(P 411) TFCP2 FUSION-POSITVE RHABDOMYOSARCOMAS: A REPORT OF 10 CASES AND A REVIEW OF THE LITERATURE

Objective: The fusion of the TFCP2 gene with either EWSR1 or FUS is associated with the spindle cell and/or epithelioid variant of rhabdomyosarcoma. This is an ultra-rare fusion associated sarcoma, only reported in case reports and small case series. Herein, we look to describe the clinical characteristics and treatment course of patients with TFCP2 fusion sarcomas.

Methods: In this retrospective case series, we identified 10 patients in our hospital system with TFCP2 fusion sarcomas. We also identified 43 reported cases in the literature. We assessed primary tumor characteristics, treatment regimens, and outcomes among all cases.

Results: In our institution’s series of 10 patients, seven had FUS-TFCP2 fusion and three had EWSR1-TFCP2 fusion. We find that TFCP2 fusion sarcomas most commonly occur in young adults (median age: 33 years) and arise in craniofacial bones (70%). The median overall survival in our cohort was 24.7 months. Four patients were treated with upfront surgery, and all developed recurrent disease with median time to recurrence being 2.1 months. Five patients received systemic therapy, and the median progression-free survival was 1.6 months. We reviewed 43 cases in the literature, again highlighting the predilection for craniofacial bones (69.8%) and incidence in young adults (median age: 30 years). Median overall survival amongst all cases in the literature was 17 months. For the 17 patients with localized disease, the median recurrence-free survival was 4 months. For the 25 cases with metastatic disease, the median progression-free survival was 2 months. Concomitant ALK overexpression is nearly universal, and two of our patients were treated with ALK inhibitors; one patient had a near complete response before eventual progression after 6 months, while the other had progressive disease after 2 months. This pattern of limited response is mirrored amongst the 11 patients who have received ALK inhibitors in the literature.

Conclusion: TFCP2 fusion sarcomas are characterized by aggressive biology and have poor prognoses. The 43 patients previously reported in the literature had similar clinical characteristics as our cohort with most cases occurring in the craniofacial bones of young adults. ALK overexpression was again demonstrated in nearly all patients, however, there was not a clinically meaningful survival benefit seen with the use of ALK inhibitors for the few who received this therapy. Additional work is needed to find the optimal treatment course for these sarcomas.