Long-Term Feasibility of 13.56 MHz Modulated Electro-Hyperthermia-Based Preoperative Thermoradiochemotherapy in Locally Advanced Rectal Cancer

SIMPLE SUMMARY: We demonstrated that a 13.56 MHz modulated electro-hyperthermia (mEHT) boost is feasible in neoadjuvant treatment for rectal cancer. Herein, we attempted to present the long-term results for this phase 2 trial. Although there are many reports on the usefulness of thermoradiochemotherapy for loco-regional control, so far, only a few cases of survival benefit exist. Thus, this study assessed whether this limitation of hyperthermia could be overcome through the mEHT method featuring an applied energy variable. Following a median follow-up of 58 months for 60 patients, mEHT boost showed comparable results with conventional hyperthermia; potential therapeutic effects were also observed. Moreover, mEHT could be considered a useful tool in combination treatment with radiotherapy owing to its low thermotoxicity and improved treatment compliance. ABSTRACT: We evaluated the effect of 13.56 MHz modulated electro-hyperthermia (mEHT) boost in neoadjuvant treatment for cT3-4- or cN-positive rectal cancer. Sixty patients who completed the mEHT feasibility trial (ClinicalTrials.gov Identifier: NCT02546596) were analyzed. Whole pelvis radiotherapy of 40 Gy, mEHT boost twice a week during radiotherapy, and surgical resection 6–8 weeks following radiotherapy were performed. The median age was 59. The median follow-up period was 58 (6–85) months. Total/near total tumor regression was observed in 20 patients (33.3%), including nine cases of complete response. T- and N-downstaging was identified in 40 (66.6%) and 53 (88.3%) patients, respectively. The 5-year overall and disease-free survival were 94.0% and 77.1%, respectively. mEHT energy of ≥3800 kJ potentially increased the overall survival (p = 0.039). The ypN-stage and perineural invasion were possible significant factors in disease-free (p = 0.003 and p = 0.005, respectively) and distant metastasis-free (p = 0.011 and p = 0.034, respectively) survival. Tumor regression, resection margin status, and other molecular genetic factors showed no correlation with survival. Although a limited analysis of a small number of patients, mEHT was feasible considering long-term survival. A relatively low dose irradiation (40 Gy) plus mEHT setting could ensure comparable clinical outcomes with possible mEHT-related prognostic features.