Full Dose SBRT in Combination With Mediastinal Chemoradiation for Locally Advanced, Non-Small Cell Lung Cancer: A Practical Guide for Planning, Dosimetric Results From a Phase 2 Study, and a Treatment Planning Guide for the Phase 3 NRG Oncology LU-008 Trial

Abstract

Stereotactic body radiation therapy (SBRT) has been utilized with high effectiveness in early stage NSCLC but has not been studied extensively in locally advanced NSCLC. We conducted a phase II study delivering SBRT to the primary tumor followed by conventionally fractionated chemoradiation to the involved lymph nodes for patients with node positive locally advanced NSCLC. This manuscript serves as both a guide to planning techniques utilized on this trial and the subsequent phase III study, NRG Oncology LU-008, and to report patient dosimetry and toxicity results. We initiated a phase II multi-center single arm study evaluating SBRT to the primary tumor (50-54 Gy in 3-5 fractions) followed by conventionally fractionated chemoradiation to 60 Gy in 2 Gy fractions with doublet chemotherapy to the involved lymph nodes for patients with stage III or unresectable stage II NSCLC. Patients eligible for adjuvant immunotherapy received up to 12 months of durvalumab. We report a detailed guide for the entire treatment process from CT simulation through treatment planning and delivery. The dosimetric outcomes from the 60 patients who completed therapy on study are reported both for target coverage and normal structure doses. We also report correlation between radiation related toxicities and dosimetric parameters. 60 patients were enrolled between 2017-2022. Planning techniques utilized were primarily VMAT for both SBRT to the primary tumor and conventionally fractionated radiation to the involved nodes, with a minority of cases utilizing dynamic conformal arcs technique or static DMLC IMRT. Grade 2 or higher pneumonitis was associated with lung dose V5Gy >70 % and grade 2 or higher pulmonary toxicity was associated with lung dose V10Gy>50%. Only 3 patients (5%) experienced grade 3 or higher pneumonitis. Grade 2 or higher esophagitis was associated with esophageal doses, including mean dose >20Gy, V60Gy >7%, and D1cc >55Gy. Only one patient (1.7%) experienced grade 3 esophagitis. SBRT to the primary tumor followed by conventionally fractionated chemoradiation to the involved lymph nodes is feasible with planning techniques as described. Radiation related toxicity on this phase II study was low. This manuscript serves as a guideline for the recently activated NRG Oncology LU-008 phase III trial evaluating this experimental regimen.