Impact of vulnerability on concurrent chemoradiotherapy outcomes in patients with locally advanced non-small cell...

The effect of vulnerability on the outcomes of patients with locally advanced non-small cell lung cancer (NSCLC) undergoing concurrent chemoradiotherapy (CCRT) remains unclear.

To examine the impact of vulnerability on the outcomes in patients with locally advanced NSCLC undergoing CCRT.

We analyzed data from the Japan Lung Cancer Society Integrated Clinical Trial Database, which included 1288 patients with locally advanced NSCLC treated with CCRT.

Vulnerability was defined as meeting one or more of the following: age ⩾75 years; history of chronic obstructive pulmonary disease (COPD) or emphysema; chronic kidney disease with at least one other comorbidity; or cancer cachexia (C-reactive protein >1.0 mg/dL and albumin <3.5 g/dL).

Among 741 eligible patients, 283 (38.2%) were classified as vulnerable. Vulnerable patients had significantly shorter overall survival (OS; 19.7 vs 27.4 months, p = 0.003), whereas progression-free survival (PFS) did not differ significantly (8.8 vs 10.4 months, p = 0.151). In multivariate analysis adjusted for factors including cisplatin (CDDP) use, the association between vulnerability and OS was attenuated (hazard ratio = 1.221, 95% confidence interval: 0.959-1.555, p = 0.105). The vulnerable patients were significantly less likely to undergo subsequent therapies (60.4% vs 71.6%, p = 0.003). Among the vulnerability components, cachexia showed the strongest association with shorter PFS (8.0 vs 10.5 months, p = 0.009) and OS (16.5 vs 27.4 months, p < 0.001).

Clinical vulnerability was associated with poorer OS after CCRT, mediated by multiple factors, including reduced CDDP use, lower subsequent therapy rates, and cachexia. Individualized strategies that balance treatment intensity, supportive care, and access to post-CCRT are essential for improving outcomes.