The Effect of Temperature and Perfusion Time on Response, Toxicity, and Survival in Patients with In-transit Melanoma Metastases Treated with Isolated Limb Perfusion

Dimitrios Katsarelias,Ilan Ben-Shabat,Roger Olofsson Bagge,Jan Mattsson,Erik Rådbo

doi:10.1245/s10434-018-6459-9

Dimitrios Katsarelias, Ilan Ben-Shabat + Show 3 more

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https://doi.org/10.1245/s10434-018-6459-9

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Abstract

BackgroundIsolated limb perfusion (ILP) is used to treat in-transit metastases of melanoma of the extremities when surgical excision is not possible. The optimal setting concerning temperature and perfusion time is unknown. The purpose of this study was to analyze these factors concerning their effects on response, toxicity, and survival.MethodsA retrospective analysis of 284 consecutive stage III melanoma patients treated with melphalan ILP for the first time in our institution, during a 31-year period (July 1986–May 2017), was performed. Our series was divided in four time periods, according to perfusion temperature and duration. Demographical data, stage, number, and size of lesions were retrieved from our prospective database.ResultsOverall response (OR) rate 83% and a complete response (CR) rate of 59%. Significant predictive factors for CR in multivariate analysis were non-bulky tumor, fewer metastases, and a perfusion time of 120 min. Predictive factors for increased local toxicity were femoral ILP and higher perfusion temperatures. The median overall survival was 30 months, and the independent negative prognostic factors were lymph-node status, bulky tumors, response, upper limb perfusion, and 120 min perfusion at 39–40 °C.ConclusionsModern ILP uses diminished perfusion time and lower temperature, leading to a decrease in toxicity. However, our data also show a decrease in response, which indicates that optimal perfusion time and temperature regimen remain to be determined.

Highlights

Isolated limb perfusion (ILP) is used to treat in-transit metastases of melanoma of the extremities when surgical excision is not possible
Our data show a decrease in response, which indicates that optimal perfusion time and temperature regimen remain to be determined
An early pharmacokinetic study using melphalan in an ILP setting showed that high peak perfusate concentrations were achieved (6–115 mg/ml) and that these levels could be 20–100 times higher than the peak levels achieved with the usual intravenous doses of melphalan.[3]

Summary

Introduction

Isolated limb perfusion (ILP) is used to treat in-transit metastases of melanoma of the extremities when surgical excision is not possible. Significant predictive factors for CR in multivariate analysis were non-bulky tumor, fewer metastases, and a perfusion time of 120 min. The median overall survival was 30 months, and the independent negative prognostic factors were lymph-node status, bulky tumors, response, upper limb perfusion, and 120 min perfusion at 39–40 °C. An early pharmacokinetic study using melphalan in an ILP setting showed that high peak perfusate concentrations were achieved (6–115 mg/ml) and that these levels could be 20–100 times higher than the peak levels achieved with the usual intravenous doses of melphalan.[3] In 1967, Cavaliere reported the effects of ILP using only hyperthermia in 22 patients with recurrent extremity tumors. Twelve of the patients were alive without evidence of disease at 3–28 months of follow-up.[4]

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