Management of Advanced and Terminal Hepatocellular Carcinoma: When and How to Treat, and When not to Treat?

AbstractHepatocellular carcinoma (HCC) is the third leading cause of cancer worldwide according to the National Cancer Institute. If treated with liver directed therapy, patients' median overall survival is significantly improved at 20.1 versus 4.3 months without treatment. The purpose of this article is to give an overview on when and how to treat, and when not to treat patients with advanced or terminal HCC. Treatment of patients with advanced HCC can be challenging, as patients are often already debilitated due to their chronic underlying liver disease. Performance status, hepatic function, tumor characteristics, and the patient's desire to maintain their quality of life should be at the forefront of deciding when and how to treat this patient population. If patients are found to be outside treatment criteria, referral to palliative care can be beneficial.

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Assessment of radioembolization among patients who met the inclusion criteria for Sorafenib Hepatocellular Carcinoma Assessment Randomized Protocol (SHARP).

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.e14654 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. e14654-e14654 ◽

Cited By ~ 1

Author(s):

Bruno Sangro ◽

Livio Carpanese ◽

Roberto Cianni ◽

Daniele Gasparini ◽

Rita Golfieri ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Overall Survival ◽

Liver Function ◽

Median Overall Survival ◽

Performance Status ◽

Advanced Hepatocellular Carcinoma ◽

Inclusion Criteria ◽

Ecog Performance Status ◽

Advanced Hcc ◽

Good Liver Function

e14654 Background: SHARP was pivotal in determining the safety and efficacy of sorafenib in advanced hepatocellular carcinoma (HCC) in patients with predominately good liver function. In practice, many patients with advanced HCC receive radioembolization (RE). Investigators from the European Network on RE with yttrium-90 resin microspheres (ENRY) group conducted an analysis of safety and survival among consecutive patients who met the SHARP inclusion criteria. Methods: 58% of patients (189 of 325) who had received RE between 09/2003 and 12/2009 were considered SHARP-equivalents. Of these, 11.6% received sorafenib 4.7 months (median) after RE for a median duration of 2.8 months. Safety and tolerability analyses were conducted up to day 90 post RE; changes from baseline were recorded and transitions in CTCAE grades >3 tested. Statistical analyses used SAS (SAS, Cary NC) version 9.2 XP Pro. Results: Like the SHARP sorafenib cohort, most patients had advanced HCC (BCLC stage C: 72.5%), good liver function (Child–Pugh class A: 100%) and ECOG performance status (0–1: 90.5%). Macroscopic vascular invasion (MVI), extrahepatic spread (EHD) or both was present in 33.9%. 20.1% had received prior surgical procedures, 8.5% prior ablative procedures and 33.3% prior vascular [chemo]embolization. RE was predominantly a single whole-liver procedure (median activity 1.7 GBq). Median overall survival was 10.8 months (95% CI: 8.8–12.8) in the SHARP-equivalent cohort, 10.2 months (8.3–11.8) in patients with MVI/EHD, 9.7 months (7.6–10.9) in advanced HCC (BCLC stage C) and 16.6 months (11.2–22.8) in intermediate HCC (BCLC stage B). Treatment-related adverse events (all grades; grade >3) were: fatigue (50.3%; 2.1%), abdominal pain (25.9%; 2.1%), nausea/vomiting (31.2%; 0.5%) and GI ulcer (3.2%; 1.0%). At baseline, raised bilirubin (all grades) was present in 20.3%, increasing to 49.4% of patients evaluated up to day 90. Bilirubin grade was unchanged in 58.1% and increased in 37.8%; 4.0% had ≥grade 3 events. Conclusions: In patients matching the inclusion criteria for SHARP, RE was well tolerated with a median overall survival which compares favorably with sorafenib.

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Low energy amplitude modulated radiofrequency electromagnetic fields in combination with standard treatment or as monotherapy to show improvement in quality of life in patients with advanced hepatocellular carcinoma.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.3_suppl.290 ◽

2021 ◽

Vol 39 (3_suppl) ◽

pp. 290-290

Author(s):

Micelange Carvalho Sousa ◽

Frederico Costa ◽

Pablo Diego Lima ◽

Yone De Camargo Setogute ◽

Brenda Pires Gumz ◽

...

Keyword(s):

Quality Of Life ◽

Hepatocellular Carcinoma ◽

Electromagnetic Fields ◽

Combination Treatment ◽

Treatment Modality ◽

Advanced Hepatocellular Carcinoma ◽

Single Treatment ◽

Advanced Hcc ◽

Radiofrequency Electromagnetic Fields

290 Background: Hepatocellular carcinoma (HCC) is a fatal cancer without curative option for most patients. Hence the importance to improve health related quality of life (HRQoL). Amplitude-modulated radiofrequency electromagnetic fields (EMF), as a novel and non-toxic therapy, has potential for improving HRQoL in advanced HCC patients. Methods: An open-label, single center, prospective clinical protocol was performed in advanced HCC patients as an initial and salvage treatment modality. Systemic exposure to EMF was used in combination with a systemic conventional treatment or as a single treatment. A spoon-shaped antenna placed in the oral cavity delivered EMF over 90 minutes with monthly repetitions until death or consent withdrawal. The effect on HRQoL was the primary objective of this study. Patients answered the EORTC-C30 v3.0 questionnaires prior to every EMF exposure. Clinically meaningful change (CMC) and time to deterioration (TTD) for Global Health (QoL), Role Functioning (RF) and Physical Functioning (PF) were used in the analysis. Results: From March 2018 to April 2020, 55 advanced HCC patients were submitted to 373 EMF exposures. 41/55 (75%) patients had repetitive exposures (mean # 4, ranging from 2-16). 87% were male, median age was 67, 84% were BLCL-C, 16% were Child-Pugh B, 29% had extra-hepatic metastasis, 55% had failed previous treatment and 71% had documented radiological progression. 31(56%) patients received EMF in combination with systemic therapy (28 TKI and 3 anti-PDL1). 24 patients received EMF as a single treatment modality. The mean baseline score was 68.1 for QoL and 77.1 for RF and PF. 61%, 76% and 49% of patients experienced positive change in QoL, RF and PS scores immediately prior to the second exposure, respectively. +CMC was reported in 20%, 17% and 32% of patients, respectively for QoL, RF and PS. The median QoL TTD was not reached. The median RF TTD was 7.2 month and the median PF TTD was 11.9 month. The median RF TTD for patients in combination treatment was 11.4 months and in a single treatment was 13.5 month. The median PF TTD for patients in combination treatment was 12.8 months and in single treatment was 14.5 month. Conclusions: Advanced HCC patients showed positive changes in QoL, RF and PF HRQoL scores after single exposure to EMF. The benefit from EMF in HRQoL was durable both in combination with TKI or as a single modality in advanced HCC patients. These results support future development as a novel palliative treatment modality in advanced HCC patients. Clinical trial information: NCT 01686412.

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Outcomes and Quality of Life of Systemic Therapy in Advanced Hepatocellular Carcinoma

Cancers ◽

10.3390/cancers11060861 ◽

2019 ◽

Vol 11 (6) ◽

pp. 861 ◽

Cited By ~ 6

Author(s):

Kehua Zhou ◽

Christos Fountzilas

Keyword(s):

Quality Of Life ◽

Hepatocellular Carcinoma ◽

Kinase Inhibitors ◽

Advanced Hepatocellular Carcinoma ◽

Term Outcome ◽

Long Term Outcome ◽

Advanced Hcc ◽

Treatment Interruptions ◽

Systemic Treatments

Hepatocellular carcinoma (HCC) is one of the most commonly diagnosed cancers worldwide; most patients are diagnosed with advanced disease for which there is no known cure. Tremendous progress has been made over the past decade in the development of new agents for HCC, including small-molecule kinase inhibitors such as sorafenib, lenvatinib, cabozantinib, regorafenib, and monoclonal antibodies like ramucirumab, nivolumab, and pembrolizumab. Ideal use of these agents in clinics has improved the long-term outcome of patients with advanced HCC as well as introduced unique toxicities that can affect quality of life. These toxicities usually are thought to be partially related to cirrhosis, a major risk factor for the development of HCC and a pathophysiological barrier complicating the optimal delivery of antineoplastic therapy. Additionally, side effects of medications together with advanced HCC symptoms not only decrease quality of life, but also cause treatment interruptions and dose reductions that can potentially decrease efficacy. Physicians caring for patients with advanced HCC are called to optimally manage HCC along with cirrhosis in order to prolong life while at the same time preserve the quality of life. In this review, we aimed to summarize outcomes and quality of life with the use of modern systemic treatments in advanced HCC and provide a physician reference for treatment toxicity and cirrhosis management.

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Current Treatment Landscape for Advanced Hepatocellular Carcinoma: Patient Outcomes and the Impact on Quality of Life

Cancers ◽

10.3390/cancers11060841 ◽

2019 ◽

Vol 11 (6) ◽

pp. 841 ◽

Cited By ~ 10

Author(s):

Daneng Li ◽

Sabrina Sedano ◽

Rebecca Allen ◽

Jun Gong ◽

May Cho ◽

...

Keyword(s):

Quality Of Life ◽

Hepatocellular Carcinoma ◽

Kinase Inhibitors ◽

Current Treatment ◽

Advanced Hepatocellular Carcinoma ◽

Advanced Hcc ◽

Physician Decision Making ◽

Treatment Sequencing ◽

The Impact

Hepatocellular carcinoma (HCC) is the fifth most common cancer and the second leading cause of cancer mortality worldwide. Heterogeneity of clinical conditions contributes to the complex management of care for patients with advanced HCC. Recently, the treatment landscape for advanced HCC has expanded rapidly, with the additional FDA approvals of several oral tyrosine kinase inhibitors (lenvatinib, regorafenib, and cabozantinib), as well as immunotherapies such as immune check point inhibitors (nivolumab and pembrolizumab) and the monoclonal IgG1 antibody, ramucirumab. This expansion has generated a need for novel treatment sequencing strategies in this patient population. In light of these developments, an evaluation of the impact of FDA-approved therapeutics on patient-centered outcomes such as health-related quality of life (HRQoL) is warranted. An increased understanding of HRQoL in patients included in advanced HCC clinical trials could potentially help physician decision-making for treatment sequencing in patients with advanced HCC.

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Investigation of the Karnofsky Performance Status as a measure of quality of life.

Health Psychology ◽

10.1037//0278-6133.3.2.129 ◽

1984 ◽

Vol 3 (2) ◽

pp. 129-142 ◽

Cited By ~ 7

Author(s):

Charles J. Long

Keyword(s):

Quality Of Life ◽

Karnofsky Performance Status ◽

Performance Status

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Predictors of Health-Related Quality of Life in Hepatocellular Carcinoma

PsycEXTRA Dataset ◽

10.1037/e622422009-001 ◽

2009 ◽

Author(s):

Leigh A. Gemmell ◽

T. Clark Gamblin ◽

Jennifer M. Hammond ◽

Sonja Likumahuwa ◽

Richard Schulz ◽

...

Keyword(s):

Quality Of Life ◽

Hepatocellular Carcinoma ◽

Health Related Quality ◽

Related Quality ◽

Health Related

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Attitudes of Elderly People in the South Moravian Region to Further Education

Lifelong Learning ◽

10.11118/lifele2014040254 ◽

2014 ◽

Vol 4 (2) ◽

pp. 54-78

Author(s):

Petr Adamec ◽

Marián Svoboda

Keyword(s):

Quality Of Life ◽

Elderly People ◽

Further Education ◽

The South ◽

The Third ◽

Interesting Insight ◽

Survey Results ◽

Insight Into ◽

Demographic Features

This paper deals with the results of sociological survey focused on identification of the attitudes of elderly people to further education. The research was carried out in September 2010. Experience of elderly people with further education, their readiness (determination) for further education as well as their motivation and barriers in further education were also subjects of this research. Detecting elderly population’s awareness of universities of the third age and finding out their further education preferences were an integral part of the research. Research sample consisted of citizens over 55 years living in the South Moravian region. The survey results are structured by socio-demographic features e.g.: age, sex, educational attainment etc. and provide an interesting insight into the attitudes of the target group to one of the activities that contributes to improvement of their quality of life.

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The Analysis of Nutritional Habits of the Third Age Students in Poznań

Open Agriculture ◽

10.1515/opag-2020-0003 ◽

2020 ◽

Vol 5 (1) ◽

pp. 21-29

Author(s):

Magdalena Pracka ◽

Marcin Dziedziński ◽

Przemysław Łukasz Kowalczewski

Keyword(s):

Quality Of Life ◽

Physical Activity ◽

Eating Habits ◽

The Elderly ◽

The Body ◽

Nutritional Habits ◽

Third Age ◽

Waist To Hip Ratio ◽

The Third

AbstractIn recent years have seen increasing percentage of the elderly in the overall population. This has driven the attention to the lifestyle factors that influence the health and quality of life of this social group, including their nutrition and physical activity. Universities of the Third Age (U3A) are a valuable platform for the dissemination and broadening of the knowledge related to these topics. The nutritional habits of 61 U3A students in Poznań were evaluated on the basis of a modified KomPAN questionnaire. Their nutritional status was determined using the body mass index (BMI) and waist to hip ratio (WHR) indices. Nearly half of the respondents were overweight and 16% had first degree obesity. The WHR index in women was on average 0.8, while in men it was 1.01. Only 13% of the students declared regular eating, with 60% consuming 4-5 meals a day. Women were found to eat snacks between meals more often than men. It was also found that the majority of the elderly do not add salt to ready meals or sweeten beverages with sugars. Taking into account the observed nutritional problems and the occurrence of improper eating habits of the elderly, it is recommended to continue the education on the prevention of common diet-related diseased.

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Prospective cohort study of surgical outcome for spinal metastases in patients aged 70 years or older

The Bone & Joint Journal ◽

10.1302/0301-620x.102b12.bjj-2020-0566.r1 ◽

2020 ◽

Vol 102-B (12) ◽

pp. 1709-1716

Author(s):

Yutaro Kanda ◽

Kenichiro Kakutani ◽

Yoshitada Sakai ◽

Takashi Yurube ◽

Shingo Miyazaki ◽

...

Keyword(s):

Quality Of Life ◽

Performance Status ◽

Eastern Cooperative Oncology Group ◽

Spinal Metastases ◽

Palliative Surgery ◽

Advanced Age ◽

Health State ◽

Survival Times ◽

The Mean

Aims With recent progress in cancer treatment, the number of advanced-age patients with spinal metastases has been increasing. It is important to clarify the influence of advanced age on outcomes following surgery for spinal metastases, especially with a focus on subjective health state values. Methods We prospectively analyzed 101 patients with spinal metastases who underwent palliative surgery from 2013 to 2016. These patients were divided into two groups based on age (< 70 years and ≥ 70 years). The Eastern Cooperative Oncology Group (ECOG) performance status (PS), Barthel index (BI), and EuroQol-5 dimension (EQ-5D) score were assessed at study enrolment and at one, three, and six months after surgery. The survival times and complications were also collected. Results In total, 65 patients were aged < 70 years (mean 59.6 years; 32 to 69) and 36 patients were aged ≥ 70 years (mean 75.9 years; 70 to 90). In both groups, the PS improved from PS3 to PS1 by spine surgery, the mean BI improved from < 60 to > 80 points, and the mean EQ-5D score improved from 0.0 to > 0.7 points. However, no significant differences were found in the improvement rates and values of the PS, BI, and EQ-5D score at any time points between the two groups. The PS, BI, and EQ-5D score improved throughout the follow-up period in approximately 90% of patients in each group. However, the improved PS, BI, and EQ-5D scores subsequently deteriorated in some patients, and the redeterioration rate of the EQ-5D was significantly higher in patients aged ≥ 70 than < 70 years (p = 0.027). Conclusion Palliative surgery for spinal metastases improved the PS, activities of daily living, and quality of life, regardless of age. However, clinicians should be aware of the higher risk of redeterioration of the quality of life in advanced-age patients. Cite this article: Bone Joint J 2020;102-B(12):1709–1716.

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