Source: Pediatrics  |  Posted 5 years ago

By Chris Berrie

VENICE, ITALY -- December 6, 2006 -- Isolated limb perfusion (ILP) salvaged 75% of limbs in patients with soft tissue sarcoma (STS) that were initially unresectable, thus saving the extremities from amputation or debilitating surgery, researchers reported here at the 13[^]th[] Congress of the European Society of Surgical Oncology (ESSO).

These findings, from a retrospective study conducted in a tertiary centre with a multidisciplinary approach, were presented by principal investigator St?phane Cherix, MD, and resident, orthopaedics and traumatology, University Hospital Lausanne, Lausanne, Switzerland.

This retrospective study looked at the experience of 51 patients with a mean age of 54.8 years (male, 47.1%) with 57 ILPs between 1992 and 2006. Six (11.8%) of these patients underwent 2 ILPs.

Soft tissue sarcomas (STS) represent fewer than 1% of newly diagnosed malignancies. "About half of them are located at the extremities, with about 10% nonresectable, and we known that amputation does not improve overall survival," Dr. Cherix said in a presentation on November 30[^]th[].

As a new strategy, ILP has been reported to provide limb salvage in more than 80% of patients using local high-dose infusion of tumour necrosis factor-alpha (TNF-alpha) and melphalan, a potent chemotherapeutic agent. This approach can provide a 70% or greater tumour response for STS, Dr. Cherix said.

The goal of the present study was to evaluate the possibilities for saving extremities from amputation or debilitating surgery in nonresectable sarcomas, through local control of the tumour, and surgical marginal (R1) resection after its regression.

Patients received neoadjuvant ILP with TNF-alpha and melphalan, repeated as necessary, and response was assessed clinically and with magnetic resonance imaging (MRI). The study design was to have tumour resection without functional sacrifice, and adjuvant radiotherapy or chemotherapy was considered in patients who did not have complete response.

The surgical technique involved cannulation of the vessels at the root of the limb, application of a tourniquet proximal to the cannula, and limb perfusion with extracorporeal circulation. Systemic leakage was monitored, and the procedure was carried out under mild hyperthermia (38-40 degrees Celsius).

The indications for ILP were for STS close to or invading a joint, surrounding a major nerve, multiple or bulky in form, or recurrent. Contraindications were for severe general status or organ dysfunction, severe local vascular or cardiac disease, or infection. Dr. Cherix also stressed that regional or distant spread of STS was not a contraindication to ILP surgery.

The majority of patients (86.3%) had STS of the lower limbs, and 58% were liposarcomas or undifferentiated pleiomorphic sarcomas. In all, 90.2% had localised disease at diagnosis, 88% were of a high grade, and 86% were at an advanced stage.

The reasons for ILP were: extracompartmental location (19.6%); contiguity to nervous or vascular structures (19.6%); size of lesion alone (up to 28 cm; 19.6%); and local spread of tumour (39.2%).

Excision of the tumour remnant consisted of 65% resections, 81% of which were distant or marginal, 9% intra-tumoural. Primary or early amputations were needed in 14%, due to insufficient response to ILP, with 2 further amputations after a second ILP, and 3 late or secondary amputations; the total amputation rate was 23.5%.

Reconstructive surgery was used for 32% of patients (plastic surgery, 26%; orthopaedic, 6%), and complementary treatment in 27% (radiation therapy, 18%; chemotherapy, 6%; combined, 3%).

After a follow-up of 38.9 months (range, 4-159 months), 25% of patients showed complete response, 42% had partial responses; 5% were not assessable, 14% showed no change, and 14% had progressive disease.

There were early complications in 21% of patients, with 2 life-threatening retroperitoneal bleedings, 1 thigh compartment syndrome, and rare significant transient haematological or single-organ dysfunction (liver, kidney). There were no treatment-related deaths. "Generally, even though complications can be severe, they are predictable and they can be managed," Dr. Cherix noted.

Late complications were seen in 23% of patients, of which 8 were cutaneous, 7 neurological, and 2 orthopaedic.

Local disease recurrence was seen in 37% of patients, with a recurrence-free survival of 20.3 months (range, 2-78 months), and distant metastases in 51% with 12.4 months (range, 2-43 months), respectively. Overall, the disease-free interval was 14.9 months (range, 2-49 months), with a 5-year survival of 43.5%.

Dr. Cherix concluded, "ILP is dedicated to nonresectable tumours, it's a heavy procedure, and it's for specialise oncological centres only, but you can save three quarters of the limbs affected."

[Presentation title: The Swiss Experience With Isolated Limb Perfusion, a Limb Salvage Strategy for Non-Resectable Soft Tissue Sarcomas of the Extremities. Abstract 043]