Immunotherapy with radiotherapy fails to improve prognosis of patients with stage IV non-small cell lung cancer: a retrospective cohort analysis of the THUNDER-2 study

Abstract

Background: Radiotherapy (RT) may enhance the systemic antitumor reaction to immunotherapy (IT).Currently, the effect of RT in stage IV non-small cell lung cancer (NSCLC) patients treated with IT is uncertain. This study aimed to confirm the role of RT in these patients. Methods:We enrolled 120 stage IV NSCLC patients who had been treated with IT and had received external beam radiation therapy (EBRT) or radioactive particle implantation (RPI) at 3 oncology centers in Shandong province between 2019 and 2021. We assessed relevant clinical factors and regular follow-up was conducted via electronic medical records and telephone. The primary endpoint was overall survival (OS).Different combination models in various populations were compared by generating Kaplan-Meier curves and Cox regression analysis. Results:The OS for the overall population was 5 months (range, 0-31 months) and the overall survival rate was 47.5%. Patients receiving IT with RPI had the least favorable prognostic trend (median survival: 2 months) compared to those receiving IT without RT (median survival: 9 months) and IT with EBRT (median survival: 10 months), but this difference was not significant (P=0.148). In subgroup analysis, patients treated with IT with RPI appeared to have a worse prognosis in some specific cohorts, such as ^ ORCID: 0000-0002-5454-8093. males [hazard ratio (HR) =2.433, P=0.031], non-squamous carcinoma histologies (HR =2.680, P=0.034), patients with oligometastases (HR =7.967, P=0.024), patients with liver metastases (HR =10.808, P=0.011) or brain metastases (HR =20.087, P=0.005), and those with Eastern Cooperative Oncology Group (ECOG) performance score ≥2 (HR =2.769, P=0.043). Multivariate Cox analysis of total population revealed that ECOG score and IT stage were the independent prognostic factors. IT combined with EBRT did not have a significant survival benefit in all subgroups. Concurrent IT with RT and first-line and second-line IT combined with RT trended toward improved long-term prognosis.Conclusions: While the robustness of the present conclusions is limited by relatively small sample size and retrospective nature of this research, the addition of EBRT or RPI to IT did not significantly improve patients' OS in stage IV NSCLC. Early combination IT after RT may benefit patients with long-term survival.

Correlation between Circulating miR-16, miR-29a, miR-144 and miR-150, and the Radiotherapy Response and Survival of Non-Small-Cell Lung Cancer Patients

“…In the case of inoperable lung cancer, the current standard therapy is radiotherapy combined with chemotherapy. Although both therapies have undergone further development in the last decades and immunotherapy has become a new option for NSCLC patients, a partial response and acquisition of resistance prevents treatment success, and this disease is still associated with a very poor patient prognosis (Chen et al, 2020, Lafaze et al, 2023, Zhou et al, 2023 [ 2 , 3 , 4 , 5 , 6 , 7 , 8 ]).…”