Carbon ion radiotherapy with pencil beam scanning for stage III non-small cell lung cancer: toxicity profiles, survival outcomes, and prognostic indicators.

Abstract

Purpose: To evaluate the toxicities and survival outcomes associated with carbon ion radiotherapy (CIRT) using pencil beam scanning (PBS) and to assess the prognostic factors for patients with stage III non-small cell lung cancer (NSCLC) using a local effect model (LEM)-based biological dose calculation.

Methods: This analysis included patients with stage III NSCLC (n = 181) who received CIRT between December 2016 and June 2023. CIRT was administered at a relative biological effectiveness (RBE)-weighted dose of 77 Gy (range, 69-83.6 Gy) in 22 fractions (Fx) (range, 19-24 Fx). Most patients (96.1%) underwent systemic therapy before and/or after CIRT. Toxicities and survival outcomes were recorded, and statistical analyses conducted.

Results: The median follow-up period was 18.2 months. Grades 1, 2, 3, and 4 acute toxicities were observed in 62.4%, 30.4%, 2.8%, and 0.6% of patients, respectively, with hematological toxicities accounting for all grade ≥ 3 acute toxicities. Grades 1, 2, 3, and 4 late toxicities occurred in 40.3%, 30.9%, 4.4%, and 1.7% of patients, respectively, with most grade ≥ 3 CIRT-induced late toxicities (72.7%) observed in patients receiving a CIRT dose ≥ 79.2 Gy. The median overall survival (OS) and progression-free survival (PFS) were 37.1 and 16.7 months, respectively. The 2-year locoregional control (LRC), OS, PFS, and distant metastasis-free survival (DMFS) rates were 66.1%, 64.2%, 40.3%, and 49.5%, respectively. Patients who received a CIRT dose ≤ 77 Gy had better OS (p = 0.047), but worse LRC compared to those who received higher doses (p = 0.026). Post-CIRT immunotherapy was an independent prognostic factor for improved OS, DMFS, and PFS (p = 0.002, p < 0.001, and p < 0.001, respectively).

Conclusions: CIRT with PBS was effective for locally advanced NSCLC, resulting in acceptable toxicities and promising OS outcomes, particularly with doses of 69-77 Gy and post-CIRT immunotherapy.