# Carbon-Ion radiotherapy alone for inoperable locally advanced Non-Small cell lung cancer: A Japanese National registry study (J-CROS-LUNG)

## TL;DR

Carbon-ion radiotherapy shows promising results for treating advanced lung cancer with minimal side effects.

## Contribution

A nationwide registry study in Japan evaluates carbon-ion radiotherapy for inoperable lung cancer patients ineligible for surgery or chemoradiotherapy.

## Key findings

- 3-year overall survival rate was 49.1% with acceptable toxicity.
- Concomitant interstitial pneumonia was a significant factor affecting survival.
- No grade ≥4 toxicity was observed in patients treated with carbon-ion radiotherapy.

## Abstract

Carbon-ion radiotherapy (CIRT) offers high-dose concentration and enhanced biological effects. Since 2016, a nationwide prospective registry study of CIRT for locally advanced non-small cell lung cancer (LA-NSCLC) has been conducted in Japan. This study aimed to evaluate clinical outcomes of CIRT in patients with LA-NSCLC who were ineligible for surgery or chemoradiotherapy (CCRT).

Patients with inoperable LA-NSCLC treated with CIRT in Japan from May 2016 to June 2020 were included. Most patients received 64–72 Gy in 16 fractions per the Japanese Society for Radiation Oncology (JASTRO) unified policy. Elective nodal irradiation was allowed for nodal disease. No systemic therapy was administered before or after CIRT. Overall and progression-free survival were estimated by the Kaplan–Meier method; local failure was evaluated using the cumulative incidence function (CIF) with Gray’s test. Two-sided P < 0.05 was considered significant.

Median follow-up was 28 months for all patients and 36 months for survivors. Of the 55 patients, clinical stages (UICC 8th) were: IIB (26), IIIA (17), and IIIB (12). A clinical diagnosis without histological confirmation was established in four patients (7.3%), and interstitial pneumonia (IP) was present in nine (16.4%). The 3-year overall survival and progression-free survival were 49.1% (95% confidence interval [CI], 33.8–62.7%) and 28.3% (95% CI, 16.6–41.3%), respectively. Using competing risks, the 3-year CIF was 37.4% (95% CI, 24.2–50.5%). No grade ≥ 4 toxicity was observed; grade 2 and 3 pneumonitis occurred in 3 (5.5%) and 2 (3.6%) patients, respectively. In multivariable analysis, concomitant IP was a significant factor for overall survival (P = 0.011).

CIRT demonstrated favorable tumor control with acceptable toxicity in patients with LA-NSCLC ineligible for surgery or CCRT. It may be a promising treatment option for this patient population.

The online version contains supplementary material available at 10.1007/s11604-025-01925-z.