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

Li Liu; Meng Yuan; Zhaolei Ding; Hui Feng; Xiaotao Zhang; Ning Liang; Wei Wang; Jun Wang; Yan Zhang; Shengjian Zhou; Anthony W Kim; Simona Castiglioni; Rafal Suwinski; Hang Wang; Pingping Hu; Jiandong Zhang

doi:10.21037/tlcr-22-843

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

Transl Lung Cancer Res. 2022 Dec;11(12):2507-2520. doi: 10.21037/tlcr-22-843.

Authors

Li Liu^#^{1

2

3}, Meng Yuan^#⁴, Zhaolei Ding⁵, Hui Feng⁶, Xiaotao Zhang⁷, Ning Liang^{1

2

3}, Wei Wang⁸, Jun Wang⁹, Yan Zhang³, Shengjian Zhou¹⁰, Anthony W Kim¹¹, Simona Castiglioni¹², Rafal Suwinski¹³, Hang Wang^{2

14}, Pingping Hu^{1

2

3}, Jiandong Zhang^{1

2

3}

Affiliations

¹ Department of Oncology, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, China.
² Department of Oncology, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Shandong Key Laboratory of Rheumatic Disease and Translational Medicine, Shandong Lung Cancer Institute, Jinan, China.
³ Medical Integration and Practice Center, Cheeloo College of Medicine, Shandong University, Jinan, China.
⁴ Department of Oncology, Shandong Provincial Qianfoshan Hospital, Weifang Medical University, Shandong Key Laboratory of Rheumatic Disease and Translational Medicine, Shandong Lung Cancer Institute, Jinan, China.
⁵ Department of Respiratory Medicine, Weifang People's Hospital, Weifang, China.
⁶ Department of Radiation Therapy, Linyi Cancer Hospital, Linyi, China.
⁷ Department of Radiation Oncology, The Affiliated Qingdao Central Hospital of Qingdao University, Qingdao, China.
⁸ Department of Thoracic Surgery, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Shandong Medicine and Health Key Laboratory of Emergency Medicine, Shandong Lung Cancer Institute, Shandong Institute of Respiratory Diseases, Jinan, China.
⁹ Department of Radiation Oncology, Fourth Hospital of Hebei Medical University, Shijiazhuang, China.
¹⁰ Department of Oncology, Liangshan County People's Hospital, Jining, China.
¹¹ Division of Thoracic Surgery, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
¹² Radiation Oncology Unit, Casa di Cura San Pio X Humanitas, Milan, Italy.
¹³ Radiotherapy and Chemotherapy Clinic and Teaching Hospital, Maria Sklodowska-Curie National Research Institute of Oncology, Gliwice, Poland.
¹⁴ Department of Oncology, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Shandong First Medical University, Jinan, China.

^# Contributed equally.

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 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.

Keywords: Immunotherapy (IT); radiotherapy (RT); stage IV non-small cell lung cancer (stage IV NSCLC).