[Questionnaire Survey on Early-Stage Hepatocellular Carcinoma in Patients and Physicians].

We conducted an online questionnaire survey to investigate changes in well-being and anxiety in patients with hepatocellular carcinoma requiring repeated locoregional therapy(hepatectomy/ablation)and the differences between patients' and treating physicians' perceptions of what is important to patients when selecting treatment. Between December 2022 and January 2023, we collected responses from 162 patients and 115 physicians in Japan. Results showed no clinically significant changes in well-being over time. Patients experiencing recurrences and repeated locoregional therapy reported increased anxiety regarding"effectiveness of treatment"and"how to handle the disease."As"factors that patients consider important when receiving locoregional therapy,"many patients and physicians selected suppression of recurrence, prolonged survival, and safety; however, patients placed more importance on"reducing the number of locoregional therapies"as they repeatedly experienced recurrence and therapy. Regarding"information that patients consider important when selecting adjuvant therapy,""effectiveness of treatment"and"adverse effects of treatment"were important to both patients and physicians, while"maintaining a normal daily life"was more important in patients and"length of treatment"was more important in physicians. In conclusion, some factors are perceived by both physicians and patients as important when selecting treatment, but there is a gap in perception for other factors. Physicians and patients should discuss their opinions on what is important in treatment before deciding on a treatment strategy.

Nonadherence to oral cancer chemotherapy in hepatocellular carcinoma: prevalence and predictive factors in Vietnam.

PURPOSE: Standard oral cancer chemotherapy (OCT) or targeted therapy (OTT) has expanded the treatment methods for hepatocellular carcinoma (HCC). However, its principal nonadherence causes a reduction in efficacy. We aimed to evaluate the status of nonadherence and influencing factors among outpatient patients with HCC. PATIENTS AND METHODS: In 2021, a prospective observational study was conducted on 384 patients with either old or newly diagnosed HCC treated with OTT. Nonadherence to OCT was determined using the eight-item Morisky Medication Adherence Scale, with a score < 6 points. The patients were finished with a six-month follow-up investigation by questionnaires. RESULTS: 54,8% of HCC outpatients were nonadherent to OCT, with a mean Morisky score of 5.19. They dropped out of the treatment mainly because of drug side effects, such as fatigue (72.4%), hand-foot syndrome (42.7%), diarrhea (38.3%), nausea (25%), insomnia (24.7%), abdominal pain (12%), and anxiety about these adverse events (65.9%). Additionally, financial difficulties and low relative copayments were significantly correlated with the noncompliant treatment of patients (OR = 2.29, 95% CI = 1.32-3.98, P = 0.003; OR = 4.36, 95% CI = 0.95-19.93, P = 0.039, respectively). Moreover, inadequate individual information about the clinical course, the art of treatment, and medication usage instructions were suggestive barriers to adherence to treatment (OR = 1.96, 95% CI = 1.08-3.55, P = 0.024; OR = 1.86, 95% CI = 1.1-3.14, P = 0.02; OR = 2.34, 95% CI = 1.29-4.26, P = 0.004, respectively). Finally, a low level of trust in doctors was an essential factor in nonadherence (Mean of the Anderson Trust in Physician Scale scores counted 38.12 vs. 43.97, respectively for non-adherence vs. adherence, P = 0.00001). CONCLUSIONS: This study suggests a high rate of primary nonadherence to standard oral targeted therapy among HCC outpatient patients because of drug side effects, patient awareness of treatment, and lack of confidence in healthcare providers. Close supervision, proper medication instructions, appropriate dosage reductions, and comprehensive patient counseling might be necessary to control nonadherence.

Mental health and quality of life in patients with chronic liver disease: a single-center structural equation model.

BACKGROUND: Chronic liver disease (CLD) is one of the leading disease burdens in Pakistan. Until now, there has only been limited focus in the country on providing health services through tertiary services in urban cities, whereas there is almost no research in Pakistan on the mental health and quality of life of CLD patients. This study aimed to understand which predictors influence the mental health and quality of life of CLD patients in order to advise better policy protection. METHODS: Data was collected from CLD patients at the Pakistan Kidney and Liver Institute and Research Centre, Lahore, Pakistan. A total of 850 respondents were part of the final sample. The age of respondents ranged from 18 to 79 years and included the following diagnosis: (i) Chronic Viral Hepatitis (n = 271), (ii) Cirrhosis (n = 259), (iii) Hepatocellular Carcinoma (n = 193), and (iv) Non-viral Liver Disease (n = 127). RESULTS: Mean results reveal that females as well as illiterate patients need more support for mental health and communication with their physician; whereas men need more support to develop coping strategies. Structural equation modelling results reveal that the severity of symptoms (ß = 0.24, p < 0.001), coping strategies (ß=-0.51, p < 0.001), and doctor communication (ß=-0.35, p < 0.001) predict mental health. Quality of life is associated with the severity of symptoms (ß=-0.36, p < 0.001), coping strategies (ß = 0.26, p < 0.05), and doctor communication (ß = 0.09, p < 0.05). CONCLUSIONS: A 'bio-psycho-social-spiritual' model is recommended for Pakistan's CLD patients which includes the integration of social officers to provide support in four key areas to secure mental health and quality of life of patients.

Effect of Family Music Therapy on Patients with Primary Liver Cancer Undergoing Palliative Care and their Caregivers: A Retrospective Study.

OBJECTIVE: The effectiveness of family music therapy for patients with advanced palliative care hepatocellular carcinoma and their main caregivers was investigated. METHODS: The clinical data of liver cancer patients and their main caregivers admitted to Wuwei City People's Hospital from August 2022 to April 2023 were retrospectively analysed. Patients were divided into observation group A and control group A according to whether they received family music therapy, and caregivers were divided into control group B and observation group B. The general demographic data, self-rating depression scale (SDS), self-rating anxiety scale (SAS), cancer-related fatigue scale (CFS), Pittsburgh sleep quality index (PSQI), anticipatory grief scale (AGS), and caregiver burden inventory (CBI) scores of the patients and their primary caregivers were collected. Propensity score matching (PSM) was used to balance the baseline data of the two groups. Then, data were analysed using t-test and chi-squared (χ2) test. RESULTS: After 1:1 PSM, 45 samples were included in each group. Before management, no significant differences in SDS, SAS, AGS, CFS, PSQI and CBI scores were found among the groups (P > 0.05). After management, the SDS, SAS and CFS scores of observation group A were lower than those of control group A (P < 0.05). The AGS, PSQI and CBI scores of observation group B were lower than those of control group B (P < 0.05). CONCLUSIONS: The effect of family music supplement therapy is ideal, which can relieve the negative emotions of patients, reduce the degree of cancer-related fatigue, enhance the sleep quality of the main caregivers and reduce anticipatory grief and the burden of care.

Differences in influencing mechanism of clinicians' adoption behavior for liver cancer screening technology between the leading and subordinate hospitals within medical consortiums.

BACKGROUND: Medical consortiums have been extensively established to facilitate the integration of health resources and bridge the technical gap among member institutions. However, some commonly appropriate technologies remain stagnant in subordinate hospitals, although they have been routinely applied in leading hospitals. Besides, the mechanism underlying differences in clinicians' adoption behavior at different levels of institutions was unknown. Therefore, this study aimed to investigate the differences in influencing mechanisms of clinicians' hepatic contrast-enhanced ultrasound technology (CEUS) utilization behavior between leading and subordinate hospitals within medical consortiums, thus providing clues for expanding effective and appropriate technologies within integrated care systems. METHODS: A self-designed scale was developed based on the theory of planned behavior (TPB). A multistage sampling method was applied to investigate clinicians who were aware of CEUS and worked in liver disease-related departments within the sampled medical institutions. The final sample size was 289. AMOS 24.0 software was used to construct multi-group structural equation modeling (SEM) to validate the hypotheses and determine the mechanism of hepatic CEUS utilization. RESULTS: It revealed that behavioral intention significantly influenced adoption behavior, regardless of whether it was in leading hospitals or subordinate hospitals (ß = 0.283, p < 0.001). Furthermore, behavioral attitude (ß = 0.361, p < 0.001) and perceived behavioral control (ß = 0.582, p < 0.001) exerted significant effects on adoption behavior through behavioral intention. However, in leading hospitals, subjective norm had a significant positive effect on behavioral intention (ß = 0.183, p < 0.01), while it had a significant negative impact on behavioral intention in the subordinate hospitals (ß = -0.348, p < 0.01). CONCLUSION: To effectively translate the adoption intention into actual behavior, it is recommended to elucidate the demand and facilitators involved in the process of health technology adoption across leading and subordinate hospitals. Additionally, bolstering technical support and knowledge dissemination within subordinate hospitals while harnessing the influential role of key individuals can further enhance this transformative process.

Persistent Fatigue in Patients With Hepatocellular Carcinoma Receiving Radiotherapy.

BACKGROUND: Radiation therapy has attracted much attention in the treatment of patients with hepatocellular carcinoma (HCC). However, the association between radiotherapy-related fatigue and HCC has been examined in only a few studies. PURPOSE: This study was designed to explore the change over time in fatigue in patients with HCC treated with radiotherapy and related factors. METHODS: One hundred patients were enrolled in this prospective longitudinal study using convenience sampling at a medical center in northern Taiwan. The Functional Assessment of Chronic Illness Therapy-Fatigue scale, the Brief Pain Inventory-Short Form, and the psychological subscale of Memorial Symptom Assessment Scale-Short Form were used to assess the symptoms at five time points: before radiotherapy (T0), during treatment (T1), and at 1 month (T2), 3 months (T3), and 6 months (T4) after radiotherapy. The generalized estimating equations method was used to determine the changes in fatigue and the influencing factors. RESULTS: Fatigue levels at T1, T2, T3, and T4 were significantly higher than that at T0. Higher fatigue was significantly associated with lower income and poorer functional status. Having worse pain levels and psychological symptoms were both associated with higher fatigue. CONCLUSIONS/IMPLICATIONS FOR PRACTICE: The results indicate fatigue does not recover to the baseline (pretherapy) level by 6 months after radiotherapy. Thus, fatigue in patients with HCC receiving radiotherapy should be regularly and effectively assessed, and patients experiencing pain and psychological symptoms should be given greater attention from clinicians.

Effects of traditional Chinese culture-based bibliotherapy on the spiritual health of patients with liver cancer.

BACKGROUND: Liver cancer is a serious global health problem and is associated with poor spiritual health. Bibliotherapy is beneficial in improving health outcomes in cancer patients, yet there is a lack of empirical evidence of its effect on the spiritual health of liver cancer patients in China. The study aimed to investigate the effects of bibliotherapy based on Chinese traditional culture on the spiritual health of patients with liver cancer in China. This study was approved by the Ethics Committee of Hunan Normal University School of Medicine and registered with the Chinese Clinical Trial Registry with the registration (No: 2021260), which registration in June 30th 2021. METHODS: A total of 60 patients with liver cancer were divided into the intervention group (n = 30) and the control group (n = 30) through WeChat. The intervention group received bibliotherapy therapy based on traditional Chinese culture, while the control group received routine care. Spiritual health was assessed using the Spiritual Attitude and Involvement List (SAIL) and compared before and after the intervention between the two groups. The chi-square test and t-test were used to analyze the intervention effects. RESULTS: The two groups were comparable in all baseline characteristics including the SAIL score. After 5 weeks of intervention, the score of SAIL increased significantly from 96.76 ± 15.08 to 106.93 ± 13.82 in the intervention group (t = - 29.380, p < 0.001), while no significant difference in SAIL score was observed in the control group (from 95.27 ± 16.40 to 95.31 ± 16.24, t = - 0.189, p = 0.852). Similar patterns were also observed in its three dimensions of connecting with oneself, connecting with the environment, and connecting with transcendence. CONCLUSIONS: Our study showed that bibliotherapy based on traditional Chinese culture using the WeChat platform can greatly improve the spiritual health of patients with liver cancer and has the potential to be widely applied to cancer patients to improve their well-being.

Economic Burden and Quality of Life of Hepatocellular Carcinoma in Greater China: A Systematic Review.

Background: Hepatocellular carcinoma (HCC) accounts for more than 85%-90% of primary liver cancer globally, and approximately 45% of deaths from HCC occur in greater China. This disease poses a significant economic burden for patients, payers and society and significantly affects patients' quality of life (QoL). However, such impact of HCC in greater China has not been well characterized. This review was conducted to analyze the current evidence about the economic and humanistic impact of HCC in greater China for informing national disease management and identifying clinical gaps yet to be resolved. Methods: A systematic search literature using seven databases (Web of Science, PubMed, Medline, Cochrane Central, China National Knowledge Infrastructure, Wanfang, and Weipu) was performed to identify interventional and observational studies that reported the impact of HCC on cost or QoL and published before April 6, 2021. The focus population included adult patients with HCC in greater China. This review excluded any studies that focused on any specific treatment. Study quality was assessed using the Effective Public Health Practice Project tool. Results: Of 39,930 studies retrieved, 27 were deemed eligible for inclusion. The methodologies, perspectives and data sources used in studies were heterogeneous. In greater China, while few studies reported the health expenditures of HCC patients and investigations about economic burden at national level was lacking, the significant economic impact of HCC on patients and their families had been reported. Health-related costs increased as the disease deteriorated. Additionally, HCC also has a negative impact on the QoL of patients, mostly in terms of physical, cognitive, social functioning and severe symptoms. Conclusions: HCC has brought significant economic and QoL burden to patients in greater China. Both physical and psychological factors predicted QoL in patients with HCC in greater China. Future studies should explore the disease-related economic effects on Chinese patients and their families, the effects of physical and psychological factors on QoL and the relationships of physical and psychological factors in the region.Systematic Review Registration: www.crd.york.ac.uk/prospero/display_record.php?RecordID=278421, PROSPERO: CRD42021278421.

A randomized clinical trial of guided self-help intervention based on mindfulness for patients with hepatocellular carcinoma: effects and mechanisms.

BACKGROUND: Compared with face-to-face mindfulness-based interventions (MBIs), online mindfulness interventions may be more convenient for patients with limited resources and can provide self-help mindfulness methods to improve the quality of life of cancer patients. This study investigated the effects of guided self-help mindfulness-based interventions (GSH-MBIs) on psychological distress, quality of life and sleep quality in patients with hepatocellular carcinoma and explored the underlying mechanisms. METHODS: A total of 122 patients with hepatocellular carcinoma were randomly divided into the intervention group or the conventional treatment group. Psychological distress, quality of life, sleep quality, psychological flexibility and perceived stress were evaluated in the groups before the intervention at baseline, after the intervention, at 1-month follow-up and 3-month follow-up. The intervention's effects over time and the potential mediating effects were analysed using generalized estimating equations (GEE). RESULTS: GEE results indicated significant time-group interaction effects on psychological distress (P < 0.001) and sleep quality (P < 0.001). The intervention significantly improved psychological flexibility (ß, -2.066; 95% CI, -3.631, -0.500) and reduced perceived stress (ß, -2.639; 95% CI, -4.110, -1.169). Psychological flexibility and perceived stress played a mediating role in the observed results. CONCLUSION: GSH-MBIs can improve psychological distress and sleep quality via changing the psychological flexibility and perceived stress in hepatocellular carcinoma patients.

Nivolumab versus sorafenib in advanced hepatocellular carcinoma (CheckMate 459): a randomised, multicentre, open-label, phase 3 trial.

BACKGROUND: Single-agent nivolumab showed durable responses, manageable safety, and promising survival in patients with advanced hepatocellular carcinoma in the phase 1-2 CheckMate 040 study. We aimed to investigate nivolumab monotherapy compared with sorafenib monotherapy in the first-line setting for patients with advanced hepatocellular carcinoma. METHODS: In this randomised, open-label, phase 3 trial done at medical centres across 22 countries and territories in Asia, Australasia, Europe, and North America, patients at least 18 years old with histologically confirmed advanced hepatocellular carcinoma not eligible for, or whose disease had progressed after, surgery or locoregional treatment; with no previous systemic therapy for hepatocellular carcinoma, with Child-Pugh class A and Eastern Cooperative Oncology Group performance status score of 0 or 1, and regardless of viral hepatitis status were randomly assigned (1:1) via an interactive voice response system to receive nivolumab (240 mg intravenously every 2 weeks) or sorafenib (400 mg orally twice daily) until disease progression or unacceptable toxicity. The primary endpoint was overall survival assessed in the intention-to-treat population. Safety was assessed in all patients who received at least one dose of study drug. This completed trial is registered with ClinicalTrials.gov, NCT02576509. FINDINGS: Between Jan 11, 2016, and May 24, 2017, 743 patients were randomly assigned to treatment (nivolumab, n=371; sorafenib, n=372). At the primary analysis, the median follow-up for overall survival was 15·2 months (IQR 5·7-28·0) for the nivolumab group and 13·4 months (5·7-25·9) in the sorafenib group. Median overall survival was 16·4 months (95% CI 13·9-18·4) with nivolumab and 14·7 months (11·9-17·2) with sorafenib (hazard ratio 0·85 [95% CI 0·72-1·02]; p=0·075; minimum follow-up 22·8 months); the protocol-defined significance level of p=0·0419 was not reached. The most common grade 3 or worse treatment-related adverse events were palmar-plantar erythrodysaesthesia (1 [<1%] of 367 patients in the nivolumab group vs 52 [14%] of patients in the sorafenib group), aspartate aminotransferase increase (22 [6%] vs 13 [4%]), and hypertension (0 vs 26 [7%]). Serious treatment-related adverse events were reported in 43 (12%) patients receiving nivolumab and 39 (11%) patients receiving sorafenib. Four deaths in the nivolumab group and one death in the sorafenib group were assessed as treatment related. INTERPRETATION: First-line nivolumab treatment did not significantly improve overall survival compared with sorafenib, but clinical activity and a favourable safety profile were observed in patients with advanced hepatocellular carcinoma. Thus, nivolumab might be considered a therapeutic option for patients in whom tyrosine kinase inhibitors and antiangiogenic drugs are contraindicated or have substantial risks. FUNDING: Bristol Myers Squibb in collaboration with Ono Pharmaceutical.

Qualidade de vida de pacientes com metástase hepática em decorrência de câncer colorretal / Calidad de vida de los pacientes con metástasis hepática por cáncer colorrectal / Quality of life of patients with liver metastasis due to colorectal cancer

Objetivo: avaliar e correlacionar os domínios da qualidade de vida de pacientes com metástase hepática de câncer colorretal em tratamento quimioterápico. Método: estudo transversal, observacional, com 106 pacientes selecionados em três hospitais do Sul do Brasil. Os dados foram coletados com o Quality of Life Questionnaire Core 30 e Quality of Life Questionnaire Colorectal Liver Metastases, analisados descritivamente e pelo teste de correlação de Spearman. Resultados: a vida sexual (45,08%), função emocional (43,08%) e fadiga (40,15%) tiveram os piores escores com o Quality of Life Questionnaire Colorectal Liver Metastases. Todas as correlações entre os domínios são significativas, demonstrando que um domínio com escore baixo interfere em todos os demais. Conclusão: os pacientes com metástase hepática de câncer colorretal em tratamento quimioterápico apresentaram alteração nos domínios de qualidade de vida.

Objetivo: evaluar y correlacionar los dominios de calidad de vida de pacientes con metástasis hepática de cáncer colorrectal sometidos a quimioterapia. Método: estudio observacional transversal con 106 pacientes seleccionados en tres hospitales del sur de Brasil. Los datos fueron recolectados mediante el Quality of Life Questionnaire Core 30 y Quality of Life Questionnaire Colorectal Liver Metastases, analizados descriptivamente y mediante la prueba de correlación de Spearman. Resultados: la vida sexual (45,08%), la función emocional (43,08%) y la fatiga (40,15%) tuvieron las peores puntuaciones con el Quality of Life Questionnaire Colorectal Liver Metastases. Todas las correlaciones entre los dominios son significativas, demostrando que un dominio con una puntuación baja interfiere en todos los demás. Conclusión: los pacientes con metástasis hepática por cáncer colorrectal sometidos a quimioterapia mostraron cambios en los dominios de calidad de vida.

Objective: to evaluate and correlate the quality of life domains of patients with liver metastasis of colorectal cancer undergoing chemotherapy. Method: cross-sectional, observational study with 106 patients selected in three hospitals in southern Brazil. Data were collected using the Quality of Life Questionnaire Core 30 and Quality of Life Questionnaire Colorectal Liver Metastases, analyzed descriptively and by Spearman's correlation test. Results: sexual life (45.08%), emotional function (43.08%) and fatigue (40.15%) had the worst scores with the Quality of Life Questionnaire Colorectal Liver Metastases. All correlations between the domains are significant, demonstrating that a domain with a low score interferes in all others. Conclusion: patients with liver metastasis from colorectal cancer undergoing chemotherapy showed changes in quality of life domains.

The impact of hepatocellular carcinoma diagnosis on patients' health-related quality of life.

BACKGROUND: Patients with hepatocellular cancer (HCC) are known to have worse health-related quality of life (HRQL) than the general population. However, the change in HRQL from before the diagnosis to after diagnosis remains unknown and is difficult to estimate. We aimed to compare HCC cases with matched controls to evaluate the differences in change in HRQL from before to after HCC diagnosis. METHODS: We performed propensity score-matched analysis using the self-reported HRQL data from the Surveillance, Epidemiology, and End Results registries (SEER) data linked with Medicare Health Outcomes Survey (MHOS) data (1998-2014). Cases were selected as Medicare beneficiaries (aged ≥65 years) who were diagnosed with HCC between their baseline assessment and follow-up assessment. Matched controls were selected from the same data resource and the same time period to include subjects without cancer diagnosis by propensity scores. HRQL was assessed using the Medical Outcomes Study Short Form-36 (SF-36). RESULTS: The study included 62 subjects who developed HCC and 365 matched controls. Compared to their baseline HRQL scores, after diagnosis of HCC, subjects were more likely to report declines in scores related to the mental component of HRQL. When stratified by time since diagnosis, mental component remained significantly lower as the disease advanced. In contrast, only general health aspects of physical health worsened after HCC diagnosis. CONCLUSIONS: Diagnosis of HCC has a profound negative impact on patients' HRQL. Mental health component deteriorated significantly over time. The need of including mental health services within a multidisciplinary HCC care model is clearly evident.

Health-related quality of life in locally advanced hepatocellular carcinoma treated by either radioembolisation or sorafenib (SARAH trial).

BACKGROUND: The aim of this ancillary study of the SARAH trial is to compare health-related quality of life (HRQoL) in patients with locally advanced or inoperable hepatocellular carcinoma (HCC) treated with transarterial radioembolisation (TARE) or sorafenib. METHODS: This study included randomised patients who received either TARE or at least one dose of sorafenib with no major deviation in the protocol and who had at least one QoL follow-up assessment in addition to the baseline evaluation. QoL was assessed from the date of randomisation using the European Organisation for Research and Treatment of Cancer QLQ-C30 questionnaire, until disease progression or other reasons for stopping study participation. Data were analysed using linear mixed and time-dependent models. RESULTS: A total of 285 patients were included (122 and 163, in the TARE and sorafenib groups, respectively). Questionnaire completion rates were similar (77.5% versus 80.4%, in the TARE and sorafenib groups, respectively, p = 0.25). Longitudinal HRQoL analysis showed a significant treatment and time effects for fatigue and global health status, and significant treatment, time and treatment by time interaction effects for appetite loss, diarrhoea and social functioning. The median time to deterioration for the global health status was 3.9 months (95% confidence interval [CI] 3.7-4.3) versus 2.6 months (95% CI 2.0-3.0) in the TARE and sorafenib groups, respectively. CONCLUSIONS: HRQoL was preserved longer with TARE than with sorafenib in locally advanced HCC. These data could be used to optimise management of patients with advanced or inoperable HCC.

Relationship between hepatocellular carcinoma and depression via online database analysis.

There may be a mutually reinforcing relationship between hepatocellular carcinoma (HCC) and depression, but the mechanism is unknown. This study used bioinformatics to evaluate the relationship between HCC and depression at the genetic level. Genes associated with HCC and depression were obtained from pubmed2ensemble. Overlapping genes were annotated by gene ontology (GO) function and enriched by Kyoto Encyclopedia of Genes and Genomes (KEGG) signal pathway. The cluster-1 genes obtained by Cytoscape were analyzed by GEPIA for expression and overall survival in HCC and, finally, introduced target genes to DGIdb to get associated drugs. A total of 199 genes were found to be in common between HCC and depression. GO term enrichment analysis on DAVID found the top-6 biological processes to be mainly associated with cell death and apoptosis. The top-6 cellular component terms are extracellular. The top-6 of molecular function terms are mainly associated with receptor binding. The top-6 pathways enriched by KEGG are mainly related to inflammatory response. IGF1, VEGFA, and SERPINE1 had statistical differences in expression and 10-year survival rate. There are total 45 drugs that act on VEGFA and SERPINE1. Based on our findings, we hypothesize that the mechanism of the interaction between HCC and depression may be related to cell death or apoptosis. Further studies are needed to verify this hypothesis.

A Phase 2 Study of Image-Guided Proton Therapy for Operable or Ablation-Treatable Primary Hepatocellular Carcinoma.

PURPOSE: Because most previous data on proton therapy for hepatocellular carcinoma (HCC) were retrospectively collected from inoperable or previously treated cases, our aim was to evaluate the outcome of image-guided proton therapy (IGPT) for operable or radiofrequency ablation-treatable primary HCC. METHODS AND MATERIALS: This phase 2 study prospectively investigated the efficacy and safety of IGPT and quality of life (QoL) after IGPT for operable/ablatable HCC. The primary endpoint was overall survival, and the secondary endpoints were local control, incidence of grade ≥3 adverse events, and changes in QoL. Toxicities were evaluated with Common Terminology Criteria for Adverse Events, version 4.0. QoL scores were assessed with European Organization for Research and Treatment of Cancer Quality of Life Questionnaire, version 3.0, and Quality of Life Questionnaire-Hepatocellular Carcinoma/Primary Liver Cancer Module. IGPT was performed using respiratory-gated techniques. RESULTS: Forty-five patients (median age: 68 years; range, 36-80 years) were enrolled between June 2013 and February 2016; 38 were considered operable and 14 were indicated for radiofrequency ablation. The major underlying liver diseases were hepatitis B (n = 16), hepatitis C (n = 13), alcoholic hepatitis (n = 3), and nonalcoholic fatty liver disease (n = 13). The Child-Pugh score was A5 in 32 patients, A6 in 9 patients, and B7 in 4 patients. Thirty-seven patients with a peripherally located tumor were given 66 Gy relative biological effectiveness in 10 fractions, and 8 patients with a centrally located tumor received 72.6 Gy relative biological effectiveness in 22 fractions. The median follow-up period of surviving patients was 60 months (range, 42-75 months). Two- and 5-year overall survival rates were 84% (95% confidence interval [CI], 74%-95%) and 70% (95% CI, 56%-84%), respectively, and local control rates were 95% (95% CI, 89%-100%) and 92% (95% CI, 84%-100%), respectively. Grade 3 radiation-induced liver disease was observed in 1 patient. No significant changes were noted in QoL scores 1 year after treatment, except for body image. CONCLUSIONS: Although the primary endpoint did not meet statistical significance as planned in the study design, IGPT is a safe and effective treatment for solitary primary HCC and may become a treatment option.

Quality of Life after Transcatheter Arterial Chemoembolization Combined with Radiofrequency Ablation in Patients with Unresectable Hepatocellular Carcinoma Compared with Transcatheter Arterial Chemoembolization alone.

AIM: The aim of this study was to assess quality of life (QoL) in patients with unresectable hepatocellular carcinoma (HCC) after transcatheter arterial chemoembolization (TACE) compared to TACE plus radiofrequency ablation (RFA) done at the same sitting, and to assess tumor therapy response after these 2 palliative interventions. METHODS: 73 patients with unresectable HCC (BCLC-B) were included. Patients with tumor ≤ 5 cm were subjected to TACE (N = 45) while patients with tumors > 5 cm were subjected to TACE followed immediately by RFA (N = 28). QoL was evaluated with two validated questionnaires (EORTC QLQ-30 and EORTC HCC18). These questionnaires were filled out before intervention, 2 weeks and 2 months after intervention. Pre/post interventional changes were analyzed. The modified response evaluation criteria in solid tumor (mRECIST) were employed for the evaluation of therapeutic efficacy. RESULTS: Baseline global health status/QoL was significantly higher in TACE group (64.1%) compared to TACE-RFA group (51.2%). Two weeks after intervention: the absolute decrease in global health state was higher in TACE-RFA (- 12.1%) compared to TACE (- 6.3%, p = 0.411). Less impairment was found in TACE group compared to TACE-RFA group for physical/social functioning, fatigue and pain but it was statistically insignificant. Two months after intervention; TACE-RFA group showed significant improvement in global health score, social and physical functioning scores, as well as significant improvement in pain and fatigue compared to TACE group. The therapeutic efficacy of TACE-RFA was better than TACE alone: complete remission, partial remission, stable disease and progressive disease were 17.9%, 32.1%, 42.9% and 7.1% Vs11.1%, 22.2%, 48.9% and 17.8%, respectively). CONCLUSION: Neither TACE nor TACE-RFA showed a significant decrease in QoL in patients with unresectable HCC two weeks after intervention. However, two months after intervention; TACE-RFA showed significant improvement in global health score compared to TACE monotherapy. TACE-RFA appeared safe, effective and more favorable than TACE monotherapy.
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A closer look at quality of life in the hepatocellular carcinoma literature.

PURPOSE: Adults with hepatocellular carcinoma (HCC) have a high symptom burden. Their quality of life (QOL) has been shown to be significantly impacted by both the disease and its treatment, adding to the high symptom burden that these patients experience. The primary aims of this paper are as follows: (1) to identify how QOL is being defined in HCC literature and (2) to identify how QOL is being measured in the HCC literature using Ferrell's model of QOL. METHODS: A systematic review was completed of relevant studies published after 2014, using PubMed, CINHAL, and PsycInfo. Relevant studies were reviewed by 2 reviewers using PRISMA guidelines. RESULTS: From a total of 1312 papers obtained in the initial database search, 30 met inclusion criteria and are included in this review. From the included articles, 10% included a definition of QOL and 3% addressed the spiritual domain of QOL. Majority of study participants were in the early stage of HCC, though the majority of adults with HCC are diagnosed in the advanced stage. Only 3% of included studies included greater than 22% population of advanced stage of HCC. CONCLUSION: The results of this systematic review demonstrate the need for future research into QOL in the advanced stage of QOL. It also identified gap in the literature concerning the definition of QOL in HCC and the spiritual domain of QOL in HCC.

Health-related quality-of-life impact of pembrolizumab versus best supportive care in previously systemically treated patients with advanced hepatocellular carcinoma: KEYNOTE-240.

BACKGROUND: Health-related quality of life (HRQoL) is an important outcome measure and prognostic indicator in hepatocellular carcinoma (HCC). KEYNOTE-240 (NCT02702401) assessed the efficacy and safety of pembrolizumab plus best supportive care (BSC) versus placebo plus BSC in patients with HCC who previously received sorafenib. This study presents the results of a prespecified exploratory analysis of patient-reported outcomes. METHODS: Patients completed the European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30) and its HCC supplement (EORTC QLQ-HCC18) electronically at baseline; at weeks 2, 3, 4, 6, 9, 12, and 18; and then every 9 weeks until 1 year or end of treatment, and at the 30-day safety follow-up visit. RESULTS: The HRQoL population included 271 and 127 patients randomly assigned to pembrolizumab and placebo, respectively. From baseline to week 12, changes in both scores were similar between pembrolizumab and placebo; global health status/QoL scores were stable. The proportions of patients who improved, remained stable, or deteriorated across all functional domain and symptom scores were generally similar between pembrolizumab and placebo. Time to deterioration was similar between the 2 arms based on the prespecified analysis of EORTC QLQ-HCC18 domains of abdominal swelling, fatigue, and pain. CONCLUSION: Pembrolizumab preserved HRQoL during treatment for advanced HCC. Combined with efficacy and safety results from KEYNOTE-240, these findings support a positive benefit/risk profile for pembrolizumab in a second-line treatment setting for patients with HCC who previously received sorafenib.

Effects of high-quality nursing care on psychological outcomes and quality of life in patients with hepatocellular carcinoma: A protocol of systematic review and meta-analysis.

BACKGROUND: High quality nursing care (HQNC) has been reported to effectively prevent psychological disorders and improve the quality of life (QoL) in patients with hepatocellular carcinoma (HCC) during the treatment. However, the exact effect of HQNC remains controversial. This systematic review will be aimed to assess the effectiveness of HQNC on psychological disorders and QoL in patients with HCC. METHODS: Eligible prospective controlled clinical trials were searched from Google Scholar, Medline, Excerpt Medica Database (Embase), PubMed, Web of Science (WOS), Cochrane Library, China Scientific Journal Database (CSJD), China National Knowledge Infrastructure (CNKI), Chinese BioMedical Database (CBM) and Wanfang Database. Papers in English or Chinese published from January 2000 to July 2020 will be included without any restrictions. The clinical outcomes including psychological outcomes, QoL, and adverse events of HQNC in patients with HCC were systematically evaluated.Study selection and data extraction will be performed independently by two reviewers. Stata 14.0 and Review Manager 5.3 were used for data analysis. Methodological quality for each eligible study will be assessed by using Cochrane risk of bias tool. Subgroup and meta-regression analysis will be carried out depending on the availability of sufficient data. RESULTS: The results of this systematic review will be published in a peer-reviewed journal. CONCLUSION: The results of this study may provide helpful evidence of HQNC on psychological effects and QoL in patients with HCC. INPLASY REGISTRATION NUMBER: INPLASY202070096.