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The use of radiation therapy (RT) for pancreatic cancer continues to be controversial, despite recent technical advances. Improvements in systemic control have created an evolving role for RT and the need for improved local tumor control, but currently, no standardized approach exists. Advances in stereotactic body RT, motion management, real-time image guidance, and adaptive therapy have renewed hopes of improved outcomes in this devastating disease with one of the lowest survival rates. This case-based guide provides a practical framework for delivering stereotactic body RT for locally advanced pancreatic cancer. In conjunction with multidisciplinary care, an intradisciplinary approach should guide treatment of the high-risk cases outlined within these guidelines for prospective peer review and treatment safety discussions., Competing Interests: Disclosures Christopher H. Crane receives consulting fees from Trisalis and honoraria from Elekta and has stock options in Oncternal. Karyn A. Goodman serves on the advisory board of RenovoRx and leadership in the NCI GI Steering Committee. Percy Lee receives consulting fees from Varian, ViewRay, AstraZeneca, Genentech, Johnson & Johnson, RTOG Foundation, honoraria from Varian, ViewRay, AstraZeneca, and travel support from Radiosurgery Society; serves on the advisory board for Genentech, ViewRay, AstraZeneca, Roche, and leadership of Radiosurgery Society, ASTRO. Michael D. Chuong receives grants, consulting fees, honoraria, and travel support from ViewRay, and serves on the advisory board of ViewRay., (Copyright © 2024 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

Purpose: At our institution, we treat patients with a daily vaginal dilator (VD) during chemoradiation (CRT) for squamous cell carcinoma of the anus (SCCA). We evaluated compliance with daily VD use, radiation dose to the vaginal wall (VW), and anterior vaginal wall (AVW), and patient-reported long-term sexual function., Methods and Materials: We included women with SCCA who received definitive, intensity-modulated radiation therapy-based CRT. Women who were alive without evidence of disease received a patient-reported outcome survey, which included the Female Sexual Function Index (FSFI). We identified factors associated with FSFI, such as radiation dose to the VW and AVW using linear regression models and used Youden index analysis to estimate a dose cutoff to predict sexual dysfunction., Results: Three hundred thirty-nine consecutively treated women were included in the analysis; 285 (84.1%) were treated with a daily VD. Of 184 women alive without disease, 90 patients (49%) completed the FSFI, and 51 (56.7%) were sexually active with valid FSFI scores. All received therapy with a daily VD. Forty-one women (80%) had sexual dysfunction. Univariate analysis showed higher dose to 50% (D50%) of the AVW correlated with worse FSFI (β -.262; P = .043), worse desire FSFI subscore (β -.056; P = .003), and worse pain FSFI subscore (β -.084; P = .009). Younger age correlated with worse pain FSFI subscale (β .067; P = .026). Age (β .070; P = .013) and AVW D50% (β -.087; P = .009) were significant on multivariable analysis. AVW D50% >48 Gy predicted increased risk of sexual dysfunction., Conclusions: Daily VD use is safe and well tolerated during CRT for SCCA. Using a VD during treatment to displace the AVW may reduce the risk for sexual dysfunction. Limiting the AVW D50% <48 Gy may further reduce the risk but additional data are needed to validate this constraint., Competing Interests: Disclosures None., (Copyright © 2023. Published by Elsevier Inc.)

Purpose: To provide a detailed description of practical approaches to dose escalation in pancreatic cancer., Methods and Materials: The current paper represents an international collaborative effort of radiation oncologists from the MR-linac consortium with expertise in pancreatic dose escalation., Results: A 15-fraction hypofractionated intensity modulated radiation therapy (67.5 Gy in 15 fractions) and 5-fraction stereotactic body radiation therapy case (50 Gy in 5 fractions) are presented with information regarding patient selection, target volumes, organs at risk, dose constraints, and specific considerations regarding quality assurance. Additionally, we address barriers to dose escalation and briefly discuss future directions in dose escalation for pancreatic cancer, including particle therapy and magnetic resonance guided radiation therapy., Conclusions: This article on dose escalation for pancreatic cancer may help to guide academic and community based physicians and to serve as a reference for future therapeutic trials., (Copyright © 2020 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

Purpose: This study aimed to determine the feasibility and maximally tolerated dose of hypofractionated, conformal radiation therapy (RT) in patients with liver metastases., Methods and Materials: Nonsurgical patients with ≤5 liver metastases (sum of maximal diameter of all lesions ≤8 cm) were included in the study. There were 4 dose levels: 35 Gy, 40 Gy (starting level), 45 Gy, and 50 Gy, in 10 fractions. The clinical target volume included metastases identified on contrast computed tomography or magnetic resonance imaging with a 5-mm margin within the liver. The planning target volume margin ranged from 4 to 30 mm, depending on breathing motion. Dose-limiting toxicities were defined as RT-related grade ≥4 hepatic or gastrointestinal toxicities or thrombocytopenia occurring within 90 days of the start of RT., Results: A total of 26 patients with metastases from colorectal (8 patients), breast (7 patients) and other malignancies (11 patients) were enrolled between November 2005 and December 2010. Twenty-three patients were evaluable (8, 7, and 8 on the 40, 45, and 50 Gy dose levels, respectively). Two patients assigned to 50 Gy received 35 Gy owing to normal tissue limits, so 2 additional patients were treated to 50 Gy. There were no dose-limiting toxicities on any of the dose levels. On the 45 Gy dose level, 1 patient developed reversible grade 3 enteritis (37 days from RT start) and diarrhea (22 days); another patient developed grade 3 lymphopenia (23 days). At the 50 Gy dose level, 1 patient had grade 3 hyperglycemia (74 days), and another patient developed grade 3 lymphopenia (13 days), colonic hemorrhage (325 days), and colonic gastrointestinal obstruction (325 days). With a potential median follow-up of 66.1 months (range, 34.6-89.0 months), no other late toxicities were observed., Conclusions: Treatment of liver metastases with 50 Gy in 10 fractions was feasible and safe in a multi-institutional setting., (Copyright © 2019 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

Purpose: Local recurrence is a common and morbid event in patients with unresectable pancreatic adenocarcinoma. A more conformal and targeted radiation dose to the macroscopic tumor in nonmetastatic pancreatic cancer is likely to reduce acute toxicity and improve local control. Optimal soft tissue contrast is required to facilitate delineation of a target and creation of a planning target volume with margin reduction and motion management. Magnetic resonance imaging (MRI) offers considerable advantages in optimizing soft tissue delineation and is an ideal modality for imaging and delineating a gross tumor volume (GTV) within the pancreas, particularly as it relates to conformal radiation planning. Currently, no guidelines have been defined for the delineation of pancreatic tumors for radiation therapy treatment planning. Moreover, abdominal MRI sequences are complex and the anatomy relevant to the radiation oncologist can be challenging. The purpose of this study is to provide recommendations for delineation of GTV and organs at risk (OARs) using MRI and incorporating multiple MRI sequences., Methods and Materials: Five patients with pancreatic cancer and 1 healthy subject were imaged with MRI scans either on 1.5T or on 3T magnets in 2 separate institutes. The GTV and OARs were contoured for all patients in a consensus meeting., Results: An overview of MRI-based anatomy of the GTV and OARs is provided. Practical contouring instructions for the GTV and the OARs with the aid of MRI were developed and included in these recommendations. In addition, practical suggestions for implementation of MRI in pancreatic radiation treatment planning are provided., Conclusions: With this report, we attempt to provide recommendations for MRI-based contouring of pancreatic tumors and OARs. This could lead to better uniformity in defining the GTV and OARs for clinical trials and in radiation therapy treatment planning, with the ultimate goal of improving local control while minimizing morbidity., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: Fifteen fraction treatment schedules are increasingly used to deliver high doses of radiation therapy (RT) to both lung and hepatobiliary malignancies. The purpose of our study was to examine the incidence and predictors of chest wall (CW) toxicity in patients treated with this regimen., Methods and Materials: We evaluated 135 patients treated with RT to doses ≥52.5 Gy in 15 fractions for thoracic and hepatobiliary malignancies between January 2009 and December 2012. We documented patient characteristics and CW dosimetric parameters for each case. Toxicity was scored using the Common Terminology Criteria for Adverse Events, version 4.0, criteria for radiation dermatitis and CW pain. Patient characteristics and CW dosimetric parameters were evaluated for their association with CW toxicity using proportional hazards regression., Results: Median follow-up was 9 months from the start of RT. Forty-eight patients (36%) developed dermatitis at a median time of 18 days. In multivariable analysis, the absolute volume of CW (in cm 3 ) receiving 40 Gy (V40) ≥120 cm 3 was associated with the occurrence of dermatitis (hazard ratio, 3.12; 95% confidence interval, 1.74-5.60; P < .001). Twenty-one patients (16%) developed CW pain (20 grade 1, 1 grade 2) at a median time of 3 months. In multivariable analysis, CW V40 ≥150 cm 3 was associated with the occurrence of CW pain (hazard ratio, 2.65; 95% confidence interval, 1.12-6.24; P = .03). The absolute rate of CW pain in patients with V40 <150 cm 3 was 11% versus 26% in patients with V40 ≥150 cm 3 (P = .03)., Conclusions: Hypofractionated RT with 15 fraction regimens results in an acceptable incidence of CW toxicity, specifically CW pain. We recommend a dose constraint of V40 <150 cm 3 to minimize this adverse event., (Copyright © 2016 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

Purpose: To summarize results of a Clinical Practice Statement on radiation therapy for stage II-III rectal cancer, which addressed appropriate customization of (neo)adjuvant radiation therapy and use of non-surgical therapy for patients who are inoperable or refuse abdominoperineal resection., Methods and Materials: The RAND/University of California, Los Angeles, Appropriateness Method was applied to combine current evidence with multidisciplinary expert opinion. A systematic literature review was conducted and used by the expert panel to rate appropriateness of radiation therapy options for different clinical scenarios. Treatments were categorized by median rating as Appropriate, May Be Appropriate, or Rarely Appropriate., Results: In the neoadjuvant setting, chemoradiation was rated Appropriate and the ratings indicated short-course radiation therapy, chemotherapy alone, and no neoadjuvant therapy are potential options in selected patients. However, neoadjuvant endorectal brachytherapy was rated Rarely Appropriate. For adjuvant therapy, chemoradiation (plus ≥4 months of chemotherapy) was rated Appropriate and chemotherapy alone May Be Appropriate for most scenarios. For medically inoperable patients, definitive external beam radiation therapy and chemotherapy alone were rated May Be Appropriate, whereas endorectal brachytherapy and chemoradiation plus endorectal brachytherapy were possible approaches for some scenarios. The last option, definitive chemoradiation, was rated Appropriate to May Be Appropriate based on performance status. Finally, for patients with low-lying tumors refusing abdominoperineal resection, definitive chemoradiation alone, chemoradiation plus endorectal brachytherapy, and chemoradiation plus external beam radiation therapy were all rated Appropriate., Conclusions: This Clinical Practice Statement demonstrated the central role of radiation therapy in stage II-III rectal cancer management and evaluated ways to better individualize its use in the neoadjuvant, adjuvant, and definitive settings. Ongoing trials may clarify areas of continuing uncertainty and allow further customization., (Copyright © 2015 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

Purpose: To standardize upper abdominal normal organ contouring guidelines for Radiation Therapy Oncology Group (RTOG) trials., Methods and Materials: Twelve expert radiation oncologists contoured the liver, esophagus, gastroesophageal junction (GEJ), stomach, duodenum, and common bile duct (CBD), and reviewed and edited 33 additional normal organ and blood vessel contours on an anonymized patient computed tomography (CT) dataset. Contours were overlaid and compared for agreement using MATLAB (MathWorks, Natick, MA). S95 contours, defined as the binomial distribution to generate 95% group consensus contours, and normal organ contouring definitions were generated and reviewed by the panel., Results: There was excellent consistency and agreement of the liver, duodenal, and stomach contours, with substantial consistency for the esophagus contour, and moderate consistency for the GEJ and CBD contours using a Kappa statistic. Consensus definitions, detailed normal organ contouring recommendations and high-resolution images were developed., Conclusions: Consensus contouring guidelines and a CT image atlas should improve contouring uniformity in radiation oncology clinical planning and RTOG trials., (Copyright © 2014 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

Purpose: The goal of this study was to determine the incidence and risk factors associated with gastric bleeding in patients treated with radiation therapy for intrahepatic cholangiocarcinoma., Methods and Materials: Between November 2002 and December 2008, 33 patients with intrahepatic cholangiocarcinoma were treated with radiation therapy to the primary site. Twenty-nine (88%) patients were previously treated with chemotherapy, including gemcitabine and cisplatin in 19 patients. The median dose of radiation therapy was 50.4 Gy (range, 35-70 Gy). Twenty-seven (82%) patients received concurrent therapy, with capecitabine in 26 and bevacizumab in 1 patient., Results: Nine of the 33 patients developed gastric bleeding, with a 1-year actuarial rate of 36%. Of these 9 patients, 7 presented with bleeding symptoms and 2 presented with anemia. All 9 patients were documented to have gastritis on endoscopy. The absolute and percent volumes of stomach receiving 40 and 50 Gy were significantly associated with the risk of gastric bleeding., Conclusions: Patients with intrahepatic cholangiocarcinoma have a significant risk of developing gastric bleeding after radiation therapy. Hence, the volume of stomach exposed to radiation therapy should be minimized in patients receiving radiation therapy for intrahepatic cholangiocarcinoma., (Copyright © 2013 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

Purpose: Volumetric modulated arc therapy (VMAT), an evolution of intensity modulated radiation therapy (IMRT), utilizes the dynamic modulation of angular dose rate through changes in gantry speed, linear accelerator dose rate, and multileaf collimator motion to deliver a treatment fraction in rotational fashion with improved efficiency and in shorter time. In general, target coverage relative to adjacent organ-at-risk sparing is highly dependent on the complexity of the treatment site. Therefore, we critically evaluated VMAT compared to IMRT for definitive treatment of anal carcinoma with respect to dosimetry and efficiency., Methods and Materials: Using SmartArc (Philips Healthcare, Andover, MA), VMAT treatment plans were generated for 10 patients treated at our institution for anal carcinoma, and compared to the IMRT plans used for clinical treatment. The patients were all female, had T classification TX/1 (n = 5), T2 (n = 3) or T3 (n = 2), were node-negative (n = 6) or node-positive (n = 4), and were treated to a total dose of 50 to 58 Gy. Pairwise comparisons were made between VMAT and IMRT plans with respect to dose-volume histogram parameters relating the dose received by target volumes, relevant organs at risk, and normal tissues. The plans were machine-delivered, with actual beam delivery times measured., Results: VMAT plans had superior planning target volume coverage and dose homogeneity, with improved conformality in treatment of the elective nodal volume, in comparison to IMRT. Mean dose to the small bowel, genitalia, and femoral heads were significantly lower with VMAT, and similar with respect to bladder, pelvic bones, and normal tissues. Integral dose was comparable between the 2 techniques. VMAT plans required 36.8% fewer monitor units, and beam delivery time was shorter by 9 minutes., Conclusions: Our results indicate that VMAT represents an ideal treatment modality for anal carcinoma, generating plans with excellent target coverage, lower doses to organs at risk, and shorter treatment times, in comparison to IMRT., (Copyright © 2011 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)