Histology, Tumor Volume, and Radiation Dose Predict Outcomes in Non-Small Cell Lung Cancer Patients after Stereotactic Ablative Radiation Therapy

Abstract

Histology, tumor volume, and radiation dose have been separately reported as possible predictors of recurrence in non-small cell lung cancer following stereotactic ablative body radiotherapy (SABR). However, it remains unclear if histology should be independently considered when choosing SABR dose prescriptions. The study population included 508 patients with 561 lesions treated between 2000 and 2016, of which 442 patients with 482 lesions had complete dosimetric information. The primary endpoint was in-field tumor control censored by either death or progression. Involved lobe control was also assessed. At a median follow-up of 6.7 years, 3-year in-field control, involved lobe control, overall survival, and progression-free survival were 88.1%, 80.0%, 49.4%, and 37.2%, respectively. Gross tumor volume (GTV, HR=1.01 per mL, p=0.0044) and histology (p=0.0225) were independently associated with involved lobe failure; GTV (HR=1.013, p=0.001) and radiation dose to the GTV (cutoff of 110Gy, biologically effective dose with α/β=10 [BED10], HR=2.380, p=0.0084) were independently associated with in-field failure. For squamous cell carcinomas, lower prescription doses were associated with worse in-field control independent of GTV (≤ vs. >110Gy BED10: HR=3.621, p=0.0147; 12Gyx4 or 10Gyx5 vs. 18Gy or 20Gyx3: HR=3.530, p=0.0447). For adenocarcinomas, there were no differences in in-field control observed using the above dose groupings (p=0.12 and p=0.31). GTV, dose to GTV, and histology are important factors contributing to involved lobe and in-field recurrence risk. A dose local control relationship was observed for squamous cell carcinomas treated with commonly used SABR dose prescriptions. In the absence of level I data to guide management, we posit that GTV and histology should be considered to personalize radiation dose for SABR. We suggest lower prescription doses (i.e., 12Gyx4 or 10Gx5) should be avoided for squamous cell carcinomas if there are no concerns about normal tissue toxicity.