Proton and Carbon Ion Therapy for Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) remains a leading cause of cancer mortality worldwide, with many patients presenting with unresectable or locally advanced disease. Proton beam therapy (PBT) and carbon ion radiotherapy (CIRT) employ charged particles whose physical dose deposition peaks within the tumour (the Bragg peak), thus sparing surrounding healthy liver parenchyma. Carbon ions additionally confer a higher relative biological effectiveness (RBE) and greater linear energy transfer (LET) than protons, potentially enhancing tumour cell kill and enabling hypofractionated regimens. Clinical series and phase I–II trials have demonstrated local control rates often exceeding 80%, with acceptable toxicity profiles even in cirrhotic livers. Attention to patient selection, underlying hepatic reserve (commonly assessed by Child–Pugh score), and integration with systemic or locoregional therapies is critical. Technological advances such as pencil-beam scanning, image-guided delivery and advanced radiobiological modelling continue to refine treatment planning. As HCC incidence rises in diverse regions, proton and carbon ion modalities represent an important therapeutic alternative to conventional photon-based radiotherapy and other local ablation techniques, offering renewed prospects for durable tumour control and preservation of liver function.

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Proton and Carbon Ion Therapy for Hepatocellular Carcinoma publication trend

The graph below shows the total number of articles in proton and carbon ion therapy for hepatocellular carcinoma across all publications each year (not limited to Nature Index journals).

Technical terms

Proton beam therapy (PBT): Radiotherapy using protons whose depth–dose profile concentrates energy at a defined distal range, reducing exit dose.

Carbon ion radiotherapy (CIRT): Use of accelerated carbon ions that combine precise dose deposition with higher biological effectiveness than photons or protons.

Bragg peak: The sharp maximum of energy deposition by charged particles at the end of their range, allowing conformal dose delivery.

Relative biological effectiveness (RBE): Ratio comparing the biological damage of one type of radiation to a reference, typically X-rays, for a given dose.

Linear energy transfer (LET): Measure of energy deposited per unit track length by radiation, with higher LET correlating with greater cell kill.

Hypofractionation: Delivery of larger radiation doses per fraction over fewer sessions, often achievable with particle therapy.

Child–Pugh score: Clinical classification of liver function based on laboratory and clinical parameters, guiding treatment eligibility and prognosis.

References

1. Carbon ion radiotherapy of hepatocellular carcinoma provides excellent local control: The prospective phase I PROMETHEUS trial. JHEP Reports (2024).
2. Proton Beam Therapy for Treating Patients with Hepatocellular Carcinoma with Major Portal Vein Tumor Invasion: A Single Center Retrospective Study. Cancers (2024).
3. Longer Survival and Preserved Liver Function after Proton Beam Therapy for Patients with Unresectable Hepatocellular Carcinoma. Current Oncology (2023).