Abscopal Effect and Long-Term Survival in a PD-L1-Negative Advanced NSCLC Patient Treated with Radiotherapy and Immunochemotherapy

This case study challenges conventional NSCLC treatment paradigms by demonstrating complete remission of brain metastases and sustained progression-free survival in a PD-L1-negative, driver gene-negative advanced non-small cell lung cancer patient following combined radiotherapy and immunotherapy. The findings highlight the potential of integrating radiotherapy with immunomodulatory therapies in refractory cases, regardless of PD-L1 status.

 

Literature Overview
The article, published in Frontiers in Immunology, reports on the treatment course and abscopal effect observed in a PD-L1-negative advanced NSCLC patient.

Background Knowledge
Non-small cell lung cancer (NSCLC) represents the most common lung cancer subtype, with brain metastases frequently occurring during advanced stages. Historically, intracranial metastases have been managed with whole-brain radiotherapy or stereotactic radiosurgery. Recent evidence suggests that combining radiotherapy with immune checkpoint inhibitors (e.g., PD-1/PD-L1 inhibitors) can induce abscopal effects - systemic tumor regression in non-irradiated sites - indicating localized radiotherapy may activate systemic anti-tumor immunity. While PD-L1 expression is commonly used to predict immunotherapy response, PD-L1-negative patients are generally considered poor responders. This study challenges this paradigm by demonstrating rapid intracranial remission and prolonged survival in a PD-L1-negative patient through combined radiotherapy and immunochemotherapy.

 

 

Research Methods and Experiments
A 68-year-old male diagnosed with stage IA right lower lobe adenocarcinoma in 2020 showed no detectable driver gene mutations and PD-L1-negative status. In February 2022, multiple brain and left iliac bone metastases were identified. The patient received intensity-modulated radiotherapy (IMRT, 36 Gy in 12 fractions) to metastatic sites, combined with pemetrexed, cisplatin, and sintilizumab during radiotherapy. Subsequent maintenance therapy included carboplatin plus pemetrexed and sintilizumab. Tumor burden, immune cell dynamics, and progression-free survival were evaluated over 35 months of follow-up.

Key Conclusions and Perspectives

• PD-L1-negative advanced NSCLC patients can achieve complete brain metastasis remission through radiotherapy combined with immunotherapy, suggesting abscopal effects may occur independently of PD-L1 expression.
• Sustained peripheral CD8+ T-cell elevation indicates radiotherapy combined with immunotherapy can effectively activate and maintain anti-tumor immune responses.
• The patient's 35-month progression-free survival and 40+ month overall survival significantly exceed average advanced NSCLC survival rates, demonstrating potential survival benefits of this combination approach.
• Radiotherapy-induced immunogenic cell death releases tumor antigens, while PD-1 inhibitors reverse T-cell exhaustion, enhancing systemic immune control.
• TP53 mutations may enhance immunogenicity through increased neoantigen burden, promoting abscopal effect development.

Research Significance and Prospects
This study establishes combination therapy potential in PD-L1-negative advanced NSCLC, suggesting personalized strategies can overcome PD-L1 status limitations. Future approaches could integrate molecular imaging (e.g., CXCR4-PET) for dynamic immune activation monitoring and optimize treatment timing. Patient-derived organoid models may further validate abscopal mechanisms and identify predictive biomarkers.

 

 

Conclusion
This case provides novel therapeutic strategies for PD-L1-negative, driver gene-negative advanced NSCLC patients, demonstrating that combined radiotherapy and immunotherapy can induce abscopal effects and achieve rapid complete remission of intracranial metastases. The findings suggest this combination may enable long-term disease control through CD8+ T-cell activation, tumor antigen release, and enhanced immune recognition even in PD-L1-deficient settings. This evidence supports the clinical potential of integrating radiotherapy with immunomodulatory treatments in advanced NSCLC management.

 

Qiang Wen, Weiqi Wang, Ke Zhang, Zhihua Liu, and Lei Wang. Case Report: Abscopal effect and long-term survival in a PD-L1 negative NSCLC patient treated with radiotherapy and immuno-chemotherapy. Frontiers in Immunology.