Hyperthermia Combined with Concurrent Radiochemotherapy for 373 Patients with Cervical Cancer Stage IB-IV

Abstract

Hyperthermia (HT) is a commonly used approach in tumor patients, but the efficacy was still uncertain on cervical cancer (CC) treatment. This study was to evaluate if HT combined with concurrent radiochemotherapy (RCT) could render a better survival in CC patients with International Federation of Gynecology and Obstetrics (FIGO) stage IB-IV, and did not increase treatment related toxicity. This study was conducted between 2009 and 2013 in CC patients. Patient eligibility criteria included: (1) age between 25-70 years old; (2) Karnofsky ≥ 70; (3) FIGO stages IB-IV; (4) no prior RT, CT or surgery; (5) histologically confirmed cervical squamous carcinoma; (6) no RT and CT contraindications, no HT contraindications (no cardiac pacemaker, no body metal); (7) normal blood routine, liver and renal function, no vital organ function failure; (8) no double primary cancer (no malignancy except cervical cancer). Patients were randomly assigned into two treatment groups according to a computer-generated random number list: RCT and RCT+HT (RCHT). All patients were treated with external beam radiotherapy (EBRT), 1.8–2.0Gy/fraction per day, 5 days per week, to a total dose of 50.4 or 50Gy. A High-Dose-Rate intracavitary brachytherapy (HDRICB) application delivering a further dose of 5Gy/fraction, 4 or 5 fractions, twice every week, to a total dose of 20∼25Gy to point A. One week after the first EBRT, all patients were treated with cisplatin (PDD) and 5-fluorouracil (5-Fu) regimen (PF): PDD 30 mg/m2, d1-3; 5-Fu 350mg/m2, d1-5. HT was delivered after PF regimen in RCHT group using Radio Frequency HT machine. Temperature was controlled above average 40.5°C (range from 39.5∼41.5°C) for 60 minutes, twice a week, to a total of 6 fractions. Primary end points were 5-year overall survival (OS) and late toxicity. Secondary end points included local-regional relapse (LRFS) and acute toxicity. Analysis was done by per protocol approach. 373 patients completed treatment and were analyzed. 5-year overall survival (OS) in RCHT group (81.9%) was better than that in RCT group (72.3%) and the log-rank test showed statistically significant difference (p = 0.040). Univariate and multivariate COX regression analysis for 5-year OS showed statistically significant difference (p = 0.043, p = 0.045, respectively). 5-year local relapse-free survival (LRFS) in RCHT (86.8%) was also better than that in RCT (82.7%), but the difference was not significant. Acute or late toxicity was not significantly different between two groups. Advanced FIGO stage and larger tumor size showed higher risk of death and relatively poor prognosis in univariate and multivariate analysis. HT combined to RCT yielded a better 5-year OS in CC without increasing treatment related toxicity. Therefore, hyperthermia will be one of the most effective additional treatments. FIGO stage and tumor size were independent prognostic factors in CC.