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Pan Z, Ye YS, Wang ZP, Li W. Predictive value of early-stage postoperative albumin-bilirubin grade on the overall survival of hepatocellular carcinoma patients undergoing resection. Eur J Gastroenterol Hepatol 2024; 36:1464-1469. [PMID: 39475785 DOI: 10.1097/meg.0000000000002866] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/07/2024]
Abstract
OBJECTIVES The albumin-bilirubin (ALBI) and ΔALBI grades have attracted substantial attention for their ability to predict the overall survival (OS) of patients with hepatocellular carcinoma (HCC). This retrospective study aimed to evaluate the predictive value of the ALBI grade at different time points for the OS of patients with HCC who underwent surgical resection. METHODS The clinical data of patients with HCC who underwent radical resection in our hospital were collected and analyzed. The survival rate was analyzed using the Kaplan-Meier method and log-rank test. The risk factors influencing OS were identified via univariate and multivariate Cox regression analyses. RESULTS A total of 104 patients with HCC were included in this study. The 1-, 3-, and 5-year OS rates of these patients were 91.3%, 64.0%, and 60.2%, respectively. The OS rates were significantly higher in patients with early-stage postoperative ALBI grade 2 than in those with grade 3 (P < 0.001); however, the preoperative ALBI grade, later-stage postoperative ALBI grade, ΔALBI grade (early stage), or ΔALBI grade (later stage) did not affect the OS rate. Furthermore, resection of ≥3 Couinaud liver segments [hazard ratio (HR) = 4.74; 95% confidence interval (CI), 2.32-9.67; P < 0.001], occurrence of postoperative complications (HR = 2.95; 95% CI, 1.38-6.31; P = 0.005), and early-stage postoperative ALBI grade 3 (HR = 2.50; 95% CI, 1.18-5.31; P = 0.02) were identified as independent risk factors for the OS of patients with HCC. CONCLUSION Early-stage postoperative ALBI grade can be used to predict the OS of patients with HCC who have undergone radical hepatectomy. Early-stage postoperative ALBI grade 3, resection of ≥3 Couinaud liver segments, and occurrence of postoperative complications are independent risk factors affecting the OS of these patients.
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Affiliation(s)
- Zheng Pan
- Department of Hepatobiliary-Pancreatic Surgery, China-Japan Union Hospital of Jilin University, Changchun, Jilin Province, China
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Gkika E, Radicioni G, Eichhorst A, Kirste S, Sprave T, Nicolay NH, Fichtner-Feigl S, Thimme R, Wiehle R, Brunner TB, Grosu AL. The role of ALBI score in patients treated with stereotactic body radiotherapy for locally advanced primary liver tumors: a pooled analysis of two prospective studies. Front Oncol 2024; 14:1427332. [PMID: 39421444 PMCID: PMC11484445 DOI: 10.3389/fonc.2024.1427332] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2024] [Accepted: 09/10/2024] [Indexed: 10/19/2024] Open
Abstract
Introduction To evaluate the outcomes after stereotactic body radiotherapy (SBRT) for locally advanced primary liver cancer. Materials and methods Patients with locally advanced liver cancer unsuitable for other loco-regional treatments were treated with SBRT with 50-60 Gy in 3-12 fractions in two consecutive prospective trials. Results A total of 83 patients were included, of whom 14 were excluded, leaving 69 evaluable patients with 74 treated lesions. A total of 50 patients had hepatocellular carcinoma (HCC), and 11 patients had cholangiocarcinoma (CCC). Approximately 76% had a Child-Pugh (CP) score of A, while 54% had an albumin-bilirubin (ALBI) score of 1. With a median follow-up of 29 months, the median overall survival (OS) was 11 months, and the progression-free survival (PFS) was 18 months. The ALBI score was an important predictor of overall survival (HR 2.094, p = 0.001), which remained significant also in the multivariate analysis. Patients with an ALBI grade of ≥1 had an OS of 4 months versus 23 months in patients with an ALBI grade of 1 (p ≤ 0.001). The local control at 1 and 2 years was 91%. Thirteen patients developed grade ≥ 3 toxicities, of whom nine patients experienced liver toxicities. Patients with a higher ALBI score had a high risk for developing hepatic failure (OR 6.136, p = 0.006). Discussion SBRT is a very effective treatment with low toxicity and should be considered as a local treatment option in patients with HCC and CCC. Patients with a higher ALBI grade are at risk for developing toxicities after SBRT and have a significantly lower survival rate.
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Affiliation(s)
- Eleni Gkika
- Department of Radiation Oncology, Medical Center - University of Freiburg, Freiburg, Germany
- German Cancer Consortium (DKTK) Partner Site Freiburg, Freiburg, Germany
- Faculty of Medicine, University of Freiburg, Freiburg, Germany
- Department of Radiation Oncology, University Clinic Bonn - University of Bonn, Bonn, Germany
| | - Gianluca Radicioni
- Department of Radiation Oncology, Medical Center - University of Freiburg, Freiburg, Germany
- German Cancer Consortium (DKTK) Partner Site Freiburg, Freiburg, Germany
| | - Alexandra Eichhorst
- Department of Radiation Oncology, Medical Center - University of Freiburg, Freiburg, Germany
- German Cancer Consortium (DKTK) Partner Site Freiburg, Freiburg, Germany
| | - Simon Kirste
- Department of Radiation Oncology, Medical Center - University of Freiburg, Freiburg, Germany
- German Cancer Consortium (DKTK) Partner Site Freiburg, Freiburg, Germany
| | - Tanja Sprave
- Department of Radiation Oncology, Medical Center - University of Freiburg, Freiburg, Germany
- German Cancer Consortium (DKTK) Partner Site Freiburg, Freiburg, Germany
- Faculty of Medicine, University of Freiburg, Freiburg, Germany
| | - Nils Henrik Nicolay
- Department of Radiation Oncology, Medical Center - University of Freiburg, Freiburg, Germany
- German Cancer Consortium (DKTK) Partner Site Freiburg, Freiburg, Germany
- Faculty of Medicine, University of Freiburg, Freiburg, Germany
- Department of Radiation Oncology, University Medical Center Leipzig, Leipzig, Germany
| | - Stefan Fichtner-Feigl
- Faculty of Medicine, University of Freiburg, Freiburg, Germany
- Department of General and Visceral Surgery, Medical Center - University of Freiburg, Freiburg, Germany
| | - Robert Thimme
- Faculty of Medicine, University of Freiburg, Freiburg, Germany
- Department of Medicine II, Gastroenterology, Hepatology, Endocrinology and Infectious Diseases, Medical Center - University of Freiburg, Freiburg, Germany
| | - Rolf Wiehle
- Department of Radiation Oncology, Medical Center - University of Freiburg, Freiburg, Germany
- German Cancer Consortium (DKTK) Partner Site Freiburg, Freiburg, Germany
| | - Thomas B. Brunner
- Department of Radiation Oncology, University Medical Center Graz, Graz, Austria
| | - Anca-Ligia Grosu
- Department of Radiation Oncology, Medical Center - University of Freiburg, Freiburg, Germany
- German Cancer Consortium (DKTK) Partner Site Freiburg, Freiburg, Germany
- Faculty of Medicine, University of Freiburg, Freiburg, Germany
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3
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Brunner TB, Boda-Heggemann J, Bürgy D, Corradini S, Dieckmann UK, Gawish A, Gerum S, Gkika E, Grohmann M, Hörner-Rieber J, Kirste S, Klement RJ, Moustakis C, Nestle U, Niyazi M, Rühle A, Lang ST, Winkler P, Zurl B, Wittig-Sauerwein A, Blanck O. Dose prescription for stereotactic body radiotherapy: general and organ-specific consensus statement from the DEGRO/DGMP Working Group Stereotactic Radiotherapy and Radiosurgery. Strahlenther Onkol 2024; 200:737-750. [PMID: 38997440 PMCID: PMC11343978 DOI: 10.1007/s00066-024-02254-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2024] [Accepted: 06/02/2024] [Indexed: 07/14/2024]
Abstract
PURPOSE AND OBJECTIVE To develop expert consensus statements on multiparametric dose prescriptions for stereotactic body radiotherapy (SBRT) aligning with ICRU report 91. These statements serve as a foundational step towards harmonizing current SBRT practices and refining dose prescription and documentation requirements for clinical trial designs. MATERIALS AND METHODS Based on the results of a literature review by the working group, a two-tier Delphi consensus process was conducted among 24 physicians and physics experts from three European countries. The degree of consensus was predefined for overarching (OA) and organ-specific (OS) statements (≥ 80%, 60-79%, < 60% for high, intermediate, and poor consensus, respectively). Post-first round statements were refined in a live discussion for the second round of the Delphi process. RESULTS Experts consented on a total of 14 OA and 17 OS statements regarding SBRT of primary and secondary lung, liver, pancreatic, adrenal, and kidney tumors regarding dose prescription, target coverage, and organ at risk dose limitations. Degree of consent was ≥ 80% in 79% and 41% of OA and OS statements, respectively, with higher consensus for lung compared to the upper abdomen. In round 2, the degree of consent was ≥ 80 to 100% for OA and 88% in OS statements. No consensus was reached for dose escalation to liver metastases after chemotherapy (47%) or single-fraction SBRT for kidney primaries (13%). In round 2, no statement had 60-79% consensus. CONCLUSION In 29 of 31 statements a high consensus was achieved after a two-tier Delphi process and one statement (kidney) was clearly refused. The Delphi process was able to achieve a high degree of consensus for SBRT dose prescription. In summary, clear recommendations for both OA and OS could be defined. This contributes significantly to harmonization of SBRT practice and facilitates dose prescription and reporting in clinical trials investigating SBRT.
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Affiliation(s)
- Thomas B Brunner
- Department of Radiation Oncology, Medical University of Graz, Auenbruggerplatz 32, 8036, Graz, Austria.
- Department of Therapeutic Radiology and Oncology, Comprehensive Cancer Center, Medical University of Graz, 8036, Graz, Austria.
| | - Judit Boda-Heggemann
- Department of Radiation Oncology, University Medicine Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
| | - Daniel Bürgy
- Department of Radiation Oncology, University Medicine Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
| | - Stefanie Corradini
- Department of Radiation Oncology, University Hospital, LMU Munich, Munich, Germany
| | - Ute Karin Dieckmann
- Department of Radiation Oncology, Medical University of Graz, Auenbruggerplatz 32, 8036, Graz, Austria
| | - Ahmed Gawish
- Department of Radiotherapy, University Medical Center Giessen-Marburg, Marburg, Germany
| | - Sabine Gerum
- Department of Radiation Oncology, Paracelsus University Salzburg, Salzburg, Austria
| | - Eleni Gkika
- Department of Radiation Oncology, University Hospital Bonn, 53127, Bonn, Germany
| | - Maximilian Grohmann
- Department of Radiotherapy and Radiation Oncology, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany
| | - Juliane Hörner-Rieber
- Department of Radiation Oncology, Heidelberg University Hospital, Im Neuenheimer Feld 400, 69120, Heidelberg, Germany
| | - Simon Kirste
- Department of Radiation Oncology, Medical Center-University of Freiburg, Faculty of Medicine, Freiburg, Germany
| | - Rainer J Klement
- Department of Radiotherapy and Radiation Oncology, Leopoldina Hospital Schweinfurt, Robert-Koch-Straße 10, 97422, Schweinfurt, Germany
| | - Christos Moustakis
- Department of Radiation Oncology, University Hospital Leipzig, Stephanstraße 9a, 04103, Leipzig, Germany
| | - Ursula Nestle
- Department of Radiation Oncology, Kliniken Maria Hilf, Moenchengladbach, Germany
| | - Maximilian Niyazi
- Department of Radiation Oncology, Eberhard Karls University Tübingen, Tübingen, Germany
| | - Alexander Rühle
- Department of Radiation Oncology, University Hospital Leipzig, Stephanstraße 9a, 04103, Leipzig, Germany
| | - Stephanie-Tanadini Lang
- Department of Radiation Oncology, University Hospital Zurich, University of Zurich, Rämistrasse 100, 8091, Zurich, Switzerland
| | - Peter Winkler
- Department of Radiation Oncology, Medical University of Graz, Auenbruggerplatz 32, 8036, Graz, Austria
- Department of Therapeutic Radiology and Oncology, Comprehensive Cancer Center, Medical University of Graz, 8036, Graz, Austria
| | - Brigitte Zurl
- Department of Therapeutic Radiology and Oncology, Comprehensive Cancer Center, Medical University of Graz, 8036, Graz, Austria
| | | | - Oliver Blanck
- Department of Radiation Oncology, University Medical Center Schleswig-Holstein, Arnold-Heller-Straße 3, 24105, Kiel, Germany
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Yoshino Y, Suzuki G, Shiomi H, Kimoto T, Seri S, Yamazaki H, Yamada K. Albumin-bilirubin score is a useful predictor of worsening liver reserve after stereotactic body radiation therapy in elderly Japanese patients with hepatocellular carcinoma. JOURNAL OF RADIATION RESEARCH 2024; 65:244-250. [PMID: 38415344 PMCID: PMC10959440 DOI: 10.1093/jrr/rrae006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/25/2023] [Revised: 01/09/2024] [Indexed: 02/29/2024]
Abstract
The prognosis of patients with hepatocellular carcinoma (HCC) is closely related to their liver reserves. The Child-Pugh (CP) score has traditionally been used to evaluate this reserve, with CP Grade B (CP score ≥ 7) associated with a higher risk of radiation-induced liver disease after stereotactic body radiation therapy (SBRT). However, the CP score has limitations, as it does not accurately assess liver reserve capacity. The albumin-bilirubin (ALBI) score has been introduced as a meticulous indicator of liver reserve for the treatment of HCC. We retrospectively evaluated the role of the ALBI score in estimating the worsening liver reserve in 42 patients with HCC treated with SBRT using CyberKnife between 2015 and 2023. The median biologically effective dose (α/β = 10 Gy) was 100 Gy. For a median follow-up duration of 17.4 months, the 1-year overall survival (OS), local control (LC) and progression-free survival (PFS) rates were 100, 98 and 62%, respectively. Worsening liver reserve was defined as an increase in the modified ALBI grade or CP score within 1 year after SBRT. Univariate and multivariate analyses showed that the baseline ALBI score (≥-2.7 vs <-2.7) was the only significantly different predictor of worsening liver reserve. The OS and LC rates after SBRT for HCC were satisfactory. However, the PFS was poor, and recurrent HCC will require additional treatment. It is clinically important to predict the liver reserve capacity after SBRT, and the baseline ALBI score is a useful predictor.
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Affiliation(s)
- Yuki Yoshino
- Department of Radiology, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan
| | - Gen Suzuki
- Department of Radiology, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan
| | - Hiroya Shiomi
- Department of Radiation Oncology, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan
- Department of Radiology, Soseikai CyberKnife Center, Fushimi-ku, Kyoto 612-8248, Japan
| | - Takuya Kimoto
- Department of Radiology, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan
| | - Sho Seri
- Department of Radiology, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan
| | - Hideya Yamazaki
- Department of Radiology, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan
| | - Kei Yamada
- Department of Radiology, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan
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Tsai YL, Yu PC, Nien HH, Lu TP. Time variation of high-risk groups for liver function deteriorations within fluctuating long-term liver function after hepatic radiotherapy in patients with hepatocellular carcinoma. Eur J Med Res 2024; 29:104. [PMID: 38326881 PMCID: PMC10848403 DOI: 10.1186/s40001-024-01692-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2023] [Accepted: 01/20/2024] [Indexed: 02/09/2024] Open
Abstract
PURPOSE The purpose of this study is to find essential risk factors associated with liver function (LF) deteriorations within fluctuating long-term LF and their time-varying effects in patients with hepatocellular carcinoma (HCC) receiving hepatic radiotherapy and to identify high-risk groups for adverse LF deteriorations and their changes over time in facilitating the prevention of hepatic decompensation and the improvement of survival. MATERIALS AND METHODS A total of 133 HCC patients treated by hepatic radiotherapy were enrolled. A study design was conducted to convert posttreatment long-term LF with fluctuating levels over time to recurrent LF events using defined upgrades in a grading scale. The hazard ratios (HR) of pretreatment biochemical, demographic, clinical, and dosimetric factors in developing posttreatment LF events were estimated using the Cox model. Methodologies of the counting process approach, robust variance estimation, goodness-of-fit testing based on the Schoenfeld residuals, and time-dependent covariates in survival analysis were employed to handle the correlation within subjects and evaluate the time-varying effects during long-term follow-up. RESULTS Baseline LF score before radiotherapy and gender were significant factors. Initial HR in developing LF events was 1.17 (95% CI 1.11-1.23; P < 0.001) for each increase of baseline LF score and kept almost constant over time (HR, 1.00; 95% CI 1.00-1.01; P = 0.065). However, no difference was observed regarding initial hazards for gender (HR, 1.00; 95% CI 0.64-1.56; P = 0.994), but the hazard for women got higher monthly over time compared with men (HR, 1.04; 95% CI 1.01-1.07; P = 0.006). CONCLUSIONS High-risk groups for adverse LF deteriorations after hepatic radiotherapy may change over time. Patients with poor baseline LF are vulnerable from the beginning. Women require prevention strategies and careful monitoring for deteriorations at a later stage.
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Affiliation(s)
- Yu-Lun Tsai
- Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan
- Department of Radiation Oncology, Cathay General Hospital, Taipei, Taiwan
| | - Pei-Chieh Yu
- Department of Radiation Oncology, Cathay General Hospital, Taipei, Taiwan
- School of Medicine, China Medical University, Taichung, Taiwan
| | - Hsin-Hua Nien
- Department of Radiation Oncology, Cathay General Hospital, Taipei, Taiwan
- School of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan
- Institute of Biomedical Engineering, College of Electrical and Computer Engineering, National Yang Ming Chiao Tung University, Hsinchu, Taiwan
| | - Tzu-Pin Lu
- Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan.
- Bioinformatics and Biostatistics Core, Center of Genomic and Precision Medicine, National Taiwan University, Taipei, Taiwan.
- Institute of Health Data Analytics and Statistics, College of Public Health, National Taiwan University, Taipei, Taiwan.
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Chiu SH, Lin HH, Feng AC, Lo CH, Hsieh CB, Chen PK, Chang WC. Safety evaluation of combination treatment of drug-eluting bead transarterial chemoembolization and immune checkpoint inhibitors for hepatocellular carcinoma: An increased risk of liver abscess with treatment interval less than one month. Eur J Radiol 2024; 170:111266. [PMID: 38185027 DOI: 10.1016/j.ejrad.2023.111266] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2023] [Revised: 11/17/2023] [Accepted: 12/12/2023] [Indexed: 01/09/2024]
Abstract
PURPOSE To analyze the safety of combination treatment comprising drug-eluting bead transarterial chemoembolization (DEB-TACE) and immune checkpoint inhibitors (ICIs) in hepatocellular carcinoma (HCC). METHOD In total, 208 HCC patients receiving DEB-TACE were enrolled for this retrospective single-institution study. Among them, 50 patients who received ICIs at an interval less than one month from DEB-TACE were categorized into the DEB-ICI group; the remaining 158 patients were categorized into the DEB group. Albumin-bilirubin (ALBI) score before and at three months after DEB-TACE were recorded to evaluate liver function changes. Adverse events within three months after DEB-TACE were considered TACE-related and were compared between the two groups. RESULTS The DEB-ICI group had significantly higher incidence of liver abscess than the DEB group (14.0 % versus 5.1 %, p-value = 0.0337). No significant difference in the other TACE-related adverse events and change of ALBI score between the groups. Univariate logistic regression confirmed that combination with ICIs was an independent risk factor for liver abscess after DEB-TACE (odds ratio = 3.0523, 95 % confidence interval: 1.0474-8.8947, p-value = 0.0409); other parameters including subjective angiographic chemoembolization endpoint scale and combined targeted therapy were nonsignificant risk factors in this study population. In the DEB-ICI group, patients who received ICIs before DEB-TACE exhibited a trend toward liver abscess formation compared with those who received DEB-TACE before ICIs (23.8 % versus 6.9 %, p-value = 0.0922). CONCLUSIONS Combination treatment involving DEB-TACE and ICIs at an interval less than one month increased the risk of liver abscess after DEB-TACE. Greater caution is therefore warranted for HCC patients who receive ICIs and DEB-TACE with this short interval.
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Affiliation(s)
- Sung-Hua Chiu
- Department of Radiology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan; Department of Electrical Engineering, National Taipei University of Technology, Taipei, Taiwan
| | - Hsuan-Hwai Lin
- Division of Gastroenterology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
| | - An-Chieh Feng
- Division of General Surgery, Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
| | - Cheng-Hsiang Lo
- Department of Radiotherapy, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
| | - Chung-Bao Hsieh
- Division of General Surgery, Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
| | - Pin-Ko Chen
- Department of Radiology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
| | - Wei-Chou Chang
- Department of Radiology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
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Elaimy AL, Cao Y, Lawrence TS. Evolution of Response-Based Radiotherapy for Hepatocellular Cancer. Cancer J 2023; 29:266-271. [PMID: 37796644 PMCID: PMC10558084 DOI: 10.1097/ppo.0000000000000679] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/07/2023]
Abstract
ABSTRACT Stereotactic body radiation therapy has emerged as a safe and effective treatment modality for properly selected hepatocellular cancer (HCC) patients with normal liver function. However, many HCC patients have reduced baseline liver function due to underlying cirrhosis or prior liver-directed therapies. Therefore, because of the increased risk of hepatotoxicity, the use of stereotactic body radiation therapy for patients with reduced liver function has been approached with caution. Individualized, response-based radiotherapy incorporates models, imaging tools, and biomarkers that determine the dose-response relationship of the liver before, during, and after treatment and has been useful in reducing the likelihood of liver damage without sacrificing tumor control. This review discusses the evolution of response-based radiotherapy for HCC and highlights areas for further investigation.
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Affiliation(s)
- Ameer L Elaimy
- From the Department of Radiation Oncology, University of Michigan, Ann Arbor, MI
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8
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Joo J, Jeon H, Kim D, Kim W, Nam J, Kim D, Park D, Kim C, Ki Y. Predictive Power of the Albumin-Bilirubin Score for Hepatotoxicity in Stereotactic Ablative Radiation Therapy for Hepatocellular Carcinoma. Cancers (Basel) 2023; 15:3777. [PMID: 37568593 PMCID: PMC10416911 DOI: 10.3390/cancers15153777] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2023] [Revised: 07/14/2023] [Accepted: 07/18/2023] [Indexed: 08/13/2023] Open
Abstract
Assessment of liver function is crucial in predicting treatment outcomes for hepatocellular carcinoma (HCC). This study aimed to evaluate the prognostic performance of the albumin-bilirubin (ALBI) score for predicting hepatotoxicity following stereotactic body radiation therapy (SBRT) in HCC patients. A retrospective analysis was conducted on 123 HCC cases treated between 2018 and 2020. ALBI and Child-Turcotte-Pugh (CTP) scores were calculated, and hepatotoxicity was defined as a post-SBRT CTP score increase ≥2. Receiver operating characteristic (ROC) curves were used for comparison. The optimal cutoff value of the ALBI score was determined. Among the 121 patients analyzed, hepatotoxicity occurred in 5%. The ALBI score showed better predictive accuracy (area under the ROC curve: 0.77) than the CTP score. The optimal cutoff value of the ALBI score was -2.47, with a sensitivity of 85.7% and a specificity of 71.1%. Multivariable analysis revealed that ALBI score and PTV were significant factors for hepatotoxicity. In conclusion, the ALBI score demonstrated prognostic value for hepatotoxicity prediction after SBRT in HCC patients. Considering the ALBI score and PTV provides valuable insights for assessing hepatotoxicity risk during SBRT treatment for HCC.
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Affiliation(s)
- Jihyeon Joo
- Department of Radiation Oncology, Pusan National University School of Medicine, Yangsan 50612, Republic of Korea; (J.J.)
- Department of Radiation Oncology, Pusan National University Yangsan Hospital, Yangsan 50612, Republic of Korea
| | - Hosang Jeon
- Department of Radiation Oncology, Pusan National University Yangsan Hospital, Yangsan 50612, Republic of Korea
| | - Dongwoon Kim
- Department of Radiation Oncology, Pusan National University Yangsan Hospital, Yangsan 50612, Republic of Korea
| | - Wontaek Kim
- Department of Radiation Oncology, Pusan National University School of Medicine, Yangsan 50612, Republic of Korea; (J.J.)
- Department of Radiation Oncology, Pusan National University Hospital, Busan 49241, Republic of Korea
| | - Jiho Nam
- Department of Radiation Oncology, Pusan National University Hospital, Busan 49241, Republic of Korea
| | - Donghyun Kim
- Department of Radiation Oncology, Pusan National University School of Medicine, Yangsan 50612, Republic of Korea; (J.J.)
- Department of Radiation Oncology, Pusan National University Hospital, Busan 49241, Republic of Korea
| | - Dahl Park
- Department of Radiation Oncology, Pusan National University Hospital, Busan 49241, Republic of Korea
| | - Choongrak Kim
- Department of Statistics, Pusan National University, Busan 46241, Republic of Korea
| | - Yongkan Ki
- Department of Radiation Oncology, Pusan National University School of Medicine, Yangsan 50612, Republic of Korea; (J.J.)
- Department of Radiation Oncology, Pusan National University Yangsan Hospital, Yangsan 50612, Republic of Korea
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9
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Liu Y, Chou B, Yalamanchili A, Lim SN, Dawson LA, Thomas TO. Local Therapies for Hepatocellular Carcinoma and Role of MRI-Guided Adaptive Radiation Therapy. J Clin Med 2023; 12:jcm12103517. [PMID: 37240623 DOI: 10.3390/jcm12103517] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2023] [Revised: 04/19/2023] [Accepted: 05/06/2023] [Indexed: 05/28/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the most common liver tumor, with a continually rising incidence. The curative treatment for HCC is surgical resection or liver transplantation; however, only a small portion of patients are eligible due to local tumor burden or underlying liver dysfunction. Most HCC patients receive nonsurgical liver-directed therapies (LDTs), including thermal ablation, transarterial chemoembolization (TACE), transarterial radioembolization (TARE), and external beam radiation therapy (EBRT). Stereotactic ablative body radiation (SABR) is a specific type of EBRT that can precisely deliver a high dose of radiation to ablate tumor cells using a small number of treatments (or fractions, typically 5 or less). With onboard MRI imaging, MRI-guided SABR can improve therapeutic dose while minimizing normal tissue exposure. In the current review, we discuss different LDTs and compare them with EBRT, specifically SABR. The emerging MRI-guided adaptive radiation therapy has been reviewed, highlighting its advantages and potential role in HCC management.
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Affiliation(s)
- Yirong Liu
- Department of Radiation Oncology, Northwestern Medicine, Chicago, IL 60611, USA
| | - Brian Chou
- Department of Radiation Oncology, Loyola University Medical Center, Maywood, IL 60153, USA
| | - Amulya Yalamanchili
- Department of Radiation Oncology, Northwestern Medicine, Chicago, IL 60611, USA
| | - Sara N Lim
- Department of Radiation Oncology, Northwestern Medicine, Chicago, IL 60611, USA
| | - Laura A Dawson
- Department of Radiation Oncology, Princess Margaret Cancer Centre, University of Toronto, Toronto, ON M5S 1A1, Canada
| | - Tarita O Thomas
- Department of Radiation Oncology, Northwestern Medicine, Chicago, IL 60611, USA
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10
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Su TS, Liang SX, Li LQ, Liu QH, Duan XZ, Sun J, Zeng H, Zhu HS, Li JX, Zhu XF, Zhuang HQ, Liang P, Huang Y. New Staging Model for Radiation-based Hepatocellular Carcinoma Treatment: A National Multicenter Study. J Clin Transl Hepatol 2023; 11:341-349. [PMID: 36643048 PMCID: PMC9817045 DOI: 10.14218/jcth.2022.00002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/01/2022] [Revised: 04/23/2022] [Accepted: 05/05/2022] [Indexed: 01/18/2023] Open
Abstract
BACKGROUND AND AIMS The study aimed to create a new staging model for radiotherapy-based treatment for prognostic hepatocellular carcinoma (HCC) classification. METHODS The training cohort comprised 658 patients receiving stereotactic body radiotherapy and external validation cohort comprised 533 patients receiving three-dimensional conformal radiotherapy and intensity-modulated radiotherapy. We established a modified staging system as follows: stage I, solitary nodule without macrovascular invasion, or 2-3 nodules no more than 3.0 cm apart, and performance status (PS) 0-2 (Ia: ALBI-1 grade; Ib: ALBI-2 or 3 grade); stage II: 2-3 nodules with any one nodule more than 3.0-cm apart, or ≥4 nodules, and performance status 0-2 (IIa: ALBI-1 grade; IIb: ALBI-2 grade); stage III: macrovascular invasion, regional lymph node metastasis or distant metastasis, and performance status 0-2 (IIIa: ALBI-1 grade; IIIb: ALBI-2 grade); stage IV: performance status 3-4, or performance status 0-2 with ALBI-3 grade. We analyzed long-term overall survival based on different stages. RESULTS The staging model showed an excellent ability to discriminate patients according to four stages and seven substages with notably different curves in the training and validation cohort. The median survival decreased from stages I to IV with 63.0 months in stage I (not reached in Ia, and 53.0 months in Ib), 24.0 months in stage II (28.0 months in IIa, and 22.0 months in IIb), 11.0 months in stage III (18.0 months in IIIa, and 9.0 months in IIIb), and less than 9.0 months in stage IV in the training cohort. CONCLUSIONS The modified staging model may provide an alternative for clinical radiation oncologists.
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Affiliation(s)
- Ting-Shi Su
- Department of Radiation Oncology, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, China
- Correspondence to: Ting-Shi Su, Department of Radiation Oncology, Guangxi Medical University Cancer Hospital, Nanning, Guangxi 530001, China. ORCID: https://orcid.org/0000-0003-3097-4394. Tel: +86-18878708186, Fax: +86-771-5331466, E-mail:
| | - Shi-Xiong Liang
- Department of Radiation Oncology, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, China
| | - Li-Qing Li
- Department of Radiation Oncology, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, China
| | - Qiu-Hua Liu
- Department of Radiation Oncology, Ruikang Hospital, Nanning, Guangxi, China
| | - Xue-Zhang Duan
- Radiation Oncology Department, The Fifth Medical Center of PLA General Hospital, Beijing, China
| | - Jing Sun
- Radiation Oncology Department, The Fifth Medical Center of PLA General Hospital, Beijing, China
| | - Hai Zeng
- Department of Oncology, First Affiliated Hospital of Yangtze University, Jingzhou, Hubei, China
| | - Hai-Sheng Zhu
- Department of Oncology, Sixth Affiliated Hospital of Guangxi Medical University, First People’s Hospital of Yulin, Yulin, Guangxi, China
| | - Jian-Xu Li
- Department of Radiation Oncology, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, China
| | - Xiao-Fei Zhu
- Department of Radiation Oncology, Changhai Hospital Affiliated to Navy Medical University, Shanghai, China
| | - Hong-Qing Zhuang
- Department of Radiation Oncology, Peking University Third Hospital, Beijing, China
| | - Ping Liang
- Department of Radiation Oncology, Ruikang Hospital, Nanning, Guangxi, China
- Department of Radiation Oncology, Nanning First People’s Hospital, Nanning, Guangxi, China
| | - Yong Huang
- Department of Radiation Oncology, Ruikang Hospital, Nanning, Guangxi, China
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11
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Jeng LB, Chan WL, Teng CF. Prognostic Significance of Serum Albumin Level and Albumin-Based Mono- and Combination Biomarkers in Patients with Hepatocellular Carcinoma. Cancers (Basel) 2023; 15:cancers15041005. [PMID: 36831351 PMCID: PMC9953807 DOI: 10.3390/cancers15041005] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2023] [Revised: 01/31/2023] [Accepted: 02/03/2023] [Indexed: 02/08/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the predominant form of primary liver cancer. Although many surgical and nonsurgical therapeutic options have been established for treating HCC, the overall prognosis for HCC patients receiving different treatment modalities remains inadequate, which causes HCC to remain among the most life-threatening human cancers worldwide. Therefore, it is vitally important and urgently needed to develop valuable and independent prognostic biomarkers for the early prediction of poor prognosis in HCC patients, allowing more time for more timely and appropriate treatment to improve the survival of patients. As the most abundant protein in plasma, human serum albumin (ALB) is predominantly expressed by the liver and exhibits a wide variety of essential biological functions. It has been well recognized that serum ALB level is a significant independent biomarker for a broad spectrum of human diseases including cancer. Moreover, ALB has been commonly used as a potent biomaterial and therapeutic agent in clinical settings for the treatment of various human diseases. This review provides a comprehensive summary of the evidence from the up-to-date published literature to underscore the prognostic significance of serum ALB level and various ALB-based mono- and combination biomarkers in the prediction of the prognosis of HCC patients after treatment with different surgical, locoregional, and systemic therapies.
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Affiliation(s)
- Long-Bin Jeng
- Organ Transplantation Center, China Medical University Hospital, Taichung 404, Taiwan
- Department of Surgery, China Medical University Hospital, Taichung 404, Taiwan
- Cell Therapy Center, China Medical University Hospital, Taichung 404, Taiwan
| | - Wen-Ling Chan
- Department of Bioinformatics and Medical Engineering, Asia University, Taichung 413, Taiwan
- Epigenome Research Center, China Medical University Hospital, Taichung 404, Taiwan
| | - Chiao-Fang Teng
- Organ Transplantation Center, China Medical University Hospital, Taichung 404, Taiwan
- Graduate Institute of Biomedical Sciences, China Medical University, Taichung 404, Taiwan
- Program for Cancer Biology and Drug Development, China Medical University, Taichung 404, Taiwan
- Research Center for Cancer Biology, China Medical University, Taichung 404, Taiwan
- Correspondence: ; Tel.: +886-4-2205-2121; Fax: +886-4-2202-9083
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Kim TH, Kim BH, Park JW, Cho YR, Koh YH, Chun JW, Oh ES, Lee DY, Lee SU, Suh YG, Woo SM, Moon SH, Kim SS, Lee WJ. Proton Beam Therapy for Treatment-Naïve Hepatocellular Carcinoma and Prognostic Significance of Albumin-Bilirubin (ALBI) Grade. Cancers (Basel) 2022; 14:cancers14184445. [PMID: 36139604 PMCID: PMC9497120 DOI: 10.3390/cancers14184445] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2022] [Revised: 09/08/2022] [Accepted: 09/12/2022] [Indexed: 11/16/2022] Open
Abstract
To evaluate the efficacy of proton beam therapy (PBT) as an initial treatment in treatment-naïve hepatocellular carcinoma (HCC) patients and to assess the prognostic significance of albumin-bilirubin (ALBI) grade, 46 treatment-naïve HCC patients treated with PBT were analyzed. The ALBI grade distribution was grade 1 in 11 (23.9%) patients, grade 2 in 34 (73.9%) patients, and grade 3 in 1 (2.2%) patient. The median duration of follow-up was 56.5 months (95% confidence interval [CI], 48.2−64.7). Among the 46 patients, disease progression was observed in 23 (50%) patients: local progression in 3 (6.5%) patients; intrahepatic progression in 22 (47.8%); and extrahepatic progression in 5 (10.9%). The 5-year freedom from local progression (FFLP), progression-free survival (PFS), and overall survival (OS) rates were 92.7% (95% CI, 84.7−100.7), 43.3% (95% CI, 28.2−58.4), and 69.2% (95% CI, 54.9−83.5), respectively. In multivariate analysis, there were no independent factors for FFLP (p > 0.05 each), but tumor stage and ALBI grade were independent factors for PFS and OS (p < 0.05 each). PBT could result in comparable OS in treatment-naïve HCC patients to other recommended first-line treatments, and ALBI grade, in addition to tumor stage, could be useful for predicting OS.
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Affiliation(s)
- Tae Hyun Kim
- Center for Liver and Pancreatobiliary Cancer, National Cancer Center, Goyang 10408, Korea
- Center for Proton Therapy, National Cancer Center, Goyang 10408, Korea
- Correspondence: ; Tel.: +82-31-920-1725; Fax: +82-31-920-0149
| | - Bo Hyun Kim
- Center for Liver and Pancreatobiliary Cancer, National Cancer Center, Goyang 10408, Korea
| | - Joong-Won Park
- Center for Liver and Pancreatobiliary Cancer, National Cancer Center, Goyang 10408, Korea
| | - Yu Ri Cho
- Center for Liver and Pancreatobiliary Cancer, National Cancer Center, Goyang 10408, Korea
| | - Young-Hwan Koh
- Center for Liver and Pancreatobiliary Cancer, National Cancer Center, Goyang 10408, Korea
| | - Jung Won Chun
- Center for Liver and Pancreatobiliary Cancer, National Cancer Center, Goyang 10408, Korea
| | - Eun Sang Oh
- Center for Proton Therapy, National Cancer Center, Goyang 10408, Korea
| | - Do Yeul Lee
- Center for Proton Therapy, National Cancer Center, Goyang 10408, Korea
| | - Sung Uk Lee
- Center for Proton Therapy, National Cancer Center, Goyang 10408, Korea
| | - Yang-Gun Suh
- Center for Proton Therapy, National Cancer Center, Goyang 10408, Korea
| | - Sang Myung Woo
- Center for Liver and Pancreatobiliary Cancer, National Cancer Center, Goyang 10408, Korea
| | - Sung Ho Moon
- Center for Proton Therapy, National Cancer Center, Goyang 10408, Korea
| | - Sang Soo Kim
- Center for Proton Therapy, National Cancer Center, Goyang 10408, Korea
| | - Woo Jin Lee
- Center for Liver and Pancreatobiliary Cancer, National Cancer Center, Goyang 10408, Korea
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13
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Nehlsen AD, Sindhu KK, Wolken T, Khan F, Kyriakakos CK, Ward SC, Moshier E, Taouli B, Buckstein M. Characterization and Prediction of Signal Intensity Changes in Normal Liver Parenchyma on Gadoxetic Acid-enhanced MRI Scans after Liver-directed Radiation Therapy. Radiol Imaging Cancer 2022; 4:e210100. [PMID: 35904411 PMCID: PMC9358658 DOI: 10.1148/rycan.210100] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2021] [Revised: 05/17/2022] [Accepted: 06/15/2022] [Indexed: 06/15/2023]
Abstract
Purpose To better characterize and understand the significance of focal liver reaction (FLR) development in a large cohort of patients who underwent gadoxetic acid-enhanced MRI after being treated with radiation therapy (RT) for hepatobiliary tumors. Materials and Methods This retrospective study evaluated 100 patients (median age, 65 years [first and third quartiles, 60-69 years]; 80 men) who underwent RT for hepatocellular carcinoma, bile duct tumors, or liver metastases at Mount Sinai Hospital between March 1, 2018, and February 29, 2020. CT simulation scans were fused to MRI scans obtained 1-6 months and 6-12 months after RT, using the hepatobiliary phase of the MRI. To define FLR volume, two radiation oncologists independently delineated the borders of the hypointensity observed on MRI scans in the liver region where RT was delivered. Biologically effective dose (BED) thresholds for the formation of FLRs were calculated, along with albumin-bilirubin (ALBI) scores and grades, and overall survival. Results Most patients developed FLRs, which decreased in volume over time. Median BED threshold values for FLR development were 63.6 Gy at 1-6 months and 88.7 Gy at 6-12 months. While higher baseline ALBI scores were associated with a lower rate of FLRs, there was a significant association between FLR volume and increase in ALBI score at 1-6 months (P = .048). Twelve- and 24-month survival estimates for the cohort were 81% and 48%, respectively. Histopathologic analysis of seven explanted liver specimens demonstrated findings consistent with radiation-induced liver disease. Conclusion FLRs were a clear measure of liver damage after RT and were associated with the development of liver dysfunction and focal radiation-induced liver disease. Keywords: MRI, Radiation Therapy Supplemental material is available for this article. © RSNA, 2022.
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14
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Child-Pugh Score and ABCG2-rs2231142 Genotype Independently Predict Survival in Advanced Hepatoma Patients Treated with Sorafenib. J Clin Med 2022; 11:jcm11092550. [PMID: 35566676 PMCID: PMC9105641 DOI: 10.3390/jcm11092550] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2022] [Revised: 04/29/2022] [Accepted: 04/29/2022] [Indexed: 01/27/2023] Open
Abstract
Patients with advanced hepatocellular carcinoma (HCC) are treated by immunotherapy and/or targeted agents, such as sorafenib. Several single nucleotide polymorphisms (SNPs) and clinical scores have been proposed as prognostic markers in HCC patients treated with sorafenib. This study aimed to validate the prognostic values of these markers in a tertiary referral medical center. Two independent cohorts (cohort-1 [n = 97] and cohort-2 [n = 60]) of advanced HCC patients treated with sorafenib monotherapy were enrolled. Univariate followed by multivariate Cox proportional hazard analysis identified Child−Pugh (CP) score (p < 0.001) and renal insufficiency during treatment (p < 0.001) as independent predictors in cohort-1 patients. The same analytic method revealed ascites (p = 0.000), CP score (p = 0.001), infection during treatment (p < 0.001), and ATP-binding cassette subfamily G member 2 (ABCG2)-rs2231142 genotype (p = 0.003) as independent predictors in cohort-2 patients. ABCG2-rs2231142 genotype “CC” was associated with unfavorable overall survival in sorafenib-treated HCC patients. In conclusion, the CP score and ABCG2-rs2231142 genotype served as independent survival predictors for advanced HCC patients receiving sorafenib treatment.
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15
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D'Avola D, Granito A, Torre-Aláez MDL, Piscaglia F. The importance of liver functional reserve in the non-surgical treatment of hepatocellular carcinoma. J Hepatol 2022; 76:1185-1198. [PMID: 34793869 DOI: 10.1016/j.jhep.2021.11.013] [Citation(s) in RCA: 46] [Impact Index Per Article: 15.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/08/2020] [Revised: 11/02/2021] [Accepted: 11/05/2021] [Indexed: 02/08/2023]
Abstract
The aim of any oncological treatment is not just to eliminate the tumour, but to maximise patient survival and quality of life. Since the liver has a vital function, any radical treatment that severely compromises liver function will result in a shortening of life expectancy, rather than a prolongation. Furthermore, even non-severe liver damage may prevent the delivery of further effective therapies. This is particularly important in the case of hepatocellular carcinoma (HCC), as it is associated with underlying cirrhosis in most patients - cirrhosis itself is not only a potentially lethal disease and independent prognostic factor in HCC, but it also makes liver function fragile. Accordingly, some information about liver dysfunction is included in most staging systems for HCC and can be used to guide the selection of treatments that the functional liver reserve can tolerate. Unfortunately, the prediction of functional damage to the liver in the case of antitumor treatments is very challenging and still suboptimal in any given patient. Moreover, while the assessment of functional reserve can now be used to avoid postoperative liver failure in the surgical setting, its use has been less well clarified for non-surgical therapies, which is of particular relevance today, as several lines of effective non-surgical treatments, including systemic therapies, have become available. The present article will a) critically review the implications of the assessment of liver functional reserve in patients with HCC, b) illustrate the available tools to assess liver functional reserve and c) discuss the role of functional assessment for each type of non-surgical therapy for HCC.
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Affiliation(s)
- Delia D'Avola
- Liver Unit, Internal Medicine Department, Clinica Universidad de Navarra, Pamplona and Madrid, Spain; Centro de Investigación Bio Medica en Red de Enfermedades Hepáticas y Digestivas (Ciberehd), Pamplona, Spain
| | - Alessandro Granito
- Division of Internal Medicine, Hepatobiliary and Immunoallergic Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Italy; Department of Medical and Surgical Sciences, University of Bologna, Italy
| | - Manuel de la Torre-Aláez
- Liver Unit, Internal Medicine Department, Clinica Universidad de Navarra, Pamplona and Madrid, Spain
| | - Fabio Piscaglia
- Division of Internal Medicine, Hepatobiliary and Immunoallergic Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Italy; Department of Medical and Surgical Sciences, University of Bologna, Italy.
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16
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Johnson PJ, Pinato DJ, Kalyuzhnyy A, Toyoda H. Breaking the Child-Pugh Dogma in Hepatocellular Carcinoma. J Clin Oncol 2022; 40:2078-2082. [PMID: 35344390 DOI: 10.1200/jco.21.02373] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Affiliation(s)
- Philip James Johnson
- Department of Molecular and Clinical Cancer Medicine, University of Liverpool, Liverpool, United Kingdom
| | - David J Pinato
- Department of Surgery & Cancer, Imperial College London, Hammersmith Hospital, London, United Kingdom.,Division of Oncology, Department of Translational Medicine, University of Piemonte Orientale, Novara, Italy
| | - Anton Kalyuzhnyy
- Computational Biology Facility, University of Liverpool, Liverpool, United Kingdom
| | - Hidenori Toyoda
- Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Ogaki, Japan
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17
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Dong D, Zhu X, Wang H, Li L, Wan M, Li S, Zhang Y, Geng J, Li Y, Wang W. Prognostic significance of albumin-bilirubin score in patients with unresectable hepatocellular carcinoma undergoing combined immunotherapy and radiotherapy. J Med Imaging Radiat Oncol 2022; 66:662-670. [PMID: 35243796 DOI: 10.1111/1754-9485.13398] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2021] [Revised: 01/17/2022] [Accepted: 02/15/2022] [Indexed: 01/27/2023]
Abstract
INTRODUCTION We aimed to explore the prognostic value of albumin-bilirubin (ALBI) scores in unresectable hepatocellular carcinoma (HCC) treated with combined immune checkpoint inhibitors (ICIs) and radiotherapy (RT). METHODS Patients with unresectable HCC receiving combined ICI and RT (July 2018 to February 2021) were retrospectively enrolled and analysed. Cox regression modelling was implemented to identify prognostic factors. Survival analysis was performed using the Kaplan-Meier method. Survival was compared using log-rank tests. RESULTS A total of 38 patients were enrolled. The median follow-up was 16.5 months (range: 6.7-29.9). The objective response rate (ORR) was 28.9%, including complete response in three (7.9%) patients. The median progression-free survival (PFS) was 5.6 months (95% confidence interval (CI): 3.2-8.0), and the median overall survival (OS) was 12.9 months (95% CI: 8.3-17.6). In the multivariate Cox regression analysis, ALBI score and age were identified as independent prognostic factors for PFS and OS. Patients with grade 1 ALBI scores who were ≥53 years of age (the low-risk group) had statistically significantly higher ORRs (50.0% vs. 13.6%) and prolonged median PFS (15.3 vs. 2.7 months) and OS (not reached vs. 10.1 months). Grade 3 haematological toxicities and/or liver function abnormalities occurred in 15 (39.5%) patients; treatment was not interrupted. No grade 4 or higher side effects were observed. CONCLUSION Combined ICI and RT is an effective modality for treating unresectable HCC with moderate side effects. ALBI scores merits consideration when applying this combined treatment modality. These results should be validated within large cohort studies.
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Affiliation(s)
- Dezuo Dong
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Radiation Oncology, Peking University Cancer Hospital & Institute, Beijing, China
| | - Xianggao Zhu
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Radiation Oncology, Peking University Cancer Hospital & Institute, Beijing, China
| | - Hongzhi Wang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Radiation Oncology, Peking University Cancer Hospital & Institute, Beijing, China
| | - Lijuan Li
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Radiation Oncology, Peking University Cancer Hospital & Institute, Beijing, China
| | - Meng Wan
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Radiation Oncology, Peking University Cancer Hospital & Institute, Beijing, China
| | - Shuai Li
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Radiation Oncology, Peking University Cancer Hospital & Institute, Beijing, China
| | - Yangzi Zhang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Radiation Oncology, Peking University Cancer Hospital & Institute, Beijing, China
| | - Jianhao Geng
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Radiation Oncology, Peking University Cancer Hospital & Institute, Beijing, China
| | - Yongheng Li
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Radiation Oncology, Peking University Cancer Hospital & Institute, Beijing, China
| | - Weihu Wang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Radiation Oncology, Peking University Cancer Hospital & Institute, Beijing, China
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Leveraging Blood-Based Diagnostics to Predict Tumor Biology and Extend the Application and Personalization of Radiotherapy in Liver Cancers. Int J Mol Sci 2022; 23:ijms23041926. [PMID: 35216045 PMCID: PMC8879105 DOI: 10.3390/ijms23041926] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2022] [Revised: 02/01/2022] [Accepted: 02/03/2022] [Indexed: 01/27/2023] Open
Abstract
While the incidence of primary liver cancers has been increasing worldwide over the last few decades, the mortality has remained consistently high. Most patients present with underlying liver disease and have limited treatment options. In recent years, radiotherapy has emerged as a promising approach for some patients; however, the risk of radiation induced liver disease (RILD) remains a limiting factor for some patients. Thus, the discovery and validation of biomarkers to measure treatment response and toxicity is critical to make progress in personalizing radiotherapy for liver cancers. While tissue biomarkers are optimal, hepatocellular carcinoma (HCC) is typically diagnosed radiographically, making tumor tissue not readily available. Alternatively, blood-based diagnostics may be a more practical option as blood draws are minimally invasive, widely availability and may be performed serially during treatment. Possible blood-based diagnostics include indocyanine green test, plasma or serum levels of HGF or cytokines, circulating blood cells and genomic biomarkers. The albumin–bilirubin (ALBI) score incorporates albumin and bilirubin to subdivide patients with well-compensated underlying liver dysfunction (Child–Pugh score A) into two distinct groups. This review provides an overview of the current knowledge on circulating biomarkers and blood-based scores in patients with malignant liver disease undergoing radiotherapy and outlines potential future directions.
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Mak SH, Wong SMN, Chiu WHK, Chiang CL, Yip WLW, Ho HMC, Yeung SYC, Chan KHM, Lee WYV, Lee ASF. Presence of tumour capsule on contrast-enhanced CT is associated with improved outcomes of stereotactic body radiation therapy in hepatocellular carcinoma patients. Strahlenther Onkol 2022; 198:639-647. [PMID: 34988623 DOI: 10.1007/s00066-021-01879-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2021] [Accepted: 11/01/2021] [Indexed: 10/19/2022]
Abstract
PURPOSE Stereotactic body radiation therapy (SBRT) is a novel local therapy for the treatment of hepatocellular carcinoma (HCC). While effective, there is currently no reliable radiological marker to guide patient selection. In this study, we investigated the prognostic value of capsule appearance on contrast-enhanced computed tomography (CT) for patients undergoing SBRT. MATERIALS AND METHODS Between 2006 and 2017, 156 consecutive patients with Child-Pugh score class A/B and HCC ≥ 5 cm who underwent SBRT were retrospectively analysed. Baseline triple-phase CTs of the abdomen were reviewed for the presence of capsule appearances and correlated with objective response rate (ORR), overall survival (OS) and pattern of treatment failure. RESULTS Capsule appearance on CT was present in 83 (53.2%) patients. It was associated with improved ORR by Response Evaluation Criteria in Solid Tumours (RECIST) (60.2 vs. 24.7%, p < 0.001) and Modified Response Evaluation Criteria in Solid Tumours (mRECIST) (78.3 vs. 34.2%, p < 0.001). The presence of a capsule was also associated with superior 2‑year local control (89.1 vs. 51.4%, p < 0.001) and 2‑year OS (34.1 vs. 14.8%, p < 0.01). Hepatic out-field failure was the dominant mode of progression, which was less common in patients with intact capsule (54.2 vs. 60.3%, p = 0.01). CONCLUSION Capsule appearance on CT could potentially be a non-invasive prognostic marker for selecting HCC patients to undergo SBRT. A larger cohort is warranted to validate our findings.
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Affiliation(s)
- Siu Hin Mak
- Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
| | | | - Wan Hang Keith Chiu
- Department of Diagnostic Radiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
| | - Chi Leung Chiang
- Department of Clinical Oncology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
| | | | - Hoi Man Connie Ho
- Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
| | | | - Ka Heng Mark Chan
- Department of Radiation Oncology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.,Groningen Proton Therapy Center, University Medical Center Groningen, Groningen, The Netherlands
| | - Wan Yan Venus Lee
- Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
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20
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Mullikin TC, Pepin KM, Evans JE, Venkatesh SK, Ehman RL, Merrell KW, Haddock MG, Harmsen WS, Herman MG, Hallemeier CL. Evaluation of Pretreatment Magnetic Resonance Elastography for the Prediction of Radiation-Induced Liver Disease. Adv Radiat Oncol 2021; 6:100793. [PMID: 34820550 PMCID: PMC8601961 DOI: 10.1016/j.adro.2021.100793] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2021] [Accepted: 08/26/2021] [Indexed: 11/29/2022] Open
Abstract
Purpose Magnetic resonance (MR) elastography (E) is a noninvasive technique for quantifying liver stiffness (LS) for fibrosis. This study evaluates whether LS is associated with risk of developing radiation-induced liver disease (RILD) in patients receiving liver-directed radiation therapy (RT). Methods and Materials Based on prior studies, LS ≤3 kPa was considered normal and LS >3.0 kPa as representing fibrosis. RILD was defined as an increase in Child-Pugh (CP) score of ≥2 from baseline within 1 year of RT. Univariate and multivariate Cox models were used to assess correlation. Results One hundred two patients, 51 with primary liver tumors and 51 with liver metastases, were identified with sufficient follow-up. In univariate models, pre-RT LS >3.0 kPa (hazard ratio [HR] 4.9; 95% confidence interval [CI], 1.6-14; P = .004), body mass index (BMI), clinical cirrhosis, CP score, albumin-bilirubin (ALBI) grade 2, primary liver tumor, and mean liver dose were significantly associated with risk of post-RT RILD. In a multivariate analysis, LS >3.0 and mean liver dose both were significantly associated with RILD risk. Conclusions Elevated pre-RT LS is associated with an increased risk of RILD in patients receiving liver-directed RT.
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Affiliation(s)
- Trey C Mullikin
- Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota
| | - Kay M Pepin
- Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota
| | - Jaden E Evans
- Department of Radiation Oncology, Intermountain Health Care, Ogden, Utah
| | | | | | | | | | - William S Harmsen
- Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota
| | - Michael G Herman
- Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota
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Demirtas CO, D’Alessio A, Rimassa L, Sharma R, Pinato DJ. ALBI grade: Evidence for an improved model for liver functional estimation in patients with hepatocellular carcinoma. JHEP Rep 2021; 3:100347. [PMID: 34505035 PMCID: PMC8411239 DOI: 10.1016/j.jhepr.2021.100347] [Citation(s) in RCA: 97] [Impact Index Per Article: 24.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/11/2021] [Revised: 07/19/2021] [Accepted: 07/22/2021] [Indexed: 01/27/2023] Open
Abstract
Hepatocellular carcinoma (HCC) usually arises in the context of a chronically damaged liver. Liver functional estimation is of paramount importance in clinical decision making. The Child-Pugh score (CPS) can be used to categorise patients into 3 classes (A to C) based on the severity of liver functional impairment according to 5 parameters (albumin, bilirubin, prothrombin time, presence of ascites and hepatic encephalopathy). The albumin-bilirubin (ALBI) grade has emerged as an alternative, reproducible and objective measure of liver functional reserve in patients with HCC, defining worsening liver impairment across 3 grades (I to III). The ALBI score can identify different subgroups of patients with different prognoses across the diverse Barcelona Clinic Liver Cancer stages and CP classes, making it an appealing clinical predictor. In patients treated with potentially curative approaches (resection, transplantation, radiofrequency ablation, microwave ablation), ALBI grade has been shown to correlate with survival, tumour relapse, and post-hepatectomy liver failure. ALBI grade also predicts survival, toxicity and post-procedural liver failure in patients treated with transarterial chemoembolisation, radioembolisation, external beam radiotherapy as well as multi-kinase inhibitors (sorafenib, lenvatinib, cabozantinib, regorafenib) and immune checkpoint inhibitor therapy. In this review, we summarise the body of evidence surrounding the role of ALBI grade as a biomarker capable of optimising patient selection and therapeutic sequencing in HCC.
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Key Words
- ALBI, albumin-bilirubin
- APRI, aspartate aminotransferase to platelet count index
- BCLC, Barcelona Clinic Liver Cancer
- CLD, chronic liver disease
- CPS, Child-Pugh score
- Child-Pugh
- HCC
- HCC, hepatocellular carcinoma
- ICIs, immune checkpoint inhibitors
- LT, liver transplantation
- MELD, model for end-stage liver disease
- ORR, objective response rate
- OS, overall survival
- PHLF, post-hepatectomy liver failure
- RFS, recurrence-free survival
- TACE, transarterial chemoembolisation
- TARE, transarterial radioembolisation
- cirrhosis
- liver function
- mAb, monoclonal antibody
- prognosis
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Affiliation(s)
- Coskun O. Demirtas
- Marmara University, School of Medicine, Department of Gastroenterology, Istanbul, Turkey
| | - Antonio D’Alessio
- Department of Surgery & Cancer, Imperial College London, Hammersmith Hospital, London, UK
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy
| | - Lorenza Rimassa
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy
- Medical Oncology and Hematology Unit, Humanitas Cancer Center, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy
| | - Rohini Sharma
- Department of Surgery & Cancer, Imperial College London, Hammersmith Hospital, London, UK
| | - David J. Pinato
- Department of Surgery & Cancer, Imperial College London, Hammersmith Hospital, London, UK
- Division of Oncology, Department of Translational Medicine, University of Piemonte Orientale, Novara, Italy
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22
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Bhangoo RS, Mullikin TC, Ashman JB, Cheng TW, Golafshar MA, DeWees TA, Johnson JE, Shiraishi S, Liu W, Hu Y, Merrell KW, Haddock MG, Krishnan S, Rule WG, Sio TT, Hallemeier CL. Intensity Modulated Proton Therapy for Hepatocellular Carcinoma: Initial Clinical Experience. Adv Radiat Oncol 2021; 6:100675. [PMID: 34409199 PMCID: PMC8361033 DOI: 10.1016/j.adro.2021.100675] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2020] [Revised: 01/14/2021] [Accepted: 02/10/2021] [Indexed: 02/08/2023] Open
Abstract
Purpose Our purpose was to assess the safety and efficacy of intensity modulated proton therapy (IMPT) for the treatment of hepatocellular carcinoma (HCC). Methods and Materials A retrospective review was conducted on all patients who were treated with IMPT for HCC with curative intent from June 2015 to December 2018. All patients had fiducials placed before treatment. Inverse treatment planning used robust optimization with 2 to 3 beams. The majority of patients were treated in 15 fractions (n = 30, 81%, 52.5-67.5 Gy, relative biological effectiveness), whereas the remainder were treated in 5 fractions (n = 7, 19%, 37.5-50 Gy, relative biological effectiveness). Daily image guidance consisted of orthogonal kilovoltage x-rays and use of a 6° of freedom robotic couch. Outcomes (local control, progression free survival, and overall survival) were determined using Kaplan-Meier methods. Results Thirty-seven patients were included. The median follow-up for living patients was 21 months (Q1-Q3, 17-30 months). Pretreatment Child-Pugh score was A5-6 in 70% of patients and B7-9 in 30% of patients. Nineteen patients had prior liver directed therapy for HCC before IMPT. Eight patients (22%) required a replan during treatment, most commonly due to inadequate clinical target volume coverage. One patient (3%) experienced a grade 3 acute toxicity (pain) with no recorded grade 4 or 5 toxicities. An increase in Child-Pugh score by ≥ 2 within 3 months of treatment was observed in 6 patients (16%). At 1 year, local control was 94%, intrahepatic control was 54%, progression free survival was 35%, and overall survival was 78%. Conclusions IMPT is safe and feasible for treatment of HCC.
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Affiliation(s)
- Ronik S Bhangoo
- Department of Radiation Oncology, Mayo Clinic, Phoenix, Arizona
| | - Trey C Mullikin
- Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota
| | | | - Tiffany W Cheng
- Department of Radiation Oncology, Mayo Clinic, Phoenix, Arizona
| | | | - Todd A DeWees
- Department of Radiation Oncology, Mayo Clinic, Phoenix, Arizona.,Department of Health Sciences Research, Mayo Clinic, Scottsdale, Arizona
| | | | - Satomi Shiraishi
- Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota
| | - Wei Liu
- Department of Radiation Oncology, Mayo Clinic, Phoenix, Arizona
| | - Yanle Hu
- Department of Radiation Oncology, Mayo Clinic, Phoenix, Arizona
| | | | | | - Sunil Krishnan
- Department of Radiation Oncology, Mayo Clinic, Jacksonville, Florida
| | - William G Rule
- Department of Radiation Oncology, Mayo Clinic, Phoenix, Arizona
| | - Terence T Sio
- Department of Radiation Oncology, Mayo Clinic, Phoenix, Arizona
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23
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Uchinami Y, Katoh N, Abo D, Taguchi H, Yasuda K, Nishioka K, Soyama T, Morita R, Miyamoto N, Suzuki R, Sho T, Nakai M, Ogawa K, Kakisaka T, Orimo T, Kamiyama T, Shimizu S, Aoyama H. Treatment outcomes of stereotactic body radiation therapy using a real-time tumor-tracking radiotherapy system for hepatocellular carcinomas. Hepatol Res 2021; 51:870-879. [PMID: 33894086 DOI: 10.1111/hepr.13649] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/22/2021] [Revised: 04/07/2021] [Accepted: 04/17/2021] [Indexed: 01/07/2023]
Abstract
AIM To report the outcomes of stereotactic body radiotherapy using a real-time tumor-tracking radiotherapy system for hepatocellular carcinoma patients. METHODS From January 2005 to July 2018, 63 patients with 74 lesions with a maximum diameter ≤52 mm were treated by stereotactic body radiotherapy using a real-time tumor-tracking radiotherapy system. No patient with a Child-Pugh Score ≥9 was included, and 85.6% had a score of 5 or 6. Using the biological effective dose (BED) with an α/β ratio of 10 (BED10 ), the median dose in BED10 at the reference point was 76.8 Gy (range 60-122.5 Gy). Overall survival (OS) and local control rates were assessed using the Kaplan-Meier method. RESULTS With a median follow-up period of 24.6 months (range 0.9-118.4 months), the 1-year and 2-year OS rates were 86.8% (95% confidence interval [95% CI] 75.8-93.3) and 71.1% (57.8-81.6), respectively. The 2-year OS was 89.6% in patients with the baseline modified albumin-bilirubin (mALBI) grade =1, and 61.7% in patients with grade ≥2a. In the multivariate analysis, the mALBI grade (=1 vs. ≥2a) was a significant factor for OS (p = 0.028, 95% CI 1.11-6.18). The 1-year and 2-year local control rates were 100% (100-100%) and 92.0% (77.5-97.5%). The local control rates were significantly higher in the BED10 ≥100 Gy group than in the BED10 <100 Gy group (2-year 100% vs. 86.5%, p = 0.049) at the reference point. CONCLUSION This retrospective study of stereotactic body radiotherapy using real-time tumor-tracking radiotherapy for hepatocellular carcinoma showed favorable outcomes with lower incidence of toxicities, especially in patients treated with BED10 ≥100 Gy to the reference point.
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Affiliation(s)
- Yusuke Uchinami
- Department of Radiation Oncology, Faculty of Medicine, Hokkaido University, Sapporo, Hokkaido, Japan
| | - Norio Katoh
- Department of Radiation Oncology, Faculty of Medicine, Hokkaido University, Sapporo, Hokkaido, Japan
| | - Daisuke Abo
- Department of Diagnostic and Interventional Radiology, Hokkaido University Hospital, Sapporo, Hokkaido, Japan
| | - Hiroshi Taguchi
- Department of Radiation Oncology, Hokkaido University Hospital, Sapporo, Hokkaido, Japan
| | - Koichi Yasuda
- Department of Radiation Oncology, Hokkaido University Hospital, Sapporo, Hokkaido, Japan
| | - Kentaro Nishioka
- Department of Radiation Medical Science and Engineering, Faculty of Medicine, Hokkaido University, Sapporo, Hokkaido, Japan
| | - Takeshi Soyama
- Department of Diagnostic and Interventional Radiology, Hokkaido University Hospital, Sapporo, Hokkaido, Japan
| | - Ryo Morita
- Department of Diagnostic Imaging, Faculty of Medicine, Hokkaido University, Sapporo, Hokkaido, Japan
| | - Naoki Miyamoto
- Department of Medical Physics, Hokkaido University Hospital, Sapporo, Hokkaido, Japan
| | - Ryusuke Suzuki
- Department of Medical Physics, Hokkaido University Hospital, Sapporo, Hokkaido, Japan
| | - Takuya Sho
- Department of Gastroenterology and Hepatology, Faculty of Medicine, Hokkaido University, Sapporo, Hokkaido, Japan
| | - Masato Nakai
- Department of Gastroenterology and Hepatology, Faculty of Medicine, Hokkaido University, Sapporo, Hokkaido, Japan
| | - Koji Ogawa
- Department of Gastroenterology and Hepatology, Faculty of Medicine, Hokkaido University, Sapporo, Hokkaido, Japan
| | - Tatsuhiko Kakisaka
- Department of Gastroenterological Surgery I, Faculty of Medicine, Hokkaido University, Sapporo, Hokkaido, Japan
| | - Tatsuya Orimo
- Department of Gastroenterological Surgery I, Faculty of Medicine, Hokkaido University, Sapporo, Hokkaido, Japan
| | - Toshiya Kamiyama
- Department of Gastroenterological Surgery I, Faculty of Medicine, Hokkaido University, Sapporo, Hokkaido, Japan
| | - Shinichi Shimizu
- Department of Radiation Medical Science and Engineering, Faculty of Medicine, Hokkaido University, Sapporo, Hokkaido, Japan
| | - Hidefumi Aoyama
- Department of Radiation Oncology, Faculty of Medicine, Hokkaido University, Sapporo, Hokkaido, Japan
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24
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Jackson WC, Hartman HE, Gharzai LA, Maurino C, Karnak DM, Mendiratta-Lala M, Parikh ND, Mayo CS, Haken RKT, Schipper MJ, Cuneo KC, Lawrence TS. The Potential for Midtreatment Albumin-Bilirubin (ALBI) Score to Individualize Liver Stereotactic Body Radiation Therapy. Int J Radiat Oncol Biol Phys 2021; 111:127-134. [PMID: 33878421 DOI: 10.1016/j.ijrobp.2021.04.012] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2021] [Revised: 03/29/2021] [Accepted: 04/11/2021] [Indexed: 12/17/2022]
Abstract
PURPOSE Our individualized functional response adaptive approach to liver stereotactic body radiation therapy (SBRT) with assessment of indocyanine green (ICG) retention at baseline and midtreatment to detect subclinical changes in liver function, permitting dose adjustment, has decreased toxicity while preserving efficacy. We hypothesized that assessment of the albumin-bilirubin (ALBI) score at baseline and midtreatment would allow for more practical identification of patients at risk for treatment-related toxicity (TRT). METHODS AND MATERIALS Patients with hepatocellular carcinoma were treated on 3 prospective institutional review board-approved trials using baseline and midtreatment ICG to deliver individualized functional response adaptive liver SBRT. Patients received 3 or 5 fractions, with fraction 3 followed by a 1-month treatment break. TRT was a ≥2-point rise in Child-Pugh score within 6 months of SBRT. Logistic regression was used to estimate odds ratios (ORs) and confidence intervals (CIs) for assessment of TRT. Area under the receiver operating curve was used to compare predictive ability across models. RESULTS In total, 151 patients underwent 166 treatments. Baseline Child-Pugh class and ALBI grade were A (66.9%), B (31.3%), or C (1.8%) and 1 (25.9%), 2 (65.7%), or 3 (8.4%), respectively. Thirty-five patients (20.3%) experienced TRT. On univariate analysis, baseline ALBI (OR, 1.8; 95% CI, 1.24-2.62; P = .02), baseline ICG (OR, 1.66; 95% CI, 1.17-2.35; P = .04), and change in ALBI (OR, 3.07; 95% CI, 1.29-7.32; P = .003) were associated with increased odds of TRT. ALBI-centric models performed similarly to ICG-centric models on multivariate analyses predicting toxicity (area under the receiver operating curve of 0.79 for both). In a model incorporating baseline and midtreatment change in ALBI and ICG, both ALBI values were statistically significantly associated with toxicity, whereas ICG values were not. CONCLUSIONS Incorporation of midtreatment change in ALBI in addition to baseline ALBI improves the ability to predict TRT in patients with hepatocellular carcinoma receiving SBRT. Our findings suggest that functional response adaptive treatment could be implemented in a practical manner because the ALBI score is easily obtained from standard laboratory values.
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Affiliation(s)
| | | | | | | | | | | | - Neehar D Parikh
- Gastroenterology, University of Michigan Ann Arbor, Michigan
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25
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Shanker MD, Liu HY, Lee YY, Stuart KA, Powell EE, Wigg A, Pryor DI. Stereotactic radiotherapy for hepatocellular carcinoma: Expanding the multidisciplinary armamentarium. J Gastroenterol Hepatol 2021; 36:873-884. [PMID: 32632941 DOI: 10.1111/jgh.15175] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/14/2020] [Revised: 06/23/2020] [Accepted: 07/01/2020] [Indexed: 12/14/2022]
Abstract
Hepatocellular carcinoma (HCC) is the fifth most common malignancy worldwide and the third most common cause of cancer-related death. Long-term prognosis remains poor with treatment options frequently limited by advanced tumor stage, tumor location, or underlying liver dysfunction. Stereotactic ablative body radiotherapy (SABR) utilizes technological advances to deliver highly precise, tumoricidal doses of radiation. There is an emerging body of literature on SABR in HCC demonstrating high rates of local control in the order of 80-90% at 3 years. SABR is associated with a low risk of radiation-induced liver disease or decompensation in appropriately selected HCC patients with compensated liver function and is now being incorporated into guidelines as an additional treatment option. This review outlines the emerging role of SABR in the multidisciplinary management of HCC and summarizes the current evidence for its use as an alternative ablative option for early-stage disease, as a bridge to transplant, and as palliation for advanced-stage disease. We outline specific considerations regarding patient selection, toxicities, and response assessment. Finally, we compare current international guidelines and recommendations for the use of SABR and summarize ongoing studies.
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Affiliation(s)
- Mihir D Shanker
- Department of Radiation Oncology, Princess Alexandra Hospital, Brisbane, Queensland, Australia.,Faculty of Medicine, University of Queensland, Brisbane, Queensland, Australia
| | - Howard Y Liu
- Department of Radiation Oncology, Princess Alexandra Hospital, Brisbane, Queensland, Australia.,Faculty of Medicine, University of Queensland, Brisbane, Queensland, Australia
| | - Yoo Young Lee
- Department of Radiation Oncology, Princess Alexandra Hospital, Brisbane, Queensland, Australia.,Faculty of Medicine, University of Queensland, Brisbane, Queensland, Australia
| | - Katherine A Stuart
- Faculty of Medicine, University of Queensland, Brisbane, Queensland, Australia.,Department of Gastroenterology and Hepatology, Princess Alexandra Hospital, Brisbane, Queensland, Australia
| | - Elizabeth E Powell
- Faculty of Medicine, University of Queensland, Brisbane, Queensland, Australia.,Department of Gastroenterology and Hepatology, Princess Alexandra Hospital, Brisbane, Queensland, Australia
| | - Alan Wigg
- Hepatology and Liver Transplantation Medicine Unit, Flinders Medical Centre, Adelaide, South Australia, Australia
| | - David I Pryor
- Department of Radiation Oncology, Princess Alexandra Hospital, Brisbane, Queensland, Australia.,Faculty of Medicine, University of Queensland, Brisbane, Queensland, Australia
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Lo CH, Lee HL, Hsiang CW, Chiou JF, Lee MS, Chen SW, Shen PC, Lin CS, Chang WC, Yang JF, Dai YH, Chen CY, Chia-Hsien Cheng J, Huang WY. Pretreatment Neutrophil-to-Lymphocyte Ratio Predicts Survival and Liver Toxicity in Patients With Hepatocellular Carcinoma Treated With Stereotactic Ablative Radiation Therapy. Int J Radiat Oncol Biol Phys 2021; 109:474-484. [PMID: 32898609 DOI: 10.1016/j.ijrobp.2020.09.001] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2019] [Revised: 08/12/2020] [Accepted: 09/01/2020] [Indexed: 12/14/2022]
Abstract
PURPOSE The objective of this study was to determine whether pretreatment neutrophil-to-lymphocyte ratio (NLR) could predict survival outcomes and liver toxicity in hepatocellular carcinoma (HCC) patients treated with stereotactic ablative radiation therapy (SABR). METHODS AND MATERIALS In this retrospective study we collected pretreatment NLR of HCC patients treated with SABR between December 2007 and August 2018 and determined its association with overall survival (OS), progression-free survival, and radiation-related liver toxicity defined as an increase in the Child-Turcotte-Pugh score by ≥2 within 3 months after SABR in the absence of disease progression. RESULTS A total of 153 patients with a median follow-up of 13.3 months were included. Receiver operating characteristic curve analysis found that an NLR ≥2.4 was optimum (area under the curve, 0.762; 95% confidence interval [CI], 0.682-0.841, P < .001) for predicting poor 1-year OS (38.2% vs 83.6%, P < .001). Multivariable analysis demonstrated that NLR was significantly associated with OS, both as a continuous (P = .006) and a binary variable (NLR set at 2.4; P = .003). Multiple tumors (P = .003), macrovascular invasion (P = .024), extrahepatic spread (P = .002), and albumin-bilirubin score (P = .020) were also significant predictors of OS. Elevated NLR independently prognosticated poor progression-free survival (P = .016). Liver toxicity was seen in 22 evaluable patients (15.4%). Receiver operating characteristic curve analysis found NLR ≥4.0 was optimum at predicting liver toxicity (31.4% vs 10.2%, P = .005). A higher NLR (P = .049) and albumin-bilirubin score (P = .002) were independent risk factors for liver toxicity. CONCLUSIONS NLR is an objective and ubiquitous inflammatory marker that can predict OS and liver toxicity in HCC patients undergoing SABR. NLR could be a useful biomarker for patient risk stratification and therapeutic decision-making.
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Affiliation(s)
- Cheng-Hsiang Lo
- Department of Radiation Oncology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
| | - Hsin-Lun Lee
- Department of Radiation Oncology, Taipei Medical University Hospital, Taipei Medical University, Taipei, Taiwan; Taipei Cancer Center, Taipei Medical University, Taipei, Taiwan
| | - Chih-Weim Hsiang
- Department of Radiology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
| | - Jeng-Fong Chiou
- Department of Radiation Oncology, Taipei Medical University Hospital, Taipei Medical University, Taipei, Taiwan; Taipei Cancer Center, Taipei Medical University, Taipei, Taiwan; Department of Radiology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
| | - Meei-Shyuan Lee
- School of Public Health, National Defense Medical Center, Taipei, Taiwan
| | - Shang-Wen Chen
- Department of Radiology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; Department of Radiation Oncology, China Medical University Hospital, Taichung, Taiwan; Graduate Institute of Biomedical Sciences, School of Medicine, College of Medicine, China Medical University, Taichung, Taiwan
| | - Po-Chien Shen
- Department of Radiation Oncology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
| | - Chun-Shu Lin
- Department of Radiation Oncology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
| | - Wei-Chou Chang
- Department of Radiology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
| | - Jen-Fu Yang
- Department of Radiation Oncology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
| | - Yang-Hong Dai
- Department of Radiation Oncology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
| | - Chun-You Chen
- Department of Radiation Oncology, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan; Graduate Institute of Biomedical Informatics, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan
| | - Jason Chia-Hsien Cheng
- Division of Radiation Oncology, Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan; Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan; Graduate Institute of Oncology, National Taiwan University College of Medicine, Taipei, Taiwan.
| | - Wen-Yen Huang
- Department of Radiation Oncology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan; Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan.
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27
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Park JY. Functional Assessment of Liver for Radiation Oncologist. RADIOTHERAPY OF LIVER CANCER 2021:51-57. [DOI: 10.1007/978-981-16-1815-4_4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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28
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Cousins MM, Morris E, Maurino C, Devasia TP, Karnak D, Ray D, Parikh ND, Owen D, Ten Haken RK, Schipper MJ, Lawrence TS, Cuneo KC. TNFR1 and the TNFα axis as a targetable mediator of liver injury from stereotactic body radiation therapy. Transl Oncol 2020; 14:100950. [PMID: 33395747 PMCID: PMC7744766 DOI: 10.1016/j.tranon.2020.100950] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2020] [Revised: 10/30/2020] [Accepted: 11/05/2020] [Indexed: 02/08/2023] Open
Abstract
Elevated soluble TNFR1 levels are predictive of liver toxicity among patients receiving radiation. Soluble TNFR1 levels do not independently predict liver toxicity when included in models with ALBI and mean liver dose. Data suggest that liver inflammation mediates toxicity after liver irradiation and that the TNFα axis is associated with this inflammation. Future studies of should evaluate approaches that target pre-treatment inflammation to reduce the risk of toxicity. Introduction Radiation therapy for the management of intrahepatic malignancies can adversely affect liver function. Liver damage has been associated with increased levels of inflammatory cytokines, including tumor necrosis factor alpha (TNFα). We hypothesized that an inflammatory state, characterized by increased soluble TNFα receptor (sTNFR1), mediates sensitivity of the liver to radiation. Materials/Methods Plasma samples collected during 3 trials of liver radiation for liver malignancies were assayed for sTNFR1 level via enzyme-linked immunosorbent assay (ELISA). Univariate and multivariate logistic regression and longitudinal models were used to characterize associations between liver toxicity (defined as a ≥2-point increase in Child-Pugh [CP] score within 6 months of radiation treatment) and sTNFR1 levels, ALBI score, biocorrected mean liver dose (MLD), age, and baseline laboratory values. Results Samples from 78 patients given liver stereotactic body radiation therapy [SBRT] (92%) or hypofractionated radiation were examined. There was a significant association between liver toxicity and sTNFR1 levels, and higher values were associated with increased toxicity over a range of mean liver doses. When ALBI score and biocorrected dose were included in the model with sTNFR1, baseline ALBI score and change in ALBI (ΔALBI) were significantly associated with toxicity, but sTNFR1 was not. Baseline aminotransferase levels also predicted toxicity but not independently of ALBI score. Conclusions Elevated plasma sTNFR1 levels are associated with liver injury after liver radiation, suggesting that elevated inflammatory cytokine activity is a predictor of radiation-induced liver dysfunction. Future studies should determine whether administration of agents that decrease inflammation prior to treatment is warranted.
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Affiliation(s)
- Matthew M Cousins
- Department of Radiation Oncology, University of Michigan, UH B2C490, 1500 E Medical Center Dr, Ann Arbor, MI 48109-5010, USA
| | - Emily Morris
- Department of Radiation Oncology, University of Michigan, UH B2C490, 1500 E Medical Center Dr, Ann Arbor, MI 48109-5010, USA
| | - Christopher Maurino
- Department of Radiation Oncology, University of Michigan, UH B2C490, 1500 E Medical Center Dr, Ann Arbor, MI 48109-5010, USA
| | - Theresa P Devasia
- Department of Radiation Oncology, University of Michigan, UH B2C490, 1500 E Medical Center Dr, Ann Arbor, MI 48109-5010, USA
| | - David Karnak
- Department of Radiation Oncology, University of Michigan, UH B2C490, 1500 E Medical Center Dr, Ann Arbor, MI 48109-5010, USA
| | - Dipankar Ray
- Department of Radiation Oncology, University of Michigan, UH B2C490, 1500 E Medical Center Dr, Ann Arbor, MI 48109-5010, USA
| | - Neehar D Parikh
- Department of Internal Medicine, University of Michigan, 3110 Taubman Center, SPC 5368, 1500 E Medical Center Dr, Ann Arbor, MI 48109-5368, USA
| | - Dawn Owen
- Department of Radiation Oncology, University of Michigan, UH B2C490, 1500 E Medical Center Dr, Ann Arbor, MI 48109-5010, USA
| | - Randall K Ten Haken
- Department of Radiation Oncology, University of Michigan, UH B2C490, 1500 E Medical Center Dr, Ann Arbor, MI 48109-5010, USA
| | - Matthew J Schipper
- Department of Radiation Oncology, University of Michigan, UH B2C490, 1500 E Medical Center Dr, Ann Arbor, MI 48109-5010, USA
| | - Theodore S Lawrence
- Department of Radiation Oncology, University of Michigan, UH B2C490, 1500 E Medical Center Dr, Ann Arbor, MI 48109-5010, USA
| | - Kyle C Cuneo
- Department of Radiation Oncology, University of Michigan, UH B2C490, 1500 E Medical Center Dr, Ann Arbor, MI 48109-5010, USA.
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Abstract
INTRODUCTION Stereotactic Body Radiotherapy (SBRT) in liver tumors allows ablative radiation doses in tumors preserving the liver tissue. However, liver is a parallel organ allowing high doses in a small region to preserve its function. If this is not possible, radio-induced liver toxicity is produced. Radio-induced liver toxicity or radio-induced liver disease (RILD) is the most serious toxicity in liver radiotherapy. AREAS COVERED In this review, we analyzed published literature on PubMed and MEDLINE. We included papers in English language with information about RILD characteristics, diagnostic, risk factors, pathophysiology, and treatment. All citations were evaluated for relevant content and validation. EXPERT OPINION The study of RILD is fundamental before the implementation of liver SBRT. Radio-induced liver toxicity is a complication that can be fatal for patients. This is a diagnosis of exclusion and it is essential that experts in the treatment of hepatic SBRT know about it and anticipate its development. The study and development of molecular or imaging biomarkers could be key in their diagnosis and prevention.
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Bannaga A, Arasaradnam RP. Neutrophil to lymphocyte ratio and albumin bilirubin grade in hepatocellular carcinoma: A systematic review. World J Gastroenterol 2020; 26:5022-5049. [PMID: 32952347 PMCID: PMC7476180 DOI: 10.3748/wjg.v26.i33.5022] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/26/2020] [Revised: 08/10/2020] [Accepted: 08/25/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) is a frequent cause of cancer related death globally. Neutrophil to lymphocyte ratio (NLR) and albumin bilirubin (ALBI) grade are emerging prognostic indicators in HCC.
AIM To study published literature of NLR and ALBI over the last five years, and to validate NLR and ALBI locally in our centre as indicators of HCC survival.
METHODS A systematic review of the published literature on PubMed of NLR and ALBI in HCC over the last five years. The search followed the guidelines of the preferred reporting items for systematic reviews and meta-analyses. Additionally, we also investigated HCC cases between December 2013 and December 2018 in our centre.
RESULTS There were 54 studies describing the relation between HCC and NLR and 95 studies describing the relation between HCC and ALBI grade over the last five years. Our local cohort of patients showed NLR to have a significant negative relationship to survival (P = 0.011). There was also significant inverse relationship between the size of the largest HCC nodule and survival (P = 0.009). Median survival with alpha fetoprotein (AFP) < 10 KU/L was 20 mo and with AFP > 10 KU/L was 5 mo. We found that AFP was inversely related to survival, this relationship was not statically significant (P = 0.132). Mean survival for ALBI grade 1 was 37.7 mo, ALBI grade 2 was 13.4 months and ALBI grade 3 was 4.5 mo. ALBI grades performed better than Child Turcotte Pugh score in detecting death from HCC.
CONCLUSION NLR and ALBI grade in HCC predict survival better than the conventional alpha fetoprotein. ALBI grade performs better than Child Turcotte Pugh score. These markers are done as part of routine clinical care and in cases of normal alpha fetoprotein, these markers could give a better understanding of the patient disease progression. NLR and ALBI grade could have a role in modified easier to learn staging and prognostic systems for HCC.
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Affiliation(s)
- Ayman Bannaga
- Department of Gastroenterology and Hepatology, University Hospital Coventry and Warwickshire NHS Trust, Coventry CV2 2DX, West Midlands, United Kingdom
- Warwick Medical School, University of Warwick, Coventry CV4 7HL, West Midlands, United Kingdom
| | - Ramesh P Arasaradnam
- Department of Gastroenterology and Hepatology, University Hospital Coventry and Warwickshire NHS Trust, Coventry CV2 2DX, West Midlands, United Kingdom
- Warwick Medical School, University of Warwick, Coventry CV4 7HL, West Midlands, United Kingdom
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Zhao S, Wang M, Yang Z, Tan K, Zheng D, Du X, Liu L. Comparison between Child-Pugh score and Albumin-Bilirubin grade in the prognosis of patients with HCC after liver resection using time-dependent ROC. ANNALS OF TRANSLATIONAL MEDICINE 2020; 8:539. [PMID: 32411762 PMCID: PMC7214905 DOI: 10.21037/atm.2020.02.85] [Citation(s) in RCA: 28] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
Abstract
Backgrounds The Child-Pugh score is a scoring system used to measure liver function and predict postoperative outcomes in patients with hepatocellular carcinoma (HCC). Recently, the Albumin-Bilirubin (ALBI) grade has been proposed for the evaluation of hepatic reserve function in HCC. This study aimed to assess and compare the capability of ALBI grade and Child-Pugh score in predicting overall survival (OS). Methods A total of 196 consecutive HCC patients who treated with hepatectomy were enrolled in this retrospective study. The prognostic values of ALBI grade and Child-Pugh score in predicting postoperative OS were respectively estimated using the Kaplan-Meier method and time-dependent receiver operating curves (ROC). Univariate and multivariate Cox regression analyses were performed to investigate the prognostic factors for OS. Results Stratified by the Albumin-Bilirubin (ALBI) system, there were 81 (41.3%) patients with grade 1 and 115 (58.7%) patients with grade 2. The cumulative 1-, 3-, 5-year OS rates in patients with ALBI-1 were 82.7%, 51.5% and 35.5%, respectively. For patients with ALBI-2, the cumulative 1-, 3-, 5-year OS rates were 57.6%, 19.4% and 0%, respectively. Based on the Child-Pugh classification, 136 (69.4%) patients had a score of 5, and 60 (30.6%) patients had a score of 6. Patients with Child-Pugh-A5 showed a better OS than those with Child-Pugh-A6, with respective OS at 1, 3 and 5 years (72.7%, 29.2%, 20.3% vs. 53.9%, 21.1%, 0%, Log-rank P<0.001). Besides, the ALBI grade revealed two prognostic groups within Child-Pugh-A5 (P<0.001), while the Child-Pugh score did not distinguish ALBI-2 in different prognostic groups (P=0.705). The multivariate analysis indicated that both ALBI grade and Child-Pugh score could significantly stratify the patients with different OS [hazard ratio (HR), 3.088 and 1.783; 95% confidence interval (CI), 1.985 to 4.805 and 1.272 to 2.731; P<0.001 and P=0.032 for ALBI grade and Child-Pugh score, respectively]. Additionally, time-dependent ROC analysis in the entire cohort proved that the ALBI grade had a better discriminatory ability than the Child-Pugh score in predicting survival, especially for long-term outcomes. According to the subgroup analyses, the ALBI grade had a better discriminatory ability and survival prediction accuracy in overall subsets than the Child-Pugh score for the prediction of OS. Conclusions ALBI grade supplied better prognostic performance and distribution of liver function than Child-Pugh score in stratifying prognosis for HCC patients treated by hepatectomy. These results declared that ALBI grade could be an alternative liver function grading system for stratification in patients with HCC.
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Affiliation(s)
- Shoujie Zhao
- Department of General Surgery, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, China
| | - Mengmeng Wang
- Department of Drug and Equipment, Aeromedicine Identification and Training Centre of Air Force, Xi'an 710069, China
| | - Zhenyu Yang
- Department of General Surgery, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, China
| | - Kai Tan
- Department of General Surgery, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, China
| | - Desha Zheng
- Department of Nursing, Fourth Military Medical University, Xi'an 710032, China
| | - Xilin Du
- Department of General Surgery, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, China
| | - Lei Liu
- Department of Gastroenterology, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, China
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Sun J, Zhang A, Li W, Wang Q, Wang J, Fan Y, Sun Y, Li D, Zhang D, Duan X. CyberKnife Stereotactic Body Radiation Therapy as an Effective Treatment for Hepatocellular Carcinoma Patients With Decompensated Cirrhosis. Front Oncol 2020; 10:100. [PMID: 32158688 PMCID: PMC7052044 DOI: 10.3389/fonc.2020.00100] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2019] [Accepted: 01/20/2020] [Indexed: 12/24/2022] Open
Abstract
Purpose: The aim of our study was to evaluate the curative effect and safety of CyberKnife stereotactic body radiation therapy in treating decompensated cirrhosis hepatocellular carcinoma (HCC) patients. Methods: From March 2011 to December 2015, 32 HCC patients who refused or were ineligible for other treatments were treated with CyberKnife stereotactic body radiation therapy. Among these patients, 17 were Child-Pugh score 7 (53.13%), 7 were Child-Pugh score 8 (21.87%), 4 were Child-Pugh score 9 (12.50%), and 4 were Child-Pugh score 10 (12.50%). A total dose of 45-54 Gy in 5-10 fractions was given according to the location of lesions. Results: The median follow-up period was 30 months (8-46 months). By July 2019, the tumors were recurrent or metastasized in 17 patients. The overall survival rates of 1, 2, and 3 years were 84.4, 61.8, and 46.0%, respectively. After 1, 2, and 3 years, the local control rates were 92.9%. The progression-free survival rates of the 1, 2, and 3-year treatments were 73.8, 44.6, and 33.4%, respectively. Conclusions: CyberKnife stereotactic body radiation therapy was an effective option for HCC patients with decompensated cirrhosis. The liver injury occurrence rate was acceptable in our study.
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Affiliation(s)
| | | | | | | | | | | | | | | | | | - Xuezhang Duan
- Radiation Oncology Center, The Fifth Medical Center of PLA General Hospital (Beijing 302 Hospital), Beijing, China
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Rong W, Yu W, Wang L, Wu F, Zhang K, Chen B, Miao C, Liu L, An S, Tao C, Wang W, Wu J. Adjuvant radiotherapy in central hepatocellular carcinoma after narrow-margin hepatectomy: A 10-year real-world evidence. Chin J Cancer Res 2020; 32:645-653. [PMID: 33223759 PMCID: PMC7666779 DOI: 10.21147/j.issn.1000-9604.2020.05.09] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
Objective A prospective randomized control study investigated the feasibility and efficacy of adjuvant radiotherapy on patients with central hepatocellular carcinoma (HCC) after narrow-margin hepatectomy (<1 cm). This study presents an updated 10-year real-world evidence to further characterize the role of adjuvant radiotherapy. Methods Patients with central HCC after narrow-margin hepatectomy (<1 cm) were prospectively assigned to adjuvant radiotherapy group and control group. Patients' outcome, adverse events, long-term recurrence and survival rates were investigated. Results The 1-, 5-, and 10-year recurrence-free survival (RFS) rates were 81.0%, 43.9%, and 38.7%, respectively in adjuvant radiotherapy group and 71.7%, 35.8%, and 24.2%, respectively in control group (log-rank test, P=0.09). The 1-, 5-, and 10-year overall survival (OS) rates were 96.6%, 54.7%, and 42.8%, respectively in adjuvant radiotherapy group and 90.2%, 55.1%, and 30.0%, respectively in control group (log-rank test, P=0.20). The 1-, 5-, and 10-year RFS rates for patients with small HCC (≤5 cm) were 91.1%, 51.6%, and 48.4%, respectively in adjuvant radiotherapy group and 80.0%, 36.6%, and 26.6%, respectively in control group (log-rank test, P=0.03). Landmark analysis demonstrated that patients with small HCC in adjuvant radiotherapy group had a significantly improved OS in second five years after treatment in comparison to patients in control group (log-rank test, P=0.05). Conclusions Our updated results showed a sustained clinical benefit on reducing recurrence, improving long-term survival for small central HCC by adjuvant radiotherapy after narrow-margin hepatectomy. Long-term survival data also indicated that hepatectomy is an optimal treatment for selected patients with central HCC.
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Affiliation(s)
- Weiqi Rong
- Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Weibo Yu
- Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USA
| | - Liming Wang
- Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Fan Wu
- Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Kai Zhang
- Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Bo Chen
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Chengli Miao
- Department of Retroperitoneal Tumor Surgery, Peking University International Hospital, Beijing 102206, China
| | - Liguo Liu
- Department of General Surgery, China-Japan Friendship Hospital, Beijing 100029, China
| | - Songlin An
- Department of Peritoneal Cancer Surgery, Beijing Shijitan Hospital, Capital Medical University Beijing, Beijing 100038, China
| | - Changcheng Tao
- Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Weihu Wang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Radiation Oncology, Peking University Cancer Hospital & Institute, Beijing 100142, China
| | - Jianxiong Wu
- Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
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Su TS, Yang HM, Zhou Y, Huang Y, Liang P, Cheng T, Chen L, Li LQ, Liang SX. Albumin - bilirubin (ALBI) versus Child-Turcotte-Pugh (CTP) in prognosis of HCC after stereotactic body radiation therapy. Radiat Oncol 2019; 14:50. [PMID: 30917853 PMCID: PMC6436219 DOI: 10.1186/s13014-019-1251-y] [Citation(s) in RCA: 33] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2019] [Accepted: 03/05/2019] [Indexed: 02/08/2023] Open
Abstract
Background Child-Turcotte-Pugh (CTP) score extensively used to assess hepatic function, predicting postoperative outcome of hepatocellular carcinoma (HCC) patients. Lately, the albumin–bilirubin (ALBI) grade has been identified to be a predictor of overall survival of HCC patients. In this investigation, we compared the pre-SBRT ALBI and CTP scores with the prognosis of patients with HCC. Methods This cohort study included 594 HCC patients who treated with SBRT. Overall survival (OS) rates were measured from treatment date to death date or last follow-up. We compared ALBI score with the CTP score in predicting long-term survival. Results The average follow-up time was 21 months (1 to 82 months). The CTP and ALBI ratings have discriminatory for long-term survival across the groups. CTP class was significantly related to OS, with a median OS of 29.9 months in CTP-A, 11.5 in CTP-B (P < 0.0001). ALBI grade is also significantly related to OS, with a median OS of 53.0 months in ALBI-1, 19.5 months in ALBI-2, and 6.5 months in ALBI-3(P < 0.0001). Within CTP-A class, CTP score-A5/A6 and ALBI grade has a similar predictive power (all P < 0.001). However, both CTP score and ALBI grade have no predictive power in CTP ≥ B7 class (all P>0.05). Conclusions To assess liver dysfunction in HCC patients before SBRT, traditional CTP classification is a necessary but imperfect tool for assessing HCC liver injury. The ALBI score is a more objective, discriminatory and evidence-based approach in CTP-A groups, and need to be validated in CTP ≥ B7 class.
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Affiliation(s)
- Ting-Shi Su
- Department of Radiation Oncology, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, 530001, Guangxi Zhuang Autonomous Region, China.,Department of Hepatobiliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, 530001, Guangxi Zhuang Autonomous Region, China
| | - Hai-Ming Yang
- Department of Radiation Oncology, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, 530001, Guangxi Zhuang Autonomous Region, China
| | - Ying Zhou
- Department of Radiation Oncology, Rui Kang Hospital, Guangxi Traditional Chinese Medical University, Nanning, 530001, Guangxi Zhuang Autonomous Region, China
| | - Yong Huang
- Department of Radiation Oncology, Rui Kang Hospital, Guangxi Traditional Chinese Medical University, Nanning, 530001, Guangxi Zhuang Autonomous Region, China
| | - Ping Liang
- Department of Radiation Oncology, Rui Kang Hospital, Guangxi Traditional Chinese Medical University, Nanning, 530001, Guangxi Zhuang Autonomous Region, China
| | - Tao Cheng
- Department of Radiation Oncology, Rui Kang Hospital, Guangxi Traditional Chinese Medical University, Nanning, 530001, Guangxi Zhuang Autonomous Region, China
| | - Long Chen
- Department of Radiation Oncology, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, 530001, Guangxi Zhuang Autonomous Region, China.
| | - Le-Qun Li
- Department of Hepatobiliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, 530001, Guangxi Zhuang Autonomous Region, China.
| | - Shi-Xiong Liang
- Department of Radiation Oncology, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, 530001, Guangxi Zhuang Autonomous Region, China.
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Sanford NN, Pursley J, Noe B, Yeap BY, Goyal L, Clark JW, Allen JN, Blaszkowsky LS, Ryan DP, Ferrone CR, Tanabe KK, Qadan M, Crane CH, Koay EJ, Eyler C, DeLaney TF, Zhu AX, Wo JY, Grassberger C, Hong TS. Protons versus Photons for Unresectable Hepatocellular Carcinoma: Liver Decompensation and Overall Survival. Int J Radiat Oncol Biol Phys 2019; 105:64-72. [PMID: 30684667 DOI: 10.1016/j.ijrobp.2019.01.076] [Citation(s) in RCA: 93] [Impact Index Per Article: 15.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2018] [Revised: 12/29/2018] [Accepted: 01/13/2019] [Indexed: 12/23/2022]
Abstract
PURPOSE Ablative radiation therapy is increasingly being used for hepatocellular carcinoma (HCC) resulting in excellent local control rates; however, patients without evidence of disease progression often die from liver failure. The clinical benefit of proton- over photon-based radiation therapy is unclear. We therefore sought to compare clinical outcomes of proton versus photon ablative radiation therapy in patients with unresectable HCC. METHODS AND MATERIALS This is a single-institution retrospective study of patients treated during 2008 to 2017 with nonmetastatic, unresectable HCC not previously treated with liver-directed radiation therapy and who did not receive further liver-directed radiation therapy within 12 months after completion of index treatment. The primary outcome, overall survival (OS), was assessed using Cox regression. Secondary endpoints included incidence of non-classic radiation-induced liver disease (defined as increase in baseline Child-Pugh score by ≥2 points at 3 months posttreatment), assessed using logistic regression, and locoregional recurrence, assessed using Fine-Gray regression for competing risks. All outcomes were measured from radiation start date. RESULTS The median follow-up was 14 months. Of 133 patients with median age 68 years and 75% male, 49 (37%) were treated with proton radiation therapy. Proton radiation therapy was associated with improved OS (adjusted hazard ratio, 0.47; P = .008; 95% confidence interval [CI], 0.27-0.82). The median OS for proton and photon patients was 31 and 14 months, respectively, and the 24-month OS for proton and photon patients was 59.1% and 28.6%, respectively. Proton radiation therapy was also associated with a decreased risk of non-classic radiation-induced liver disease (odds ratio, 0.26; P = .03; 95% CI, 0.08-0.86). Development of nonclassic RILD at 3 months was associated with worse OS (adjusted hazard ratio, 3.83; P < .001; 95% CI, 2.12-6.92). There was no difference in locoregional recurrence, including local failure, between protons and photons. CONCLUSIONS Proton radiation therapy was associated with improved survival, which may be driven by decreased incidence of posttreatment liver decompensation. Our findings support prospective investigations comparing proton versus photon ablative radiation therapy for HCC.
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Affiliation(s)
- Nina N Sanford
- Harvard Radiation Oncology Program, Massachusetts General Hospital, Boston, Massachusetts; Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts
| | - Jennifer Pursley
- Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts
| | - Bridget Noe
- Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts
| | - Beow Y Yeap
- Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts
| | - Lipika Goyal
- Department of Medical Oncology, Massachusetts General Hospital, Boston, Massachusetts
| | - Jeffrey W Clark
- Department of Medical Oncology, Massachusetts General Hospital, Boston, Massachusetts
| | - Jill N Allen
- Department of Medical Oncology, Massachusetts General Hospital, Boston, Massachusetts
| | | | - David P Ryan
- Department of Medical Oncology, Massachusetts General Hospital, Boston, Massachusetts
| | - Cristina R Ferrone
- Department of Surgery, Massachusetts General Hospital, Boston, Massachusetts
| | - Kenneth K Tanabe
- Department of Surgery, Massachusetts General Hospital, Boston, Massachusetts
| | - Motaz Qadan
- Department of Surgery, Massachusetts General Hospital, Boston, Massachusetts
| | - Christopher H Crane
- Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Eugene J Koay
- Department of Radiation Oncology, MD Anderson Cancer Center, Houston, Texas
| | - Christine Eyler
- Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts
| | - Thomas F DeLaney
- Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts
| | - Andrew X Zhu
- Department of Medical Oncology, Massachusetts General Hospital, Boston, Massachusetts
| | - Jennifer Y Wo
- Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts
| | - Clemens Grassberger
- Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts
| | - Theodore S Hong
- Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts.
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Xu YX, Wang YB, Tan YL, Xi C, Xu XZ. Prognostic value of pretreatment albumin to bilirubin ratio in patients with hepatocellular cancer: A meta-analysis. Medicine (Baltimore) 2019; 98:e14027. [PMID: 30633195 PMCID: PMC6336617 DOI: 10.1097/md.0000000000014027] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/27/2023] Open
Abstract
BACKGROUND Hepatic function is closely associated with prognosis in patients with hepatocellular cancer (HCC). In this study, a meta-analysis of the published studies was performed to assess the prognostic value of ALBI grade in HCC patients. METHODS Databases, including PubMed, EMbase, Web of Science, and Cochrane Library were retrieved up to August 2018. The primary outcome was OS and secondary outcome was DFS, the prognostic impact of which was assessed by using hazard ratio (HRs) with corresponding 95% confidence intervals (CIs). The enrolled studies were analyzed by using STATA version 12.0 software. RESULTS A total of 22,911 patients with HCC in 32 studies were included. Our results demonstrated that high pretreatment ALBI is associated with poor OS (HR = 1.719, 95%CI: 1.666-1.771, P = .000, univariate results; HR = 1.602, 95%CI: 1.470-1.735, P = .000, multivariate results) and poor DFS (HR = 1.411, 95%CI: 1.262-1.561, P = .000, univariate results; HR = 1.264, 95%CI: 1.042-1.485, P = .000, multivariate results). Meanwhile, when the analysis was stratified into subgroups, such as treatment methods, sample size, geographic area, and ALBI grade, the significant correlation in ALBI and poor long-term survival was not altered. CONCLUSION High pretreatment ALBI is closely associated with poor prognosis in HCC, and High ALBI should be treated as an ideal predictor during hepatocellular therapy.
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