A. Tam1, C. J. Ladbury1, R. S. Davis2, J. R. Liu1, N. J. Eustace1, A. Kassardjian1, J. G. Bazan Jr1, Y. Xing3, A. Amini1, and S. Yoon1; 1Department of Radiation Oncology, City of Hope National Medical Center, Duarte, CA, 2City of Hope Comprehensive Cancer Center, Duarte, CA, 3Department of Medical Oncology, City of Hope National Medical Center, Duarte, CA
Purpose/Objective(s): The oligometastatic (OM) hypothesis has challenged the perspective that metastatic disease is inherently a disseminated process, and perhaps patients (pts) with limited metastatic sites (mets) [commonly defined as <5] may be cured with metastasis-directed therapy with local therapies (LTs) to most or all sites of disease. Indeed, single-arm series of metastasectomies along with novel systemic agents (e.g. immunotherapy [IO], targeted therapies) have found improvement in survival to as high as 34 months in OM melanoma patients. However, these studies excluded patients with brain mets (a group generally considered to have a poorer prognosis) and no comparator to the current standard-of-care (SOC) approach of novel systemic agents and LTs to a few select sites. Given the lack of clarity on the benefits of LTs, we conducted a retrospective study to test the hypothesis that OS after LTs published in the literature is higher compared to SOC. Materials/
Methods: We identified 355 consecutive melanoma pts with =1 brain met who were treated at a comprehensive cancer network from five network sites from Jan 2013 to Dec 2021. Records were reviewed to confirm OM disease, defined as having 1-5 lesions upon first presentation of metastasis. Clinical and treatment data were collected and summarized descriptively. Overall survival (OS) was estimated using Kaplan-Meier analysis. Survival endpoints and confidence intervals (CI) in our cohort were compared to published data for MDT. Univariate analysis for OS was performed using Cox proportional hazard model. All statistical analysis was conducted in R version 2023.12.1. Results: Of the 43 (12.1%) pts had OM (53.5% synchronous vs. 46.5% metachronous). Median age was 65.8 years (IQR 52.9 – 72.0). The median number of mets was 3 (IQR 2-3).13 (30.2%) and 21 (48.8%) pts had mets involving only the brain or both brain and visceral organs, respectively. A majority (n=31, 72.1%) of pts received IO, whereas 4 (9.3%) pts received BRAF/MEK-inhibitors. 125 lesions were treated with local therapies (28 [22.4%] lesions with surgery and 97 [77.6%] lesions with radiation treatment [RT]). Thirty (69.8%) pts received steroids. The majority of pts (48.8%) exhibited stable disease after treatment. No abscopal response for non-treated mets. With median follow-up of 18.5 months (mos), the median OS was 45.2 mos (95% CI, 26.8 – not reached [NR]). This was not significantly different from what was previously reported of OS 34.2 mos, which crosses the 95% CI from our study. On univariate analysis, only age was associated with worse OS (hazard ratio [HR] 1.04; p=0.04). Conclusion: Median OS after MDT in OM melanoma reported in the literature was not statistically different from our cohort treated of patients enriched with brain mets with current SOC. This is one of the largest series of treatment outcomes for OM melanoma in the literature. Future studies are needed to confirm whether MDT in melanoma offers improvement in OS over SOC.
