March 16, 2017
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Regional chemotherapy prevents amputation in advanced sarcoma

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Chemotherapy directed to limbs with advanced soft tissue sarcoma preserved arms and legs that otherwise might have required amputation, according to a 22-year research study published in Journal of the American College of Surgeons.

The innovative technique, known as regional chemotherapy with isolated limb infusion (ILI), salvaged limbs in 78% of cases.

John E. Mullinax

“Conventionally, what people think of when they think about treating patients with advanced cancer is surgery, radiation therapy or systemic chemotherapy, John E. Mullinax, MD, surgical oncologist in the sarcoma department at Moffitt Cancer Center, told HemOnc Today. “Isolated limb infusion is a technique where you can isolate the chemotherapy just to the region with the disease and with extremities that works well. It is something that is not commonly done even though it is relatively straightforward.”

Used primarily for melanoma, ILI circulates melphalan and actinomycin D chemotherapy into the blood vessels of the affected areas of the arm or leg through arterial and venous catheters, with a tourniquet used to block the chemotherapy agents from circulating through the rest of the body.

Researchers collected data from 77 patients with 17 different subtypes of sarcoma who underwent 84 ILIs at five different cancer institutions in the United States and Australia from 1994 to 2014. All patients faced amputation prior to their procedures.

Researchers circulated melphalan (median, 7.2 mg/L) and actinomycin D (median, .0885 mg/L) for 30 minutes after complete tourniquet occlusion of the patient’s limb (tourniquet median time, 51 minutes), then flushed the chemotherapy-laden blood with saline.

The median initial limb temperature of 37.5°C rose 30 minutes postinfusion to 38.9°C.

Researchers performed 63 infusions on the lower extremities of 58 patients, and 21 infusions on the upper extremities of 19 patients.

Median follow-up was 20.6 months (range, 0.6-146.1).

The 3-month overall response rate for the entire cohort was 58.4% and the complete response rate was 29.9%. Researchers observed a statistically significant difference between the ORR for lower extremity (66%) and upper-body extremity (37%; P = .03) infusions.

At the time of analysis, 21 patients (27.2%) remained alive with disease and 20 (25.9%) without evidence of disease. Median OS was 44.3 months and was longer among patients with lower-extremity disease (56.6 months vs. 27.9 months; P = .04).

The overall limb salvage rate was 77.9%. Seventeen patients (22.1%) eventually underwent amputation due to progression of disease, after a median time to amputation of 4.5 months. Seven patients (9.1%) underwent a repeat ILI procedure. Twenty-six patients (33.8%) developed distant metastatic disease, with a median time to progression of 9 months.

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Responders demonstrated longer distant metastatic–free survival than nonresponders (not reached vs. 13.6 months; P = .02), but there was no difference in disease-specific survival between these groups.

“The fact that the vast majority of the patients were able to keep their extremities was certainly surprising when you consider these were patients with advanced sarcoma that would otherwise require amputation,” Mullinax said. “About 78% of the patients went on over the course of the study with their limb and did not require and amputation. Even if [their cancer] was going to progress, most patients would prefer to do so with their extremity.”

The median length of hospital stay following ILI was 7 days (range, 3-28); upper-extremity patients averaged 5 days in the hospital and lower-extremity patients averaged 7 days. After 51 procedures, the toxicity rate — which consisted of grade 1 or grade 2 toxicities — was 60.7%, and no toxicity-related amputations occurred.

Researchers followed an independent cohort of 72 patients who underwent extremity amputation. These patients achieved a median OS of 18.5 months. Almost half (49%; n = 35) progressed with distant disease after amputation.

Researchers acknowledged they did not directly compare patients who underwent ILI with those who required amputation, which may have limited the study.

“It’s worth getting the message out that there are other options available for these patients rather than just systemic chemotherapy or radiation,” Mullinax said. “It’s a procedure most patients aren’t aware of.” – by Chuck Gormley

For more information:

John E. Mullinax, MD, can be reached at Moffitt Cancer Center, 12902 USF Magnolia Drive, Tampa, FL 33612; email: john.mullinax@moffitt.org.

Disclosure: The researchers report no relevant financial disclosures.