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Importance: For many types of epithelial malignant neoplasms that are treated with definitive radiotherapy (RT), treatment prolongation and interruptions have an adverse effect on outcomes., Objective: To analyze the association between RT duration and outcomes in patients with esophageal cancer who were treated with definitive chemoradiotherapy (CRT)., Design, Setting, and Participants: This study was an unplanned, post hoc secondary analysis of 3 prospective, multi-institutional phase 3 randomized clinical trials (Radiation Therapy Oncology Group [RTOG] 8501, RTOG 9405, and RTOG 0436) of the National Cancer Institute-sponsored NRG Oncology (formerly the National Surgical Adjuvant Breast and Bowel Project, RTOG, and Gynecologic Oncology Group). Enrolled patients with nonmetastatic esophageal cancer underwent definitive CRT in the trials between 1986 and 2013, with follow-up occurring through 2014. Data analyses were conducted between March 2022 to February 2023., Exposures: Treatment groups in the trials used standard-dose RT (50 Gy) and concurrent chemotherapy., Main Outcomes and Measures: The outcomes were local-regional failure (LRF), distant failure, disease-free survival (DFS), and overall survival (OS). Multivariable models were used to examine the associations between these outcomes and both RT duration and interruptions. Radiotherapy duration was analyzed as a dichotomized variable using an X-Tile software to choose a cut point and its median value as a cut point, as well as a continuous variable., Results: The analysis included 509 patients (median [IQR] age, 64 [57-70] years; 418 males [82%]; and 376 White individuals [74%]). The median (IQR) follow-up was 4.01 (2.93-4.92) years for surviving patients. The median cut point of RT duration was 39 days or less in 271 patients (53%) vs more than 39 days in 238 patients (47%), and the X-Tile software cut point was 45 days or less in 446 patients (88%) vs more than 45 days in 63 patients (12%). Radiotherapy interruptions occurred in 207 patients (41%). Female (vs male) sex and other (vs White) race and ethnicity were associated with longer RT duration and RT interruptions. In the multivariable models, RT duration longer than 45 days was associated with inferior DFS (hazard ratio [HR], 1.34; 95% CI, 1.01-1.77; P = .04). The HR for OS was 1.33, but the results were not statistically significant (95% CI, 0.99-1.77; P = .05). Radiotherapy duration longer than 39 days (vs ≤39 days) was associated with a higher risk of LRF (HR, 1.32; 95% CI, 1.06-1.65; P = .01). As a continuous variable, RT duration (per 1 week increase) was associated with DFS failure (HR, 1.14; 95% CI, 1.01-1.28; P = .03). The HR for LRF 1.13, but the result was not statistically significant (95% CI, 0.99-1.28; P = .07)., Conclusions and Relevance: Results of this study indicated that in patients with esophageal cancer receiving definitive CRT, prolonged RT duration was associated with inferior outcomes; female patients and those with other (vs White) race and ethnicity were more likely to have longer RT duration and experience RT interruptions. Radiotherapy interruptions should be minimized to optimize outcomes.

With increasing use of low-dose screening CT scans, the diagnosis of early-stage small-cell lung cancer (SCLC) without evidence of mediastinal nodal or distant metastasis is likely to become more common, but the role of adjuvant therapies such as prophylactic cranial irradiation (PCI) are not well understood in this population. We performed a review of the literature pertaining to the impact of PCI in patients who underwent surgical resection of early-stage SCLC. Four studies were identified that were pertinent including three single-institution retrospective analyses and a National Cancer Database analysis. Based upon these studies, we estimate the rate of brain metastases to be 10-15% for Stage I and 15-25% for Stage II disease without PCI. However, the impact of PCI on the development of brain metastases and its ultimate impact on overall survival were not consistent across these studies. In summary, there is sparse evidence to guide recommendations for PCI following resection of early-stage SCLC. While it may be reasonable to offer PCI to maximize likelihood of cure, alternative strategies such as observation with close imaging follow-up can also be considered for the appropriate patient given the known neurocognitive side effects of PCI.

Introduction: Approximately 50% of recurrences after standard-dose chemoradiation for locally advanced esophageal cancer occur within the gross tumor volume (GTV). In this prospective phase I/II clinical trial, we explored the use of a simultaneous integrated boost (SIB) dose to the GTV., Methods: Forty-four patients with unresectable esophageal cancer received chemoradiation with an SIB of 58.8 to 63 Gy to the GTV and 50.4 Gy to the planning target volume, all in 28 fractions, with 5 weeks of concurrent docetaxel and fluorouracil or capecitabine. The end points were maximum tolerated dose, time to local failure, and clinical response., Results: Excluding those with less than 6 months of follow-up, 38 patients were evaluated at the time of analysis. The median age was 65 years (range 37-84). Most patients (71%) were men; 84% had T3 disease, 37% had N1 disease, 26% had N2 disease, 13% had M1 disease, and 50% had adenocarcinoma. The maximum tolerated SIB dose was 63 Gy. None experienced Common Terminology Criteria for Adverse Events grade 4 or 5 toxicity. At a median follow-up time of 13.3 months (range 1.2-36.2), 11 (29%) had local failure (median time to local failure 2.5 months [range 1.5-23.9]). A comparison with 97 similar patients who received 50.4 Gy without an SIB showed that the SIB reduced the local failure rate for patients with node-positive disease (13% versus 56%, p = 0.04), adenocarcinoma (26% versus 59%, p = 0.02), or stage III-IV disease (29% versus 55%, p = 0.04)., Conclusions: SIB intensity-modulated radiation therapy to gross primary disease may improve local control for patients with unresectable locally advanced esophageal cancer, especially those with adenocarcinoma., (Copyright © 2017 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

Introduction: The impact of selective surgical resection for patients with esophageal cancer treated with definitive chemoradiation has not been clearly evaluated long-term., Methods: NRG (National Surgical Adjuvant Breast and Bowel Project, Radiation Therapy Oncology Group, Gynecologic Oncology Group) Oncology Radiation Therapy Oncology Group 0246 was a multi-institutional, single-arm, open-label, nonrandomized phase II study that enrolled 43 patients from September 2003 to March 2008 with clinical stage T1-4N0-1M0 squamous cell or adenocarcinoma of the esophagus or gastroesophageal junction from 19 sites. Patients received induction chemotherapy with fluorouracil (650 mg/m 2 /d), cisplatin (15 mg/m 2 /d), and paclitaxel (200 mg/m 2 /d) for two cycles followed by concurrent chemoradiation consisting of 50.4 Gy of radiation (1.8 Gy per fraction) and daily fluorouracil (300 mg/m 2 /d) with cisplatin (15 mg/m 2 /d) over the first 5 days. After definitive chemoradiation, patients were evaluated for residual disease. Selective esophagectomy was considered only for patients with residual disease after chemoradiation (clinical incomplete response) or recurrent disease on surveillance., Results: This report looks at the long-term outcome of this selective surgical strategy. With a median follow-up of 8.1 years (minimum to maximum for 12 alive patients 7.2-9.8 years), the estimated 5- and 7-year survival rates are 36.6% (95% confidence interval [CI]: 22.3-51.0) and 31.7% (95% CI: 18.3-46.0). Clinical complete response was achieved in 15 patients (37%), with 5- and 7-yearr survival rates of 53.3% (95% CI: 26.3-74.4) and 46.7% (95% CI: 21.2-68.7). Esophageal resection was not required in 20 of 41 patients (49%) on this trial., Conclusions: The long-term results of NRG Oncology Radiation Therapy Oncology Group 0246 demonstrate promising efficacy of a selective surgical resection strategy and suggest the need for larger randomized studies to further evaluate this organ-preserving approach., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2016 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

Radiation therapy controls local disease but also prompts the release of tumor-associated antigens and stress-related danger signals that primes T cells to promote tumor regression at unirradiated sites known as the abscopal effect. This may be enhanced by blocking inhibitory immune signals that modulate immune activity through a variety of mechanisms. Indeed, abscopal responses have occurred in patients with lung cancer or melanoma when given anti-CTLA4 antibody and radiation. Other approaches involve expanding and reinfusing T or NK cells or engineered T cells to express receptors that target specific tumor peptides. These approaches may be useful for immunocompromised patients receiving radiation. Preclinical and clinical studies are testing both immune checkpoint-based strategies and adoptive immunotherapies with radiation.