Cost-effectiveness analysis of amivantamab plus chemotherapy for non-small cell lung cancer patients with epidermal growth factor receptor exon 20 insertions in the United States.

BACKGROUND: Although amivantamab has shown clinical benefits for non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) exon 20 insertions, its cost-effectiveness requires further investigation. AIM: To evaluate the cost-effectiveness of amivantamab plus chemotherapy for the treatment of NSCLC patients with EGFR exon 20 insertions from the United States payer perspective. METHOD: A partitioned survival model was developed based on the data from the PAPILLON trial. Costs were derived from the pricing files of Medicare and Medicaid Services and published literature, and utility values were derived from previous studies. A 3% annual discount rate was applied to both costs and outcomes. The primary outcome was the incremental cost-effectiveness ratio (ICER). One-way sensitivity analysis, probabilistic sensitivity analysis and scenario analysis, were conducted to test the model stability. RESULTS: Amivantamab plus chemotherapy yielded an additional 1.12 quality-adjusted life years (QALYs) while increasing costs by $483,769.50 relative to the chemotherapy regimen, leading to an ICER of $432,401.16/QALY. The combination of amivantamab with chemotherapy was not cost effective at a threshold of $150,000/QALY. In the scenario analysis, the results showed that the ICERs were $263,680.69/QALY and $418,416.35/QALY when different utility values and 10-year time horizons were adopted, respectively. For PSA, the probability that amivantamab plus chemotherapy would be cost-effective was 0% if the willingness-to-pay (WTP) threshold was $150,000/QALY. CONCLUSION: Amivantamab plus chemotherapy is unlikely to be a cost-effective option for NSCLC patients with EGFR exon 20 insertions. Reducing the cost of amivantamab may produce favorable economic outcomes.

Associations between modifiable risk factors and hepatocellular carcinoma: a trans-ancestry Mendelian randomization study.

BACKGROUND: Potentially modifiable risk factors for hepatocellular carcinoma (HCC) have been investigated in observational epidemiology studies in East Asian and European populations, whereas the causal associations of most of these risk factors remain unclear. METHODS: We collected genome-wide association summary statistics of 22 modifiable risk factors in East Asians and 33 risk factors in Europeans. Genetic summary statistics of HCC were sourced from the Biobank Japan study (1,866 cases and 195,745 controls) for East Asians, and the deCODE genetics study (406 cases and 49,302 controls) and the UK Biobank (168 cases and 372 016 controls) for Europeans. Two-sample Mendelian randomization (MR) analyses were performed independently for East Asian and European populations. RESULTS: In East Asians, genetically predicted alcohol frequency, ever drinkers, aspartate aminotransferase (AST), hypothyroidism, chronic hepatitis B, and chronic hepatitis C, metabolic dysfunction-associated steatotic liver disease (MASLD), and autoimmune hepatitis were significantly associated with an increased HCC risk (P < 0.05/22). Among European population, alanine transaminase, AST, MASLD, percent liver fat, and liver iron content were significantly associated with a higher risk of HCC (P < 0.05/33). The replication dataset and meta-analysis further confirmed these results. CONCLUSIONS: Although East Asian and European populations have different factors for HCC, their common modifiable risk factors AST and MASLD for HCC, offer valuable insights for targeted intervention strategies to mitigate society burden of HCC.

The assessment and detection rate of intrinsic capacity deficits among older adults: a systematic review and meta-analysis.

BACKGROUND: Assessing and monitoring intrinsic capacity (IC) is an effective strategy to promote healthy ageing by intervening early in high-risk populations. This review systematically analyzed the global detection rates of IC deficits and explored variations across diverse populations and data collection methods. METHODS: This study was preregistered with PROSPERO, CRD42023477315. In this systematic review and meta-analysis, we systematically searched ten databases from January 2015 to October 2023, for peer-reviewed, observational studies or baseline survey of trials that assessed IC deficits among older adults aged 50 and above globally following the condition, context and population approach. The main outcome was intrinsic capacity deficits which could be assessed by any tools. Meta-analyses were performed by a random-effect model to pool the detection rates across studies and subgroup analyses were conducted by populations and data collection methods. RESULTS: Fifty-six studies conducted in 13 countries were included in the review and 44 studies with detection rates of IC were included in the meta-analysis. The pooled detection rate of IC deficits was 72.0% (65.2%-78.8%) and deficits were most detected in sensory (49.3%), followed by locomotion (40.0%), cognition (33.1%), psychology (21.9%), and vitality (20.1%). Variations in detection rates of IC deficits were observed across studies, with higher rates observed in low- and middle-income countries (74.0%) and hyper-aged societies (85.0%). Study population and measurement tools also explained the high heterogeneity across studies. CONCLUSION: IC deficits are common among older adults, while heterogeneity exists across populations and by measurement. Early monitoring with standardized tools and early intervention on specific subdomains of IC deficits are greatly needed for effective strategies to promote healthy ageing.

Cytological diagnosis of patients with embryonal rhabdomyosarcoma of the cervix: case report and literature review.

Cervical embryonal rhabdomyosarcoma(ERMS) is a rare malignancy. To date, no cases of ERMS diagnosed by cervical cytology have been reported. In this study, we report a case of cervical ERMS identified by a liquid-based cytology test and cell blocks in a 46-year-old postmenopausal woman. We describe the cytological features of ERMS, with the aim of helping cytopathologists recognize this rare cervical tumor.

Impact of continuity of care based on Triangle theory on nutritional status of patients after pancreatic cancer surgery: a retrospective study.

OBJECTIVE: To evaluate the impact of Triangle theory-based continuity of care on postoperative malnutrition in pancreatic cancer patients. METHODS: We retrospectively analyzed the data from 184 patients with pancreatic cancer admitted to The Second People's Hospital of Lanzhou City from January 2020 to May 2023. Patients were divided into a control group receiving conventional care (n = 114) and a study group receiving Triangle theory-based care (n = 70). Postoperative nutritional status and prognosis were compared between the two groups. Nutritional indexes included serum total protein (STP), albumin (ALB), and hemoglobin (HB). Self-care ability was assessed using the Exercise of Self-care Agency (ESCA). Quality of life was measured using the Quality-of-Life Questionnaire for Pancreatic Cancer 26 (QLQ-PAN-26), and the incidence of malnutrition was evaluated using the Patient-Generated Subjective Global Assessment (PG-SGA). Multifactorial logistic regression was applied to analyze risk factors for malnutrition. RESULTS: At ten days post-operation, the study group showed significantly better nutritional levels (P < 0.05). After three months, the, study group also exhibited superior self-care ability and quality of life scores (all P < 0.001). The incidence of malnutrition was 42.39%. Independent risk factors for malnutrition included routine care (OR = 3.459), operation time ≥ 90 min (OR = 2.277), intraoperative bleeding ≥ 200 mL (OR = 2.590), postoperative day 1 ALB < 37.5 g/L (OR = 3.975), and HB < 95.5 g/L (OR = 6.068). CONCLUSION: Triangle theory-based continuity of care significantly improves nutritional status and quality of life in postoperative pancreatic cancer patients, demonstrating its potential for broader clinical use.

Cost-effectiveness of adjuvant endocrine treatment with tamoxifen for male breast cancer.

BACKGROUND: Tamoxifen (TAM) is recommended as the first-line strategy for men with estrogen receptor (ER)-positive early breast cancer who are candidates for adjuvant endocrine therapy in ASCO guideline. Our study aims to analyze the cost-effectiveness of receiving adjuvant endocrine therapy with TAM compared to no TAM, and to assess the cost-effectiveness of using TAM with high adherence over low adherence for ER-positive early male breast cancer in the USA. METHODS: Two Markov models comprising three mutually exclusive health states were constructed: (1) the first Markov model compared the cost-effectiveness of adding TAM with not using TAM (TAM versus Not-TAM); (2) the second model compared the cost-effectiveness of receiving TAM with high adherence and low adherence (High-adherence-TAM versus Low-adherence-TAM). The simulation time horizon for both models was the lifetime of patients. The efficacy and safety data of two models were elicited from the real-world studies. Model inputs were derived from the US website and published literature. The main outcomes of two models both included the total cost, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs). RESULTS: In the first model, TAM yielded an ICER of $5707.29 per QALY compared to Not-TAM, which was substantially below the WTP threshold of $50,000.00 per QALY in the USA. Probabilistic sensitivity analysis results demonstrated a 100.00% probability of cost-effectiveness for this strategy. In the second model, High-adherence-TAM was dominated absolutely compared to Low-adherence-TAM. The High-adherence-TAM was cost-effective with a 99.70% probability over Low-adherence-TAM when WTP was set as $50,000.00/QALY. All of these parameters within their plausible ranges did not reversely change the results of our models. CONCLUSIONS: Our study will offer valuable guidance for physicians or patients when making treatment decisions and provide an effective reference for decision-making to consider the appropriate allocation of funds to this special group.

One-pot synthesis and hydrogen peroxide electrochemical sensing of 3D TiO2/MnO2 nanorods assembled microspheres.

Nanorods assembled 3D microspheres of TiO2/MnO2 were prepared via a simple one-pot hydrothermal approach. The resultant composite material exhibited remarkable electrocatalytic activity for hydrogen peroxide (H2O2) in comparison to each single component. The electrochemical sensor constructed with TiO2/MnO2 exhibited a linear relationship within the range 0.0001-5.6 mmol·L-1 for H2O2. The limit of detection (LOD) and sensitivity for H2O2 were 0.03 µmol·L-1 (S/N = 3) and 316.6 µA (mmol·L-1)-1 cm-2. Moreover, this sensor can be employed to detect trace amount of H2O2 in serum and urine samples successfully, supporting an insight and strategy for a more sensitive electrochemical sensor.

Association between novel genetic variants of Notch signaling pathway genes and survival of hepatitis B virus-related hepatocellular carcinoma.

BACKGROUND: Although the Notch pathway plays an important role in formation and progression of hepatocellular carcinoma (HCC), few studies have reported the associations between functional genetic variants and the survival of hepatitis B virus (HBV)-related HCC. METHODS: In the present study, we performed multivariable Cox proportional hazard regression analysis to evaluate associations between 36,101 SNPs in 264 Notch pathway-related genes and overall survival (OS) of 866 patients with HBV-related HCC. RESULTS: It was found that three independent SNPs (NEURL1B rs4868192, CNTN1 rs444927 and FCER2 rs1990975) were significantly associated with the HBV-related HCC OS. The number of protective genotypes (NPGs) were significantly associated with better survival in a dose-response manner (ptrend <0.001). Compared with the model with sole clinical factors, the addition of protective genotypes to the predict models significantly increased the AUC, i.e., from 72.72% to 75.13% (p = 0.002) and from 72.04% to 74.76 (p = 0.004) for 3-year and 5-year OS, respectively. The expression quantitative trait loci (eQTL) analysis further revealed that the rs4868192 C allele was associated with lower mRNA expression levels of NEURL1B in the whole blood (p = 1.71 × 10-3), while the rs1990975 T allele was correlated with higher mRNA expression levels of FCER2 in the whole blood and normal liver tissues (p = 3.51 × 10-5 and 0.033, respectively). CONCLUSIONS: Three potentially functional SNPs of NEURL1B, CNTN1 and FCER2 may serve as potential prognostic biomarkers for HBV-related HCC.

Benign metastasizing fumarate hydratase (FH)-deficient uterine leiomyomas: clinicopathological and molecular study with first documentation of multi-organ metastases.

Leiomyoma is the most prevalent benign tumor of the female reproductive system. Benign metastasizing leiomyoma (BML) is a rare phenomenon that presents at distant sites, typically the lungs, exhibiting histopathological features similar to the primary uterine tumor in the absence of malignancy features in both. Fumarate hydratase-deficient uterine leiomyoma (FH-d UL) is an uncommon subtype among uterine smooth muscle tumors (0.5-2%), showing distinctive histomorphology and FH inactivation. The majority of FH-d ULs are sporadic, caused by somatic FH inactivation, while a minority of cases occur in the context of the hereditary leiomyomatosis and renal cell carcinoma (HLRCC) syndrome caused by germline FH inactivation. Metastasizing FH-d UL has not been well documented and might be under-reported. Here, we present two cases (21- and 34-year-old females) who presented with metastasizing FH-d UL after myomectomy/hysterectomy with histologically proven multiple lung metastases in both, in addition to multi-organ involvement in one case (cervical-thoracic lymph nodes, left kidney, perihepatic region, left zygomatic bone, and soft tissues). Pathological examination confirmed FH-d leiomyomas in the primary/recurrent uterine tumors, multiple lung lesions, and a renal mass. The minimal criteria for diagnosis of leiomyosarcoma were not fulfilled. Genetic testing revealed germline pathogenic FH variants in both cases (c.1256C > T; p.Ser419Leu in Case 1 and c.425A > G; p.Gln142Arg in Case 2). These novel cases highlight a rare but possibly under-recognized presentation of FH-d BML. Our study suggests that FH-d BML cases might be enriched for the HLRCC syndrome.

Genetic variants in m5C modification genes are associated with survival of patients with HBV-related hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors with a high mortality rate. The 5-methylcytosine (m5C), a type of RNA modification, plays crucial regulatory roles in HCC carcinogenesis, metastasis, and prognosis. However, a few studies have investigated the effect of genetic variants in m5C modification genes on survival of patients with hepatitis B virus (HBV)-related HCC. In the present study, we evaluated associations between 144 SNPs in 15 m5C modification genes and overall survival (OS) in 866 patients with the HBV-related HCC. Expression quantitative trait loci (eQTL) analysis and differential expression analysis were conducted to investigate biological mechanisms. As a result, we identified that two SNPs (NSUN7 rs2437325 A > G and TRDMT1 rs34434809 G > C) were significantly associated with HBV-related HCC OS with adjusted allelic hazards ratios of 1.25 (95% confidence interval = 1.05-1.48 and P = 0.011) and 1.19 (1.02-1.38 and P = 0.027), respectively, with a trend of combined risk genotypes (Ptrend < 0.001). Moreover, the results of eQTL analyses showed that both NSUN7 rs2437325 G and TRDMT1 rs34434809 C alleles were associated with a reduced mRNA expression level in 208 normal liver tissues (P = 0.007 and P < 0.001, respectively). Taken together, genetic variants in the m5C modification genes may be potential prognostic biomarkers of HBV-related HCC after hepatectomy, likely through mediating the mRNA expression of corresponding genes.

Is circulating tumor cell count-driven cost-effective for first-line therapy choice in HR+/HER2- metastatic breast cancer in the United States?

BACKGROUND: Circulating tumor cell (CTC) counting may be a useful non-invasive biomarker that helps patients choose first-line treatment options. Nevertheless, the cost of CTC inspection may impose an economic burden on patients, necessitating the simultaneous consideration of both its clinical effectiveness and cost. We evaluated the cost-effectiveness of CTC count-guided chemotherapy and endocrine therapy as first-line therapy for HR+/HER2-metastatic breast cancer (MBC) from the perspective of US payers. METHODS: Based on the STIC CTC trial, a Markov model was constructed for three health states, and health outcomes were measured in quality-adjusted life years (QALYs) and incremental cost-effectiveness ratio (ICER). One-way and probabilistic sensitivity analyses were performed to assess the robustness of the incremental cost per QALY. RESULTS: The base-case analysis revealed that CTC count-driven treatment was associated with improved effectiveness by 0.07 QALYs and increased the overall cost by $9187.05 compared with clinician-driven first-line treatment choices, leading to an ICER of $138 354.15 per QALY. One-way sensitivity analysis indicated that the model was most sensitive to the cost of treatment for neutropenia and the utility for PFS; probability sensitivity analysis indicated that CTC count-driven treatment choices would be considered the cost-effective option at a willingness-to-pay threshold of $150 000 per QALY. CONCLUSIONS: The findings of this cost-effectiveness analysis suggest that, at the current price of CTC enumeration, choosing first-line treatment options based on CTC count is a cost-effectiveness approach for treating patients with HR+/HER2- MBC in the US.

Anastrozole for the prevention of breast cancer in high-risk postmenopausal women: cost-effectiveness analysis in the UK and the USA.

PURPOSE: The effectiveness of anastrozole for breast cancer prevention has been demonstrated. The objective of this study was to evaluate the cost-effectiveness of anastrozole for the prevention of breast cancer in women with a high risk of breast cancer and to determine whether anastrozole for the primary prevention of breast cancer can improve the quality of life of women and save health-care resources. METHODS: A decision-analytic model was used to assess the costs and effects of anastrozole prevention versus no prevention among women with a high risk of breast cancer. The key parameters of probability were derived from the IBIS-II trial, and the cost and health outcome data were derived from published literature. Costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs) were calculated for the two strategies,One-way and probabilistic sensitivity analyses were performed. RESULTS: In the base case, the incremental cost per QALY of anastrozole prevention was £125,705.38/QALY in the first 5 years compared with no prevention in the UK, above the threshold of WTP (£3,000/QALY),and in the 12-year period, the ICER was £8,313.45/QALY, less than WTP. For the US third-party payer, ICER was $134,232.13/QALY in the first 5 years and $8,843.30/QALY in the 12 years, both less than the WTP threshold ($150,000/QALY). CONCLUSION: In the UK and US, anastrozole may be a cost-effective strategy for the prevention of breast cancer in high-risk postmenopausal women. Moreover, the longer the cycle of the model, the higher the acceptability. The results of this study may provide a scientific reference for decision-making for clinicians, patients, and national medical and health care government departments.

Functional genetic variants of the disulfidptosis-related INF2 gene predict survival of hepatitis B virus-related hepatocellular carcinoma.

Disulfidptosis is a novel form of programmed cell death involved in migration and invasion of cancer cells, but few studies investigated the roles of genetic variants in disulfidptosis-related genes in survival of patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). We used Cox proportional hazards regression analyses, Kaplan-Meier curves and receiver operating characteristic curves to assess effects of genetic variants in 14 disulfidptosis-related genes on overall survival of 866 HBV-HCC patients. The Bayesian false discovery probability was used for multiple testing corrections. We also investigated biological mechanisms of the significant variants through expression quantitative trait loci analyses using the data from publicly available databases, luciferase reporter assays and differential expression analyses. As a result, we identified two independently functional single nucleotide polymorphisms (SNPs) (INF2 rs4072285 G > A and INF2 rs4444271 A > T) that predicted overall survival of HBV-HCC patients, with adjusted hazard ratios of 1.60 (95% CI = 1.22-2.11, P = 0.001) and 1.50 (95% CI = 1.80-1.90, P < 0.001), respectively, after multiple testing correction. Luciferase reporter assays indicated that both INF2 rs4072285 A and INF2 rs4444271 T alleles increased INF2 mRNA expression levels (P < 0.001) that were also higher in HCC tumor tissues than in adjacent normal tissues (P < 0.001); such elevated INF2 expression levels were associated with a poorer survival of HBV-HCC patients (P < 0.001) in the TCGA database. In summary, this study supported that INF2 rs4072285 and INF2 rs4444271 may be novel biomarkers for survival of HBV-HCC patients.

A meta-analysis of the impact of pharmacist interventions on clinical outcomes in patients with type-2 diabetes.

OBJECTIVE: To evaluate the effects of pharmacist interventions in type-2 diabetes patients by collecting and evaluating literature. METHODS: A systematic search was conducted across six databases, including CNKI, Wanfang Data, VIP, PubMed, Web of Science, and Cochrane Library, from January 2001 to January 2023. Randomized controlled trials evaluating the clinical outcomes of pharmacist interventions on type-2 diabetes patients were searched, and data were extracted and analysed by RevMan version 5.4 software. RESULTS: A total of 35 studies involving 4827 patients were included. Meta-analysis demonstrated that pharmacist interventions had an influence on improving patients' HbA1c (MD=-0.70), LDL-C (MD=-5.51), SBP (MD=-4.58), DBP (MD=-1.90], BMI (MD=-0.47) and FBG (MD=-19.82), but there was no evidence from the study that pharmacist interventions could significantly improve HDL-C (MD=-0.61), TC (MD=-5.12) or TG (MD=-3.14). In addition, medication adherence was significantly improved. CONCLUSION: Pharmacist interventions significantly improved HbA1c, BP, and LDL-C control levels, BMI, and medication adherence in type-2 diabetes patients, but there was no evidence from this study that pharmacist interventions significantly improved HDL-C, TC, or TG. PRACTICE IMPLICATIONS: Effective pharmacist interventions are important to improve type-2 diabetes patients' clinical outcomes.

Development and evaluation of a polygenic risk score for lung cancer in never-smoking women: A large-scale prospective Chinese cohort study.

The proportion of lung cancer in never smokers is rising, especially among Asian women, but there is no effective early detection tool. Here, we developed a polygenic risk score (PRS), which may help to identify the population with higher risk of lung cancer in never-smoking women. We first performed a large GWAS meta-analysis (8595 cases and 8275 controls) to systematically identify the susceptibility loci for lung cancer in never-smoking Asian women and then generated a PRS using GWAS datasets. Furthermore, we evaluated the utility and effectiveness of PRS in an independent Chinese prospective cohort comprising 55 266 individuals. The GWAS meta-analysis identified eight known loci and a novel locus (5q11.2) at the genome-wide statistical significance level of P < 5 × 10-8 . Based on the summary statistics of GWAS, we derived a polygenic risk score including 21 variants (PRS-21) for lung cancer in never-smoking women. Furthermore, PRS-21 had a hazard ratio (HR) per SD of 1.29 (95% CI = 1.18-1.41) in the prospective cohort. Compared with participants who had a low genetic risk, those with an intermediate (HR = 1.32, 95% CI: 1.00-1.72) and high (HR = 2.09, 95% CI: 1.56-2.80) genetic risk had a significantly higher risk of incident lung cancer. The addition of PRS-21 to the conventional risk model yielded a modest significant improvement in AUC (0.697 to 0.711) and net reclassification improvement (24.2%). The GWAS-derived PRS-21 significantly improves the risk stratification and prediction accuracy for incident lung cancer in never-smoking Asian women, demonstrating the potential for identification of high-risk individuals and early screening.

Integrative analyses of N6-methyladenosine-associated single-nucleotide polymorphisms (m6A-SNPs) identify tumor suppressor gene AK9 in lung cancer.

N6 -methyladenosine (m6 A) modification has been identified as one of the most important epigenetic regulation mechanisms in the development of human cancers. However, the association between m6 A-associated single-nucleotide polymorphisms (m6 A-SNPs) and lung cancer risk remains largely unknown. Here, we identified m6 A-SNPs and examined the association of these m6 A-SNPs with lung cancer risk in 13,793 lung cancer cases and 14,027 controls. In silico functional annotation was used to identify causal m6 A-SNPs and target genes. Furthermore, methylated RNA immunoprecipitation and quantitative real-time polymerase chain reaction (MeRIP-qPCR) assay was performed to assess the m6 A modification level of different genotypes of the causal SNP. In vitro assays were performed to validate the potential role of the target gene in lung cancer. A total of 8794 m6 A-SNPs were detected, among which 397 SNPs in nine susceptibility loci were associated with lung cancer risk, including six novel loci. Bioinformatics analyses indicated that rs1321328 in 6q21 was located around the m6 A modification site of AK9 and significantly reduced AK9 expression (ß = -0.15, p = 2.78 × 10-8 ). Moreover, AK9 was significantly downregulated in lung cancer tissues than that in adjacent normal tissues of samples from the Cancer Genome Atlas and Nanjing Lung Cancer Cohort. MeRIP-qPCR assay suggested that C allele of rs1321328 could significantly decrease the m6 A modification level of AK9 compared with G allele. In vitro assays verified the tumor-suppressing role of AK9 in lung cancer. These findings shed light on the pathogenic mechanism of lung cancer susceptibility loci linked with m6 A modification.

Potentially functional genetic variants in ferroptosis-related CREB3 and GALNT14 genes predict survival of hepatitis B virus-related hepatocellular carcinoma.

BACKGROUND: Ferroptosis is a known crucial player in the development of cancers. However, the effect of single nucleotide polymorphisms (SNPs) in ferroptosis-related genes on survival in hepatitis B virus (HBV)-related hepatocellular carcinoma (HBV-HCC) patients remains unknown. METHODS: We used two-stage multivariable Cox proportional hazards regression analyses to estimate the associations between 48,774 SNPs in 480 ferroptosis-related genes and overall survival (OS) of 866 HBV-HCC patients. RESULTS: We identified that two potentially functional SNPs (CREB3 rs10814274 C > T and GALNT14 rs17010547 T > C) were significantly independently associated with the OS of HBV-HCC patients (CT + TT verse CC, hazards ratio (HR) = 0.77, 95% confidence interval (CI) = 0.67-0.89, p < 0.001 for rs10814274 and TC + CC verse TT, HR = 0.66, 95% CI = 0.53-0.82, p < 0.001 for rs17010547, respectively). Additional joint assessment of protective genotypes of these two SNPs showed that patients with 1-2 protective genotypes had a significantly better OS compared with those carrying 0 protective genotypes (HR = 0.56, 95% CI = 0.45-0.70, p < 0.001). Moreover, the expression quantitative trait loci (eQTL) analysis revealed that the survival-associated SNP rs10814274 T allele was significantly correlated with reduced CREB3 transcript levels in both normal liver tissues and whole blood cells, while the GALNT14 rs17010547 C allele had a significant correlation with increased GALNT14 transcript levels in whole blood cells. CONCLUSION: These results suggest that genetic variants of CREB3 and GALNT14 may affect the survival of HBV-HCC patients, likely via transcriptional regulation of respective genes. However, further studies are required to confirm these findings.

Is Alpelisib Plus Fulvestrant Cost-Effective for Treating PIK3CA-Mutation, HR+/HER2- Advanced Breast Cancer in the USA?

BACKGROUND AND OBJECTIVE: There is a considerable survival benefit of alpelisib in patients with PIK3CA-mutated, hormone receptor-positive and human epidermal growth factor receptor 2-negative advanced breast cancer (HR+/HER2- ABC), yet the financial burden may limit its use. Therefore, this study evaluated the cost-effectiveness of alpelisib plus fulvestrant in patients with PIK3CA-mutated, HR+/HER2- ABC in the USA. METHODS: A Markov model was constructed to simulate the progression of PIK3CA-mutated, HR+/HER2- ABC. Efficacy and safety data were derived from the SOLAR-1 trial. A parametric survival model was used to explore the long-term effect. From a US payer perspective, only direct medical costs were considered. The cost data were estimated based on local pricing and relevant literature. The health outcomes were expressed in quality-adjusted life years (QALYs). Model stability was assessed using one-way sensitivity analysis and probability sensitivity analysis. Subgroup analyses were performed to explore cost-effectiveness outcomes for patients with different clinical characteristics. RESULTS: The QALY increased by 0.28 with alpelisib plus fulvestrant with an additional cost of $94,345.87 compared with placebo plus fulvestrant, leading to an incremental cost-effectiveness ratio (ICER) of $340,153.30/QALY gained. Sensitivity analyses suggested that the model is most sensitive to the price of alpelisib. At a willingness-to-pay (WTP) threshold of $150,000/QALY, alpelisib plus fulvestrant was cost effective when the cost of alpelisib was less than $71 per 300 mg (36.5 % of the original price), whereas this cost would be less than $168 per 300 mg (86.5 % of the original price) at a WTP threshold of $300,000/QALY. In addition, alpelisib + fulvestrant was not cost effective in all subgroups compared with placebo + fulvestrant at the WTP threshold of $150,000/QALY. In contrast, at the WTP threshold of $300,000/QALY, alpelisib + fulvestrant was cost effective in nearly all subgroups except for endocrine-sensitive patients. CONCLUSION: At current drug prices, alpelisib plus fulvestrant is not cost effective for patients with PIK3CA-mutated, HR+/HER2- ABC from a US payer perspective. Given the considerable progression-free survival (PFS) and overall survival (OS) benefits observed with alpelisib in this setting, further discussion and negotiation of the price of alpelisib are warranted to provide more favorable economic outcomes and thereby increase the value of the alpelisib plus fulvestrant regimen in patients.

Potentially Functional Genetic Variants in the NRF2 Signaling Pathway Genes are Associated With HBV-related Hepatocellular Carcinoma Survival.

The nuclear factor E2-related factor 2 (NRF2) signaling pathway is one of the most important cell defense pathways. However, it is unclear whether genetic variants in NRF2 signaling pathway genes are associated with the survival of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). In the present study, we utilized a new hypothesis-driven approach based on biological pathways to investigate the associations between 17919 single nucleotide polymorphisms (SNPs) in 137 NRF2 signaling pathway genes and the overall survival (OS) of 866 patients with HBV-related HCC. As a result, two independent SNPs with potential biological function were identified to be significantly associated with HBV-related HCC OS: [SLC2A9 rs28643326 T>C: hazard ratio (HR) = 0.74, 95% confidence interval (95% CI) = 0.62-0.89, P < 0.001 and SLC5A10 rs2472711 G>T: HR = 0.81, 95% CI = 0.71-0.93, P = 0.003, respectively]. The expression quantitative trait loci (eQTL) analysis further revealed that the rs28643326 C allele was significantly associated with increased levels of SLC2A9 mRNA expression (P < 0.001), and higher mRNA expression levels of SLC2A9 in adjacent normal liver tissues were associated with better survival. Although the association between the rs2472711 T allele and the mRNA expression of SLC5A10 was not statistically significant (P = 0.200), the fact that rs2472711 is located at the DNase I hypersensitivity site and is a marker for promoter and enhancer histones also suggests that it may have the function of regulating its corresponding gene expression. In conclusion, genetic variants of NRF2 signaling pathway genes may serve as potential prognostic biomarkers for HBV-related HCC and also provide a solid basis for further mechanistic exploration.

Correlation between serum lipid levels and endocrine resistance in patients with ER-positive breast cancer.

Lipid metabolism may be involved in the development of endocrine drug resistance in ER-positive (ER+) breast cancer (BC). This study aimed to investigate the relationship between serum lipid levels, risk stratification of dyslipidemia, and endocrine resistance. We collected the data from 166 ER + breast cancer patients who received endocrine therapy (ET). 73 of 166 patients (44.0%)developed endocrine resistance. Univariate and multivariate COX regression were conducted to explore the potential factors affecting endocrine resistance in BC. The clinical T stage, mean serum lipid levels in ET progression-free-survival (total cholesterol, triglycerides, low-density lipoprotein cholesterol, apolipoprotein A, and triglycerides/high-density lipoprotein cholesterol) were correlated with endocrine resistance (R = 0.214, P = .006; R = 0.268, P < .001; R = 0.182, P = .019;R = 0.197, P = .011; R = 0.211, P = .006; R = 0.159, P < .041). Clinical stage, triglycerides (TG) in endocrine therapy progression-free-survival (ePFS) and low-density lipoprotein cholesterol (LDL-C) in ePFS were independent predictors of endocrine resistance (P < .05; OR = 1.406, CI 1.108-1.783, P < .05; OR = 1.309, CI 1.026-1.669, P < .05, respectively). Moreover, in clinical stage III, the ePFS was worse in patients with in the high-risk and extremely high-risk group the median ePFS time was 8.0 months (95% CI: 1.140-14.860, P < .05). Clinical stage, TG in ePFS and LDL-C in ePFS may act as a new predictive biomarker for endocrine resistance in BC. The lipid levels of BC patients should be closely monitored throughout the treatment process, and patients with dyslipidemia should receive treatment immediately.