Combination treatment of trans-arterial chemo-embolisation, radiotherapy and hyperthermia (CERT) for hepatocellular carcinoma with portal vein tumour thrombosis: Interim analysis of prospective phase II trial

Abstract

Objectives This study evaluated the objective response to and toxicity of trans-arterial chemo-embolisation (TACE) followed by radiotherapy and hyperthermia (CERT) in hepatocellular carcinoma patients with portal vein tumour thrombosis. Methods The study design was a single-centre prospective phase II trial. Patients were first treated with TACE, with the first hyperthermia session 1 week later. Respiration-gated radiotherapy (RT) was delivered in 10 fractions of 3-5 Gy after another week. Six sessions of hyperthermia were delivered twice a week according to an energy escalation protocol. Response evaluation was planned at 1 month after RT completion using the modified Response Evaluation Criteria in Solid Tumors (RECIST). Toxicity was determined using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Results Interim analysis was conducted on patients enrolled from October 2013 to November 2014. During this period, 46 patients (90.2%) who received at least one hyperthermia session were eligible and enrolled. Median follow-up was 6.7 months (range 2.0-15.0 months). Complete response was observed in 10 (21.7%) patients and partial response in 27 (47.8%). Most toxicities were grade I or II. One death was related to severe pneumonia of unknown cause in the left lung and one patient could not complete planned treatment because of continuous elevation of bilirubin after TACE. Late, asymptomatic gastroduodenal toxicities were noticed in 13 (28.3%) patients. Conclusion Preliminary evaluation of CERT showed a promising response rate with acceptable toxicities.

Combination treatment with transarterial chemoembolization, radiotherapy, and hyperthermia (CERT) for hepatocellular carcinoma with portal vein tumor thrombosis: Final results of a prospective phase II trial

“…PVTT was confirmed on computed tomography (CT) or magnetic resonance imaging (MRI) with the characteristic enhancement pattern of a portal venous intraluminal lesion. Detailed inclusion or exclusion criteria of the present study were described in our previous article [ 23 ].…”

“…Based on the synergistic effects of RT and hyperthermia, we performed a prospective phase II trial evaluating the effectiveness and safety of TACE followed by RT and hyperthermia (CERT) in patients with HCC and PVTT. We previously reported initial outcomes focusing on the safety of this treatment [ 23 ].…”

Evidence based tools to improve efficiency of currently administered oncotherapies for tumors of the hepatopancreatobiliary system

“…Combining transcatheter arterial chemoembolization, radiotherapy and hyperthermia[ 43 , 44 ], conformal radiotherapy with hyperthermia[ 20 ], and mEHT with sorafenib[ 42 ] or traditional Chinese herbal remedy therapy[ 59 ] were shown to improve the normalization of laboratory results, disease control rate, progression-free and overall survival, and 1-year recurrence and mortality rates. Results of the CERT[ 43 , 44 ] study supplement the above with the following: (1) radiotherapy related gastroduodenal toxicity ( e.g.…”

“…Combining transcatheter arterial chemoembolization, radiotherapy and hyperthermia[ 43 , 44 ], conformal radiotherapy with hyperthermia[ 20 ], and mEHT with sorafenib[ 42 ] or traditional Chinese herbal remedy therapy[ 59 ] were shown to improve the normalization of laboratory results, disease control rate, progression-free and overall survival, and 1-year recurrence and mortality rates. Results of the CERT[ 43 , 44 ] study supplement the above with the following: (1) radiotherapy related gastroduodenal toxicity ( e.g. , ulcers, gastroduodenitis, and others) were significantly lower in the hyperthermia cohort; and (2) patients with better tolerance for higher power hyperthermia had the same treatment response rate and survival, suggesting that an increased power output level did not adds to treatment efficacy.…”

Immunogenic Effect of Hyperthermia on Enhancing Radiotherapeutic Efficacy

“…As the hyperthermia technology and equipment developed, various types of non-invasive hyperthermia treatment methods and according outcomes were suggested in recent studies [ 135 ]. In recent decades, hyperthermia was delivered through radiofrequency-, microwave-, and electromagnetic-capacitive hyperthermia, with highly sensitive temperature control capacity [ 136 , 137 , 138 ]. The safety of non-invasive hyperthermia treatment was proven in recent studies [ 139 , 140 ].…”