Wake Forest Baptist Medical Center Winston Salem, NC
A. R. Choi1, C. M. Lanier1, S. E. Glynn1, R. DAgostino Jr2, M. Farris1, M. Abdulhaleem3, Y. Wang4, M. Smith4, J. Ruiz5, T. Lycan5, W. Petty5, C. K. Cramer1, S. B. Tatter6, A. Laxton6, J. White6, W. Li7, J. Su8, C. T. Whitlow9, F. Xing10, and M. D. Chan1; 1Department of Radiation Oncology, Wake Forest University School of Medicine, Winston-Salem, NC, 2Department of Biostatistics and Data Science, Wake Forest University School of Medicine, Winston -Salem, NC, 3Division of Hematology/Oncology, West Virginia University Cancer Institute, Morgantown, WV, 4Department of Molecular and Cellular Bioscience, Wake Forest University School of Medicine, Winston-Salem, NC, 5Department of Internal Medicine, Section of Hematology and Oncology, Wake Forest University School of Medicine, Winston-Salem, NC, 6Department of Neurosurgery, Wake Forest University School of Medicine, Winston-Salem, NC, 7Department of Pathology, Wake Forest School of Medicine, Winston Salem, NC, 8Department of Biostatistical Sciences, Wake Forest School of Medicine, Winston-Salem, NC, 9Department of Radiology, Wake Forest School of Medicine, Winston-Salem, NC, 10Department of Cancer Biology, Wake Forest University School of Medicine, Winston-Salem, NC
Purpose/Objective(s):We recently presented a genomic signature that was predictive of both oligometastatic disease state and oligometastatic progression in patients with brain metastases. We sought to validate this oligometastatic genomic signature using an independent dataset of patients without brain metastases.Materials/
Methods: Patients with non-small cell lung cancer (NSCLC) and without brain metastases were identified in our departmental database. Electronic medical records were used to identify patients for whom liquid biopsy-based comprehensive genomic profiling (Guardant Health) was available. Oligometastatic disease was defined as patients having =5 extracranial metastases without diffuse involvement of a single organ. Patients were given a risk score for oligometastatic disease based on the previously derived genomic signature consisting of genes associated with oligometastatic disease (ATM, JAK2, MAP2K2, and NTRK1) and with widespread disease (ARID1A and CCNE1). Scores were summed for each patient to create a risk score for the likelihood of oligometastatic disease, with scores subsequently correlated to the likelihood of having oligometastatic disease vs widespread disease. For oligometastatic patients, a competing risk analysis was then performed to assess the cumulative incidence of oligometastatic progression accounting for the potential competing risks of widespread progression of extracranial disease or death. Cox regression was used to determine association between oligometastatic risk score and oligometastatic progression. Results: 225 patients met study criteria and were included in the validation dataset. 158 patients (70%) had oligometastatic disease. Patients with positive and neutral/negative risk scores for oligometastatic disease had a 70% vs 48% likelihood of having oligometastatic disease, respectively (p=0.03 from Fisher’s exact test), demonstrating that the genomic profile was again statistically significantly associated with the likelihood of oligometastatic disease on our validation dataset. Patients with positive risk scores for oligometastatic disease more frequently experienced oligometastatic progression with a hazard ratio of 1.72 (p=0.11 from competing risk model). Overall survival for patients with positive and neutral/negative risk scores for oligometastatic disease was 92% vs 79% at 6 months; 46% vs 60% at 12 months; 23% vs 34% at 24 months (p=0.25). Conclusion: The results of the validation dataset are consistent with our previously reported genomic profile for oligometastatic disease in patients with brain metastases. In this larger, independent dataset, our genomic signature predicted oligometastatic disease state and showed a trend towards prediction of oligoprogression. With further study, our findings may suggest a biomarker with future potential to direct local therapies in oligometastatic patients with NSCLC.
