Background and methods

We examined the outcomes of synovial sarcoma (SS) patients in a national database. We identified 1,189 patients from the Surveillance, Epidemiology, and End Results (SEER) database with data on site and extent of surgery. We excluded patients diagnosed before 1990, <18 years, or lacking pathologic confirmation. Using Kaplan-Meier and Cox proportional hazards analyses, we determined predictors of overall (OS) and disease-specific survival (DSS).

Results

The mean age was 41, 49.3% were female, and 82.2% were white. Radiotherapy (RT) was administered to 57.5%. On multivariable analysis, age at diagnosis, sex, race, anatomic site, SEER summary stage, tumor size, surgery type, and RT predicted OS. Similar predictors of DSS were identified. The hazard ratio (HR) for OS was 0.65 (95% CI 0.48-0.88) in favor of RT and 0.62 (95% CI 0.45-0.86) for DSS. Five-year OS improved 8.4 ± 1.0% with RT (P=0.003), and five-year DSS improved 7.7 ± 1.0% with RT (P=0.015).

Conclusions

In the largest study to date examining the role of RT in synovial sarcoma, we observed that RT was associated with a statistically significant improvement in oncologic outcome among SS patients. These data support the use of RT in the multi-modality treatment of patients with SS.

Background

Despite effective local therapy with surgery and radiotherapy (RT), ~50 % of patients with high-grade soft tissue sarcoma (STS) will relapse and die of disease. Since experimental data suggest a significant synergistic effect when antiangiogenic targeted therapies such as sorafenib are combined with RT, we chose to evaluate preoperative combined modality sorafenib and conformal RT in a phase I/II trial among patients with extremity STS amenable to treatment with curative intent.

Methods

For the phase I trial, eight patients with intermediate- or high-grade STS >5 cm in maximal dimension or low-grade STS >8 cm in maximal dimension received concomitant sorafenib (dose escalation cohort 1:200 twice daily, cohort 2:200/400 daily) and preoperative RT (50 Gy in 25 fractions). Sorafenib was continued during the entire period of RT as tolerated. Surgical resection was completed 4-6 weeks following completion of neoadjuvant sorafenib/RT. Three sorafenib dose levels were planned. Primary endpoints of the phase I trial were maximal tolerated dose and dose-limiting toxicity (DLT).

Results

Eight patients were enrolled in the phase I (five females, median age 44 years, two high-grade pleomorphic, two myxoid/round cell liposarcoma, four other). Median tumor size was 16 cm (range 8-29), and all tumors were located in the lower extremity. Two of five patients treated at dose level 2 developed DLT consisting of grade 3 rash not tolerating drug reintroduction. Other grade 3 side effects included anemia, perirectal abscess, and supraventricular tachycardia. Radiation toxicity (grade 1 or 2 dermatitis; N = 8) and post-surgical complications (three grade 3 wound complications) were comparable to historical controls and other series of preoperative RT monotherapy. Complete pathologic reponse (≥95 % tumor necrosis) was observed in three patients (38 %).

Conclusion

Neoadjuvant sorafenib in combination with RT is tolerable and appears to demonstrate activity in locally advanced extremity STS. Further study to determine efficacy at dose level 1 is warranted. (ClinicalTrials.gov identifier NCT00805727).