CIC-DUX4 sarcoma (CDS) represent the second most prevalent subset of high grade round cell sarcomas after Ewing sarcomas. The natural history might be diverse and probably underscores a heterogeneous group. Moreover, treatment strategy can differ according to institutions. The main goals of this retrospective study was to describe characteristics, treatments and outcome for patients with CDS included in the French NETSARC database.
Pediatric and adult patients from 11 French centers with a diagnosis of CDS were registered from October 2008 to March 2021. Patients and tumors characteristics were collected from the national network NETSARC+ database. CDS diagnosis was histologically and molecularly confirmed with a central review by expert pathologists. Two groups of patients were studied: those treated similarly to classical Ewing sarcomas especially with multi-agent chemotherapy in neoadjuvant and adjuvant setting (cohort 1) and those treated as high-grade soft tissue sarcomas according to ESMO and/or EpSSG guidelines (cohort 2).
Among the 64 patients with confirmed CDS, the sex ratio was 0.9 and the median age at diagnosis was 25 years (range 11-87) including 19 patients < 18. Three patients (5%) had a previous cancer history. Population and tumor characteristics were not statistically different between cohort 1 (N=38, 60%) and cohort 2 (N=26, 40%). With a median follow-up of 37 months (range 3-252), 32 patients (50%) died of the disease. Median overall survival from diagnosis was 4 years, with no significant difference between both cohorts (Log-rank test, P=0.99). Nevertheless, when focusing on patients with metastatic disease at diagnosis (N=18), all patients from cohort 2 (N=6) died due to progressive disease while 7 patients from cohort 1 are still alive and in complete remission, resulting in a significantly better OS (Log-rank test, P<0.05).
FSG experience confirms the aggressive clinical course of CDS patients regardless of chemotherapy regimen, even if this study suggests that metastatic patients should not benefit from a therapeutic de-escalation. Molecular studies are urgently needed to improve understanding and treatment of this orphan disease.
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