SBRT compared to CONV is associated with improved LF rates and OS. Our data supports the continued use and expansion of SBRT as the standard of care treatment for inoperable early-stage NSCLC.

Introduction Higher target conformity and better sparing of organs at risk with modern radiotherapy (RT) may result in higher tumor control and less toxicities. In this study, we compare our institutional multimodality therapy experience of adjuvant chemotherapy and hemithoracic intensity-modulated pleural RT (IMPRINT) to previously used adjuvant conventional RT (CONV) in patients with malignant pleural mesothelioma (MPM) treated with lung-sparing pleurectomy/decortication (P/D). Methods We analyzed 209 patients who underwent P/D and adjuvant RT (n[CONV]=131, n[IMPRINT]=78) for MPM between 1974 and 2015. The primary endpoint was overall survival (OS). The Kaplan-Meier method and Cox proportional hazards model were used to calculate OS; competing ri sks analysis was performed for local failure-free (LFFS) and progression-free survival (PFS). Univariate (UVA) and multivariate analysis (MVA) was performed with relevant clinical and treatment factors. Results The median age was 64 years, 80% were male. Patients receiving IMPRINT had significantly higher rates of epithelial histology, advanced pStage and chemotherapy treatment. OS was significantly higher after IMPRINT (median 20.2 vs 12.3 months, p=0.001). Higher Karnofsky performance score (KPS), epithelioid histology, macroscopically complete resection (MCR), and use of chemotherapy/IMPRINT were found to be significant factors for longer OS upon MVA. No significant predictive factors were identified for local failure or progression. Fewer patients developed grade ≥2 esophagitis after IMPRINT compared to CONV (23% vs 47%). Conclusions Trimodality therapy including adjuvant hemithoracic IMPRINT, chemotherapy, and P/D is associated with promising OS rates and decreased toxicities in patients with MPM. Dose constraints should be applied vigilantly to minimize serious adverse events.

PurposeThe objective of this study was to evaluate adverse events (AEs) in patients who received both immune checkpoint inhibitors and thoracic radiation therapy (RT). In particular, we compared the rate of toxicities of concurrent versus sequential delivery of thoracic RT and checkpoint inhibitors.Methods and MaterialsPatient and treatment characteristics were collected on all patients at our institution who were treated with programmed cell death protein 1 (PD-1), programmed death-ligand 1 (PD-L1), and/or cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitors and underwent thoracic RT (n = 79). Receiving both treatments within 1 month was considered concurrent (n = 35; 44%), and any treatment up to 6 months apart was considered sequential (n = 44; 56%). The primary endpoint of this study was the rate of Grade ≥2 AEs from combination therapy (immunotherapy and RT), specifically those that are relevant to thoracic RT: Pneumonitis, other pulmonary events, esophagitis, dermatitis, and fatigue. Further univariate analysis was performed to compare AE rates with clinical and therapy-related variables.ResultsA total of 79 patients were identified, with lung cancer (n = 45) and melanoma (n = 15) being the most common primary histology. Sixty-two (78%) patients were treated with anti-PD-1 or anti-PD-L1 antibodies, 12 (15%) with anti-CTLA-4 antibodies, and 5 (6%) received both anti-PD-1/PD-L1 and anti-CTLA-4 antibodies. The median follow-up for survivors was 5.9 months (range, 2.4-55.6 months). Grade ≥2 AEs included pneumonitis (n = 5; 6%), esophagitis (n = 6; 8%), and dermatitis (n = 8; 10%). No statistically significant correlation was found between these AEs when comparing concurrent versus sequential treatment. The only significant variable was a correlation of immunotherapy drug category with Grade ≥2 esophagitis (P = .04).ConclusionsOverall, Grade ≥2 AE rates of thoracic RT and immunotherapy appeared as expected and acceptable. The lack of significant differences in AE rates with concurrent versus sequential treatment suggests that even concurrent immunotherapy and thoracic RT may be safe.

Purpose Stereotactic body radiation therapy (SBRT) has emerged as an effective treatment for early-stage lung cancer. Histologic subtyping in surgically resected lung adenocarcinomas is recognized as a prognostic factor, with the presence of solid or micropapillary patterns predicting poor outcomes. Herein, we describe outcomes following SBRT for early-stage lung adenocarcinoma by histologic subtype. Materials and Methods We identified 119 consecutive patients (124 lesions) with stage I-IIA lung adenocarcinoma who were treated with definitive SBRT at our institution between August 2008 and August 2015 and had undergone core biopsy. Histologic subtyping was performed according to the 2015 WHO Classification. Thirty-seven tumors (30%) were of high risk subtype, defined as containing a component of solid and/or micropapillary pattern. Cumulative incidences of local, nodal, regional and distant failure were compared between high risk vs. non-high risk adenocarcinoma subtypes with Gray’s test, and multivariable-adjusted hazard ratios were estimated from propensity score-weighted Cox regression models. Results Median follow-up for the entire cohort was 17 months and 21 months for surviving patients. The 1-year cumulative incidence and adjusted hazard ratio (HR) of local, nodal, regional and distant failure, respectively, in high risk versus non-high risk lesions were 7.3% vs 2.7% (HR 16.8; 95% CI 3.5–81.4), 14.8% vs 2.6% (HR 3.8; 95% CI 0.95–15.0), 4.0% vs 1.2% (HR 20.9; 95% CI 2.3–192.3) and 22.7% vs 3.6% (HR 6.9; 95% CI 2.2–21.1). No significant difference was seen with regard to overall survival. Conclusions Outcomes following SBRT for early-stage adenocarcinoma of the lung are highly correlated with histologic subtype, with micropapillary and solid tumors portending significantly higher rates of locoregional and metastatic progression. In this context, histologic subtype based on core biopsies is a prognostic factor and may have important implications for patient selection, adjuvant treatment, biopsy methods and clinical trial design.

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