The abscopal effect in metastatic lung cancer: a retrospective analysis of combined radiotherapy and immunotherapy

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BACKGROUND: The abscopal effect (AbE) refers to the regression of non-irradiated tumors following localized radiotherapy (RT), suggesting a systemic immune-mediated response. The combination of RT with immunotherapy (IO) has been proposed to enhance the AbE by overcoming RT-induced immunosuppressive mechanisms, but robust evidence, specifically in non-small cell lung cancer (NSCLC), is lacking. This study aimed to determine the prevalence of the AbE and its association with progression-free survival (PFS) and overall survival (OS) in metastatic lung cancer patients receiving RT and IO. MATERIALS AND METHODS: We analyzed consecutive metastatic lung cancer patients who received IO at a certified lung cancer center in Germany between 2009 and 2021. Inclusion required RT to at least one lesion and at least one measurable non-irradiated lesion. The AbE was defined as radiological regression of a non-irradiated lesion following RT. PFS and OS were analyzed using Kaplan-Meier estimates and Cox regression models. Factors influencing survival, such as RT site selection and IO duration, were assessed in univariable and multivariable analyses. RESULTS: A total of 72 patients were included. The AbE was observed in 9.3% (n = 7). While the AbE was significantly associated with prolonged PFS (HR = 0.41, 95% CI: 0.19-0.92, p = 0.03), it did not significantly impact OS (HR = 0.70, 95% CI: 0.30-1.64, p = 0.41). In contrast, RT to the primary tumor (HR = 0.16, p = 0.004) and longer IO duration (HR = 0.83, p = 0.001) were strong predictors of improved OS. CONCLUSION: While the AbE remains an intriguing phenomenon, its occurrence was rare and not significantly associated with OS. Strategic RT site selection and optimized treatment sequencing were more strongly linked to improved survival outcomes, highlighting the need for refined radioimmunotherapy strategies.

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