Lung Cancer

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TU_26_3578 - Analysis of Circulating Tumor DNA Kinetics during Stereotactic Ablative Radiation Therapy for Non-Small Cell Lung Cancer

Tuesday, October 23
2:45 PM - 4:15 PM
Location: Innovation Hub, Exhibit Hall 3

Analysis of Circulating Tumor DNA Kinetics during Stereotactic Ablative Radiation Therapy for Non-Small Cell Lung Cancer
E. L. Chen, A. A. Chaudhuri, B. Y. Nabet, J. J. Chabon, D. J. Merriott, B. W. Loo Jr, A. A. Alizadeh, and M. Diehn; Stanford Cancer Institute, Stanford, CA

Purpose/Objective(s): The kinetics of circulating tumor DNA (ctDNA) release during stereotactic ablative radiotherapy (SABR) have not been described. We hypothesized that ctDNA levels rise shortly after the first fraction of SABR due to acute tumor cell death. Cancer Personalized Profiling by deep Sequencing (CAPP-Seq) is an ultra-sensitive blood-based assay that uses next-generation sequencing to quantitate ctDNA. Here we used CAPP-Seq to measure ctDNA before and shortly after the first fraction of SABR in patients with early-stage non-small cell lung cancer (NSCLC).

Materials/Methods: We applied CAPP-Seq to pre-treatment blood samples from 15 patients treated for stage I NSCLC with 25-60 Gy in 1-8 fractions. Twelve patients also had blood collected for ctDNA analysis within 24 hours after 1st fraction of SABR. ctDNA response kinetics were quantitated as fold-rise from pre-treatment to 24 hours after the 1st fraction.

Results: Gross tumor volumes (GTV) ranged from 1.24 to 75.2 mL. Seven patients (47%) had detectable ctDNA pre-treatment, with a median ctDNA concentration of 0.018% (range 0.004-0.31%). GTV was positively correlated with pre-treatment ctDNA concentration (R = 0.78, P = 0.0003). Four patients (100%) with detectable ctDNA pre-treatment who also had plasma collected within 24 hours after the 1st SABR fraction showed an increase in ctDNA concentration at the second time point, with a median fold-rise of 4.5 (range 2.2-5.3; P = 0.01). One of eight patients (13%) with undetectable pre-treatment ctDNA had detectable ctDNA 24 hours after a single fraction of 12.5 Gy (ctDNA concentration = 0.011%).

Conclusion: Our results suggest that ctDNA concentrations rise within 24 hours after the first fraction of SABR, likely as a result of early tumor cell killing. Furthermore, blood collection shortly after start of SABR may allow detection of ctDNA in some patients who have undetectable ctDNA pre-treatment. Prospective expansion of our cohort is ongoing.

Author Disclosure: E.L. Chen: None. A.A. Chaudhuri: Honoraria; Varian Medical Systems. Consultant; Oscar Health. B.Y. Nabet: Patent/License Fees/Copyright; University of Pennsylvania. J.J. Chabon: None. D.J. Merriott: None. B.W. Loo: Research Grant; RaySearch, Varian Medical Systems Inc. Stock; TibaRay, Inc. Vice-chair; National Comprehensive Cancer Network. Chair; American College of Radiology. Board Member; TibaRay, Inc. A.A. Alizadeh: Consultant; Roche. Stock; CiberMed. M. Diehn: Employee; Kaiser Permanente. Consultant; Roche. Stock; CiberMed.

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