(P 201) LOCAL CONTROL AND SURVIVAL OUTCOMES IN PEDIATRIC NON-RHABDOMYOSARCOMA SOFT TISSUE SARCOMA: THE MAYO CLINIC EXPERIENCE

Objective: Pediatric patients with non-rhabdomyosarcoma soft tissue sarcoma (NRSTS) undergo aggressive multimodality treatment at our institution. This includes external beam radiation (EBRT), with intra-operative (IORT) or brachytherapy boost for cases of anticipated suboptimal tumor resection to target residual disease and spare nearby organs at risk. This single institutional analysis of outcomes in pediatric patients treated for NRSTS over the last three decades explored factors that may be associated with local control and survival.

Methods: Pediatric patients (≤18 years old) diagnosed with NRSTS between 10/1990 and 11/2021 who received radiation therapy (RT) at our institution were retrospectively identified. Overall Survival (OS) and disease-free survival (DFS) analysis were performed for the entire cohort using the Kaplan Meier method from the start of RT. Cumulative incidence of local and distant failure were estimated, and univariate analysis was conducted to assess for variable associations with oncologic endpoints. Secondary malignancies were considered RT-associated if they arose in a previously irradiated field.

Results: Fifty-one patients with 14 different NRSTS histologies were included, most commonly synovial sarcoma (14/51, 27%) and fibrosarcoma (8/51, 16%). Median age at diagnosis was 14 years (range: 0.1-18.0). Limbs were the most common primary tumor site (33/51, 65%) followed by pelvis (6/51, 12%). Median tumor size was 6.0 cm (range:1.0-18.0). Eighty percent of tumors were T1 or T2 (per AJCC 8th Edition). At presentation, 46 (90%) had localized disease. Most patients underwent surgery (49/51, 96%), with an R0 resection performed in 32 (65%). All patients received EBRT (median EQD2 50 Gy, range 42.4-76.9). Preoperative RT was delivered in 22 (43%). Brachytherapy or IORT boost was used in 21 (41%) (mean EQD2 24.5 Gy). Chemotherapy was administered in 34 (66.7%).

With a median follow up of 5.7 years, OS at 2 and 5 years was 85.0% (95% CI 75.2-95.9%) and 70.7 % (95% CI 56.6-86.6%), respectively. DFS at 2 and 5 years was 70.5% (95% CI 58.2-84.8%) and 67.9% (95% CI 53.4-82.8%), respectively. Local failure occurred in 6 patients, all within 1.4 years of RT. Three (50%) of these had positive surgical margins. The 2-year local failure rate was 12.8% (95% CI 6.1-27.1). The EBRT alone group was at a non-significant increased risk of local failure compared to EBRT+boost: 2-year incidence 18.1% vs. 5.26% respectively (HR 3.67, p=0.24). In patients treated with EBRT alone, 3 of 13 with positive surgical margins eventually had local recurrence (23%). In the EBRT+ boost group, 2 had positive margins, neither with local recurrence. Overall, there was a non-significant increased risk of local failure at 2 years for those with positive margins compared to negative margins: 21.0% vs. 6.8% respectively (HR 3.80, p=0.14). On univariate analysis, positive margins were associated with worse OS compared with negative margins (2-year OS 71.4% vs. 93.1%, 5-year OS 47.6% vs. 80.2%, p=0.02). Four of 8 (50%) secondary malignancies were RT-associated, with a median time to diagnosis of 7.5 years.

Conclusion: Our results demonstrate aggressive multimodality therapy for the treatment of pediatric NRSTS results in 5-year OS and DFS of approximately 70%. Obtaining a negative surgical margin is essential to optimize local control and survival outcomes in this population. Though statistically not significant, patients who receive an RT boost may have a lower risk of local failure. Future efforts should focus on identifying the higher risk patients most likely to benefit from an RT boost, especially given the prevalence of secondary cancers in this population.