Movsas, Benjamin

PURPOSE For patients with breast cancer undergoing breast conservation, escalating the dose (boost) of radiation to the lumpectomy cavity after whole-breast irradiation (WBI) reduces ipsilateral breast recurrence (IBR) but extends treatment duration. This phase III trial investigated whether boost delivery during WBI versus after WBI provides noninferior IBR and preserves cosmetic appearance. METHODS NRG/RTOG 1005 randomly assigned patients at higher risk for IBR after lumpectomy and axillary surgery to either a sequential boost of 12 Gy in six fractions(F) or 14 Gy in 7F after WBI of 50 Gy in 25F or 42.7 Gy in 16F (sequential arm) or a concurrent boost of 8 Gy in 15F of 0.53 Gy per day with WBI of 40 Gy in 15F (concurrent arm) using 3-dimensional conformal radiation therapy (RT) or intensity-modulated RT. Based on 1.59% 5-year IBR for the sequential arm, defining the noninferiority margin as a hazard ratio upper limit on the 90% CI of 2.12, 2,312 patients provide 80% power for noninferiority of IBR as first recurrence for the concurrent arm. Secondary end points included disease-free survival and overall survival, adverse events (AEs), and cosmetic outcomes. RESULTS Between May 24, 2011, and June 20, 2014, 2,354 patients were randomly assigned, with 2,255 eligible for analysis (sequential arm, n = 1,118; concurrent arm, n = 1,137). With median follow-up of 7.3 years, there were 56 IBR events; 5- and 7-year IBR were 2.1% and 2.2% on the sequential arm and 1.9% and 2.6% on the concurrent arm, respectively. The noninferiority criterion was met: HR (90% CI): 1.31 (0.84 to 2.04), P = .037. No differences were observed in AEs, cosmetic outcomes, or survival between arms. CONCLUSION Concurrent boost during WBI results in noninferior IBR compared with sequential boost without worsening toxicity or cosmetic outcomes and reduces overall treatment time.

Abstract Background NRG/RTOG 1010 evaluated trastuzumab added to trimodality therapy for HER2+ localized esophageal adenocarcinoma (EAC) management. Secondary PRO objectives assessed improvement in the FACT‐Esophageal Cancer Subscale (ECS), version 4, with trastuzumab, and if improved ECS correlated with pathologic complete response (pCR). Methods Patients were randomized to weekly paclitaxel/carboplatin/radiation (chemoradiation, CRT) followed by surgery ± trastuzumab (CRT + Tras). Disease‐free survival (DFS) was the primary end point. The projected PRO sample size of 158 patients, based on an 80% participation rate of the DFS primary endpoint sample size of 197 HER2+ patients, would provide ≥ 89% power to detect ≥25% increase in the proportion of CRT + Tras patients with ECS improvement from baseline to 6–8 weeks post‐CRT; one‐sided α = 0.05, using a χ 2 test. Improvement in ECS and its swallowing index (SI) and eating index (EI) was defined as 5‐, 2‐, and 2‐point increases, respectively, from baseline to 6–8 weeks post‐CRT. Univariate logistic regression was assessed if pCR was associated with improved ECS. Results From 2010 to 2015, 203 HER2+ patients were randomized and 194 were eligible. Of 171 PRO consenting patients, the ECS was completed by 162 (95%) at baseline, 108 (64%) 6–8 weeks, 82 (49%) 1 year, and 55 (33%) at 2 years. The proportion of patients with an improvement in 6–8 weeks ECS was higher on the CRT + Tras arm (46% vs. 38%), although not significantly different ( p = .39). There was no correlation between pCR and ECS scores at 1 year, with 39% and 37% of pCR and non‐pCR patients, respectively, having improved 1‐year ECS scores. Conclusions The addition of trastuzumab to CRT for localized HER2+ EAC did not improve PROs.

TPS9082 Background: Limited stage small cell lung cancer (LS-SCLC) is treated with standard of care platinum/etoposide (EP) and thoracic radiation therapy (TRT) with curative intent, however the majority of patients are not cured and median overall survival is approximately 30 months. Addition of atezolizumab to chemotherapy in extensive stage SCLC has improved progression free and overall survival in a non-curative setting leading to hope that addition of an immune checkpoint inhibitor to standard chemoradiotherapy could benefit LS-SCLC patients. LU005 is a randomized phase II/III trial of standard concurrent chemoradiation with or without atezolizumab for patients with LS-SCLC. Methods: Patients are randomly assigned in a 1:1 ratio to standard EP chemotherapy with concurrent TRT (45 Gy BID or 66 Gy QD) with or without atezolizumab beginning concurrently with TRT, and continued every 3 weeks for up to 12 months. Eligible patients have LS-SCLC, PS 0-2, adequate organ function, no concerning comorbidities (including no active autoimmune disease) and are eligible for TRT. Patients are randomized prior to their second cycle of EP and thoracic radiation begins with the second overall cycle of chemotherapy (first cycle of study therapy) in both treatment arms. Prophylactic cranial radiation (PCI) is recommended for patients who respond to treatment. The phase II/III primary endpoints are progression free (PFS) and overall survival (OS) respectively. Secondary endpoints include objective response rates, local and distant disease control, and quality of life/patient reported outcomes assessment. Translational science component includes blood and tissue based immune related assays. This study activated in May 2019. 50 of 506 planned patients have been accrued as of 2/1/2020. Supported by grants U10CA180868 (NRG Oncology Operations), U10CA180822 (NRG Oncology SDMC), U23CA180803 (IROC) from the National Cancer Institute (NCI) and Genentech. *Authors Ross and Higgins are co-first authors and contributed equally to this work. Clinical trial information: NCT03811002.

Abstract BACKGROUND The influence of subtotal resection (STR) on neurocognitive function (NCF), quality of life, and symptom burden in glioblastoma is unknown. If bevacizumab preferentially benefits patients with STR is unknown. OBJECTIVE To examine these uncertainties. METHODS NCF and patient reported outcomes (PRO) were prospectively collected in NRG Oncology RTOG 0525 and 0825. Changes in NCF and PRO measures from baseline to prespecified times were examined by Wilcoxon test, and mixed effects longitudinal modeling, to assess differences between patients who received STR vs gross-total resection. Changes were also compared among STR patients on 0825 receiving placebo vs bevacizumab to assess for a preferential therapeutic effect. Overall survival between STR and gross-total resection patients was compared using the Kaplan–Meier method. RESULTS A total of 427 patients were eligible with STR present in 37%. At baseline, patients with STR had worse NCF, worse MD Anderson Symptom Inventory Brain Tumor Neurological Factor ratings ( P = .004), and European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire ( P = .002). Longitudinal multivariate analysis associated STR with worse NCF (Hopkins Verbal Learning Test–Revised Delayed Recognition [ P = .048], Trail Making Test Part A [ P = .035], and Controlled Oral Word Association [ P = .049]). One hundred eighty-three STR patients from 0825 were analyzed (89 bevacizumab, 94 placebo); bevacizumab failed to demonstrate improvement in select NCF or PRO measures. CONCLUSION STR patients had worse NCF and PROs before therapy. During adjuvant therapy, STR patients had worse objective NCF, despite accounting for tumor location. STR did not result in a detriment to OS. The addition of bevacizumab did not preferentially improve PRO or NCF outcomes in STR patients.

Purpose: To present the most updated American College of Radiology consensus guidelines formed from an expert panel on treatment of locally advanced, high-risk prostate cancer Methods: The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer-reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment. Results: The panel summarized the most recent and relevant literature on the topic and voted on 4 clinical variants illustrating the appropriate management of locally advanced, high-risk cancer. Numerical rating and commentary reflecting the panel consensus was given for each treatment approach in each variant. Conclusions: Aggressive local approaches including surgery followed by adjuvant XRT, beam combined with androgen deprivation therapy, and beam combined with brachytherapy have resulted in unpresented success in locally advanced, high-risk prostate cancer. By combining most recent medical literature and expert opinion, this guideline can aid clinicians in the appropriate integration of available therapeutic modalities.

Objectives: The primary objective of NRG Oncology Radiation Therapy Oncology Group 0123 was to test the ability of the angiotensin-converting enzyme inhibitor captopril to alter the incidence of pulmonary damage after radiation therapy for lung cancer; secondary objectives included analyzing pulmonary cytokine expression, quality of life, and the long-term effects of captopril. Materials and Methods: Eligible patients included stage II-IIIB non–small cell lung cancer, stage I central non–small cell lung cancer, or limited-stage small cell. Patients who met eligibility for randomization at the end of radiotherapy received either captopril or standard care for 1 year. The captopril was to be escalated to 50 mg three times a day. Primary endpoint was incidence of grade 2+ radiation-induced pulmonary toxicity in the first year. Results: Eighty-one patients were accrued between June 2003 and August 2007. Given the low accrual rate, the study was closed early. No significant safety issues were encountered. Eight patients were ineligible for registration or withdrew consent before randomization and 40 patients were not randomized postradiation. Major reasons for nonrandomization included patients’ refusal and physician preference. Of the 33 randomized patients, 20 were analyzable (13 observation, 7 captopril). The incidence of grade 2+ pulmonary toxicity attributable to radiation therapy was 23% (3/13) in the observation arm and 14% (1/7) in the captopril arm. Conclusions: Despite significant resources and multiple amendments, NRG Oncology Radiation Therapy Oncology Group 0123 was unable to test the hypothesis that captopril mitigates radiation-induced pulmonary toxicity. It did show the safety of such an approach and the use of newer angiotensin-converting enzyme inhibitors started during radiotherapy may solve the accrual problems.