Sequencing in management of in-transit melanoma metastasis: Diphencyprone versus isolate limb infusion.

BACKGROUND: In-transit metastases (ITMs) in melanoma are associated with poor prognosis, however a significant proportion of these patients survive for extended periods without further disease progression. We routinely use locoregional treatment e.g. Diphencyprone (DPCP) and/or isolated limb infusion (ILI) as long-term palliation. This study aimed to identify correct sequencing of these therapies based on disease burden and progression. METHOD: Retrospective evaluation of all melanoma patients with ITMs treated with DPCP/ILI/both from 2010 to 2017 at our Cancer Centre was performed. Patients were initially assessed in a multidisciplinary setting and empirically prescribed DPCP for low-disease burden, ILI for high-disease burden. Patient demographics, tumour characteristics, response to therapy, ITM progression and patient outcomes were analysed. RESULTS: 78 patients (M:F = 30:48), aged 47-95years (median 74years) treated with DPCP/ILI/both (n = 44/21/13) were identified. Progression-free survival (PFS) was significantly increased in patients responsive to DPCP or ILI as initial treatment. Patients who failed on DPCP and subsequently treated with ILI had a significantly increased PFS compared to DPCP alone (p = 0.026, HR = 0.048). This was not the case with patients who were treated with DPCP following failed ILI. All patients who failed to respond to the initial therapy progressed within 6 months. CONCLUSION: Our study shows that careful stratification ITM patients according to disease burden is fundamental to optimal outcomes. High-disease burden patients benefit from initial ILI; low-disease burden patients should commence on DPCP. ILI can be considered in DPCP patients who fail early. Systemic therapy should be considered when locoregional therapies fail after 12 months or after rapid relapse following ILI.

Reconstructive burden and financial implications of wider excision margins for invasive primary cutaneous melanoma.

BACKGROUND: For invasive primary cutaneous melanoma, wider excision is advocated to reduce local recurrence risk and improve patient outcomes. Excision detail is controversial, especially in intermediate- and high-risk primary melanoma (AJCC pT2-pT4). Guidance varies from sizes 1 to 3 cm (translating into large defects of 2-6 cm). The aim of this study was to determine the reconstructive and resource burden of wider excision margins (EMs). METHODS: Data analysis from our prospective database (2008-2017) included 1184 patients (563F:621 M) with cutaneous melanoma (pT1b-pT4b). Procedure tariff data were sourced from our financial services department. RESULTS: Two hundred twenty-nine patients had a narrower EM (1 cm) and 995 (80.7%) had a wider EM (2-3 cm). Reconstructive requirement significantly increased with a wider EM collectively (11.3% vs 29.3%, odds ratio (OR) = 3.2; p < 0.0001), in the extremities (15.2% vs 42.0%; p < 0.0001), and in the head and neck (H&N) (23.5 % vs 64.7%; p < 0.0001). Reconstruction significantly increased hospitalisation rates (26.6% vs 63.0%, OR = 4.7; p < 0.0001) collectively, in the H&N (26.8 % vs 53.9%), and in the upper (18.9 % vs 42.3%) and lower extremities (34.8% vs 77.3%). Narrower EMs significantly reduced hospitalisation rates in the upper and lower extremities (7.1% vs 28.5%; p = 0.004, 37.9% vs 58.5%; p = 0.005, respectively). Overall procedure cost significantly increased by £180 (mean, p < 0.0001) and £346 (median, p = 0.0004) per patient when reconstruction was required. CONCLUSIONS: Our data suggest substantial impact of wider EM on patients, which more than doubled in the functionally and cosmetically sensitive extremities and the H&N region. Reconstructions add significant financial and healthcare service burden. Without randomised controlled trial (RCT) evidence demonstrating increased efficacy of wider EM, narrower EM is advocated whilst awaiting future planned RCT results specifically investigating on this.