Title: Should Post-Operative Radiotherapy be Considered in High Risk Melanoma Treated with Adjuvant Immunotherapy?
Abstract: Prior to widespread use of immunotherapy (IT), post-operative radiation therapy (PORT) was used to decrease the risk of loco-regional recurrence (LRR) in melanoma with high risk features (HRF). IT with checkpoint inhibitors has altered the disease course of melanoma by improving both disease free survival (DFS) and OS. However, the impact of IT on preventing LRR is unclear. We sought to broadly examine the patterns of failure in patients with node positive melanoma treated with adjuvant IT, as well as in a pre-specified subgroup of those with HRF. We performed a retrospective chart review of patients diagnosed with melanoma, who had at least one pathologically confirmed positive lymph node and received adjuvant IT. Additionally, we defined HRF based on those who would have been eligible for PORT prior to the IT era as: palpable lymph nodes (LN), ECE, one involved parotid LN, >1 involved cervical or axillary LN, or >2 involved inguinal LN. Clinical, histologic and treatment characteristics, as well as disease outcomes were obtained from the electronic medical record. This study was approved by the institutional review board. Forty-two patients fitting our inclusion criteria were identified in the period 2016-2018. Of these, 36 patients with follow up greater than 6 months were included in the analysis. Fifty percent of patients were men, median age was 54 (range 15 - 82) and 30% of patients harbored B-Raf mutations. No patients received PORT. Sixty-three percent of patients were treated with nivolumab, 11% with ipilimumab and the remaining received pembrolizumab. One third of patients underwent completion lymph node dissection. Fifty-five percent of patients had HRF. With median follow-up of 20 months, DFS for the entire cohort was 76%. Seventeen percent of patients experienced an LRR, with an isolated LRR in 11%. Median time to progression was 12 months. Among the largest treatment subgroup of patients, those who received nivolumab, DFS was 80% with median follow-up of 17 months. Sixteen percent of these patients experienced an LRR and 12% had an isolated LRR. Of the 20 patients with HRF, the overall recurrence rate was 25%, and 4 of the 5 patients who experienced a recurrence had LRR. The recurrence rate in the 12 HRF patients treated with nivolumab was also 25%, and all of them experienced LRR. At recurrence, patients underwent resection, change in immunotherapy or were started on targeted B-Raf therapy. In this hypothesis generating study, LRR appears to be a significant problem in node positive melanoma patients, and in particular those with HRF, despite treatment with adjuvant IT. Some of the patients with HRF may benefit from PORT. Prospective studies are needed to address this question.
Publication Year: 2020
Publication Date: 2020-10-23
Language: en
Type: article
Indexed In: ['crossref']
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