Robinson, Steven I.

Perioperative radiation therapy (RT) has been associated with reduced local recurrence in patients with retroperitoneal sarcomas (RPS); however, selection criteria remain unclear. We hypothesized that perioperative RT would improve survival in patients with RPS and would be associated with pathological factors. The National Cancer Database (NCDB) from 2004 to 2012 was reviewed for patients with nonmetastatic RPS undergoing curative intent resection. Tumor size was dichotomized at 15 cm based on 8th edition American Joint Committee on Cancer (AJCC) staging. Patients with the highest comorbidity score were excluded. Unadjusted Kaplan–Meier and adjusted Cox proportional hazards modeling analyzed overall survival (OS). Multivariable logistic regression modeled margin positivity. A total of 2,264 patients were included; 727 patients (32.1%) had perioperative radiation in whom 203 (9.0%) had radiation preoperatively. Median (IQR) RPS size was 17.5 [11.0–27.0] cm. Histopathology was high grade in 1048 patients (43.7%). Multivariable analysis revealed that perioperative radiation was independently associated with decreased mortality (HR 0.72, 95% confidence intervals (CIs) 0.62–0.84,p<0.001), and preoperative RT was associated with reduced margin positivity (HR 0.72, 95% CI 0.53–0.97,p=0.032). Stratified survival analysis showed that radiation was associated with prolonged median OS for RPS that were high-grade (64.3 vs. 43.6 months,p<0.001), less than 15 cm (104.1 vs. 84.2 months,p=0.007), and leiomyosarcomatous (104.8 vs. 61.8 months,p<0.001). Perioperative radiation is independently associated with decreased mortality in patients with high-grade, less than 15 cm, and leiomyosarcomatous tumors. Preoperative radiation is independently associated with margin-negative resection. These data support the selective use of perioperative radiation in the multidisciplinary management of RPS.

TPS11081 Background: AAS is an aggressive soft tissue sarcoma (STS) of endothelial cell origin with an expected median overall survival of 8-12 months. Pazopanib (P) is approved for treatment of advanced STS following progression on chemotherapy. In a retrospective study of 40 AAS patients treated with single agent P the median PFS was 3.1 months and median OS 9.9 months with no complete responses. Endoglin is an essential angiogenic receptor expressed on AAS that is upregulated following VEGF inhibition, and TRC105, an endoglin antibody, given with P produced durable complete responses in AAS patients with median PFS of 5.6 months in refractory patients including those receiving prior P. The TAPPAS trial is the first randomized Phase 3 trial performed in AAS, and was initiated following protocol assistance from the EMA and Special Protocol Assessment from the FDA. Methods: TAPPAS is a randomized multicenter study of TRC105/P vs P alone in the United States and Europe that is actively enrolling cutaneous and non-cutaneous AAS patients and incorporates an adaptive enrichment design. Key inclusion criteria: 0, 1 or 2 prior lines of therapy, ECOG ≤ 1. Primary endpoint is PFS and secondary endpoints include ORR and OS. The initial sample size of 124 patients, followed until 95 PFS events, provides more than 80% power to detect a hazard ratio of 0.55. At the time of interim analysis, projected to occur upon the occurrence of 40 events in approximately 70 patients, the result will be classified as belonging to either the favorable, promising, enrichment or unfavorable zones, based on conditional power. The sample size and PFS events will be unchanged in the favorable and unfavorable zones, and will be increased to a total of 200 patients followed for 170 PFS events in the promising zone. The trial will enroll 100 additional patients, with cutaneous disease only, in the enrichment zone and will follow them until 110 events are observed in the total cutaneous population. An independent DMC will follow the trial for safety and futility. The adaptive design requires the enrollment of fewer patients, preserves type-1 error, and protects power to detect a clinically meaningful survival benefit. (NCT 02979899). Clinical trial information: NCT02979899.

11073 Background: RMS typically occurs in children. Vincristine, Actinomycin and Cyclophosphamide (VAC) based chemotherapy is the current standard. Limited data exist on the frequency of the histologic subtypes and optimal chemotherapy regimen for the treatment of adult patients with RMS. Methods: We retrospectively identified patients ≥18 years with RMS seen at our institution from 2000-2015. The analysis was performed with JMP statistical software. Results: We identified 73 patients, with a median age of 51 (range 18-85 years). The majority of patients were male (40 of 73) and presented with localized disease (59 of 73). Histologic subtypes were as follows: 32% embryonal (E), 27% alveolar (A), 36% pleomorphic (P), and 6% variants (V) (botryoid and spindle cell/sclerosing). The median overall survival (OS) for patients with localized disease was 16.2 months and metastatic disease 9 months. The median OS for patients with localized disease treated with VAC was 20.3 months (4A, 7E, 3P) and VDC (vincristine doxorubicin cyclophosphamide) was 14.1 months (3A, 3E, 2P). For those with localized disease treated with a VAC/actinomycin-based chemotherapy had a median OS of 19.5 months (4A, 9E, 3P) and with a VDC/doxorubicin-based chemotherapy had a median OS of 15.9 months (8A, 5E, 13P, 2V). Conclusions: Adult patients with RMS have an even distribution among the histologic subtypes. Given the small, unbalanced number of patients in each histologic subtype treated with VAC/actinomycin-based or VDC/Doxorubicin-based regimens, the overall survival benefit favoring the use of VAC/actinomycin-based is hypothesis generating and confirmatory studies are needed to truly determine the optional regimen for adult patients with RMS.