Radiation Underused as 'Bridge' to Transplant in Liver Cancer

Roxanne Nelson, RN, BSN

October 27, 2021

CHICAGO — Only 4% of patients with liver cancer who are awaiting transplant undergo external-beam radiotherapy (EBRT), even though this is a safe and effective bridging therapy. It is greatly underutilized compared to other liver-directed therapies, say researcher who presented the new findings.

"This highlights a real-world gap in the treatment armamentarium for hepatocellular carcinoma [HCC]," commented Nima Nabavizadeh, MD, associate professor of radiation oncology and residency program director at the Oregon Health and Science University, Portland, Oregon.

He was speaking here at the American Society for Radiation Oncology (ASTRO) 2021 Annual Meeting.

These new data suggest there is reluctance within transplant programs to utilize radiotherapy as a bridging therapy prior to liver transplant, commented Hyun Kim, MD, chief, GI Service, Department of Radiation Oncology, Washington University School of Medicine and the Siteman Cancer Center, St. Louis, Missouri.

"This is despite 10-year-old data from Princess Margaret and Toronto General Hospital showing that external-beam radiation is a safe and feasible bridging therapy," he said. "More modern data from the same institutions indicate that patients bridged with stereotactic body radiotherapy ablative radiation doses delivered with high conformality have similar survival as patients bridged with radiofrequency ablation."

Kim also noted that even after transplant, rates of intrahepatic recurrence can be as high as 10%. Approximately 60% of patients experience recurrence of any type within 3 years.

"Nonablative local therapies leave viable disease, which may permit metastatic progression while the patient awaits transplant," he told Medscape Medical News. This new analysis highlights the need for well-designed clinical trials with modern endpoints to evaluate which bridging therapy is most beneficial for the patient, he added.

In this current "era of radiomics, deep learning, and liquid biopsies, we have unprecedented tools and responsibility to ensure that our practice continues to improve in a data-centric fashion and not remain paused in the paradigm of a previous era," Kim said.

A Leading Cause of Death Worldwide

HCC is a leading cause of cancer death worldwide, and the incidence is rising within the United States. Transplant is often the best option for long-term survival for patients with localized HCC and advanced cirrhosis, Nabavizadeh told the meeting.

Because patients often have to wait months to over a year for a transplant, many patients receive liver-directed bridging therapy to prevent tumor growth or spread and to maintain their eligibility for transplant, he explained.

These bridging therapies include thermal ablation procedures, transarterial chemoembolization (TACE), and Y-90 radioembolization, as well as EBRT.

To investigate how these therapies were being used, Nabavizadeh and colleagues conducted a retrospective study in which they analyzed data from the United Network for Organ Sharing, a nonprofit organization that manages the only national liver transplant waiting list in the United States.

They identified patients on the transplant list who had applied for Model of End-Stage Liver Disease (MELD) exceptions so as to be prioritized on the waiting list.

A total of 18,447 HCC patients submitted MELD exception applications during the study period (October 2013 to June 2020). More than half of these patients (n = 11,171; 60.6%) received a transplant. After submitting the exception application, the median time for receiving a transplant was 7 months.

Of the total group, 15,759 (85.4%) patients received liver-directed therapy while waiting for the transplant, but only 658 patients (3.6% of the overall cohort) received EBRT, either alone or in combination with another therapy.

"The majority of patients received chemoembolization, and ERBT represents a very small percentage," Nabavizadeh said.

During the study period, the use of transarterial chemoembolization decreased. It has largely been replaced by thermal ablation and Y-90 radioembolization. The analysis also showed that the use of EBRT had increased over the past several years, but its utilization still remained well below that of the other therapies.

TACE was the most utilized therapy. It was used for 39.6% of patients, followed by thermal ablation (12.8%) and radioembolization (8.7%). Almost a quarter of patients (22.2%) received a combination of non-EBRT therapies.

"We found that EBRT use significantly differed by region," Nabavizadeh commented. The highest usage (8.7%) was in Great Lakes states. In the Southeast, it was used for only 1.7% patients.

No statistical differences were observed in clinicopathologic factors between the patients who received EBRT and those who did not.

Transplant Is Curative

Transplant is curative both for cancer and underlying cirrhosis, but patients may experience disease progression while waiting for transplant, noted Jessica Karen Wong, MD, MEng, assistant professor, Department of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania, who was approached for comment.

"Radiation, specifically, stereotactic body radiation therapy (SBRT), is a safe and effective bridging therapy but was only used in a small minority of eligible patients in this national database," she said. "Although the use of radiation as bridging therapy is increasing over time, it continues to be underutilized. Increasing the use of radiation provides an opportunity to improve patient care for hepatocellular carcinoma patients awaiting a liver transplant."

Nabavizadeh and Wong have disclosed no relevant financial relationships. Kim has received research funding and speaker honorarium from Varian and ViewRay.

American Society for Radiation Oncology (ASTRO) 2021 Annual Meeting: Presented October 24, 2021. Abstract 2078.

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