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

PLoS One. 2018 Sep 11;13(9):e0203854. doi: 10.1371/journal.pone.0203854. eCollection 2018.

Abstract

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 cm3 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 cm3 (median = 673.8 cm3), eSLV ranged from 889.3 to 1290.0 cm3 (median = 1104.5 cm3), 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 cm3 (median = 391.2 cm3). 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 cm3 (median = 488.2 cm3), 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 cm3, 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Carcinoma, Hepatocellular / mortality
  • Carcinoma, Hepatocellular / pathology*
  • Carcinoma, Hepatocellular / radiotherapy*
  • Female
  • Follow-Up Studies
  • Humans
  • Liver / pathology*
  • Liver / radiation effects
  • Liver Neoplasms / mortality
  • Liver Neoplasms / pathology*
  • Liver Neoplasms / radiotherapy*
  • Male
  • Middle Aged
  • Organ Size
  • Pilot Projects
  • Precision Medicine
  • Proton Therapy* / methods
  • Radiation Injuries / etiology
  • Radiation Injuries / pathology
  • Radiotherapy Dosage
  • Retrospective Studies
  • Treatment Outcome

Grants and funding

This study is supported by the grant CIRPG3D0143, CMRPG3H0471, CIRPD1D0071, CIRPD1D0072, and CIRPD1D0073 from Chang Gung Memorial Hospital and Chang Gung University. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.