Sources of support: This work was funded by the American Society for Radiation Oncology. Task Force Members' Disclosure Statements: All task force members' disclosure statements were shared with other task force members throughout the guideline's development. Those disclosures are published within this report. Where potential conflicts were detected, remedial measures to address them were taken.

BackgroundIn this single-arm study, the efficacy and safety of neoadjuvant pembrolizumab plus chemotherapy were evaluated in patients with resectable esophageal squamous cell carcinoma (ESCC).MethodsThis study included patients with ESCC of clinical stages II–IVA who underwent surgery within 4 to 6 weeks after completing treatment with pembrolizumab (200 mg) combined with a conventional chemotherapy regimen (3 cycles). The safety and efficacy of this combination treatment were evaluated as primary endpoints of the study.ResultsFrom April 2019 to August 2020, a total of 18 patients (including 14 men) were enrolled, of whom 13 patients progressed to surgery. Postoperative pathology revealed a major pathological response (MPR) in 9 cases (9/13, 69.2%) and a pathological complete response (pCR) in 6 cases (6/13, 46.2%). Five patients (5/18, 27.8%) experienced serious treatment-related adverse events (AEs) of grades 3–4. At the time of data cutoff (Mar 25, 2022), the shortest duration of follow-up was 17.8 months. Programmed death-ligand 1 (PD-L1) expression in pretreatment specimens was not significantly associated with the percentage of residual viable tumor (RVT) (r=−0.55, P=0.08). Changes in counts of CD68+ macrophage between pre- and post-treatment specimens were weakly correlated with RVT (r=0.71; P=0.07), while a positive correlation was observed between postoperative forkhead box P3-positive (Foxp3)+T cells/CD4+Tcells ratios and RVT (r=0.84, P=0.03).ConclusionsThe combination of neoadjuvant immunotherapy and chemotherapy for ESCC is associated with a high pathological response and immunologic effects in the tumor microenvironment (TME). It has acceptable toxicity and great efficacy, suggesting a strong rationale for its further evaluation in randomized clinical trials (RCTs).Trial RegistrationChiCTR2100048917.

Purpose/Objective(s): To evaluate the role of the albumin-bilirubin (ALBI) score and grade and the inflammation-based index (IBI) for treatment outcome and morbidity assessment in patients with hepatocellular carcinoma treated with stereotactic body radiotherapy (SBRT). Materials/Methods: Patients with HCCs with Barcelona-Clinic Liver Cancer (BCLC) classification stage B or C were treated with SBRT in 3 to 12 fractions. The ALBI grade and the IBI were calculated at different time points (baseline, during and at the end of treatment and at follow up) and were compared with the Child-Turcotte-Pugh (CTP) score. Results: Forty patients with 47 lesions were treated with SBRT. The median follow-up was 14.3 months. The median overall survival (OS) from SBRT was 10 (95% CI 8.3-11.6) months and the local control at 1 year was 79%. Predictors associated with OS were CTP score at first follow up (pZ0.05) and IBI during treatment (pZ0.03). Higher C-reactive protein (CRP) serum concentrations at baseline (HR: 1.043, pZ0.001), during treatment (HR: 1.024, pZ0.02) and at the end of treatment (HR: 1.031, pZ0.02) correlated with worse OS. Higher IBI at the first follow up (18 vs 8 months, pZ0.006) correlated with a worse overall survival. Patients with higher CTP (pZ0.001) and ALBI score (pZ0.02) at baseline were at risk for grade > 2 toxicities. Conclusion: Both ALBI score and CTP are useful for risk assessment in patients treated with SBRT and IBI could be a predictor for OS. These results should be further evaluated in prospective studies.

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Background and ObjectivesLymphopenia associated with chemoradiotherapy predicts prognosis in esophageal carcinoma. The purpose of our study was to evaluate alterations in hematologic measures of inflammation during chemoradiation.MethodsWe performed an observational study evaluating adults treated with chemoradiation in the neoadjuvant or definitive setting for stage II‐III esophageal carcinoma. Multivariable logistic regression evaluated predictors of pathologic response. Survival was analyzed by time‐varying multivariable Cox proportional hazards regressions.ResultsA total of 94 patients were included with median follow‐up of 1.6 years. Elevated neutrophil:lymphocyte ratio (NLR) was predictive of incomplete pathologic response to neoadjuvant chemoradiation (OR, 1.07; P = .0030) as well as shorter distant metastasis‐free survival (HR, 1.01; P = .0369) and reduced overall survival (HR, 1.01; P = .0448). An NLR > 5.55 in week two of chemoradiation predicted shorter overall survival (P = .0070). Upon adjusted analysis, NLR was independently associated with reduced probability of complete pathologic response (OR, 0.80; P = .0291), as well as poor histologic response to neoadjuvant chemoradiation (OR, 1.05; P = .0303), shorter disease‐free survival (HR, 1.02; P = .0077), and reduced overall survival (HR, 1.02; P = .0070).ConclusionsDynamic time‐dependent changes in NLR during chemoradiation predict response, relapse, metastasis, and survival in esophageal carcinoma. Prospective validation is warranted.

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Total skin electron therapy (TSET) has been used to treat mycosis fungoides since the 1950s. Practitioners of TSET rely on relatively crude, phantom-based point measurements for commissioning and treatment plan dosimetry. Using Monte Carlo simulation techniques, this study presents whole-body dosimetry for a patient receiving rotational, dual-field TSET. The Monte Carlo codes, BEAMnrc/DOSXYZnrc, were used to simulate 6 MeV electron beams to calculate skin dose from TSET. Simulations were validated with experimental measurements. The rotational dual-field technique uses extended source-to-surface distance with an acrylic beam degrader between the patient and incident beams. Simulations incorporated patient positioning: standing on a platform that rotates during radiation delivery. Resultant patient doses were analyzed as a function of skin depth-dose coverage and evaluated using dose-volume-histograms. Good agreement was obtained between simulations and measurements. For a cylinder with a 30 cm diameter, the depths that dose fell to 50% of the surface dose was 0.66 cm, 1.15 cm and 1.42 cm for thicknesses of 9 mm, 3 mm and without an acrylic scatter plate, respectively. The results are insensitive to cylinder diameter. Relatively uniform skin surface dose was obtained for skin in the torso area although large dose variations (>25%) were found in other areas resulting from partial beam shielding of the extremities. To achieve 95% mean dose to the first 5 mm of skin depth, the mean dose to skin depth of 5–10 mm and depth of 10–15 mm from the skin surface was 74% (57%) and 50% (25%) of the prescribed dose when using a 3 mm (9 mm) thickness scatter plate, respectively. As a result of this investigation on patient skin dose distributions we changed our patient treatments to use a 3 mm instead of a 9 mm thickness Acrylic scatter plate for clinically preferred skin depth dose coverage.