Context Patients with early stage but medically inoperable lung cancer patients have a poor rate of primary tumor control (30-40%) and a high rate of mortality (3-year survival 20-35%) with current management. Objective To evaluate the toxicity and efficacy of stereotactic body radiation therapy in a high risk population of patients with early stage but medically inoperable lung cancer. Design, Setting, and Patients Phase 2 North American multicenter study of patients with biopsy-proven peripheral T1-T2, N0, M0 non-small cell tumors less than 5 cm in diameter and medical conditions precluding surgical treatment. The prescription dose was 18 Gy per fraction times 3 fractions (54 Gy total) delivered in 1½-2 weeks. The study opened May 26, 2004, and closed October 13, 2006; data were analyzed through August 31, 2009. Main Outcome Measures The primary endpoint was primary tumor control with overall survival, disease free survival, adverse events, involved lobe, regional, and disseminated recurrence as secondary endpoints. Results A total of 59 patients accrued, of which 55 were evaluable (44 T1 and 11 T2 tumors) with a median follow-up of 34.4 months (range, 4.8 to 49.9 months). Only 1 patient had a primary tumor failure; the estimated 3-year primary tumor control rate was 97.6% (95% confidence interval [CI], 84.3%, 99.7%). Three patients had recurrence within the involved lobe; the 3-year primary tumor and involved lobe (local) control rate was 90.6% (95% CI, 76.0%, 96.5%). Two patients experienced regional failure; the local-regional control rate was 87.2% (95%CI, 71.0%, 94.7%). Eleven patients experienced disseminated recurrence; the 3-year rate of disseminated failure was 22.1% (95% CI, 12.3%, 37.8%). The rates of disease-free and overall survival at 3 years were 48.3% (95% CI, 34.4%, 60.8%) and 55.8% (95% CI, 41.6%, 67.9%), respectively. The median overall survival was 48.1 months (95% CI, 29.6% to not reached). Protocol specified treatment-related grade 3 adverse events were reported in 7 patients (12.7%; 95% CI, 9.6%, 15.8%); grade 4 events were reported in 2 patients (3.6%; 95%CI, 2.7%, 4.5%). No grade 5 adverse events were reported. Conclusion Patients with inoperable non-small cell lung cancer who received stereotactic body radiation therapy had a survival rate of 55.8% at 3 years, high rates of local tumor control, and moderate treatment-related morbidity.

PURPOSE Patients with centrally located early-stage non–small-cell lung cancer (NSCLC) are at a higher risk of toxicity from high-dose ablative radiotherapy. NRG Oncology/RTOG 0813 was a phase I/II study designed to determine the maximum tolerated dose (MTD), efficacy, and toxicity of stereotactic body radiotherapy (SBRT) for centrally located NSCLC. MATERIALS AND METHODS Medically inoperable patients with biopsy-proven, positron emission tomography–staged T1 to 2 (≤ 5 cm) N0M0 centrally located NSCLC were accrued into a dose-escalating, five-fraction SBRT schedule that ranged from 10 to 12 Gy/fraction (fx) delivered over 1.5 to 2 weeks. Dose-limiting toxicity (DLT) was defined as any treatment-related grade 3 or worse predefined toxicity that occurred within the first year. MTD was defined as the SBRT dose at which the probability of DLT was closest to 20% without exceeding it. RESULTS One hundred twenty patients were accrued between February 2009 and September 2013. Patients were elderly, there were slightly more females, and the majority had a performance status of 0 to 1. Most cancers were T1 (65%) and squamous cell (45%). Organs closest to planning target volume/most at risk were the main bronchus and large vessels. Median follow-up was 37.9 months. Five patients experienced DLTs; MTD was 12.0 Gy/fx, which had a probability of a DLT of 7.2% (95% CI, 2.8% to 14.5%). Two-year rates for the 71 evaluable patients in the 11.5 and 12.0 Gy/fx cohorts were local control, 89.4% (90% CI, 81.6% to 97.4%) and 87.9% (90% CI, 78.8% to 97.0%); overall survival, 67.9% (95% CI, 50.4% to 80.3%) and 72.7% (95% CI, 54.1% to 84.8%); and progression-free survival, 52.2% (95% CI, 35.3% to 66.6%) and 54.5% (95% CI, 36.3% to 69.6%), respectively. CONCLUSION The MTD for this study was 12.0 Gy/fx; it was associated with 7.2% DLTs and high rates of tumor control. Outcomes in this medically inoperable group of mostly elderly patients with comorbidities were comparable with that of patients with peripheral early-stage tumors.

SBRT has an important role to play in treating early-stage NSCLC, particularly for medically inoperable patients with limited other treatment options. Shared decision-making with patients should be performed in all cases to ensure the patient understands the risks related to SBRT, the side effects, and the alternative treatments available.

Purpose To compare 2 stereotactic body radiotherapy (SBRT) schedules for medically inoperable early-stage lung cancer to determine which produces the lowest rate of grade ≥ 3 protocol-specified adverse events (psAEs) at 1 year. Methods Patients with biopsy-proven peripheral (greater than 2 cm from the central bronchial tree) T1/T2, N0 (clinically node negative by positron emission tomography), M0 tumors were eligible. Patients were randomized to receive either 34 Gy in one fraction (Arm 1) or 48 Gy in 4 consecutive daily fractions (Arm 2). Rigorous central accreditation and quality assurance confirmed treatment per protocol guidelines. This study was designed to detect a psAEs rate > 17% at a 10% significance level (1-sided) and 90% power. Secondary endpoints included rates of primary tumor control (PC), overall survival (OS) and disease-free survival (DFS) at 1 year. Designating the better of the two regimens was based on pre-specified rules of psAEs and PC for each Arm. Results Ninety four patients were accrued between September 2009 and March 2011. Median follow up time was 30.2 months. Of 84 analyzable patients, 39 were in Arm 1 and 45 in Arm 2. Patient and tumor characteristics were balanced between Arms. Four (10.3%) patients on Arm 1 (95% confidence interval (CI): 2.9%-24.2%) and six (13.3%) patients on Arm 2 (95% CI: 5.1%-26.8%) experienced psAEs. The 2-year OS rate was 61.3% (95% CI: 44.2%-74.6%) for Arm 1 patients and 77.7% (95% CI: 62.5%-87.3%) for Arm 2. The 2-year DFS was 56.4% (95% 39.6%-70.2%) for Arm 1 and 71.1% (95% CI: 55.5%-82.1%) for Arm 2. The 1-year PC rate was 97.0% (95% CI: 84.2%-99.9%) for Arm 1 and 92.7% (80.1%-98.5%) for Arm 2. Conclusions 34 Gy in 1 fraction met pre-specified criteria and of the two schedules, warrants further clinical research.

Purpose-This study was designed to determine the effect of dose and fractionation schedule of prophylactic cranial irradiation (PCI) on the incidence of chronic neurotoxicity (CNt) and changes in quality of life (QoL) for selected patients (pts) with limited disease small cell lung cancer (LD SCLC). Methods and Materials-Pts with LD SCLC who achieved a complete response (CR)following chemotherapy and thoracic irradiation were eligible for randomization to undergo PCI to a total dose of 25 Gy in 10 daily fractions (Fxs) (Arm 1) vs. the experimental cohort of 36 Gy. Those receiving 36 Gy underwent a secondary randomization between daily 18 Fxs (Arm 2) and

Patients should be informed of these potential adverse effects, as well as the benefit of PCI on survival and BM. PCI with a total dose of 25 Gy remains the standard of care in limited-stage SCLC.

LSCLC patients who continue to smoke during CHT/RT have poorer survival rates than those who do not. Smoking did not have an impact on the rate of treatment interruptions attributed to toxicity.

clinicaltrials.gov Identifier: NCT00655876.