Factors predicting toxicity and response following isolated limb infusion for melanoma: An international multi-centre study.
INTRODUCTION: Isolated limb infusion (ILI) is a minimally-invasive procedure for delivering high-dose regional chemotherapy to treat melanoma in-transit metastases confined to a limb. The aim of this international multi-centre study was to identify predictive factors for toxicity and response. METHODS: Data of 687 patients who underwent a first ILI for melanoma in-transit metastases confined to the limb between 1992 and 2018 were collected at five Australian and four US tertiary referral centres. RESULTS: After ILI, predictive factors for increased limb toxicity (Wieberdink grade III/IV limb toxicity, n = 192, 27.9%) were: female gender, younger age, procedures performed before 2005, lower limb procedures, higher melphalan dose, longer drug circulation and ischemia times, and increased tissue hypoxia. No patient experienced grade V toxicity (necessitating amputation). A complete response (n = 199, 28.9%) was associated with a lower stage of disease, lower burden of disease (BOD) and thinner Breslow thickness of the primary melanoma. Additionally, an overall response (combined complete and partial response, n = 441, 64.1%) was associated with female gender, Australian centres, procedures performed before 2005, lower limb procedures and lower actinomycin-D doses. On multivariate analysis, higher melphalan dose remained a predictive factor for toxicity, while lower stage of disease and lower BOD remained predictive factors for overall response. CONCLUSION: ILI is safe and effective to treat melanoma in-transit metastases. Predictive factors for toxicity and response identified in this study will allow improved patient selection and optimization of intra-operative parameters to increase response rates, while keeping toxicity low.
Kenyon-Smith, TJ; Kroon, HM; Miura, JT; Teras, J; Beasley, GM; Mullen, D; Farrow, NE; Mosca, PJ; Lowe, MC; Farley, CR; Potdar, A; Daou, H; Sun, J; Farma, JM; Henderson, MA; Speakman, D; Serpell, J; Delman, KA; Smithers, BM; Barbour, A; Coventry, BJ; Tyler, DS; Zager, JS; Thompson, JF
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