Background and purpose With the escalating global incidence and mortality of lung cancer, immunotherapy has achieved modest success while facing persistent challenges. The immunomodulatory effect of radiotherapy has gradually gained attention, especially the abscopal effect observed in the combination of radiotherapy and immunotherapy. Although mechanistically controversial, its clinical significance in lung cancer treatment is noteworthy. Therefore, this study aims to delve into the therapeutic differences between immunotherapy using immune checkpoint inhibitors (ICI) combined with radiotherapy (RT) and traditional immunotherapy alone, aiming to provide scientific evidence for optimizing lung cancer treatment strategies, improving patient outcomes, and enhancing survival rates. Methods Literature searches were conducted in PubMed, Embase, Web of Science, and the Cochrane Library up to 26 March 2024. Heterogeneity, sensitivity analysis, forest plots, clipping plots, and publication bias were analysed using RevMan5.4 and Stata 12.0. Results This meta-analysis included 19 articles, encompassing 5109 lung cancer patients in the ICI + RT group and 4686 patients in the ICI group. Meta-analysis revealed that the progression-free survival (PFS) (HR = 0.68, 95%CI [0.62–0.75], p < 0.00001) and overall survival (OS) (HR = 0.70, 95%CI [0.62–0.79], p < 0.00001) of lung cancer patients in the ICI + RT treatment group were longer than those in the ICI treatment group, and ICI + RT or ICI treatment for lung cancer patients did not affect adverse events (OR = 1.09, 95%CI [0.80–1.50], p > 0.05) or death (HR = 1.03, 95%CI [0.30–3.57], p < 0.05).The subgroup analysis showed that within the PFS group, RCT (HR = 0.73, 95%CI [0.62–0.85], p < 0.00001), Non-RCT (HR = 0.61, 95%CI [0.49–0.76], p < 0.00001), Nivolumab (HR = 0.57, 95%CI [0.46–0.71], p < 0.00001), Pembrolizumab (HR = 0.67, 95%CI [0.57–0.80], p < 0.00001), stating ICI or during ICI (HR = 0.69, 95%CI [0.61–0.79], p < 0.00001), during ICI (HR = 0.70, 95%CI [0.58–0.85], p < 0.001), squamous (HR = 0.57, 95%CI [0.41–0.79], p < 0.001), Non-squamous (HR = 0.63, 95%CI [0.47–0.83], p < 0.001), smoking (HR = 0.46, 95%CI [0.39–0.95], p < 0.05), no smoking or smoking history (HR = 0.73, 95%CI [0.63–0.92], p < 0.01), ECOG = 0 (HR = 0.53, 95%CI [0.37–0.75], p < 0.01), ECOG > = 1 (HR = 0.61, 95%CI [0.45–0.83], p < 0.01) were significant, male (HR = 0.56, 95%CI [0.44–0.70], p < 0.0001), female (HR = 0.74, 95%CI [0.52–1.05], p > 0.05) were only significant in males, PD-1 high expression (HR = 0.92, 95%CI [0.48–1.78], p > 0.05), PD-1 low expression (HR = 0.61, 95%CI [0.40–0.92], p < 0.05) were significant only in PD-1 low expression; within the OS group, RCT (HR = 0.65, 95%CI [0.55–0.76], p < 0.00001), Non-RCT (HR = 0.77, 95%CI [0.65–0.91], p < 0.01), Nivolumab (HR = 0.73, 95%CI [0.54–0.99], p < 0.05), Pembrolizumab (HR = 0.64, 95%CI [0.55–0.75], p < 0.00001), stating ICI or during ICI (HR = 0.74, 95%CI [0.64–0.86], p < 0.00001), during ICI (HR = 0.65, 95%CI [0.52–0.82], p < 0.001), Smoking (HR = 0.61, 95%CI [0.28–0.75], p < 0.01), No smoking or smoking history (HR = 0.76, 95%CI [0.62–0.86], p < 0.001) were significant, male (HR = 0.59, 95%CI [0.44–0.78], p < 0.0001), female (HR = 1.01, 95%CI [0.68–1.48], p > 0.05) were only significant in males, PD-1 high expression (HR = 0.53, 95%CI [0.22–1.26], p > 0.05), PD-1 low expression (HR = 0.60, 95%CI [0.39–0.94], p < 0.05) were significant only in PD-1 low expression, ECOG = 0 (HR = 0.51, 95%CI [0.31–0.82], p < 0.01), ECOG > = 1 (HR = 0.80, 95%CI [0.52–1.23], p > 0.05) were significant only in ECOG = 0. Conclusion The results of this study indicate that the combination of ICI and RT significantly prolongs the Progression-Free-Survival and Overall Survival of lung cancer patients compared to the use of ICI alone, demonstrating a certain therapeutic advantage across different subgroups. This finding provides robust evidence supporting the widespread adoption of ICI+RT combination therapy for lung cancer, potentially leading to more effective treatment strategies, improved patient outcomes, and higher survival rates. Trial registration <a href="https://www.crd.york.ac.uk/prospero/">https://www.crd.york.ac.uk/prospero/</a>, identifier CRD42024544343.

Immunotherapy combined with radiotherapy in the treatment of lung cancer: a meta-analysis of therapeutic effectiveness, safety considerations, and abscopal effect

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2025年7月17日

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Min Gao,
Mingxuan Su,
Jinyuan Wang,
Rutong Wang,
Jiawei Yi,
Keming Xiang,
Renhe Deng,
Linxi Jiang,
Yu Zeng,
Junhui He,
Yuqiang Lv

摘要

Background and purpose

With the escalating global incidence and mortality of lung cancer, immunotherapy has achieved modest success while facing persistent challenges. The immunomodulatory effect of radiotherapy has gradually gained attention, especially the abscopal effect observed in the combination of radiotherapy and immunotherapy. Although mechanistically controversial, its clinical significance in lung cancer treatment is noteworthy. Therefore, this study aims to delve into the therapeutic differences between immunotherapy using immune checkpoint inhibitors (ICI) combined with radiotherapy (RT) and traditional immunotherapy alone, aiming to provide scientific evidence for optimizing lung cancer treatment strategies, improving patient outcomes, and enhancing survival rates.

Methods

Literature searches were conducted in PubMed, Embase, Web of Science, and the Cochrane Library up to 26 March 2024. Heterogeneity, sensitivity analysis, forest plots, clipping plots, and publication bias were analysed using RevMan5.4 and Stata 12.0.

Results

This meta-analysis included 19 articles, encompassing 5109 lung cancer patients in the ICI + RT group and 4686 patients in the ICI group. Meta-analysis revealed that the progression-free survival (PFS) (HR = 0.68, 95%CI [0.62–0.75], p < 0.00001) and overall survival (OS) (HR = 0.70, 95%CI [0.62–0.79], p < 0.00001) of lung cancer patients in the ICI + RT treatment group were longer than those in the ICI treatment group, and ICI + RT or ICI treatment for lung cancer patients did not affect adverse events (OR = 1.09, 95%CI [0.80–1.50], p > 0.05) or death (HR = 1.03, 95%CI [0.30–3.57], p < 0.05).The subgroup analysis showed that within the PFS group, RCT (HR = 0.73, 95%CI [0.62–0.85], p < 0.00001), Non-RCT (HR = 0.61, 95%CI [0.49–0.76], p < 0.00001), Nivolumab (HR = 0.57, 95%CI [0.46–0.71], p < 0.00001), Pembrolizumab (HR = 0.67, 95%CI [0.57–0.80], p < 0.00001), stating ICI or during ICI (HR = 0.69, 95%CI [0.61–0.79], p < 0.00001), during ICI (HR = 0.70, 95%CI [0.58–0.85], p < 0.001), squamous (HR = 0.57, 95%CI [0.41–0.79], p < 0.001), Non-squamous (HR = 0.63, 95%CI [0.47–0.83], p < 0.001), smoking (HR = 0.46, 95%CI [0.39–0.95], p < 0.05), no smoking or smoking history (HR = 0.73, 95%CI [0.63–0.92], p < 0.01), ECOG = 0 (HR = 0.53, 95%CI [0.37–0.75], p < 0.01), ECOG > = 1 (HR = 0.61, 95%CI [0.45–0.83], p < 0.01) were significant, male (HR = 0.56, 95%CI [0.44–0.70], p < 0.0001), female (HR = 0.74, 95%CI [0.52–1.05], p > 0.05) were only significant in males, PD-1 high expression (HR = 0.92, 95%CI [0.48–1.78], p > 0.05), PD-1 low expression (HR = 0.61, 95%CI [0.40–0.92], p < 0.05) were significant only in PD-1 low expression; within the OS group, RCT (HR = 0.65, 95%CI [0.55–0.76], p < 0.00001), Non-RCT (HR = 0.77, 95%CI [0.65–0.91], p < 0.01), Nivolumab (HR = 0.73, 95%CI [0.54–0.99], p < 0.05), Pembrolizumab (HR = 0.64, 95%CI [0.55–0.75], p < 0.00001), stating ICI or during ICI (HR = 0.74, 95%CI [0.64–0.86], p < 0.00001), during ICI (HR = 0.65, 95%CI [0.52–0.82], p < 0.001), Smoking (HR = 0.61, 95%CI [0.28–0.75], p < 0.01), No smoking or smoking history (HR = 0.76, 95%CI [0.62–0.86], p < 0.001) were significant, male (HR = 0.59, 95%CI [0.44–0.78], p < 0.0001), female (HR = 1.01, 95%CI [0.68–1.48], p > 0.05) were only significant in males, PD-1 high expression (HR = 0.53, 95%CI [0.22–1.26], p > 0.05), PD-1 low expression (HR = 0.60, 95%CI [0.39–0.94], p < 0.05) were significant only in PD-1 low expression, ECOG = 0 (HR = 0.51, 95%CI [0.31–0.82], p < 0.01), ECOG > = 1 (HR = 0.80, 95%CI [0.52–1.23], p > 0.05) were significant only in ECOG = 0.

Conclusion

The results of this study indicate that the combination of ICI and RT significantly prolongs the Progression-Free-Survival and Overall Survival of lung cancer patients compared to the use of ICI alone, demonstrating a certain therapeutic advantage across different subgroups. This finding provides robust evidence supporting the widespread adoption of ICI+RT combination therapy for lung cancer, potentially leading to more effective treatment strategies, improved patient outcomes, and higher survival rates.

Trial registration

https://www.crd.york.ac.uk/prospero/, identifier CRD42024544343.