Neoadjuvant Hypofractionated Radiotherapy and Chemotherapy in High-Grade Extremity Soft Tissue Sarcomas: Phase 2 Clinical Trial Protocol

Abstract

Background: Neoadjuvant radiotherapy (RT) and chemotherapy are applied to large, high-grade extremity soft tissue sarcomas to treat metastatic disease earlier and sterilize margins to perform R0 surgery. However, preoperative RT increases wound complication rates (rWC), delaying adjuvant chemotherapy or preventing it from being administered altogether. Hypofractionated neoadjuvant RT can be offered in this situation, concomitant to chemotherapy, allowing patients to receive chemotherapy as a preoperative treatment in less time with an acceptable rWC.

Objective: The objectives of this protocol are to maintain low rates of morbidity and mortality compared to literature data, improving survival rates and avoiding poor responders from receiving unnecessary adjuvant chemotherapy.

Methods: This noncontrolled, single-arm, phase 2 clinical trial recruited patients aged over 18 years with high-grade soft tissue sarcomas in the girdles or extremities. Three neoadjuvant chemotherapy (ifosfamide and doxorubicin) cycles were administered with 5 days of hypofractionated RT (25 Gy in 5 fractions) in the second cycle of doxorubicin only. Viable cell counts in the surgical specimen were measured, and patients in whom this value was less than 30% continued to receive an additional 3 full chemotherapy cycles as adjuvant treatment.

Results: Primary endpoint will be disease-specific survival measured by the evaluation of local and distant recurrence after neoadjuvant treatment. The secondary endpoints will be wound complication and amputation rates and chemotherapy toxicity. We also will record the viable cell rates after the schema and correlate this with survival.

Conclusions: As seems with other solid tumors, hypofractionated RT has comparable efficacy and safety as conventional fractionation. This modality of treatment combined with chemotherapy could increase the pathological response rates and improve the outcomes of select patients.

Trial registration: ClinicalTrials.gov NCT02812654; https://clinicaltrials.gov/ct2/show/NCT02812654 (Archived by WebCite at http://www.webcitation.org/6qC3puBOy).

Keywords: dose fractionation; hypofractionated doses; neoadjuvant treatment; radiotherapy; soft tissue sarcoma; toxicity.

Figure 1

Scheme and treatment schedule illustration.