The Tumor Immune Microenvironment Drives Survival Outcomes and Therapeutic Response in an Integrated Molecular Analysis of Gastric Adenocarcinoma.

Purpose: We performed an integrated analysis of molecular classification systems proposed by The Cancer Genome Atlas (TCGA), the Asian Cancer Research Group (ACRG), and the tumor microenvironment (TME) score to identify which classification scheme(s) are most promising to pursue in subsequent translational investigations.

Experimental Design: Supervised machine learning classifiers were created using 10-fold nested cross-validation for TCGA, ACRG, and TME subtypes and applied to 2,202 patients with gastric cancer from 11 separate publicly available datasets. Overall survival was assessed with a multivariable Cox proportional hazards model.

A first-in-human phase I trial of daily oral zelenirstat, a N-myristoyltransferase inhibitor, in patients with advanced solid tumors and relapsed/refractory B-cell lymphomas.

Myristoylation, the N-terminal addition of the fatty acid myristate to proteins, regulates membrane-bound signal transduction pathways important in cancer cell biology. This modification is catalyzed by two N-myristoyltransferases, NMT1 and NMT2. Zelenirstat is a first-in-class potent oral small molecule inhibitor of both NMT1 and NMT2 proteins.

Feature-specific quantile normalization and feature-specific mean-variance normalization deliver robust bi-directional classification and feature selection performance between microarray and RNAseq data.

Background: Cross-platform normalization seeks to minimize technological bias between microarray and RNAseq whole-transcriptome data. Incorporating multiple gene expression platforms permits external validation of experimental findings, and augments training sets for machine learning models. Here, we compare the performance of Feature Specific Quantile Normalization (FSQN) to a previously used but unvalidated and uncharacterized method we label as Feature Specific Mean Variance Normalization (FSMVN).

Individual Survival Distributions Generated by Multi-Task Logistic Regression Yield a New Perspective on Molecular and Clinical Prognostic Factors in Gastric Adenocarcinoma.

Recent advances in our understanding of gastric cancer biology have prompted a shift towards more personalized therapy. However, results are based on population-based survival analyses, which evaluate the average survival effects of entire treatment groups or single prognostic variables. This study uses a personalized survival modelling approach called individual survival distributions (ISDs) with the multi-task logistic regression (MTLR) model to provide novel insight into personalized survival in gastric adenocarcinoma.

A phase 2, multicenter, open-label study of anti-LAG-3 ieramilimab in combination with anti-PD-1 spartalizumab in patients with advanced solid malignancies.

Ieramilimab, a humanized anti-LAG-3 monoclonal antibody, was well tolerated in combination with the anti-PD-1 antibody spartalizumab in a phase 1 study. This phase 2 study aimed to further investigate the efficacy and safety of combination treatment in patients with selected advanced (locally advanced or metastatic) solid malignancies. Eligible patients with non-small cell lung cancer (NSCLC), melanoma, renal cell carcinoma (RCC), mesothelioma, and triple-negative breast cancer (TNBC) were grouped depending on prior anti-PD-1/L1 therapy (anti-PD-1/L1 naive or anti-PD-1/L1 pretreated).

Increased CD4/CD8 Lymphocyte ratio predicts favourable neoadjuvant treatment response in gastric cancer: A prospective pilot study.

Background: Despite optimal neoadjuvant chemotherapy only 40% of gastric cancer tumours achieve complete or partial treatment response. In the absence of treatment response, neoadjuvant chemotherapy in gastric cancer contributes to adverse events without additional survival benefit compared to adjuvant treatment or surgery alone. Additional strategies and methods are required to optimize the allocation of existing treatment regimens such as FLOT chemotherapy (5-Fluorouracil, Leucovorin, Oxaliplatin and Docetaxel).

Murine and Human Gastric Tissue Establishes Organoids after 48 Hours of Cold Ischemia Time during Shipment.

An inadequate supply of fresh tissue is a major limitation of three-dimensional patient-derived gastric organoid research. We propose that tissue procurement for organoid culture could be increased by developing a cold storage shipment protocol for fresh surgical tissues. Sixty stomach specimens from C57BL/6J mice were resected, of which forty-five were stored in Hank's Balanced Salt (HBSS), University of Wisconsin (UW), or Histidine-Tryptophan-Ketoglutarate (HTK) solutions for subsequent organoid culture.

Real-world treatment patterns, clinical outcomes, and health care resource utilization in advanced unresectable hepatocellular carcinoma.

The incidence of advanced unresectable hepatocellular carcinoma (HCC) is increasing in developed countries and the prognosis of advanced HCC remains poor. Real-world evidence of treatment patterns and outcomes can highlight the unmet clinical need. We conducted a retrospective population-based cohort study of patients with advanced unresectable HCC diagnosed in Alberta, Canada (2008-2018) using electronic medical records and administrative claims data.

Novel, First-in-Human, Oral PCLX-001 Treatment in a Patient with Relapsed Diffuse Large B-Cell Lymphoma.

Patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) have limited treatment options, particularly if they are transplantation or chimeric antigen receptor (CAR) T-cell ineligible, and novel therapeutics are needed. An 86-year-old woman with relapsed DLBCL received a novel, first-in-class small molecule inhibitor of N-myristoyltransferase (NMT) as the initial patient on a phase I dose escalation trial. Daily oral administration of 20 mg PCLX-001 tablets produced a pharmacokinetic profile suitable for single daily dosing: rapid oral absorption, followed by an apparent elimination half-life of 16 h, without systemic accumulation of drug by day 15.

Changing Rates of Goals of Care Designations in Patients With Advanced Pancreatic Cancer During a Multifactorial Advanced Care Planning Initiative: A Real-World Evidence Study.

Purpose: Goals of care (GoC) designations are an important part of advanced care planning (ACP) for patients with incurable cancers. Studies of outpatient oncology records show that most patients do not have GoC documented. We performed a retrospective analysis of changes in GoC designations in patients with advanced pancreatic cancer in Northern Alberta, Canada, during a system-wide ACP quality improvement initiative.

Real-world patterns of adjuvant chemotherapy treatment for patients with resected pancreatic adenocarcinoma.

The aim of the study was to analyze the real-world treatment patterns of adjuvant chemotherapy administration among patients with resected pancreatic adenocarcinoma. Cases with non-metastatic pancreatic adenocarcinoma, diagnosed 2007-2018, treated with upfront surgical resection, and recorded within Alberta Cancer registry were accessed. Multivariable logistic regression analysis was conducted to evaluate factors predicting use of adjuvant chemotherapy.

A Population-Based Retrospective Study of Biliary Tract Cancers in Alberta, Canada.

Biliary tract cancers (BTC) are uncommon malignancies and are underrepresented in the literature. We performed a retrospective population-based review of adult patients with biopsy-confirmed BTC in Alberta from 2000 to 2015. Demographic data, risk factors, symptoms, treatment, and staging data were collected and analyzed.

Impact of dose-capping chemotherapy in concurrent chemoradiotherapy in rectal cancer patients.

Introduction: The study evaluated the effect of chemotherapy dose-capping on disease recurrence, toxicity and survival of rectal cancer patients treated with chemoradiotherapy (CRT).

Methods: 601 consecutive rectal cancer patients treated with concurrent CRT were retrospectively analysed. Dose-capped patients were defined as having a body surface area (BSA) ≥2.

Vitamin and herbal supplements' use among patients with advanced gastrointestinal cancers included in eight clinical trials.

Objective: To evaluate the patterns of vitamin and herbal supplement use among patients with advanced gastrointestinal (GI) cancers and the association of such behavior with the efficacy and toxicity of systemic anticancer treatment.

Methods: Project data sphere (PDS) was used to access de-identified datasets of eight clinical trials of advanced GI cancers. Multivariable logistic regression analysis was used to identify factors predicting the use of supplements.

Predictive and Prognostic Properties of Human Equilibrative Nucleoside Transporter 1 Expression in Gemcitabine-Treated Pancreatobiliary Cancer: A Meta-Analysis.

Purpose: Gemcitabine, the primary drug for the treatment of pancreatobiliary cancer (PBC), requires human equilibrative nucleoside transporter 1 (hENT1) to enter cells. High tumoral hENT1 expression has been linked with improved survival among patients with PBC treated with gemcitabine; however, this finding has been inconsistent, and studies used different expression assays.

Methods: Databases were reviewed for studies that examined hENT1 and clinical outcome in PBC.

Prolonged Response to Regorafenib in a Patient with Iodine Refractory Thyroid Cancer.

Thyroid cancer is the most common type of endocrine malignancy. Cornerstones of thyroid cancer treatment include surgery, radioactive iodine ablation, and thyroid stimulating hormone suppression. The National Comprehensive Cancer Network guidelines recommend two tyrosine kinase inhibitors for thyroid cancer patients who are non-responsive to iodine: sorafenib and lenvatinib.

Real-world Outcomes Among Patients Treated With Gemcitabine-based Therapy Post-FOLFIRINOX Failure in Advanced Pancreatic Cancer.

Objectives: Limited evidence exists for chemotherapy selection in advanced pancreatic cancer (APC) after first-line FOLFIRINOX. Second-line gemcitabine/nab-paclitaxel (GEMNAB) is publicly funded in the Canadian provinces of Alberta (AB) and Manitoba (MB), but not in British Columbia (BC). We compared population-based outcomes by region to examine the utility of second-line GEMNAB versus gemcitabine (GEM) alone.

Accuracy of Resting Energy Expenditure Predictive Equations in Patients With Cancer.

Background: Our purpose was to assess the accuracy of resting energy expenditure (REE) equations in patients with newly diagnosed stage I-IV non-small cell lung, rectal, colon, renal, or pancreatic cancer.

Methods: In this cross-sectional study, REE was measured using indirect calorimetry and compared with 23 equations. Agreement between measured and predicted REE was assessed via paired t-tests, Bland-Altman analysis, and percent of estimations ≤ 10% of measured values.

Effect of proximity to specialty care on outcomes for biliary cancers: a population-based retrospective cohort study.

Background: The management of biliary cancers is complex and requires a multidisciplinary approach. Because it is unknown how access to specialty care affects resource use and survival in patients with biliary cancer, we conducted a population-based study to understand the needs of these patients and the relation of geography to care delivery and clinical outcomes for biliary cancer in Alberta.

Methods: All patients with biliary cancer diagnosed in Alberta from Sept.

Safety and efficacy of nivolumab in combination with sunitinib or pazopanib in advanced or metastatic renal cell carcinoma: the CheckMate 016 study.

Background: Combination treatment with immune checkpoint inhibitors and antiangiogenic drugs has shown encouraging preliminary antitumor activity across various tumor types including advanced or metastatic renal cell carcinoma (aRCC). The open-label, parallel-cohort, dose-escalation, phase I CheckMate 016 study evaluated the efficacy and safety of nivolumab in combination with antiangiogenic tyrosine kinase inhibitors or ipilimumab. Long-term outcomes from this study for the combination of nivolumab plus sunitinib or pazopanib in aRCC are presented.

A multicentre, open-label phase II study of Irinotecan, capecitabine (Xeloda®), and Oxaliplatin (IXO) as first-line treatment in patients with metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma.

Purpose Chemotherapy remains the primary treatment for metastatic gastric/GEJ cancer but optimal agents and schedule remain controversial. This study examined the safety and efficacy of first-line Irinotecan, capecitabine (Xeloda®), and Oxaliplatin (IXO). Patients and Methods Eligible patients with HER2-unamplified/unknown, metastatic gastric/GEJ adenocarcinoma were treated with 21-day cycle IXO at dose level 1 (DL1: Day 1 O-100 mg/m & I-160 mg/m IV, Day 2-15 X-1900 mg/m/day PO divided doses) or modified IXO (mIXO): Day 1 O-85 mg/m & I-120 mg/m IV, Day 2-15 X-1425 mg/m/day PO divided doses).

Survival Impact of CAPOX Versus FOLFOX in the Adjuvant Treatment of Stage III Colon Cancer.

Background: Capecitabine and oxaliplatin (CAPOX) and folinic acid, fluorouracil, and oxaliplatin (FOLFOX) are both used in the adjuvant treatment of colon cancer, and while their efficacy is assumed to be similar, they have not been directly compared. We reviewed the toxicity profiles, relative dose intensity (RDI), and survival associated with these regimens across a multi-institutional cohort.

Patients And Methods: We identified 394 consecutively treated patients with stage III colon cancer who received an oxaliplatin-containing regimen.

Safety and Efficacy of Nivolumab in Combination With Ipilimumab in Metastatic Renal Cell Carcinoma: The CheckMate 016 Study.

Purpose Combination treatment with immune checkpoint inhibitors has shown enhanced antitumor activity compared with monotherapy in tumor types such as melanoma. The open-label, parallel-cohort, dose-escalation, phase I CheckMate 016 study evaluated the efficacy and safety of nivolumab plus ipilimumab in combination, and nivolumab plus a tyrosine kinase inhibitor in metastatic renal cell carcinoma (mRCC). Safety and efficacy results from the nivolumab plus ipilimumab arms of the study are presented.

Predictive Impact of Clinical Benefit in Chemotherapy-treated Advanced Pancreatic Cancer Patients in Northern Alberta.

Objectives: Patients with advanced pancreatic cancer (APC) have a poor prognosis and experience a large burden of disease-related symptoms. Despite advancements in the treatment of APC, survival is dismal and controlling disease-related symptoms and maintaining quality of life is paramount. We hypothesize that an improvement in disease-related symptoms, and therefore, a clinical benefit, while on chemotherapy is a predictive marker in APC.