A National Phase II Study of Proton Therapy in Hepatocellular Carcinoma

Prior treatment

• Previous x-ray-based radiotherapy in the liver
• Previous Selective internal radiation therapy (SIRT)
• Patients with metal implants where beam entrance through the metal implants cannot be avoided (not applicable for fiducial markers implanted for radiotherapy use)
• Patients for whom it is not possible to implant fiducial markers e.g. due to insufficient coagulation of the blood.

Other illness

• Episode of bleeding esophageal varices within the past month. If active bleeding from esophageal varices has occurred, a gastroscopy should be performed 4 weeks after the bleeding episode to ensure maximum grade 1 varices.

Other

• Child Pugh score \>8
• Tumor less than 1 cm from any critical organs at risk (OAR) (duodenum, kidney, stomach, intestines).
• Episode of hepatic encephalopathy within the last 6 months
• Uncontrolled ascites with need for drainage \> 1 per month
• Patients for whom it is not possible to produce a robust treatment plan following the technical guidelines (Appendix A)

• Patients with HCC based on classical radiologic findings as defined by the American Association for the Study of Liver Diseases (AASLD) criteria or verified by biopsy
• No extra-hepatic disease
• Deemed ineligible for resection or Radiofrequency Ablation (RFA), or the patients should refuse RFA or surgery
• Age ≥ 18 years
• Performance status ≤ 2
• Total diameter of tumor(s) ≤ 12 cm and a maximum of 3 tumors
• Adequate liver function as measured by Child-Pugh score (Child-Pugh score ≤ 8), or absence of cirrhosis
• Has recovered adequately from toxicity and/or complications from any previous local interventions
• Patients with past or ongoing hepatitis C infection are allowed, but treatment for hepatitis C must have been completed one month before study entry
• Patients with hepatitis B infection is allowed if antiviral therapy have been given for at least 4 weeks and Hepatitis B Virus (HBV) viral load is less than 100 IU/ml. The active therapy must continue throughout the radiation therapy. Patients who are Total hepatitis B core antibody (anti-HBc)(+), negative for Hepatitis B surface antigen (HbsAg) and negative or positive for Hepatitis B surface antibody (anti-HBs) with a HBV viral load under 100 IU/mL do not require HBV anti-viral prophylaxis
• Adequate organ function
  • hematological: hemoglobin ≥ 6 mmol/l, absolute neutrophil count (ANC) ≥ 1,5 x 109/L, platelets ≥ 50 x 109/L
  • hepatic: bilirubin ≤ 1.5 x ULN, alanin-aminotransferase (ALAT) ≤ 1.5 x ULN
  • renal: creatinine ≤ 1.5 x ULN
• Ability to adhere to procedures for study and follow-up
• Signed informed consent to participate
• Final decisions on inclusion and treatment with proton therapy are at the discretion of the investigator