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Samson, Pamela P

0000-0003-2448-2123

Mayo Clinic

Department of Radiation Oncology, Washington University, St. Louis, Missouri.

Citations 1

Early ctDNA Stratifies Survival in Locally Advanced and Oligometastatic Lung Cancer Treated with Radiotherapy
Hashmi, Ayesha , Linford, Jessica , Chauhan, Pradeep S, Parikh, K, Pillai, Malvika , Guittar, John , Ben-Shachar, Rotem , Patel, Jyoti , Nimeiri, Halla , Bergsagel, Matteo , Park, S, Olivier, Kenneth R. , Owen, Dawn , Lee, K.N. , Morgensztern, Daniel, Robinson, Clifford G, Bergom, Carmen , Samson, Pamela , Pellini, B., Vlacich, Gregory , Chaudhuri, Aadel A, Chauhan, Pradeep S. , Ben‐Shachar, Rotem , Chauhan, Pradeep S , Parikh, Kaushal , Patel, Jyoti , Semenkovich, Nicholas P , Park, Sean S , Owen, Dawn , Routman, David M , Lee, Katie N , Sherry, Alexander D , Mansfield, Aaron S , Morgensztern, Daniel , Govindan, Ramaswamy , Robinson, Clifford , Bergom, Carmen , Waqar, Saiama N , Samson, Pamela P , Pellini, Bruna , Vlacich, Gregory R , Chaudhuri, Aadel A , Patel, Jyoti D. , Semenkovich, Nicholas P. , Routman, David M. , Sherry, Alexander D. , Mansfield, Aaron S. , Morgensztern, Daniel , Govindan, Ramaswamy , Pellini, Bruna , Chaudhuri, Aadel A.

Clinical Cancer Research | April 30, 2026 | Volume: 32 | Issue: 14 | Pages: 2945-2956

10.1158/1078-0432.ccr-25-4983 Get It

Abstract Purpose: Circulating tumor fraction estimate (ctFE) is a machine learning–derived composite metric of circulating tumor DNA (ctDNA) burden. We hypothesized that pre-treatment and early on-treatment ctFE could robustly risk-stratify patients with locally advanced (LA) and oligometastatic non–small cell lung cancer (NSCLC) treated with radiotherapy (RT). Experimental Design: In a prospective phase II clinical trial (NCT03916419), 26 patients with unresectable stage IIB to IIIC NSCLC received magnetic resonance (MR)-guided hypofractionated chemoradiotherapy (chemoRT) followed by immunotherapy. Plasma ctDNA was profiled at baseline and mid-treatment (days 10–14) to derive ctFE and maximum variant allele frequency (Max VAF). A burden-based ctFE threshold derived from baseline samples was applied unchanged to mid-treatment samples and validated in two external cohorts: LA NSCLC treated with chemoRT (LA-RW; n = 94) and oligometastatic NSCLC treated with RT (OM-RW; n = 309). Results: Pre- and mid-treatment ctFE burden strongly stratified overall survival (OS) and progression-free survival (PFS), outperforming Max VAF and ctFE detectability. The baseline ctFE was prognostic for OS (HR 5.93, P = 0.005) and PFS (HR 11.08, P < 0.001) and remained significant at mid-treatment (OS: HR 7.08; PFS: HR 12.06; both P < 0.001). Early ctFE dynamics defined three molecular response groups with OS separation (median OS 60.8 vs. 13.0 vs. 2.9 months; P < 0.001). ctFE remained associated with survival in both validation cohorts. Conclusions: Early ctFE derived from a clinically available, tumor-naïve ctDNA assay enables noninvasive risk stratification in LA and oligometastatic NSCLC treated with RT, supporting its use as a practical biomarker for precision treatment adaptation.