Improving survival models in healthcare: a novel matching approach.

We present, to our knowledge, the first methodological study aimed at enhancing the prognostic power of Cox regression models, widely used in survival analysis, through optimized data selection. Our approach employs a novel two-stage mechanism: by framing the prognostic stratum matching problem intuitively, we select prognostically representative patient observations to create a more balanced training set. This enables the model to assign equal attention to distinct prognostic subgroups.

Hepatectomy versus systemic therapy for liver-limited BRAF V600E-mutated colorectal liver metastases: multicentre retrospective study.

Background: To date, only two studies have compared the outcomes of patients with liver-limited BRAF V600E-mutated colorectal liver metastases (CRLMs) managed with resection versus systemic therapy alone, and these have reported contradictory findings.

Methods: In this observational, international, multicentre study, patients with liver-limited BRAF V600E-mutated CRLMs treated with resection or systemic therapy alone were identified from institutional databases. Patterns of recurrence/progression and overall survival were compared using multivariable analyses of the entire cohort and a propensity score-matched cohort.

Germline variants in patients diagnosed with pediatric soft tissue sarcoma.

Background: While soft tissue sarcomas affect younger patients, few studies have assessed the distribution of underlying pathogenic germline variants.

Patients And Methods: We retrospectively identified all pediatric and young adult patients (0-22 years) at Haukeland University Hospital, Norway (1981-2019), through clinical and pathological records. We identified n = 46 eligible patients.

epialleleR: an R/Bioconductor package for sensitive allele-specific methylation analysis in NGS data.

Low-level mosaic epimutations within the BRCA1 gene promoter occur in 5-8% of healthy individuals and are associated with a significantly elevated risk of breast and ovarian cancer. Similar events may also affect other tumor suppressor genes, potentially being a significant contributor to cancer burden. While this opens a new area for translational research, detection of low-level mosaic epigenetic events requires highly sensitive and robust methodology for methylation analysis.

DNA methylation changes in response to neoadjuvant chemotherapy are associated with breast cancer survival.

Background: Locally advanced breast cancer is a heterogeneous disease with respect to response to neoadjuvant chemotherapy (NACT) and survival. It is currently not possible to accurately predict who will benefit from the specific types of NACT. DNA methylation is an epigenetic mechanism known to play an important role in regulating gene expression and may serve as a biomarker for treatment response and survival.

Using Artificial Intelligence to Find the Optimal Margin Width in Hepatectomy for Colorectal Cancer Liver Metastases.

Importance: In patients with resectable colorectal cancer liver metastases (CRLM), the choice of surgical technique and resection margin are the only variables that are under the surgeon's direct control and may influence oncologic outcomes. There is currently no consensus on the optimal margin width.

Objective: To determine the optimal margin width in CRLM by using artificial intelligence-based techniques developed by the Massachusetts Institute of Technology and to assess whether optimal margin width should be individualized based on patient characteristics.

Simultaneous Quantification of Aromatase Inhibitors and Estrogens in Postmenopausal Breast Cancer Patients.

Context: Currently there are no assays that can simultaneously quantify serum levels of the third-generation aromatase inhibitors (AIs): letrozole, anastrozole, and exemestane, and the ultra-low levels of estrogens in postmenopausal breast cancer patients on AI treatment. Such measurements may be pivotal for the determination of optimal and individualized treatment regimens. We aimed at developing a liquid chromatography-tandem mass spectrometry (MS/MS) method for simultaneous assessment of letrozole, anastrozole, exemestane, and 17-hydroxyexemestane as well as subpicomolar levels of estradiol and estrone.

Mutant KRAS as a prognostic biomarker after hepatectomy for rectal cancer metastases: Does the primary disease site matter?

Background: The prognostic implication of mutant KRAS (mKRAS) among patients with primary disease in the rectum remains unknown.

Methods: From 2000 to 2018, patients undergoing hepatectomy for colorectal liver metastases at 10 collaborating international institutions with documented KRAS status were surveyed.

Results: A total of 834 (65.

ramr: an R/Bioconductor package for detection of rare aberrantly methylated regions.

Motivation: With recent advances in the field of epigenetics, the focus is widening from large and frequent disease- or phenotype-related methylation signatures to rare alterations transmitted mitotically or transgenerationally (constitutional epimutations). Merging evidence indicate that such constitutional alterations, albeit occurring at a low mosaic level, may confer risk of disease later in life. Given their inherently low incidence rate and mosaic nature, there is a need for bioinformatic tools specifically designed to analyze such events.

Correction: The novel microRNAs hsa-miR-nov7 and hsa-miR-nov3 are over-expressed in locally advanced breast cancer.

[This corrects the article DOI: 10.1371/journal.pone.

Performance of two prognostic scores that incorporate genetic information to predict long-term outcomes following resection of colorectal cancer liver metastases: An external validation of the MD Anderson and JHH-MSK scores.

Introduction: Two novel clinical risk scores (CRS) that incorporate KRAS mutation status were developed: modified CRS (mCRS) and GAME score. However, they have not been tested in large national and international cohorts. The aim of this study was to validate the prognostic discrimination utility and determine the clinical usefulness of the two novel CRS.

The optimal cut-off values for tumor size, number of lesions, and CEA levels in patients with surgically treated colorectal cancer liver metastases: An international, multi-institutional study.

Background And Objectives: Despite the long-standing consensus on the importance of tumor size, tumor number and carcinoembryonic antigen (CEA) levels as predictors of long-term outcomes among patients with colorectal liver metastases (CRLM), optimal prognostic cut-offs for these variables have not been established.

Methods: Patients who underwent curative-intent resection of CRLM and had available data on at least one of the three variables of interest above were selected from a multi-institutional dataset of patients with known KRAS mutational status. The resulting cohort was randomly split into training and testing datasets and recursive partitioning analysis was employed to determine optimal cut-offs.

An Ultrasensitive Routine LC-MS/MS Method for Estradiol and Estrone in the Clinically Relevant Sub-Picomolar Range.

Background: Current analytical routine methods lack the sensitivity to monitor plasma estrogen levels in breast cancer patients treated with aromatase inhibitors. Such monitoring is warranted for premenopausal patients treated with an aromatase inhibitor and an LH-releasing hormone analogue in particular. Therefore, we aimed to develop a routine tandem mass spectroscopy combined with liquid chromatography (LC-MS/MS) method for estradiol (E2) and estrone (E1) for use in the sub-picomolar range.

The novel microRNAs hsa-miR-nov7 and hsa-miR-nov3 are over-expressed in locally advanced breast cancer.

miRNAs are an important class of small non-coding RNAs, which play a versatile role in gene regulation at the post-transcriptional level. Expression of miRNAs is often deregulated in human cancers. We analyzed small RNA massive parallel sequencing data from 50 locally advanced breast cancers aiming to identify novel breast cancer related miRNAs.

Golgi-Localized PAQR4 Mediates Antiapoptotic Ceramidase Activity in Breast Cancer.

The metabolic network of sphingolipids plays important roles in cancer biology. Prominent sphingolipids include ceramides and sphingosine-1-phosphate that regulate multiple aspects of growth, apoptosis, and cellular signaling. Although a significant number of enzymatic regulators of the sphingolipid pathway have been described in detail, many remained poorly characterized.

The Prognostic Impact of Primary Tumor Site Differs According to the KRAS Mutational Status: A Study By the International Genetic Consortium for Colorectal Liver Metastasis.

Objective: To examine the prognostic impact of tumor laterality in colon cancer liver metastases (CLM) after stratifying by Kirsten rat sarcoma 2 viral oncogene homolog (KRAS) mutational status.

Background: Although some studies have demonstrated that patients with CLM from a right sided (RS) primary cancer fare worse, others have found equivocal outcomes of patients with CLM with RS versus left-sided (LS) primary tumors. Importantly, recent evidence from unresectable metastatic CRC suggests that tumor laterality impacts prognosis only in those with wild-type tumors.

Prognostic Factors Change Over Time After Hepatectomy for Colorectal Liver Metastases: A Multi-institutional, International Analysis of 1099 Patients.

Objective: To evaluate the changing impact of genetic and clinicopathologic factors on conditional overall survival (CS) over time in patients with resectable colorectal liver metastasis.

Background: CS estimates account for the changing likelihood of survival over time and may reveal the changing impact of prognostic factors as time accrues from the date of surgery.

Methods: CS analysis was performed in 1099 patients of an international, multi-institutional cohort.

Human endotrophin as a driver of malignant tumor growth.

We have previously reported that the carboxy-terminal proteolytic cleavage product of the COL6α3 chain that we refer to as "endotrophin" has potent effects on transformed mammary ductal epithelial cells in rodents. Endotrophin (ETP) is abundantly expressed in adipose tissue. It is a chemoattractant for macrophages, exerts effects on endothelial cells and through epithelial-mesenchymal transition (EMT) enhances progression of tumor cells.

MYC-Induced miR-203b-3p and miR-203a-3p Control Bcl-xL Expression and Paclitaxel Sensitivity in Tumor Cells.

Taxanes are chemotherapeutic agents used in the treatment of solid tumors, particularly of breast, ovarian, and lung origin. However, patients show divergent therapy responses, and the molecular determinants of taxane sensitivity have remained elusive. Especially the signaling pathways that promote death of the taxane-treated cells are poorly characterized.