(P 320) WHAT IS THE ROLE OF CHEMOTHERAPY IN PATIENTS (PTS) WITH SPINDLE CELL/SCLEROSING RHABDOMYOSARCOMA (SCRMS): A CANADIAN SARCOMA RESEARCH AND CLINICAL COLLABORATION (CANSARCC) STUDY

Objective: SCRMS comprise genomically heterogeneous subtypes of rhabdomyosarcoma often affecting adolescent and young adults. SCRMS harboring mutations in MYOD1 are high risk with very poor outcome. They can occur anywhere but have a predilection for the head/neck. In comparison, young children can have gene rearrangements in other genes including NCOA2 with a very favorable biology. Our aim is to better understand whether chemotherapy has any role in improving outcome in SCRMS.

Methods: After research ethics board approval, data was obtained retrospectively from the CanSaRCC national database. SCRMS pts included were diagnosed between Aug 1998 to Sep 2023 from 12 sites across Canada. Pathology was reviewed by local experts at all institutions. Descriptive statistics were performed; best response to chemotherapy was assessed by local investigators using RECIST 1.1. Event free (diagnosis to recurrence/death) and overall survival (diagnosis to death from any cause) were estimated using the Kaplan Meier method (SAS 9.4). Cox regression was used to estimate factors influencing outcomes by univariable (UVA) and multivariable (MVA) analysis.

Results: 62 pts had a median age at diagnosis of 33.7 yrs (range 0.04 – 85.2; 3 pts under age 12 mo), 21 (33.9%) female. The most frequent primary site was extremity (n=23, 37.1%) followed by head/neck (non-parameningeal; n=16, 25.8%), trunk (n=7, 11.3%), paratesticular (n=7, 11.3%) and other (n=9, 14.5%). 7 (11.3%) pts had metastatic disease at diagnosis. MYOD1 mutational status is as follows: negative 5 (8%), positive 19 (30.6%), and not done 38 (61%). Median time to last follow up for alive pts was 3.5 yrs (range 0.5-16.1).

Treatment and outcome listed in Table 1. See Figure 1 for median OS and EFS.

Pts with localised disease at diagnosis (54/62 (87.1%)); 37 (68.5%) received systemic therapy. Of those, 17 (45.9%) received neo-adjuvant treatment (prior to surgery or RT), where best response could be assessed for 8 pts of whom 7 had SD, 1 PD (Table 1). Median lines of therapy was 1 (range 1-10). 23 pts (42.6%) had recurrence: 10 local (43.5%) and 13 (56.5%) distant as their first event. Chemotherapy did not impact EFS [HR:1.3, 95%CI 0.5-3.2, p=0.6] nor OS [HR:1.1, 95%CI 0.4-3.1, p=0.8]. (Figure 2) In multivariate analysis of EFS, older age was associated with unfavorable survival [HR:1.03, 95% CI 1-1.06, p=0.03].

Pts with metastatic disease at diagnosis (8/62 (12.9%)); 3 (37.5%) pts received systemic therapy. One patient is currently alive with disease in palliation (1.6 yrs); the rest have died.

Conclusion: Chemotherapy did not improve outcome in pts with localized SCRMS and all pts with metastatic disease died quickly. We are working towards identifying other genetic alterations in this series. Perhaps pts would benefit from identification of molecular targets as alternatives to cytotoxic chemotherapy (ie. PIK3CA inhibitors) to avoid unnecessary toxicity.