Proton Beam Therapy for Hepatocellular Carcinoma: A Comparison of Three Treatment Protocols

Mizumoto, Masashi; Okumura, Toshiyuki; Hashimoto, Takayuki; Fukuda, Kuniaki; Oshiro, Yoshiko; Fukumitsu, Nobuyoshi; Abei, Masato; Kawaguchi, Atsushı; Hayashi, Yasutaka; Ookawa, Ayako; Hashii, Haruko; Kanemoto, Ayae; Moritake, Takashi; Tohno, Eriko; Tsuboi, Koji; Sakae, Takeji; Sakurai, Hideyuki

doi:10.1016/j.ijrobp.2010.07.015

Cited by 149 publications

(140 citation statements)

References 41 publications

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“…These 4 patients were Child‐Pugh class B with other active HCCs, although it was difficult to conclude whether the cause of death was radiation‐induced liver failure, tumor progression, side effects caused by other therapies, or the natural course of their liver disease. In fact, this study revealed that patients classified as Child‐Pugh class B had a significantly higher mortality rate than those classified as Child‐Pugh class A; this finding is similar to reports evaluating SBRT9, 30 and proton therapy 12, 31. This suggests that patients with poor liver function, such as those who have Child‐Pugh class B or worse disease, and especially those with other active HCCs should be treated with caution when they are undergoing radiotherapy, including CIRT.…”

Section: Discussionsupporting

confidence: 90%

Progressive hypofractionated carbon‐ion radiotherapy for hepatocellular carcinoma: Combined analyses of 2 prospective trials

Kasuya

Kato²,

Yasuda

et al. 2017

Cancer

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BACKGROUNDThe objective of this study was to evaluate the safety and efficacy of carbon‐ion radiotherapy (CIRT) in patients with hepatocellular carcinoma (HCC) with stepwise dose escalation and hypofractionation in 2 combined prospective trials.METHODSSequential phase 1/2 (protocol 9603) and phase 2 (protocol 0004) trials were conducted for patients with histologically proven HCC. The phase 1 component of protocol 9603 was a dose‐escalation study; CIRT was delivered in 12, 8, or 4 fractions. After determination of the recommended dose, 2 phase 2 trials were performed in an expanded cohort, and the data were pooled to analyze toxicity, local control, and overall survival.RESULTSIn the phase 1 component of protocol 9603, 69.6, 58.0, and 52.8 Gy (relative biological effectiveness [RBE]) in 12, 8, and 4 fractions, respectively, constituted the maximum tolerated doses, and 52.8 Gy (RBE) in 4 fractions was established as the recommended dose regimen for the 2 phase 2 studies. In 124 patients with a total of 133 lesions, few severe adverse effects occurred, and local‐control and overall survival rates at 1, 3, and 5 years were 94.7% and 90.3%, 91.4% and 50.0%, and 90.0% and 25.0%, respectively; this included 1‐, 3‐, and 5‐year local‐control rates of 97.8%, 95.5%, and 91.6%, respectively, in the phase 2 study. In a multivariate analysis, Child‐Pugh class B and the presence of a tumor thrombus were significant factors for mortality.CONCLUSIONSThe safety and efficacy of CIRT in 12, 8, and 4 fractions were confirmed, with 52.8 Gy (RBE) in 4 fractions established as the recommended treatment course for eligible HCC patients. Cancer 2017;123:3955‐65. © 2017 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society.

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Section: Discussionsupporting

confidence: 90%

Progressive hypofractionated carbon‐ion radiotherapy for hepatocellular carcinoma: Combined analyses of 2 prospective trials

Kasuya

Kato²,

Yasuda

et al. 2017

Cancer

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“…Modern photon therapy techniques such as intensity-modulated radiation therapy (IMRT) may achieve prescription conformity similar to that of a proton treatment plan, but the amount of dose scattered to the remainder of the liver is still higher owing to the physical nature of photon beams. There is evidence that normal liver function is significantly positively correlated to the percentage of normal that is not irradiated (21). Reduction of integral dose to remaining liver may help preserve liver function, decrease the risk of secondary malignancies, and also allow for future retreatment of the liver.…”

Section: The Rationale For Proton Therapy In Hccmentioning

confidence: 99%

Proton therapy for hepatocellular carcinoma

Ling

Kang

Bush

et al. 2012

Chin. J. Cancer Res.

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Proton radiotherapy has seen an increasing role in the treatment of hepatocellular carcinoma (HCC). Historically, external beam radiotherapy has played a very limited role in HCC due to a high incidence of toxicity to surrounding normal structures. The ability to deliver a high dose of radiation to the tumor is a key factor in improving outcomes in HCC. Advances in photon radiotherapy have improved dose conformity and allowed dose escalation to the tumor. However, despite these advances there is still a large volume of normal liver that receives a considerable radiation dose during treatment. Proton beams do not have an exit dose along the beam path once they enter the body. The inherent physical attributes of proton radiotherapy offer a way to maximize tumor control via dose escalation while avoiding excessive radiation to the remaining liver, thus increasing biological effectiveness. In this review we discuss the physical attributes and rationale for proton radiotherapy in HCC. We also review recent literature regarding clinical outcomes of using proton radiotherapy for the treatment of HCC.

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“…We have shown that PBT is effective for treatment of HCC regardless of tumor size and underlying liver function [7][8][9]. In this case, the patient had a very large HCC with PVTT in the main and right main portal vein, and PBT appeared to be the only treatment method.…”

Section: Discussionmentioning

confidence: 76%

Aggressive proton beam therapy followed by liver transplantation for a patient with large HCC with portal vein tumor thrombus

et al. 2012

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We describe the case of a patient with large hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT) who was successfully treated with two courses of proton beam therapy (PBT) followed by liver transplantation. The patient was a 69-year-old man with hepatitis C viral infection who was diagnosed with a diffuse HCC, 8 cm in size, and a PVTT that occluded the right portal vein and reached the main trunk of the portal vein. A large tumor in the right lobe and PVTT in the main and right main portal vein were treated by PBT. PVTT in the left main portal vein developed thereafter and was treated with a second course of PBT. Although the tumor was well controlled with two courses of PBT, liver function gradually deteriorated to an irreversible status 20 months after initiation of the first course of PBT. Liver transplantation was successfully performed to maintain liver function. The patient is still alive with no evidence of disease 7 years after the first course of PBT. This case shows that aggressive PBT can be used for treating advanced HCC, with subsequent liver transplantation for hepatic failure that may be caused by PBT.

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Proton Beam Therapy for Hepatocellular Carcinoma: A Comparison of Three Treatment Protocols

Cited by 149 publications

References 41 publications

Progressive hypofractionated carbon‐ion radiotherapy for hepatocellular carcinoma: Combined analyses of 2 prospective trials

Progressive hypofractionated carbon‐ion radiotherapy for hepatocellular carcinoma: Combined analyses of 2 prospective trials

Proton therapy for hepatocellular carcinoma

Aggressive proton beam therapy followed by liver transplantation for a patient with large HCC with portal vein tumor thrombus

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