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Although rare, the rate of squamous cell carcinoma of the anus (SCCA) is rising globally. Most patients present with nonmetastatic disease and are curable with appropriate treatment, which has evolved significantly over the last several decades. Before the 1970s, SCCA was managed with radical surgery, resulting in a permanent colostomy. Researchers found that preoperative treatment with chemotherapy and concurrent radiation could achieve a pathologic complete response. After this observation, definitive therapy shifted from radical surgery to sphincter-preserving chemoradiation. Investigations into the necessity of chemotherapy and the optimal regimen found that chemotherapy with mitomycin-C and 5-fluorouracil is required for cure. Further studies evaluating the addition of induction or maintenance chemotherapy, monoclonal antibody therapy, or higher radiation doses have demonstrated no significant benefit to disease control. Advanced radiation delivery with intensity-modulated radiotherapy techniques is now considered the standard of care because of its prospectively determined, favorable acute toxicity profile compared with 3-dimensional conformal radiation. It is important to note that chemoradiation treatment response may be slow (up to 26 weeks) and should be assessed through serial clinical examinations. Today, surgical management of SCCA is reserved only for the lowest risk, early stage tumors or for recurrent/persistent disease. Current studies are evaluating radiation dose de-escalation in early stage disease and radiation dose escalation and the addition of immune checkpoint inhibitors in locally advanced cancers. In reviewing how and why modern-day treatment of SCCA was established, the objective of this report is to reenforce adherence to current treatment paradigms to assure the best possible outcomes for patients.

PURPOSE In oncology trials, the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) is the standard tool for reporting adverse events (AEs), but it may underreport symptoms experienced by patients. This analysis of the NRG Oncology RTOG 1203 compared symptom reporting by patients and clinicians during radiotherapy (RT). PATIENTS AND METHODS Patients with cervical or endometrial cancer requiring postoperative RT were randomly assigned to standard 4-field RT or intensity-modulated RT (IMRT). Patients completed the 6-item patient-reported outcomes version of the CTCAE (PRO-CTCAE) for GI toxicity assessing abdominal pain, diarrhea, and fecal incontinence at various time points. Patients reported symptoms on a 5-point scale. Clinicians recorded these AEs as CTCAE grades 1 to 5. Clinician- and patient-reported AEs were compared using McNemar’s test for rates > 0%. RESULTS Of 278 eligible patients, 234 consented and completed the PRO-CTCAE. Patients reported high-grade abdominal pain 19.1% ( P < .0001), high-grade diarrhea 38.5% ( P < .0001), and fecal incontinence 6.8% more frequently than clinicians. Similar effects were seen between grade ≥ 1 CTCAE toxicity and any-grade patient-reported toxicity. Between-arm comparison of patient-reported high-grade AEs revealed that at 5 weeks of RT, patients who received IMRT experienced fewer GI AEs than patients who received 4-field pelvic RT with regard to frequency of diarrhea (18.2% difference; P = .01), frequency of fecal incontinence (8.2% difference; P = .01), and interference of fecal incontinence (8.5% difference; P = .04). CONCLUSION Patient-reported AEs showed a reduction in symptoms with IMRT compared with standard RT, whereas clinician-reported AEs revealed no difference. Clinicians also underreported symptomatic GI AEs compared with patients. This suggests that patient-reported symptomatic AEs are important to assess in this disease setting.

PURPOSE Radiation dose to the neuroregenerative zone of the hippocampus has been found to be associated with cognitive toxicity. Hippocampal avoidance (HA) using intensity-modulated radiotherapy during whole-brain radiotherapy (WBRT) is hypothesized to preserve cognition. METHODS This phase III trial enrolled adult patients with brain metastases to HA-WBRT plus memantine or WBRT plus memantine. The primary end point was time to cognitive function failure, defined as decline using the reliable change index on at least one of the cognitive tests. Secondary end points included overall survival (OS), intracranial progression-free survival (PFS), toxicity, and patient-reported symptom burden. RESULTS Between July 2015 and March 2018, 518 patients were randomly assigned. Median follow-up for alive patients was 7.9 months. Risk of cognitive failure was significantly lower after HA-WBRT plus memantine versus WBRT plus memantine (adjusted hazard ratio, 0.74; 95% CI, 0.58 to 0.95; P = .02). This difference was attributable to less deterioration in executive function at 4 months (23.3% v 40.4%; P = .01) and learning and memory at 6 months (11.5% v 24.7% [ P = .049] and 16.4% v 33.3% [ P = .02], respectively). Treatment arms did not differ significantly in OS, intracranial PFS, or toxicity. At 6 months, using all data, patients who received HA-WBRT plus memantine reported less fatigue ( P = .04), less difficulty with remembering things ( P = .01), and less difficulty with speaking ( P = .049) and using imputed data, less interference of neurologic symptoms in daily activities ( P = .008) and fewer cognitive symptoms ( P = .01). CONCLUSION HA-WBRT plus memantine better preserves cognitive function and patient-reported symptoms, with no difference in intracranial PFS and OS, and should be considered a standard of care for patients with good performance status who plan to receive WBRT for brain metastases with no metastases in the HA region.

Purpose: NRG Oncology's RTOG 0933 demonstrated benefits to memory preservation after hippocampal avoidant whole-brain radiation therapy (HA-WBRT), the avoidance of radiation dose to the hippocampus (using intensity modulated radiation planning and delivery techniques) during WBRT, supporting the hypothesis of hippocampal radiosensitivity and associated memory specificity. However, some patients demonstrated cognitive decline, suggesting mechanisms outside hippocampal radiosensitivity play a role. White matter injury (WMI) has been implicated in radiation therapy–induced neurocognitive decline. This secondary analysis explored the relationship between pretreatment WMI and memory after HA-WBRT. Methods and Materials: Volumetric analysis of metastatic disease burden and disease-unrelated WMI was conducted on the pretreatment magnetic resonance image. Correlational analyses were performed examining the relationship between pretreatment WMI and Hopkins Verbal Learning Test-Revised (HVLT-R) outcomes at baseline and 4 months after HA-WBRT. Results: In the study, 113 patients received HA-WBRT. Of 113 patients, 33 underwent pretreatment and 4-month posttreatment HVLT testing and pretreatment postcontrast volumetric T1 and axial T2/fluid-attenuated inversion recovery magnetic resonance imaging. Correlation was found between larger volumes of pretreatment WMI and decline in HVLT-R recognition (r = 0.54, P

Objective Women with endometrial or cervical cancer at risk for recurrence receive postoperative radiation therapy (RT). A patient reported outcomes (PRO) instrument to assess bowel and urinary toxicities is the Expanded Prostate Cancer Index Composite (EPIC), which has been validated in men with prostate cancer. As this instrument specifically measures bowel toxicity and the degree to which this is a problem, it was used in NRG Oncology/RTOG 1203 to compare intensity modulated RT (IMRT) to standard RT. This paper reports on the expanded validation of EPIC for use in women receiving pelvic RT. Methods In addition to the EPIC bowel domain, urinary toxicity (EPIC urinary domain), patient reported bowel toxicities (PRO-CTCAE) and quality of life (Functional Assessment of Cancer Therapy (FACT)) were completed before, during and after treatment. Sensitivity, reliability and concurrent validity were assessed. Results Mean bowel and urinary scores among 278 women enrolled were significantly worse during treatment and differed between groups. Acceptable to good reliability for bowel and urinary domain scores were obtained at all time points with the exception of one at baseline. Correlations between function and bother scores within the bowel and urinary domains were consistently stronger than those across domains. Correlations between bowel domain scores and PRO-CTCAE during treatment were stronger than those with the FACT. Conclusion Correlations within and among the instruments indicate EPIC bowel and urinary domains are measuring conceptually discrete components of health. These EPIC domains are valid, reliable and sensitive instruments to measure PRO among women undergoing pelvic radiation.

Purpose A multi-institutional phase 2 trial assessed long-term outcomes of dose-painted intensity modulated radiation therapy (IMRT) with 5-fluorouracil (5FU) and mitomycin-C (MMC) for anal canal cancer. Methods and Materials T2-4N0-3M0 anal cancers received 5FU (1000 mg/m2/d, 96-hour infusion) and MMC (10 mg/m2 bolus) on days 1 and 29 of dose-painted IMRT prescribed as follows: T2N0 = 42 Gy elective nodal and 50.4 Gy anal tumor planning target volumes, 28 fractions; T3-4N0-3 = 45Gy elective nodal, 50.4 Gy ≤3 cm and 54 Gy >3cm metastatic nodal and 54 Gy anal tumor planning target volumes, 30 fractions. Local-regional failures, distant metastases, and colostomy failures were assessed using the cumulative incidence method, and disease-free survival, overall survival, and colostomy-free survival were assessed using the Kaplan-Meier method. Late effects were scored using National Cancer Institute-Common Terminology Criteria for Adverse Events v3. Results Of 52 patients, 54% were stage II, 25% were stage IIIA, and 21% were stage IIIB. Median follow-up was 7.9 years (min-max, 0.02-9.2 years). Local-regional failure, colostomy failures, distant metastases, overall survival, disease-free survival, and colostomy-free survival at 5 years are 16% (95% confidence interval [CI], 7%-27%), 10% (95% CI, 4%-20%), 16% (95% CI, 7%-27%), 76% (95% CI, 61%-86%), 70% (95% CI, 56%-81%), and 74% (95% CI, 59%-84%); and at 8 years they are 16% (95% CI, 7%-27%), 12% (95% CI, 5%-23%), 22% (95% CI, 12%-34%), 68% (95% CI, 53%-79%), 62% (95% CI, 47%-74%) and 66% (95% CI, 51%-77%), respectively. Eight patients experienced local-regional failure, with 5 patients having persistent disease at 12 weeks. No isolated nodal failures occurred in the microscopic elective nodal volumes. Six patients required colostomy—5 for local-regional salvage and 1 for a temporary ostomy for anorectal dysfunction. Rates of late adverse events included: 28 patients (55%) with grade 2, 8 patients (16%) with grade 3, 0 patients with grade 4, and 2 patients (4%) with grade 5 events (sinus bradycardia and myelodysplasia, possibly owing to chemotherapy). Only 11 patients reported grade 1 to 3 sexual dysfunction. Conclusions Dose-painted IMRT with 5FU/MMC for the treatment of anal canal cancer yields comparable long-term efficacy as conventional radiation cohorts. Enhanced normal tissue protection lowered rates of grade 3 and higher late effects without compromising pelvic tumor control.

Purpose/Objective(s) Standard of care for locally advanced anal carcinoma is definitive chemoradiation with IMRT. Currently, target and organ-at-risk (OAR) volumes are created using a pre-treatment CT-simulation scan. However, during the course of radiotherapy, there is often change in the size and/or position of the tumor and surrounding normal structures. Therefore, we hypothesize that the implementation of an adaptive radiation therapy treatment protocol in anal cancer may reduce radiation dose to critical surrounding normal structures, such as the bowel, through the use of anatomy-adapted replanning. Materials/Methods Retrospective daily adaptive CTs were created for 4 patients (54 Gy, 30 fraction VMAT) in an oncology imaging informatics system using the Adaptive Calculation and Tracking for Offline Plan Review (ACTOR) toolkit. Each adaptive CT was created by deformable image registration (dir) of the planning CT to the daily CBCT. The structure sets from the planning CT were deformed onto each adaptive CT and ultimately corrected and revised by two qualified radiation oncologists. The adaptive CTs were transferred to a treatment planning system for recalculation. The original treatment plan was recalculated on each fraction adaptive CT to establish the real dose received during treatment. A two-sample t-test was used to compare the average real dose received dosimetric values to the values obtained on trigger-based adaptive planning. Results Using dose prescriptions for target volumes and normal tissue dose constraints as defined in RTOG 0529 (Kachnic et al 2013), normal bowel dose metrics, including bowel V45 20cc as trigger 1, there was a significant reduction in bowel V45 for each patient (table), with an average reduction in bowel V45 of 86.7% (P = 0.0001) across all patients. Adapting only the 5 fractions with the highest values for bowel V45 (trigger 2), we also found a significant reduction for each patient (table), with an average reduction of 20.8 % (P = 0.0011) across all patients. Conclusion Our study demonstrated that triggered adaptive re-planning using bowel V45 > 20cc could likely achieve reductions in normal tissue dose. Adaptive planning during radiation treatment of anal cancer may therefore be beneficial for reduction of treatment-related GI toxicity. These results can help inform a future randomized trial of adaptive therapy vs. standard planning.

Purpose/Objective(s) Approximately one in eight women in the United States is diagnosed with breast cancer and eligible for mastectomy with implant reconstruction. Although it has been suggested that patients with breast cancer or those who are at high risk for breast cancer may have an increased risk of anaplastic large cell lymphoma (ALCL) after breast implantation, no studies have explored the association in this population. Our objective was to determine the relative and absolute risks of breast ALCL after post-mastectomy implant reconstruction for breast cancer compared with the general population. Materials/Methods This population-based study obtained incidence data on breast ALCL in the general population from the Surveillance, Epidemiology, and End Results (SEER) program from 2000 – 2017. Patients who underwent post-mastectomy implant reconstruction for primary breast cancer from 2000 – 2016 were identified and followed through 2017. Because breast implant-associated ALCL has been documented as early as 2 months after implantation, patients with less than two months of follow-up were excluded. Observed-to-expected ratios for breast ALCL were derived from multiple primary – standardized incidence ratios in the study population versus the general U.S. population after adjusting for age, sex, race, anatomical site, and year of diagnosis. For external validation, we compared the number of cases of breast ALCL diagnosed in SEER with the estimated number of FDA-reported cases over a similar time period. Results The incidence rate of breast ALCL in the general U.S. female population was 0.08 – 0.12 per 1,000,000 persons per year and was rising. 52,882 women were identified that received post-mastectomy implant reconstruction for primary breast cancer and were followed for a median of 69 months, including 10,979 patients with follow-up time greater than or equal to 10 years (range 2 – 215 months). After adjusting for demographical characteristics of the cohort, the expected incidence rate of breast ALCL was 0.25 – 0.34 per 1,000,000 persons per year versus an observed rate of 5.8 – 8.7 per 1,000,000 persons per year (standardized incidence ratio 23.4 [95% confidence interval 2.8 – 84.7]). These findings corresponded well with FDA-reported cases; 353 SEER versus 333 FDA cases, respectively. Conclusion Although breast cancer patients who receive post-mastectomy implant reconstruction are at increased risk of breast ALCL, the absolute risk remains extremely low. Furthermore, the risk does not appear to be increased compared to patients that receive implantation (for cosmesis or reconstruction) in previously reported literature.

From the time of initial incorporation of the of the American Board of Medical Specialties (ABMS) in 1933, through the early 1990s, diplomates of 23 of its 24 member boards understood that their initial certification awards extended throughout the continuum of their careers. From the time of its founding in 1969, only the American Board of Family Medicine required continuous certification. As early as the post–World War II era, the appropriateness of this “once and done” certification process was questioned by medical educators, and more recently by legislators, regulators, and the public. To meet the demands of rapidly changing scientific and clinical advances, and to maintain the values accrued by hard-fought self-regulation, the ABMS and its member boards agreed to implement programs that required continuous elements of professionalism, attainment, and assessment of current medical skills and knowledge and elements of practice improvement, throughout the career of each certified physician. Each of the medical specialty boards was provided some flexibility to determine specifics of their program within the general framework of the ABMS core competencies and four defined maintenance of certification (MOC) foundational parts. Herein, we describe the programs in general and more specifically, as they relate to the field of radiation oncology.

Locally advanced, unresectable pancreatic ductal adenocarcinoma has a poor prognosis with a median overall survival of 10-16 months. It is defined by tumor involvement of neighboring blood vessels that precludes resection. Standard doses of conventionally fractionated radiation have had little effect on overall survival in this setting, although they are associated with improved progression-free survival and time off chemotherapy. Evolving radiotherapy techniques have allowed for higher, ablative doses of radiotherapy to target tumor while also respecting normal tissue constraints of neighboring radiosensitive structures in the gastrointestinal tract. Moreover, advancements in image guidance, organ motion management, and the use of adaptive planning have enabled safe delivery of higher, ablative doses of radiation. This has resulted in improved survival. This review will summarize the expanding role of radiotherapy in the management of locally advanced, unresectable pancreatic cancer.

Background Resection of T4 colon cancer remains challenging compared to lower T stages. Data on the effect of neoadjuvant radiation to improve resectability and survival are lacking. The purpose of this study is to describe the use and outcomes of neoadjuvant radiation therapy in clinical T4 colon cancer. Methods Adults with clinical evidence of T4 locally advanced colon cancer were included from the National Cancer Database (2004–2014). Bivariate and multivariable analyses were used to examine the association between neoadjuvant radiation therapy and R 0 resection rate, multivisceral resection, and overall survival. Results Fifteen thousand two hundred and seven patients with clinical T4 disease who underwent resection were identified over the study period. One hundred ninety-five (1.3%) underwent neoadjuvant radiation therapy. Factors associated with the use of neoadjuvant radiation therapy included younger age, male sex, private insurance, lower Charlson Comorbidity Index score, and treatment at an academic research program. Neoadjuvant radiation therapy was associated with superior R 0 resection rates (87.2% neoadjuvant radiation therapy vs 79.8% no neoadjuvant radiation therapy; P = .009). Five-year overall survival was increased in the neoadjuvant radiation therapy group (62.0% neoadjuvant radiation therapy vs 45.7% no neoadjuvant radiation therapy; P P = .01). In a subgroup analysis of T4b patients, there was an even greater size effect in adjusted overall survival (odds ratio 1.71; 95% confidence interval 1.07–2.72; P = .02). Conclusion Although radiation is rarely used in locally advanced colon cancer, this National Cancer Database analysis suggests that the use of neoadjuvant radiation for clinical T4 disease may be associated with superior R 0 resection rates and improved overall survival. Patients with clinical T4b disease may benefit the most from treatment. Neoadjuvant radiation therapy should be considered on a case-by-case basis in locally advanced colon cancer.

BACKGROUND Chemoradiation with 5-fluorouracil and mitomycin remains the standard of care for squamous cell carcinoma (SCC) of the anal canal. A prolonged treatment time is associated with inferior disease-specific outcomes. Radiation Therapy Oncology Group trial 0529 demonstrated decreased toxicity and fewer treatment breaks with intensity-modulated radiotherapy (IMRT), but this has not been assessed in a randomized trial. Using data from the National Cancer Data Base (NCDB), this study evaluated the impact of IMRT on treatment time and survival in anal SCC. METHODS The NCDB was used to identify patients with anal cancer from 2004 to 2013. The included patients were those with stage I to III squamous cell cancer of the anal canal who had received definitive chemoradiation by IMRT or 3-dimensional conformal radiation therapy (3DCRT). Statistical analyses were performed with logistic regression, Kaplan-Meier analysis, Cox proportional hazards analysis, and propensity score-matched analysis. RESULTS Of 6814 patients, 57.4% were treated with 3DCRT, whereas 42.6% received IMRT. Patients receiving IMRT had a reduced risk of a long treatment time in a multivariate analysis (P < .001). The 5-year overall survival (OS) rates with IMRT and 3DCRT were 80.8% and 78.9%, respectively (P = .0036). According to a propensity analysis, patients receiving IMRT had improved OS (P = .039) and a reduced risk of a long treatment time (P < .0001) in a multivariate analysis. CONCLUSIONS IMRT use was associated with significantly reduced overall treatment time and improved survival in comparison with 3DCRT. It is important to note that NCDB data are not as robust as randomized data. However, these results further support the use of IMRT as part of sphincter-preserving therapy for the anal canal.

This prospective pilot study evaluated (1) the potential for collecting structured longitudinal data on patient-reported non-routine events (PNREs) (i.e., events that deviate from expected or optimal care) during pediatric and adult radiation cancer therapies and (2) the potential relationship between PNREs, Patient-Reported Outcomes Measures (PROMs), and unplanned treatment events (UTEs). Along with PNREs, data were collected on patient’s background, distress, quality of life, hospital system care experience rating, and treatment intensity, during a 3-month period; UTEs were retrospectively captured through review of patients’ records. Initial results suggest a relationship exists between both PNREs and safety-relevant PNREs with patient distress, quality of life, and care experience ratings. UTEs occurred more often in pediatric patients and were primarily related to patients’ underlying disease. This systems-safety approach to identifying at-risk points in treatment pathways has the potential to provide actionable information for the mitigation of shortcomings in cancer therapy.

Skeletal-related events (SREs), common sequelae of metastatic cancer, are reduced by bisphosphonates. In this study, it was postulated that radiopharmaceuticals, added to bisphosphonates, could further decrease the incidence of SREs. NRG Oncology RTOG 0517 randomized patients with breast, lung, and prostate cancer and blastic bone metastases to either zoledronic acid (ZA) alone or ZA plus radiopharmaceuticals (Sr-89 or Sm-153). The primary endpoint was time to development of SREs. Secondary objectives included quality of life (QOL), pain control, overall survival (OS), and toxicity. 261 patients (median age 68; 62% male; 55% prostate, 35% breast, 10% lung) were accrued between July 2006 and February 2011. The study closed early due to a lower than expected rate of SREs. 52 (42%) patients in the ZA arm and 49 (40%) in the radiopharmaceutical arm experienced an SRE. Median time free of SREs was 29.9 and 27.4 months, respectively (p = 0.84). Median OS in the ZA arm and radiopharmaceutical arms was 32.1 and 26.9 months, respectively (p = 0.37). Cox proportional hazards regression model showed that primary disease site (lung) and number of bone metastases (> 2) had a negative impact on OS (p

The Radiation Therapy Committee of SWOG periodically evaluates its strategic plan in an effort to maintain a current and relevant scientific focus, and to provide a standard platform for future development of protocol concepts. Participants in the 2017 Strategic Planning Workshop included leaders in cancer basic sciences, molecular theragnostics, pharmaceutical and technology industries, clinical trial design, oncology practice, and statistical analysis. The committee discussed high-priority research areas, such as optimization of combined modality therapy, radiation oncology–specific drug design, identification of molecular profiles predictive of radiation-induced local or distant tumor responses, and methods for normal tissue-specific mitigation of radiation toxicity. The following concepts emerged as dominant questions ready for national testing: (i) what is the role of radiotherapy in the treatment of oligometastatic, oligorecurrent, and oligoprogressive disease? (ii) How can combined modality therapy be used to enhance systemic and local response? (iii) Can we validate and optimize liquid biopsy and other biomarkers (such as novel imaging) to supplement current response criteria to guide therapy and clinical trial design endpoints? (iv) How can we overcome deficiencies of randomized survival endpoint trials in an era of increasing molecular stratification factors? And (v) how can we mitigate treatment-related side effects and maximize quality of life in cancer survivors? The committee concluded that many aspects of these questions are ready for clinical evaluation and example protocol concepts are provided that could improve rates of cancer cure and quality of survival. Clin Cancer Res; 24(15); 3500–9. ©2018 AACR.

Management of anal carcinoma began as abdominoperineal resection and has evolved to combined chemotherapy and radiation. Early randomized trials demonstrated superior clinical outcomes of combined modality therapy over radiotherapy alone. Subsequent trials investigated alterations in the standard backbone of radiotherapy concurrent with 5-fluorouracil and mitomycin C with intent to maintain clinical outcomes while reducing treatment-related morbidity. The addition of intensity-modulated radiotherapy to radiation planning and delivery has subsequently reduced acute toxicity and detrimental treatment breaks. Ongoing and future trials are aimed at reducing therapy in favorable patient populations to decrease morbidity while intensifying treatment in patients with negative prognostic factors.

Management of locally advanced rectal cancer has evolved over time from surgical resection alone to multimodality therapy with preoperative radiation, chemotherapy, and total mesorectal excision resulting in excellent local control rates. Refinements in neoadjuvant therapies and their sequencing have improved pathologic complete response rates such that consideration of selective radiation and nonoperative management are now active clinical trial questions. Advances in radiation treatment planning and delivery techniques may allow for further reduction in acute treatment-related toxicity in select patient populations. Collectively, therapeutic strategies remain focused on improving outcomes for patients with higher-risk disease and reducing the morbidity of treatment.

Purpose NRG Oncology RTOG 0529 assessed the feasibility of dose-painted intensity modulated radiation therapy (DP-IMRT) to reduce the acute morbidity of chemoradiation with 5-fluorouracil (5FU) and mitomycin-C (MMC) for T2-4N0-3M0 anal cancer. This secondary analysis was performed to identify patient and treatment factors associated with acute and late gastrointestinal (GI) adverse events (AEs). Methods and Materials NRG Oncology RTOG 0529 treatment plans were reviewed to extract dose-volume data for tightly contoured small bowel, loosely contoured anterior pelvic contents (APC), and uninvolved colon outside the target volume (UC). Univariate logistic regression was performed to evaluate association between volumes of each structure receiving doses ≥5 to 60 Gy (V5-V60) in 5-Gy increments between patients with and without grade ≥2 acute and late GI AEs, and grade ≥3 acute GI AEs. Additional patient and treatment factors were evaluated in multivariate logistic regression (acute AEs) or Cox proportional hazards models (late AEs). Results Among 52 evaluable patients, grade ≥2 acute, grade ≥2 late, and grade ≥3 acute GI AEs were observed in 35, 17, and 10 patients, respectively. Trends (P 4 cm, and worse Zubrod performance status. Small bowel volumes of 186.0 cc, 155.0 cc, 41.0 cc, and 30.4 cc receiving doses greater than 25, 30, 35, and 40 Gy, respectively, correlated with increased risk of acute grade ≥2 GI AEs. Conclusions Acute and late GI AEs from 5FU/MMC chemoradiation using DP-IMRT correlate with radiation dose to the small bowel and APC. Such associations will be incorporated in the dose-volume normal tissue constraint design for future NRG oncology anal cancer studies.

BACKGROUND NRG-CC001 sought to evaluate the neuro-protective effects of avoiding the peri-hippocampal stem cell niche using intensity-modulated radiotherapy during WBRT. METHODS Patients with brain metastasis were stratified by RPA class and prior radiosurgery/surgery and randomized to WBRT+M or HA-WBRT+ Memantine (M) (30Gy in 10 fractions). Standardized NCF tests and the M.D. Anderson Symptom Inventory Brain Tumor (MDASI-BT) were obtained at baseline, 2, 4, 6, and 12 months (mos). The primary endpoint was NCF failure defined using the reliable change index. Pre-specified secondary endpoints included patient-reported symptoms using the MDASI-BT. Time to NCF was reported as cumulative incidence (with death without NCF failure as a competing risk); between-arms differences were tested using Gray’s test. Deterioration at discrete time-points were tested using chi-square tests. MDASI-BT symptom burden, interference, and cognitive and neurologic burden were analyzed using mixed effects models and t-tests within the model using Hochberg’s multiplicity adjustment. RESULTS A total of 518 patients were randomized from 7/2016 to 3/2018. Median follow-up for alive patients was 12.1 mos, with no difference between arms in terms of toxicity, overall survival or intracranial progression-free survival. HA-WBRT+M was associated with lower risk of NCF failure (adjusted HR=0.739, 95% CI: 0.577–0.945, p=0.0.016), with differences first noted at 4 mos in Trail Making Test Part-B (23.3% vs. 40.4% deteriorated, p=0.012). Age did not dilute treatment effect. HA-WBRT+M was associated with reduced cognitive symptom burden in an imputed model (estimate=-0.29, p=0.0425), and also reduced overall symptom burden (p< 0.0001) and interference (p< 0.0016) at 6 mos. CONCLUSIONS The addition of HA to WBRT+M preserved NCF and reduced patient reported cognitive symptom burden, overall symptom burden and symptom interference and should be considered standard of care for any patient fit enough to have WBRT. Supported by grants UG1CA189867 (NCORP), U10CA180868 (NRG Oncology Operations), DCP from the National Cancer Institute.

Importance Total neoadjuvant therapy (TNT) is often used to downstage locally advanced rectal cancer (LARC) and decrease locoregional relapse; however, more than one-third of patients develop recurrent metastatic disease. As such, novel combinations are needed. Objective To assess whether the addition of pembrolizumab during and after neoadjuvant chemoradiotherapy can lead to an improvement in the neoadjuvant rectal (NAR) score compared with treatment with FOLFOX (5-fluorouracil, leucovorin, and oxaliplatin) and chemoradiotherapy alone. Design, setting, and participants In this open-label, phase 2, randomized clinical trial (NRG-GI002), patients in academic and private practice settings were enrolled. Patients with stage II/III LARC with distal location (cT3-4 ≤ 5 cm from anal verge, any N), with bulky disease (any cT4 or tumor within 3 mm of mesorectal fascia), at high risk for metastatic disease (cN2), and/or who were not candidates for sphincter-sparing surgery (SSS) were stratified based on clinical tumor and nodal stages. Trial accrual opened on August 1, 2018, and ended on May 31, 2019. This intent-to-treat analysis is based on data as of August 2020. Interventions Patients were randomized (1:1) to neoadjuvant FOLFOX for 4 months and then underwent chemoradiotherapy (capecitabine with 50.4 Gy) with or without intravenous pembrolizumab administered at a dosage of 200 mg every 3 weeks for up to 6 doses before surgery. Main outcomes and measures The primary end point was the NAR score. Secondary end points included pathologic complete response (pCR) rate, SSS, disease-free survival, and overall survival. This report focuses on end points available after definitive surgery (NAR score, pCR, SSS, clinical complete response rate, margin involvement, and safety). Results A total of 185 patients (126 [68.1%] male; mean [SD] age, 55.7 [11.1] years) were randomized to the control arm (CA) (n = 95) or the pembrolizumab arm (PA) (n = 90). Of these patients, 137 were evaluable for NAR score (68 CA patients and 69 PA patients). The mean (SD) NAR score was 11.53 (12.43) for the PA patients (95% CI, 8.54-14.51) vs 14.08 (13.82) for the CA patients (95% CI, 10.74-17.43) (P = .26). The pCR rate was 31.9% in the PA vs 29.4% in the CA (P = .75). The clinical complete response rate was 13.9% in the PA vs 13.6% in the CA (P = .95). The percentage of patients who underwent SSS was 59.4% in the PA vs 71.0% in the CA (P = .15). Grade 3 to 4 adverse events were slightly increased in the PA (48.2%) vs the CA (37.3%) during chemoradiotherapy. Two deaths occurred during FOLFOX: sepsis (CA) and pneumonia (PA). No differences in radiotherapy fractions, FOLFOX, or capecitabine doses were found. Conclusions and relevance Pembrolizumab added to chemoradiotherapy as part of total neoadjuvant therapy was suggested to be safe; however, the NAR score difference does not support further study. Trial registration ClinicalTrials.gov Identifier: NCT02921256.

Over the past decade, significant strides have been made in improving local control for stage II and III rectal cancer, including the use of neoadjuvant chemoradiation and total mesorectal excision. These advancements have led to a remarkable 10-year local failure rate of just 7.1 %. This has come, however, at the cost of moderate treatment-related morbidity, emphasizing a need for further refinement of management strategies. This article will explore recent innovations and novel approaches involving radiation therapy to address these issues, including the use of intensity-modulated radiation therapy, avoidance of radical resection with the use of chemoradiation alone, total neoadjuvant chemotherapy with the selective use of chemoradiation, and the use of local excision approaches following neoadjuvant treatment. Although many of these novel strategies appear promising, data from prospective randomized trials will be necessary before implementation into standard practice.

BACKGROUND Enrollment rates onto cancer clinical trials are low and reflect a small subset of the population of which even fewer participants come from populations of racial or ethnic diversity or low socioeconomic status. There is a need to increase enrollment onto cancer clinical trials with a focus on recruitment of a diverse, underrepresented patient population. OBJECTIVE To use the electronic medical record (EMR) to understand the eligibility and enrollment rates for all available cancer trials in the ambulatory care setting at an urban safety net hospital to identify specific strategies for enhanced accrual onto cancer clinical trials of diverse and underserved patients. METHODS A clinical trial screening note was created for the EMR by the clinical trials office at an urban safety net hospital. 847 cancer clinical trial screening notes were extracted from the EMR between January 1, 2010 and December 31, 2010. During that time, 99 cancer trials were registered for accrual, including clinical treatment, survey, data repository, imaging, and symptom management trials. Data on eligibility, enrollment status, and relationship to sociodemographic status were compared. LIMITATIONS This is a single-institution and retrospective study. CONCLUSIONS The findings demonstrate that a formal process of tracking cancer clinical trial screens using an EMR can document baseline rates of institution-specific accrual patterns and identify targeted strategies for increasing cancer clinical trial enrollment among a vulnerable patient population. Offering nontreatment trials may be an important and strategic method of engaging this vulnerable population in clinical research.

8 Background: This NCTN multi-arm randomized phase II modular clinical trial platform utilizes TNT with parallel EAs in LARC. EAs are not intended for direct comparison, but rather to test a variety of sensitizers or hypotheses in a consistent and homogenous high-risk pt population with correlative biomarkers. Here we report the primary and available secondary endpoints (EPs). Methods: Stage II/III LARC pts (with ONE or more of the following: distal location [cT3-4 ≤5cm from anal verge, any N]; bulky [any cT4 or tumor within 3mm of mesorectal fascia]; high risk for metastatic disease [cN2]; or not a sphincter-sparing surgery [SSS] candidate) were randomized to neoadjuvant FOLFOX x 4mo → chemoRT (capecitabine with 50.4Gy +/- pembrolizumab 200mg IV Q3 wks x 6 doses) → surgery 8-12 wks following last dose of radiotherapy. Primary EP: Improvement in Neoadjuvant Rectal Cancer (NAR) score for EA v control potentially representing a 3-4% absolute OS improvement. Secondary EPs: Comparisons of OS, DFS, toxicity, pCR, cCR, therapy completion, negative surgical margins, sphincter sparing surgery (SSS), and exploratory assessments of molecular and radiographic predictors of response and distant failure. Binary EPs compared by Fisher’s exact test. Reported p-values are two-sided. Results: From 8/2018-5/2019, 185 pts were randomized to control (n=95) or pembrolizumab (n= 90). Baseline characteristics were relatively well balanced. 137 pts were evaluable for NAR (68 control, 69 pembrolizumab). Mean NAR was 14.08 for control (95% CI: 10.7-17.4) v 11.53 for pembrolizumab (CI: 8.5-14.6) (p=0.26). pCR=29.4% v 31.9% (p=0.75); cCR=13.6% v 13.9% (p=0.95); and SSS=71.0% v 59.4% (p=0.15). The side effects on Arm 3 were consistent with both CRT and pembrolizumab safety profile. Grade 3/4 AEs were slightly increased on the pembrolizumab arm during and after CRT (48.2 v 37.3%). There were 2 deaths during FOLFOX, one on the control arm due to sepsis; the other on the EA due to pneumonia. There were no statistically significant differences in RT (fractions, dose, boost fractions, or boost dose), FOLFOX or capecitabine doses. Conclusions: Pembrolizumab added to chemoRT as part of TNT was safe and without unexpected short-term toxicities but failed to improve the NAR score. The secondary endpoints including PFS and OS have not been reached. Correlative analysis for both T-cell and myeloid cell populations in the tissue and blood in addition to comprehensive cytokine analysis is ongoing. NCT02921256. Support: U10CA180868, -180822; UG1-189867; U24-196067. Clinical trial information: NCT02921256.

Purpose In studies evaluating the benefit of adjuvant therapies, immortal time bias (ITB) can affect the results by incorrectly reporting a survival advantage. It does so by including all deceased patients who may have been planned to receive adjuvant therapy within the observation cohort. Given the increase in National Cancer Database (NCDB) analyses evaluating postoperative radiation therapy (PORT) as an adjuvant therapy, we sought to examine how often such studies accounted and adjusted for ITB. Methods and Materials A systematic review was undertaken to search MEDLINE and EMBASE from January 2014 until May 2019 for NCDB studies evaluating PORT. After appropriate exclusion criteria were applied, 60 peer-reviewed manuscripts in which PORT was compared with postoperative observation or maintenance therapy were reviewed. The manuscripts were reviewed to evaluate whether ITB was accounted for, the method with which it was adjusted for, impact factor, year of publication, and whether PORT was beneficial. Results Of the 60 publications reviewed, 23 studies (38.3%) did not include an adjustment for ITB. Most studies that did adjust for ITB employed a single landmark (LM) time (n = 31), 4 used a sequential landmark analyses, and 2 used a time-dependent Cox model. In 23 of 31 studies (74.2%) that did adjust for ITB via a single LM time, the rationale behind why the specified LM time was chosen was not clearly explained. There was no relationship between adjusting for ITB and year of publication (P = .074) or whether the study was published in a high-impact journal (P = .55). Conclusions Studies assessing adjuvant radiation therapy by analyzing the NCDB are susceptible to ITB, which overestimates the effect size of adjuvant therapies and can provide misleading results. Adjusting for this bias is essential for accurate data representation and to better quantify the impact of adjuvant therapies such as PORT.

Graphical abstract, Highlights • We aimed at quantifying inter-observer Pancoast tumors delineation variability. • Experts’ delineations were used to define ground truth. • Other observers’ delineations were compared against ground truth. • High degree of variability was noted for most target volumes except GTV_P. • This unveils potentials for protocol modification for future IMRT studies., Introduction Target delineation variability is a significant technical impediment in multi-institutional trials which employ intensity modulated radiotherapy (IMRT), as there is a real potential for clinically meaningful variances that can impact the outcomes in clinical trials. The goal of this study is to determine the variability of target delineation among participants from different institutions as part of Southwest Oncology Group (SWOG) Radiotherapy Committee’s multi-institutional in-silico quality assurance study in patients with Pancoast tumors as a “dry run” for trial implementation. Methods CT simulation scans were acquired from four patients with Pancoast tumor. Two patients had simulation 4D-CT and FDG-FDG PET-CT while two patients had 3D-CT and FDG-FDG PET-CT. Seventeen SWOG-affiliated physicians independently delineated target volumes defined as gross primary and nodal tumor volumes (GTV_P & GTV_N), clinical target volume (CTV), and planning target volume (PTV). Six board-certified thoracic radiation oncologists were designated as the ‘Experts’ for this study. Their delineations were used to create a simultaneous truth and performance level estimation (STAPLE) contours using ADMIRE software (Elekta AB, Sweden 2017). Individual participants’ contours were then compared with Experts’ STAPLE contours. Results When compared to the Experts’ STAPLE, GTV_P had the best agreement among all participants, while GTV_N showed the lowest agreement among all participants. There were no statistically significant differences in all studied parameters for all TVs for cases with 4D-CT versus cases with 3D-CT simulation scans. Conclusions High degree of inter-observer variation was noted for all target volume except for GTV_P, unveiling potentials for protocol modification for subsequent clinically meaningful improvement in target definition. Various similarity indices exist that can be used to guide multi-institutional radiotherapy delineation QA credentialing.

PURPOSE: NRG CC001, a phase III trial of WBRT plus memantine with or without hippocampal avoidance, sought to evaluate the neuro-protective effects of avoiding the hippocampus using intensity-modulated radiotherapy. METHODS: Adult patients with brain metastases were stratified by RPA class and receipt of prior radiosurgery/surgery and randomized to WBRT+memantine (WBRT+M) versus hippocampal-avoidant WBRT+memantine (HA-WBRT+M) (30Gy in 10 fractions). Standardized NCF tests were performed at baseline, 2, 4, 6, and 12 months. The primary endpoint was time to NCF failure, defined as decline on at least one of the following tests using the reliable change index: Hopkins Verbal Learning Test-Revised, Trail Making Test, or Controlled Oral Word Association. Cumulative incidence was used to estimate time to NCF failure (death without NCF failure was treated as competing risk) with between-arms differences tested using Grays test. To detect an 11% absolute reduction in 6-month NCF failure, 382 analyzable patients were required for 90% power with two-sided =0.05. Due to possible non-compliance, the sample size was increased by 25% (510 patients). RESULTS: From July 2016 to March 2018, 518 patients were randomized. Median age was 61.5 years. Median follow-up for alive patients was 6.1 months. Treatment arms did not differ in grade3 toxicity, overall survival, intracranial progression, or baseline NCF. Time to NCF failure was significantly longer in favor of HA-WBRT+M (p=0.012). The 6-month NCF failure rates were 69.1% (95% CI:61.8–75.3%) vs. 58.0% (95% CI:50.2–64.9%) for WBRT+M vs. HA-WBRT+M, respectively. After adjusting for stratification factors, HA-WBRT+M (hazard ratio (HR)=0.73, 95%CI:0.56–0.94, p=0.016) and age 61 years (HR=0.61, 95%CI:0.46–0.81, p=0.0006) remained significant. CONCLUSION: Preliminary analysis confirms that conformal avoidance of the neuro-regenerative hippocampal stem cell compartment during WBRT preserves neurocognitive function while achieving similar intracranial control and survival. Supported by grants UG1CA189867 (NCORP), U10CA180868 (NRG Oncology Operations), DCP from the National Cancer Institute.

PurposeThere is considerable interest in very short (ultrahypofractionated) radiation therapy regimens to treat prostate cancer based on potential radiobiological advantages, patient convenience, and resource allocation benefits. Our objective is to demonstrate that detectable changes in health-related quality of life measured by the bowel and urinary domains of the Expanded Prostate Cancer Index Composite (EPIC-50) were not substantially worse than baseline scores.Methods and materialsNRG Oncology's RTOG 0938 is a nonblinded randomized phase 2 study of National Comprehensive Cancer Network low-risk prostate cancer in which each arm is compared with a historical control. Patients were randomized to 5 fractions (7.25 Gy in 2 weeks) or 12 fractions (4.3 Gy in 2.5 weeks). The co-primary endpoints were the proportion of patients with a change in EPIC-50 bowel score at 1 year (baseline to 1 year) >5 points and in EPIC-50 urinary score >2 points tested with a 1-sample binomial test.ResultsThe study enrolled 127 patients to 5 fractions (121 analyzed) and 128 patients to 12 fractions (125 analyzed). Median follow-up for all patients at the time of analysis was 3.8 years. The 1-year frequency for >5 point change in bowel score were 29.8% (P < .001) and 28.4% (P < .001) for 5 and 12 fractions, respectively. The 1-year frequencies for >2 point change in urinary score were 45.7% (P < .001) and 42.2% (P < .001) for 5 and 12 fractions, respectively. For 5 fractions, 32.9% of patients had a drop in 1-year EPIC-50 sexual score of ≥11 points (P = .34); for 12 fractions, 30.9% of patients had a drop in 1-year EPIC-50 sexual score of ≥ 11 points (P = .20). Disease-free survival at 2 years is 99.2% (95% confidence interval: 97.5-100) in the 5-fraction arm and 97.5% (95% confidence interval: 94.6-100) in the 12-fraction arm. There was no late grade 4 or 5 treatment-related urinary or bowel toxicity.ConclusionsThis study confirms that, based on changes in bowel and urinary domains and toxicity (acute and late), the 5- and 12-fraction regimens are well tolerated. These ultrahypofractionated approaches need to be compared with current standard radiation therapy regimens.

Purpose NRG Oncology/RTOG 1203 was designed to compare patient-reported acute toxicity and health-related quality of life during treatment with standard pelvic radiation or intensity-modulated radiation therapy (IMRT) in women with cervical and endometrial cancer. Methods Patients were randomly assigned to standard four-field radiation therapy (RT) or IMRT radiation treatment. The primary end point was change in patient-reported acute GI toxicity from baseline to the end of RT, measured with the bowel domain of the Expanded Prostate Cancer Index Composite (EPIC). Secondary end points included change in patient-reported urinary toxicity, change in GI toxicity measured with the Patient-Reported Outcome Common Terminology Criteria for Adverse Events, and quality of life measured with the Trial Outcome Index. Results From 2012 to 2015, 289 patients were enrolled, of whom 278 were eligible. Between baseline and end of RT, the mean EPIC bowel score declined 23.6 points in the standard RT group and 18.6 points in the IMRT group ( P = .048), the mean EPIC urinary score declined 10.4 points in the standard RT group and 5.6 points in the IMRT group ( P = .03), and the mean Trial Outcome Index score declined 12.8 points in the standard RT group and 8.8 points in the IMRT group ( P = .06). At the end of RT, 51.9% of women who received standard RT and 33.7% who received IMRT reported frequent or almost constant diarrhea ( P = .01), and more patients who received standard RT were taking antidiarrheal medications four or more times daily (20.4% v 7.8%; P = .04). Conclusion Pelvic IMRT was associated with significantly less GI and urinary toxicity than standard RT from the patient’s perspective.

BACKGROUND: NRG CC001, a phase III trial of WBRT+memantine (WBRT+M) with or without Hippocampal Avoidance (HA), sought to assess the neuro-protective effects of lowering the radiation dose received by the hippocampus. METHODS: Patients (pts) with brain metastases were stratified by RPA class and prior radiosurgery/surgery and randomized to either WBRT+M or HA-WBRT+M (30Gy/10 fractions). Standardized neurocognitive function (NCF) tests were performed at baseline, 2, 4, 6, and 12 months (mos.). The primary endpoint was NCF failure, defined as decline using the reliable change index on Hopkins Verbal Learning Test-Revised, Trail Making Test, or Controlled Oral Word Association. Cumulative incidence estimated NCF failure (death without NCF failure was competing risk); between-arms differences tested using Gray’s test. Deterioration at each collection time point was tested using a chi-square test. Patient-reported symptoms were assessed using the MD Anderson Symptom Inventory with Brain Tumor module and analyzed using mixed effects models and t-tests. RESULTS: From 7/2016 to 3/2018, 518 patients were randomized. Median follow-up was 7.9 mos. HA-WBRT+M was associated with lower NCF failure risk (adjusted HR=0.74, p=0.02) due to lower risk of deterioration in executive function at 4 mos. (p=0.01); and encoding (p=0.049) and consolidation (p=0.02) at 6 mos. Age≤61 predicted for lower NCF failure risk (HR=0.60, p=0.0002); non-significant test for interaction indicated independent effects of HA and age. Patient-reported fatigue (p=0.036); difficulty speaking (p=0.049); and problems remembering things (p=0.013) at 6 mos. favored the HA-WBRT+M arm. Imputation models accounting for missing data also favored the HA-WBRT+M arm for patient-reported cognition (p=0.011) and symptom interference (p=0.008) at 6 mos. Treatment arms did not significantly differ in toxicity; intracranial progression or overall survival. CONCLUSIONS: While achieving similar intracranial control and survival; Hippocampal Avoidance during WBRT+M for brain metastases better preserves NCF and patient-reported symptoms. Supported by UG1CA189867 (NCORP) and DCP from the NCI.

Background Infection with the human immunodeficiency virus (HIV) remains associated with a greater risk of anal cancer, despite widespread use of combination antiretroviral therapy. Evidence concerning the acceptability of anal cancer screening gives little attention to women. Because HIV-infected women have a high prevalence of depression and history of sexual trauma, understanding acceptability among this group is critical. Purpose We sought to assess barriers and motivators to participation in anal cancer screening research among a racial/ethnically diverse HIV-infected female population. Methods We conducted a survey based on the Health Belief Model to identify characteristics of women willing to participate in anal cancer screening research ( n = 200). Bivariate analyses examined associations between willingness to participate and sociodemographics, clinical characteristics, and health beliefs. Logistic regression modeled willingness to participate in research. Main Findings Of the women who participated, 37% screened positive for depression, 43% reported a high trauma history, and 36% screened positive for posttraumatic stress disorder. Overall, 65% reported willingness to participate in research. Those likely to participate were older, reported intravenous drug use as their HIV risk factor, and had a history of prior high-resolution anoscopy (HRA) compared with those unwilling to participate. The most commonly reported barrier to anal Pap testing was fear of pain. In adjusted analyses, a lack of fear of pain and prior experience with HRA significantly predicted willingness to participate. Conclusions Findings suggest that, to increase participation in anal Pap and HRA-related research for HIV-infected women, a single approach may not be adequate. Rather, we must harness patients' previous experiences and address psychosocial and financial concerns to overcome barriers to participation.

Background The purpose of this study was to evaluate how gross tumor volume (GTV) affects treatment outcome among different race/ethnic groups in patients with head and neck cancer receiving definitive radiotherapy (RT). Methods Ninety-one patients with head and neck cancer were treated to a median RT dose of 69.96 Gy in 33 fractions. The patient's self-reported race/ethnicity, primary tumor, and nodal GTV were obtained. Two-year actuarial local, nodal, and distant control, and overall and disease-free survival were calculated. Results The patients were categorized as white (n = 43) or non-white (n = 48), which included 29 African Americans, 11 Hispanics, 5 Asians, and 3 others. The mean primary GTV was 21.0 cc and 39.9 cc for whites and non-whites, respectively (p = .011). White patients reported improved overall survival of 85.4% compared to non-whites (65.8%; p = .006). Improvements in local and nodal control and disease-free survival rates were also observed. Conclusion White patients demonstrated improved treatment outcomes compared with non-whites, which may be reflective of tumor volume. © 2014 Wiley Periodicals, Inc. Head Neck, 2015

Purpose We sought to evaluate the incidence of vaginal stenosis (VS) and identify clinical and treatment factors that predict for VS in female patients with anal cancer treated with definitive chemoradiation. Methods and materials The cohort included 95 consecutive women receiving definitive chemoradiation between 2003 and 2012. All but 1 received intensity modulated radiation therapy; median primary tumor dose 50.4 Gy (range, 41.4‐60). A modified National Cancer Institute Common Terminology Criteria for Adverse Events version 4 was used to score VS based on the medical record description of dyspareunia, pain with dilator use, vaginal dryness, or difficult pelvic examination. Ordered logistic regression was performed to assess VS predictors. Results Median age was 60.4 years (range, 19‐97). With median follow-up of 2.5 years, 70 women (74%) had adequate information to assess VS. Of these, VS grade distribution was 21.4% grade 0, 14.3% grade 1, 27.1% grade 2, and 37.1% grade 3. By multivariable ordered logistic regression, younger age (P = .02), higher tumor dose (P = .06), and earlier treatment year (P = .04) were associated with higher grade of VS. Conclusions VS is a common late complication in women treated definitively with chemoradiation for anal canal cancer. Younger age, higher tumor dose, and earlier year of treatment were associated with a higher grade of stenosis. Prospective investigation into patient reported outcomes is warranted, including sexual function and VS prevention strategies to better understand its effect on long-term survivorship.

Purpose Beginning in 2010, the ABR has administered triennial clinical practice analysis surveys to inform examination development volunteers and staff about the actual state of radiation oncology practice. Methods and Materials As reported here, the 2016 survey was designed to provide objective data regarding actual patient volumes of specific disease sites and subjective insight as to the importance and relevance of site-specific therapy to individual practices. Results The survey instrument was circulated to 4,075 radiation oncologists listed in the membership database of the American Society for Radiation Oncology, and responses were received from 690 (16.9%); a total of 287 (41.5%) self-identified as being in academic practice. Even in the academic setting, a majority (216 of 287, or 75.3%) indicated that they spend most of their time in clinical practice. Conclusions Data from the survey are informative regarding changes in the practice of radiation oncology over the past 6 years.

Locally advanced rectal cancer (LARC) carries higher risks of local and distant recurrence when treated with surgical resection alone. Multiple treatment strategies have been investigated to reduce recurrence risk and improve survival. Currently, there are 3 primary strategies for managing LARC: (1) preoperative long-course radiotherapy (RT) combined with radiosensitizing chemotherapy, which is better tolerated than postoperative chemoradiotherapy and provides tumor downstaging and improved pathologic complete response (pCR), followed by postoperative chemotherapy; (2) preoperative short-course RT alone as an alternative strategy for reducing the risk of local recurrence, followed by adjuvant postoperative chemotherapy; and (3) total neoadjuvant therapy with induction chemotherapy followed by chemoradiotherapy to improve pCR and reduce the difficulty of delivering chemotherapy in the postoperative setting. In addition to these currently recommended treatment paradigms, promising new strategies are available for treatment reduction. Neoadjuvant chemotherapy alone may allow for omission of RT in select patients with favorable LARC. For patients who have complete clinical responses to neoadjuvant chemotherapy and RT, nonoperative management is being considered for sphincter preservation, with surgery used as salvage. These are active areas of investigation in both institutional and cooperative group trials. The results are anticipated to provide better tailoring of neoadjuvant therapy based on patient tumor and disease response characteristics.