Results from a phase II study from Korea demonstrated high rates of tumor local control, overall survival (OS), and grade 1/2 gastrointestinal and hepatic toxicities in patients who received stereotactic body radiotherapy (SBRT) for unresectable hepatocellular carcinoma (HCC) after incomplete transarterial chemoembolization (TACE).
Won Il Jang, MD
Results from a phase II study from Korea demonstrated high rates of tumor local control, overall survival (OS), and grade 1/2 gastrointestinal and hepatic toxicities in patients who received stereotactic body radiotherapy (SBRT) for unresectable hepatocellular carcinoma (HCC) after incomplete transarterial chemoembolization (TACE).1
The standard treatment for HCC is surgery, by hepatic resection or liver transplantation. Unfortunately, less than 20% of patients are eligible for the procedure. In the remaining patients with inoperable and advanced HCC, TACE has been used. Using TACE alone, however, rarely results in a complete response and recurrence is common. Information about optimal treatment indications, doses, and methods remains limited for SBRT.
The multicenter trial enrolled 73 patients from 6 institutions from January 2012 through April 2015. The trial’s primary endpoint was treatment-related toxicity-free survival, said Won Il Jang, MD, Department of Radiation Oncology, Korea Institute of Radiological & Medical Science (KIRAM) during the 2016 ASTRO Annual Meeting.
Secondary outcomes measured included OS, progression-free survival, intrahepatic recurrence free survival, and local control rate. He noted that several small studies have reported high tumor response and local control rate after SBRT alone or with TACE for inoperable HCC, and in a phase II trial at KIRAM, GI toxicities over 10% were reported.2
In this previous study, the overall response rate was 73% and the 2-year local control rate was reported as 95%. Jang et al reported severe gastrointestinal toxicity of 11% because there was no normal tissue constraint for the gastrointestinal tract and dosage to the gastrointestinal tract was restricted to the lowest levels possible. In addition, the researchers found that the presence of gastroduodenal ulcer before SBRT was significantly influenced by severe gastrointestinal toxicity. These findings prompted this follow-up study.
Patients were enrolled in the trial if they were found to be unsuitable for surgery or local ablation, experienced incomplete response after 1-5 sessions of TACE, had a Child-Pugh score of A5-B7, tumor diameter < 10 cm, and normal liver volume ≥ 700 ml. Exclusion criteria were previous history of abdominal radiation and direct invasion to esophagus, colon, or stomach by HCC.
Patients were a median age of 61 years (44-84), with more men (55) enrolled than women (18). Fifty-three percent of patients had recurrence and for 47% of patients, this was an initial diagnosis. A total of 39 patients had previous treatment before recurrence, with 41% having surgery, 44% having radiofrequency ablation (RFA), and 15% having a combination of surgery and RFA. Only 2 patients received TACE.
Median tumor size was reported as 2.4 cm (1.0-9.9), with 85% of patients having 1 lesion and 15% of patients having 2 lesions. The researchers staged the tumors based on UICC (1-4), BCLC (0-D), and HKLC (I-VB) characteristics, with the majority of patients exhibiting tumors as T1 (45%), BCLC A (51%), and HKLC stage I (85%). Patients underwent esophagogastroduodenoscopy (EGD) before SBRT to evaluate gastroduodenal ulcer.
Individualized radiotherapy doses were delivered at 45-60 Gy for 3 fractions over 14 days, and the interval between fractions was ≥ 48 hours, and according to normal tissue constraints. EGD was carried out before and after SBRT.
Researchers report that after 2 years, OS was 83.5%, progression-free survival (PFS) was 47.2%, and local control was 94 months. After 3 years, OS was reported as 75.1%, PFS was 37.2%, and LC was 89 months. Median follow-up was reported at 19 months (2-42 months).
Kang reported 1 case of severe toxicity at 4 months (non-classic radiation-induced liver disease [RILD]). Kang noted that “classic” RILD is characterized by anicteric ascites and hepatomegaly, and is unlikely to occur after a mean liver dose of approximately 30 Gy in conventional fractionation. At 6 months, 1 case of grade 3 esophageal ulcer with stenosis was reported. Severe toxicity of 3.2% was reported at 1 year.
“These findings warrant confirmation in further randomized controlled trials,” Kang said. The current trial is listed on ClinicalTrials.gov (NCT01850667).