Optimising isolated limb perfusion for melanoma: perfusion time improves response while temperature drives toxicity
Sophie Elizabeth Orme, Jan Mattson, Måns Kadefors, Roger Olofsson BaggeAbstract
Introduction
Isolated limb perfusion (ILP) is an established treatment for melanoma in-transit metastases (ITM), but the optimal balance between perfusion duration and temperature to maximise response while minimising toxicity remains unclear.
Methods
A single-centre retrospective analysis of 411 patients undergoing first-time ILP for melanoma ITM, with or without nodal disease, between 1976 and 2025. The primary outcome was complete response (CR). Perfusion time and ingoing perfusate temperature were analysed as continuous variables using multivariable logistic regression with a time–temperature interaction term. Tumour burden, prior systemic therapy, melphalan dose, and treatment era were included as covariates. Toxicity (Wieberdink grade III–IV versus I–II) was assessed secondarily.
Results
The CR rate was 56%, with a modest decline across eras coinciding with shorter perfusion durations. Longer perfusion time increased odds of CR (OR 1.14 per 10 min, 95% c.i. 1.04–1.27; P = 0.009). A significant interaction with temperature (OR 0.981; P = 0.019) demonstrated attenuation of the time effect at higher temperatures. Increasing tumour burden was associated with reduced response (OR 0.985 per lesion; P = 0.001), with stepwise reductions for 10–30 and >30 metastases. Among 387 patients, 40% developed grade III–IV toxicity. Higher temperature increased toxicity (OR 1.91; P = 0.001), whereas perfusion time was not associated. External iliac access was associated with lower toxicity (OR 0.43; P = 0.007). Findings were unchanged after adjustment for tumour burden, prior systemic therapy, melphalan dose, and treatment era.
Discussion
Perfusion duration and temperature have distinct roles in ILP, duration influencing efficacy and temperature determining toxicity. Extending perfusion duration at lower temperatures may improve response without increasing clinically relevant toxicity.