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Li Y, Zhong JH, Zhu XD, Han CY, Wang JB, Liu HZ, Hu K, Pan YX, Sun HC, Peng T, Liu LX, Zeng YY, Zhou LD, Xu L, Wang NY. Efficacy and safety of combined targeted therapy and immunotherapy versus targeted monotherapy in older patients with uHCC. Front Oncol 2025; 15:1515640. [PMID: 40356761 PMCID: PMC12066334 DOI: 10.3389/fonc.2025.1515640] [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: 10/23/2024] [Accepted: 03/31/2025] [Indexed: 05/15/2025] Open
Abstract
Background The prevalence of hepatocellular carcinoma (HCC) among older patients is rising due to the aging population. This study aimed to compare the efficacy and safety of targeted therapy alone versus its combination with immunotherapy in older patients (≥ 65 years old) with unresectable HCC (uHCC). Methods We retrospectively analyzed 158 patients aged ≥ 65 diagnosed with uHCC who received targeted therapy alone or in combination with immunotherapy from the CLEAP database between March 2019 and July 2023. The primary endpoint was overall survival (OS), with secondary endpoints including progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and safety assessments for adverse events (AEs). Results The ORR was 3.6% in the targeted monotherapy group compared to 29.4% in the combination therapy group, while the DCRs were 53.6% and 54.9%, respectively. Survival analysis indicated a median PFS of 7.3 months for monotherapy versus 13.2 months for combination therapy (P = 0.137) and a median OS of 16.0 months versus 20.0 months, respectively (P = 0.140). AEs occurred in 44.6% of the monotherapy group and 58.8% in the combination therapy group, with 20.5% in the combination group withdrawing due to adverse reactions, significantly higher than in monotherapy group. Conclusion Among older patients with uHCC, the combination therapy demonstrated higher ORR and longer PFS and OS, although it had higher incidences of AEs and drug withdrawal.
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Affiliation(s)
- Yu Li
- Department of Phase I Clinical Trial Center, The First Hospital of Jilin University, Changchun, Jilin, China
| | - Jian-Hong Zhong
- Department of Hepatobiliary Surgery, The Affiliated Cancer Hospital of Guangxi Medical University, Nanning, Guangxi, China
| | - Xiao-Dong Zhu
- Department of Liver Surgery and Transplantation, Liver Cancer Institute and Zhongshan Hospital, Fudan University, Shanghai, China
| | - Chuang-Ye Han
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China
| | - Jia-Bei Wang
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of University of Science and Technology of China (USTC), Hefei, Anhui, China
| | - Hong-Zhi Liu
- Department of Hepatobiliary Surgery, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, Fujian, China
| | - Kuan Hu
- Department of Hepatobiliary Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Yang-Xun Pan
- Department of Liver Surgery, Sun Yat-Sen University Cancer Center, Sun Yat-Sen University, Guangzhou, Guangdong, China
| | - Hui-Chuan Sun
- Department of Liver Surgery and Transplantation, Liver Cancer Institute and Zhongshan Hospital, Fudan University, Shanghai, China
| | - Tao Peng
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China
| | - Lian-Xin Liu
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of University of Science and Technology of China (USTC), Hefei, Anhui, China
| | - Yong-Yi Zeng
- Department of Hepatobiliary Surgery, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, Fujian, China
| | - Le-Du Zhou
- Department of Hepatobiliary Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Li Xu
- Department of Liver Surgery, Sun Yat-Sen University Cancer Center, Sun Yat-Sen University, Guangzhou, Guangdong, China
| | - Nan-Ya Wang
- Department of Phase I Clinical Trial Center, The First Hospital of Jilin University, Changchun, Jilin, China
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Donia T, Ali EMM, Kalantan AA, Alzahrani FA, Eid TM, Khamis AA. Synergistic anticancer efficacy of polydatin and sorafenib against the MCF-7 breast cancer cell line via inhibiting of PI3K/AKT/mTOR pathway and reducing resistance to treatment. Biochem Biophys Res Commun 2024; 739:150972. [PMID: 39541924 DOI: 10.1016/j.bbrc.2024.150972] [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: 08/14/2024] [Revised: 10/25/2024] [Accepted: 11/08/2024] [Indexed: 11/17/2024]
Abstract
Polydatin (PD), a glucoside derivative of resveratrol, has been investigated for its potential to mitigate sorafenib (SOF) side effects and combat multidrug resistance in cancer treatment. The study evaluated its mechanism of action for inhibiting the protein kinase B/mTOR pathway in promoting breast cancer proliferation. The combined PD and SOF have synergistic effects with a combination index (CI) < 1 in the liver (HepG2) and breast (MCF-7) cancer cell lines. Molecular docking studies were conducted to analyze interactions of PD& SOF with protein kinases as well as apoptotic and multidrug resistance proteins, including AKT1, PI3K, mTOR, Apaf-1, and ABCB1 in MCF-7 cells. Experimental validation through real-time PCR confirmed. PD has a strong binding affinity, particularly with AKT1 (-56 kcal/mol) and ABCB1 (-27.16 kcal/mol), a gene associated with multidrug resistance. These interactions were linked to anti-proliferative anti-angiogenic effects and reduced resistance to treatment, demonstrating PD has potential therapeutic benefits. Furthermore, PD combined with SOF induced apoptosis, inhibited cell growth, and arrested MCF-7 cells in the sub-G1 phase with increased intracellular ROS. This was accompanied by reduced expression of AKT1 and ABCB1 genes, reinforcing the anticancer efficacy of PD/SOF combination therapy. In conclusion, the findings suggest that PD/SOF could serve as a promising anticancer treatment strategy, warranting further investigation for potential clinical applications and mechanistic studies in vivo.
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Affiliation(s)
- Thoria Donia
- Division of Biochemistry, Department of Chemistry, Faculty of Science, Tanta University, Tanta, Egypt.
| | - Ehab M M Ali
- Division of Biochemistry, Department of Chemistry, Faculty of Science, Tanta University, Tanta, Egypt; Department of Biochemistry, Faculty of Sciences, King Abdulaziz University, 21589 Jeddah, Saudi Arabia.
| | - Abdulaziz A Kalantan
- Department of Biochemistry, Faculty of Sciences, King Abdulaziz University, 21589 Jeddah, Saudi Arabia.
| | - Faisal Ay Alzahrani
- Department of Chemistry, College of Sciences & Arts, King Abdulaziz University, 21911 Rabigh, Saudi Arabia.
| | - Thamir M Eid
- Department of Biochemistry, Faculty of Sciences, King Abdulaziz University, 21589 Jeddah, Saudi Arabia.
| | - Abeer A Khamis
- Division of Biochemistry, Department of Chemistry, Faculty of Science, Tanta University, Tanta, Egypt.
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Xiang Z, Huang Y, Ma J, Lin Y, Wen Y, Zhou Y, Liu J. Temporal trends of incidence, mortality, and survival of liver cancer during 2011-2020 in Fujian Province, Southeast China. Arch Public Health 2024; 82:233. [PMID: 39633411 PMCID: PMC11616380 DOI: 10.1186/s13690-024-01462-7] [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: 03/22/2024] [Accepted: 11/25/2024] [Indexed: 12/07/2024] Open
Abstract
BACKGROUND Liver cancer is a common malignant tumor of the digestive system. We aimed to estimate the trend in the burden of liver cancer in Fujian Province, China, during 2011-2020. METHODS The population-based cancer data was collected from the cancer registry in Fujian Province during 2011-2020. Segi's world standard population was used to calculate the age-standardized incidence rates and age-standardized mortality rates. The temporal trend of liver cancer was displayed by annual percentage change and average annual percentage change (AAPC). Relative survival of liver cancer was calculated as the ratio of observed survival to expected survival. The age-standardized relative survival was calculated according to the International Cancer Survival Standards 1. RESULTS There were 14,725 patients diagnosed with liver cancer and 12,698 patients died between 2011 and 2020. For males, there was a downward trend in incidence and mortality (AAPC: -3.86%, -3.44%). Similarly, the downward trend was also shown in females (AAPC: -3.96%, -2.79%). The highest age-specific incidence and mortality were in the 75-79 age group (146.59/100,000 and 137.99/100,000, respectively), and there was no downward trend in this group during the period. The overall age-standardized 5-year relative survival was 10.77% in 2011-2015 and 14.54% in 2016-2020. During the study period, the percentage improvement of survival was higher in males than in females (34.75% and 25.33%). The percentage improvement of survival in urban was higher than that in rural (38.64% and 28.75%). Except for the age group over 75, the survival of patients in other age groups all has improved. CONCLUSIONS Liver cancer remains a serious public health problem in Fujian Province, China, which needs to be solved, especially in some high-risk groups such as the elderly, high-risk males, and rural populations. Early detection and treatment is the key to the prevention and treatment of liver cancer.
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Affiliation(s)
- Zhisheng Xiang
- Department of Epidemiology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, No.420 Fuma Road, Fuzhou, 350014, China
| | - Yongying Huang
- Department of Epidemiology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, No.420 Fuma Road, Fuzhou, 350014, China
| | - Jingyu Ma
- Department of Epidemiology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, No.420 Fuma Road, Fuzhou, 350014, China
| | - Yongtian Lin
- Department of Epidemiology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, No.420 Fuma Road, Fuzhou, 350014, China
| | - Yeying Wen
- Department of Epidemiology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, No.420 Fuma Road, Fuzhou, 350014, China
| | - Yan Zhou
- Department of Epidemiology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, No.420 Fuma Road, Fuzhou, 350014, China.
| | - Jingfeng Liu
- Department of Hepatopancreatobiliary Surgery, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, No.420 Fuma Road, Fuzhou, 350014, China.
- Fujian Key Laboratory of Advanced Technology for Cancer Screening and Early Diagnosis, Fuzhou, 350014, China.
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Oura K, Morishita A, Takuma K, Nakahara M, Tadokoro T, Fujita K, Mimura S, Tani J, Ono M, Himoto T, Masaki T. Efficacy and outcome of molecular targeted therapies in elderly patients with hepatocellular carcinoma: Relative dose intensity associated with overall survival. Cancer Med 2023; 12:22023-22037. [PMID: 38062925 PMCID: PMC10757153 DOI: 10.1002/cam4.6783] [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: 11/15/2022] [Revised: 11/16/2023] [Accepted: 11/22/2023] [Indexed: 12/31/2023] Open
Abstract
AIM Indications of drug therapies to elderly patients with hepatocellular carcinoma (HCC) should be carefully determined. The current study assessed the safety and efficacy of molecular targeted agents (MTAs) in the elderly patients with HCC, and identified factors associated with prognosis in a real-world clinical setting. METHODS In a retrospective observational study, clinical data of patients with unresectable HCC treated with sorafenib or lenvatinib as first-line treatment at our hospital between 2011 and 2022, were investigated. Clinical parameters, therapeutic effects, adverse events (AEs), and prognosis were evaluated separately for the non-elderly (<75 years old) and elderly patients (≥75 years old). RESULTS Overall, 111 patients were enrolled, including 59 non-elderly and 52 elderly patients. Compared to the non-elderly patients, the elderly patients had significantly lower skeletal muscle mass and a significantly lower percentage of patients in poor general condition with performance status 2 or higher, but there were no differences in parameters related to liver function or nutritional status. There were no significant differences in the incidence of severe AEs and therapeutic effects between the groups. No significant difference in progression-free survival was observed in the elderly and non-elderly patients; however, overall survival (OS) for sorafenib treatment was shorter in the elderly patients than in the non-elderly patients. Elderly patients consumed lower doses of both the drugs, and relative dose intensity (RDI) 4 weeks after treatment (4W-RDI) was associated with OS. Further, OS in the elderly patients was significantly longer in the subgroup with high 4W-RDI as compared to that in the subgroup with low 4W-RDI. CONCLUSIONS MTAs can be safely administered to elderly patients with HCC. Furthermore, 4W-RDI is associated with longer OS. Maintaining RDI in the early phase is crucial in predicting the success of treatment with MTAs, especially in the elderly patients.
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Affiliation(s)
- Kyoko Oura
- Department of Gastroenterology and Neurology, Faculty of MedicineKagawa UniversityKagawaJapan
| | - Asahiro Morishita
- Department of Gastroenterology and Neurology, Faculty of MedicineKagawa UniversityKagawaJapan
| | - Kei Takuma
- Department of Gastroenterology and Neurology, Faculty of MedicineKagawa UniversityKagawaJapan
| | - Mai Nakahara
- Department of Gastroenterology and Neurology, Faculty of MedicineKagawa UniversityKagawaJapan
| | - Tomoko Tadokoro
- Department of Gastroenterology and Neurology, Faculty of MedicineKagawa UniversityKagawaJapan
| | - Koji Fujita
- Department of Gastroenterology and Neurology, Faculty of MedicineKagawa UniversityKagawaJapan
| | - Shima Mimura
- Department of Gastroenterology and Neurology, Faculty of MedicineKagawa UniversityKagawaJapan
| | - Joji Tani
- Department of Gastroenterology and Neurology, Faculty of MedicineKagawa UniversityKagawaJapan
| | - Masafumi Ono
- Department of Gastroenterology and Neurology, Faculty of MedicineKagawa UniversityKagawaJapan
| | - Takashi Himoto
- Department of Medical TechnologyKagawa Prefectural University of Health SciencesKagawaJapan
| | - Tsutomu Masaki
- Department of Gastroenterology and Neurology, Faculty of MedicineKagawa UniversityKagawaJapan
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Ahmed FA, Khan SA, Hafeez MS, Jehan FS, Aziz H. Outcomes in elderly patients undergoing hepatic resection compared to ablative therapy for hepatocellular carcinoma. J Surg Oncol 2023; 128:803-811. [PMID: 37288805 DOI: 10.1002/jso.27369] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2022] [Revised: 05/21/2023] [Accepted: 05/27/2023] [Indexed: 06/09/2023]
Abstract
BACKGROUND AND OBJECTIVES Hepatic resection is an excellent option in the care of patients with hepatocellular carcinoma (HCC). Elderly patients often forego hepatic resection in favor of liver-directed ablative therapies due to the increased likelihood of adverse postoperative outcomes due to age. We sought to determine long-term outcomes in patients who underwent hepatic resection compared to liver-directed ablative therapy in this patient population. METHODS We queried the National Cancer Database for elderly patients (≥70 years) diagnosed with HCC between 2004 and 2018. The primary outcome was overall survival (OS) computed using the Kaplan-Meier method and Cox proportional hazard regression. RESULTS A total of 10 032 patients were included in this analysis. On unadjusted analysis (p < 0.001) as well as multivariable analysis (hazard ratio: 0.65, 95% confidence interval: 0.57-0.73), hepatic resection was associated with improved OS. The protective association between hepatic resection and OS persisted after 1:1 propensity score matching. CONCLUSIONS Hepatic resection is associated with improved survival for well-selected elderly patients with HCC. While age is often thought of as influencing the decision to offer surgery, our study, in combination with others, demonstrates that it should not. Instead, other objective indicators of performance and functional status may be considered.
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Affiliation(s)
- Fasih A Ahmed
- Division of Surgical Oncology, University Hospitals Cleveland Medical Center, Cleveland, Ohio, USA
| | - Sameer A Khan
- Department of Surgery, University of Pennsylvania Hospitals System, Philadelphia, Pennsylvania, USA
| | - Muhammad S Hafeez
- Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
| | - Faisal S Jehan
- Department of Surgery, Westchester Medical Center-New York Medical College, Valhalla, New York, USA
| | - Hassan Aziz
- Division of Transplant and Hepatobiliary Surgery, University of Iowa Hospitals and Clinics, Iowa City, Iowa, USA
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Soria A, Calvo M, Casas M, Vidales Z, Muñoz-Martínez S, Sapena V, Puigvehi M, Canillas L, Guardeño R, Gallego A, Mínguez B, Horta D, Clos A, Montoliu S, Roget M, Reig M, Vergara M. Survival and adverse events of elderly patients treated with sorafenib for hepatocellular carcinoma. Front Oncol 2022; 12:829483. [PMID: 35982971 PMCID: PMC9380437 DOI: 10.3389/fonc.2022.829483] [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: 12/05/2021] [Accepted: 06/28/2022] [Indexed: 11/13/2022] Open
Abstract
Introduction The first-line treatment for advanced hepatocellular carcinoma (HCC) is atezolizumab plus bevacizumab, but its availability is not universal and elderly patients are underrepresented in clinical trials. There is little evidence of efficacy and tolerability in elderly patients under systemic treatment. The aims of this study were to characterize the profile of elderly patients treated with sorafenib, assess their survival and safety profile in order to extrapolate their eligibility for systemic treatment. Methods Retrospective multicentre study of HCC patients aged ≥75 years old treated with sorafenib from January 2008 to December 2019. Demographic data, baseline characteristics, and variables related to HCC and sorafenib were recorded. Overall survival (OS) and safety were analyzed. Results The study included 206 patients from 11 hospitals, median age 77.9 years; 71.4% men and 62.6% stage Barcelona Clinic Liver Cancer- C (BCLC-C). The main causes of cirrhosis were hepatitis C (60.7%) and alcohol (14.7%). Most patients (84.5%) started with sorafenib 800mg and 15.5% at lower dosage. Arterial hypertension (AHT) (74.2 vs 62.2%; standardized mean differences (STD): 26) and baseline ECOG-PS>0 (45.3 vs 34.7%; STD: 38.2) differed significantly between patients receiving low and full doses. Median OS was 15.4 months (18.2 in BCLC-B vs 13.6 in BCLC-C). OS was not modified by comorbidities, age or period with more expertise. Conclusions Sorafenib appears to be safe in elderly patients with HCC. This is the first study to characterize the profile of elderly patients to be considered for systemic treatment. These findings could be used as the reference profile for elderly candidates for atezolizumab-bevacizumab.
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Affiliation(s)
- Anna Soria
- Department of Digestive Diseases, Liver Unit, Parc Taulí University Hospital, Investigation and Innovation Institute Parc Taulí I3PT, Universitat Autònoma of Barcelona, Sabadell, Spain
| | - Mariona Calvo
- Medical Oncology Department, Catalan Institute of Oncology, Hospitalet, Barcelona, Spain
| | - Meritxell Casas
- Department of Digestive Diseases, Liver Unit, Parc Taulí University Hospital, Investigation and Innovation Institute Parc Taulí I3PT, Universitat Autònoma of Barcelona, Sabadell, Spain
| | - Zara Vidales
- Medical Oncology Department, Catalan Institute of Oncology, Hospitalet, Barcelona, Spain
| | - Sergio Muñoz-Martínez
- Barcelona Clinic Liver Cancer (BCLC) Group, Liver Unit, Clinical Insitute of Digestive and Metabolic Diseases (ICMDiM), Clinic Hospital, Barcelona University, Barcelona, Spain
- Biomedical Research Center in Digestive and Liver Diseases Network (CIBERehd), Instituto Carlos III, Madrid, Spain
| | - Victor Sapena
- Barcelona Clinic Liver Cancer (BCLC) Group, Liver Unit, Clinical Insitute of Digestive and Metabolic Diseases (ICMDiM), Clinic Hospital, Barcelona University, Barcelona, Spain
- Medical Statistics Core Facility, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clinic Barcelona, Barcelona, Spain
- Liver Unit, University Hospital Vall d’Hebron, Liver Diseases Research Group, Vall d’Hebron Institut of Research (VHIR), Universitat Autònoma of Barcelona, Barcelona, Spain
| | - Marc Puigvehi
- Department of Digestive Diseases, Liver Unit, Hospital del Mar Medical Research Institute, Barcelona, Spain
| | - Lidia Canillas
- Department of Digestive Diseases, Liver Unit, Hospital del Mar Medical Research Institute, Barcelona, Spain
| | - Raquel Guardeño
- Medical Oncology Department, Josep Trueta University Hospital, Catalan Institute of Oncology, Girona, Spain
| | - Adolfo Gallego
- Department of Digestive Diseases, Sant Pau i Santa Creu University Hospital, Barcelona, Spain
| | - Beatriz Mínguez
- Biomedical Research Center in Digestive and Liver Diseases Network (CIBERehd), Instituto Carlos III, Madrid, Spain
- Liver Unit, University Hospital Vall d’Hebron, Liver Diseases Research Group, Vall d’Hebron Institut of Research (VHIR), Universitat Autònoma of Barcelona, Barcelona, Spain
| | - Diana Horta
- Biomedical Research Center in Digestive and Liver Diseases Network (CIBERehd), Instituto Carlos III, Madrid, Spain
- Department of Gastroenterology, University Hospital Mútua Terrassa, Barcelona University, Terrassa, Spain
| | - Ariadna Clos
- Department of Digestive Diseases, Germans Trias i Pujol University Hospital, Badalona, Spain
| | - Silvia Montoliu
- Department of Digestive Diseases, Joan XXIII University Hospital, Tarragona, Spain
| | - Mercè Roget
- Department of Digestive Diseases, Liver Unit, Consorci Sanitari de Terrassa, Terrassa, Spain
| | - Maria Reig
- Barcelona Clinic Liver Cancer (BCLC) Group, Liver Unit, Clinical Insitute of Digestive and Metabolic Diseases (ICMDiM), Clinic Hospital, Barcelona University, Barcelona, Spain
- Biomedical Research Center in Digestive and Liver Diseases Network (CIBERehd), Instituto Carlos III, Madrid, Spain
| | - Mercedes Vergara
- Department of Digestive Diseases, Liver Unit, Parc Taulí University Hospital, Investigation and Innovation Institute Parc Taulí I3PT, Universitat Autònoma of Barcelona, Sabadell, Spain
- Biomedical Research Center in Digestive and Liver Diseases Network (CIBERehd), Instituto Carlos III, Madrid, Spain
- *Correspondence: Mercedes Vergara,
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Singh D, Khan MA, Akhtar K, Arjmand F, Siddique HR. Apigenin alleviates cancer drug Sorafenib induced multiple toxic effects in Swiss albino mice via anti-oxidative stress. Toxicol Appl Pharmacol 2022; 447:116072. [DOI: 10.1016/j.taap.2022.116072] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2022] [Revised: 05/12/2022] [Accepted: 05/14/2022] [Indexed: 12/14/2022]
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Yen YH, Li WF, Kee KM, Wang CC, Cheng YF, Wang JH, Lu SN, Hung CH. The characteristics of patients with macrovascular invasion in hepatocellular carcinoma: when East meets West. Langenbecks Arch Surg 2021; 407:225-234. [PMID: 34825277 DOI: 10.1007/s00423-021-02370-y] [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: 07/23/2021] [Accepted: 10/27/2021] [Indexed: 11/25/2022]
Abstract
PURPOSE To evaluate the prevalence and extension of macrovascular invasion (MaVI) in a large cohort of hepatocellular carcinoma (HCC) patients and analyze the association between MaVI and overall survival (OS). METHODS From 2011 to 2018, 2540 patients with newly diagnosed HCC who were managed in our institution were enrolled in this retrospective study. Tumor invasion of the intrahepatic branches of the portal or hepatic veins was defined as peripheral MaVI. Tumor invasion of the main portal vein or inferior vena cava was defined as central MaVI. RESULTS MaVI prevalence was 16.2% (n = 411). Among patients with Barcelona Clinic Liver Cancer (BCLC) stage C and Child-Pugh class A, 165 patients presented with peripheral MaVI and 89 patients with central MaVI. The median OS was 13.2 months (95% confidence interval [CI]: 11.4-15.4) in the peripheral MaVI group and 6.6 months (95% CI: 3.6-9.5) in the central MaVI group (p < 0.001). In patients with BCLC stage C and Child-Pugh class B or BCLC stage D, 68 patients presented with peripheral MaVI and 89 patients with central MaVI. The median OS was 3.6 months (95% CI: 3.1-4.2) in the peripheral MaVI group and 2.8 months (95% CI: 2.1-3.4) in the central MaVI group (p = 0.674). CONCLUSION The extension of MaVI significantly affected patient survival only in those with BCLC stage C and Child-Pugh class A. In patients with BCLC stage C and Child-Pugh class B or BCLC stage D, survival was poor irrespective of MaVI status.
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Affiliation(s)
- Yi-Hao Yen
- Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, 123 Ta Pei Road, Kaohsiung, Taiwan.
| | - Wei-Feng Li
- Liver Transplantation Center and Department of Surgery, Kaohsiung Chang Gung Memorial Hospital, 123 Ta Pei Road, Kaohsiung, Taiwan
| | - Kwong-Ming Kee
- Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, 123 Ta Pei Road, Kaohsiung, Taiwan
| | - Chih-Chi Wang
- Liver Transplantation Center and Department of Surgery, Kaohsiung Chang Gung Memorial Hospital, 123 Ta Pei Road, Kaohsiung, Taiwan.
| | - Yu-Fan Cheng
- Liver Transplantation Center, Department of Diagnostic Radiology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Jing-Houng Wang
- Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, 123 Ta Pei Road, Kaohsiung, Taiwan
| | - Sheng-Nan Lu
- Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, 123 Ta Pei Road, Kaohsiung, Taiwan
| | - Chao-Hung Hung
- Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, 123 Ta Pei Road, Kaohsiung, Taiwan
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Gao M, Deng C, Dang F. Synergistic antitumor effect of resveratrol and sorafenib on hepatocellular carcinoma through PKA/AMPK/eEF2K pathway. Food Nutr Res 2021; 65:3602. [PMID: 34776832 PMCID: PMC8559449 DOI: 10.29219/fnr.v65.3602] [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: 06/03/2019] [Revised: 03/31/2021] [Indexed: 11/24/2022] Open
Abstract
Although sorafenib (Sor) is the only effective drug for hepatocellular carcinoma (HCC), its therapeutic potential to date is mainly limited to the low tumor response. This study was designed to explore whether resveratrol (Res) could potentiate the anticancerous activity of Sor. We used HepG2 and Huh7 HCC cell lines and BALB/c nude mice for in vitro and in vivo studies, respectively. The cultured cell lines and tumor induction in the mice were treated with different concentrations of Res and Sor alone, and the combination of Res and Sor to observe the antitumor effects. Significant inhibitory effects were observed in the combined treatment of Res and Sor compared to Res and Sor alone treatments both in vitro and in vivo as demonstrated by significantly high number of S phase cells and apoptotic cells. Moreover, these findings were accompanied by the reduction of CDK2, CDC25A, PKA, p-AMPK, and eEF2K protein levels and the increment of cyclin A, cleavage caspase-3, caspase-8, and caspase-9 protein levels. The combinational treatment exhibited more significant anticancerous effect than the Res and Sor alone treatments in mice-bearing HepG2 xenograft. Overall, our results suggest that PKA/AMPK/eEF2K pathway is involved in the synergistic anticancerous activity of Res and Sor combination treatment in HCC cells. Thus, Res and Sor combination therapy may be promising in increasing the tumor response of Sor in the future.
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Affiliation(s)
- Meili Gao
- Department of Biological Science and Engineering, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, China
| | - Chun Deng
- Department of Biological Science and Engineering, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, China
| | - Fan Dang
- Department of Biological Science and Engineering, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, China
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Macias RI, Monte MJ, Serrano MA, González-Santiago JM, Martín-Arribas I, Simão AL, Castro RE, González-Gallego J, Mauriz JL, Marin JJ. Impact of aging on primary liver cancer: epidemiology, pathogenesis and therapeutics. Aging (Albany NY) 2021; 13:23416-23434. [PMID: 34633987 PMCID: PMC8544321 DOI: 10.18632/aging.203620] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2021] [Accepted: 09/28/2021] [Indexed: 01/18/2023]
Abstract
Aging involves progressive physiological and metabolic reprogramming to adapt to gradual deterioration of organs and functions. This includes mechanisms of defense against pre-malignant transformations. Thus, certain tumors are more prone to appear in elderly patients. This is the case of the two most frequent types of primary liver cancer, i.e., hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA). Accordingly, aging hallmarks, such as genomic instability, telomere attrition, epigenetic alterations, altered proteostasis, mitochondrial dysfunction, cellular senescence, exhaustion of stem cell niches, impaired intracellular communication, and deregulated nutrient sensing can play an important role in liver carcinogenesis in the elders. In addition, increased liver fragility determines a worse response to risk factors, which more frequently affect the aged population. This, together with the difficulty to carry out an early detection of HCC and iCCA, accounts for the late diagnosis of these tumors, which usually occurs in patients with approximately 60 and 70 years, respectively. Furthermore, there has been a considerable controversy on what treatment should be used in the management of HCC and iCCA in elderly patients. The consensus reached by numerous studies that have investigated the feasibility and safety of different curative and palliative therapeutic approaches in elders with liver tumors is that advanced age itself is not a contraindication for specific treatments, although the frequent presence of comorbidities in these individuals should be taken into consideration for their management.
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Affiliation(s)
- Rocio I.R. Macias
- Experimental Hepatology and Drug Targeting (HEVEPHARM) Group, University of Salamanca, IBSAL, Salamanca, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Carlos III National Institute of Health, Madrid, Spain
| | - Maria J. Monte
- Experimental Hepatology and Drug Targeting (HEVEPHARM) Group, University of Salamanca, IBSAL, Salamanca, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Carlos III National Institute of Health, Madrid, Spain
| | - Maria A. Serrano
- Experimental Hepatology and Drug Targeting (HEVEPHARM) Group, University of Salamanca, IBSAL, Salamanca, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Carlos III National Institute of Health, Madrid, Spain
| | - Jesús M. González-Santiago
- Department of Gastroenterology and Hepatology, University Hospital of Salamanca, IBSAL, Salamanca, Spain
| | - Isabel Martín-Arribas
- Department of Gastroenterology and Hepatology, University Hospital of Salamanca, IBSAL, Salamanca, Spain
| | - André L. Simão
- Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Lisbon, Portugal
| | - Rui E. Castro
- Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Lisbon, Portugal
| | - Javier González-Gallego
- Institute of Biomedicine (IBIOMED), University of León, León, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Carlos III National Institute of Health, Madrid, Spain
| | - José L. Mauriz
- Institute of Biomedicine (IBIOMED), University of León, León, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Carlos III National Institute of Health, Madrid, Spain
| | - Jose J.G. Marin
- Experimental Hepatology and Drug Targeting (HEVEPHARM) Group, University of Salamanca, IBSAL, Salamanca, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Carlos III National Institute of Health, Madrid, Spain
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11
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Monteiro AR, Conde RS, Basto R, Sclafani F, Deleporte A, Hendlisz A, Dal Lago L. Targeted agents in older patients with gastrointestinal cancers - An overview. J Geriatr Oncol 2021; 12:1240-1252. [PMID: 34226158 DOI: 10.1016/j.jgo.2021.06.013] [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: 04/07/2021] [Revised: 06/12/2021] [Accepted: 06/25/2021] [Indexed: 12/24/2022]
Abstract
Targeted agents have been increasingly used in different malignancies and are associated with improved survival outcomes, including gastrointestinal cancers. Their use in the treatment of older patients is appealing given their favorable toxicity profile. In the last years, this subgroup of patients has been attracting increased interest given their representativeness and specific clinical needs. Nonetheless, the lack of data on efficacy and safety of standard treatments in older patients hinders proper evidence-based decision-making, leaving most therapeutic recommendations to be extrapolated from registration trials with low representation of older and frail patients. However, even if most decisions regarding the use of targeted agents in older patients with gastrointestinal cancer remain guided by subanalyses of large trials, data from recent older adult-specific trials are beginning to emerge, particularly in colorectal cancer. This review aims to summarize the existing evidence on treatment of older patients with gastrointestinal carcinomas (colon and rectum, stomach, esophagus, liver, and pancreas) with targeted agents (cetuximab, panitumumab, bevacizumab, ramucirumab, aflibercept, regorafenib, encorafenib, trastuzumab, sorafenib, lenvatinib, cabozantinib, erlotinib, olaparib), and place the evidence in a geriatric oncology perspective.
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Affiliation(s)
- Ana Raquel Monteiro
- Instituto Português de Oncologia de Coimbra Francisco Gentil, Department of Medical Oncology, Av. Bissaya Barreto 98, 3000-075 Coimbra, Portugal.
| | - Rita Saúde Conde
- Instituto Português de Oncologia de Lisboa Francisco Gentil, Department of Medical Oncology, Rua Professor Lima Basto, 1099-023 Lisboa, Portugal.
| | - Raquel Basto
- Instituto Português de Oncologia de Coimbra Francisco Gentil, Department of Medical Oncology, Av. Bissaya Barreto 98, 3000-075 Coimbra, Portugal.
| | - Francesco Sclafani
- Institut Jules Bordet, Department of Medicine, Blvd de Waterloo 121, 1000 Brussels, Belgium.
| | - Amélie Deleporte
- Institut Jules Bordet, Department of Medicine, Blvd de Waterloo 121, 1000 Brussels, Belgium.
| | - Alain Hendlisz
- Institut Jules Bordet, Department of Medicine, Blvd de Waterloo 121, 1000 Brussels, Belgium.
| | - Lissandra Dal Lago
- Institut Jules Bordet, Department of Medicine, Blvd de Waterloo 121, 1000 Brussels, Belgium.
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12
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Cammarota A, D'Alessio A, Pressiani T, Rimassa L, Personeni N. Systemic Treatment for Older Patients with Unresectable Hepatocellular Carcinoma. Drugs Aging 2021; 38:579-591. [PMID: 34152589 DOI: 10.1007/s40266-021-00871-5] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/22/2021] [Indexed: 12/25/2022]
Abstract
The incidence rate of hepatocellular carcinoma is growing and age at diagnosis is increasing; however, despite the unprecedented wealth of therapeutic options for advanced HCC, its optimal management in some categories, such as older adults, is yet to be defined. Even though age is not an exclusion criterion per se, most of the landmark trials enrolled a limited number of senior patients, raising some concerns on the potential benefit of active treatments in this group. The identification of more vulnerable patients remains a crucial issue in clinical practice. In fact, the suitability assessment for systemic therapy through performance status metrics might underestimate or conversely overestimate the fitness of older patients, failing to detect other relevant impairments. Thus, the assessment of frailty through geriatric screening scales is largely necessary. In addition, most of the available data relate to the use of sorafenib, while very little is known about the most recent therapeutic agents. Age subgroup analyses provided by many of the pivotal trials did not find significant efficacy or safety differences across ages; however, the most widely used cut-off age of 65 years may not be very informative for the current older population. Regarding immunotherapy, the clinical benefit reported with immune checkpoint inhibitors reassures their safe use in senior patients and supports further investigations to assess their efficacy in this population.
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Affiliation(s)
- Antonella Cammarota
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, Pieve Emanuele, 20090, Milan, Italy.,Medical Oncology and Hematology Unit, Humanitas Cancer Center, IRCCS Humanitas Research Hospital, Via Manzoni 56, Rozzano, 20089, Milan, Italy
| | - Antonio D'Alessio
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, Pieve Emanuele, 20090, Milan, Italy.,Medical Oncology and Hematology Unit, Humanitas Cancer Center, IRCCS Humanitas Research Hospital, Via Manzoni 56, Rozzano, 20089, Milan, Italy
| | - Tiziana Pressiani
- Medical Oncology and Hematology Unit, Humanitas Cancer Center, IRCCS Humanitas Research Hospital, Via Manzoni 56, Rozzano, 20089, Milan, Italy
| | - Lorenza Rimassa
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, Pieve Emanuele, 20090, Milan, Italy. .,Medical Oncology and Hematology Unit, Humanitas Cancer Center, IRCCS Humanitas Research Hospital, Via Manzoni 56, Rozzano, 20089, Milan, Italy.
| | - Nicola Personeni
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, Pieve Emanuele, 20090, Milan, Italy.,Medical Oncology and Hematology Unit, Humanitas Cancer Center, IRCCS Humanitas Research Hospital, Via Manzoni 56, Rozzano, 20089, Milan, Italy
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13
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Meriggi F, Graffeo M. Clinical Characterisation and Management of the Main Treatment-Induced Toxicities in Patients with Hepatocellular Carcinoma and Cirrhosis. Cancers (Basel) 2021; 13:584. [PMID: 33540870 PMCID: PMC7867371 DOI: 10.3390/cancers13030584] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2021] [Revised: 01/24/2021] [Accepted: 01/28/2021] [Indexed: 12/12/2022] Open
Abstract
The incidence of hepatocellular carcinoma (HCC) continues to increase worldwide, particularly in Western countries. In almost all cases, HCC develops in subjects with hepatic cirrhosis, often as the result of hepatitis B or C virus infection, alcohol abuse or metabolic forms secondary to non-alcoholic steatohepatitis. Patients with HCC and hepatic symptoms can therefore present symptoms that are attributable to both conditions. These patients require multidisciplinary management, calling for close interaction between the hepatologist and the oncologist. Indeed, the treatment of HCC requires, depending on the disease stage and the degree of hepatic impairment, locoregional therapies that can in turn be broken down into surgical and nonsurgical treatments and systemic treatments used in the event of progression after the administration of locoregional treatments. The past decade has seen the publication of countless papers of great interest that have radically changed the scenario of treatment for HCC. Novel therapies with biological agents and immunotherapy have come to be standard options in the approach to treatment of this cancer, obtaining very promising results where in the past chemotherapy was almost never able to have an impact on the course of the disease. However, in addition to being costly, these drugs are not devoid of adverse effects and their management cannot forgo the consideration of the underlying hepatic impairment. Patients with HCC and cirrhosis therefore require special attention, starting from the initial characterisation needed for an appropriate selection of those to be referred for treatment, as these patients are almost never fit. In this chapter, we will attempt to investigate and clarify the key points of the management of the main toxicities induced by locoregional and systemic treatments for HCC secondary to cirrhosis.
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Affiliation(s)
- Fausto Meriggi
- Oncology Department, Istituto Ospedaliero Fondazione Poliambulanza, Via Leonida Bissolati 57, 25124 Brescia, Italy
| | - Massimo Graffeo
- Hepatology Unit, Istituto Ospedaliero Fondazione Poliambulanza, Via Leonida Bissolati 57, 25124 Brescia, Italy;
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14
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Hajiev S, Allara E, Motedayеn Aval L, Arizumi T, Bettinger D, Pirisi M, Rimassa L, Pressiani T, Personeni N, Giordano L, Kudo M, Thimme R, Park JW, Taddei TH, Kaplan DE, Ramaswami R, Pinato DJ, Sharma R. Impact of age on sorafenib outcomes in hepatocellular carcinoma: an international cohort study. Br J Cancer 2021; 124:407-413. [PMID: 33071284 PMCID: PMC7852559 DOI: 10.1038/s41416-020-01116-9] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2020] [Revised: 09/15/2020] [Accepted: 09/25/2020] [Indexed: 02/08/2023] Open
Abstract
BACKGROUND There is no consensus on the effect of sorafenib dosing on efficacy and toxicity in elderly patients with hepatocellular carcinoma (HCC). Older patients are often empirically started on low-dose therapy with the aim to avoid toxicities while maximising clinical efficacy. We aimed to verify whether age impacts on overall survival (OS) and whether a reduced starting dose impacts on OS or toxicity experienced by the elderly. METHODS In an international, multicentre cohort study, outcomes for those aged <75 or ≥75 years were determined while accounting for common prognostic factors and demographic characteristics in univariable and multivariable models. RESULTS Five thousand five hundred and ninety-eight patients were recruited; 792 (14.1%) were aged ≥75 years. The elderly were more likely to have larger tumours (>7 cm) (39 vs 33%, p < 0.01) with preserved liver function (67 vs 57.7%) (p < 0.01). No difference in the median OS of those aged ≥75 years and <75 was noted (7.3 months vs 7.2 months; HR 1.00 (95% CI 0.93-1.08), p = 0.97). There was no relationship between starting dose of sorafenib 800 mg vs 400 mg/200 mg and OS between those <75 and ≥75 years. The elderly experienced a similar overall incidence of grade 2-4 sorafenib-related toxicity compared to <75 years (63.5 vs 56.7%, p = 0.11). However, the elderly were more likely to discontinue sorafenib due to toxicity (27.0 vs 21.6%, p < 0.01). This did not vary between different starting doses of sorafenib. CONCLUSIONS Clinical outcomes in the elderly is equivalent to patients aged <75 years, independent of dose of sorafenib prescribed.
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Affiliation(s)
- Saur Hajiev
- Division of Surgery and Cancer, Imperial College London, Hammersmith Hospital, Du Cane Road, London, W12 0NN, UK
| | - Elias Allara
- Division of Surgery and Cancer, Imperial College London, Hammersmith Hospital, Du Cane Road, London, W12 0NN, UK
- Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK
| | - Leila Motedayеn Aval
- Division of Surgery and Cancer, Imperial College London, Hammersmith Hospital, Du Cane Road, London, W12 0NN, UK
| | - Tadaaki Arizumi
- Department of Gastroenterology and Hepatology, Kinki University School of Medicine, Osaka-Sayama, Japan
| | - Dominik Bettinger
- Department of Medicine II, University Medical Center, Freiburg, Germany
- Berta-Ottenstein Programme, Faculty of Medicine, University of Freiburg, Freiburg, Germany
| | - Mario Pirisi
- Department of Translational Medicine, Università degli Studi del Piemonte Orientale, Novara, Italy
| | - Lorenza Rimassa
- Medical Oncology and Hematology Unit, Humanitas Cancer Center, Humanitas Clinical and Research Center-IRCCS, Rozzano (Milan), Italy
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele (Milan), Italy
| | - Tiziana Pressiani
- Medical Oncology and Hematology Unit, Humanitas Cancer Center, Humanitas Clinical and Research Center-IRCCS, Rozzano (Milan), Italy
| | - Nicola Personeni
- Medical Oncology and Hematology Unit, Humanitas Cancer Center, Humanitas Clinical and Research Center-IRCCS, Rozzano (Milan), Italy
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele (Milan), Italy
| | - Laura Giordano
- Medical Oncology and Hematology Unit, Humanitas Cancer Center, Humanitas Clinical and Research Center-IRCCS, Rozzano (Milan), Italy
| | - Masatoshi Kudo
- Department of Gastroenterology and Hepatology, Kinki University School of Medicine, Osaka-Sayama, Japan
| | - Robert Thimme
- Department of Medicine II, University Medical Center, Freiburg, Germany
| | | | - Tamar H Taddei
- University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA
| | - David E Kaplan
- University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA
| | - Ramya Ramaswami
- Division of Surgery and Cancer, Imperial College London, Hammersmith Hospital, Du Cane Road, London, W12 0NN, UK
| | - David J Pinato
- Division of Surgery and Cancer, Imperial College London, Hammersmith Hospital, Du Cane Road, London, W12 0NN, UK
| | - Rohini Sharma
- Division of Surgery and Cancer, Imperial College London, Hammersmith Hospital, Du Cane Road, London, W12 0NN, UK.
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15
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Kudo M. Recent Advances in Systemic Therapy for Hepatocellular Carcinoma in an Aging Society: 2020 Update. Liver Cancer 2020; 9:640-662. [PMID: 33442538 PMCID: PMC7768150 DOI: 10.1159/000511001] [Citation(s) in RCA: 85] [Impact Index Per Article: 17.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/23/2020] [Accepted: 08/17/2020] [Indexed: 02/04/2023] Open
Abstract
Systemic therapy for hepatocellular carcinoma (HCC) has changed markedly since the introduction of the molecular targeted agent sorafenib in 2007. Sorafenib increased the available treatment options for patients with extrahepatic spread and vascular invasion and improved survival in patients with advanced HCC; however, various shortcomings such as low response rates and relatively high toxicity (e.g., hand-foot skin reaction) prompted concerted efforts aimed at developing new molecular targeted agents to provide more treatment options and second-line agents for patients with disease progression or intolerance to sorafenib. Despite many attempts to develop new drugs between 2007 and 2016, all first-line and second-line clinical trials conducted during this period failed. However, between 2017 and 2019, 4 drugs (lenvatinib as a first-line agent and regorafenib, cabozantinib, and ramucirumab as second-line agents) emerged in quick succession from clinical trials and became available for clinical use. In addition, nivolumab and pembrolizumab were approved as second-line agents after sorafenib. A recent phase III trial (IMbrave150) showed that combination immunotherapy with atezolizumab plus bevacizumab increases overall survival compared with sorafenib therapy; Food and Drug Agency already approved this combination therapy, and worldwide approval is expected soon. This review describes the recent advances in systemic therapy and the use of tyrosine kinase inhibitors (sorafenib, lenvatinib, regorafenib, and cabozantinib), monoclonal antibodies (ramucirumab and bevacizumab), and immune checkpoint inhibitors (nivolumab, pembrolizumab, and atezolizumab) in elderly patients and the similarity of their efficacy and safety profiles to those in the general population.
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Affiliation(s)
- Masatoshi Kudo
- Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka-Sayama, Japan
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16
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Schotten C, Wedemeyer H, Best J. Reply to the Letter to the Editor: "Comparison of the Safety and Efficacy of Yttrium-90 Radioembolization for Nonalcoholic Fatty Liver Disease-Associated and Hepatitis B Virus-Associated Hepatocellular Carcinoma". Liver Cancer 2020; 9:363-364. [PMID: 32647638 PMCID: PMC7325123 DOI: 10.1159/000506947] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/27/2020] [Accepted: 03/02/2020] [Indexed: 02/04/2023] Open
Affiliation(s)
- Clemens Schotten
- Department of Gastroenterology and Hepatology, Essen University Hospital, Essen, Germany
| | - Heiner Wedemeyer
- Department of Gastroenterology and Hepatology, Essen University Hospital, Essen, Germany
| | - Jan Best
- Department of Gastroenterology and Hepatology, Essen University Hospital, Essen, Germany
- Department of Gastroenterology, Hepatology and Infectious Diseases, Otto von Guericke University Magdeburg, Magdeburg, Germany
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17
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Cho E, Cho HA, Jun CH, Kim HJ, Cho SB, Choi SK. A Review of Hepatocellular Carcinoma in Elderly Patients Focused on Management and Outcomes. In Vivo 2020; 33:1411-1420. [PMID: 31471386 DOI: 10.21873/invivo.11618] [Citation(s) in RCA: 42] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2019] [Revised: 06/19/2019] [Accepted: 06/20/2019] [Indexed: 02/07/2023]
Abstract
Recent studies report a significant age-specific increase in hepatocellular carcinoma (HCC) development among persons over 75 years old. Therefore, there is an urgent need to determine the optimal treatment strategy in elderly patients with HCC. This systemic review examines the clinical characteristics, efficacy, and safety of first-line treatment modalities. The literature was searched regarding epidemiology and clinical outcomes in elderly patients (age ≥75 years) undergoing first-line treatment for HCC. Causative or comorbid conditions of HCC in elderly patients differed from those in younger patients. Radiofrequency ablation may be effective and safe in early stages. Surgical resection may also be feasible in the early stages for selected patients. Transarterial chemoembolization may be safe and effective for intermediate HCC, and sorafenib may be feasible in elderly patients with advanced HCC. Prospective randomized trials are needed to establish the treatment strategy for elderly patients with HCC.
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Affiliation(s)
- Eunae Cho
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chonnam National University Medical School, Gwanjgu, Republic of Korea
| | - Hyun A Cho
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chonnam National University Medical School, Gwanjgu, Republic of Korea
| | - Chung Hwan Jun
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chonnam National University Medical School, Gwanjgu, Republic of Korea
| | - Hee Joon Kim
- Department Surgery, Chonnam National University Medical School, Gwanjgu, Republic of Korea
| | - Sung Bum Cho
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chonnam National University Medical School, Gwanjgu, Republic of Korea
| | - Sung Kyu Choi
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chonnam National University Medical School, Gwanjgu, Republic of Korea
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18
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Arora SP, Liposits G, Caird S, Dunne RF, Moffat GT, Okonji D, Rodriquenz MG, Dua D, Dotan E. Hepatocellular carcinoma in older adults: A comprehensive review by Young International Society of Geriatric Oncology. J Geriatr Oncol 2019; 11:557-565. [PMID: 31704038 DOI: 10.1016/j.jgo.2019.10.007] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2019] [Revised: 09/12/2019] [Accepted: 10/03/2019] [Indexed: 02/08/2023]
Abstract
Given the prevalence and the rising incidence of hepatocellular carcinoma (HCC) in older adults worldwide, there is an urgent need to improve our understanding of the implications of treatment modalities in this population. The care of older patients with HCC is challenging due to the lack of evidence-based recommendations in this population. The current treatment approach for older patients relies on extrapolation of data from clinical trials conducted mostly in younger patients or fit older adults. Further, in the last few years, the arsenal of systemic treatments has increased with currently seven FDA-approved therapies available for patients with advanced HCC. Therefore, understanding how to apply current data to this unique and diverse patient population is necessary. This review will aim to shed light on the approach to older adults with HCC through an assessment of available data in the literature.
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Affiliation(s)
- Sukeshi Patel Arora
- Mays Cancer Center, University of Texas Health San Antonio, Leader in Gastrointestinal Malignancies, 7979 Wurzbach Rd, 78229 San Antonio, TX, USA.
| | | | - Susan Caird
- Gold Coast University Hospital, Southport, Australia, Griffith University, School of Medicine, Australia
| | - Richard F Dunne
- Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, NY, USA
| | | | - David Okonji
- Wellington Blood and Cancer Centre, Wellington Regional Hospital, Wellington, New Zealand
| | | | | | - Efrat Dotan
- Fox Chase Cancer Center, Philadelphia, PA, USA
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19
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Schotten C, Bechmann LP, Manka P, Theysohn J, Dechêne A, El Fouly A, Barbato F, Neumann U, Radünz S, Sydor S, Heider D, Venerito M, Canbay A, Gerken G, Herrmann K, Wedemeyer H, Best J. NAFLD-Associated Comorbidities in Advanced Stage HCC Do Not Alter the Safety and Efficacy of Yttrium-90 Radioembolization. Liver Cancer 2019; 8:491-504. [PMID: 31799206 PMCID: PMC6883476 DOI: 10.1159/000501484] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/25/2019] [Accepted: 06/12/2019] [Indexed: 02/04/2023] Open
Abstract
BACKGROUND Patients with advanced hepatocellular carcinoma (HCC) arising in nonalcoholic fatty liver disease (NAFLD) may not be suitable for systemic therapy due to metabolic syndrome-related diseases. Recent trials did not show a survival benefit of radioembolization (RE) compared to sorafenib in advanced stage HCC but RE may represent an adequate alternative in patients with contraindications to systemic therapy due to its favorable safety profile. AIM To investigate the impact of NAFLD-related comorbidities on safety and efficacy of RE for HCC treatment in a retrospective monocentric cohort study. PATIENTS AND METHODS Safety and efficacy of RE were evaluated in patients with NAFLD-associated HCC. Hepatitis B virus (HBV)-related HCC patients served as controls, exhibiting matching Barcelona Liver Cancer Clinic (BCLC) stages while showing significantly fewer metabolic comorbidities. RESULTS Overall, 87 HCC patients with NAFLD (mean age 71.3 ± 6.9 years) and 62 HCC patients with HBV (mean age 58.8 ± 10.9 years) not amenable to surgical or conventional locoregional treatments were included. Patients with HBV-related HCC had a comparable liver function to HCC patients with NAFLD. RE treatment-related toxicity did not differ between the two groups (increase in bilirubin Common Terminology Criteria for Adverse Events grade in 29 [38.7%] NAFLD and 20 [39.2%] HBV patients, p = 0.91). Overall survival was similar in HCC patients with NAFLD and HBV (11.1 [interquartile range, IQR, 18.27] vs. 9.3 months [IQR 14.73], p = 0.38), also in the subgroup analyses of BCLC B and C stages. CONCLUSION RE showed similar survival outcomes at a comparable toxicity profile in HCC patients with NAFLD and HBV. NAFLD-associated metabolic comorbidities did not exhibit limitations for RE while offering comparable therapeutic efficacy as compared to HBV patients.
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Affiliation(s)
- Clemens Schotten
- Department of Gastroenterology and Hepatology, Essen University Hospital, Essen, Germany
| | - Lars P. Bechmann
- Department of Gastroenterology, Hepatology and Infectious Diseases, Otto von Guericke University, Magdeburg, Germany
| | - Paul Manka
- Department of Gastroenterology and Hepatology, Essen University Hospital, Essen, Germany
| | - Jens Theysohn
- Institute for Diagnostic and Interventional Radiology and Neuroradiology, Essen University Hospital, Essen, Germany
| | - Alexander Dechêne
- Department of Gastroenterology and Hepatology, Essen University Hospital, Essen, Germany,Department of Internal Medicine 6, Paracelsus Medical University Nürnberg, Nürnberg, Germany
| | - Amr El Fouly
- Endemic Medicine Department, Helwan University, Cairo, Egypt
| | - Francesco Barbato
- Department of Nuclear Medicine, Essen University Hospital, Essen, Germany
| | - Ursula Neumann
- Department of Mathematics and Computer Science, Philipps University of Marburg, Marburg, Germany
| | - Sonia Radünz
- Department of General Surgery and Transplantation, Essen University Hospital, Essen, Germany
| | - Svenja Sydor
- Department of Gastroenterology, Hepatology and Infectious Diseases, Otto von Guericke University, Magdeburg, Germany
| | - Dominik Heider
- Department of Mathematics and Computer Science, Philipps University of Marburg, Marburg, Germany
| | - Marino Venerito
- Department of Gastroenterology, Hepatology and Infectious Diseases, Otto von Guericke University, Magdeburg, Germany
| | - Ali Canbay
- Department of Gastroenterology, Hepatology and Infectious Diseases, Otto von Guericke University, Magdeburg, Germany
| | - Guido Gerken
- Department of Gastroenterology and Hepatology, Essen University Hospital, Essen, Germany
| | - Ken Herrmann
- Department of Nuclear Medicine, Essen University Hospital, Essen, Germany
| | - Heiner Wedemeyer
- Department of Gastroenterology and Hepatology, Essen University Hospital, Essen, Germany
| | - Jan Best
- Department of Gastroenterology and Hepatology, Essen University Hospital, Essen, Germany,Department of Gastroenterology, Hepatology and Infectious Diseases, Otto von Guericke University, Magdeburg, Germany,*Jan Best, MD, Department of Gastroenterology, Hepatology and Infectious Diseases, University Hospital Magdeburg, Otto von Guericke University, Leipziger Strasse 44, DE–39120 Magdeburg (Germany), E-Mail
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20
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Kondo M, Morimoto M, Kobayashi S, Ohkawa S, Hidaka H, Nakazawa T, Aikata H, Hatanaka T, Takizawa D, Matsunaga K, Okuse C, Suzuki M, Taguri M, Ishibashi T, Numata K, Maeda S, Tanaka K. Randomized, phase II trial of sequential hepatic arterial infusion chemotherapy and sorafenib versus sorafenib alone as initial therapy for advanced hepatocellular carcinoma: SCOOP-2 trial. BMC Cancer 2019; 19:954. [PMID: 31615466 PMCID: PMC6794885 DOI: 10.1186/s12885-019-6198-8] [Citation(s) in RCA: 58] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2019] [Accepted: 09/24/2019] [Indexed: 02/06/2023] Open
Abstract
Background The efficacy of hepatic arterial infusion chemotherapy (HAIC) for advanced hepatocellular carcinoma (HCC) remains unclear. We conducted a multi-center randomized phase II study comparing a sequential HAIC-sorafenib regimen versus sorafenib alone as an initial therapy for HCC. Methods Patients were randomly assigned (ratio, 1:1) to receive sequential HAIC with cisplatin followed by sorafenib (HAIC group, n = 35) or sorafenib alone (sorafenib group, n = 33) as an initial therapy. The primary endpoint was the one-year survival rate. Secondary endpoint included overall survival (OS), the 2-year survival rate, the time-to-progression (TTP), the objective response rate (ORR), the disease control rate (DCR), and safety. Results For the primary endpoint, the one-year survival rates were 46% in the HAIC group and 58% in the sorafenib group. The median OS period was 10.0 months (95% CI, 7.0–18.8) in the HAIC group and 15.2 months (95% CI, 8.2–19.7) in the sorafenib group (hazard ratio [HR], 1.08; 95% CI, 0.63 to 1.86, P = 0.78). The median TTP, ORR and DCR in the HAIC group were 2.8 months (95% CI, 1.7–5.5), 14.3, and 45.7%, respectively, while those in the sorafenib group were 3.9 months (95% CI, 2.3–6.8), 9.1, and 45.5%, respectively. No unexpected adverse events related to HAIC or sorafenib were observed in either group. Conclusions Sequential HAIC with cisplatin and sorafenib does not improve the survival benefit, compared with sorafenib alone, when used as an initial therapy for advanced HCC. However, this study was underpowered in regard to its primary and secondary endpoints, so the results should be interpreted with caution. Trial registration UMIN ID 000006147, registration data: August 11, 2011.
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Affiliation(s)
- Masaaki Kondo
- Gastroenterological Center, Yokohama City University Medical Center 4-57, Urafune-cho, Minami-ku, Yokohama, Kanagawa, 232-0024, Japan. .,Department of Gastroenterology, Yokohama City University Hospital; 3-9, Fukuura, Kanazawa-ku, Yokohama, Kanagawa, 236-0004, Japan.
| | - Manabu Morimoto
- Gastroenterological Center, Yokohama City University Medical Center 4-57, Urafune-cho, Minami-ku, Yokohama, Kanagawa, 232-0024, Japan.,Hepatobiliary and Pancreatic Medical Oncology, Kanagawa Cancer Center Hospital; 1-1-2, Nakao, Asahi-ku, Yokohama, Kanagawa, 241-0815, Japan
| | - Satoshi Kobayashi
- Hepatobiliary and Pancreatic Medical Oncology, Kanagawa Cancer Center Hospital; 1-1-2, Nakao, Asahi-ku, Yokohama, Kanagawa, 241-0815, Japan
| | - Shinichi Ohkawa
- Hepatobiliary and Pancreatic Medical Oncology, Kanagawa Cancer Center Hospital; 1-1-2, Nakao, Asahi-ku, Yokohama, Kanagawa, 241-0815, Japan
| | - Hisashi Hidaka
- Gastroenterology Division of Internal Medicine, Kitasato University Hospital; 1-15-1, Kitasato, Minami-ku, Sagamihara, Kanagawa, 252-0329, Japan
| | - Takahide Nakazawa
- Gastroenterology Division of Internal Medicine, Kitasato University Hospital; 1-15-1, Kitasato, Minami-ku, Sagamihara, Kanagawa, 252-0329, Japan
| | - Hiroshi Aikata
- Department of Gastroenterology and Metabolism, Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University; 1-2-3, Kasumi, Minami-ku, Hiroshima, Hiroshima, 734-8551, Japan
| | - Takeshi Hatanaka
- Department of Internal Medicine, Isesaki Municipal Hospital; 12-1, Tsunatorihonmachi, Isesaki, Gunma, 372-0817, Japan
| | - Daichi Takizawa
- Department of Internal Medicine, Isesaki Municipal Hospital; 12-1, Tsunatorihonmachi, Isesaki, Gunma, 372-0817, Japan
| | - Kotaro Matsunaga
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, St Marianna University School of Medicine; 2-16-1, Sugao, Miyamae-ku, Kawasaki, Kanagawa, 216-8511, Japan
| | - Chiaki Okuse
- Division of Gastroenterology and Hepatology, Kawasaki Municipal Tama Hospital; 1-30-37, Shukugawara, Tama-ku, Kawasaki, Kanagawa, 214-8525, Japan
| | - Michihiro Suzuki
- Division of Gastroenterology and Hepatology, Kawasaki Municipal Tama Hospital; 1-30-37, Shukugawara, Tama-ku, Kawasaki, Kanagawa, 214-8525, Japan
| | - Masataka Taguri
- Department of Data Science, Yokohama City University School of Data Science; 3-9, Fukuura, Kanazawa-ku, Yokohama, Kanagawa, 236-0004, Japan
| | - Takako Ishibashi
- Yokohama City University Center for Novel and Exploratory Clinical trials; 1-1-1, Fukuura, Kanazawa-ku, Yokohama, Kanagawa, 236-0004, Japan
| | - Kazushi Numata
- Gastroenterological Center, Yokohama City University Medical Center 4-57, Urafune-cho, Minami-ku, Yokohama, Kanagawa, 232-0024, Japan
| | - Shin Maeda
- Department of Gastroenterology, Yokohama City University Hospital; 3-9, Fukuura, Kanazawa-ku, Yokohama, Kanagawa, 236-0004, Japan
| | - Katsuaki Tanaka
- Gastroenterological Center, Yokohama City University Medical Center 4-57, Urafune-cho, Minami-ku, Yokohama, Kanagawa, 232-0024, Japan.,Gastroenterology Division, Hadano Red Cross Hospital; 1-1-1, Tatenodai, Hadano, Kanagawa, 257-0017, Japan
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21
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Carrier P, Debette-Gratien M, Jacques J, Loustaud-Ratti V. Cirrhotic patients and older people. World J Hepatol 2019; 11:663-677. [PMID: 31598192 PMCID: PMC6783402 DOI: 10.4254/wjh.v11.i9.663] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/17/2019] [Revised: 06/18/2019] [Accepted: 07/16/2019] [Indexed: 02/06/2023] Open
Abstract
The global population is aging, and so the number of older cirrhotic patients is increasing. Older patients are characterised by a risk of frailty and comorbidities, and age is a risk factor for mortality in cirrhotic patients. The incidence of non-alcoholic fatty liver disease as an aetiology of cirrhosis is increasing, while that of chronic viral hepatitis is decreasing. Also, cirrhosis is frequently idiopathic. The management of portal hypertension in older cirrhotic patients is similar to that in younger patients, despite the greater risk of treatment-related adverse events of the former. The prevalence of hepatocellular carcinoma increases with age, but its treatment is unaffected. Liver transplantation is generally recommended for patients < 70 years of age. Despite the increasing prevalence of cirrhosis in older people, little data are available and few recommendations have been proposed. This review suggests that comorbidities have a considerable impact on older cirrhotic patients.
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Affiliation(s)
- Paul Carrier
- Fédération d’Hépatologie, Centre Hospitalier Universitaire Dupuytren de Limoges, Limoges 87042, France
- Faculté de Médecine et de Pharmacie de Limoges, Rue Docteur Marcland, Limoges 87042, France
| | - Marilyne Debette-Gratien
- Fédération d’Hépatologie, Centre Hospitalier Universitaire Dupuytren de Limoges, Limoges 87042, France
- Faculté de Médecine et de Pharmacie de Limoges, Rue Docteur Marcland, Limoges 87042, France
| | - Jérémie Jacques
- Service de Gastroentérologie, Centre Hospitalier Universitaire Dupuytren de Limoges, Limoges 87042, France
| | - Véronique Loustaud-Ratti
- Fédération d’Hépatologie, Centre Hospitalier Universitaire Dupuytren de Limoges, Limoges 87042, France
- Faculté de Médecine et de Pharmacie de Limoges, Rue Docteur Marcland, Limoges 87042, France.
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22
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Chu KKW, Chok KSH. Is the treatment outcome of hepatocellular carcinoma inferior in elderly patients? World J Gastroenterol 2019; 25:3563-3571. [PMID: 31367157 PMCID: PMC6658391 DOI: 10.3748/wjg.v25.i27.3563] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/30/2019] [Revised: 05/15/2019] [Accepted: 06/22/2019] [Indexed: 02/06/2023] Open
Abstract
In view of the increasing life expectancy in different parts of the world, a larger proportion of elderly patients with hepatocellular carcinoma (HCC) requiring oncological treatment is expected. The clinicopathological characteristics of HCC in elderly patients and in younger patients are different. Elderly patients, in general, also have more comorbidities. Evaluation of the efficacy of different HCC treatment options in elderly patients is necessary to optimize treatment outcomes for them. Treatment modalities for HCC include hepatectomy, liver transplantation, radiofrequency ablation, transarterial chemoembolization, and molecular-targeted therapy with sorafenib. In this review, current evidence on the risks and outcomes of the different HCC treatments for elderly patients are discussed. According to data in the literature, elderly patients and younger patients benefited similarly from HCC treatments. More clinical data are needed for the determination of selecting criteria on elderly HCC patients to maximize their chance of getting the most appropriate and effective treatments. As such, further studies evaluating the outcomes of different HCC treatment modalities in elderly patients are warranted.
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Affiliation(s)
| | - Kenneth Siu Ho Chok
- Department of Surgery and State Key Laboratory for Liver Research, The University of Hong Kong, Hong Kong, China
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23
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Zarour LR, Billingsley KG, Walker BS, Enestvedt CK, Orloff SL, Maynard E, Mayo SC. Hepatic resection of solitary HCC in the elderly: A unique disease in a growing population. Am J Surg 2019; 217:899-905. [PMID: 30819401 DOI: 10.1016/j.amjsurg.2019.01.030] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2018] [Revised: 12/11/2018] [Accepted: 01/14/2019] [Indexed: 12/12/2022]
Abstract
BACKGROUND Management of elderly patients with solitary hepatocellular carcinoma (sHCC) is challenging with perceived clinicopathologic differences driving treatment options. We sought to determine factors predictive of disease control and survival after hepatic resection of sHCC in elderly patients. METHODS We identified n = 45 elderly patients (³≥65 yo) with sHCC treated with hepatic resection alone from our prospective database from 2003-16. Clinicopathologic data were analyzed and survival was assessed from the time of hepatic resection. RESULTS The median age was 75-years-old. Less than half of patients (47%) had viral hepatitis. At resection, the median Child-Pugh score was A6, median tumor size 5 cm, and mean AFP of 1050 (ng/mL). Major hepatectomy was performed in 23 patients (51%) with R0 resection achieved in 96%. Two patients (4%) had Grade III complications with no mortalities at 30 days and one death (2%) at 90-days. After R0 resection 44% (n = 20) had intrahepatic recurrence at a median of 32 months (95% CI: 15-46) with 20% (n = 9) developing extrahepatic recurrence at a median of 78 months (95% CI: 78-.). The median survival was 72 months (95% CI: 30-108 months). For patients with at least 3 years of follow-up, the 1-, 3-, and 5-year overall survival was 74%, 59%, and 50%, respectively. Mortality was associated with higher AFP and lower Prognostic Nutritional Index (PNI). CONCLUSION Carefully selected elderly patients with sHCC appear to have unique disease that is amenable to hepatic resection with low morbidity and mortality with excellent overall and recurrence-free survival.
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Affiliation(s)
- Luai R Zarour
- Oregon Heath & Science University (OHSU), Department of Surgery, Division of Surgical Oncology, Portland, OR, 97239, USA
| | - Kevin G Billingsley
- Oregon Heath & Science University (OHSU), Department of Surgery, Division of Surgical Oncology, Portland, OR, 97239, USA; The Knight Cancer Institute at OHSU, Portland, OR, 97239, USA
| | - Brett S Walker
- Oregon Heath & Science University (OHSU), Department of Surgery, Division of Surgical Oncology, Portland, OR, 97239, USA
| | - C Kristian Enestvedt
- OHSU, Department of Surgery, Division of Transplant Surgery, Portland, OR, 97239, USA
| | - Susan L Orloff
- OHSU, Department of Surgery, Division of Transplant Surgery, Portland, OR, 97239, USA
| | - Erin Maynard
- OHSU, Department of Surgery, Division of Transplant Surgery, Portland, OR, 97239, USA
| | - Skye C Mayo
- Oregon Heath & Science University (OHSU), Department of Surgery, Division of Surgical Oncology, Portland, OR, 97239, USA; The Knight Cancer Institute at OHSU, Portland, OR, 97239, USA.
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24
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Tovoli F, Negrini G, Benevento F, Faggiano C, Goio E, Granito A. Systemic treatments for hepatocellular carcinoma: challenges and future perspectives. Hepat Oncol 2018; 5:HEP01. [PMID: 30302192 PMCID: PMC6168042 DOI: 10.2217/hep-2017-0020] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2017] [Accepted: 01/16/2018] [Indexed: 02/07/2023] Open
Abstract
Sorafenib has been the only approved systemic treatment of hepatocellular carcinoma (HCC) for almost a decade. Recently, two new drugs showed positive results in two Phase III studies. The RESORCE trial identified regorafenib as a valid second-line treatment for patients progressing to sorafenib, the REFLECT trial showed that lenvatinib is noninferior to sorafenib as front-line treatment. Following these trials, the therapeutic scenario will be dominated by anti-VEGFR drugs, with three different molecules showing a proven anticancer activity. Some open problems still remain and different immunotherapy trials are underway, following promising preliminary results. In this review we analyze: the most recent advancements about patients treated with sorafenib; the results of RESORCE and REFLECT trials; and the ongoing Phase III clinical trials. Finally, we discuss how they could address the current problems and possibly reshape the future of the systemic treatments for HCC.
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Affiliation(s)
- Francesco Tovoli
- Department of Medical & Surgical Sciences, University of Bologna, S Orsola-Malpighi Hospital, Bologna, Italy
| | - Giulia Negrini
- Department of Medical & Surgical Sciences, University of Bologna, S Orsola-Malpighi Hospital, Bologna, Italy
| | - Francesca Benevento
- Department of Medical & Surgical Sciences, University of Bologna, S Orsola-Malpighi Hospital, Bologna, Italy
| | - Chiara Faggiano
- Department of Medical & Surgical Sciences, University of Bologna, S Orsola-Malpighi Hospital, Bologna, Italy
| | - Elisabetta Goio
- Department of Medical & Surgical Sciences, University of Bologna, S Orsola-Malpighi Hospital, Bologna, Italy
| | - Alessandro Granito
- Department of Medical & Surgical Sciences, University of Bologna, S Orsola-Malpighi Hospital, Bologna, Italy
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