Proton beam therapy for hepatocellular carcinoma associated with inferior vena cava tumor thrombus

Sekino, Yuta; Okumura, Toshiyuki; Fukumitsu, Nobuyoshi; Iizumi, Takashi; Numajiri, Haruko; Mizumoto, Masashi; Nakai, Kei; Nonaka, Tetsuo; Ishikawa, Hitoshi; Sakurai, Hideyuki

doi:10.1007/s00432-019-03096-7

Cited by 21 publications

(26 citation statements)

References 39 publications

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“…The proton beam used in PBT has a narrow energy peak called the Bragg peak that can reduce the dose area compared to photon beam therapy, such as stereotactic body radiotherapy and intensity modulated radiotherapy [29][30][31][32]. Therefore, the dose distribution in PBT is favorable for HCC, and PBT is widely indicated for HCC, including in patients with large HCC [10,15] and PVTT [9,14]. The results of PBT for HCC have been favorable, with liver function defined by Child-Pugh score or ICG-R15 well preserved in these reports [20,21].…”

Section: Discussionmentioning

confidence: 99%

“…Surgery is the first treatment choice, but highly accurate radiotherapy has also been used in recent years [ 4 , 5 , 6 ]. As one modality of radiotherapy, we have obtained many favorable results of proton beam therapy (PBT) for HCC [ 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 ], including good preservation of liver function after PBT [ 21 ]. However, liver function defined by the Child–Pugh score and indocyanine green retention rate at 15 min (ICG-R15) can be affected by tumor progression or liver cirrhosis, and this can make direct liver damage due to radiotherapy unclear.…”

Section: Introductionmentioning

confidence: 99%

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Transitions of Liver and Biliary Enzymes during Proton Beam Therapy for Hepatocellular Carcinoma

Sumiya

Mizumoto

Oshiro

et al. 2020

Cancers

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Proton beam therapy (PBT) is a curative treatment for hepatocellular carcinoma (HCC), because it can preserve liver function due to dose targeting via the Bragg peak. However, the degree of direct liver damage by PBT is unclear. In this study, we retrospectively analyzed liver/biliary enzymes and total bilirubin (T-Bil) as markers of direct liver damage during and early after PBT in 300 patients. The levels of these enzymes and bilirubin were almost stable throughout the treatment period. In patients with normal pretreatment levels, aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), gamma-glutamyl transpeptidase (GGT), and T-Bil were abnormally elevated in only 2 (1.2%), 1 (0.4%), 0, 2 (1.2%), and 8 (3.5%) patients, respectively, and in 8 of these 13 patients (61.5%) the elevations were temporary. In patients with abnormal pretreatment levels, the levels tended to decrease during PBT. GGT and T-Bil were elevated by 1.62 and 1.57 times in patients who received 66 Gy (RBE) in 10 fractions and 74 Gy (RBE) in 37 fractions, respectively, but again these changes were temporary. These results suggest that direct damage to normal liver caused by PBT is minimal, even if a patient has abnormal pretreatment enzyme levels.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Transitions of Liver and Biliary Enzymes during Proton Beam Therapy for Hepatocellular Carcinoma

Sumiya

Mizumoto

Oshiro

et al. 2020

Cancers

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“…Among the 18 studies, 8 were single arm studies [19][20][21][22][31][32][33][34] that were categorized into the surgery subgroup, another 8 were single arm studies [24,[35][36][37][38][39][40][41] categorized into the EBRT subgroup, and 2 were controlled studies [42,43] comprising 2 cohorts that compared surgery and EBRT. Eight studies (44%) were from mainland China, 6 from Japan (33%), 2 from Korea (11%), and 1 from Taiwan All rights reserved.…”

Section: Study Inclusion and General Informationmentioning

confidence: 99%

Surgery versus external beam radiotherapy for hepatocellular carcinoma involving the inferior vena cava or right atrium: A systematic review and meta-analysis

Lee

Park

Seo

et al. 2020

Preprint

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Purpose: As the treatment efficacy of systemic therapy for patients with advanced stage HCC is insufficient, locoregional therapies are performed in the clinical practice. We investigated the efficacy and safety of two most potent therapies, surgery and external beam radiotherapy (EBRT), in patients with HCC involving the IVC and/or right atrium (RA) through comparative meta-analysis. Method: A systematic search of Pubmed, MEDLINE, EMBASE, and the Cochrane library was performed for entries up to July 2020. The primary endpoints were 1 and 2 year overall survival (OS) rates, while secondary endpoints were response rate, local control rate, and grade >=3 toxicities. Results: Eighteen studies with 22 cohorts were included, encompassing 755 patients. The pooled median OS and 1 and 2 year OS rates were 14.2 months, 55.6%, and 27.4%, respectively. The pooled median OS in the surgery and EBRT arms were 15.3 and 11.7 months, respectively. The pooled 1 year OS rate of the surgery arm was significantly higher than that of the EBRT arm (62.4%, 95% CI: 53.8–70.3 vs. 48.8%, 95% CI: 40.9–56.8; p=0.023). However, the 2 year OS rates were comparable (26.9%, 95% CI: 20.7–34.2 vs. 27.5%, 95% CI: 19.7–37.1; p=0.913). The pooled response and local control rates in the EBRT arm were 74.3% and 87.2%, respectively. In the surgical arm, the perioperative mortality and grade >=3 complication rates were 0–7.6% and 3.9–67%, respectively. Grade >=3 complications and radiation induced liver disease were rarely observed in the EBRT arm. Conclusions: Both surgery and EBRT are effective treatment options for patients with HCC involving IVC/RA invasion. Outcomes and safety should be further evaluated in well-controlled clinical trials.

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“…[ 10 ] RT for IVCTT shows good local control rate, at 80% to 90% at the treatment site, but the median overall survival of patients who received RT was only 6 to 10 months. [ 6 , 7 , 9 , 11 ] This study aimed to analyze the clinical outcome of RT for IVCTT by investigating the disease progression pattern and cause of death after RT, as well as local control. In addition, we tried to evaluate the toxicity of RT, specifically, the occurrence of pulmonary embolism, a critical complication that can be caused by dislodgement of tumor thrombus during RT.…”

Section: Introductionmentioning

confidence: 99%

Clinical outcome and toxicity of radiotherapy for inferior vena cava tumor thrombus in HCC patients

2021

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Hepatocellular carcinoma (HCC) involving the inferior vena cava rarely occurs, but its prognosis is extremely poor, with no established treatment to date. This study aimed to analyze the clinical outcome and toxicity of radiotherapy (RT) targeting inferior vena cava tumor thrombus (IVCTT) in HCC patients. From November 2011 to July 2020, medical record of 19 HCC patients who were treated with RT for IVCTT was retrospectively reviewed. RT was delivered using 3-dimensional conformal radiation therapy, intensity-modulated radiation therapy, and stereotactic body radiation therapy. The median radiation dose was 50 Gy (range, 45–55.8 Gy) for intensity-modulated radiation therapy and three-dimensional conformal radiotherapy. Stereotactic body radiation therapy was performed in 5 patients, for a total of 32 Gy in 4 fractions. The median follow-up duration was 8.1 months (range, 3.3–26.5 months). The median overall survival was 9.4 months (range, 3.7–26.5 months), and the 1-year overall survival rate was 37.1%. Eight of 19 patients (42.1%) had extrahepatic metastasis at the start of RT. Six of 11 patients (54.5%) who did not have extrahepatic metastasis at the start of RT showed extrahepatic metastasis after RT. The major cause of death was progression of extrahepatic metastasis (11 patients, 57.9%). The overall response rate of IVCTT for RT was 84.2%, and the local control rate at the time of the last follow-up was 89.4%. After RT, the most common first progression site was the lungs (9 patients, 47.4%). Most toxicities were grade 1 to 2 gastrointestinal (26.3%) and liver enzyme elevation (68.4%). Three patients occurred pulmonary embolism after RT later than 5 months after. RT is a feasible and safe local therapy for IVCTT, with favorable tumor control and acceptable toxicity. Extrahepatic metastasis is the major progression pattern and a leading cause of death in patients treated with RT. The combination of effective systemic therapy with RT may have to be considered.

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Proton beam therapy for hepatocellular carcinoma associated with inferior vena cava tumor thrombus

Cited by 21 publications

References 39 publications

Transitions of Liver and Biliary Enzymes during Proton Beam Therapy for Hepatocellular Carcinoma

Transitions of Liver and Biliary Enzymes during Proton Beam Therapy for Hepatocellular Carcinoma

Surgery versus external beam radiotherapy for hepatocellular carcinoma involving the inferior vena cava or right atrium: A systematic review and meta-analysis

Clinical outcome and toxicity of radiotherapy for inferior vena cava tumor thrombus in HCC patients

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