OSTEOGENIC SARCOMA: ASSESSMENT OF TUMOR NECROSIS WITH DYNAMIC MR IMAGING AFTER NEOADJUVANT CHEMOTHERAPY - WORK IN PROGRESS

Panicek DM, Dyke JP, Ballon DJ, Koutcher JA, Schwartz LH, Healey JH, Meyers PA, Huvos AG (Memorial Sloan-Kettering Cancer Center, New York, NY 10021).

HISTOLOGIC RESPONSE OF HIGH GRADE SOFT TISSUE SARCOMAS TO INDUCTION CHEMOTHERAPY

Henshaw RM, Shmookler BM, Malawer MM (Washington Cancer Inst. Washington DC 20010).

Effects of chemotherapy on osteosarcoma have been well documented since the introduction of induction (neo-adjuvant) chemotherapy in the 1970’s. Increasing interest in the use of chemotherapy for soft tissue sarcomas has led to the introduction of similar treatment protocols used for bone sarcomas. However, the effects and efficacy of chemotherapy on soft tissue sarcomas remain unknown.

Purpose: To describe the histologic effects of induction chemotherapy on high-grade soft tissue sarcomas.

Methods: Consenting patients who presented with isolated, high grade soft tissue sarcomas of the pelvis and extremities were treated with 2 or 3 cycles of induction chemotherapy prior to surgical resection. An experienced musculoskeletal pathologist performed detailed histologic evaluation of the resection specimens. Specimens were processed using techniques anaologous to those performed for bony sarcomas. Slabs were created along the maximum diameter of the tumor, which were then sectioned in grid-like fashion and sequentially coded with an accompanying diagram. Patterns of histologic necrosis and a semi-quantitative estimate of the chemotherapy killing effect were recorded similar to that described for bone sarcomas. Routine evaluation of surgical margins was also performed.

Results: 46 patients with high-grade extremity sarcomas underwent induction chemotherapy prior to surgical resection. 5 patients had a subtotal intralesional resection prior to referral and did not have any residual viable tumor following chemotherapy and re-resection. Two different protocols were used, the first consisting of 2 cycles of adriamycin and cis-platinum, the second adding a 3^rd cycle of adriamycin and ifosfamide. Specific tumors treated included 24 MFHs, 10 liposarcomas, 5 leiomyosarcomas, 3 undifferentiated sarcomas, 2 synovial cell sarcomas, 1 adult rhabdomyosarcoma and 1 MPNST. Histologic patterns of chemotherapy obliterated tumor resembled a reactive/reparative process with regions of sclerosis, hemosiderin deposition, vascular proliferation and chronic inflammatory infiltration. Broad sheets of necrotic cells and "ghost" cells were typical in specimens having a high percentage of necrosis. Poor tumor response typically had large regions of viable tumor cells with isolated, scattered foci of necrosis. Overall, the median chemotherapy killing effect was 95% (95% for Protocol 1 and 90% for Protocol 2) with a maximum of 100% and a minimum of 5%. Median necrosis and range by tumor types were as follows: MFH 93.5% (50-100), liposarcoma 95% (60-98), leiomyosarcoma 40% (10-100), undifferentiated 98% (98-99), synovial cell 85% (5-100), rhabdomyosarcoma 75%, and MPNST 98%.

Conclusions: 1. Induction chemotherapy can achieve a high degree of histologic necrosis in a wide variety of high-grade soft tissue sarcomas. 2. Patterns of necrosis are similar to those seen in classical osteosarcoma and other high-grade bone sarcomas. 3. Tumors thought to be relatively chemo-resistant can undergo impressive amounts of necrosis with induction treatment. 4. The prognostic significance of these findings for soft tissue sarcomas may be analogous to that already confirmed for osteosarcoma, although many more patients will be required to determine if the percentage of necrosis has prognostic significance.