Meyer, Christian F.

The NCCN Guidelines for Soft Tissue Sarcoma provide recommendations for the diagnosis, evaluation, treatment, and follow-up for patients with soft tissue sarcomas. These NCCN Guidelines Insights summarize the panel discussion behind recent important updates to the guidelines, including the development of a separate and distinct guideline for gastrointestinal stromal tumors (GISTs); reconception of the management of desmoid tumors; inclusion of further recommendations for the diagnosis and management of extremity/body wall, head/neck sarcomas, and retroperitoneal sarcomas; modification and addition of systemic therapy regimens for sarcoma subtypes; and revision of the principles of radiation therapy for soft tissue sarcomas.

Purpose. There are no known effective medical treatments for refractory MPNST. Inactivation of the NF1 tumor suppressor in MPNST results in upregulation of mTOR (mammalian target of rapamycin) signaling and angiogenesis, which contributes to disease progression. We conducted a phase II study for patients (pts) with refractory MPNST combining everolimus (10 mg PO once daily) with bevacizumab (10 mg/kg IV every 2 weeks) to determine the clinical benefit rate (CBR) (complete response, partial response (PR), or stable disease (SD) ≥ 4 months). Patients and Methods. Patients ≥18 years old with chemotherapy refractory sporadic or NF1 MPNST were eligible. Tumor response was assessed after every 2 cycles (the WHO criteria). A two-stage design targeting a 25% CBR was used: if ≥ 1/15 pts in stage 1 responded, enrollment would be expanded by 10 pts, and if ≥ 4/25 patients had clinical benefit, the combination would be considered active. Results. Twenty-five pts, 17 with NF1 and 8 with sporadic MPNST, enrolled. One of 15 pts in stage 1 had clinical benefit. Of 10 additional pts enrolled, 2 had clinical benefit. The median number of completed cycles was 3 (range 1–16). Adverse events were similar to those known for this combination. Conclusion. With a CBR of 12% (3/25), the combination of everolimus and bevacizumab did not reach the study’s target response rate and is not considered active in refractory MPNST.