Rethinking the Role of Radiation Therapy in the Treatment of Unresectable Hepatocellular Carcinoma: A Data Driven Treatment Algorithm for Optimizing Outcomes

Abstract

Hepatocellular carcinoma (HCC) is the second most common cause of cancer death worldwide, with a majority of HCC patients not suitable for curative therapies. Approximately 70% of initially diagnosed patients cannot undergo surgical resection or transplantation due to locally advanced disease, poor liver function/underlying cirrhosis, or additional comorbidities. Local therapeutic options for patients with unresectable HCC, who are not suitable for thermal ablation, include transarterial embolization (bland, chemoembolization, radioembolization) and/or external beam radiation therapy (EBRT). Regarding EBRT specifically, technological advancements provide a means for safe and effective radiotherapy delivery in a wide spectrum of HCC patients. In multiple prospective studies, EBRT delivery in a variety of different fractionation schemes or in combination with transcatheter arterial chemoembolization (TACE) demonstrate improved outcomes, particularly with combination therapy. The Barcelona Clinic Liver Cancer classification provides a framework for treatment selection; however, given the growing complexity of treatment strategies, this classification system tends to simplify decision-making. In this review, we discuss the current literature regarding unresectable HCC and propose a modified treatment algorithm that emphasizes the role of radiation therapy for Child-Pugh score A or B patients with ≤3 nodules measuring >3 cm, multinodular disease or portal venous thrombosis.

<p>GRK2 Suppresses Hepatocellular Carcinoma Metastasis and Invasion Through Down-Regulation of Prostaglandin E Receptor 2</p>

“…Worldwide, more than 90% of primary liver cancer cases are due to HCC. 23 Its malignancy is high, easy to relapse and metastasis. The incidence and mortality of HCC in recent years are still rising, especially occurs in Eastern and South-Eastern Asia and Western Africa.…”

Combination of Immunotherapy and Radiation Therapy in Gastrointestinal Cancers: An Appraisal of the Current Literature and Ongoing Research

“…In cases where the disease is confined to the liver, liver-directed therapies such as transarterial radioembolization (TARE) or chemoembolization (TACE), radiofrequency ablation (RFA), microwave ablation (MWA), stereotactic body RT (SBRT), or hypofractionated RT can be used as a definitive treatment, bridging therapy, or to downstage transplant eligibility [28]. Fractionated RT has yielded a response rate of 50-90% with a 1-year OS of 50-100%, which has improved with modern SBRT regimens and techniques to a 2-year local control of 70-95% [29].…”

Neoadjuvant radiotherapy for resectable hepatocellular carcinoma with portal vein tumor thrombus: a systematic review

“…Several studies of surgery-based comprehensive treatment such as surgery after radiotherapy (RT) for HCC. RT, which makes unresectable HCC eligible for surgical resection, combined with surgery, may improve these patients’ OS ( 12 , 13 ). Also, RT has emerged as an effective modality for HCC with PVTT ( 14 , 15 ).…”