Datopotamab Deruxtecan Versus Docetaxel for Previously Treated Advanced or Metastatic Non-Small Cell Lung Cancer: The Randomized, Open-Label Phase III TROPION-Lung01 Study.

Purpose: The randomized, open-label, global phase III TROPION-Lung01 study compared the efficacy and safety of datopotamab deruxtecan (Dato-DXd) versus docetaxel in patients with pretreated advanced/metastatic non-small cell lung cancer (NSCLC).

Methods: Patients received Dato-DXd 6 mg/kg or docetaxel 75 mg/m once every 3 weeks. Dual primary end points were progression-free survival (PFS) and overall survival (OS).

EGFR and PI3K Signalling Pathways as Promising Targets on Circulating Tumour Cells from Patients with Metastatic Gastric Adenocarcinoma.

The prognosis for metastatic gastric adenocarcinoma (mGAC) remains poor. Gene alterations in receptor tyrosine kinases (RTKs) such as epidermal growth factor receptor and their downstream effectors including catalytic subunit alpha of the phosphatidylinositol 3-kinase are common in mGAC. Targeted RTK and phosphatidylinositol-3-kinase (PI3K) treatments have demonstrated clinical benefits in other solid tumours and are key potential targets for clinical development against mGAC given the presence of recurrent alterations in these pathways.

A Machine Learning-Driven Comparison of Ion Images Obtained by MALDI and MALDI-2 Mass Spectrometry Imaging.

Matrix-assisted laser desorption ionization mass spectrometry imaging (MALDI-MSI) enables label-free imaging of biomolecules in biological tissues. However, many species remain undetected due to their poor ionization efficiencies. MALDI-2 (laser-induced post-ionization) is the most widely used post-ionization method for improving analyte ionization efficiencies.

Metastatic Ductal Eccrine Adenocarcinoma with Excellent Response to Immunotherapy.

Eccrine carcinoma, a subtype of which is ductal eccrine adenocarcinoma (DEA), is a rare cutaneous malignancy. For metastatic eccrine carcinoma, there are very limited data to guide treatment. Conventional chemotherapy is of limited benefit and there is only a small body of evidence for the use of immunotherapy in non-DEA eccrine carcinomas.

Sex as a Predictor of Response to Immunotherapy in Advanced Cutaneous Squamous Cell Carcinoma.

Approximately 3-5% of patients with cutaneous squamous cell carcinoma (CSCC) develop advanced disease, accounting for roughly 1% of all cancer deaths in Australia. Immunotherapy has demonstrated significant clinical benefit in advanced CSCC in several key phase II studies; however, there are limited data for patients treated outside of clinical trials. This is particularly relevant in advanced CSCC, which is most often seen in elderly patients with significant comorbidities.

Efficacy and safety of cosibelimab, an anti-PD-L1 antibody, in metastatic cutaneous squamous cell carcinoma.

Background: Programmed cell death receptor-1 (PD-1)-blocking antibodies are approved to treat metastatic or locally advanced cutaneous squamous cell carcinoma (CSCC) cases ineligible for curative surgery or radiation. Notwithstanding, some patients experience inadequate responses or severe immune-related adverse events (AEs), indicating the need for improved therapies. Cosibelimab is a high-affinity programmed cell death-ligand 1 (PD-L1)-blocking antibody that activates innate and adaptive immunity by blocking PD-L1 interaction with PD-1 and B7-1 receptors.

Low Pretreatment CD4:CD8 T Cell Ratios and CD39CD73CD19 B Cell Proportions Are Associated with Improved Relapse-Free Survival in Head and Neck Squamous Cell Carcinoma.

The ectonucleotidases CD39 and CD73 are present on immune cells and play important roles in cancer progression by suppressing antitumour immunity. As such, CD39 and CD73 on peripheral blood mononuclear cells (PBMCs) are emerging as potential biomarkers to predict disease outcomes and treatment responses in cancer patients. This study aimed to examine T and B cells, including CD39 and CD73 expressing subsets, by flow cytometry in PBMCs from 28 patients with head and neck squamous cell carcinoma (HNSCC) and to assess the correlation with the treatment modality, human papillomavirus (HPV) status, and relapse-free survival (RFS).

HER2-Positive Gastroesophageal Cancers Are Associated with a Higher Risk of Brain Metastasis.

Brain metastasis from gastroesophageal adenocarcinomas (GOCs) is a rare but a devastating diagnosis. Human epidermal growth factor receptor 2 (HER2) is a prognostic and predictive biomarker in GOCs. The association of HER2 with GOC brain metastasis is not known.

Sunvozertinib, a Selective EGFR Inhibitor for Previously Treated Non-Small Cell Lung Cancer with EGFR Exon 20 Insertion Mutations.

Unlabelled: Epidermal growth factor receptor exon 20 insertion mutations (EGFRexon20ins) are detected in approximately 2% of patients with non-small cell lung cancer (NSCLC). Due to a lack of effective therapy, the prognosis of these patients is typically poor. Sunvozertinib (DZD9008) was designed as an oral, potent, irreversible, and selective EGFR tyrosine kinase inhibitor, showing activity against EGFRexon20ins and other mutations.

Clinical and molecular profile of young adults with early-onset colorectal cancer: Experience from four Australian tertiary centers.

Background: Patients with early-onset colorectal cancer (EO-CRC) have unique characteristics. Contemporary data on the pathological and molecular features, and survival of EO-CRC are limited in the Australian context.

Aim: To determine the demographic, histopathological and molecular characteristics of adults with EO-CRC, and their survival.

Rectal cancer treatment and outcomes in elderly patients treated with curative intent.

The elderly population comprises a significant proportion of patients diagnosed with rectal cancer. However, there is a lack of evidence to guide treatment decisions in this group. Thus, this multicentre study compares the histopathology, treatment patterns and outcomes between the elderly and young populations with non-metastatic rectal cancer.

Experimental and Clinical Evidence Supports the Use of Urokinase Plasminogen Activation System Components as Clinically Relevant Biomarkers in Gastroesophageal Adenocarcinoma.

Gastric and oesophageal cancers (GOCs) are lethal cancers which metastasise early and recur frequently, even after definitive surgery. The urokinase plasminogen activator system (uPAS) is strongly implicated in the invasion and metastasis of many aggressive tumours including GOCs. Urokinase plasminogen activator (uPA) interaction with its receptor, urokinase plasminogen activator receptor (uPAR), leads to proteolytic activation of plasminogen to plasmin, a broad-spectrum protease which enables tumour cell invasion and dissemination to distant sites.

Combination chemotherapy with NAB -paclitaxel and capecitabine for patients with advanced biliary tract cancer (NAP-CAPABIL Pilot Study).

Background:  Advanced biliary tract cancer (ABTC) is a highly aggressive malignancy, with a 5-year overall survival of < 10%. Although preliminary evidence suggests a role of targeted treatments or immunotherapy in a subset of patients, chemotherapy remains the standard second-line treatment in the majority. We conducted a pilot study of second-line chemotherapy with capecitabine and nab-paclitaxel after failure of gemcitabine and platinum.

Single-Cell Analysis of BRAF and NRAS Mutation Status in Melanoma Cell Lines as Method Generation for Circulating Melanoma Cells.

Molecular testing of tumor biopsies allows for the identification of the key mutations driving a patient's cancer. However, this is limited to singular nodes and may not accurately reflect cancer heterogeneity. Circulating tumor cell (CTC) analyses offer a noninvasive method of interrogating the genomic profile of patient-derived tumor material.

PD-L1 Detection on Circulating Melanoma Cells.

The advent of personalized medicines targeting cell signaling pathways has radically improved melanoma patient outcomes. More recently, immune-modulating therapies disrupting the PD-1/PD-L1 axis have become a powerful tool in the treatment of a range of melanoma, showing a profound improvement in the overall survival outcomes. However, immune checkpoint inhibitors (ICIs) are associated with considerable toxicities and appear to only be efficacious in a subset of melanoma patients.

Pancreatitis and Biliary Obstruction Secondary to Duodenal Metastasis from Rapidly Progressing Lung Adenocarcinoma Treated with Common Bile Duct Stenting.

Non-small cell lung cancer (NSCLC) is characterised by diffuse metastases, with common sites being the brain, liver, bones, and adrenal glands. Small bowel metastasis from NSCLC is a rare phenomenon, particularly in patients with an adenocarcinoma histology. We report the case of a 56-year-old lung adenocarcinoma patient with a duodenal metastasis diagnosed on FDG/PET-CT and confirmed on duodenal biopsy.

High body mass index is associated with an increased overall survival in rectal cancer.

Background: The impact of increased body mass index (BMI) on clinical outcomes in locoregional rectal cancer is unknown.

Methods: This is a retrospective cohort study which included 453 consecutive rectal cancer patients undergoing definitive treatment, with confirmed stage I, II or III rectal adenocarcinoma. The association of BMI at diagnosis with overall survival (OS), cancer specific survival (CSS) and disease-free survival (DFS) was explored, controlling for key covariates using multivariable analyses.

Central Venous Catheter Thrombosis in Cancer: A Multi-Centre Retrospective Study Investigating Risk Factors and Contemporary Trends in Management.

Objectives: Central venous access is needed to facilitate chemotherapy for many cancer patients. Central venous catheter-related thrombosis (CVCT) is a major complication that can cause significant morbidity and mortality. We sought to explore the rate of CVCT in a general cancer population in Australia and to identify factors associated with increased risk of thrombosis.

Comparison of peripheral blood mononuclear cell isolation techniques and the impact of cryopreservation on human lymphocytes expressing CD39 and CD73.

CD39 and CD73 are ecto-nucleotidases present on human peripheral blood mononuclear cells (PBMCs) and are emerging biomarkers on these cells in various disorders including cancer. Many factors influence PBMC quality, so it is essential to validate sample processing methods prior to incorporation in clinical studies. This study examined the impact of both PBMC cryopreservation and PBMC isolation using SepMate density gradient centrifugation on CD39 and CD73 expressing subsets.

Factors influencing recurrence of stage I-III rectal cancer in regional Australia.

Background: As treatments for rectal cancer improve with developments in surgical techniques, radiotherapy and chemotherapy, the nature of recurrences are evolving. We used a comprehensive database of a large Australian population with stage I-III rectal adenocarcinoma to identify timing and prognostic significance of recurrences, and factors associated with risk of developing recurrent disease.

Methods: All patients with locoregional rectal cancer treated with curative intent in our health district from 2006 to 2017 were included.

Retrospective Evaluation of the Use of Pembrolizumab in Malignant Mesothelioma in a Real-World Australian Population.

Introduction: We investigated the efficacy and toxicity of pembrolizumab in patients with mesothelioma from a real-world Australian population. We aimed to determine clinical factors and predictive biomarkers that could help select patients who are likely to benefit from pembrolizumab.

Method: Patients with mesothelioma who were treated with pembrolizumab as part of the Insurance and Care New South Wales compensation scheme were included.

The Role of Liquid Biopsies in Detecting Molecular Tumor Biomarkers in Brain Cancer Patients.

Glioblastoma multiforme (GBM) is one of the most lethal primary central nervous system cancers with a median overall survival of only 12-15 months. The best documented treatment is surgical tumor debulking followed by chemoradiation and adjuvant chemotherapy with temozolomide, but treatment resistance and therefore tumor recurrence, is the usual outcome. Although advances in molecular subtyping suggests GBM can be classified into four subtypes, one concern about using the original histology for subsequent treatment decisions is that it only provides a static snapshot of heterogeneous tumors that may undergo longitudinal changes over time, especially under selective pressure of ongoing therapy.