Multimodal Treatment of Sarcomas Linked to BCOR-CCNB3 Fusion in Pediatrics: A 3-Patient Case Series

Background: Molecular genetic testing in cancer diagnosis has resulted in subclassifications of malignancies previously grouped together. In 2012, a new entity was classified according to fusion of the B-cell lymphoma (BCL-6) co-repressor (BCOR) gene and the testis-specific cyclin B3 (CCNB3) gene on the X-chromosome, known as a BCOR-CCNB3 fusion positive sarcoma. Previous studies have focused on clinical and pathologic characterization of this specific malignancy, but standard treatment modalities are not well documented. Objectives: Given their relatively new classification, the treatment approach has remained variable. We describe three pediatric patients with BCOR-CCNB3 fusion positive sarcomas. In summarizing treatments and outcomes, we aim to add to the body of knowledge for this subtype. Design/Method: This was a retrospective study of three de-identified patient charts. BCOR-CCNB3 fusions were confirmed in all three patients using fluorescence in-situ hybridization (FISH). Results: Case 1 - A 2-year-old Black female presented with a firm, right calcaneal mass measuring 5.6 x 3.7 x 3.1 cm. Following diagnosis of BCOR-CCNB3 fusion sarcoma, she was promptly started on an interval compressed regimen of alternating vincristine-doxorubicin-cyclophosphamide and ifosfamide-etoposide with local control accomplished through amputation of the right foot. She has been in remission for two years. Case 2 - A 12-year-old Caucasian female presented with a two-week history of unilateral right hip pain that worsened with activity. Imaging revealed a 8.2 x 6.0 x 8.3 cm mass on the right pubic bone. She began treatment with 6-cycles of ifosfamide and doxorubicin. For local control, the patient underwent radical resection of the right pubic bone. She remains free of disease and fully active 2.5 years following completion of therapy. Case 3 - A 16-year-old Black male presented with right lateral ankle pain and swelling and was unable to bear weight. MRI revealed a soft tissue mass, measuring 6.0 x 4.0 x 6.6 cm. The mass was grossly excised with positive margins. Therapy consisted of compressed alternating cycles of interval vincristine-doxorubicin-cyclophosphamide and ifosfamide-etoposide with daily proton beam therapy starting cycle 7. The patient remains in remission at his last visit 2 years from completion of therapy. Conclusion: We notice Cases 1 and 3 were treated using 5-drug Ewing sarcoma treatment protocol while Case 2 received two drug therapy using combination of ifosfamide and doxorubicin. The variation in treatment regimens highlight existing lack of consensus and we hope that a multi-institutional trial will help solidify future course.