1. PD-L1, Tumor Mutational Burden (TMB) and Intracranial Outcomes in Patients with Non-Small Cell Lung Cancer (NSCLC) and Brain Metastases.
- Author
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Adib, E., Nassar, A.H., Kwiatkowski, D.J., and Aizer, A.A.
- Subjects
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IMMUNE checkpoint inhibitors , *NON-small-cell lung carcinoma , *WOMEN'S hospitals , *SURVIVAL rate , *OVERALL survival - Abstract
Brain metastases (BM) affect up to 50% of patients with NSCLC and are associated with poor prognosis in patients with non-targetable genomic alterations. Radiation forms the typical mainstay of intracranial management in such patients given the historically guarded intracranial efficacy of most systemic options. Immunotherapy-based approaches have shown promise but the extent that patients with BM may display extended survival with combination radiotherapeutic and immunotherapy-based approaches remains unclear. We identified 160 patients harboring non-squamous NSCLC with 486 newly-diagnosed BM between 2015-2023 managed with brain-directed radiation (either stereotactic-based, SRT or whole brain radiation therapy, WBRT) and immune checkpoint inhibition within 3 months of radiation at Dana-Farber Cancer Institute/Brigham and Women's Hospital (Boston, MA). PD-L1 tumor expression was categorized as <1%, 1-49%, 50-89%, and ≥90% based on immunohistochemistry. TMB was assessed via targeted next-generation sequencing. Cox-proportional hazards regression was used to assess all-cause mortality. Mixed-effects Fine-Gray models were used for per-metastasis outcomes, including rates of local control (LC) and radiation necrosis (RN). The median number of BM was 3 (IQR 1-7). Neurosurgical resection in advance of radiation was performed in 51/160 (32%) pts. SRT was used in 130/160 (81%) versus 30/160 (19%) patients treated with WBRT, respectively. Median follow-up time was 30.1 months (mo). Higher PD-L1 expression was associated with significantly longer overall survival (OS) with a median survival in patients with PD-L1<1%, 1-49%, 50-89% and ≥90% being 11.8, 14.4, 29.5 and 33.1 mo, respectively (Table). Two-year LC rates were excellent and similar across PD-L1 categories. Two-year rates of RN were numerically higher in patients with higher PD-L1 (Table). Higher TMB (≥90th vs. <90th percentile) was not associated with significantly longer OS, or higher LC or RN rates (Table). Higher PD-L1 tumor expression was associated with improved all-cause mortality. A significant percentage of patients with a very high PD-L1 displayed long-term survival, highlighting the potential importance of multimodality therapy in such patients, and demonstrating that clinicians should be cognizant of treatment-associated long-term toxicities in this population. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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