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Updated: Apr 7, 2026
Establishment of a Primary Culture of Patient-derived Soft Tissue Sarcoma
Published on: April 11, 2018
Phase 1 adaptive dose-finding study of neoadjuvant gemcitabine combined with radiation therapy for patients with
William W Tseng1,2, Shouhao Zhou3, Christina A To4
1Section of Surgical Oncology, Department of Surgery, Keck School of Medicine, University of Southern California, Los Angeles, California.
Background:
This study was performed to determine the maximum tolerated dose (MTD) of gemcitabine given concurrently with preoperative, fixed-dose external-beam radiation therapy (EBRT) for patients with resectable, high-risk extremity and trunk soft tissue sarcoma (STS).
Methods:
Gemcitabine was administered on days 1, 8, 22, 29, 43, and 50 with EBRT (50 Gy in 25 fractions over 5 weeks). The gemcitabine MTD was determined with a toxicity severity weight method (TSWM) incorporating 6 toxicity types. The TSWM is a Bayesian procedure that choses each cohort's dose to have a posterior mean total toxicity burden closest to a predetermined clinician-defined target. Clinicopathologic and outcome data were also collected.
Results:
Thirty-six patients completed the study. According to the TSWM, the gemcitabine MTD was 700 mg/m(2). At this dose level, 4 patients (24%) experienced grade 4 toxicity; no toxicity-related deaths occurred. All tumors were resected with microscopically negative margins. Pathologic responses of >90% tumor necrosis were achieved in 17 patients (47%); 14 (39%) had complete responses. With a median follow-up of 6.2 years, the 5-year locoregional recurrence-free survival, distant metastasis-free survival, and overall survival rates were 85%, 80%, and 86%, respectively.
Conclusions:
The TSWM combines data from qualitatively different toxicities and can be used to determine the MTD for a drug given as part of a multimodality treatment. Neoadjuvant gemcitabine plus radiation therapy is feasible and safe in patients with high-risk extremity and trunk STS. Major pathologic responses can be achieved, and after complete resection, long-term clinical outcomes are encouraging.
