Isolated Limb Infusion in a Series of Over 100 Infusions: A Single-Center Experience

Abstract

Introduction Isolated limb infusion (ILI) is a therapeutic option for patients with recurrent, unresectable extremity malignancies. Methods A prospectively collected single institution database of patients undergoing ILI was analyzed for preoperative, intraoperative, and postoperative parameters and outcomes. Results From 5/2007-1/2012, 76 patients successfully underwent initial ILI, and 28 following either previous hyperthermic isolated limb perfusion (HILP) or ILI. Seventy-nine (74%) patients had melanoma, 24 (22%) sarcoma, 3 (3%) Merkel cell and 1 (1%) squamous cell carcinoma. There were 55 (72%) initial and 22 (79%) repeat lower extremity (LE) ILI’s, and 21 (78%) initial and 6 (22%) repeat upper extremity (UE) ILI’s. Serologic toxicity, measured by serum creatine kinase (CK), peaked higher and later in LE ILI’s, median 620 vs. 124 IU/L and postoperative day 4 vs. 2, respectively, P<0.05. LE ILI’s had a longer hospital length of stay (LOS), median 6 vs. 5 days (P<0.0001). A median of grade II Wieberdink regional toxicity was observed. Three-month follow-up was available in 94 (90%). A response (ORR) was seen in 72% of ILI’s performed for melanoma and 58% for sarcoma. No difference in response was observed between UE vs. LE or between initial vs. repeat ILI’s. Repeat UE ILI’s, however, appeared to have an improved ORR than repeat LE ILI’s, 83% vs. 64%. Conclusion ILI may be successfully performed for cutaneous and soft tissue malignancies. LE ILI’s have higher CK levels and slightly longer LOS. Repeat ILI’s are not associated with increased toxicity and similar ORR. UE ILI’s may have better overall response rates.

Burden of Disease Predicts Response to Isolated Limb Infusion with Melphalan and Actinomycin D in Melanoma

“…4-6 Several different groups have reported single and multi-institution studies ILI with melphalan (ILI-M), with overall response rates ranging from 53-84%, and complete responses occurring in 25-38% of patients. 7-10 …”

Regional therapy in metastatic melanoma: an update on minimally invasive intraarterial isolated limb infusion and percutaneous hepatic perfusion

“…In addition, in another study where patients underwent repeat ILI, those patients who had upper extremity ILI had better overall response rates than those with lower extremity ILI [17]. Reported CR rates have been 40 --80% and 30 --38% for HILP and ILI, respectively [8,12,13].…”

“…There was no statistical difference in survival or toxicity after the repeat procedures Vohra et al [16] 22 STS ILI Retrospective 42% overall response rate (24% CR, 18% PR, 18% SD, 41% PD), unknown duration of response Wong et al [17] 77 in humans. Because of these features, melphalan is considered the drug of choice for both HILP and ILI [8,23].…”

“…For example, it has been shown that patients who demonstrate a partial response (PR) are more likely to have an increased disease-free survival if lesions are resected after ILI when compared to cases that do not demonstrate a PR [17]. In addition, patients with a lower overall tumor burden demonstrate improved overall response rates to ILI than those with a higher tumor burden in the affected limb [33].…”

Regional Therapies for Cancer

“…Their large series with few complications and no amputations reinforces this important therapeutic option. 11 In an attempt to understand from preprocedure and pathologic factors who will respond to limb infusion for unresectable in transit melanoma, Shetty et al have administered a cytokine assay on preinfusion plasma of patients who gained a complete response following therapy versus those who had progression of disease. This work emphasizes the marked decrease of immune-activating cytokines and further supports the role for immune-targeted therapy in patients with regionally advanced melanoma.…”