2394 - Molecular Markers in Lung Cancer as a Predictor of Response to SBRT
Presenter(s)
R. Kaila1, G. Dyson2, S. R. Miller II3, and M. M. Dominello4; 1WAYNE STATE UNIVERSITY/DETROIT MEDICAL CENTER, DETROIT, MI, 2Karmanos Cancer Institute, Detroit, MI, 3Wayne State University, Detroit, MI, 4Department of Radiation Oncology, Karmanos Cancer Center, Detroit, MI
Purpose/Objective(s): This study evaluates the role of molecular markers in non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) patients treated with stereotactic body radiotherapy (SBRT). SBRT delivers high-dose radiation in 1 to 5 fractions for early, metastatic, and advanced lung cancers (NRG LU008). Eligibility for SBRT and dose prescriptions are determined by tumor size, location, and nearby organ-at-risk constraints. Here, we seek to correlate molecular profiles with response to SBRT, potentially paving the way for more personalized local treatment strategies.
Materials/Methods: A retrospective analysis of Stage I-IV NSCLC/SCLC patients with identifiable molecular markers as evaluated by CARIS Life Sciences between 2019 and 2024 was performed under an IRB-approved protocol. Next-generation sequencing results, clinical data, along with CT, MRI, and PET scans, were reviewed for changes in tumor volume and SUV over 12 months post-treatment. A linear mixed model was utilized to account for multiple observations per patient. Biomarkers were evaluated as potential predictors of response to treatment with SBRT over time.
Results: A total of 38 patients, aged 45-85 were included in the analysis. Lung, bone, and adrenal gland were the most common treatment sites. Among the 30 patients with available PDL1 data, PDL1-high status, defined henceforth as >60%, in a model adjusted for visit epoch and tumor stage was indicative of a better response to SBRT (p<0.001) defined as any decrease in target volume over time. A high PDL1 status was associated with a lower initial target tumor volume (p=0.045) Patients with high PDL1 continued to have superior volume-responses over time. Univariate p-values of other evaluable markers were nonsignificant: KRAS-0.373, EGFR-0.420, BRAFv600e-0.264, TP53-0.488, and ROS-1/ALK-NA (limited by mutation frequency).
Conclusion: A high PDL1 measurement > 60% predicted for a lower initial target tumor volume and better initial response to SBRT. Patients with high PDL1 continued to have superior volume-responses over time, showing the potential importance of PDL1 as a predictive marker for SBRT durability. Further evaluation of molecular markers and additional patient evaluations are planned for the final analysis.