This article is more than 5 years old. Information may no longer be current.
Radiotherapy with transarterial chemoembolization extends survival for certain patients with advanced hepatocellular carcinoma
Click Here to Manage Email Alerts
A combination of transarterial chemoembolization and external beam radiotherapy prolonged PFS and OS among patients with advanced hepatocellular carcinoma with macroscopic vascular invasion, according to results of a randomized clinical trial.
“The results of this study represent a significant advance in addressing an urgent unmet need in treating patients with advanced HCC,” Sang Min Yoon, MD, PhD, of the department of radiation oncology in Asan Liver Center at Asan Medical Center in Seoul, South Korea, and colleagues wrote. “Our study may also be significant in that it is one of the few randomized clinical trials conducted specifically for patients with HCC showing macroscopic vascular invasion; previous trials for patients with advanced HCC included patients showing macroscopic vascular invasion as a subgroup.”
Earlier clinical trials demonstrated radiotherapy can lead to sustained local control and serve as an alternative treatment option for patients with HCC. Observational studies have shown the combination of radiotherapy and transarterial chemoembolization (TACE) improved response and survival rates.
Yoon and colleagues studied the safety and efficacy of this combination compared with sorafenib (Nexavar, Bayer) among patients with HCC and macroscopic vascular invasion.
In a single-center, open-label trial, researchers randomly assigned 90 treatment-naive patients (median age, 55 years; men, n = 77) with liver-confined cancer to 400 mg sorafenib twice daily (n = 45) or TACE every 6 weeks plus radiotherapy within 3 weeks of initial TACE (n = 45).
All participants presented with portal vein invasion of HCC and Child-Pugh class A liver function, and 78.9% had multiple lesions.
Twelve-week PFS by intention-to-treat analysis served as the primary endpoint.
Crossover was allowed upon disease progression.
The mean daily dose of sorafenib was 739 mg. Fourteen of 44 patients who received sorafenib required dose modifications due to adverse events. The median number of TACE procedures was four (interquartile range[IQR], 3-4). The median dose of radiotherapy within 3 weeks after the first TACE procedure was 40 Gy (IQR, 30-45 Gy) in 2.5- to 3-Gy doses per fraction.
Patients who received TACE plus chemotherapy achieved significantly higher rates of 12-week PFS (86.7% vs. 34.3%; P < .001) and radiologic response at 24 weeks (33.3% vs. 2.2%; P < .001). They also experienced longer median time to disease progression (31 weeks vs. 11.7 weeks; P < .001) and longer median OS (55 weeks vs. 43 weeks; P = .04).
At 48 weeks, a higher percentage of those who received TACE plus chemotherapy remained alive (55.4% vs. 44.4%).
At last follow-up, 18 patients — 12 in the combination group and six in the sorafenib group — remained alive.
All living patients who received sorafenib switched to TACE plus radiotherapy due to disease progression.
Nearly all patients in both groups experienced adverse events (93.2% for sorafenib and 91.1% for combination therapy). Five patients in each group experienced serious adverse events.
One patient in the sorafenib group discontinued treatment due to severe mucositis. One patient in the combination group experienced transient grade 3 elevation in total bilirubin level; however, the patient discontinued treatment due to lung metastasis.
Limitations of the study included an opportunity for bias due to the open-label design of the trial, infeasibility of blinded assessment, and the fact 84.4% of patients had hepatitis B virus infection-associated HCC.
“The treatment strategy described may not be extrapolatable to patients with HCC not associated with hepatitis B virus,” the researchers wrote.
Although the results are positive, the outcomes and study design present notable caveats, according to Khashayar Farsad, MD, PhD, FSIR, associate professor of interventional radiology in the Charles T. Dotter department of interventional radiology at Oregon Health & Science University, and colleagues wrote in an accompanying editorial. These included a small sample size, presence of hepatitis B virus-related liver disease and a shorter median time to progression in the sorafenib arm compared with other clinical trials.
“Thus, the relevance of the findings to other patient populations must be made cautiously,” Farsad and colleagues wrote.
However, the data from Yoon and colleagues highlight the need for additional prospective trials to validate the findings in other patient populations.
“Potentially, the future for HCC therapy will continue to show that multimodality treatments will outperform single-treatment paradigms,” Farsad and colleagues wrote. “For those of us managing these patients daily in our clinics and procedure suites, it is encouraging to know there is hope ahead.” – by Melinda Stevens
Disclosures: One author reports advisory roles with and research funding from Bayer HealthCare and Gilead Sciences. The other study authors and the editorial authors report no relevant financial disclosures.
Perspective
Back to Top
The authors should be congratulated for successfully conducting a prospective randomized trial in this high-risk population of patients with HCC and macroscopic vascular invasion, historically an ominous finding associated with hepatic decompensation and rapid progression. This study demonstrated that among these patients, locoregional therapy with TACE and early radiation improves PFS and OS over systemic therapy with sorafenib.
The combination of regional therapy with selective TACE and tumor thrombus-directed radiotherapy overcomes the potential limitations of each modality, allowing for intensification of both regional and local therapy. In this patient population, this resulted in longer OS (55 vs. 43 weeks; P = .04) despite a 90% crossover rate in the sorafenib arm. Remarkably, 11% of patients treated with TACE plus radiotherapy on this trial were sufficiently downstaged to undergo resection.
Caveats include the small number of patients, all from Asia with predominance of hepatitis B. Confirmation in a larger trial can better establish the preference for early locoregional therapy among patients with HCC with macroscopic vascular invasion, rather than proceeding to systemic therapy. Further work should determine the relative contribution of radiotherapy and TACE because radiotherapy alone may be just as effective. Radiotherapy with or without sorafenib is being investigated in RTOG 1112. Additionally, combination of immunotherapy with local and regional therapies should be investigated. This is indeed an exciting time in the treatment of HCC.
Click Here to Manage Email Alerts