Patterns of care and outcomes of patients with METAstatic soft tissue SARComa in a real-life setting: the METASARC observational study

Marion Savina, Axel Le Cesne, Jean-Yves Blay, Isabelle Ray-Coquard, Olivier Mir, Maud Toulmonde, Sophie Cousin, Philippe Terrier, Dominique Ranchere-Vince, Pierre Meeus, Eberhard Stoeckle, Charles Honoré, Paul Sargos, Marie-Pierre Sunyach, Cécile Le Péchoux, Antoine Giraud, Carine Bellera, François Le Loarer, Antoine Italiano, Marion Savina, Axel Le Cesne, Jean-Yves Blay, Isabelle Ray-Coquard, Olivier Mir, Maud Toulmonde, Sophie Cousin, Philippe Terrier, Dominique Ranchere-Vince, Pierre Meeus, Eberhard Stoeckle, Charles Honoré, Paul Sargos, Marie-Pierre Sunyach, Cécile Le Péchoux, Antoine Giraud, Carine Bellera, François Le Loarer, Antoine Italiano

Abstract

Background: Well-designed observational studies of individuals with rare tumors are needed to improve patient care, clinical investigations, and the education of healthcare professionals.

Methods: The patterns of care, outcomes, and prognostic factors of a cohort of 2225 patients with metastatic soft tissue sarcomas who were diagnosed between 1990 and 2013 and documented in the prospectively maintained database of the French Sarcoma Group were analyzed.

Results: The median number of systemic treatments was 3 (range, 1-6); 27% of the patients did not receive any systemic treatment and 1054 (49%) patients underwent locoregional treatment of the metastasis. Half of the patients who underwent chemotherapy (n = 810) received an off-label drug. Leiomyosarcoma was associated with a significantly better outcome than the other histological subtypes. With the exception of leiomyosarcomas, the benefit of a greater than third-line regimen was very limited, with a median time to next treatment (TNT) and overall survival (OS) ranging between 2.3 and 3.7 months and 5.4 and 8.5 months, respectively. The TNT was highly correlated with OS. Female sex, leiomyosarcoma histology, locoregional treatment of metastases, inclusion in a clinical trial, and treatment with first-line polychemotherapy were significantly associated with improved OS in the multivariate analysis.

Conclusions: The combination of doxorubicin with a second drug, such as ifosfamide, represents a valid option, particularly when tumor shrinkage is expected to provide clinical benefits. After failure of the second-line therapy, best supportive care should be considered, particularly in patients with non-leiomyosarcoma histology who are not eligible to participate in a clinical trial. Locoregional treatment of metastasis should always be included in the therapeutic strategy when feasible. TNT may represent a useful surrogate endpoint for OS in clinical studies.

Keywords: Chemotherapy; Metastases; Outcome; Patterns of care; Sarcoma; Surgery.

Figures

Fig. 1
Fig. 1
Prognostic factors of time to next treatment – Kaplan–Meier curves. Kaplan-Meier Curves of time to next treatment according to (a) gender, (b) grade, (c) locoregional treatment of metastases, and (d) type of systemic treatment
Fig. 2
Fig. 2
Prognostic factors of overall survival – Kaplan–Meier curves. Kaplan-Meier curves of Overall survival according to (a) gender, (b) grade, (c) number of metastatic sites, (d) locoregional treatment of metastases, (e) inclusion in a clinical trial, (f) type of systemic treatment, (g) histological subtype
Fig. 3
Fig. 3
Prognostic factors for 5-year survival – Odd ratios with 95% Wald’s confidence intervals

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