2473 - Long-Term Survival and Undetectable Circulating Tumor DNA Following Comprehensive Involved Site Radiotherapy for Oligometastases
Presenter(s)
M. Schmalzle1,2, R. Radigan1,2, M. Krainock3, M. C. Liu3, V. Gupta1, S. Missios4, J. Hsu4, A. Sangal4, M. T. Milano5, and J. Kao1,2; 1New York Institute of Technology College of Osteopathic Medicine, Old Westbury, NY, 2Good Samaritan University Hospital, Department of Radiation Oncology, West Islip, NY, 3Natera, San Carlos, CA, 4Good Samaritan University Hospital, West Islip, NY, 5Department of Radiation Oncology, University of Rochester Medical Center, Rochester, NY
Purpose/Objective(s): Distant metastases account for ~90% of cancer deaths and major responses with systemic therapy alone for metastatic cancers are so rare that the National Cancer Institute launched the Exceptional Responders Initiative. Comprehensive involved site radiotherapy (ISRT) is a promising treatment for oligometastases, but the role of circulating tumor DNA (ctDNA) to confirm durable molecular response following treatment remains unexplored. Our objectives were to assess the clinical and treatment characteristics of patients who achieved durable radiologic and molecular complete responses following comprehensive ISRT for oligometastases.
Materials/Methods: The study population consisted of 597 consecutive adult patients with metastatic solid tumor malignancy treated with radiation therapy by a single radiation oncologist from 2014 through 2021. Patients were categorized into those with polymetastases and those with oligometastases. Patients with oligometastases were all treated with comprehensive ISRT and within this subset the exceptional responders (ER) were identified and characterized by age, sex, ECOG performance status, serum albumin, tumor sites, radiation dose, and type of systemic therapy. ER were statistically compared to non-exceptional responders using Pearson’s chi-square for categorical variables and a 2-sided student’s t-test for continuous variables (with Stata 13.1). The clinically validated Signatera ctDNA assay (Natera) was used to detect and quantify minimal residual disease following treatment.
Results: Among the study population, 133 (22%) had oligometastatic disease and 464 (78%) had polymetastatic disease. The 5-year overall survival was 38% for oligometastases vs. 3% for polymetastases (p<0.001). At a median follow-up of 71 months after treatment of oligometastases, 37 (28%) ER remained alive and recurrence-free at =2 year follow-up. Among ER, 49% underwent stereotactic radiotherapy (median 27 Gy in 3 fractions), 65% underwent intensity-modulated radiotherapy (median 53 Gy in 24 fractions), and 76% received additional systemic therapy. Comparing ER to non-exceptional responders, patient and treatment characteristics were similar except for more patients with normal albumin (81% vs. 60%, p=0.05) and fewer patients with liver metastases (0% vs. 14%, p=0.02) in the ER cohort. Twelve out of the 37 ER successfully underwent posttreatment ctDNA testing and remarkably all 12 specimens tested negative for ctDNA, signifying molecular complete remission.
Conclusion: Long-term complete responses, including molecular complete responses, are achievable with comprehensive ISRT in diverse oligometastatic presentations. Although ctDNA testing was not possible in most ER due to patient refusal or tumor specimen quality, all 12 ER tested ctDNA-negative.