Age and the association of radiotherapy with survival in extensive-stage small-cell lung cancer: an exploratory secondary analysis of two observational cohorts.
7 affiliations
- 1Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
- 2Day Surgery Center, West China Hospital, Sichuan University, Chengdu, China.
- 3Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu, China.
- 4Department of Respiratory and Critical Care Medicine, Institute of Respiratory Health, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, China.
- 5Division of Biliary Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, China.
- 6Department of Respiratory and Critical Care Medicine, The Second People's Hospital of Yibin, Yibin, China.
- 7Lung Cancer Center/Lung Cancer Institute, West China Hospital, Sichuan University, Chengdu, China.
Abstract
Thoracic radiotherapy is an option for some patients with extensive-stage small-cell lung cancer (ES-SCLC), but it is unclear how it should be used after first-line chemoimmunotherapy and whether its value differs with age. In two observational datasets that defined radiotherapy exposure differently, we asked whether age changed the association between radiotherapy and overall survival (OS). We studied a historical Surveillance, Epidemiology, and End Results (SEER) cohort diagnosed in 2010-2015 and re-analyzed a previously published multicenter cohort of 171 patients given first-line chemoimmunotherapy in Sichuan. In SEER the exposure was recorded first-course radiotherapy, which is not the same as consolidative thoracic radiotherapy (cTRT). The primary SEER cohort contained 13,676 patients with distant metastasis, and one global propensity-score match (PSM) produced 4,116 pairs. In the institutional cohort we fitted a time-varying Cox model for cTRT and OS; 33 patients with 33 deaths had complete data for the adjusted model. Age was treated as continuous, and we tested treatment-by-age interactions in both cohorts. In SEER, recorded first-course radiotherapy was associated with lower all-cause mortality in the multivariable model [hazard ratio (HR) 0.75, 95% confidence interval (CI): 0.72-0.78; P<0.001]; the matched cohort gave a similar estimate (HR 0.72, 95% CI: 0.69-0.75; P<0.001). Age did not interact with radiotherapy (ratio of HRs per 10-year increase 1.02, 95% CI: 0.98-1.06; likelihood-ratio P=0.36). In the institutional time-varying Cox analysis, cTRT was associated with lower mortality (HR 0.40, 95% CI: 0.17-0.98; P=0.04), and here the interaction was apparent (ratio 0.27 per 10-year increase, 95% CI: 0.11-0.64; Wald P=0.003; likelihood-ratio P=0.01). At age 65 years, the model-derived cTRT HR was 0.35 (95% CI: 0.16-0.78; P=0.01). In the SEER cohort, recorded first-course radiotherapy was associated with OS, and the interaction with age was not statistically significant. In the Sichuan cohort, the time-varying model gave an overall cTRT HR of 0.40 and a significant continuous age-by-cTRT interaction. That model, however, rested on 33 complete cases and on covariates chosen by outcome screening, two of which were measured after treatment began. These findings establish neither a validated age threshold nor a causal age-specific treatment effect.
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BibTeX
@article{zhang2026association,
title = {{Age and the association of radiotherapy with survival in extensive-stage small-cell lung cancer: an exploratory secondary analysis of two observational cohorts.}},
author = {Shengxin Zhang and Yang Liu and Xueyan Zhou and Keqin Tan and Nan Lin and Xiang Lin and Xinggang Yang and Xiao Liang and Rongxing Zhou and Bo Li and Jingsi Dong and Xuelei Ma},
journal = {Translational lung cancer research},
year = {2026},
month = oct,
doi = {10.21037/tlcr-2026-1062},
url = {https://europepmc.org/article/MED/42999421},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Age and the association of radiotherapy with survival in extensive-stage small-cell lung cancer: an exploratory secondary analysis of two observational cohorts.
AU - Shengxin Zhang
AU - Yang Liu
AU - Xueyan Zhou
AU - Keqin Tan
AU - Nan Lin
AU - Xiang Lin
AU - Xinggang Yang
AU - Xiao Liang
AU - Rongxing Zhou
AU - Bo Li
AU - Jingsi Dong
AU - Xuelei Ma
PY - 2026
DA - 2026/10/23
JO - Translational lung cancer research
DO - 10.21037/tlcr-2026-1062
UR - https://europepmc.org/article/MED/42999421
AB - Thoracic radiotherapy is an option for some patients with extensive-stage small-cell lung cancer (ES-SCLC), but it is unclear how it should be used after first-line chemoimmunotherapy and whether its value differs with age. In two observational datasets that defined radiotherapy exposure differently, we asked whether age changed the association between radiotherapy and overall survival (OS). We studied a historical Surveillance, Epidemiology, and End Results (SEER) cohort diagnosed in 2010-2015 and re-analyzed a previously published multicenter cohort of 171 patients given first-line chemoimmunotherapy in Sichuan. In SEER the exposure was recorded first-course radiotherapy, which is not the same as consolidative thoracic radiotherapy (cTRT). The primary SEER cohort contained 13,676 patients with distant metastasis, and one global propensity-score match (PSM) produced 4,116 pairs. In the institutional cohort we fitted a time-varying Cox model for cTRT and OS; 33 patients with 33 deaths had complete data for the adjusted model. Age was treated as continuous, and we tested treatment-by-age interactions in both cohorts. In SEER, recorded first-course radiotherapy was associated with lower all-cause mortality in the multivariable model [hazard ratio (HR) 0.75, 95% confidence interval (CI): 0.72-0.78; P<0.001]; the matched cohort gave a similar estimate (HR 0.72, 95% CI: 0.69-0.75; P<0.001). Age did not interact with radiotherapy (ratio of HRs per 10-year increase 1.02, 95% CI: 0.98-1.06; likelihood-ratio P=0.36). In the institutional time-varying Cox analysis, cTRT was associated with lower mortality (HR 0.40, 95% CI: 0.17-0.98; P=0.04), and here the interaction was apparent (ratio 0.27 per 10-year increase, 95% CI: 0.11-0.64; Wald P=0.003; likelihood-ratio P=0.01). At age 65 years, the model-derived cTRT HR was 0.35 (95% CI: 0.16-0.78; P=0.01). In the SEER cohort, recorded first-course radiotherapy was associated with OS, and the interaction with age was not statistically significant. In the Sichuan cohort, the time-varying model gave an overall cTRT HR of 0.40 and a significant continuous age-by-cTRT interaction. That model, however, rested on 33 complete cases and on covariates chosen by outcome screening, two of which were measured after treatment began. These findings establish neither a validated age threshold nor a causal age-specific treatment effect.
SN - 2218-6751
SN - 2226-4477
ER -