Transarterial Chemoembolization Versus Proton Beam Radiotherapy for the Treatment of Hepatocellular Carcinoma

• Time to progression [ Time Frame: Lifetime ] [ Designated as safety issue: No ]
• Downstaging [ Time Frame: Lifetime ] [ Designated as safety issue: No ]

Patients with tumor burden that exceeds Milan criteria are considered to receive one of the following locoregional treatments: transarterial chemoembolization, radiofrequency ablation, percutaneous ethanol injection and proton beam radiation. The goals of these treatments are to control tumor growth, to downstage tumor size to meet Milan criteria, and to improve survival. Patients who exceed the Milan criteria benefit from downstaging, so they can be qualified for liver transplant. Patients who meet Milan criteria benefit from tumor control to bridge them to liver transplantation. TACE is considered the most common locoregional treatment that is used to treat HCC. Proton beam radiotherapy has been used in treating HCC in a few centers across the globe. Phase I and II trials showed a satisfactory safety and efficacy results. Loma Linda University Medical Center is one of these pioneering centers that use proton beam as a treatment for HCC. This is the first randomized trial in the medical field that will compare head-to-head the efficacy of TACE versus proton beam in treating HCC patients.

• Procedure: Transarterial Chemoembolization
  Application of carboplatin, doxorubicin in ethiodol into the artery for one or more sessions.
  Other Name: (TACE)
• Radiation: Proton Beam Radiotherapy
  Fifteen consecutive sessions

• Active Comparator: 1
  Transarterial Chemoembolization
  Intervention: Procedure: Transarterial Chemoembolization
• Active Comparator: 2
  Proton Beam Radiotherapy
  Intervention: Radiation: Proton Beam Radiotherapy

Inclusion Criteria:

1. Patients are candidates to receive both proton beam and TACE
2. Patients with no evidence of metastasis or macrovascular invasion
3. Patients with tumor burden that meets San Francisco criteria

Exclusion Criteria:

1. Patients who are candidates for surgical resection
2. Patients with lesion < 2 cm
3. Patients who have contraindication to receive either TACE or proton
4. Patients with serum alpha fetoprotein > 500
5. Patients with metastasis or macrovascular invasion
6. Patients treated previously for HCC by any locoregional treatment
7. Patients with prior liver transplant
8. Patients with Child class C
9. Patients with MELD score of > 25
10. Patients with other comorbid diseases that may impact survival
11. Patients with ongoing alcohol intake
12. Patients with active sepsis
13. Patients with gastrointestinal bleeding within a week
14. Patients unwilling to sign informed consent form
15. Patients with history of noncompliance