Liver cancer

Our clinical trial : Hepatocellular Carcinoma

Trial status : recruiting

First posted : 30 January 2023

Last updated : 30 January 2023

 

Full Title

Multi-institutional study: Phase III randomized controlled trial between stereotactic body radiotherapy (SBRT) vs stereotactic body proton therapy (SBPT) and for unresectable hepatocellular carcinoma

Purpose

Local therapy options for HCC include transplantation, surgical resection, ablative procedures, and radiation therapy. Surgery remains the gold standard, but many patients are technically or medically inoperable. Historically, the efficacy of RT in liver cancer has been limited by low liver tolerance to whole liver irradiation. The most concerning and dose-limiting toxicity of liver radiation is a radiation-induced liver disease (RILD) because it can lead to liver failure and death. As a result, RT played a minor role in managing liver tumors. However, recent advances in radiation planning and delivery technology have facilitated safer delivery of ablative radiation therapy doses, which are increasingly used for HCC.

The more commonly available treatment modality for ablative radiation therapy is the photon. However, photon therapy has a deposit dose along the exit beam path beyond the target volume, leading to an unwanted dose to the nontarget liver and other surrounding organs. In contrast, proton radiotherapy offers dosimetric advantages because of its superior physical properties. A proton beam has a finite range of energy deposition with no exit dose after the target. This physical advantage over photon beams could reduce the unwanted spreading of the dose to the surrounding normal liver and adjacent organs.

There have only been two retrospective studies showing the clinical benefits of proton radiotherapy over photon radiotherapy. The Massachusetts General Hospital study from the Massachusetts General Hospital (MGH) demonstrates survival benefit, which may be driven by decreased incidence of posttreatment liver decompensation. In Taiwan, a propensity score-matched cohort study based on a multi-institution medical organization research database, demonstrated that proton radiotherapy could deliver a higher radiation dose than photon radiotherapy without increasing the risk of RILD and result in a better overall survival rate. (3)

Although dosimetric and retrospective studies have demonstrated an advantage in using proton therapy, there has been no randomized controlled trial comparing proton and photon ablative radiation therapy. Therefore, in this study, we conducted a randomized controlled trial to investigate and compare the clinical outcomes of the two modalities.

Eligibility

To be eligible for this study, patients must meet following requirements, including:

  • Patients must have a diagnosis of HCC by at least one criterion listed below
    • Pathologically (histologically or cytologically) proven diagnosis of HCC.
    • At least one solid liver lesion size > 1 cm with arterial enhancement and delayed washout on multiphasic computerized tomography (CT) or magnetic resonance imaging (MRI) or presence of vascular tumor thrombosis (involving portal vein, IVC, and/or hepatic vein) in the setting of cirrhosis or chronic hepatitis B or C without cirrhosis.
  • Measurable hepatic disease and/or presence of vascular tumor thrombosis on liver CT or MRI within 28 days prior to study entry
  • Age > 18
  • ECOG 0 – 2 within 14 days prior to study entry
  • All blood work obtained within 14 days prior to study entry
    • Absolute neutrophil count ³ 1500 cell/mm3
    • Platelet ³ 70,000 cell/mm3
    • Hemoglobin ³ 8 g/dl (Note: The use of transfusion or other intervention to achieve Hb ³ 8 g/dl is acceptable)
    • Total bilirubin < 3 mg/dL
    • Prothrombin time/INR < 2.3
    • Albumin > 2.8 g/dL
    • AST and ALT < 6 times ULN
  • BCLC stage: Intermediate (B) or advanced (C) within 14 days prior to study entry
  • Unsuitable for resection or transplant
  • Unsuitable for or refractory to transarterial hepatic chemoembolization (TACE) or drug-eluting beads (DES)
  • Child-Pugh score less than 9 within 14 days prior to study entry

 

Exclusion Criteria

  • Extrahepatic metastases or malignant nodes
  • Prior or simultaneous malignancies within the past two years
  • Pregnant women, women planning to become pregnant, and women that are nursing
  • Prior radiotherapy treatment to the region of the liver that would result in excessive doses to normal tissue due to overlap of radiation therapy fields
  • Prior selective internal/hepatic arterial Yttrium therapy
  • Any one hepatocellular carcinoma > 15 cm
  • Total maximal sum of hepatocellular carcinoma > 20 cm
  • More than 3 discrete intrahepatic parenchymal foci of HCC
  • Normal liver volume (Liver volume minus intrahepatic GTV) less than 700 cc
  • Severe, active co-morbidity including congestive heart failure, angina, severe peripheral vascular disease

 Phase : III

 Disease Status : Locally advanced stage

 Investigator : Chonlakiet Khorprasert

 Co-Investigators

  • Napapat Amornwichet
  • Petch Alisanant
  • Kanokphorn Thonglert

Diseases : Hepatocellular carcinoma

Locations : King Chulalongkorn Memorial hospital