223 - Blood Biomarkers of Survival in Patients Receiving Stereotactic Radiotherapy with or without Immunotherapy for Oligometastatic Disease

10:45am - 10:55am PT

Room 153

Presenter(s)

Juan Zafra-Martin, MD, PhD - Hospital Universitario Virgen de la Victoria, Málaga, Andalucia

J. Zafra-Martin^1,2, J. L. Onieva^2,3, H. Jimenez Rodriguez¹, B. Martinez-Galvez^2,3, L. C. Figueroa^2,3, A. Roman¹, R. Ordoñez-Marmolejo¹, E. Perez-Ruiz^2,4, A. Mesas³, J. M. Jurado⁴, M. A. Berciano⁴, B. Salas⁵, E. Salcedo⁵, I. Padilla⁶, R. Chicas Sett^7,8, A. Rueda-Dominguez^2,3, and I. Barragan^2,3; ¹Department of Radiation Oncology, Virgen de la Victoria University Hospital, Malaga, Spain, ²Group of Translational Research in Cancer Immunotherapy and Epigenetics (CIMO-2), IBIMA Plataforma BIONAND, Malaga, Spain, ³Medical Oncology Unit, Virgen de la Victoria University Hospital, Malaga, Spain, ⁴Medical Oncology Unit, Regional Hospital, Malaga, Spain, ⁵Department of Radiation Oncology, University Hospital of Gran Canaria Dr. Negrín, Las Palmas de Gran Canaria, Spain, ⁶Faculty of Medicine, University of Malaga (UMA), Malaga, Spain, ⁷Department of Radiation Oncology, ASCIRES Grupo Biomedico, Valencia, Spain, ⁸Department of Radiation Oncology, La Fe University Hospital, Valencia, Spain

Purpose/Objective(s): SABR can be useful in oligoprogressive disease to overcome the resistance to immune checkpoint inhibitors (ICI) and extend the clinical benefit (CB) of systemic therapy. However, there are no defined biomarkers to aid in patient selection. We hypothesize that cell-free DNA (cfDNA) and the neutrophil-lymphocyte ratio (NLR) are inexpensive and convenient biomarkers that may predict the clinical benefit from SABR and ICI in clinical practice.

Materials/Methods: Ongoing prospective multicenter study in two cohorts. Cohort A consists of metastatic patients in oligoprogression to ICI (1-5 extracranial sites) but maintaining the same agent due to CB. Patients receive concomitant SABR (35 Gy in 5 fractions, fx) to all oligoprogressive lesions. Cohort B is a comparative group of oligorecurrent patients receiving only SABR in ablative doses. Blood samples are gathered before SABR (T1), after the first (T2) and last (T3) fx, two months after SABR (T4) and at further progression (TP). Response is evaluated two months after SABR and subsequently every three months by iRECIST and defined by the objective response rate (ORR) in all lesions (in and out-of-field)– complete (CR) and partial responses (PR) –. The concentration of cfDNA is measured in plasma across all time points. The absolute neutrophil and lymphocyte counts are obtained from T1 and T4 samples. Differential results are correlated with progression-free survival (PFS) and overall survival (OS).

Results: Of 163 patients recruited, 104 (61 from cohort A and 43 from B) had undergone at least one re-evaluation after treatment. In A, most patients had lung cancer (51%) under pembrolizumab (41%) with a single progressing lesion (61%) located in nodal sites (46%). In B, most had lung cancer (30%) with a single oligorecurrent lesion (72%) located in the lungs (60%). With a median follow-up of 12 months (range, 3-37 months) ORR was 59% in A (26% CR and 33% PR) and 65% in B (37% CR and 28% PR). Median (m) PFS in A was 15 months (95% CI, 8 months-NR) and 21 months (95% CI, 8 months-NR) in B. mOS times were not reached.

In cohort A, a decrease in cfDNA > 14% from T1 to T4 correlated with better mPFS (NR vs 8 months, p = 0.015). In T3, levels < 0.37 ng/uL also correlated with improved 1-year OS (91% vs 62%, p = 0.031). In contrast, in cohort B, an increase > 3% from T2 to T4 associated with better mPFS (NR vs 7.8 months, p = 0.042) and OS (NR vs 9.9 months, p = 0.004).

In A, low NLR (< 1.81) at T1 was predictive of better mPFS (NR vs 7.5 months, p = 0.034) and 1-year OS (100% vs 70%, p = 0.01). In B, low NLR (< 4) at T4 correlated with improved mPFS (NR vs 3.1 months, p = 0.001) and OS (NR vs 9.9 months, p = 0.005).

Conclusion: The concentration of cfDNA and the NLR are accessible biomarkers that seem to predict the CB of SABR in oligoprogressive/recurrent disease. Differences in dynamics in cfDNA may be indicative of the distinct biological effects of SABR when administered alone in ablative doses or in moderate doses to pursue an immunogenic synergy with immunotherapy.