Theodore S. Lawrence, MD, PhD, FASCO
In a single-center phase II study reported in JAMA Oncology, Feng and colleagues found that individualized adaptive stereotactic body radiotherapy achieved high rates of local tumor control with low complication rates in patients with liver tumors and preexisting liver dysfunction. Theodore S. Lawrence, MD, PhD, FASCO, of the Department of Radiation Oncology, University of Michigan Medical Center, Ann Arbor, is the corresponding author of the JAMA Oncology article.
The study included 90 patients with intrahepatic cancer and previous liver-directed therapy enrolled between 2010 and 2014 at the University of Michigan Medical Center. Indocyanine green retention at 15 minutes (ICGR15) was used as a direct biomarker of liver function, with planned stereotactic body radiotherapy of 5 fractions being individually modified midway through the course of therapy to maintain liver function after course completion. The initial goal of adaptation was to ensure that final ICGR15 at 1 month after completion of stereotactic body radiotherapy was < 39%; the goal was subsequently modified to ICGR15 < 44% after absence of significant toxic events in the earliest enrolled patients.
Patients were aged 34 to 85 years, 70% were male, 69% had cirrhosis, and 23% had Child-Pugh grade B disease. Overall, 77% had hepatocellular carcinoma, 19% had metastases, and 4% had intrahepatic cholangiocarcinoma; the median tumor size was 3 cm, and 18% of patients had portal vein involvement. The 90 patients received treatment to 116 tumors. The primary outcome measure was local tumor control. All patients had at least 1 year of potential follow-up.
Treatment Outcome
The median delivered dose was 49 Gy (range = 23–60 Gy). The full planned 5-fraction course of stereotactic body radiotherapy was delivered to 64 tumors (55%). Treatment was adapted for 52 (45%) of the tumors; 26 were treated with only 3 fractions, and 26 received lower doses for the last 2 fractions. Rates of local tumor control at 1 and 2 years were 99% and 95%, respectively.
No classical radiation-induced liver disease was observed, and there was a lower-than-expected rate of complications without adaptation. Grade 3 elevations in aspartate transaminase, alanine transaminase, and total bilirubin were observed in one, two, and one patient within 6 months of stereotactic body radiotherapy, respectively; 14% and 7% of patients had 1 and 2 point declines in Child-Pugh score, with all but one of these patients having prior cirrhosis.
The investigators concluded: “We demonstrated that the treatment strategy of individualized adaptive therapy based on a direct biomarker of liver function can be used to achieve both high rates of local control and a high degree of safety without sacrificing either. Individualized adaptive radiotherapy may represent a new treatment paradigm in which dose is based on individual, rather than population-based, tolerance to treatment.” ■
