Total neoadjuvant therapy in early-onset rectal cancer: A multicentre prospective cohort study.

Aim: The incidence of early-onset (age <50 years) rectal cancer (EORC) is rising globally, often presenting at an advanced stage. Total neoadjuvant therapy (TNT) is increasingly utilised in the management of advanced rectal cancers due to improved response and survival rates. However, it remains unclear whether EORC in an unscreened population responds similarly to TNT compared to average or late-onset (age ≥50 years) rectal cancer (AORC).

A Systematic Review and Meta-Analysis of 16S rRNA and Cancer Microbiome Atlas Datasets to Characterize Microbiota Signatures in Normal Breast, Mastitis, and Breast Cancer.

The breast tissue microbiome has been increasingly recognized as a potential contributor to breast cancer development and progression. However, inconsistencies in microbial composition across studies have hindered the identification of definitive microbial signatures. We conducted a systematic review and meta-analysis of 11 studies using 16S rRNA sequencing to characterize the bacterial microbiome in 1260 fresh breast tissue samples, including normal, mastitis-affected, benign, cancer-adjacent, and cancerous tissues.

Enhancement of Doxorubicin Efficacy by Bacopaside II in Triple-Negative Breast Cancer Cells.

Background: Triple-negative breast cancer (TNBC) is an aggressive subtype with limited treatment options and high resistance to chemotherapy. Doxorubicin is commonly used, but its efficacy is limited by variable sensitivity and resistance. Bacopaside II, a saponin compound, has shown anti-cancer potential.

Differential antiangiogenic and anticancer activities of the active metabolites of ginsenoside Rg3.

Background: Epimers of ginsenoside Rg3 (Rg3) have a low bioavailability and are prone to deglycosylation, which produces epimers of ginsenoside Rh2 (S-Rh2 and R-Rh2) and protopanaxadiol (S-PPD and R-PPD). The aim of this study was to compare the efficacy and potency of these molecules as anti-cancer agents.

Methods: Crystal violet staining was used to study the anti-proliferatory action of the molecules on a human epithelial breast cancer cell line, MDA-MB-231, and human umbilical vein endothelial cells (HUVEC) and compare their potency.

Association Between RAS/BRAF Mutations and Complete Response Following Total Neoadjuvant Therapy in Patients with Rectal Cancer: A Prospective Multicentered Study.

Background: The impact of RAS/BRAF mutation on primary response rates after total neoadjuvant therapy (TNT) in patients with advanced rectal cancer is unclear. The aim of this study was to assess complete response rates after TNT according to RAS/BRAF mutation status.

Methods: A prospective observational study was performed in patients with rectal cancer who underwent TNT with curative intent at three South Australian hospitals between 2019 and 2023.

What Therapeutic Biomarkers in Gastro-Esophageal Junction and Gastric Cancer Should a Pathologist Know About?

Malignancies of upper gastrointestinal tract are aggressive, and most locally advanced unresectable and metastatic cancers are managed by a combination of surgery and neoadjuvant/adjuvant chemotherapy and radiotherapy. Current therapeutic recommendations include targeted therapies based on biomarker expression of an individual tumor. All G/gastro-esophageal junction (GEJ) cancers should be tested for HER2 status as a reflex test at the time of diagnosis.

Plasma Cetuximab Concentrations Correlate With Survival in Patients With Advanced KRAS Wild Type Colorectal Cancer.

Background: Cetuximab is a standard of care therapy for patients with RAS wild-type (WT) advanced colorectal cancer. Limited data suggest a wide variation in cetuximab plasma concentrations after standard dosing regimens. We correlated cetuximab plasma concentrations with survival and toxicity.

Can sarcopenia predict complete response after total neoadjuvant therapy in advanced rectal cancer? A multicentre observational cohort study.

Background: The association between sarcopenia and response to neoadjuvant treatment remains unclear. This study investigates sarcopenia as a predictor of overall complete response (oCR) after Total Neoadjuvant Therapy (TNT) for advanced rectal cancer.

Method: A prospective observational study was performed of patients with rectal cancer undergoing TNT at three South Australian hospitals between 2019 and 2022.

Australasian Consensus Statement on the Identification, Prevention, and Management of Hormonal Crises in Patients with Neuroendocrine Neoplasms Undergoing Peptide Receptor Radionuclide Therapy.

Hormonal crises are a rare but increasingly recognized phenomenon following peptide receptor radionuclide therapy (PRRT) in patients with neuroendocrine neoplasms (NENs). Due to the paucity of published studies, approaches to the identification, prevention, and management of risk factors are inconsistent between different institutions. This consensus statement aimed to provide guidance for NEN patients undergoing PRRT.

Phase I Trial of nab-Paclitaxel Administered Concurrently With Radiotherapy in Patients With Locally Advanced Inoperable Pancreatic Adenocarcinoma.

Objectives: Nab-paclitaxel has radiosensitizing antitumor efficacy in pancreatic cancer. We aimed to establish maximum tolerated dose (MTD) of nab-paclitaxel with radiotherapy in unresectable locally advanced pancreatic cancer.

Methods: In a phase I dose escalation trial patients received weekly nab-paclitaxel for 6 weeks with external beam radiotherapy (EBRT).

Young-Onset Gastrointestinal Adenocarcinoma Incidence and Survival Trends in the Northern Territory, Australia, with Emphasis on Indigenous Peoples.

Background and Aims: A concerning rise in incidence of young-onset cancers globally led to the examination of trends in incidence and survival of gastrointestinal (GI) adenocarcinomas in the Northern Territory (NT), Australia, over a 28-year period, with a special emphasis on Indigenous peoples. Methods: This cross-sectional analysis of a prospective longitudinal database, NT Cancer Registry (1990−2017), includes all reported cases of GI (oesophagus, gastric, small intestinal, pancreas, colon, and rectum) adenocarcinomas. Poisson regression was used to estimate incidence ratio ratios, and survival was modelled using Cox proportional hazard models separately for people aged 18−50 years and >50 years.

Accuracy and Completeness of Intermediate-Level Nursery Descriptions on Hospital Websites.

Importance: Birth at hospitals with an appropriate level of neonatal intensive care units is associated with better neonatal outcomes. The primary sources for information about hospital neonatal unit levels for prospective parents, referring physicians, and the public are hospital websites, but the accuracy of neonatal unit capacity is unclear.

Objective: To determine if hospital websites accurately report the capabilities of intermediate (ie, level II) units, which are intended for care of newborns with low to moderate illness levels or the stabilization of newborns prior to transfer.

VEGF-A, VEGFR1 and VEGFR2 single nucleotide polymorphisms and outcomes from the AGITG MAX trial of capecitabine, bevacizumab and mitomycin C in metastatic colorectal cancer.

The phase III MAX clinical trial randomised patients with metastatic colorectal cancer (mCRC) to receive first-line capecitabine chemotherapy alone or in combination with the anti-VEGF-A antibody bevacizumab (± mitomycin C). We utilised this cohort to examine whether single nucleotide polymorphisms (SNPs) in VEGF-A, VEGFR1, and VEGFR2 are predictive of efficacy outcomes with bevacizumab or the development of hypertension. Genomic DNA extracted from archival FFPE tissue for 325 patients (69% of the MAX trial population) was used to genotype 16 candidate SNPs in VEGF-A, VEGFR1, and VEGFR2, which were analysed for associations with efficacy outcomes and hypertension.

Can pressurised intraperitoneal aerosol chemotherapy with oxaliplatin (PIPAC-O+) be added to standard treatment for resectable high-risk gastric cancer patients? A study protocol.

Objectives: Gastric cancer remains one of the most fatal cancers, despite an intensive treatment regime of chemotherapy-surgery-chemotherapy. Peritoneal metastatic disease is commonly diagnosed post treatment regime and once established, patients are likely to die in 3-9 months. Systemic chemotherapy does not increase survival for these patients due to the poor vascularisation of this area.

Sotorasib for previously treated colorectal cancers with KRAS mutation (CodeBreaK100): a prespecified analysis of a single-arm, phase 2 trial.

Background: Sotorasib, a specific, irreversible KRAS protein inhibitor, has shown monotherapy clinical activity in KRAS-mutated solid tumours, including colorectal cancer, in the CodeBreaK100 phase 1 trial. We aimed to investigate the activity and safety of sotorasib in phase 2 of the trial.

Methods: In this single-arm, phase 2 trial, adult patients with KRAS-mutated advanced solid tumours were enrolled, from 59 medical centres in 11 countries, if they were aged 18 years or older, had at least one measurable lesion according to the Response Evaluation Criteria in Solid Tumours (RECIST) version 1.

Prognostic Differences of RAS Mutations: Results from the South Australian Metastatic Colorectal Registry.

Background: Effective targeting of RAS mutations has proven elusive until recently. Novel agents directly targeting KRAS G12C have shown promise in early-phase clinical trials that included patients with metastatic colorectal cancer. Prior reports have suggested that G12C mutation may be predictive of poor outcome.

Survey of germline variants in cancer-associated genes in young adults with colorectal cancer.

Colorectal cancer (CRC) incidence in young adults is rising. Identifying genetic risk factors is fundamental for the clinical management of patients and their families. This study aimed to identify clinically significant germline variants among young adults with CRC.

Update on optimal management for pancreatic cancer: expert perspectives from members of the Australasian Gastrointestinal Trials Group (AGITG) with invited international faculty.

Introduction: Pancreatic cancer remains a challenging malignancy due to the high proportion of patients diagnosed at advanced stages and the limited treatment options. This article discusses recent evidence in the management of both localized and advanced pancreatic cancer and offers an expert opinion on current best practice.

Areas Covered: For patients with localized disease, the evidence for adjuvant chemotherapy is discussed as well as emerging neoadjuvant approaches for resectable, borderline resectable, and locally advanced disease.

Ovarian cycle stage critically affects 21-gene recurrence scores in Mmtv-Pymt mouse mammary tumours.

Background: The Oncotype DX 21-gene Recurrence Score is predictive of adjuvant chemotherapy benefit for women with early-stage, estrogen receptor (ER)-positive, HER2-negative breast cancer. In premenopausal women, fluctuations in estrogen and progesterone during the menstrual cycle impact gene expression in hormone-responsive cancers. However, the extent to which menstrual cycling affects the Oncotype DX 21-gene signature remains unclear.

Sotorasib for Lung Cancers with p.G12C Mutation.

Background: Sotorasib showed anticancer activity in patients with p.G12C-mutated advanced solid tumors in a phase 1 study, and particularly promising anticancer activity was observed in a subgroup of patients with non-small-cell lung cancer (NSCLC).

Methods: In a single-group, phase 2 trial, we investigated the activity of sotorasib, administered orally at a dose of 960 mg once daily, in patients with p.

In Vitro Synergistic Inhibition of HT-29 Proliferation and 2H-11 and HUVEC Tubulogenesis by Bacopaside I and II Is Associated with Ca Flux and Loss of Plasma Membrane Integrity.

We previously showed how triterpene saponin bacopaside (bac) II, purified from the medicinal herb , induced cell death in colorectal cancer cell lines and reduced endothelial cell migration and tube formation, and further demonstrated a synergistic effect of a combination of bac I and bac II on the inhibition of breast cancer cell line growth. Here, we assessed the effects of bac I and II on the colorectal cancer HT-29 cell line, and mouse (2H-11) and human umbilical vein endothelial cell (HUVEC) lines, measuring outcomes including cell viability, proliferation, migration, tube formation, apoptosis, cytosolic Ca levels and plasma membrane integrity. Combined bac I and II, each applied at concentrations below IC values, caused a synergistic reduction of the viability and proliferation of HT-29 and endothelial cells, and impaired the migration of HT-29 and tube formation of endothelial cells.