Main Session
Sep 29
PQA 07 - Head and Neck Cancer, Lung Cancer/Thoracic Malignancies, and Nursing and Supportive Care

3551 - Sustained Systemic Therapy plus Brain Radiotherapy: Survival in Extensive-Stage Small-Cell Lung Cancer with Brain-Only Progression after First-Line Treatment in a Multicenter Cohort Study

03:45pm - 05:00pm ET
Poster Hall - Exhibit Hall A
Screen: 33
POSTER

Presenter(s)

Shuangqing Lu, MD - Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences,, Jinan,

S. Lu1, D. Chen2, L. Zhao3, X. Cai4, and H. Zhu5; 1Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Science, Jinan, China, 2Shandong Provincial Key Laboratory of Precision Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China, 3TIANJIN MEDICAL UNIVERSITY CANCER HOSPITAL&INSTITUTE, tianjin, China, 4Department of Radiation Oncology, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China, Shanghai, China, 5Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences Department of Radiation Oncology, Jinan, Shandong, China

Purpose/Objective(s): First-line chemoimmunotherapy has improved overall survival in extensive-stage small-cell lung cancer (ES-SCLC), but it fails to effectively reduce the incidence of brain metastases. Consequently, brain-only progression (BOP) remains a critical clinical challenge. This study aimed to elucidate the optimal second-line strategy for ES-SCLC patients experiencing BOP: whether to switch to a new systemic regimen (Substitution Therapy, ST) or to maintain the original systemic backbone while adding brain radiotherapy (OTP+BRT)

Materials/Methods: In this multicenter retrospective cohort study, we screened 889 ES-SCLC patients without baseline brain metastases who progressed after standard first-line platinum-etoposide therapy (with or without immunotherapy). We identified 203 patients who developed strictly defined BOP (intracranial progression with maintained extracranial control). Patients were categorized into three second-line strategies: OTP+BRT (n=71), ST+BRT (n=64), and ST alone (n=68). Inverse probability of treatment weighting (IPTW) based on covariate balancing propensity scores was utilized to adjust for baseline imbalances, including prior immunotherapy exposure and initial progression-free survival (iPFS). The primary endpoint was overall survival from second-line initiation (OS2).

Results: In the rigorous IPTW-weighted analysis, continuing the original systemic therapy with brain radiotherapy (OTP+BRT) demonstrated a significantly superior median OS2 of 14.7 months, compared with 10.2 months for ST (HR, 1.68; P=.028) and 9.8 months for ST+BRT (HR, 1.67; P=.023). The median second-line progression-free survival (PFS2) was also significantly longer with OTP+BRT (8.0 months) versus ST (4.0 months; P=.024). Crucially, subgroup analyses revealed that the survival advantage of OTP+BRT was most pronounced in patients who received prior immunotherapy (OS2 HR for ST, 2.32; P=.038) and in those with an iPFS =7.5 months (OS2 19.4 vs. 9.4 months, P=.001). Radiotherapy modalities (WBRT vs. SRS/SRT) did not independently impact survival outcomes, underscoring that effective local control of the CNS sanctuary is the primary driver of benefit.

Conclusion: For ES-SCLC patients developing BOP, maintaining the established first-line systemic backbone (particularly immunotherapy) combined with brain radiotherapy offers significant survival benefits over switching systemic therapies. This supports a progression-pattern-directed paradigm: leveraging local radiotherapy to overcome the CNS sanctuary effect while preserving systemic immune memory and disease control.