John E. Mullinax, MD
Isolated limb infusion (ILI) for extremity soft tissue sarcoma resulted in a 58% overall response rate (ORR) and prolonged limb salvage in nearly 80% of patients, according to results from a study published online in the Journal of the American College of Surgeons.
Treatment-resistant, locally advanced soft tissue sarcomas frequently require amputation. In an attempt to achieve limb salvage, ILI selectively delivers high-dose chemotherapy to the extremity.
From 1994 to 2016, 77 patients underwent ILIs in a retrospective study across 5 institutions. For 30 minutes, melphalan and actinomycin D were circulated after complete tourniquet occlusion of the limb, then actively washed out to prevent systemic exposure.
Of the 77 patients, the procedure was performed on 19 with upper extremity sarcoma and 58 with lower extremity sarcoma. The 58% ORR for the overall population comprised ORRs of 37% and 66% in the upper and lower extremity cohorts, respectively.
Across the entire study population, the median overall survival was 44.3 months. With a median follow-up of 20.6 months, the overall limb salvage rate was 77.9%.
For those patients who underwent amputation for progression of disease, the median time to amputation was 4.5 months. The distant metastatic-free survival was longer for responders than nonresponders, though the disease-specific survival was not different for the same groups.
In an interview with OncLive,
lead study author John E. Mullinax, MD, surgical oncologist, Sarcoma Department, Moffitt Cancer Center, discussed ILI as a limb salvage strategy for locally advanced extremity sarcoma.
OncLive: Can you start by discussing the rationale behind conducting this study?
ILI is a form of regional chemotherapy, meaning chemotherapy that is delivered just to one area of the body rather than systemic chemotherapy. The other forms would be isolated limb perfusion (ILP) instead of ILI. ILP involves a procedure where you essentially cut and identify the artery and vein and through a surgical procedure, you openly cannulate it, whereas ILI is done percutaneously, meaning it is less invasive than ILP.
Additionally, with ILI the drugs are used a little differently. Typically, in Europe, the ILP procedure is done with the addition of some other drugs that we don't use here in the States.
The reason that we put this study together was because centers do the ILI primarily for melanoma patients when patients have melanoma in extremity that's unresectable. There are a handful of centers that have done it for sarcoma, but no one has ever reported on it.
What were the most significant findings?
During the course of the study, the number of patients that retained their extremity was 77%, which was higher than we anticipated. You would imagine that if someone does not respond to the procedure, then they would progress to an amputation, but the number that progressed to an amputation was low.
Secondly, there was around 23% of patients, that ultimately had the procedure and then were able to be resected without an amputation. The efficacy when you look across these institutions certainly shows a nice response for these patients. I believe around 56% had either a complete or a partial response.
Were there any significant adverse events with this that oncologists should be aware of?
During the procedure, a tourniquet is placed on that extremity to prevent the chemotherapy from going systemically. For 30 minutes that extremity is isolated, causing patients to have redness and swelling for a couple of days, which is normal and was expected.