Children and Adolescents With Localised Non-Rhabdomyosarcoma Soft Tissue Sarcoma: Results of the CWS-96 and CWS-2002P Prospective Trials With Reclassification of the Trial Data Incorporating the Recent Soft Tissue Sarcoma Registry.

BACKGROUND

Here we report the results of the first comprehensive European trials for all soft tissue sarcoma entities, which aimed to develop a new risk stratification system, limit radiotherapy and chemotherapy for low-/standard-risk patients, and evaluate different chemotherapy regimens for high-risk patients.

PATIENTS AND

METHODS

The prospective CWS-96 and CWS-2002P trials stratified patients with non-rhabdomyosarcoma soft tissue sarcoma (NRSTS) by Intergroup Rhabdomyosarcoma Study (IRS) group, histology and grade (CWS-96) or IRS group, lymph node status, tumour histology and size (CWS-2002P). Low-risk patients received no additional treatment. Standard-risk patients were treated with 44.8 Gy radiotherapy, and in CWS-96, adjuvant chemotherapy was added for high-grade tumours (vincristine, actinomycin-D, ifosfamide, 160-240 mg/m2 adriamycin/VAIA). High-risk patients received VAIA in CWS-96 or an intensified adriamycin regimen in CWS-2002P (VAIA-III, 320 mg/m2 adriamycin), resection and/or 44.8 Gy radiotherapy, followed by maintenance treatment with cyclophosphamide and vinblastine in certain NRSTS in CWS-2002P. The trials enrolled 1249 patients with localised NRSTS, of whom 483 (CWS-96) and 445 (CWS-2002P) were eligible for survival analysis. Histological classifications were retrospectively standardised, including recent data from the soft tissue sarcoma registry.

RESULTS

Overall survival (OS) was significantly improved (5-year OS: 81% vs. 73%, p = 0.024) for patients treated in CWS-2002P compared to CWS-96, partly explained by the inclusion of more low-grade entities in CWS-2002P. The higher anthracycline dose in the VAIA-III regimen (CWS-2002P) did not improve survival (EFS: p = 0.23, OS: p = 0.73; matched pairs analysis). Re-classification revealed a higher proportion of malignant entities according to WHO in CWS-96 compared to CWS-2002P (90% vs. 81%, p < 0.001).

CONCLUSION

Complete resection alone is sufficient to cure low-risk NRSTS. Survival was not improved by dose-intensified adjuvant chemotherapy (with/without maintenance treatment). Patients with completely resected high-risk disease may not profit from adjuvant radiotherapy.