Prognostic factors in clear cell sarcoma: an analysis of soft tissue sarcoma in 43 cases

Abstract

Purpose: Clear cell sarcoma (CCS) of tendons and aponeuroses and CCS-like malignant gastrointestinal neuroectodermal tumor/sarcoma (GINET) are characterized by frequent local and distant relapses, alongside with low efficacy of all systemic treatments. We aimed to collect a comprehensive dataset to identify prognostic factors and treatment outcomes.

Methods: We performed a retrospective single center analysis for diagnosed CCS and GINET on demographic, tumor, treatment and survival data.

Results: We identified 43 patients (w:25, m:18) with a median follow-up of 35mo and a 5y-OS-rate of 42%. At diagnosis the median age was 42yrs. Median tumor size was 3.6 cm (0.3-11.1 cm), and 24/26 (94%) tissues analyzed at our institute were EWSR1::ATF1-translocation-positive. Distant extremities (incl. knee or elbow) were affected in 72.5%. Of note, 79.5% received an excisional biopsy (benign histology suspected in 30.2%) leading to frequent incomplete resection. Final R0 status correlated significantly (p = 0.017) with longer survival rates compared to R + status in localized CCS (N0M0, 5-yr OS 0% vs 64%). Radiation and systemic treatment had limited antitumor effects while isolated limb perfusion was active in some patients. 18.6% of patients showed lymphatic spread and 20.9% distant metastases. Presence of initial M + was associated with a dismal survival of 1.4 years (M +) vs 7.1 years (M0; p < .001).

Conclusion: We here present one of the largest clinical cohorts of patients with CCS/GINET. Our data underscores the exceptional risk of metastatic disease even in small tumors. As systemic treatment and radiation showed limited efficacy, complete resection was the most important treatment option.

Keywords: CCS; Clear cell sarcoma; EWSR1; Gastrointestinal sarcoma; Malignant melanoma of soft tissue; Prognostic factors.

Fig. 1

Patterns of local, locoregional (N1) and distant recurrence (M1) in CCS. a Local recurrence (LR, n = 10, only primary tumor location) in patients with final R0 vs final R1, including two patients with RTx in R0 cohort (time primary resection—recurrence, in years). b Locoregional (N1) recurrence after resection in patients with local disease, N0M0 (time primary resection—recurrence, in years). c Time to distant metastasis after local treatment (R0) for regional relapse (local or N1) compared to patients without regional relapse (time from resection to distant metastasis, in years). d Distant metastasis-free survival for patients with complete (R0) vs incomplete resection (R1 or R2) and postoperative radiotherapy (time primary resection—distant metastasis, in years)

Fig. 2

Overall survival (OS) depending on tumor size, staging at diagnosis and final R status in Kaplan–Meier estimation. a OS for all patients (time: diagnosis CCS—death, in years). b OS for all tumor sizes (T) only in patients with local disease (N0M0) and with final R0 (time: diagnosis CCS—death, in years). c OS depending on initial staging: local disease vs locoregional spread vs distant metastasis for all patients (time: diagnosis CCS—death, in years). d OS for final R0 vs final R + (R1 or R2) with localized disease at diagnosis in Kaplan-Meier estimation (N0M0) (time: diagnosis CCS – death, in years)

Fig. 3

Application of different chemo- and targeted therapies in patients with metastatic (N any, M1) CCS or GINET