The 2-year Results of Phase II Clinical Trial of Brachytherapy with Single-Channel Applicator For Cervical Carcinoma

Abstract

To evaluate whether the patent single-channel applicator( China Patent number:200710050108.1), which was modified from the traditional tandem applicator and wrapped with an oval-shield alloy around the source channel, has the same clinical efficacy and safety as the standard Fletcher-type applicator in the high-dose-rate brachytherapy for carcinoma of the cervix. This was a single blind, prospective, parallel randomized trial. This trial was registered in the Chinese Clinical Trial Registry (No. ChiCTR-TRC-12002321). All the eligible patients were randomized by random computer generation to 1 of 2 treatment groups: the Fletcher applicator group or the patent single-channel applicator group. Patients in both groups were treated with concurrent cisplatin chemotherapy and external beam radiotherapy(EBRT) followed by HDR brachytherapy (not includingⅡa1). Whole pelvis irradiation was given with 6-MV photons via a four-field box variants or anterior and posterior parallel fields. The standard prescribed dose was 46 to 50 Gy, consisting of 23 to 25 fractions 5 to 6 weeks apart. Five to six fractions with a dose of 7 Gy per fraction of intracavitary brachytherapy at point A once a week were designed for all patients after the third week of pelvic irradiation. This regimen gives a total equivalent dose in 2-Gy fractions (EQD2) of 80-90 Gy to Point A. Chemotherapy was given with intravenous cisplatin 40 mg/m2 once a week during the EBRT. The acute toxicities and the late toxicities were evaluated according to the RTOG grading scale. The Kaplan-Meier analysis was used to compare the overall survival (OS), the Progression-Free-Survival (PFS) and the locoregional failure-free survival (LRFFS). From December 1st 2011 to February 2017, 299 patients with pathologically confirmed International Federation of Gynecology and Obstetrics (FIGO 2009) stage Ⅰb2-Ⅳa carcinoma of the cervix were randomly assigned to the Fletcher applicator group(n=150) and the single-channel group (n=149). All but eight patients were treated with concurrent chemoradiotherapy. Up to February 2019, all the patients had achieved a minimum follow-up of 2 years. The 2-year OS, PFS and LRFSS was 81.4%, 77.7% and 79.5% for the Fletcher group, and for the single-channel group was 88.2%, 83.6% and 87.0%, respectively. The seriousness of acute treatment-related toxicities was similar in the two groups. The cumulative rate of late rectal complications for Grade 3-4 in the Fletcher group and the single-channel group was 4.0% and 5.4%, respectively. The cumulative rate of Grade 3-4 bladder complications was 1.3% for the Fletcher group and 0.7% for the single-channel group. The 2-year results of our study shows that the patent single-channel intracavitary applicator may be able to provide a protection for the rectum and bladder, and seems to have the same clinical efficacy as the standard Fletcher type three-channel applicator in the high-dose-rate brachytherapy for carcinoma of the cervix.