Novel Bridge to Liver Transplant May Improve Upon Standard of Care
Stereotactic Body Radiation Therapy vs Transarterial Chemoembolization
For hepatocellular carcinoma patients awaiting a liver transplant, locoregional treatment as a “bridge” is a standard strategy for reducing tumor progression. The most common approach is transarterial chemoembolization, but a study from a large-volume liver transplant center questions whether it should be the preferred strategy.1
SBRT appears equivalent to TACE at controlling the treated lesion when utilized as a bridge to transplant in Child-Pugh class A/B patients. SBRT may engender less acute toxicity, may better preserve quality of life, and it avoids hospitalizations.— Francis W. Nugent, MD
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At the 2017 Gastrointestinal Cancers Symposium, Francis W. Nugent, MD, a medical oncologist at Lahey Hospital & Medical Center, Burlington, Massachusetts, presented the preliminary findings of a randomized phase II trial that compared transarterial chemoembolization (TACE) with stereotactic body radiation therapy (SBRT) and found SBRT appears to be equivalent in efficacy and potentially advantageous in several ways.
More liver transplants are performed at Lahey than at any other New England medical center, “so this is a problem we are familiar with,” Dr. Nugent said.
Although the most common bridging procedure is TACE, this practice is not backed by level 1 evidence. “Providers can do whatever they want, and in transplant—which is an area as rigid as any in medicine—the idea that you can do whatever you want, without an idea of the advantages and disadvantages of the different approaches, is kind of crazy,” he commented.
There are a number of other bridging strategies, and there is also variation among institutions as to how TACE is performed. Furthermore, while TACE is the general standard of care, it has some disadvantages, including the need for hospitalization and a risk for major morbidity of 0.5% to 3.0%. “This threatens a patient’s eligibility for transplant. If we do a bridge to transplant, and something knocks the patient off the list, that’s a terrible thing,” he said.
SBRT, on the other hand, is seen as having some advantages over TACE. It’s a newer strategy, is performed in the outpatient setting, offers uniform delivery of the damaging agent (as opposed to relying on flow dynamics), and does not directly disrupt the tumor. It may engender fewer acute side effects and reduce the risk for major morbidity, according to Dr. Nugent.
The lack of comparative data led to this single-institution randomized trial of the 2 approaches in 30 patients to date. The primary endpoint was time to residual or recurrent disease. “Most institutions look to maximally ablate the tumor before transplant, so if there’s residual or recurrent disease, it necessitates additional treatment that poses risks,” he explained.
Transplant candidates had to have adequate hematologic and liver parameters, and no more than two malignant tumors. They had to have Child-Pugh class A/B cirrhosis, with scores initially < 8 but extended to < 9 as the study progressed (see sidebar).
Stereotactic Body Radiotherapy vs Transarterial Chemoembolization
- SBRT may offer advantages over TACE as a bridge to liver transplant.
- A randomized, single-institution study of 30 patients showed less chance of residual or recurrent disease following SBRT, as well as fewer side effects, better quality-of-life scores, and no need for hospitalization.
The TACE protocol (n = 17) involved 2 chemoembolization treatments delivered 1 month apart, using doxorubicin drug-eluting beads (investigational in the United States) at 100 mg. Under the SBRT protocol (n = 13), all patients underwent fiducial marker placement, then outpatient radiotherapy every other day for 5 treatments, totaling 40 to 50 Gy. Quality of life was measured by the 36-Item Short Form Health Survey (SF-36) before, during, and 2 weeks after treatment, then every 3 months.
Characteristics were similar between the groups. Both arms were predominantly male with early-stage disease (85%) and a single lesion; more than 50% had hepatitis C viral infection, and most patients had excellent hepatic performance.
Outcomes of the Two Strategies
The median time from screening to treatment was 16.6 days with SBRT and 25.6 days with TACE. Median follow-up posttreatment was 213 and 134 days, respectively. Follow-up time varied considerably, Dr. Nugent explained, “because it all depends on when a liver becomes available for the patient.”
The Child-Pugh score, a prognostic measure used in patients with chronic liver disease, is determined by five clinical measures, including total bilirubin level; serum albumin level; prothrombin time expressed by international normalized ratio, presence of ascites (none, mild, severe); and presence of hepatic encephalopathy (none; grade I–II; grade III–IV). Each clinical measure is assigned 1 to 3 points ranging from least severe (1 point) to most severe (3 points). A total score based on the five clinical measures is used to determine Child-Pugh class of disease (A, B, or C). ■
In the TACE arm, 24% of patients demonstrated residual or recurrent disease, observed at a median time of 83 days from the last treatment (range = 50–141). In the SBRT arm, no patient showed disease progression in the treated area.
Five patients underwent a transplant after SBRT, and two had residual disease. Six patients had a transplant following TACE, and three had residual disease, explant data showed.
Transplants were performed at a median time of 148 days after SBRT and 335 days after TACE. The SBRT arm had a shorter median time to transplant because two of the procedures involved live donors, which shortens the wait time, he explained.
In the SBRT arm, two patients had disease progression outside of the treated lesion, and one developed a second cancer. In the TACE arm, two patients died due to progression outside of the treated area, and one was lost to follow-up.
Toxicity and Quality of Life
Both approaches were well tolerated, but there was a “suggestion” that anorexia, fatigue, nausea, and pain were more frequent with TACE, he said. Also one TACE-treated patient had a “major event”—a portal vein thrombus and liver infarction. The patient was still able to undergo transplant, “but it was close,” Dr. Nugent said.
Quality-of-life scores, for both physical and mental scales of the SF-36, clearly favored SBRT, as “there was less of a diminution in the SBRT arm compared with TACE,” he said. Physical change from baseline was –0.7 with SBRT and –2.7 with TACE, whereas mental change was –0.6 and –2.6, respectively.
“These [differences] are statistically unlikely to have happened as a result of chance, but whether they are clinically meaningful is uncertain,” Dr. Nugent commented.
He concluded, “These are small numbers, but SBRT appears equivalent to TACE at controlling the treated lesion when utilized as a bridge to transplant in Child-Pugh class A/B patients. SBRT may engender less acute toxicity, may better preserve quality of life, and it avoids hospitalizations.” ■
Disclosure: Dr. Nugent has received support from Varian Medical Systems.
1. Nugent FW, Flacke S, Qamar A, et al: A randomized phase II study of individualized stereotactic body radiation therapy versus trans-arterial chemoembolization as a bridge to transplant in hepatocellular carcinoma. 2017 Gastrointestinal Cancers Symposium. Abstract 223. Presented January 19, 2017.
This was a very well done study, with the limitations that the authors acknowledged. We need now to look at SBRT on a larger scale, to see if it is feasible outside the realm of one institution.— Ghassan K. Abou-Alfa, MD
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Ghassan K. Abou-Alfa, MD, a...