Is PAX3-FOXO1 associated with worse outcome in adults with rhabdomyosarcoma (RMS)?

Abstract

e22525 Background: Rhabdomyosarcoma (RMS) is a rare soft tissue sarcoma in adults. The PAX3-FOXO1 fusion gene is associated with alveolar rhabdomyosarcoma. PAX3-FOXO1 results from a stable reciprocal translocation of chromosomes 2 and 13, which fuses in-frame the DNA binding domain of PAX3 with the transactivation domain of FOXO1. Occasionally, PAX7-FOXO1 is expressed. In children, the PAX3-FOXO1 fusion gene is associated with worse outcome. We evaluated the prognostic role of FOXO1 fusion status in adults with RMS treated in a single, large volume sarcoma centre. Methods: A retrospective review of adult RMS patients (pts) diagnosed from 1984 to 2018 was done. Information on demographics, treatment, fusion status and survival was collected. Primary favourable site was defined as tumour arising in orbit, non-bladder/prostate genitourinary system and non-parameningeal head and neck. Factors were compared using Fisher’s Exact test. Event-free survival (EFS) was estimated by the Kaplan-Meier method and compared with log rank test. FOXO1 fusion status was coded as FP (fusion positive) or FN (fusion negative). Results: Of 134 pts identified in our database, fusion testing was performed in 55 (41%). Of these, PAX3 fusion was detected in 22 (40%). PAX7 was not detected. The median age of FP and FN pts was 25 yrs (range 18, 90) and 27 yrs (range 18, 65), respectively. Gender distribution was similar between FP and FN. Favourable site was seen in 13 (60%) FP and 21 (64%) FN. Nodal disease was present in 21 (95%) FP and 21 (64%) FN (p = 0.02). Distant metastases were present in 10 (45%) FP and 9 (27%) FN (n.s.). Treatment received was as follows for FP and FN, respectively: chemotherapy (21(95%), 33(100%)), radiation (14(64%), 22(67%)) and surgery (4(18%), 17(52%)). 5-yr EFS for pts without distant metastases was 27% (CI 22.6-76.6) and 46% (CI 21.5 – 70.5) for FP and FN respectively (n.s.). Conclusions: FP and FN RMS occurs in adults of all ages. Similar to children, adults with FP are more likely to present with nodal disease. Our study did not show that fusion status was associated with poorer EFS in adult RMS, however, larger series are needed to confirm this preliminary data.