An updated systematic review of the cost-effectiveness of therapies for metastatic breast cancer

Abstract

Purpose

The goal of this systematic review is to provide an update to the review by Pouwels et al. by conducting a systematic review and an assessment of the reporting quality of the economic analyses conducted since 2014.

Methods

This systematic review identified published articles focused on metastatic breast cancer treatment using the Medline/PubMed and Scopus databases and the following search criteria: (((cost effectiveness[MeSH Terms]) OR (cost effectiveness) OR (cost-effectiveness) OR (cost utility) OR (cost–utility) OR (economic evaluation)) AND (("metastatic breast cancer") OR ("advanced breast cancer"))). The reporting quality of the included articles was evaluated using the International Society of Pharmacoeconomics and Outcomes Research (ISPOR) Consolidated Health Economic Evaluation Reporting Standards (CHEERS) checklist.

Results

Of the 256 identified articles, 67 of the articles were published after October 2014 when the prior systematic review stopped its assessment (Pouwels et al. in Breast Cancer Res Treat 165:485–498, 2017). From the 67 articles, we narrowed down to include 17 original health economic analyses specific to metastatic or advanced breast cancer. These articles were diverse with respect to methods employed and interventions included.

Conclusion

Although each of the articles contributed their own analytic strengths and limitations, the overall quality of the studies was moderate. The review demonstrated that the vast majority of the reported incremental cost-effectiveness ratios exceeded the typically employed willingness to pay thresholds used in each country of analysis. Only three of the reviewed articles studied chemotherapies rather than treatments targeting either HER2 or hormone receptors, demonstrating a gap in the literature.

http://bit.ly/2GM8itY

Patient-centered simulations to assess the usefulness of the 70-gene signature for adjuvant chemotherapy administration in early-stage breast cancer

Abstract

Purpose

From the MINDACT trial, Cardoso et al. did not demonstrate a significant efficacy for adjuvant chemotherapy (CT) for women with early-stage breast cancer presenting high clinical and low genomic risks. Our objective was to assess the usefulness of the 70-gene signature in this population by using an alternative endpoint: the number of Quality-Adjusted Life-Years (QALYs), i.e., a synthetic measure of quantity and quality of life.

Methods

Based on the results of the MINDACT trial, we simulated a randomized clinical trial consisting of 1497 women with early-stage breast cancer presenting high clinical and low genomic risks. The individual preferences for the different health states and corresponding decrements were obtained from the literature.

Results

The gain in terms of 5-year disease-free survival was 2.8% (95% CI from − 0.1 to 5.7%, from 90.4% for women without CT to 93.3% for women with CT). In contrast, due to the associated side effects, CT significantly reduced the number of QALYs by 62 days (95% CI from 55 to 70 days, from 4.13 years for women without CT to 3.96 years for women with CT).

Conclusion

Our results support the conclusions published by Cardoso et al. by providing additional evidence that the 70-gene signature can be used to avoid overtreatment by CT for women with high clinical risk but low genomic risk.

http://bit.ly/2RpoLbH

Association between breast cancer risk factors and molecular type in postmenopausal patients with hormone receptor-positive early breast cancer

Abstract

Purpose

Evidence shows that genetic and non-genetic risk factors for breast cancer (BC) differ relative to the molecular subtype. This analysis aimed to investigate associations between epidemiological risk factors and immunohistochemical subtypes in a cohort of postmenopausal, hormone receptor-positive BC patients.

Methods

The prospective, single-arm, multicenter phase IV PreFace study (Evaluation of Predictive Factors Regarding the Effectivity of Aromatase Inhibitor Therapy) included 3529 postmenopausal patients with hormone receptor-positive early BC. Data on their epidemiological risk factors were obtained from patients' diaries and their medical histories. Data on estrogen receptor, progesterone receptor, and HER2 receptor status were obtained from pathology reports. Patients with incomplete information were excluded. Data were analyzed using conditional inference regression analysis, analysis of variance, and the chi-squared test.

Results

In a cohort of 3392 patients, the strongest association with the molecular subtypes of BC was found for hormone replacement therapy (HRT) before diagnosis of early BC. The analysis showed that patients who took HRT at diagnosis had luminal A-like BC more often (83.7%) than those who had never taken HRT or had stopped taking it (75.5%). Luminal B-like BC and HER2-positive BC were diagnosed more often in women who had never taken HRT or had stopped taking it (13.3% and 11.2%, respectively) than in women who were taking HRT at diagnosis of BC (8.3% and 8.0%, respectively).

Conclusions

This analysis shows an association between HRT and the distribution of molecular subtypes of BC. However, no associations between other factors (e.g., age at diagnosis, body mass index, smoking status, age at menopause, number of deliveries, age at first delivery, breastfeeding history, or family history) were noted.

http://bit.ly/2GNYnnP

Identification of the Potential Metabolic Pathways Involved in the Hepatic Tumorigenesis of Rat Diethylnitrosamine-Induced Hepatocellular Carcinoma via 1H NMR-Based Metabolomic Analysis

The systemic investigation of the metabolic pathways associated with the hepatic tumorigenesis is important to discover novel biomarkers and identify the potential pathogenesis. Here, the 1H nuclear magnetic resonance- (1H NMR-) based metabolomic analysis was used to monitor the whole process of rat diethylnitrosamine-induced HCC. Intraperitoneal administration of diethylnitrosamine (DEN) was used to induce primary HCCs in male Sprague-Dawley rats. Magnetic resonance imaging (MRI) examinations were performed to follow the tumor formation and growth in the liver and H&E staining was used to confirm MR imaging findings. The rats with DEN treatment and control rats without DEN were euthanized at the time points of 3, 8, and 15 weeks after the start of modeling. 1H NMR-based metabolomic analysis was used to explore hepatic metabolite changes and certify key metabolic pathways in the process of tumor tumorigenesis. Our MRI results depicted the formation of HCC nodules in ten rats 14 weeks after DEN injection which were confirmed by histology. Twenty-four different metabolites were identified and quantified by 1H NMR spectroscopy; OPLS-DA models and corresponding VIP plots analysis further identified ten metabolites associated with the abnormal metabolism. The aberrant glucose, lipid, and glutathione-glutamine-glutamate metabolism could be detected involving in the process of hepatic tumorigenesis, which provides an important evidence for the in-depth study of subsequent molecular mechanisms, especially the glutathione-glutamine-glutamate metabolism.

http://bit.ly/2RuIqqE

Automated Pulmonary Nodule Classification in Computed Tomography Images Using a Deep Convolutional Neural Network Trained by Generative Adversarial Networks

Lung cancer is a leading cause of death worldwide. Although computed tomography (CT) examinations are frequently used for lung cancer diagnosis, it can be difficult to distinguish between benign and malignant pulmonary nodules on the basis of CT images alone. Therefore, a bronchoscopic biopsy may be conducted if malignancy is suspected following CT examinations. However, biopsies are highly invasive, and patients with benign nodules may undergo many unnecessary biopsies. To prevent this, an imaging diagnosis with high classification accuracy is essential. In this study, we investigate the automated classification of pulmonary nodules in CT images using a deep convolutional neural network (DCNN). We use generative adversarial networks (GANs) to generate additional images when only small amounts of data are available, which is a common problem in medical research, and evaluate whether the classification accuracy is improved by generating a large amount of new pulmonary nodule images using the GAN. Using the proposed method, CT images of 60 cases with confirmed pathological diagnosis by biopsy are analyzed. The benign nodules assessed in this study are difficult for radiologists to differentiate because they cannot be rejected as being malignant. A volume of interest centered on the pulmonary nodule is extracted from the CT images, and further images are created using axial sections and augmented data. The DCNN is trained using nodule images generated by the GAN and then fine-tuned using the actual nodule images to allow the DCNN to distinguish between benign and malignant nodules. This pretraining and fine-tuning process makes it possible to distinguish 66.7% of benign nodules and 93.9% of malignant nodules. These results indicate that the proposed method improves the classification accuracy by approximately 20% in comparison with training using only the original images.

http://bit.ly/2GQx5gq

Systematic review and meta‐analysis: non‐alcoholic fatty liver disease is associated with a history of osteoporotic fractures but not with low bone mineral density

Summary

Background

Several studies have explored the effect of non‐alcoholic fatty liver disease (NAFLD) on bone mineral density (BMD) and risk of osteoporotic fractures in adults. However, the extent to which NAFLD adversely affects bone health remains uncertain.

Aim

To provide a quantitative estimation of the magnitude of the association of NAFLD with BMD or history of osteoporotic fractures in adults.

Methods

We searched PubMed, Web of Science, and Scopus using predefined keywords to identify all observational studies, published up to 31 August 2018, in which NAFLD was diagnosed by imaging or histology; BMD was measured by dual energy X‐ray absorptiometry; and a self‐reported history of osteoporotic fractures was collected with interviewer‐assisted questionnaires. Data from selected studies were extracted, and meta‐analysis was performed using random‐effects modelling.

Results

Twelve cross‐sectional or case‐control studies with aggregate data on 30 041 adults of predominantly Asian ethnicity (30% with NAFLD) were included in the final analysis. No significant differences in BMD at different skeletal sites (whole body, lumbar spine, or femur) were observed between individuals with and without NAFLD. Conversely, NAFLD was associated with increased odds of osteoporotic fractures, especially in older Chinese men (n = 2 studies; random‐effects odds ratio 2.10, 95% CI 1.36‐3.25; I ² = 0%). Sensitivity analyses did not alter these findings. The funnel plot and Egger test did not reveal significant publication bias.

Conclusions

This meta‐analysis suggests that imaging‐defined or biopsy‐proven NAFLD is associated with a self‐reported history of osteoporotic fractures (principally in Chinese men), but not with low BMD, in middle‐aged and elderly individuals.

http://bit.ly/2QhIpSa

Community-dwelling adults with a history of falling report lower perceived postural stability during a foam eyes closed test than non-fallers

Abstract

Perceived postural stability has been reported to decrease as sway area increases on firm surfaces. However, changes in perceived stability under increasingly challenging conditions (e.g., removal of sensory inputs) and the relationship with sway area are not well characterized. Moreover, whether perceived stability varies as a function of age or history of falls is unknown. Here we investigate how perceived postural stability is related to sway area and whether this relationship varies as a function of age and fall history while vision and proprioceptive information are manipulated. Sway area was measured in 427 participants from the Baltimore Longitudinal Study of Aging while standing with eyes open and eyes closed on the floor and a foam cushion. Participants rated their stability [0 (completely unstable) to 10 (completely stable)] after each condition, and reported whether they had fallen in the past year. Perceived stability was negatively associated with sway area (cm²) such that individuals who swayed more felt less stable across all conditions (β = − 0.53, p < 0.001). Perceived stability decreased with increasing age (β = − 0.019, p < 0.001), independent of sway area. Fallers had a greater decline in perceived stability across conditions (F = 2.76, p = 0.042) compared to non-fallers, independent of sway area. Perceived postural stability declined as sway area increased during a multisensory balance test. A history of falling negatively impacts perceived postural stability when vision and proprioception are simultaneously challenged. Perceived postural stability may provide additional information useful for identifying individuals at risk of falls.

http://bit.ly/2F1mT3c