AKT/mTOR as a targetable hub to overcome multimodal resistance to EGFR inhibitors in oesophageal squamous cell carcinoma.

Background: Oesophageal squamous cell carcinoma (ESCC) is associated with late-stage diagnosis, limited treatment options, the development of drug resistance and poor outcome. Epidermal growth factor receptor is frequently dysregulated in ESCC. EGFR copy number gain and/or protein overexpression are beneficial as predictive biomarkers for EGFR inhibitor therapy; however, inherent and acquired resistance limit response rates, and durable disease control is infrequent.

Clinical and pharmacogenomic predictors of survival in tamoxifen treated breast cancer female patients: a real-world study.

Aim: To investigate the impact of tamoxifen dose, CYP2D6 inhibitors, CYP2D6*4 genotype, and non-genetic parameters on the outcomes of tamoxifen treated female breast cancer patients.

Method: We retrospectively included 3218 female patients who initiated tamoxifen following a diagnosis of breast cancer with long-term follow-up (median 7.5 years).

N-Terminal Pro-B-Type Natriuretic Peptide (NT-proBNP)-A Prognostic Biomarker in Older and/or Frail Adults with Advanced Gastroesophageal Cancer: A Post Hoc Analysis of the GO2 Clinical Trial.

Better prognostic biomarkers are needed in older adults with cancer. There are established links between N-terminal pro-B-type Natriuretic Peptide (NT-proBNP) and sarcopenia, and sarcopenia is associated with poorer cancer survival. However, there are limited data regarding baseline NT-proBNP as a biomarker of cancer outcome.

Total neoadjuvant therapy in oesophageal and gastro-oesophageal junctional adenocarcinoma.

Adenocarcinoma of the oesophagus and gastro-oesophageal junction represent a large burden of cancer death in the Western World with an increasing incidence. In the past two decades, the overall survival of patients on a potentially curative treatment pathway has more than doubled due to the addition of perioperative oncological therapies to surgery. However, patients often fail to respond to oncological treatment or struggle to complete their treatment after surgery.

Female Sex but Not Oestrogen Receptor Expression Predicts Survival in Advanced Gastroesophageal Adenocarcinoma-A Post-hoc Analysis of the GO2 Trial.

Gastroesophageal adenocarcinoma is a disease of older adults that is associated with a very poor prognosis. It is less common and has better outcomes in females. The reason for this is unknown but may relate to signalling via the main oestrogen receptors (ER) α and β.

Diagnosis, treatment, and outcome of patients with oesophagogastric cancer during the COVID-19 pandemic: national study.

Background: The national response to COVID-19 has had a significant impact on cancer services. This study investigated the effect of national lockdown on diagnosis, management, and outcomes of patients with oesophagogastric cancers in Scotland.

Methods: This retrospective cohort study included consecutive new patients presenting to regional oesophagogastric cancer multidisciplinary teams in National Health Service Scotland between October 2019 and September 2020.

Cardiotoxicity and Chemotherapy-The Role of Precision Medicine.

Cancer and cardiovascular disease are the leading causes of death in the United Kingdom. Many systemic anticancer treatments are associated with short- and long-term cardiotoxicity. With improving cancer survival and an ageing population, identifying those patients at the greatest risk of cardiotoxicity from their cancer treatment is becoming a research priority and has led to a new subspecialty: cardio-oncology.

Gastroesophageal adenocarcinoma in older adults: A comprehensive narrative review of management by the Young International Society of Geriatric Oncology.

Gastroesophageal adenocarcinoma is a disease of older adults with very poor survival rates. Its incidence has risen dramatically across the world in recent decades. Current treatment approaches for older adults are based largely on extrapolated evidence from clinical trials conducted in younger and fitter participants than those more commonly encountered in clinical practice.

Best supportive care and prognosis: advanced gastroesophageal adenocarcinoma.

Objectives: Real-world data are lacking on survival in patients with advanced gastroesophageal adenocarcinoma (GOA) treated with best supportive care (BSC) alone. This knowledge is vital to personalise cancer treatment and obtain informed consent. This study aimed to define and compare survival in patients with advanced GOA treated with and without palliative chemotherapy (CTx), and to explore the factors that impact prognosis.

Resistance to immune checkpoint inhibitors in advanced gastro-oesophageal cancers.

Immune checkpoint inhibitors (ICIs) have altered the treatment paradigm across a range of tumour types, including gastro-oesophageal cancers. For patients with any cancer type who respond, ICIs can confer long-term disease control and significantly improve survival and quality of life, but for patients with gastro-oesophageal cancer, ICIs can be transformative, as durable responses in advanced disease have hitherto been rare, especially in those patients who are resistant to first-line cytotoxic therapies. Results from trials in patients with advanced-stage gastro-oesophageal cancer have raised hopes that ICIs will be successful as adjuvant and neoadjuvant treatments in early-stage disease, when the majority of patients relapse after potential curative treatments, and several trials are ongoing.

Cancer Treatment Helpline: a retrospective study of the NHS Tayside experience.

Background: Treatment-related toxicity and delays in the management of this toxicity can impact the outcomes of patient with cancer. In Scotland, a national cancer helpline was established to provide triage assessment for patients receiving systemic anticancer therapy (SACT) in an attempt to minimise delays in toxicity management. In this article, we describe the use and impact of the helpline in our region over the last 5 years.

Real‑world challenge for clinicians treating advanced gastroesophageal adenocarcinoma (Review).

Gastroesophageal adenocarcinoma (GOA) is a disease of older people. Incidence is rising in the developed world and the majority of patients present with advanced disease. Based on clinical trial data, systemic chemotherapy in the advanced setting is associated with improvements in quality of life and survival.

The impact of COVID-19 on systemic anticancer treatment delivery in Scotland.

Understanding the impact of the COVID-19 pandemic on systemic anticancer therapy delivery (SACT) is crucial to appreciate the short- and long-term consequences for cancer patients and plan future care. Here, we report real-time national SACT delivery data from NHS Scotland. We demonstrate an initial rapid reduction in patient attendance of 28.

Interactions between anti-EGFR therapies and cytotoxic chemotherapy in oesophageal squamous cell carcinoma: why clinical trials might have failed and how they could succeed.

Purpose: Oesophageal squamous cell carcinoma (ESCC) has a poor prognosis. Advanced tumours are treated with fluoropyrimidine/platinum chemotherapy followed by irinotecan or taxane monotherapy, but resistance is common and new treatments are needed. Approximately 20% of ESCCs carry copy number gain (CNG) of the epidermal growth factor receptor (EGFR) gene.

Combining precision medicine and prophylaxis in oesophageal squamous cell carcinoma.

A trial update confirms improved survival for prophylactic elective nodal irradiation and addition of erlotinib to definitive chemoradiotherapy in oesophageal squamous cell carcinoma (ESCC). High tumour EGFR protein expression shows promise to identify those who will benefit from erlotinib. This represents therapeutic progress, and has wider relevance for precision medicine strategies in ESCC.

Novel biomarkers for risk stratification of Barrett's oesophagus associated neoplastic progression-epithelial HMGB1 expression and stromal lymphocytic phenotype.

Background: The incidence of oesophageal adenocarcinoma is increasing globally. Barrett's oesophagus (BO) is a pre-malignant condition with no biomarker to risk stratify those at highest risk of dysplasia and malignant transformation.

Methods: Subcellular epithelial protein (HMGB1, p53, RUNX3) expression, alongside expression of CD20, CD4, CD8 and Foxp3 to characterise stromal B lymphocyte, and helper, cytotoxic and regulatory T-lymphocyte cell infiltrate, respectively, was assessed by immunohistochemistry in 218 human tissue samples including normal oesophageal/gastric biopsies (n = 39), BO (non-dysplasia, dysplasia, non-dysplastic background from progressors to dysplasia or cancer, n = 121) and oesophageal adenocarcinoma (n = 58).

Gefitinib and EGFR Gene Copy Number Aberrations in Esophageal Cancer.

Purpose The Cancer Esophagus Gefitinib trial demonstrated improved progression-free survival with the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor gefitinib relative to placebo in patients with advanced esophageal cancer who had disease progression after chemotherapy. Rapid and durable responses were observed in a minority of patients. We hypothesized that genetic aberration of the EGFR pathway would identify patients benefitting from gefitinib.

Epidermal Growth Factor (EGFR) copy number aberrations in esophageal and gastro-esophageal junctional carcinoma.

Background: Clinical trials of agents targeting epidermal growth factor receptor (EGFR) in esophageal carcinoma (EC) have indicated a minority subgroup responsive to anti-EGFR therapies. Other investigations suggest increases in EGFR copy number are associated with poor prognosis in EC, but have used a variety of different techniques and tested numbers remain small. A validated assay for EGFR copy number in EC is needed, to allow investigation of EGFR copy number gain as a predictive biomarker for the anti-EGFR responsive subgroup of patients.

Biomarkers and novel agents in esophago-gastric cancer: are we making progress?

Esophago-gastric cancer (EGC) provides a formidable healthcare challenge. Conventional chemotherapy provides modest survival benefit in patients with advanced disease especially in the second-line setting. The recent paradigm shift in the oncology community towards targeting growth factor pathways and the immune system using novel targeted agents has now demonstrated clinical utility in EGC, but recent trial results have highlighted the complexity of disease pathogenesis and significant challenges remain.

Gefitinib for oesophageal cancer progressing after chemotherapy (COG): a phase 3, multicentre, double-blind, placebo-controlled randomised trial.

Background: Evidence is scarce for the effectiveness of therapies for oesophageal cancer progressing after chemotherapy, and no randomised trials have been reported. We aimed to compare gefitinib with placebo in previously treated advanced oesophageal cancer.

Methods: For this phase 3, parallel, randomised, placebo-controlled trial, eligible patients were adults with advanced oesophageal cancer or type I/II Siewert junctional tumours, histologically confirmed squamous-cell carcinoma or adenocarcinoma, who had progressed after chemotherapy, with WHO performance status 0-2, and with measurable or evaluable disease on CT scan.

Serpin b3 is associated with poor survival after chemotherapy and is a potential novel predictive biomarker in advanced non-small-cell lung cancer.

Introduction: In a previous biomarker discovery project using gene-expression profiling we identified Serpin B3 (SB3) as a predictor of resistance to platinum doublet chemotherapy (PtC) in non-small-cell lung cancer (NSCLC). This independent prospective study was designed to confirm the predictive utility of SB3.

Methods: SB3 immunohistochemistry was scored by previously validated criteria (score 0 = negative, score 1 = 1%-10% tumor cells positive, score 2 = 11%-50% tumor cells positive, and score 3 = >50% tumor cell positive) in 197 patients with stage IV NSCLC treated with PtC.