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Δευτέρα, 27 Φεβρουαρίου 2017
ILP FOR ADVANCED LIMB SARCOMAS
Patients with advanced malignant soft-tissue sarcoma of the extremities have typically faced amputation of the afflicted limb as the only treatment option. However, a technique that limits the application of chemotherapy to the cancerous region can preserve limbs in a high percentage of these patients, researchers from five cancer centers in the United States and Australia report in a study published by Mullinax et al in the Journal of the American College of Surgeons and presented at the Southern Surgical Association 128th Annual Meeting (Abstract 24).
The researchers used the treatment technique, known as regional chemotherapy with isolated limb infusion (ILI), in 77 patients with treatment-resistant, locally advanced soft-tissue sarcomas. They were able to salvage limbs in 77.9% of the cases.
“Isolated limb infusion is a safe and effective technique of treatment of patients with locally advanced soft-tissue sarcoma who otherwise might require amputation,” said lead study author John E. Mullinax, MD, a surgical oncologist in the Sarcoma Department at the Moffitt Cancer Center.
Isolated Limb Infusion
The study, conducted over a 22-year period from 1994 to 2016, is the largest one to date of limb preservation using isolated limb infusion for sarcoma. “Advocates for [isolated limb infusion] in these patients would argue that, with similar long-term survival data and meaningful overall response rates, patients would much prefer a treatment that preserves the affected extremity to one that does not,” Dr. Mullinax said. Isolated limb infusion has historically been used primarily for melanoma of the extremities, and the use of this technique in sarcoma is a novel approach. Sarcoma is a rare type of cancer in the extremities with several different subtypes; the study patients who underwent isolated limb infusion had 17 different subtypes of sarcoma.
The rationale for amputation of soft-tissue sarcoma of the arm or leg has been to prevent the cancer from metastasizing to other parts of the body. Dr. Mullinax noted that one concern with the use of isolated limb infusion in these cancers is that it does not address distant metastatic disease.
“The reality is that those patients who develop metastatic disease after amputation or isolated limb infusion likely may already have distant microscopic disease at the time of the procedure, but the radiographic staging studies are not sensitive enough to detect it,” Dr. Mullinax said. “In this sense, the treatment of the extremity disease is not to the determinant of long-term survival.”
The isolated limb infusion technique involves circulating the chemotherapy agents melphalan and actinomycin D in the blood vessels of the affected area of the arm or leg, and the use of a tourniquet to block the chemotherapy drugs from circulating through the rest of the body, thus creating a closed circuit.
The drugs circulate in the target area for 30 minutes, and then are flushed out before the tourniquet is removed and full circulation is restored. Isolated limb infusion for soft-tissue sarcoma of the extremities can be repeated, whereas another procedure to administer chemotherapy to the arms or legs, hyperthermic isolated limb infusion, requires an incision to openly cannulate the vessels and generally cannot be repeated, Dr. Mullinax explained.
In the study population, 19 patients had 21 procedures for upper-extremity disease, and 58 patients had 63 infusions for lower-extremity disease. The results varied significantly for the two groups. The overall 3-month response rate to isolated limb infusion was 58%, but it was only 37% for those with upper-extremity disease vs 66% for lower-extremity disease. Likewise, those who had upper-extremity sarcomas had a lower median overall survival than their lower-extremity counterparts, 27.9 months vs 56.6 months. For the entire study population, the median overall survival was 44.3 months.
Entering the study, all the patients had sarcomas that could only be removed with an amputation, but afterward 30% had a complete response to isolated limb infusion, many of these because patients were able to have a surgical procedure to remove the tumors without amputation. For those who eventually needed an amputation, the median time to do so was 4.5 months following isolated limb infusion.
“Most patients would prefer to have more time with their leg rather than face an amputation,” Dr. Mullinax said. “It's known that for patients with soft-tissue sarcoma, the life-limiting disease is not in the extremity, but it's actually in the metastatic disease. An inoperable sarcoma of the thigh does not affect survival to the degree that metastatic disease in the lung does.”
Dr. Mullinax said one limitation of the study was that it did not randomize patients between isolated limb infusion and amputation, so a head-to-head comparison of response to treatment and survival cannot be performed with this dataset. The study also did not evaluate quality of life or patient-related factors for those who had limb salvage vs those who had amputation.