title: Radiotherapy of liver malignancies. From whole liver irradiation to stereotactic hypofractionated radiotherapy.
abstract: OBJECTIVE
  Until recently radiotherapy of hepatic malignancies has played a limited role due to the well-known limited radiotolerance of the liver. The aim of this paper is to review the available data on the risk of radiation-induced liver disease (RILD) and to define the modern role of radiotherapy in the management of patients with metastatic or primary liver malignancies.
  
  
  METHODS
  The advent of three-dimensional conformal treatment planning with dose-volume histogram analysis has made the study of partial liver irradiation possible. Limited portions of the liver may withstand high doses of radiation with minimal risk of RILD. Patients with solitary unresectable liver tumors may be treated with high-dose radiotherapy with curative intent. Recently, the feasibility of stereotactically guided treatment techniques with a single fraction or few treatment sessions has been explored in numerous institutions.
  
  
  RESULTS
  The radiation tolerance of the whole liver found by several investigations is in the order of approximately 30 Gy, which seriously restricts its clinical application. The role of whole liver irradiation therefore appears of limited benefit in the palliation of patients with multiple liver metastases. The use of three-dimensional conformal techniques has made partial liver irradiation possible to doses in the 70-80 Gy range with conventional fractionation. At least two published series have reported improved local control and survival rates with dose escalation with three-dimensional conformal radiotherapy in patients with unresectable liver metastases. Similar outcomes have been recently reported with single dose (or hypofractionated) stereotactic radiotherapy both in metastatic and primary hepatic malignancies with minimal morbidity. Accurate target delineation and treatment reproducibility are the key to the success of this novel treatment approach, and specific treatment planning techniques and patient setup procedures must be developed to implement it.
  
  
  CONCLUSIONS
  Stereotactic high-dose radiotherapy is technically feasible for the treatment of inoperable liver malignancies, with the potential of high local control and low morbidity. Definitive evidence on the clinical advantages of this technique over other more established treatments can only be gathered from well-designed clinical studies.
authors.affiliation: Division of Radiation Oncology, European Institute of Oncology, Milan, Italy. carlo.greco@ieo.it
authors.forename: Carlo
authors.initials: C
authors.lastname: Greco
authors.forename: Gianpiero
authors.initials: G
authors.lastname: Catalano
authors.forename: Alfio
authors.initials: A
authors.lastname: Di Grazia
authors.forename: Roberto
authors.initials: R
authors.lastname: Orecchia
mesh_terms: D019583:Dose Fractionation, Radiation; D006801:Humans; D008099:Liver / Q000528:radiation effects; D008107:Liver Diseases / Q000209:etiology; D008113:Liver Neoplasms / Q000532:radiotherapy*; D011880:Radiotherapy Planning, Computer-Assisted; D020266:Radiotherapy, Conformal; D013238:Stereotaxic Techniques