, RapidArc, IMRT, and 3DCRT plans for 25 consecutive patients undergoing preoperative treatment, using spot scanning protons in a 3-beam arrangement with PA, RPO (135o), and LPO (225o) beams but did not mention accounting for intestinal gas.13Wolff HA Wagner DM Conradi LC Hennies S Ghadimi M Hess CF Christiansen H. Irradiation with protons for the individualized treatment of patients with locally advanced rectal cancer: a planning study with clinical implications. Radu et al. compared IMRT and PBT in patients with locally advanced (cT4a), unresectable rectal cancer, with SIBs to 62.5 Gy in 25 fractions.14Radu C Norrlid O Braendengen M Hansson K Isacsson U Glimelius B. Integrated peripheral boost in preoperative radiotherapy for the locally most advanced non-resectable rectal cancer patients. For the proton plans, spot scanning was utilized with RPO (140o) and LPO (220o) beams. In two plans, an additional PA beam was added due to shallow target. Intestinal gas was contoured and the plans re-calculated with water equivalent material. Interestingly, when the gas was replaced with water, the targets were no longer covered by the 95% isodose line in all proton plans. Finally, the Mayo Clinic reported on their experience treating 11 patients with preoperative short-course PBT with pencil beam scanning to 25 Gy in 5 fractions.15Jeans EB Jethwa KR Harmsen WS Neben-Wittich M Ashman JB Merrell KW Giffey B Ito S Kazemba B Beltran C Haddock MG Hallemeier CL. Clinical Implementation of Preoperative Short-Course Pencil Beam Scanning Proton Therapy for Patients With Rectal Cancer. They employed an RPO/LPO field arrangement with a hinge angle of 80o. Rectal gas was contoured and assigned Hounsfield units of -450 for optimization. Collectively, these studies highlight the heterogeneity with which beam arrangements are selected and bowel gas treated and underscore that air content is an important obstacle in the treatment of rectal cancer with proton therapy.

Whereas tissue inhomogeneity modulates the intensity of a photon-based treatment beam, it results in both range uncertainty and intensity with proton radiotherapy. Accordingly, traversing a particle beam through tissues that have inconsistent densities must be performed with care. In the present study, the single PA beam plans deteriorated with intestinal gas variations. The single PA beam field design is not practical because severe variations in intestinal gas distension may lead to larger beam range, thus resulting in loss of target coverage with dose instead spread to the anterior organs-at-risk, including the small bowel, internal genitalia, and bladder. This was evident in our analysis in the plans optimized to the planning CT and iterated across rectal diameter sizes, where with distension of the rectum to ≥3 cm CTV50Gy V100% > 90% was lost and dose constraints to the bladder and internal genitalia were compromised. Similarly, on plans optimized based on a 5 cm rectal contour, CTV50Gy V100% > 90% was lost with rectal contraction ≤3 cm due to insufficient range.

Our analysis supports an RPO/LPO arrangement over a PA/opposed lateral arrangement. Parallel opposed beams were historically favored with PBT because this arrangement is least affected by proton range uncertainty, but with higher scatter and wider dose penumbra due to greater target depth.18Trofimov A Nguyen PL Coen JJ Doppke KP Schneider RJ Adams JA Bortfeld TR Zietman AL Delaney TF Shipley WU. Radiotherapy treatment of early-stage prostate cancer with IMRT and protons: a treatment planning comparison. With the advent of robust optimization19Chen W Unkelbach J Trofimov A Madden T Kooy H Bortfeld T Craft D. Including robustness in multi-criteria optimization for intensity-modulated proton therapy., 20Liu W Zhang X Li Y Mohan R. Robust optimization of intensity modulated proton therapy., 21Unkelbach J Chan TC Bortfeld T. Accounting for range uncertainties in the optimization of intensity modulated proton therapy., other beam arrangements have gained favor due to potential improved dosimetric benefits, particularly for prostate cancer.22Cao W Lim GJ Lee A Li Y Liu W Ronald Zhu X Zhang X Uncertainty incorporated beam angle optimization for IMPT treatment planning. In addition, opposed lateral beams should be avoided in patients with hip prosthesis due to range uncertainty. When comparing the RPO/LPO with the PA/opposed lateral field designs in the present study, the 2-field design was favored. For both the 2- and 3-beam designs, target coverage was maintained across rectal diameters for plans optimized to the planning CT, but V40Gy to the small bowel was slightly higher for the 3-beam design. On plans optimized to a 5 cm diameter rectal contour, both designs were subject to severe target coverage loss with rectal contraction, though the 2-beam arrangement maintained V100% > 90% to rectal diameter as low as 3 cm, whereas the 3-beam arrangement only maintained this coverage to 4 cm. In addition, V40Gy to the small bowel were higher for the 3-beam arrangement. We conclude that based on slightly superior robustness of target coverage in the face of varying rectal distension, less dose to the small bowel, and less integral dose, the 2-beam arrangement is superior to the 3-beam arrangement. As an aside, the RPO/LPO/PA/opposed lateral field design (5 beams) should generally be avoided as its target coverage is similar to the PA/opposed lateral arrangement and results in higher integral dose.

Clinicians should in addition strongly reconsider re-simulation or noninvasive measures to reduce intestinal gas when maximal bowel diameter exceeds 3 cm in short axis. This is based on the severe loss of target coverage observed with all field designs in patients optimized to 5 cm rectal contours with contraction beyond 3 cm. Based on this observation, we optimized plans to 4 cm and then 3 cm rectal contours for the 2- and 3-beam plans. With the plans optimized to 4 cm, there was still loss of V100% > 90% with rectal contraction to 1 cm for both plans. In contrast, with plans optimized to 3 cm, coverage was maintained for contraction to as low as 1 cm for both the 2- and 3-beam plans, simulating a patient without any rectal gas. If re-simulation is not pursued, minimally invasive interventions to reduce intestinal gas such as rectal catheters and dietary changes should be strongly considered if contours exceed 3 cm in diameter in short axis. In addition, cone-beam CT imaging or verification quality assurance (QA) CT imaging should be employed when treating rectal or anal cancer with proton therapy given the varying degrees of rectal air content.

Our study has several important limitations. First, all of the treatment plans and plan evaluations were generated based on a single patient. As the goal of the present study was to demonstrate the perturbations in dose distribution and plan quality/robustness based on intestinal dilation, we feel that our results are readily generalizable even with the use of only one patient. In addition, the patient was simulated in supine positioning to improve setup reproducibility and patient comfort. We acknowledge that many centers routinely employ prone positioning in the treatment of rectal cancer.

In conclusion, our analysis of 60 plan evaluations suggests that a RPO/LPO field design is the ideal beam arrangement in the treatment of rectal cancer with proton beam therapy with pencil beam scanning to best account for internal anatomic variations due to intestinal gas. Single PA beam arrangements should be avoided. Re-simulation or other gas-reducing measures should be undertaken when maximal bowel diameter exceeds 3 cm in short axis.

Article InfoPublication History

Accepted: June 28, 2021

Received in revised form: June 10, 2021

Received: February 9, 2021

Publication stageIn Press Journal Pre-ProofFootnotes

The authors report no proprietary or commercial interest in any product mentioned or concept discussed in this article. The authors report no funding source for the research described herein. The data generated and analyzed during the current study are not publicly available but are available from the corresponding author on reasonable request.

Identification

DOI: https://doi.org/10.1016/j.adro.2021.100749

Copyright

© 2021 Published by Elsevier Inc. on behalf of American Society for Radiation Oncology.

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