Photo Credit: Mohammed Haneefa Nizamudeen

Using stereotactic body radiation therapy for hepatocellular carcinoma with multiple lesions appears feasible, with an acceptable risk profile.

Stereotactic body radiation therapy (SBRT) represents a viable option for treating patients with hepatocellular carcinoma (HCC) who have multiple intrahepatic lesions and cirrhosis that come with an “acceptable” liver-related toxicity profile, according to findings published in the Journal of Hepatocellular Carcinoma.

Jacob Hall, MD, and colleagues noted that the number of patients with HCC has grown significantly in recent years. In the past, radiotherapy came with excessive toxicity to non-cancerous tissue, and because of this, little prospective data was available on the treatment’s use in this setting. However, techniques for administering radiation therapy have improved over the years, with SBRT emerging as a technique that comes with an acceptable liver toxicity profile. Still, recurrences and multiple synchronous lesions are common, and most patients have underlying liver disease such as cirrhosis.

“Data evaluating the efficacy and safety of SBRT in cirrhotic patients who have been previously irradiated or have multiple sites within the liver being irradiated simultaneously are very limited,” Dr. Hall and colleagues wrote. “To our knowledge, only two studies have evaluated hepatotoxicity in the setting of re-irradiation using the albumin-bilirubin (ALBI) score, which is more objective than the [Child–Pugh] score. Our goal is to better characterize SBRT-related hepatic toxicity in patients with HCC and underlying cirrhosis who were treated with SBRT to multiple synchronous or metachronous targets.”

Dr. Hall and colleagues performed a retrospective analysis of 25 patients with HCC who received SBRT for at least two synchronous or recurrent liver lesions. They collected patient characteristics, information related to dosing (including cumulative planning target volume), mean liver dose, cumulative volume of liver receiving 15 Gy, cumulative effective volume, and liver-related toxicities as measured with Child-Pugh scores and ALBI score. The researchers used a linear-effects model to examine how multi-target SBRT affected changes in ALBI score.

Patient Characteristics and Outcomes

The study included 25 patients with 56 lesions who were treated at the University of North Carolina Hospitals between January 2010 and December 2022. There were 15 men and 10 women. Nearly all patients (n=24) had cirrhosis, which was diagnosed before the start of radiotherapy. Median follow-up from the start of radiation therapy to final follow-up or death was 29 months (range, 3-55 months). The patients were a median of 67 years old (range, 52-84). All received five or fewer fractions of radiotherapy and had at least two lesions, with a median tumor size of 2 cm (range, 1–5.2 cm). Patients were included in the study even if they had received previous liver-specific treatments, such as surgery, transarterial chemoembolization, radiofrequency ablation, or transarterial radioembolization.

The researchers reported that the median overall survival was 25 months. Out of all tumors, eight were considered local failures following radiotherapy, which occurred a median of 8 months after treatment (range, 4-25 months). Multivariate analysis reportedly found no association between mean liver dose, cumulative volume of liver receiving 15 Gy, cumulative effect volume, or cumulative planning target volume and ALBI score change at the 3-month or 6-month mark following therapy. Sixteen patients saw their ALBI score change at least one point at 3 months or 6 months after radiotherapy.

Impact on Child-Pugh Scores

According to Dr. Hall and colleagues, 13 patients’ Child-Pugh scores worsened by at least one point, and four saw their scores worsen by at least two points by 3 or 6 months. Of these four, three also experienced worsening ALBI scores.

ALBI score worsened by at least one point in 16 patients, and of these, 11 also experienced worsening Child-Pugh scores, the researchers report.

Only those patients whose Child-Pugh scores rose by at least two points experienced nonclassic radiation induced liver disease (RILD), and no patients had liver transaminase elevation that met the criteria for classic RILD. However, 3 months after radiotherapy, a single patient met the criteria for classic RILD by experiencing a rise in alkaline phosphatase to more than double the upper limit of normal levels, according to Hall and colleagues. This person’s Child-Pugh score also worsened by one point.

Eleven of the patients had radiotherapy for multiple lesions in a single course. Of these, five patients (45%) saw their Child-Pugh scores worsen by at least one point, and two (18%) had their scores worsen by at least two points.

Fourteen patients underwent multiple courses of radiotherapy. One-point or greater worsening of Child-Pugh scores occurred in eight of these patients (57%), whereas two patients’ scores (14%) worsened by two points or more, Dr. Hall and colleagues write.

“SBRT to multiple lesions is feasible and does not appear to lead to unacceptable risk of classic or non-classic RILD,” Dr. Hall and colleagues conclude. “The risk when treating multiple synchronous lesions does not appear to be elevated compared to treating multiple lesions in multiple SBRT courses when controlling for treatment volume.”

Key Takeaways

• Data evaluating the use of SBRT in patients with HCC and cirrhosis is limited.
• Dr. Hall and colleagues reported a median overall survival of 25 months among patients who received radiotherapy.
• Using SBRT for HCC with multiple lesions appears feasible, with an acceptable risk profile.