Exploring the association between Cultural and Linguistic Diversity (CALD) on treatment and outcomes in pancreatic cancer: an analysis of PURPLE real-world registry data from an Australian population.

Background: Culturally and/or linguistically diverse (CALD) patients have unique health needs and may face multiple barriers when accessing healthcare. This study explored the association between of CALD status on treatment received and outcomes for patients with pancreatic cancer.

Methods: Data were extracted from the multi-site PURPLE Pancreatic cancer Translational Registry between January 2016 and April 2023.

Role of Neoadjuvant Immune Checkpoint Inhibitors in Locally Advanced Rectal Cancer: A Systematic Review of Currently Available Studies.

Background: Over the last few decades, the standard of care for locally advanced rectal cancer, involving neoadjuvant chemoradiation followed by surgery, is associated with a pathological complete response rate of only 10-20%. Combination therapy with immune checkpoint inhibitors may improve treatment response.

Objective: This systematic review examines the current evidence regarding neoadjuvant immune checkpoint inhibitors in locally advanced rectal cancer in terms of treatment efficacy, impact on surgical outcomes, and potential adverse events.

Unmasking insulinoma following commencement of somatostatin analogues in malignant neuroendocrine tumours.

Objective: Somatostatin analogues (SSA) are used in the management of patients with metastatic gastroenteropancreatic neuroendocrine tumours (GEP-NET) to control hormone secretion and tumour growth. SSA can paradoxically worsen or unmask hypoglycaemia in patients with insulinoma by inhibiting counter-regulatory hormones such as glucagon and growth hormone.

Design And Methods: We present two cases of SSA use in patients with initially presumed non-functioning GEP-NET unmasking insulinoma.

Nivolumab and Ipilimumab Combination Treatment in Advanced Ovarian and Endometrial Clear Cell Cancers: A Nonrandomized Clinical Trial.

Importance: Gynecological clear cell cancers (CCCs) are aggressive malignant neoplasms with low response rate to chemotherapy. The treatment of patients with metastatic disease remains an area of significant unmet need.

Objective: To evaluate the efficacy of combined anti-programmed cell death 1 protein (PD-1)/cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) blockade using nivolumab and ipilimumab in advanced gynecological CCCs.

Skeletal muscle and visceral fat density are predictive imaging biomarkers for overall survival in patients with pancreatic adenocarcinoma: A retrospective multicenter analysis.

Rationale And Objectives: Utilizing a fully automated AI-generated body composition analysis (BCA) from PDAC staging computed tomography (CT) imaging to discover predictive imaging biomarkers for overall survival (OS).

Material And Methods: Routine PDAC staging CTs (07/2012-12/2020) and clinicopathological data (Eastern Cooperative Oncology Group (ECOG) performance status, resection status, chemotherapy, age, CA19-9, Charlson Comorbidity Index, BMI) from four tertiary centers were collected retrospectively. Using a 3:1 split (training:holdout), we fitted Cox regression OS using every possible combination of 7 clinicopathological and 9 BCA variables: skeletal muscle index (SMI), area and density of total muscle compartment (TMC), skeletal muscle (SM), subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT) and selected the combination with the lowest information complexity (ICOMP).

The Ave-Rec Trial: Phase II Trial of PDL1/PD1 Blockade with Avelumab after Chemoradiotherapy for Locally Advanced Resectable T3B-4/N1-2 Rectal Cancer.

Purpose: Long-course chemoradiotherapy (LCCRT) for locally advanced rectal cancer (LARC) achieves a pathologic complete response (pCR) in approximately 10% to 30% of cases. Radiotherapy exerts both immunostimulatory and immunosuppressive effects. Inhibition of PDL1 may augment the immunostimulatory response.

Neoadjuvant intraperitoneal chemotherapy in high-risk and cytology positive gastric cancer: a systematic review.

Background: Gastric cancer has a risk of early transcoelomic spread. Despite perioperative chemotherapy and surgery, peritoneal recurrence is a frequent contributor to mortality. The addition of neoadjuvant normothermic intraperitoneal chemotherapy (IPC) allows early treatment of microscopic disease.

Peptide receptor radionuclide therapy in malignant insulinoma.

The management of malignant insulinoma (MI) presents dual management challenges of hypoglycaemia and tumour control. This study aims to analyse long-term outcomes of PRRT for the treatment of MI. We retrospectively reviewed consecutive patients with MI treated with [177Lu]Lu-DOTATATE (LuTATE) at two Australian NET centres between 2004 and 2022.

Integration of multi-omics and single-cell transcriptome reveals mitochondrial outer membrane protein-2 (MTX-2) as a prognostic biomarker and characterizes ubiquinone metabolism in lung adenocarcinoma.

Lung adenocarcinoma (LUAD) remains to be one of the most prevalent and highly invasive forms of cancer. Mitochondrial outer membrane protein-2 or Metaxin-2 (MTX2), a key regulator of mitochondrial function, has been linked to cellular bioenergetics and stress response mechanisms. However, its roles in the progression and prognosis of LUAD remain largely unexplored.

A methodology for determining dosing recommendations for anticancer drugs in patients with reduced kidney function.

Unlabelled: Reduced kidney function (or kidney dysfunction) is commonly an exclusion criterion for randomised controlled trials (RCTs) in cancer. Consequently, high quality evidence for anticancer drug dosing in reduced kidney function is limited and no internationally agreed guidelines exist to inform prescribing decisions in this population. A methodology for guideline development was applied which did not require availability of RCTs but used critical appraisal of existing observational literature and group consensus.

Aligning kidney function assessment in patients with cancer to global practices in internal medicine.

Unlabelled: The kidney disease: Improving Global Outcomes (KDIGO) guideline recommends assessing kidney function using glomerular filtration rate (GFR) either through direct measurement or through estimation (eGFR) and describes a standardised classification of reduced kidney function. KDIGO guidelines have been adopted by most internal medicine specialities for the assessment and classification of kidney function, but not by cancer medicine. The development of the International Consensus Guideline on Anticancer Drug Dosing in Kidney Dysfunction (ADDIKD) aims to overcome the perceived challenges with KDIGO recommendations by describing their utility in patients with cancer.

Integrating International Consensus Guidelines for Anticancer Drug Dosing in Kidney Dysfunction (ADDIKD) into everyday practice.

Unlabelled: Part 2 of the International Consensus Guideline on Anticancer Drug Dosing in Kidney Dysfunction (ADDIKD) offers drug-specific consensus recommendations based on both evidence and practical experience. These recommendations build upon the kidney function assessment and classification guidelines established in Part 1 of ADDIKD. Here we illustrate how dosing recommendations differ between ADDIKD and existing guidance for four commonly used drugs: methotrexate, cisplatin, carboplatin and nivolumab.

Safety and efficacy of re-treatment with [Lu]Lu-DOTA-Octreotate radionuclide therapy in progressive gastro-entero-pancreatic neuroendocrine tumours - a single centre experience.

Aim: Patients with gastro-entero-pancreatic neuroendocrine tumours (GEP NET) who retain somatostatin receptor (SSTR) expression after initial response to [Lu]Lu-DOTA-Octreotate (LuTate) peptide receptor radionuclide therapy (PRRT) are amenable to re-treatment (R-PRRT) upon progression. We assessed the safety and efficacy of R-PRRT in patients with progressive metastatic GEP NET.

Materials And Methods: A retrospective analysis, approved by institutional ethics board, was performed in patients with GEP NET who received R-PRRT for either symptomatically or radiologically progressive disease.

Approach to the Management of Gastrointestinal Manifestations in Patients With Phaeochromocytoma and Paraganglioma.

Objective: Managing gastrointestinal symptoms in patients with phaeochromocytoma and paraganglioma (PPGL) is challenging due to the risk of catecholaminergic crisis with many commonly prescribed medications, especially in functional tumours. We reviewed gastrointestinal symptom management and outcomes in PPGL patients at our centre and developed recommendations based on a literature review and our experience.

Design, Patients, Measurement: A single-centre retrospective analysis of the management of gastrointestinal symptoms in patients with PPGL between 2019 and 2024 was completed.

Reversal of metformin's anti-proliferative effect in fission yeast and (DRP1) mutants with elongated mitochondria.

Metformin is a well-tolerated drug frequently prescribed for managing type 2 diabetes. Extended metformin use has been linked to a significant decrease in cancer incidence across both diabetic and non-diabetic populations. Here we investigate the anti-proliferative effects of metformin on fission yeast .

Feasibility and population exposure of 5-fluorouracil using therapeutic drug monitoring (PREDICT-5FU): A multicentre clinical trial.

Aim: PREDICT-5FU aimed to document 5-fluorouracil (5FU) exposure in a cancer population and to evaluate the feasibility of 5FU and capecitabine therapeutic drug monitoring (TDM) in patients receiving standard doses and schedules.

Methods: Multicentre, prospective, observational single-arm study. Eligible adult patients received 5FU (infusional ≥24 h) or capecitabine.

A non-randomised open-label exploratory 'window of opportunity' study of TG02 treatment in patients with locally advanced primary and recurrent mutant colorectal cancer.

Background: TG02 is a peptide-based cancer vaccine eliciting immune responses to oncogenic codon 12/13 mutations. This phase 1 clinical trial (NCT02933944) assessed the safety and immunological efficacy of TG02 adjuvanted by GM-CSF in patients with -mutant colorectal cancer.

Methods: In the interval between completing CRT and pelvic exenteration, patients with resectable mutation-positive, locally advanced primary or current colorectal cancer, received 5-6 doses of TG02/GM-CSF.

Peptide receptor radionuclide therapy for ectopic Cushing's syndrome caused by metastatic neuroendocrine neoplasms.

Background: Metastatic gastroenteropancreatic neuroendocrine neoplasms (GEPNEN) can cause ectopic Cushing's syndrome (ECS). ECS is highly morbid and medical therapy is complex and can be ineffective. Patients unsuitable for bilateral adrenalectomy (BA) have dismal outcomes.

Pharmacogenetic-guided dosing for fluoropyrimidine (DPYD) and irinotecan (UGT1A1*28) chemotherapies for patients with cancer (PACIFIC-PGx): A multicenter clinical trial.

PACIFIC-PGx evaluated the feasibility of implementing pharmacogenetics (PGx) screening in Australia and the impact of DPYD/UGT1A1 genotype-guided dosing on severe fluoropyrimidine (FP) and irinotecan-related toxicities and hospitalizations, compared to historical controls. This prospective single arm trial enrolled patients starting FP/irinotecan for any cancer between 7 January 2021 and 25 February 2022 from four Australian hospitals (one metropolitan, three regional). During the accrual period, 462/487 (95%) consecutive patients screened for eligibility for DPYD and 50/109 (46%) for UGT1A1 were enrolled and genotyped (feasibility analysis), with 276/462 (60%) for DPYD and 30/50 (60%) for UGT1A1 received FP/irinotecan (safety analysis).

Assessment of response to PRRT including anatomical and molecular imaging as well as novel biomarkers.

Peptide receptor radionuclide therapy (PRRT) is an effective treatment for both oncological and hormone control and is a widely accepted standard of care treatment for patients with neuroendocrine neoplasms (NEN). Its use is anticipated to increase significantly, and this demands accurate tools and paradigms to assess treatment response post PRRT. This article outlines the current role and future developments of anatomical, molecular imaging and biomarkers for response assessment to PRRT, highlighting the challenges and provides perspectives for the need to focus on a multimodality, multidisciplinary and individualised approach for patients with this complex heterogeneous disease.

Freud, bullshit, and pseudoscience.

This paper critically examines the validity of Freudian psychoanalysis within the framework of Moberger's characterisation of pseudoscience as bullshit with scientific pretensions. The central question addressed is whether Freudian psychoanalysis qualifies as "bullshit," following Moberger's guideline of looking for systematic fallacies. The analysis centres on two fundamental critiques against psychoanalysis: one posited by Popper, contending that psychoanalytic interpretation is excessively flexible, and another by Glymour, asserting that Freud's interpretative method baselessly posits associations as causes.

Preoperative Chemoradiotherapy for Resectable Gastric Cancer.

Background: In Western countries, the current standard of care for resectable gastric cancer is perioperative chemotherapy. Preoperative chemoradiotherapy has been considered, but data are limited regarding this treatment as compared with perioperative chemotherapy alone.

Methods: We conducted an international, phase 3 trial in which patients with resectable adenocarcinoma of the stomach or gastroesophageal junction were randomly assigned to receive preoperative chemoradiotherapy plus perioperative chemotherapy or perioperative chemotherapy alone (control).

Brief research report: ETS-1 blockade increases ICAM-1 expression in activated human retinal endothelial cells.

Intercellular adhesion molecule 1 (ICAM-1) is a central cell adhesion molecule for retinal transendothelial migration of the leukocytes in non-infectious posterior uveitis. Inhibiting gene transcription reduces induction of ICAM-1 in inflamed retinal endothelium. Based on published literature implicating transcription factor ETS-1 as an activator of gene transcription, we investigated the effect of ETS-1 blockade on ICAM-1 levels in cytokine-stimulated human retinal endothelial cells.