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Cancers
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Radiotherapy for Hepatocellular Carcinoma
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Radiotherapy for Hepatocellular Carcinoma

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Therapy".

Deadline for manuscript submissions: closed (30 September 2020) | Viewed by 14584

Special Issue Editor

Prof. Dr. Tatsuya Ohno

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Guest Editor
Gunma University Heavy Ion Medical Center, Gunma University, Showa 3-39-22, Maebashi, Gunma, Japan
Interests: hepatocellular carcinoma; cholangiocarcinoma; radiotherapy

Special Issue Information

Dear Colleagues,

Traditionally, the role of radiotherapy for hepatocellular carcinoma (HCC) has been limited. However, recent technological innovations such as image-guided radiotherapy, stereotactic body radiotherapy, intensity-modulated radiotherapy, proton therapy, and carbon ion radiotherapy have provided the means to deliver radical doses of radiotherapy to patients with HCC, while avoiding critical normal tissues, providing the opportunity to use radiotherapy for the curative intent treatment of HCC. Radiotherapy can be combined with other systemic treatment modalities, including transarterial chemoembolization (TACE), targeted drug, or immune therapy.

This Special Issue stimulates discussion by bringing together expert opinions and novel basic/clinical research on radiotherapy for HCC. Internal radiotherapy as radioembolization, advanced external beam radiotherapy, multimodality approach, and articles analyzing new insights into elucidating the role of radiotherapy in the management of HCC are invited.

Prof. Dr. Tatsuya Ohno
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • hepatocellular carcinoma
  • radiotherapy
  • multimodality treatment

Published Papers (6 papers)

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Research

14 pages, 3653 KiB  
Article
Efficacy and Safety of the Radiotherapy for Liver Cancer: Assessment of Local Controllability and Its Role in Multidisciplinary Therapy
by Marina Ohkoshi-Yamada, Kenya Kamimura, Osamu Shibata, Shinichi Morita, Motoki Kaidu, Toshimichi Nakano, Katsuya Maruyama, Atsushi Ota, Hirotake Saito, Nobuko Yamana, Tomoya Oshikane, Yukiyo Goto, Natsumi Yoshimura, Satoshi Tanabe, Hisashi Nakano, Madoka Sakai, Yuto Tanaka, Yohei Koseki, Yoshihisa Arao, Hiroyuki Abe, Toru Setsu, Akira Sakamaki, Takeshi Yokoo, Hiroteru Kamimura, Hidefumi Aoyama and Shuji Teraiadd Show full author list remove Hide full author list
Cancers 2020, 12(10), 2955; https://doi.org/10.3390/cancers12102955 - 13 Oct 2020
Cited by 4 | Viewed by 2985
Abstract
This study investigated the efficacy and safety of radiotherapy as part of multidisciplinary therapy for advanced hepatocellular carcinoma (HCC). Clinical data of 49 HCC patients treated with radiotherapy were assessed retrospectively. The efficacy of radiotherapy was assessed by progression-free survival, disease control rate, [...] Read more.
This study investigated the efficacy and safety of radiotherapy as part of multidisciplinary therapy for advanced hepatocellular carcinoma (HCC). Clinical data of 49 HCC patients treated with radiotherapy were assessed retrospectively. The efficacy of radiotherapy was assessed by progression-free survival, disease control rate, and overall survival. Safety was assessed by symptoms and hematological assay, and changes in hepatic reserve function were determined by Child–Pugh score and albumin–bilirubin (ALBI) score. Forty patients underwent curative radiotherapy, and nine patients with portal vein tumor thrombus (PVTT) underwent palliative radiotherapy as part of multidisciplinary therapy. Local disease control for curative therapy was 80.0% and stereotactic body radiotherapy was 86.7% which was greater than that of conventional radiotherapy (60.0%). Patients with PVTT had a median observation period of 651 days and 75% three-year survival when treated with multitherapy, including radiotherapy for palliative intent, transcatheter arterial chemoembolization, and administration of molecular targeted agents. No adverse events higher than grade 3 and no changes in the Child–Pugh score and ALBI score were seen. Radiotherapy is safe and effective for HCC treatment and can be a part of multidisciplinary therapy. Full article
(This article belongs to the Special Issue Radiotherapy for Hepatocellular Carcinoma)
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14 pages, 808 KiB  
Article
Do Biliary Complications after Proton Beam Therapy for Perihilar Hepatocellular Carcinoma Matter?
by Gyu Sang Yoo, Jeong Il Yu, Hee Chul Park, Dongho Hyun, Woo Kyoung Jeong, Ho Yeong Lim, Moon Seok Choi and Sang Yun Ha
Cancers 2020, 12(9), 2395; https://doi.org/10.3390/cancers12092395 - 24 Aug 2020
Cited by 8 | Viewed by 1687
Abstract
We aimed to evaluate the biliary complications and efficacy of proton beam therapy (PBT) for hepatocellular carcinoma (HCC). We retrospectively analyzed 167 patients who received PBT with ≥ 75 GyRBE of biological effective dose with ?/β = 10 for primary HCC. The perihilar [...] Read more.
We aimed to evaluate the biliary complications and efficacy of proton beam therapy (PBT) for hepatocellular carcinoma (HCC). We retrospectively analyzed 167 patients who received PBT with ≥ 75 GyRBE of biological effective dose with ?/β = 10 for primary HCC. The perihilar region was defined as a 1-cm area extending from the right, left, and common hepatic ducts, including the gallbladder and cystic duct. PBT-related biliary complications were defined as follows: significant elevation in bilirubin level to > 3.0 mg/dL; elevation to more than twice of the baseline level after the completion of PBT; or newly developed radiological biliary abnormalities, which were not caused by HCC progression, comorbidities, or other treatments. Eighty (47.9%) had perihilar HCC. PBT-related events occurred in seven (4.2%), three of whom had perihilar HCC. Radiologic biliary abnormalities developed in 12 patients (7.2%); however, no events were PBT-related. All patients who experienced PBT-related biliary complications had underlying liver cirrhosis. The albumin-bilirubin grade was identified as an independent factor associated with PBT-related biliary complications. PBT at the current dose showed a low rate of PBT-related biliary complications even for patients with perihilar HCC. PBT for HCC patients with risk factors requires attention to reduce PBT-related biliary complications. Full article
(This article belongs to the Special Issue Radiotherapy for Hepatocellular Carcinoma)
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13 pages, 2185 KiB  
Article
Transitions of Liver and Biliary Enzymes during Proton Beam Therapy for Hepatocellular Carcinoma
by Taisuke Sumiya, Masashi Mizumoto, Yoshiko Oshiro, Keiichiro Baba, Motohiro Murakami, Shosei Shimizu, Masatoshi Nakamura, Yuichi Hiroshima, Toshiki Ishida, Takashi Iizumi, Takashi Saito, Haruko Numajiri, Kei Nakai, Toshiyuki Okumura and Hideyuki Sakurai
Cancers 2020, 12(7), 1840; https://doi.org/10.3390/cancers12071840 - 8 Jul 2020
Cited by 5 | Viewed by 1959
Abstract
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue Radiotherapy for Hepatocellular Carcinoma)
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15 pages, 830 KiB  
Article
Phase I Radiation Dose-Escalation Study to Investigate the Dose-Limiting Toxicity of Concurrent Intra-Arterial Chemotherapy for Unresectable Hepatocellular Carcinoma
by Yeona Cho, Jun Won Kim, Ja Kyung Kim, Kwan Sik Lee, Jung Il Lee, Hyun Woong Lee, Kwang-Hun Lee, Seung-Moon Joo, Jin Hong Lim and Ik Jae Lee
Cancers 2020, 12(6), 1612; https://doi.org/10.3390/cancers12061612 - 18 Jun 2020
Cited by 3 | Viewed by 1953
Abstract
Concurrent intra-arterial chemotherapy and radiotherapy (iA-CCRT) can increase the response rate in hepatocellular carcinoma (HCC), but may cause a higher toxicity. We conducted this Phase I study to investigate the dose-limiting toxicity of iA-CCRT for HCC. In total, 52.5 Gy in 25 fractions [...] Read more.
Concurrent intra-arterial chemotherapy and radiotherapy (iA-CCRT) can increase the response rate in hepatocellular carcinoma (HCC), but may cause a higher toxicity. We conducted this Phase I study to investigate the dose-limiting toxicity of iA-CCRT for HCC. In total, 52.5 Gy in 25 fractions was prescribed as planning target volume (PTV) 1 at dose level 1. The dose escalation was 0.2 Gy per fraction and up to 2.5 Gy, with 62.5 Gy at level 3. Concurrent intra-arterial 5-fluorouracil was administered during the first and fifth weeks of radiotherapy (RT). Toxicities were graded using the Common Toxicity Criteria for Adverse Events, version 4.0. Results: Seventeen patients with HCC were analyzed: four at dose level 1, 6 at level 2, and 7 at level 3. The mean irradiated dose administered to the uninvolved liver at each dose level was 21.3, 21.6, and 18.2 Gy, respectively. There was no grade ≥3 gastrointestinal toxicity; two patients experienced grade 3 hyperbilirubinemia. All patients had Child-Pugh class A disease, but 3 patients developed class B disease after iA-CCRT. During a median follow-up of 13 months, the median progression-free survival (PFS) and overall survival (OS) were 10 and 22 months, respectively. Patients treated at dose level 3 showed improved PFS and OS. Conclusions: Radiation dose escalation of iA-CCRT did not cause any significant toxicities in patients with advanced HCC. Further large-scale studies with long-term follow-up are needed to determine the efficacy and feasibility of higher doses of iA-CCRT. Full article
(This article belongs to the Special Issue Radiotherapy for Hepatocellular Carcinoma)
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13 pages, 1242 KiB  
Article
Comparison between Y90 Radioembolization Plus Sorafenib and Y90 Radioembolization alone in the Treatment of Hepatocellular Carcinoma: A Propensity Score Analysis
by Antonio Facciorusso, Irene Bargellini, Marina Cela, Ivan Cincione and Rodolfo Sacco
Cancers 2020, 12(4), 897; https://doi.org/10.3390/cancers12040897 - 7 Apr 2020
Cited by 17 | Viewed by 2600
Abstract
Background: Adjuvant sorafenib may enhance the efficacy of transarterial radioembolization with yttrium-90 in hepatocellular carcinoma patients. The aim of this study is to assess the efficacy and safety of radioembolization plus sorafenib in comparison to radioembolization alone. Methods: Out of 175 hepatocellular carcinoma [...] Read more.
Background: Adjuvant sorafenib may enhance the efficacy of transarterial radioembolization with yttrium-90 in hepatocellular carcinoma patients. The aim of this study is to assess the efficacy and safety of radioembolization plus sorafenib in comparison to radioembolization alone. Methods: Out of 175 hepatocellular carcinoma (HCC) patients treated with radioembolization between 2011 and 2018, after propensity score matching, two groups were compared: a group of 45 patients that underwent radioembolization while being on sorafenib (Group 1) and a second group of 90 patients that underwent radioembolization alone (Group 2). Results: Baseline characteristics of the two groups were well balanced concerning liver function and tumor burden. No significant differences in survival outcomes were identified (median overall survival 10 vs. 10 months; p = 0.711), median progression-free survival 6 vs. 7 months (p = 0.992) in Group 1 and Group 2). The objective response rate in Group 1 vs. Group 2 was 45.5% vs. 42.8% (p = 1) according to mRECIST. No differences in toxicity nor in liver decompensation rates were registered. Conclusions: The association of sorafenib does not prolong survival nor delay progression in patients treated with radioembolization. Liver toxicity does not differ among the two therapeutic schemes. Full article
(This article belongs to the Special Issue Radiotherapy for Hepatocellular Carcinoma)
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15 pages, 1919 KiB  
Article
Visceral Adipose Tissue Radiodensity Is Linked to Prognosis in Hepatocellular Carcinoma Patients Treated with Selective Internal Radiation Therapy
by Maryam Ebadi, Carlos Moctezuma-Velazquez, Judith Meza-Junco, Vickie E. Baracos, Abha R. DunichandHoedl, Sunita Ghosh, Philippe Sarlieve, Richard J. Owen, Norman Kneteman and Aldo J. Montano-Loza
Cancers 2020, 12(2), 356; https://doi.org/10.3390/cancers12020356 - 4 Feb 2020
Cited by 25 | Viewed by 2930
Abstract
Hepatocellular carcinoma (HCC) constitutes the fourth leading cause of cancer-related mortality. Various factors, such as tumor size, tumor multiplicity, and liver function, have been linked to the prognosis of HCC. The aim of this study was to explore the prognostic significance of muscle, [...] Read more.
Hepatocellular carcinoma (HCC) constitutes the fourth leading cause of cancer-related mortality. Various factors, such as tumor size, tumor multiplicity, and liver function, have been linked to the prognosis of HCC. The aim of this study was to explore the prognostic significance of muscle, subcutaneous and visceral adipose tissue (VAT) mass, and radiodensity, in a cohort of 101 HCC patients treated with selective internal radiation therapy (SIRT). Muscle and adipose tissue cross sectional area (cm2/m2) and radiodensity, reported as the Hounsfield Unit (HU), were determined using pre-SIRT computed tomography images. Cox proportional hazard models and exact logistic regression were conducted to assess associations between body composition and adverse outcomes. Majority of the patients were male (88%) with a mean VAT radiodensity of −85 ± 9 HU. VAT radiodensity was independently associated with mortality (HR 1.05; 95% CI: 1.01–1.08; p = 0.01), after adjusting for cirrhosis etiology, Barcelona Clinic Liver Cancer stage, previous HCC treatment, and portal hypertension markers. Patients with a high VAT radiodensity of ≥–85 HU had a two times higher risk of mortality (HR 2.01, 95% CI 1.14–3.54, p = 0.02), compared to their counterpart. Clinical features of portal hypertension were more prevalent in patients with high VAT radiodensity. High VAT radiodensity was associated with severe adverse events after adjusting for confounding factors. High VAT radiodensity is independently associated with both increased mortality and severe adverse events in patients treated with SIRT. VAT radiodensity measurement might serve as an objective approach to identify patients who will experience the most benefit from SIRT. Full article
(This article belongs to the Special Issue Radiotherapy for Hepatocellular Carcinoma)
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