PRE-SURGICAL CHEMOTHERAPY VS IMMEDIATE SURGERY AND ADJUVANT CHEMOTHERAPY FOR NON-METASTATIC OSTEOSARCOMA. SURGICAL RESULTS OF POG 8651

Schwartzentruber DJ, Goorin AM, Gebhardt MC, Gieser P, Ayala A, Harris M, Grier H, Link M ( POG, Chicago, IL).

Previous sequential trials have reported improved event-free survival with pre-surgical chemotherapy in pediatric osteosarcoma. This randomized study evaluated the timing of surgery in relation to chemotherapy for patients with non-metastatic extremity sarcoma. 106 patients were randomly assigned to pre-surgical chemotherapy (PRE) vs immediate surgery (SURG) between 1986 and 1993 in the Pediatric Oncology Group trial 8651. Except for the timing of surgery, patients received 44 weeks of identical chemotherapy consisting of methotrexate with leucovorin rescue, doxorubicin, cisplatin, cyclophosphamide, bleomycin and dactinomycin. Six patients were excluded from analysis and of the remaining 100, 45 were randomized to PRE and 55 to SURG. Both arms were well balanced for age, sex, race and tumor location. Limb sparing (LS) surgery was performed in 50% of PRE and 55% of SURG. During PRE, 1 patient lost a LS option due to local tumor progression but 2 gained a LS option due to regression. Both arms had a similar incidence of post-operative (short + long term) complications (27% of patients PRE vs. 30% of SURG); only one local recurrence (at 13 months) was observed in the entire study. LS surgery was associated with more complications than amputation (21 of 51 patients vs. 7 of 46, respectively, p=0.0067). However, the overall rating for quality of life measures was not different between LS surgery and amputation at 6 months and 24 months. Similarly, quality of life measurements were not different between the PRE and SURG arms at 6 and 24 months. Sixty seven patients are continuously disease free and 77 remain alive. At 5 years the projected event-free survival is 65% +/-6% (61% +/-8% for PRE vs. 69% +/-8% for SURG, p=0.8) and the projected overall survival is 78% +/-5% (76% +/-7% for PRE vs. 79% +/-7% for SURG, p=0.6). We conclude, excellent local tumor control was achieved in all patients and pre-surgical chemotherapy did not result in improvement in event-free survival or overall survival. No greater incidence of limb salvage was made possible by pre-surgical chemotherapy. No difference in the incidence of post-surgical complications were noted in either arm, and quality of life measurements at 6 and 24 months were similar in both arms.