Clinical outcomes and blood-based biomarkers across two SABR-treated metastatic settings: oligoprogression under immune checkpoint inhibition and oligometastatic disease

Stereotactic ablative radiotherapy (SABR) may extend the clinical benefit of immune checkpoint inhibitors (ICI) in patients with oligoprogressive disease. However, individual benefit varies, and validated biomarkers to guide patient selection are lacking. We hypothesize that cell-free DNA (cfDNA) and the neutrophil-to-lymphocyte ratio (NLR) may be associated with outcomes after SABR in this setting. This prospective observational study included patients with oligoprogression under ICI therapy who received concomitant SABR to all oligoprogressive lesions (cohort A). Cohort B was a parallel biomarker cohort of oligometastatic patients receiving only SABR. Blood samples were collected before SABR (T1), after the first (T2) and last (T3) fractions, and two months after SABR (T4). The objective response rate (ORR) was evaluated by iRECIST in all lesions. Prespecified cfDNA and NLR time points were explored in relation to modified progression-free and overall survival (OS). We assessed 104 patients. With a median follow-up of 12 months, ORR was 59% in cohort A and 65% in cohort B. In cohort A, cfDNA <0.37 ng/µL at T3 was associated with improved 1-year OS (91% vs 62%, p = 0.031), while NLR <1.8 at T1 was associated with improved 1-year OS (100% vs 70%, p = 0.01). In cohort B, a >3% increase in cfDNA from T2 to T4 and NLR <4 at T4 were associated with improved OS. These findings support further evaluation of cfDNA and NLR as accessible biomarkers for patient stratification in oligoprogressive disease treated with SABR while maintaining an ICI.