BACKGROUND: Management of lateral pelvic lymph nodes in locally advanced rectal cancer is controversial, with limited data indicating the optimal approach. In addition, no data exist regarding the treatment of lateral nodes in the setting of short-course radiation and nonoperative intent. OBJECTIVE: To evaluate a novel approach incorporating simultaneous integrated boost to suspicious lateral nodes. DESIGN: A retrospective study. SETTING: This study was conducted at a large tertiary referral center. PATIENTS: Patients treated with radiation therapy and consolidation chemotherapy were included. All primary tumors underwent biopsy confirmation and disease staging with pelvic MRI. INTERVENTIONS: Primary tumors were biopsy proven and staged with pelvic MRI. A subset of lateral pelvic lymph node patients received a simultaneous integrated boost of 35 Gy in 5 fractions. Then, chemotherapy was administered, with the majority receiving modified folinic acid, fluorouracil, and oxaliplatin. Clinical partial response required total mesorectal excision. MAIN OUTCOME MEASURES: Patterns of failure and survival analyses by subgroup were assessed. Outcomes based on receipt of radiation were compared across node status. RESULTS: Between January 2017 and January 2022, 155 patients were treated with short-course chemotherapy, with 121 included in the final analysis. Forty-nine percent of patients underwent nonoperative management. The median follow-up was 36 months and the median age was 58 years. Thirty-eight patients (26%) had positive lateral pelvic lymph nodes. Comparing lateral node status, progression-free survival was significantly worse for patients with positive disease (p < 0.001), with a trend for worse overall survival. Receipt of nodal boost in patients with lateral nodes resulted in meaningful locoregional control. Nodal boost did not contribute to additional acute or late GI toxicity. LIMITATIONS: Limitations include retrospective nature and lack of lateral node pathology; however, a thorough radiographic review was performed. CONCLUSIONS: Lateral node-positive rectal cancer is correlated with worse oncologic outcomes and higher locoregional failure. Boost to clinically positive lateral nodes is a safe approach in the setting of short course radiation and in those receiving nonoperative intent. See Video Abstract. [GRAPHICS] (C) The ASCRS 2023

Purpose: Ablative radiation therapy for borderline resectable or locally advanced pancreatic ductal adenocarcinoma (BR/LA-PDAC) may limit concurrent chemotherapy dosing and usually is only safely deliverable to tumors distant from gastrointesti-nal organs. Magnetic resonance guided radiation therapy may safely permit radiation and chemotherapy dose escalation. Methods and Materials: We conducted a single-arm phase I study to determine the maximum tolerated dose of ablative hypofractionated radiation with full-dose gemcitabine/nab-paclitaxel in patients with BR/LA-PDAC. Patients were treated with gemcitabine/nab-paclitaxel (1000/125 mg/m2) x 1c then concurrent gemcitabine/nab-paclitaxel and radiation. Gemcita-bine/nab-paclitaxel and radiation doses were escalated per time-to-event continual reassessment method from 40 to 45 Gy 25 fxs with chemotherapy (600-800/75 mg/m(2)) to 60 to 67.5 Gy/15 fractions and concurrent gemcitabine/nab-paclitaxel (1000/ 100 mg/m(2)). The primary endpoint was maximum tolerated dose of radiation as defined by 60-day dose limiting toxicity (DLT). DLT was treatment-related G5, G4 hematologic, or G3 gastrointestinal requiring hospitalization >3 days. Secondary endpoints included resection rates, local progression free survival (LPFS), distant metastasis free survival (DMFS), and overall survival (OS). Results: Thirty patients enrolled (March 2015-February 2019), with 26 evaluable patients (2 progressed before radiation, 1 was determined ineligible for radiation during planning, 1 withdrew consent). One DLT was observed. The DLT rate was 14.1% (3.3%-24.9%) with a maximum tolerated dose of gemcitabine/nab-paclitaxel (1000/100 mg/m(2)) and 67.5 Gy/15 fractions. At a median follow-up of 40.6 months for living patients the median OS was 14.5 months (95% confidence interval [CI], 10.9-28.2 months). The median OS for patients with Eastern Collaborative Oncology Group 0 and carbohydrate antigen 19-9 <90 were 34.1 (95% CI, 13.6-54.1) and 43.0 (95% CI, 8.0-not reached) months, respectively. Two-year LPFS and DMFS were 85% (95% CI, 63%-94%) and 57% (95% CI, 34%-73%), respectively. Conclusions: Full-dose gemcitabine/nab-paclitaxel with ablative magnetic resonance guided radiation therapy dosing is safe in patients with BR/LA-PDAC, with promising LPFS and DMFS.& COPY; 2022 Elsevier Inc. All rights reserved.

Purpose: Our purpose was to evaluate the maximum tolerated dose of hypofractionated proton beam radiation therapy with concurrent weekly carboplatin/paclitaxel in patients with stage II-III non-small cell lung cancer. Methods and Materials: A phase I trial was designed using the time-to-event continuous reassessment method. Maximum tolerated dose was defined as the dose associated with a 20% probability of Common Terminology Criteria for Adverse Events protocol-specified serious adverse events (SAEs). Starting dose was 3.5 Gy/fx for 15 fractions with 2 potential escalation and de-escalation levels in 0.25 Gy/fx increments. Chemotherapy was weekly concurrent carboplatin/paclitaxel with 2 cycles of optional consolidation carboplatin/paclitaxel. Results: From May 2015 to September 2016, 23 patients enrolled at a single institution. Of 20 evaluable, median age was 66.5 years (range, 54-89) and 12 were male (60%). Fourteen (70%) had squamous cell and 15 (75%) were stage IIIA. Nineteen (95%) completed all 3 cycles of concurrent chemotherapy, and 16 (80%) received at least 1 cycle of consolidation chemotherapy. Within the 6-month time-to-event continuous reassessment method assessment window, no SAEs were reported, and most patients were treated at the highest dose level. Dose level assignment was 52.5 Gy (n = 2), 56.25 Gy (n = 4), and 60 Gy (n = 14). The posterior probability of dose-limiting toxicity for 60 Gy was 5.3% (95% confidence interval, 1%-18.1%). Acute, nonserious AEs included grade 2 esophagitis in 7 patients (35%) and grade 2 pneumonitis in 1 patient (5%). At a median follow-up of 20.3 months for all and 44.9 months for living patients, there were no grade 4 or 5 AEs, though there were 3 (21% at 24 months) SAEs outside of the dose-escalation window. The 2-year overall survival, local, regional, and distant control rates were 48%, 84%, 77%, and 79%, respectively. Conclusions: Hypofractionated proton beam radiation therapy and chemotherapy up to 60 Gy in 15 fractions is acutely well tolerated, with high rates of locoregional control and overall survival, though late SAEs were noted. (C) 2022 Elsevier Inc. All rights reserved.

INTRODUCTION:A kV imager coupled to a novel, ring-gantry radiotherapy system offers improved on-board kV-cone-beam computed tomography (CBCT) acquisition time (17-40 seconds) and image quality, which may improve CT radiotherapy image-guidance and enable online adaptive radiotherapy. We evaluated whether inter-observer contour variability over various anatomic structures was non-inferior using a novel ring gantry kV-CBCT (RG-CBCT) imager as compared to diagnostic-quality simulation CT (simCT). MATERIALS/METHODS:Seven patients undergoing radiotherapy were imaged with the RG-CBCT system at breath hold (BH) and/or free breathing (FB) for various disease sites on a prospective imaging study. Anatomy was independently contoured by seven radiation oncologists on: 1. SimCT 2. Standard C-arm kV-CBCT (CA-CBCT), and 3. Novel RG-CBCT at FB and BH. Inter-observer contour variability was evaluated by computing simultaneous truth and performance level estimation (STAPLE) consensus contours, then computing average symmetric surface distance (ASSD) and Dice similarity coefficient (DSC) between individual raters and consensus contours for comparison across image types. RESULTS:Across 7 patients, 18 organs-at-risk (OARs) were evaluated on 27 image sets. Both BH and FB RG-CBCT were non-inferior to simCT for inter-observer delineation variability across all OARs and patients by ASSD analysis (p < 0.001), whereas CA-CBCT was not (p = 0.923). RG-CBCT (FB and BH) also remained non-inferior for abdomen and breast subsites compared to simCT on ASSD analysis (p < 0.025). On DSC comparison, neither RG-CBCT nor CA-CBCT were non-inferior to simCT for all sites (p > 0.025). CONCLUSIONS:Inter-observer ability to delineate OARs using novel RG-CBCT images was non-inferior to simCT by the ASSD criterion but not DSC criterion.

PURPOSE:Short-course radiation therapy (SCRT) and nonoperative management are emerging paradigms for rectal cancer treatment. This clinical trial is the first to evaluate SCRT followed by chemotherapy as a nonoperative treatment modality.METHODS:Patients with nonmetastatic rectal adenocarcinoma were treated on the single-arm, Nonoperative Radiation Management of Adenocarcinoma of the Lower Rectum study of SCRT followed by chemotherapy. Patients received 25 Gy in 5 fractions to the pelvis followed by FOLFOX ×8 or CAPOX ×5 cycles. Patients with clinical complete response (cCR) underwent nonoperative surveillance. The primary end point was cCR at 1 year. Secondary end points included safety profile and anorectal function.RESULTS:From June 2016 to March 2019, 19 patients were treated (21% stage I, 32% stage II, and 47% stage III disease). At a median follow-up of 27.7 months for living patients, the 1-year cCR rate was 68%. Eighteen of 19 patients are alive without evidence of disease. Patients with cCR versus without had improved 2-year disease-free survival (93% vs 67%; P = .006), distant metastasis-free survival (100% vs 67%; P = .03), and overall survival (100% vs 67%; P = .03). Involved versus uninvolved circumferential resection margin on magnetic resonance imaging was associated with less initial cCR (40% vs 93%; P = .04). Anorectal function by Functional Assessment of Cancer Therapy-Colorectal cancer score at 1 year was not different than baseline. There were no severe late effects.CONCLUSIONS:Treatment with SCRT and chemotherapy resulted in high cCR rate, intact anorectal function, and no severe late effects. NCT02641691.

Purpose The purpose of this work is to create a decision support methodology to predict when patients undergoing radiotherapy treatment for locally advanced lung cancer would potentially benefit from adaptive radiotherapy. The proposed methodology seeks to eliminate the manual subjective review by developing an automated statistical learning model to predict when tumor regression would trigger implementation of adaptive radiotherapy based on quantified anatomic changes observed in individual patients on-treatment cone beam computed tomographies (CTs). This proposed process seeks to improve the efficacy and efficiency of both the existing manual and automated adaptive review processes for locally advanced stage III lung cancer. Methods A predictive algorithm was developed as a decision support tool to determine the potential utility of mid-treatment adaptive radiotherapy based on anatomic changes observed on 1158 daily CBCT images across 43 patients. The anatomic changes on each axial slice within specified regions-of-interest were quantified into a single value utilizing imaging similarity criteria comparing the daily CBCT to the initial simulation CT. The range of the quantified metrics for each fraction across all axial slices are reduced to specified quantiles, which are used as the predictive input to train a logistic regression algorithm. A "ground-truth" of the need for adaptive radiotherapy based on tumor regression was evaluated systematically on each of the daily CBCTs and used as the classifier in the logistic regression algorithm. Accuracy of the predictive model was assessed utilizing both a tenfold cross validation and an independent validation dataset, with the sensitivity, specificity, and fractional accuracy compared to the ground-truth. Results The sensitivity and specificity for the individual daily fractions ranged from 87.9%-94.3% and 91.9%-98.6% for a probability threshold of 0.2-0.5, respectively. The corresponding average treatment fraction difference between the model predictions and assessed ART "ground-truth" ranged from -2.25 to -0.07 fractions, with the model predictions consistently predicting the potential need for ART earlier in the treatment course. By initially utilizing a lower probability threshold, the higher sensitivity minimizes the chance of false negative by alerting the clinician to review a higher number of questionable cases. Conclusions The proposed methodology accurately predicted the first fraction at which individual patients may benefit from ART based on quantified anatomic changes observed in the on-treatment volumetric imaging. The generalizability of the proposed method has potential to expand to additional modes of adaptive radiotherapy for lung cancer patients with observed underlying anatomic changes.

PURPOSE: To assist radiation oncology centers in implementing Lutetium-177-dotatate (Lu-177) radiopharmaceutical therapy for midgut neuroendocrine tumors. Here we describe our workflow and how it was revised based on our initial experience on an expanded access protocol (EAP). METHODS: A treatment team/area was identified. An IV-pump-based infusion technique was implemented. Exposure-based techniques were implemented to determine completion of administration, administered activity, and patient releasability. Acute toxicities were assessed at each fraction. A workflow failure modes and effects analysis (FMEA) was performed. RESULTS: A total of 22 patients were treated: 11 patients during EAP (36 administrations) and 11 patients after EAP (44 administrations). Mean Lu-177 infusion time was 37 min (range 26-65 min). Mean administered activity was 97% (range 90-99%). Mean patient exposures at 1 m were 1.9 mR/h (range 1.0-4.1 mR/h) post-Lu-177 and 0.9 mR/h (range 0.4-1.8 mR/h) at discharge, rendering patients releasable with instructions. Treatment area was decontaminated and released same day. All patients in the EAP experienced nausea, and nearly half experienced emesis despite premedication with antiemetics. Peripheral IV-line complications occurred in six treatments (16.7%), halting administration in 2 cases (5.6%). We transitioned to peripherally inserted central catheter (PICC)-lines and revised amino acid formulary after the EAP. The second cohort of 11 patients after EAP were analyzed for PICC-line complications and acute toxicity. Nausea and emesis rates decreased (nausea G1+ 61%-27%; emesis G1+ 23%-7%), and no PICC complications were observed. FMEA revealed that a failure in amino acid preparation was the highest risk. CONCLUSION: Lu-177-dotatate can be administered safely in an outpatient radiation oncology department. (c) 2021 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

PURPOSE/OBJECTIVES:Before definitive stereotactic body radiation therapy (SBRT) for presumably node-negative, early-stage NSCLC, many patients are staged with PET/CT alone. In patients undergoing PET/CT prior to SBRT, the role of invasive nodal staging (INS) with endobronchial ultrasound (EBUS) or mediastinoscopy is uncertain. We sought to characterize the impact of nodal staging modality on outcomes. MATERIALS/METHODS:Patients receiving definitive SBRT for T1-2N0 NSCLC deemed node-negative by either PET/CT plus INS (EBUS or mediastinoscopy) or PET/CT alone were identified. Patients with initially equivocal or positive nodes on PET/CT were excluded from this analysis. All patients received 3-5 fraction SBRT according to institutional guidelines. Control was assessed by at least one follow-up CT in all patients. Multivariable logistic regression (MVA) was performed to identify variables independently associated with use of INS. RESULTS:We identified 651 eligible patients at our institution from 2005-2016. INS was performed in 15.2% of patients (n = 99) with EBUS (n = 78) or mediastinoscopy (n = 21). Median follow-up was 19.4 months (0.2-135.1). Median survival was 28.5 months (0.6-140). Factors predictive of increased likelihood of INS after negative PET/CT on MVA were age (OR for decreasing age 1.033; 95% CI 1.058-1.010), Caucasian race (OR vs. non-white 1.852; 1.044-3.289), male sex (1.629; 1.031-2.575), central location (1.978; 1.218-3.211) and squamous histology (2.564; 1.243-5.287). Nodal and/or distant control at 2 years was similar between PET/CT alone (78%, 95% CI 74-82%) and INS + PET/CT (75%, 95% CI 65-85%) (p = 0.877) as well as on MVA. Overall survival did not differ based on staging modality. CONCLUSIONS:In patients with early-stage NSCLC deemed node-negative by PET/CT, addition of INS did not appreciably alter patterns of failure or survival after definitive SBRT. This study does not question the established value of INS for equivocal or suspicious nodes.

PURPOSE:Our purpose was to describe the risk of radiation-induced brachial plexopathy (RIBP) in patients with breast cancer who received comprehensive adjuvant radiation therapy (RT).METHODS AND MATERIALS:Records for 498 patients who received comprehensive adjuvant RT (treatment of any residual breast tissue, the underlying chest wall, and regional nodes) between 2004 and 2012 were retrospectively reviewed. All patients were treated with conventional 3 to 5 field technique (CRT) until 2008, after which intensity modulated RT (IMRT) was introduced. RIBP events were determined by reviewing follow-up documentation from oncologic care providers. Patients with RIBP were matched (1:2) with a control group of patients who received CRT and a group of patients who received IMRT. Dosimetric analyses were performed in these patients to determine whether there were differences in ipsilateral brachial plexus dose distribution between RIBP and control groups.RESULTS:Median study follow-up was 88 months for the overall cohort and 92 months for the IMRT cohort. RIBP occurred in 4 CRT patients (1.6%) and 1 IMRT patient (0.4%) (P = .20). All patients with RIBP in the CRT cohort received a posterior axillary boost. Maximum dose to the brachial plexus in RIBP, CRT control, and IMRT control patients had median values of 56.0 Gy (range, 49.7-65.1), 54.8 Gy (47.4-60.5), and 54.8 Gy (54.2-57.3), respectively.CONCLUSIONS:RIBP remains a rare complication of comprehensive adjuvant breast radiation and no clear dosimetric predictors for RIBP were identified in this study. The IMRT technique does not appear to adversely affect the development of this late toxicity.

BACKGROUND:Consolidation durvalumab improved overall survival (OS) in locally advanced non-small cell lung cancer (LA-NSCLC) treated with chemoradiotherapy (CRT) in the PACIFIC trial; however, pneumonitis was increased with durvalumab. We sought to examine real-world outcomes with the PACIFIC paradigm, especially factors associated with pneumonitis, using a multi-institutional review. METHODS:Patients with LA-NSCLC treated with CRT followed by durvalumab from January 2017-February 2019 were identified at 2 institutions. We characterized demographics, tumor factors, radiotherapy, and duration of durvalumab. We examined pneumonitis outcomes including re-challenge success, with secondary endpoints of progression-free survival (PFS) and OS. RESULTS:Thirty-four patients were included with median follow-up of 12 months (range, 3 to 20 months); 94% had stage III disease. The cumulative grade >2 pneumonitis rate was 26.5% with 2 patients developing grade 3 pneumonitis and no grade 4/5 events. Median time to pneumonitis after RT was 2.4 months (range, 0 to 4.9 months). Pneumonitis management included median prednisone dose of 60 mg for median taper of 6 weeks with durvalumab held for median of 4.5 weeks (range, 2 to 8 weeks); 70% of pneumonitis patients received durvalumab re-challenge, with pneumonitis recurring in 14% of patients. 3-month and 6-month pneumonitis-free-survival were 76.9% and 73.6%, respectively; 9- and 12-month OS were 96% (75.1-99.8%), 86.6% (63.5-95.5%), respectively; 9- and 12-month PFS were 68% (47.5-82.5%), 48.7% (25.3-68.3%). Pneumonitis development did not significantly impact PFS or OS (P>0.05). CONCLUSIONS:Among LA-NSCLC patients treated with CRT followed by consolidation durvalumab, more than 25% developed symptomatic pneumonitis. In this small case series, pneumonitis did not appear to negatively impact survival, and durvalumab re-challenge appeared feasible after pneumonitis treatment with steroids.

When assessing clinical stage I non-small cell lung cancer (NSCLC) patients during consultation, identifying those at risk for adverse events remains a clinical challenge. Our objective was to develop a treatment allocation model with prospectively captured data from all Stage I NSCLC patients receiving either surgery or SBRT and evaluate if discordant treatment allocation for surgery patients was associated with an increased risk of adverse events. From 2016 – 2018, clinical Stage I NSCLC patients receiving treatment in either the Division of Cardiothoracic Surgery or Department of Radiation Oncology were invited to participate in a prospectively maintained database that included physiologic, pathologic, and functional status metrics. A multivariable logistic regression model was made to characterize the likelihood of SBRT receipt for all participating patients, and used to generate a predicted group value (allocation to surgery versus SBRT). From this, ≥ Grade 3 Common Terminology Criteria for Adverse Events (CTCAE) were compared among those surgical patients that the model allocated to surgery (concordant), versus those assigned to SBRT (discordant). In this prospective database, 104 (53%) received SBRT, 91 (47%) received surgery. Variables independently associated with allocation to SBRT included current smoking status (Odds Ratio 8.2, 95% CI 1.5 – 44.7), Global Initiative for Chronic Obstructive Lung Disease (GOLD) score ≥2, (OR 2.7, 95% CI 1.1 – 6.6), increasing 15-foot walk test time (per second increase OR 1.7, 95% CI 1.2 – 2.5), and ECOG ≥1 (OR 8.0, 95% CI 3.0 – 21.4). Of the 73 (80%) surgical patients with complete data for model allocation, 60 patients (82%) were predicted to receive surgery and 13 (18%) were predicted to receive SBRT. The rate of ≥Grade 3 CTCAE among discordantly assigned surgical patients, 6/13 (46.2%), was significantly higher than concordantly assigned surgical patients, 10/60 (16.7%), p = 0.03. Discordant allocation to SBRT demonstrated a strong association with experiencing a ≥Grade 3 CTCAE following surgery (OR 7.2, 95% CI 1.7 – 30.3). Prospectively collected patient information that includes baseline functional and performance status metrics may assist in identifying surgical patients that are high-risk for ≥ Grade 3 CTCAE events. Identifying these patients at the time of consultation may assist in consideration for SBRT and shared-decision making.

Purpose: Patients with inoperable pancreatic adenocarcinoma have limited options, with traditional chemoradiation providing modest clinical benefit and an otherwise poor prognosis. Stereotactic body radiation therapy for pancreatic cancer is limited by proximity to organs-at-risk (OAR). However, stereotactic magnetic resonance-guided adaptive radiation therapy (SMART) has shown promise in delivering ablative doses safely. We sought to demonstrate the benefits of SMART using a 5-fraction approach with daily on-table adaptation. Methods and Materials: Patients with locally advanced, nonmetastatic pancreatic adenocarcinoma were treated with 50 Gy in 5 fractions (biologically effective dose10 100 Gy) with a prescribed goal of 95% planning target volume coverage by 95% of prescription, prioritizing hard OAR constraints. Daily online adaptation was performed using magnetic resonance-guidance and on-table reoptimization. Patient outcomes, treatment factors, and daily adaptation were evaluated. Results: Forty-four patients were treated with SMART at our institution from 2014 to 2019. Median follow-up from date of diagnosis was 16 months (range, 6.7-51.6). Late toxicity was limited to 2 (4.6%) grade 3 (gastrointestinal ulcers) and 3 (6.8%) grade 2 toxicities (duodenal perforation, antral ulcer, and gastric bleed). Tumor abutted OARs in 35 patients (79.5%) and tumor invaded OARs in 5 patients (11.1%). Reoptimization was performed for 93% of all fractions. Median overall survival was 15.7 months (95% confidence interval, 10.2-21.2), while 1-year and 2-year overall survival rates were 68.2% and 37.9%, respectively. One-year local control was 84.3%. Conclusions: This is the first reported experience using 50 Gy in 5 fractions for inoperable pancreatic cancer. SMART allows this ablative dose with promising outcomes while minimizing toxicity. Additional prospective trials evaluating efficacy and safety are warranted.

Recent data show promise of short-course radiation (SCR) plus total neoadjuvant chemotherapy for rectal cancer. We evaluated the complete clinical response (cCR) rate and toxicity in patients who were treated with SCR followed by multi-agent chemotherapy (CH) and non-operative intent. From January 2018 to May 2019, 90 patients with newly diagnosed, non-metastatic rectal adenocarcinoma were treated with SCR-CH and non-operative intent at our institution. Patients received 25 Gy/5 fx to the pelvis with an optional primary boost to 30 Gy. Involved extra-mesorectal pelvic lymph nodes were boosted to 35 Gy. CH was initiated after RT. CR was assessed after CH by digital rectal examination, MRI pelvis, and endoscopy. Patients with a cCR were followed with these assessments every 3 months. Patients with a partial CR received surgery. Follow-up was calculated from CH completion. GI toxicity was graded per CTCAE v5. Of the 90 patients [median age 61 (range 25-91)], 86 (96%) had locally advanced disease (T3/4 or node positive) and median tumor size 4.6 cm (range 1.5-11 cm). The median distance from anal verge was 7 cm (range 0-13 cm). All patients completed prescribed RT. Five patients received CH ≤5 cycles due to poor tolerance. Among patients who completed CH ≥6 cycles, the initial cCR rate was 51% (43/85) overall and 49% (40/81) for patients with locally advanced disease. Median follow-up was 9.7 mos (range 0.7-21 mos) for living patients, and 44% (37/85) patients had continued cCR at last follow up. For patients with primaries ≤2 cm from anal verge, 6 (6/20, 30%) patients had an initial cCR and 5 (25%) patients had a continued cCR at last follow up. Among non-operative patients, 18 (49%) had no late GI toxicities and 0 had late G3/4 GI toxicities. In the 42 patients with a partial CR, 60% underwent low anterior resection, 29% underwent abdominoperineal resection, and 9.5% underwent transanal excision or proctectomy. Seven of 85 patients had local regrowth at a median of 8.5 mos (range 2.3-12 mos) after SCR-CH. Six cases occurred in non-operative patients requiring salvage surgery at a median of 6.0 (range 4.8-15) mos after completion of SCR-CH. Four (4/90, 4.4%) patients developed metastatic disease, all of whom had an initial partial CR and had undergone surgery. Our preliminary data show that SCR-CH can result in cCR and organ preservation in patients with locally advanced and/or low-lying rectal cancer with acceptable GI toxicity. Further follow-up is required to evaluate the durability of response and toxicity.Abstract 96; TablecT StageT212 (13%)T360 (67%)T418 (20%)cN StageN022 (24%)N127 (30%)N241 (46%)Group StageI5 (6%)II17 (19%)IIIA5 (6%)IIIB41 (45%)IIIC22 (24%)RT (Gy/fx)25/574 (82%)30/56 (7%)35/510 (11%)CH Cycles5 or fewer5 (6%)6-851 (56%)9-129 (10%)12 or more25 (28%)CH AgentsFOLFOX/mFOLFOX79 (88%)CAPOX7 (8%)Other4 (4%) Open table in a new tab

Previous work has demonstrated significant differences in the physical and functional status of clinical Stage I non-small cell lung cancer (NSCLC) patients receiving stereotactic body radiation therapy (SBRT) versus surgical resection. However, pre-treatment and longitudinal differences in quality of life measures among these groups is not currently well characterized. From 2016 – 2018, clinical Stage I NSCLC patients receiving definitive treatment in either the Department of Radiation Oncology or Division of Cardiothoracic surgery at a single institution were invited to participate in a prospective database. Consenting patients received QoL assessments pre- and post-treatment at 0, 3, 6, and 12 months. QoL modules included the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) and EORTC lung cancer specific module (QLQ-CL13), with maximum scores of 100. Differences of at least 5 points between the groups' estimated marginal mean values for individual scales were considered clinically significant on analysis of covariance (ANCOVA) testing (delineated by solid lines in Figure 1). Of the 187 participants, 59/90 (66%) SBRT patients and 44/97 (45%) surgery patients had QoL follow-up through one year. SBRT patients were significantly older (mean age 70.5 versus 66.1 years, p = 0.01), more likely to be current smokers (32% versus 16%, p<0.001), and have a Charlson-Deyo comorbidity index >3 (36% versus 11%, p<0.001). At baseline, SBRT patients reported significantly lower baseline scores for global health (64 versus 81, p<0.001), physical status (70 versus 87, p<0.001) and role functioning (76 versus 91, p<0.001). For SBRT patients, significant improvements were reported for these domains after treatment, but returned to baseline or were maintained (role functioning) at one year. For surgery patients, there was a significant decrease in role functioning at 3 months, but returned to baseline by 6 months. Surgery patients experienced subjective decreases in global health and physical functioning, but this did not reach significance. For emotional functioning, there was no difference in baseline scores by treatment type (SBRT 78 versus surgery 77.8, p = 0.7), however both groups reported improved scores following treatment that remained significantly higher at one year. In regards to role function and physical QoL instruments, SBRT patients self-report improvements in these measures after treatment, while surgical patients report reduced scores that return to baseline at one year. Emotional scores significantly improved for both groups following treatment. These findings can help with patient education and shared decision making among these two treatment modalities.

PURPOSE:The medical necessity of stereotactic radiosurgery (SRS) is nonuniform across insurance policies. The American Society for Radiation Oncology (ASTRO) created a model policy based on the consensus of the radiation oncology community to communicate medically necessary indications for SRS. We compared the current insurance policies for SRS with those of the ASTRO model policy. METHODS AND MATERIALS:We identified 58 insurance payers and 3 national benefits managers with SRS policies. Among these, 7 insurance payers were excluded for policies that were not reviewed after 2015 and for not detailing individual medically necessary indications. For each of the indications listed in ASTRO's model policy, we determined the proportion of payers that considered SRS medically necessary. We compared these proportions for national versus regional payers and policies updated in the last 12 months versus those updated less often using Fisher exact and χ2 tests. RESULTS:All insurance policies reviewed considered SRS as medically necessary for brain metastases, medically refractory trigeminal neuralgia, and arteriovenous malformations. Compared with national payers, regional payers were less likely to deem other schwannomas, and a boost for large cranial or spinal lesions medically necessary (P < .05). The indication with the lowest coverage was medically refractory movement disorders (44.4%), followed by medically refractory epilepsy (33.3%). However, policies that were updated within the last year were more likely to deem medical necessity for epilepsy, movement disorders, hemangioblastoma, pineal gland tumors, and other schwannomas. CONCLUSIONS:Significant discrepancy remains among insurance policies for several indications in ASTRO's model policy for SRS; however, national payers and those with recent policy updates have a greater concordance with the ASTRO model policy.

Stereotactic body radiation therapy (SBRT) offers excellent local control of early-stage non-small cell lung cancer (NSCLC), but there currently is a need for tolerable systemic therapy to address regional and distant disease progression. One potential option is immunotherapy, which in metastatic NSCLC has shown promise for sustained disease control in a subset of patients. There is also growing evidence for a clinical synergy between radiation and immunotherapy, with several ongoing trials studying the abscopal effect. This review summarizes the current data in the fast-changing field of immuno-radiation therapy, highlighting updates from recent clinical trials.

Purpose: Insurance payers in the United States vary in the indications for which they consider stereotactic body radiation therapy (SBRT) "medically necessary." We compared changes in policies after the last update to the American Society for Radiation Oncology's (ASTRO) SBRT model policy. Methods and Materials: We identified 77 payers with SBRT policies in 2015 from a policy aggregator, as well as 4 national benefits managers (NBMs). Of these, 65 payers and 3 NBMs had publicly available updates since 2015. For each of the indications in ASTRO's model policy, we calculated the proportion of payers that considered SBRT medically necessary. We used Fisher's exact test to compare these proportions between 2015 and now, between policies updated in the past 12 months and those updated less often, and between national and regional payers currently. Results: Payers consider SBRT medically necessary most often for primary lung cancer (97%), reirradiation to the spine (91%), prostate cancer (68%), primary liver cancer (66%), and spinal metastases with radioresistant histologies (66%). Policies have become more aligned with ASTRO's model policy over time. National payers and NBMs cover indications in higher proportions than regional payers. Conclusions: Although there have been improvements over time, more work is needed to align payer policies with ASTRO's model SBRT policy, especially at the regional level. (C) 2019 Elsevier Inc. All rights reserved.

OBJECTIVES:Chest wall invasion (CWI) is observed in 5% of localized non-small cell lung cancer (NSCLC). The role of stereotactic body radiotherapy (SBRT) in these patients is unknown. We investigate the safety and efficacy of SBRT in patients with T3N0 NSCLC due to CWI. METHODS:Patients with T3N0 NSCLC due to CWI were identified using a prospective registry. CWI was defined as radiographic evidence of soft tissue invasion or bony destruction. We excluded patients with recurrent or metastatic disease. All patients were treated with definitive SBRT. Prescribed dose was 50 Gy in 5 fractions for most patients. Kaplan-Meier analysis was used to estimate survival outcomes. RESULTS:We identified 12 patients treated between 2006 and 2017. Median age was 70 (range, 58-85). Median tumor diameter was 3.0 cm (range, 0.9-7.2). Median survival was 12.0 months (range, 2.4-63). At a median follow-up of 8.9 months (range, 2.1-63), 1-year primary tumor control was 89%, involved lobar control was 89%, local-regional control was 82%, distant control was 91%, and survival was 63%. Of the 4 patients with pre-treatment chest wall pain, 3 reported improvement after SBRT. Two patients reported new grade 1-2 chest wall pain. No grade 3+ toxicity was reported, with 1 patient experiencing grade 1 skin toxicity and 3 patients experiencing grade 1-2 radiation pneumonitis. CONCLUSIONS:SBRT for CWI NSCLC is safe, with high early tumor control and low treatment-related toxicity. Most patients with pre-treatment chest wall pain experienced relief after SBRT, with no grade 3+ toxicity observed.

BACKGROUND Intraluminal brachytherapy for advanced esophageal cancer allows durable control of tumor-related obstructive symptoms by safely delivering large local doses of radiation over just one or a few sessions. Localized, intense doses of hypofractionated radiotherapy elicits more effective anti-tumor immune response than standard doses. In addition, abscopal effect of radiation in distant metastases may be augmented by addition of immune checkpoint inhibitor. Pembrolizumab is approved for treatment of PD-L1 positive gastroesophageal cancer. We therefore propose to evaluate the combination of brachytherapy and pembrolizumab in patients with advanced esophageal cancer. Correlative studies of this study aim to identify predictive biomarkers of response and to characterize the immune response before and after brachytherapy and pembrolizumab to assess immunologic parameters associated with the abscopal effect. METHODS This is a single institution, open-label, single-dose-level phase I study combining hypofractionated brachytherapy with standard dose pembrolizumab. Primary objective of this trial is to determine the tolerability of localized esophageal hypofractionated brachytherapy administered in two fractions when combined with pembrolizumab in patients with metastatic esophageal cancer. Secondary objective is to assess the antitumor efficacy of the combination. Exploratory objectives are to determine the expression profile of immunologic biomarkers and to annotate the local and distant immune response before and after treatments.Brachytherapy is delivered using a high-dose-rate iridium-192 afterloader via a dedicated esophageal applicator at 16 Gy in 2 fractions, 7-10 days apart. Pembrolizumab is given 1 week after completion of brachytherapy at 200 mg IV every 3 weeks. Endoscopic biopsies are performed before and after brachytherapy, and optionally after 8 weeks on pembrolizumab. Peripheral blood is collected at the same time points, at 3, 6, and 12 months on pembrolizumab, and at the time of progression. Patients with metastatic esophageal cancer who are candidates for brachytherapy for treatment of dysphagia are considered eligible for this trial. Exclusion criteria included prior treatment with PD-(L)1 targeting agent, symptomatic brain metastases, or other contraindication to pembrolizumab, such as active autoimmune disease. We plan to enroll 18 patients which will provide a reasonable ability to detect serious adverse event rates as well as early efficacy signals. There is at least 85% chance of observing at least 1 protocol-specified event if the true rate is 0.1 or greater. We will estimate 95% exact binomial confidence interval of true response rate based on observed responses. 80% of patient accrual is complete as of January 2019. NCT02642809. Citation Format: Haeseong Park, Tanner M. Johanns, A. Craig Lockhart, Jeffrey Bradley, Michael Roach, Gregory Vlacich, Manik Amin, Rama Suresh, Nusayba Bagegni, Clifford G. Robinson. Combining pembrolizumab with locally delivered radiation therapy for the treatment of metastatic esophageal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr CT212.

In patients receiving definitive stereotactic body radiation therapy (SBRT) for presumably node-negative, early-stage non-small cell lung cancer (NSCLC), many patients are staged with PET-CT alone. The role of invasive nodal staging with either bronchoscopy plus endobronchial ultrasound (EBUS) or mediastinoscopy in patients undergoing PET prior to definitive lung SBRT is uncertain. We sought to characterize the impact of nodal staging modality on clinical outcomes after SBRT for early NSCLC. Patients receiving definitive SBRT for T1-2N0 NSCLC that were determined to be node-negative by either PET plus invasive nodal staging (EBUS or mediastinoscopy) or PET alone were identified using a single-institution prospective registry. All patients received 3-5 fraction SBRT with a biologically effective dose (BED10) of ≥ 100 Gy. Patients who did not undergo pre-SBRT PET, received adjuvant systemic therapy, or who were treated with additional SBRT courses for synchronous or metachronous NSCLC were excluded from the current study. Multivariable logistic regression was performed to identify which variables were independently associated with invasive mediastinal staging. Variables evaluated included staging, age, gender, ethnicity, central versus peripheral location, stage, and histology. A total of 651 patients treated from 2005 – 2016 met the above inclusion criteria. Invasive nodal staging was performed in 15.2% of patients (n=99) with either EBUS (n= 78) or mediastinoscopy (n= 21). Median age at SBRT was 75.3 years (range, 49.3 – 88.8). Median follow up was 19.4 months, and median survival was 28.5 months for all patients. Factors predictive of increased likelihood to receive invasive nodal staging on multivariable analysis were young age (OR for increasing age 0.968; 95% CI 0.945 – 0.990), white race (OR for non-white 0.540; 0.304 = 0.958), female patients (OR 1.629; 95% CI 1.031 – 2.575), central location (OR 1.978; 95% CI 1.218 – 3.211) and squamous histology (OR 2.564; 95% CI 1.243 – 5.287). On multivariable analysis, nodal and/or distant failure was not significantly different between PET alone (crude failure rate, 23.6%) versus invasive nodal staging (25.4%, p=0.714) in this patient cohort. Most patients with early stage NSCLC treated with definitive SBRT did not undergo invasive nodal staging, and we identify several factors predictive of its use. There was no significant difference in nodal or distant failure based on type of nodal staging utilized.