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Induction Chemotherapy for High Grade Extremity Soft Tissue Sarcomas: Histologic Response and Correlation of Tumor Necrosis to Long Term Disease Free and Overall Patient Survival

Theodore Robnett, MD
OncoLink Assistant Editor
Last Modified: May 21, 2000

Presenter: R.M. Henshaw
Affiliation: Washington Cancer Institute at Washington Hospital Center

Background:

The role of chemotherapy in soft tissue sarcoma remains controversial. Multiple randomized trials have shown no benefit in the addition of chemotherapy to surgery and radiation therapy (RT). High grade sarcomas have a greater propensity for dissemination. The present prospective study examines the ability of systemic therapy to address this subset of patients with a higher likelihood of metastasis at presentation.

Materials and Methods:

1. Patients with isolated extremity soft tissue sarcoma were treated with pre-operative chemotherapy using two regimens: the first used (between 1986-96) CIV adriamycin (60 mg/m²) x 2, and intra-arterial (IA) cisplatinum (120 mg/m²). The second regimen used (from 1996 onward) increased the dose of adriamycin (75 mg/m²) and included a third cycle adriamycin and ifosfamide (9 gm/m²).
2. Eligibility was restricted to patients with isolated extremity tumors.
3. Histologic evaluation was used to determine the percentage of necrosis induce by chemotherapy. No attempt was made to adjust for pre-existing necrosis prior to chemotherapy.
4. Post-operative RT was reserved for "poor responders" to chemotherapy or margin positive patients.

1. Forty-six patients were enrolled, 5 of whom had undergone prior intralesional resection with no residual tumor following treatment. Twenty four patients received the first chemotherapy regimen, while 22 received the second. Twenty- four patients had malignant fibrous histiocytoma (MFH), 10 with liposarcoma, 5 leiomyosarcoma, 3 undifferentiated, 2 synovial cell, 1 adult rhabdomyosarcoma, and 1 MPNST. Median follow up 5.2 years.
2. Median induced tumor necrosis was 95% (range 5-100%). Per cent and range of necrosis by sub- type was: MFH 93.5% (50-100), liposarcoma 95% (60-98), leiomyosarcoma 40% (10-100), undifferentiated 98% (98-99), synovial cell 85% (5-100) rhabdomyosarcoma 75%, MPNST 98%.
3. Disease free survival (DFS) and overall survival (OS) for patients with >=95% necrosis was 77% and 88% versus 65% and 74% for patients with <95%. No p values were given, but during the oral presentation the comment was made that p values for PFS and OS were not significant.
4. About one-third of patients post-operatively required radiation therapy.

1. Induction chemotherapy is effective for high grade soft tissue sarcoma.
2. The pattern of necrosis and median per cent necrosis is similar to that of classical osteosarcoma treated with induction chemotherapy.
3. Patients with higher rates of necrosis (>=95%) at resection had improved DFS and OS.

1. The results of this study are very provocative, and justify further investigation.
2. There are not enough data for the uncommon histologies to justify any conclusions.
3. The use of two chemotherapy regimens makes interpretation difficult, particularly in that ALL patients who received the second regimen must have follow up times less than the median.