Abstract
Introduction: Isolated limb perfusion (ILP) with delivery of high dose melphalan proved to be efficient in the treatment of in-transit metastases (ITM). Preoperative factors may carry an impact on patient outcome, including in-field or local progression-free survival (IPFS), time to distant metastases (TDM) and overall survival (OS). Materials and Methods: A retrospective analysis of 83 patients who underwent an ILP at our institution before the era of efficient upfront systemic therapy in high-risk cases. Patients were classified according to a modified M.D. Anderson score, with relevance for the outcome: 34 stage III A (patients with satellites and/or ITM), 31 stage III AB (patients with synchronous regional lymph node metastases and satellites and/or ITM), 11 at a new stage labelled III A(B) which takes into account a previous history of therapeutic regional node dissection and actual recurrence in the limb only, and 7 stage IV (metastatic cases with actual major problem of recurrence in the limb). Results: Our median follow-up time was 90.1 months (IQR 72.8-151.6). Median IPFS was 16.3 months (95% CI 9.5-78.5), median TDM 28.8 months (95% CI 15.4-69.6) and median OS 34.6 months (95% CI 21.1-59.5). The strongest significant prognostic factor regarding IPFS was LND before ILP (p=0.02). However, sex (p=0.03/0.07), LND before ILP (p=0.004/0.11) and some primary tumor characteristics (Clark level (p=0.15/0.07) and ulceration (p=0.006/0.04)) were prognostic regarding TDM and / or OS. Conclusion: ILP with melphalan can provide long-term regional and systemic tumor control in a selected group of patients and should be kept in mind for patients recurring after local surgery or radiotherapy and resistant to or ineligible for the newer systemic therapies.
Highlights
Isolated limb perfusion (ILP) with delivery of high dose melphalan proved to be efficient in the treatment of in-transit metastases (ITM)
Preoperative factors may carry an impact on patient outcome, including in-field or local progression-free survival (IPFS), time to distant metastases (TDM) and overall survival (OS)
In the same period of time, 14 patients addressed for an ILP were considered non-eligible for this procedure because of the small number of surgically resectable lesions (4 cases), ITM extending above the anatomical limit of the feasible limb isolation (3 cases), major vascular stenosis or complex reconstructions (2 cases), uncontrolled distant metastases (3 cases) and access site infection following regional node dissection in another hospital (1 case)
Summary
Isolated limb perfusion (ILP) with delivery of high dose melphalan proved to be efficient in the treatment of in-transit metastases (ITM). Complete resection of those can be surgically challenging, and recurrences with shortening time frames after local resection are frustrating. With those observations in mind and the possibility of isolating a limb, Creech and coworkers introduced the regional isolated limb perfusion (ILP) in 1958 [5]. We present our long-term results with ILP in a group of patients before the introduction of immunotherapy or targeted therapies to evaluate ILP as a “stand-alone intervention” in the treatment of melanoma ITM/satellite lesions and try to identify preoperative parameters that can guide patient selection for this procedure
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