How small is TOO small? New liver constraint is needed— Proton therapy of hepatocellular carcinoma patients with small normal liver

PURPOSE: This study evaluated the outcomes of hepatocellular carcinoma (HCC) patients with small normal liver volume (NLV) treated with proton beam therapy (PBT) and introduced estimated standard liver volume (eSLV) as a new constraint. MATERIALS AND METHODS: HCC patients with NLV < 800 cm(3) and no distant metastasis who received treatment in our proton center were included. The doses of PBT were mainly 72.6 Gray equivalents (GyE) in 22 fractions and 66 GyE in 10 fractions according to tumor locations. The Urata equation was used to calculate eSLV. RESULTS: Twenty-two patients were treated between November 2015 and December 2016. The 1-year progression-free and overall survival rates were 40.4% and 81.8%, respectively. The 1-year in-field failure-free rate was 95.5%. NLV ranged from 483.9 to 795.8 cm(3) (median = 673.8 cm(3)), eSLV ranged from 889.3 to 1290.0 cm(3) (median = 1104.5 cm(3)), and the resulting NLV/eSLV ratio ranged from 44.3 to 81.2% (median = 57.7%). Non-irradiated liver volume (NILV) ranged from 232.9 to 531.6 cm(3) (median = 391.2 cm(3)). The NILV/eSLV ratio ranged from 21.2 to 48.0% (median = 33.3%). NLV in the patients who received <30 GyE (rV30) ranged from 319.1 to 633.3 cm(3) (median = 488.2 cm(3)), and their rV30/eSLV ratio ranged from 30.7 to 58.0%. None of our patients developed liver failure. One patient with initial abnormal liver enzyme levels developed non-classic radiation-induced liver disease (RILD). CONCLUSION: From the viewpoint of minimal liver toxicity occurring in our patients with NLV < 800 cm(3), conventional liver constraints involving the use of absolute volume could not accurately predict the risk of RILD. It is reasonable to start using individualized constraints with eSLV for HCC patients undergoing PBT. According to the study results, an NILV/eSLV ratio of >20% and an rV30/eSLV ratio of >30% are acceptable.