Variant Classification Discordance: Contributing Factors and Predictive Models.

An ever-growing catalog of human variants is hosted in the ClinVar database. In this database, submissions on a variant are combined into a multisubmitter record; and in the case of discordance in variant classification between submitters, the record is labeled as conflicting. The current study used ClinVar data to identify characteristics that would make variants more likely to be associated with the conflict class of variants.

Future Role of Health Technology Assessment for Genomic Medicine in Oncology: A Canadian Laboratory Perspective.

Genome-based testing in oncology is a rapidly expanding area of health care that is the basis of the emerging area of precision medicine. The efficient and considered adoption of novel genomic medicine testing is hampered in Canada by the fragmented nature of health care oversight as well as by lack of clear and transparent processes to support rapid evaluation, assessment, and implementation of genomic tests. This article provides an overview of some key barriers and proposes approaches to addressing these challenges as a potential pathway to developing a national approach to genomic medicine in oncology.

Folding correctors can restore CFTR posttranslational folding landscape by allosteric domain-domain coupling.

The folding/misfolding and pharmacological rescue of multidomain ATP-binding cassette (ABC) C-subfamily transporters, essential for organismal health, remain incompletely understood. The ABCC transporters core consists of two nucleotide binding domains (NBD1,2) and transmembrane domains (TMD1,2). Using molecular dynamic simulations, biochemical and hydrogen deuterium exchange approaches, we show that the mutational uncoupling or stabilization of NBD1-TMD1/2 interfaces can compromise or facilitate the CFTR(ABCC7)-, MRP1(ABCC1)-, and ABCC6-transporters posttranslational coupled domain-folding in the endoplasmic reticulum.

Breast Cancer-Related Financial Toxicity in Sri Lanka: Insights From a Lower Middle-Income Country With Free Universal Public Healthcare.

Financial toxicity (FT) describes either objective or perceived excess financial strain due to a cancer diagnosis on the well-being of patients, families, and society. The consequences of FT have been shown to span countries of varied economic tiers and diverse healthcare models. This study attempts to describe FT and its effects in a lower- to middle-income country delivering predominantly public nonfee-levying healthcare.

Screening and Management Recommendations for Type 2 Diabetes in Women With Breast Cancer.

Breast cancer increases the risk of type 2 diabetes 1.07- to 4.27-fold, depending on patient and treatment characteristics, such as postmenopausal status, hormone therapy, and treatment with adjuvant chemotherapy.

Randomised controlled trials evaluating anticancer therapies in haematological cancers: an overview of global research activity.

Background: Design, results, and interpretation of oncology randomised controlled trials (RCTs) have changed substantially over the past decade. In this study, we describe all RCTs evaluating anticancer therapies in haematological cancers published globally during 2014-2017 with comparisons with solid tumours RCTs.

Methods: A PubMed literature search identified all phase 3 RCTs of anticancer therapy for haematological cancers and solid tumours published globally during 2014-2017.

The Choosing Wisely Oncology Canada Cancer List: An Update.

Background: Choosing Wisely (CW) Canada is a national campaign to identify unnecessary or harmful services that are frequently used in Canada. The original CW Oncology Canada Cancer list was developed in 2014. A CW Oncology Canada working group was established to review new evidence and guidelines and to update the current CW Oncology Canada Cancer List.

Allocation of authorship and patient enrollment among global clinical trials in oncology.

Background: Oncology randomized controlled trials (RCTs) are increasingly global in scope. Whether authorship is equitably shared between investigators from high-income countries (HIC) and low-middle/upper-middle incomes countries (LMIC/UMIC) is not well described. The authors conducted this study to understand the allocation of authorship and patient enrollment across all oncology RCTs conducted globally.

Malignant Superior Vena Cava Syndrome: A Scoping Review.

Malignant superior vena cava syndrome (SVCS) is a clinical problem that results from the obstruction of blood flow in the superior vena cava by an underlying malignancy. This may occur due to external compression, neoplastic invasion of the vessel wall, or internal obstruction with bland or tumor thrombus. Although symptoms are typically mild, SVCS can cause neurologic, hemodynamic, and respiratory compromise.

Multimodal Biomarkers That Predict the Presence of Gleason Pattern 4: Potential Impact for Active Surveillance.

Purpose: Latent grade group ≥2 prostate cancer can impact the performance of active surveillance protocols. To date, molecular biomarkers for active surveillance have relied solely on RNA or protein. We trained and independently validated multimodal (mRNA abundance, DNA methylation, and/or DNA copy number) biomarkers that more accurately separate grade group 1 from grade group ≥2 cancers.

Cost-effectiveness of second-line ipilimumab for metastatic melanoma: A real-world population-based cohort study of resource utilization.

Background: The efficacy-effectiveness gap between randomized trial and real-world evidence regarding the clinical benefit of ipilimumab for metastatic melanoma (MM) has been well characterized by previous literature, consistent with initial concerns raised by health technology assessment agencies (HTAs). As these differences can significantly impact cost-effectiveness, it is critical to assess the real-world cost-effectiveness of second-line ipilimumab versus non-ipilimumab treatments for MM.

Methods: This was a population-based retrospective cohort study of patients who received second-line non-ipilimumab therapies between 2008 and 2012 versus ipilimumab treatment between 2012 and 2015 (after public reimbursement) for MM in Ontario.

Media coverage of cancer therapeutics: A review of literature.

Background: Information and stories about cancer treatment are increasingly available to patients and the general public through lay media, websites, blogs and social media. While these resources may be helpful to supplement information provided during physician-patient discussions, there is growing concern about the extent to which media reports accurately reflect advances in cancer care. This review aimed to understand the landscape of published research which has described media coverage of cancer treatments.