Internal Radiation Therapy for Hepatocellular Carcinomas With Therasphere: Optimized Dosimetry Versus Standard Dosimetry

For patients suffering from hepatocellular carcinoma, a palliative treatment can be proposed if tumor expansion is limited to the liver. One of palliative treatment is the the Selective Internal Radiation Therapy (SIRT) with Therasphere®. This treatment is made secure by performing a diagnostic angiogram coupled with a hepatic perfusion scintigraph with which patients at risk of complications are identified and excluded. The treatment objective, with the standard dosimetric approach, is to deliver an absorbed dose of 120 ± 20 Gy to the treated hepatic volume, most often one lobe. Recent retrospective trials show that an optimized dosimetric approach, considering the dose absorbed by the tumor, is technically achievable and would probably make it possible to obtain a better effectiveness. In our experience, treatment personalisation have been described to be used for 60% of the patients with a tumor larger than 7 cm underlying the clinical impact of this new approach.

Inclusion criteria

• Age ≥ 18,
• Written free and informed consent,
• Histologically demonstrated Hepatocellular Carcinoma (HCC), not a candidate for surgery or local ablative treatment (radio frequency, etc.)
• Barcelona Clinic Liver Cancer (BCLC) classification A, B or C,
• At least one lesion ≥ 7 cm,
• Hepatic reserve (hepatic parenchyma not treated) after the first SIRT ≥ 30%,
• Unilateral involvement, minimal bilateral involvement allowed only with a hepatic reserve ≥ 30% after SIRT
• Child A classification only, or B but with bilirubinemia <35 micromol/L,
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1,
• Patients whose biological parameters meet the following criteria:

• Hemoglobin ≥ 8.5 g/dL,
• Granulocytes ≥ 1500/mm3,
• Platelets ≥ 50,000/mm3,
• Bilirubinemia <35 micromol per liter,
• Transaminases ≤ five times the upper limit of normal,
• Creatininemia ≤ 1.5 times the normal upper limit,
• Expected survival over 12 weeks,
• Negative pregnancy test for women of childbearing age,
• If sorafenib has been taken the diagnostic angiogram must follow it by at least four weeks after its stop.

Exclusion criteria

• HCC operable or accessible to a local ablative treatment (radio frequency),
• Hepatectomy history unless a segmental treatment is considered, with a hepatic reserve ≥ 30% after SIRT,
• Prior treatment with sorafenib unless stopped at least four weeks earlier,
• History of chemo-embolization of the principal lesion, except in case of nodular residual lesion measuring at least 7 cm or in case of progression after initial response,
• Bilateral disease requiring a whole liver injection or with a hepatic reserve < 30% after SIRT
• Treatment of another cancer less than one year earlier,
• Extra-hepatic metastases other than adenopathies of the hilum smaller than 2 cm,
• >70% tumor invasion of the liver,
• Bilirubinemia ≥ 35 µmol/L,
• A Severe underlying biliary pathology:
• Bile duct anomaly (stent, dilation) Cirrhosis of biliary origin,
• Women of childbearing age without contraception
• Pregnant or nursing women