Toxicity in patients receiving radiotherapy for ultracentral stage I non-small cell lung cancer: A secondary analysis of the LUSTRE randomized trial.

Objective: Stereotactic body radiotherapy (SBRT) carries potentially higher risks for ultracentral (UC) NSCLC with limited prospective data to guide decision making. We conducted a secondary analysis from a randomized trial of SBRT and conventionally hypofractionated radiation (CRT) to assess these risks.

Methods: Patients (n = 233) with medically inoperable stage I NSCLC were recruited from 2014 to 2020. Patients with UC targets directly overlapping the proximal bronchial tree (PBT) were identified. The primary objective was the occurrence of related grade 3-5 toxicity > 3 months following radiation. Secondary endpoints included local control, survival, and evaluation of PBT dose and its association with late toxicity.

Results: Thirty UC tumors were identified (23 - SBRT 60 Gy/8 fractions, 7 - CRT 60 Gy/15 fractions). Median age was 72 years, and median tumor size was 2.8 cm. Most patients (67 %) had histologically confirmed NSCLC. At a median follow-up of 2.9 years, 3 and 1 patients developed grade 3 and 5 toxicity respectively (all SBRT). 3-year local control was 85 %. Mean PBT dose (converted to 2 Gy dose equivalents) was higher in patients with grade ≥ 3 toxicity, particularly for 4 cc (105.5 vs 51.8 Gy, p = 0.0004), 5 cc (84 vs 46.1 Gy, p = 0.003), and volumetric doses (V65 - V100Gy). The patient with grade 5 toxicity had the highest 5 cc dose (117 Gy), V90Gy (8.2 cc), and V100Gy (7 cc).

Conclusions: SBRT for UC NSCLC provides good local control but carries a high rate of late grade 3-5 toxicity. An apparent association between toxicity and PBT volumetric dose was observed, which should be considered if SBRT is offered.