Phase I Dose-Escalation Study of Stereotactic Body Radiotherapy Boost for Cervical Cancer Unsuitable for Intracavitary Brachytherapy

Abstract

Some patients are ineligible for intracavitary brachytherapy (ICBT) for locally advanced cervical cancer. Stereotactic body radiotherapy (SBRT) could be a good treatment option for such patients. This phase I clinical trial aimed to determine the recommended dose of SBRT boost for ICBT-ineligible, cervical cancer patients. Patients with untreated uterine cervical cancer (clinical stage IB1–IIIB) who were ineligible for ICBT were enrolled. Radiotherapy consisted of whole pelvis radiotherapy (45 Gy in 25 fractions) followed by SBRT. Three dose levels of SBRT (19.5/21/22.5 Gy in 3 fractions), were set; the treatment protocol began at 21 Gy (level 2). The “rolling-six” design study was used to establish the recommended dose of SBRT. Each dose level covered three or six patients. The primary endpoint included dose-limiting toxicity (DLT), defined as occurrence of grade 3 (or worse) non-hematologic adverse effects within 6 months after SBRT. The median follow-up after registration was 17 (range, 8–32) months. Three patients were enrolled in study level 2 (SBRT of 21 Gy); no patient exhibited DLT within 6 months after treatment completion. In study level 3 (SBRT of 22.5 Gy), three patients did not exhibit DLT. While all six patients achieved locoregional control during follow-up, one patient treated with level 2 SBRT experienced distant metastases 14 months after registration. The recommended dose of SBRT boost was 22.5 Gy in 3 fractions. We plan to conduct a phase II multi-center clinical trial using the methodology obtained from the current study.