Long-Term Outcomes of Salvage Stereotactic Ablative Radiotherapy for Isolated Lung Recurrence of Non-Small Cell Lung Cancer: A Phase II Clinical Trial.

OBJECTIVES: Our goal was to evaluate stereotactic ablative radiotherapy (SABR) as a salvage option for isolated recurrence of NSCLC in the lung parenchyma after definitive treatment of stage I to III disease. METHODS: Patients who had histologically confirmed, positron emission tomography-staged, isolated NSCLC recurring locally or metastasis in the lung parenchyma (≤3 cm, suitable for SABR) after previous definitive treatment were prospectively enrolled in this trial and treated with volumetric, image-guided SABR to 50 Gy in four fractions. Patients were then followed with computed tomography or positron emission tomography/computed tomography. Primary end points included the pattern of failure after salvage SABR, overall survival (OS), and progression-free survival (PFS). RESULTS: Fifty-nine patients with recurrent disease were treated with salvage SABR. The median age was 70 years (range 45-86 years), and the median follow-up time after salvage SABR was 58.3 months. Re-recurrence after salvage SABR developed in 19 patients (32%). Measuring from the date of salvage SABR, the estimated 5-year rates of local, regional, and distant failure were 5.2%, 10.3%, and 22.4%, respectively; the estimated PFS was 46.2% at 3 years and 41.1% at 5 years; and the OS rates were 63.5% at 3 years and 56.5% at 5 years. A high post-SABR neutrophil-to-lymphocyte ratio was found to predict poor survival. Grade 3 treatment-related adverse events developed in three patients (5%). No patient had a grade 4 or 5 event. CONCLUSION: Our study showed that salvage SABR provides excellent 5-year OS, local control, and PFS rates with minimal toxicity for patients with isolated NSCLC recurrence in the lung parenchyma. These results are striking and comparable to historically reported outcomes of patients with primary early-stage NSCLC treated with definitive SABR. SABR appears to be a very effective and safe salvage option for patients with isolated lung parenchyma recurrent disease after definitive treatment and should be considered along with surgery as a potential first-line option for patients with local lung parenchymal recurrent disease.

7-year follow-up after stereotactic ablative radiotherapy for patients with stage I non-small cell lung cancer: Results of a phase 2 clinical trial.

BACKGROUND: The authors evaluated the efficacy, patterns of failure, and toxicity of stereotactic ablative radiotherapy (SABR) for patients with medically inoperable, clinical stage I non-small cell lung cancer (NSCLC) in a prospective clinical trial with 7 years of follow-up. Clinical staging was performed according to the seventh edition of the American Joint Committee on Cancer TNM staging system. METHODS: Eligible patients with histologically confirmed NSCLC of clinical stage I as determined using positron emission tomography staging were treated with SABR (50 grays in 4 fractions). The primary endpoint was progression-free survival. Patients were followed with computed tomography and/or positron emission tomography/computed tomography every 3 months for the first 2 years, every 6 months for the next 3 years, and then annually thereafter. RESULTS: A total of 65 patients were eligible for analysis. The median age of the patients was 71 years, and the median follow-up was 7.2 years. A total of 18 patients (27.7%) developed disease recurrence at a median of 14.5 months (range, 4.3-71.5 months) after SABR. Estimated incidences of local, regional, and distant disease recurrence using competing risk analysis were 8.1%, 10.9%, and 11.0%, respectively, at 5 years and 8.1%, 13.6%, and 13.8%, respectively, at 7 years. A second primary lung carcinoma developed in 12 patients (18.5%) at a median of 35 months (range, 5-67 months) after SABR. Estimated 5-year and 7-year progression-free survival rates were 49.5% and 38.2%, respectively; the corresponding overall survival rates were 55.7% and 47.5%, respectively. Three patients (4.6%) experienced grade 3 treatment-related adverse events. No patients developed grade 4 or 5 adverse events (toxicity was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events [version 3.0]). CONCLUSIONS: With long-term follow-up, the results of the current prospective study demonstrated outstanding local control and low toxicity after SABR in patients with clinical stage I NSCLC. Regional disease recurrence and distant metastases were the dominant manifestations of failure. Surveillance for second primary lung carcinoma is recommended. Cancer 2017;123:3031-39. © 2017 American Cancer Society.

Planning Target Volume D95 and Mean Dose Should Be Considered for Optimal Local Control for Stereotactic Ablative Radiation Therapy.

PURPOSE: To identify the optimal dose parameters predictive for local/lobar control after stereotactic ablative radiation therapy (SABR) in early-stage non-small cell lung cancer (NSCLC). METHODS AND MATERIALS: This study encompassed a total of 1092 patients (1200 lesions) with NSCLC of clinical stage T1-T2 N0M0 who were treated with SABR of 50 Gy in 4 fractions or 70 Gy in 10 fractions, depending on tumor location/size, using computed tomography-based heterogeneity corrections and a convolution superposition calculation algorithm. Patients were monitored by chest CT or positron emission tomography/CT and/or biopsy after SABR. Factors predicting local/lobar recurrence (LR) were determined by competing risk multivariate analysis. Continuous variables were divided into 2 subgroups at cutoff values identified by receiver operating characteristic curves. RESULTS: At a median follow-up time of 31.7 months (interquartile range, 14.8-51.3 months), the 5-year time to local recurrence within the same lobe and overall survival rates were 93.8% and 44.8%, respectively. Total cumulative number of patients experiencing LR was 40 (3.7%), occurring at a median time of 14.4 months (range, 4.8-46 months). Using multivariate competing risk analysis, independent predictive factors for LR after SABR were minimum biologically effective dose (BED10) to 95% of planning target volume (PTVD95 BED10) ≤86 Gy (corresponding to PTV D95 physics dose of 42 Gy in 4 fractions or 55 Gy in 10 fractions) and gross tumor volume ≥8.3 cm(3). The PTVmean BED10 was highly correlated with PTVD95 BED10. In univariate analysis, a cutoff of 130 Gy for PTVmean BED10 (corresponding to PTVmean physics dose of 55 Gy in 4 fractions or 75 Gy in 10 fractions) was also significantly associated with LR. CONCLUSIONS: In addition to gross tumor volume, higher radiation dose delivered to the PTV predicts for better local/lobar control. We recommend that both PTVD95 BED10 >86 Gy and PTVmean BED10 >130 Gy should be considered for SABR plan optimization.