(P 365) A SINGLE INSTITUTION COMPARISON OF OUTCOMES IN PEDIATRIC AND ADULT PATIENTS WITH GYNECOLOGIC ORIGIN RHABDOMYOSARCOMA

Objective: Rhabdomyosarcoma (RMS) represents the most common histology of soft tissue sarcomas (STS) in children and adolescents accounting for up to 8%. It is far rarer in adults comprising less than 1% of adult STS. Multiple modality treatment is standard for both local and distant control including surgery, radiation, and chemotherapy with sequencing dependent on tumor site and clinical presentation. Most common sites of origin are uterine or cervical in children and head and neck origin in adults. We aimed to investigate institutional outcomes of RMS of gynecologic (GYN) origin across the pediatric and adult populations to determine differences in presentation characteristics, management, molecular analysis, and outcome differences between the cohorts.

Methods: In this single-institution retrospective analysis, patients (pts) with RMS of GYN origin who were diagnosed between January 2000-March 2024 were included. Pt data was extracted from the electronic medical record. Pts with other STS or carcinosarcoma with rhabdomyosarcomatous differentiation were excluded. Relevant clinical factors including demographics, stage, location of primary tumor, lines of systemic therapy were correlated to progression free survival (PFS) and overall survival (OS). Kaplan-Meier methods were used for survival analysis.

Results: For 22 pts demographics included 13 adult pts (>18yo at diagnosis) and 9 pediatric (peds) pts (< 18yo at diagnosis) with a range of 0.3-78.3 years (Figure 1). All pts were female. Pt reported race was 90.9% Caucasian with remaining pts reporting African American race 9.1%. Majority of pts were IRSG stage I (N=11), 1 pt stage II, 1 pt stage III, and 8 pts stage IV, 1 pt could not be staged due to lack of complete records. Majority of adult pts were stage IV (N=6), and majority of peds pts were stage I (N=6). Median OS for all pts at 20 years of follow-up was non-evaluable as the median did not reach 50%. All pts together had 2-year OS of 85.2% (60.8-95%). Median PFS for all pts was NE (0.4-NE) with a 52.1% (29.2-70.7%) likelihood of being progression free at 2 years and no pts progressing after 2 years. Four adult pts were deceased from disease at time of data analysis, but no deaths were observed in the peds cohort with a median follow-up of 12.4 years. When divided by age, 2-year OS probability was significantly different at 100% (48.8-90.4%) and 73.3% (37.9-90.6%) for peds and adult populations respectively (P=0.0353) (Figure 1). Median PFS was NE (0.2 years-NE) for peds pts and 0.8 years (0.1 years-NE) years for adult pts with a 2-year PFS probability of 77.8% (36.5-93.9%) and 33.6% (10.4-59.1%) respectively, reaching statistical significance (p-value 0.0397) (Figure 2). All deaths were observed in IRSG stage IV pts. The mOS for adult pts with stage IV was 0.4 years (N=6, range 0.1-1.1), and the mOS for stage IV peds pts was 13.6 years (N=2, range 12.2-14.9) (Figure 4). In pts with stage IV disease, the average number of lines of therapy was 1.7 (range 1-3) in the adult cohort (N=6) and 1.5 (range, 1-2) in the peds cohort (N=2). mPFS in adult pts with IRSG Stage IV disease was 4.83 months (range, 0.97-9.73 months). The most used regimen was VAC in all IRSG Stage IV disease. Genomic testing data was available for 6 adult pts and 2 peds pts. One peds pt had diagnosis of NF1. Two peds pts were found to have DICER1 mutations. One peds pt with DICER1 mutation had pleural pulmonary blastoma diagnosed at Age 4 and subsequently developed GYN RMS at age 14. In the adult population, all tumors with genomic testing demonstrated a low TMB and MSI-stable status. Of the adults with genomic data, 2 had negative testing, 1 pt had PAX3-FOXO1 fusion, two pts with TP53 mutation, 1 pt with germline DICER1 mutation, and 1 pt with CHEK2 and PIK3CA mutations.

Conclusion: In this retrospective analysis conducted at a single institution, it was found that RMS in pediatric pts originating from GYN sites exhibit markedly superior prognosis compared to adults. This is primarily due to significantly longer mPFS and mOS observed in pediatric pts. The disparity in outcomes can be attributed to the fact that 6 of 9 pediatric pts were diagnosed with IRSG stage I at the time of presentation, whereas only 4 of 13 adult pts in this cohort presented with IRSG stage I. In the IRSG stage IV cohort 6 of 13 adult pts had a mOS of only 0.4 years whereas in the two pediatric pts with SIV disease the mOS was a striking 13.6 years. A noteworthy genomic finding in this study was the identification of DICER1 mutation, which was present in three pts within the cohort.