PURPOSE: To describe the impact of fractionation scheme and tumor location on toxicities in stereotactic body radiation therapy (SBRT) for ≥5-cm non-small cell lung cancer (NSCLC), as part of a multi-institutional analysis. METHODS: Patients with primary ≥5-cm N0 M0 NSCLC who underwent ≤5-fraction SBRT were examined across multiple high-volume SBRT centers. Collected data included clinical/treatment parameters; toxicities were prospectively assessed at each institution according to the Common Terminology Criteria for Adverse Events. Patients treated daily were compared with those treated every other day (QOD)/other nondaily regimens. Stratification between central and peripheral tumors was also performed. RESULTS: Ninety-two patients from 12 institutions were evaluated (2004-2016), with median follow-up of 12 months. In total there were 23 (25%) and 6 (7%) grade ≥2 and grade ≥3 toxicities, respectively. Grades 2 and 3 pulmonary toxicities occurred in 9% and 4%, respectively; 1 patient treated daily experienced grade 5 radiation pneumonitis. Of the entire cohort, 46 patients underwent daily SBRT, and 46 received QOD (n=40)/other nondaily (n=6) regimens. Clinical/treatment parameters were similar between groups; the QOD/other group was more likely to receive 3-/4-fraction schemas. Patients treated QOD/other experienced significantly fewer grade ≥2 toxicities as compared with daily treatment (7% vs 43%, P<.001). Patients treated daily also had higher rates of grade ≥2 pulmonary toxicities (P=.014). Patients with peripheral tumors (n=66) were more likely to receive 3-/4-fraction regimens than those with central tumors (n=26). No significant differences in grade ≥2 toxicities were identified according to tumor location (P>.05). CONCLUSIONS: From this multi-institutional study, toxicity of SBRT for ≥5-cm lesions is acceptable, and daily treatment was associated with a higher rate of toxicities.

BACKGROUND: Stereotactic body radiotherapy (SBRT) is the standard of care for patients with nonoperative, early-stage non-small cell lung cancer (NSCLC) measuring < 5 cm, but its use among patients with tumors measuring ≥5 cm is considerably less defined, with the existing literature limited to small, single-institution reports. The current multi-institutional study reported outcomes evaluating the largest such population reported to date. METHODS: Clinical/treatment characteristics, outcomes, toxicities, and patterns of failure were assessed in patients with primary NSCLC measuring ≥5 cm without evidence of distant/lymph node metastasis who underwent SBRT using ≤5 fractions. Statistics included Kaplan-Meier survival analyses and univariate/multivariate Cox proportional hazards models. RESULTS: A total of 92 patients treated from 2004 through 2016 were analyzed from 12 institutions. The median follow-up was 12 months (15 months in survivors). The median age and tumor size among the patients were 73 years (range, 50-95 years) and 5.4 cm (range, 5.0-7.5 cm), respectively. The median dose/fractionation was 50 Gray/5 fractions. The actuarial local control rates at 1 year and 2 years were 95.7% and 73.2%, respectively. The disease-free survival rate was 72.1% and 53.5%, respectively, at 1 year and 2 years. The 1-year and 2-year disease-specific survival rates were 95.5% and 78.6%, respectively. The median, 1-year, and 2-year overall survival rates were 21.4 months, 76.2%, and 46.4%, respectively. On multivariate analysis, lung cancer history and pre-SBRT positron emission tomography maximum standardized uptake value were found to be associated with overall survival. Posttreatment failures were most commonly distant (33% of all disease recurrences), followed by local (26%) and those occurring elsewhere in the lung (23%). Three patients had isolated local failures. Grade 3 to 4 toxicities included 1 case (1%) and 4 cases (4%) of grade 3 dermatitis and radiation pneumonitis, respectively (toxicities were graded according to the Common Terminology Criteria for Adverse Events [version 4.0]). Grades 2 to 5 radiation pneumonitis occurred in 11% of patients. One patient with a tumor measuring 7.5 cm and a smoking history of 150 pack-years died of radiation pneumonitis. CONCLUSIONS: The results of the current study, which is the largest study of patients with NSCLC measuring ≥5 cm reported to date, indicate that SBRT is a safe and efficacious option. Cancer 2017;123:688-696. © 2016 American Cancer Society.

PURPOSE: For inoperable stage I (T1-T2N0) small cell lung cancer (SCLC), national guidelines recommend chemotherapy with or without conventionally fractionated radiation therapy. The present multi-institutional cohort study investigated the role of stereotactic ablative radiation therapy (SABR) for this population. METHODS AND MATERIALS: The clinical and treatment characteristics, toxicities, outcomes, and patterns of failure were assessed in patients with histologically confirmed stage T1-T2N0M0 SCLC. Kaplan-Meier analysis was used to evaluate the survival outcomes. Univariate and multivariate analyses identified predictors of outcomes. RESULTS: From 24 institutions, 76 lesions were treated in 74 patients (median follow-up 18 months). The median age and tumor size was 72 years and 2.5 cm, respectively. Chemotherapy and prophylactic cranial irradiation were delivered in 56% and 23% of cases, respectively. The median SABR dose and fractionation was 50 Gy and 5 fractions. The 1- and 3-year local control rate was 97.4% and 96.1%, respectively. The median disease-free survival (DFS) duration was 49.7 months. The DFS rate was 58.3% and 53.2% at 1 and 3 years, respectively. The median, 1-year, and 3-year disease-specific survival was 52.3 months, 84.5%, and 64.4%, respectively. The median, 1-year, and 3-year overall survival (OS) was 17.8 months, 69.9%, and 34.0% respectively. Patients receiving chemotherapy experienced an increased median DFS (61.3 vs 9.0 months; P=.02) and OS (31.4 vs 14.3 months; P=.02). The receipt of chemotherapy independently predicted better outcomes for DFS/OS on multivariate analysis (P=.01). Toxicities were uncommon; 5.2% experienced grade ≥2 pneumonitis. Post-treatment failure was most commonly distant (45.8% of recurrence), followed by nodal (25.0%) and elsewhere lung (20.8%). The median time to each was 5 to 7 months. CONCLUSIONS: From the findings of the largest report of SABR for stage T1-T2N0 SCLC to date, SABR (≥50 Gy) with chemotherapy should be considered a standard option.