Real-world experience of immune checkpoint inhibitors in patients with solid tumours in the Top End of the Northern Territory, Australia from 2016 to 2021: a retrospective observational cohort study.

Background: Use of immune checkpoint inhibitors is growing, but clinical trial data may not apply to Indigenous patients or patients living in remote areas.

Aims: To provide real-world incidence of immune-related adverse events (irAE) in the Top End of the Northern Territory and compare incidence between demographic subgroups.

Methods: This retrospective, observational, cohort study collected data from electronic records of patients living in the Top End with solid organ cancer treated with immunotherapy between January 2016 and December 2021.

Intrahepatic cholangiocarcinoma hidden within cancer of unknown primary.

Background: Many patients referred with a provisional diagnosis of cancer of unknown primary (pCUP) present with presumed metastatic disease to the liver. Due to the lack of definitive histological markers, intrahepatic cholangiocarcinoma (iCCA) may be overlooked. This study assessed the frequency of iCCA within a pCUP cohort.

Plasma Tie2 trajectories identify vascular response criteria for VEGF inhibitors across advanced biliary tract, colorectal and ovarian cancers.

Background: Vascular endothelial growth factor inhibitors (VEGFi) are compromised by a lack of validated biomarkers. Previously we showed that changes in the concentration of plasma Tie2 (pTie2) was a response biomarker for bevacizumab. Here, we investigated whether pTie2 can predict response and progression cross-tumour for generic VEGFi treatment.

Prospective observational study of prevalence, assessment and treatment of pancreatic exocrine insufficiency in patients with inoperable pancreatic malignancy (PANcreatic cancer Dietary Assessment (PanDA): a study protocol.

Introduction: Pancreatic exocrine insufficiency (PEI) in patients with pancreatic malignancy is well documented in the literature and is known to negatively impact on overall survival and quality of life. A lack of consensus opinion remains on the optimal diagnostic test that can be adapted for use in a clinical setting for this cohort of patients. This study aims to better understand the prevalence of PEI and the most suitable diagnostic techniques in patients with advanced pancreatic malignancy.

Effect of oxaliplatin plus 5-fluorouracil or capecitabine on circulating and imaging biomarkers in patients with metastatic colorectal cancer: a prospective biomarker study.

Background: Patients with metastatic colorectal cancer are treated with cytotoxic chemotherapy supplemented by molecularly targeted therapies. There is a critical need to define biomarkers that can optimise the use of these therapies to maximise efficacy and avoid unnecessary toxicity. However, it is important to first define the changes in potential biomarkers following cytotoxic chemotherapy alone.

HPB cancers in older patients | inclusion of older/senior patients in clinical trials.

Liver, biliary tract and pancreatic cancers are increasingly diseases of older people and the global population is aging. 'Older/senior' patients are a heterogeneous group who vary widely in their general health, physical reserve and degree of dependence on others. Cancer is not the only disease that becomes more prevalent in old age, which means older/senior patients may also have comorbidities and lower resilience.

Systemic Treatment Selection for Patients with Advanced Pancreatic Neuroendocrine Tumours (PanNETs).

Pancreatic neuroendocrine tumours (PanNETs) are rare diseases and a good example of how research is not only feasible, but also of crucial importance in the scenario of rare tumours. Many clinical trials have been performed over the past two decades expanding therapeutic options for patients with advanced PanNETs. Adequate management relies on optimal selection of treatment, which may be challenging for clinicians due to the fact that multiple options of therapy are currently available.

Early recognition of anorexia through patient-generated assessment predicts survival in patients with oesophagogastric cancer.

Cancer cachexia is common in patients with oesophagogastric cancer (OG) and is linked to overall survival (OS). One of the key components of cachexia is anorexia; it is not known whether anorexia impacts on OS and there is no method of routine screening in current practice. Diagnosis relies on patients describing the symptoms, clinicians diagnosing anorexia and acting upon it.

Capecitabine and Temozolomide in Patients with Advanced Pulmonary Carcinoid Tumours.

Background: Temozolomide and capecitabine (CAPTEM) chemotherapy is known to be active in patients with pancreatic neuroendocrine tumours.

Objective: This retrospective analysis set out to describe the efficacy and toxicity of CAPTEM in patients with advanced pulmonary carcinoids (PCs).

Methods: Patients were included with advanced PC who had been treated with a maximum of 6 cycles of oral temozolomide 200 mg/m2 on days 10-14 and capecitabine 750 mg/m2 b.

Novel phase I trial design to evaluate the addition of cediranib or selumetinib to preoperative chemoradiotherapy for locally advanced rectal cancer: the DREAMtherapy trial.

Background: The DREAMtherapy (Dual REctal Angiogenesis MEK inhibition radiotherapy) trial is a novel intertwined design whereby two tyrosine kinase inhibitors (cediranib and selumetinib) were independently evaluated with rectal chemoradiotherapy (CRT) in an efficient manner to limit the extended follow-up period often required for radiotherapy studies.

Patients And Methods: Cediranib or selumetinib was commenced 10 days before and then continued with RT (45 Gy/25#/5 wks) and capecitabine (825 mg/m twice a day (BID)). When three patients in the cediranib 15-mg once daily (OD) cohort were in the surveillance period, recruitment to the selumetinib cohort commenced.

Plasma Tie2 is a tumor vascular response biomarker for VEGF inhibitors in metastatic colorectal cancer.

Oncological use of anti-angiogenic VEGF inhibitors has been limited by the lack of informative biomarkers. Previously we reported circulating Tie2 as a vascular response biomarker for bevacizumab-treated ovarian cancer patients. Using advanced MRI and circulating biomarkers we have extended these findings in metastatic colorectal cancer (n = 70).

The HER3 pathway as a potential target for inhibition in patients with biliary tract cancers.

Introduction: Expression of human epidermal growth factor receptor (HER)2 and HER3 have been investigated in small BTC studies using variable scoring systems.

Methods: HER2 and HER3 overexpression/amplification were explored following internationally agreed guidelines using immunohistochemistry (IHC) and fluorescent in-situ hybridisation (FISH), respectively. Logistic regression and survival analysis (Kaplan Meier, Log rank test and Cox Regression) were used for statistical analysis.

Circulating biomarkers during treatment in patients with advanced biliary tract cancer receiving cediranib in the UK ABC-03 trial.

Background: Advanced biliary tract cancer (ABC) has a poor prognosis. Cediranib, in addition to cisplatin/gemcitabine [CisGem], improved the response rate, but did not improve the progression-free survival (PFS) in the ABC-03 study. Minimally invasive biomarkers predictive of cediranib benefit may improve patient outcomes.

Somatostatin analogue-induced pancreatic exocrine insufficiency in patients with neuroendocrine tumors: results of a prospective observational study.

Background: Patients with advanced well-differentiated neuroendocrine tumours (Wd-NETs) are commonly treated with somatostatin analogues (SSAs). Some patients may develop SSA-related side effects such as pancreatic exocrine insufficiency (PEI).

Methods: In this prospective, observational study, the frequency of SSA-induced PEI in 50 sequential patients with advanced Wd-NETs treated with SSAs was investigated.

Cell Death, Inflammation, Tumor Burden, and Proliferation Blood Biomarkers Predict Lung Cancer Radiotherapy Response and Correlate With Tumor Volume and Proliferation Imaging.

Introduction: There is an unmet need to develop noninvasive biomarkers to stratify patients in drug-radiotherapy trials. In this pilot study we investigated lung cancer radiotherapy response and toxicity blood biomarkers and correlated findings with tumor volume and proliferation imaging.

Patients And Methods: Blood samples were collected before and during (day 21) radiotherapy.

Targeting the Epidermal Growth Factor Receptor in Addition to Chemotherapy in Patients with Advanced Pancreatic Cancer: A Systematic Review and Meta-Analysis.

Overexpression of epidermal growth factor receptors (EGFR) occurs in >90% of pancreatic ductal adenocarcinomas (PDACs) and is associated with a poorer prognosis. A systematic review of electronic databases identified studies exploring the addition of EGFR-targeted treatment to chemotherapy in patients with locally advanced (LA)/metastatic PDAC. Efficacy, safety and tolerability of EGFR-targeted therapy were explored using meta-analysis of randomised controlled trials (RCTs).

Systematic analysis of circulating soluble angiogenesis-associated proteins in ICON7 identifies Tie2 as a biomarker of vascular progression on bevacizumab.

Background: There is a critical need for predictive/resistance biomarkers for VEGF inhibitors to optimise their use.

Methods: Blood samples were collected during and following treatment and, where appropriate, upon progression from ovarian cancer patients in ICON7, a randomised phase III trial of carboplatin and paclitaxel with or without bevacizumab. Plasma concentrations of 15 circulating angio-biomarkers were measured using a validated multiplex ELISA, analysed through a novel network analysis and their relevance to the PFS then determined.

Chemotherapy for advanced non-pancreatic well-differentiated neuroendocrine tumours of the gastrointestinal tract, a systematic review and meta-analysis: A lost cause?

Background: Chemotherapy is well-established in the treatment of patients with well-differentiated neuroendocrine tumours (NETs) arising from the pancreas (pNETs); however, its role in patients with gastrointestinal non-pancreatic NETs (non-pNETs) is uncertain. This systematic review assesses the evidence for the role of chemotherapy in well-differentiated non-pNET patients.

Methods: Eligible studies (identified using MEDLINE) were those reporting response and/or survival data for patients with well-differentiated non-pNETs receiving systemic chemotherapy.

Discovery and Validation of Predictive Biomarkers of Survival for Non-small Cell Lung Cancer Patients Undergoing Radical Radiotherapy: Two Proteins With Predictive Value.

Lung cancer is the most frequent cause of cancer-related death world-wide. Radiotherapy alone or in conjunction with chemotherapy is the standard treatment for locally advanced non-small cell lung cancer (NSCLC). Currently there is no predictive marker with clinical utility to guide treatment decisions in NSCLC patients undergoing radiotherapy.

Cediranib or placebo in combination with cisplatin and gemcitabine chemotherapy for patients with advanced biliary tract cancer (ABC-03): a randomised phase 2 trial.

Background: Cisplatin and gemcitabine is the standard first-line chemotherapy regimen for patients with advanced biliary tract cancer; expression of VEGF and its receptors is associated with adverse outcomes. We aimed to assess the effect of the addition of cediranib (an oral inhibitor of VEGF receptor 1, 2, and 3) to cisplatin and gemcitabine on progression-free survival.

Methods: In this multicentre, placebo-controlled, randomised phase 2 study, we recruited patients aged 18 years or older with histologically confirmed or cytologically confirmed advanced biliary tract cancer from hepatobiliary oncology referral centres in the UK.

Circulating Tumor Cell Enumeration in a Phase II Trial of a Four-Drug Regimen in Advanced Colorectal Cancer.

Background: Multidrug regimens are active against advanced colorectal cancer (ACRC). However, the increased toxicity requires the use of biomarkers to select the patients who will derive the most benefit. We assessed circulating tumor cells (CTCs) as a prognostic biomarker in patients treated with a 4-drug regimen.

The combination of circulating Ang1 and Tie2 levels predicts progression-free survival advantage in bevacizumab-treated patients with ovarian cancer.

Purpose: Randomized ovarian cancer trials, including ICON7, have reported improved progression-free survival (PFS) when bevacizumab was added to conventional cytotoxic therapy. The improvement was modest prompting the search for predictive biomarkers for bevacizumab.

Experimental Design: Pretreatment training (n=91) and validation (n=114) blood samples were provided by ICON7 patients.

An integrated characterization of serological, pathological, and functional events in doxorubicin-induced cardiotoxicity.

Many efficacious cancer treatments cause significant cardiac morbidity, yet biomarkers or functional indices of early damage, which would allow monitoring and intervention, are lacking. In this study, we have utilized a rat model of progressive doxorubicin (DOX)-induced cardiomyopathy, applying multiple approaches, including cardiac magnetic resonance imaging (MRI), to provide the most comprehensive characterization to date of the timecourse of serological, pathological, and functional events underlying this toxicity. Hannover Wistar rats were dosed with 1.