N.B. Bui

The pathological features of 155 adult patients with soft-tissue sarcomas were studied retrospectively, in an attempt to set up a grading system for these tumors. As the first step, seven histological criteria (tumor differentiation, cellularity, importance of nuclear atypia, presence of malignant giant cells, mitosis count, pattern of tumor necrosis and presence of vascular emboli) were evaluated in a monofactorial analysis. Five of these (tumor differentiation, cellularity, mitosis count, tumor necrosis, and vascular emboli) were correlated with the advent of metastases and with survival. A multivariate analysis, using a Cox model, selected a minimal set of three factors (tumor differentiation, mitosis count, and tumor necrosis) the combination of which was necessary and sufficient to retain all the prognostic information. A grading system was elaborated, which turned out to be correlated with the advent of metastasis and with patients' survival. A second multivariate analysis introducing clinical prognostic features showed that the histological grade was the most important prognostic factor for soft-tissue sarcomas. Thus, this grading system appears to be highly interesting because of its prognostic value and the facility of its elaboration. However, its reproducibility should be tested.

PURPOSE: To define the prognostic factors in adult patients with locally controlled soft tissue sarcoma (STS) and to determine which patients should be considered for adjuvant treatment. PATIENTS AND METHODS: Five hundred forty-six patients with a nonmetastatic and locally controlled STS, collected in a cooperative data base by the French Federation of Cancer Centers (FNCLCC) Sarcoma Group from 1980 and 1989, were studied. Histologic slides of all patients were collegially reviewed. Initial treatment consisted of complete tumor resection with amputation in only 4% of the patients. Adjuvant radiotherapy was administered to 57.9% and adjuvant chemotherapy to 31%. Relationships between tumor characteristics were analyzed, and univariate and multivariate analyses were performed using Cox models for the hazards rate of tumor mortality, development of distant metastasis, and strictly local recurrence. RESULTS: Unfavorable characteristics with an independent prognostic value for tumor mortality were: grade 3 (P = 3 x 10(-10)), male sex (P = 1.5 x 10(-5)), no adjuvant chemotherapy (P = 5.4 x 10(-5)), tumor size > or = 5 cm (P = 3.8 x 10(-3)), and deep location (P = 4.6 x 10(-3)). Unfavorable characteristics for the development of distant metastasis were: grade 3 (P = 4 x 10(-12)), no adjuvant chemotherapy (P = 6.4 x 10(-4)), tumor size > or = 10 cm (P = 9.8 x 10(-4)), and deep location (P = 1.3 x 10(-3)). For the development of local recurrence, the unfavorable characteristics were: no adjuvant radiotherapy (P = 3.6 x 10(-6)), poor surgery (local excision) (P = 2 x 10(-4)), grade 3 (P = 7.6 x 10(-4)), and deep location (P = 10(-2)). Grade, depth, and tumor size were used to define groups of patients according to the metastatic risk. Adjuvant chemotherapy was beneficial in terms of overall survival and metastasis-free survival in grade 3 tumor patients only. Despite worse characteristics concerning tumor depth, tumor-node-metastasis (TNM) and American Joint Committee (AJC)/International Union Against Cancer (UICC) classifications and grade in patients with adjuvant radiotherapy, the latter experienced significantly fewer local recurrences than patients with no radiotherapy. CONCLUSION: Grade, tumor depth, and tumor size could be used to select patients with a high metastatic risk, for which adjuvant chemotherapy could be beneficial.

10032 Background: We previously showed in the BFR14 study that IM interruption results in increased risk of disease progression (PD) after 1 and 3 years (yr) in non progressing patients (pts). The impact of IM discontinuation on progression free survival (PFS) in responding pts at 5 yrs is unknown. Methods: This prospective multicenter BFR14 study was initiated in 06/02 and completed inclusion in 05/09. After 1, 3, and 5 yrs of IM 400 mg/day, pts free from PD were randomly offered to continue (C arm) or Stop (S arm) IM. Pts allocated to the S arm had to restart IM (same dose) in case of PD. Primary endpoint was PFS. A Bayesian model was implemented for this part of the BFR14 study. Results: Overall, 434 pts were included in the BFR14 study. Fifty-eight (n=26 vs. n=32), 50 (n=25 vs. n=25) and 21 (n=11 vs. n=10) non progressive pts at were randomized at 1, 3 or 5 yrs in the S vs C arms. The 2 yr-PFS were 13% and 16% in the S arms after 1 and 3 years of treatment compared to 62% and 80% in the C arms after 1 and 3 yrs of IM respectively. 21 pts responding to IM at 5 yrs and not previously randomized in the 1 or 3 yrs S arms were randomized after 5 yrs of IM. After a median follow-up of 12 months (6.8-15.1) from randomization, 5 of the 11 pts randomized in the S arm have relapsed while no relapse was observed among the 10 pts randomized in the C arm (p=0.035) The results compare favorably to the 1 yr and 3 yrs cohort for the C arms: 1 year after randomization at 1, 3, and 5 years, the relapse rate was 20% in the 1 yr C cohort, vs. 8% in the 3 yrs C cohort, vs. 0% in the 5-yrs C cohort. IM reintroduction in the I arm (at 1, 3 or 5 yrs) after a reprogression allowed a tumor control in all evaluable pts to date. Conclusions: Despite long term tumor control, IM interruption at 5 yrs resulted in a higher rate of progression than imatinib maintenance in patients with advanced GIST in this randomized study. IM has to be given continuously until PD or intolerance in the population of non progressing advanced or metastatic GIST. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bayer, GlaxoSmithKline, Novartis, Pfizer, PharmaMar, Roche, sanofi-aventis Chugai Pharma, GlaxoSmithKline, Novartis, Novo Nordisk, Pfizer, PharmaMar, Roche Merck, Novartis, Pfizer, Roche Novartis, PharmaMar