The effect of adjuvant therapies on long-term outcome for primary resected synovial sarcoma in a series of mainly children and adolescents

Monika Scheer,Ewa Koscielniak,The European Cooperative Weichteilsarkom Studiengruppe [Cws] ,Jörg Fuchs,Anton George Henssen,Beate Timmermann,Steffan Loff,Felix Niggli,Gustaf Ljungman,Sebastian Bauer,Christian Vokuhl,Ruth Ladenstein,Thomas Klingebiel,Marc Münter,Bernarda Kazanowska

doi:10.1007/s00432-021-03614-6

Abstract

BackgroundThe benefit of adjuvant therapy in synovial sarcoma (SS) treatment is under debate. Long-term follow-up data are missing.MethodsSS patients treated in the consecutive trials CWS-81, CWS-86, CWS-91, CWS-96, CWS-2002-P, and the SoTiSaR-registry till 2013 were analyzed.ResultsMedian age of 185 patients was 13.9 years (0.1–56)—with median follow-up of 7.4 years for 163 survivors. Most tumors (76%) were located in extremities. Size was < 3 cm in 58 (31%), 3–5 cm in 59 (32%), 5–10 cm in 42 (23%), and > 10 cm in 13 (7%) (13 missing). In 84 (45%) tumors, first excision was complete (R0 corresponding to IRS-I-group) and in 101 (55%) marginal (R1 corresponding to IRS-II-group). In a subsequent surgical intervention during chemotherapy, R0-status was accomplished in 23 additional IRS-II-group patients with secondary surgery. Radiotherapy was administered to 135 (73%), thereof 62 with R0-status and 67 R1-status (6 missing information). Adjuvant chemotherapy was administered to all but six patients. 5-year event-free (EFS) and overall survival (OS) was 82.9% ± 5.7 (95%CI) and 92.5% ± 3.9. Local and metastatic relapse-free survival was 91.3% ± 4.3 and 92.3% ± 4.1 at 5 years, respectively. In the multivariate analysis, tumor size and no chemotherapy were independently associated with EFS. Size and site were associated with OS. In a detailed analysis of local and metastatic events, tumor size was associated with an independent risk for developing metastases. No independent factor for suffering local recurrence could be identified.DiscussionOmission of chemotherapy in a non-stratified way seems not justified. Size governs survival due to high linear association with risk of suffering metastatic recurrence in a granular classification.

Highlights

Soft-tissue sarcomas represent nearly 8% of childhood malignancies
Developed for rhabdomyosarcoma, but extended to other chemotherapy-sensitive pediatric STS, the Intergroup Rhabdomyosarcoma Study (IRS) post-surgical grouping system (Maurer et al 1988) categorizes patients based on the extent of residual tumor after first surgery: primary completely excised tumors with negative microscopic margins (R0) correspond to IRS-I; primary grossly resected tumors with microscopic residual disease (R1): IRS-II; macroscopic residual disease after incomplete resection or biopsy (R2): IRS-III; and metastases at onset: IRS-IV (Maurer et al 1988)
Koscielniak et al 1992, 1999; Dantonello et al 2009), there is no consensus on how patients should be classified to receive adjuvant therapy

Summary

Introduction

Synovial sarcoma (SS) is the most common non-rhabdomyosarcoma soft-tissue sarcoma (Goldblum 2014; Pizzo and Poplack 2011), characterized by the specific translocation t(X;18). It typically affects the extremities of adolescents, as well as of young adults. Tumor size and no chemotherapy were independently associated with EFS. In a detailed analysis of local and metastatic events, tumor size was associated with an independent risk for developing metastases. Size governs survival due to high linear association with risk of suffering metastatic recurrence in a granular classification

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Conclusion