Searching for treatments for non-G12C-KRAS mutant cancers.

KRAS mutations drive a wide variety of cancers. Drugs targeting the protein product of KRAS mutations are currently being evaluated show preliminary efficacy in clinical trials. A clinical trial of VS-6766, a dual RAF-MEK inhibitor, has reported early single agent activity in non-G12C mutated KRAS driven cancers.

Abiraterone in patients with recurrent epithelial ovarian cancer: principal results of the phase II Cancer of the Ovary Abiraterone (CORAL) trial (CRUK - A16037).

Background: Recurrent epithelial ovarian cancer (EOC) remains difficult to treat, with an urgent need for more therapy options. Androgens bind to the androgen receptor (AR), commonly expressed in EOC. CYP17 inhibitor abiraterone irreversibly inhibits androgen biosynthesis.

Radical resection of large metastatic non-functioning pancreatic neuroendocrine carcinoma complicated by splenic vein thrombosis and sinistral portal hypertension.

Introduction And Importance: There are limited reports in the literature of radical surgical resection for pancreatic neuroendocrine carcinoma (PNEC). In patients with non-functioning PNEC (NF-PNEC) within the tail of the pancreas tumours can cause splenic vein thrombosis (SVT) and subsequent sinitral portal hypertension (SPH). Radical surgical resection in such patients with concomitant liver metastasis has not previously been reported.

Updated results from the international phase III ALTTO trial (BIG 2-06/Alliance N063D).

Aim: To present the pre-specified analyses of >5-years follow-up of the Phase III ALTTO trial.

Patients And Methods: 8381 patients with stage I-III HER2 positive breast cancer randomised to chemotherapy plus 1-year of trastuzumab (T), oral lapatinib (L; no longer evaluated), trastuzumab followed by lapatinib (T→L), and lapatinib + trastuzumab (L+T). The primary endpoint was disease-free survival (DFS).

Primary post-transplant lymphoproliferative disorder of the central nervous system: characteristics, management and outcome in 25 paediatric patients.

Primary central nervous system (CNS) post-transplant lymphoproliferative disorder (PTLD) in childhood is rare. Twenty-five patients were retrieved from nine European Intergroup for Childhood Non-Hodgkin's Lymphoma and/or international Berlin-Frankfurt-Münster Study Group members. Types of allografts included kidney (n = 11), liver (n = 4), heart (n = 5), bowel (n = 1) and haematopoietic stem cells (n = 4).

Bridging the age gap in breast cancer: cluster randomized trial of two decision support interventions for older women with operable breast cancer on quality of life, survival, decision quality, and treatment choices.

Background: Rates of surgery and adjuvant therapy for breast cancer vary widely between breast units. This may contribute to differences in survival. This cluster RCT evaluated the impact of decision support interventions (DESIs) for older women with breast cancer, to ascertain whether DESIs influenced quality of life, survival, decision quality, and treatment choice.

A narrative review of oligometastatic prostate cancer-an evolving paradigm.

There has been growing interest in oligometastatic prostate cancer (OMPC) with a mounting body of evidence to suggest that it is a distinct disease state, both biologically and prognostically, when compared to polymetastatic prostate cancer. Three subgroups have been recognised; de novo synchronous, metachronous/oligorecurrent and oligoprogressive disease. The belief that patients with OMPC can be treated more aggressively to improve survival is transforming patient care.

Variation in histopathological assessment and association with surgical quality indicators following oesophagectomy.

Background: Histopathological outcomes, such as lymph node yield and margin positivity, are used to benchmark and assess surgical centre quality, and are reported annually by the National Oesophago-Gastric Cancer Audit (NOGCA) in England and Wales. The variation in pathological specimen assessment and how this affects these outcomes is not known.

Methods: A survey of practice was circulated to all tertiary oesophagogastric cancer centres across England and Wales.

The efficacy of immunotherapy for in-transit metastases of melanoma: an analysis of randomized controlled trials.

Nearly 10% of patients with high-risk early-stage melanoma will develop satellite or in-transit metastases (ITM), classified as stage III disease similar to lymph node metastases. The pivotal registration trials of the CTLA-4 antibody ipilimumab, and the PD-1 antibodies nivolumab and pembrolizumab, also included patients with unresectable stage III disease. However, there has been no analysis of patients with ITM, and anecdotal retrospective small series have indicated a potential lesser effect.

Statins as Potential Chemoprevention or Therapeutic Agents in Cancer: a Model for Evaluating Repurposed Drugs.

Purpose Of Review: Repurposing established medicines for a new therapeutic indication potentially has important global and societal impact. The high costs and slow pace of new drug development have increased interest in more cost-effective repurposed drugs, particularly in the cancer arena. The conventional drug development pathway and evidence framework are not designed for drug repurposing and there is currently no consensus on establishing the evidence base before embarking on a large, resource intensive, potential practice changing phase III randomised controlled trial (RCT).

The Emergence of Immune-checkpoint Inhibitors in Colorectal Cancer Therapy.

Immunotherapy has revolutionized the treatment landscape in a number of solid tumors. In colorectal cancer, evidence suggests that microsatellite high (MSI-H) tumors are the most responsive to immune checkpoint blockade due to increased neo-antigen load and a favorable tumor microenvironment. Indeed, Pembrolizumab now represents a first-line option in such patients.

Malignant Melanoma of the Gastrointestinal Tract: Symptoms, Diagnosis, and Current Treatment Options.

Malignant melanoma (MM) has become the fifth most frequent cancer in the UK. It is the most common carcinoma to metastasize to the gastrointestinal (GI) tract. MM particularly has an affinity to spread to the small bowel, which is followed by the involvement of the stomach and large intestine.

Denosumab compared with zoledronic acid on PFS in multiple myeloma: exploratory results of an international phase 3 study.

An exploratory end point from a recent trial in patients with newly diagnosed multiple myeloma showed that median progression-free survival (PFS) was increased by 10.7 months with denosumab vs zoledronic acid. We performed additional analyses to identify factors that may have contributed to the favorable PFS with denosumab.

Multiple myeloma.

Multiple myeloma is the second most common haematological malignancy in high-income countries, and typically starts as asymptomatic precursor conditions-either monoclonal gammopathy of undetermined significance or smouldering multiple myeloma-in which initiating genetic abnormalities, such as hyperdiploidy and translocations involving the immunoglobulin heavy chain, are already present. The introduction of immunomodulatory drugs, proteasome inhibitors, and CD38-targeting antibodies has extended survival, but ultimately the majority of patients will die from their disease, and some from treatment-related complications. Disease progression and subsequent relapses are characterised by subclonal evolution and increasingly resistant disease.

Focal therapy compared to radical prostatectomy for non-metastatic prostate cancer: a propensity score-matched study.

Introduction: Focal therapy (FT) ablates areas of prostate cancer rather than treating the whole gland. We compared oncological outcomes of FT to radical prostatectomy (RP).

Methods: Using prospective multicentre databases of 761 FT and 572 RP cases (November/2005-September/2018), patients with PSA < 20 ng/ml, Gleason  View Article and Find Full Text PDF

Tissue mRNA for S100A4, S100A6, S100A8, S100A9, S100A11 and S100P Proteins in Colorectal Neoplasia: A Pilot Study.

S100 proteins are involved in the pathogenesis of sporadic colorectal carcinoma through different mechanisms. The aim of our study was to assess tissue mRNA encoding S100 proteins in patients with non-advanced and advanced colorectal adenoma. Mucosal biopsies were taken from the caecum, transverse colon and rectum during diagnostic and/or therapeutic colonoscopy.

The Mutational Concordance of Fixed Formalin Paraffin Embedded and Fresh Frozen Gastro-Oesophageal Tumours Using Whole Exome Sequencing.

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Background: The application of massively parallel sequencing has led to the identification of aberrant druggable pathways and somatic mutations within therapeutically relevant genes in gastro-oesophageal cancer. Given the widespread use of formalin-fixed paraffin-embedded (FFPE) samples in the study of this disease, it would be beneficial, especially for the purposes of biomarker evaluation, to assess the concordance between comprehensive exome-wide sequencing data from archival FFPE samples originating from a prospective clinical study and those derived from fresh-frozen material.

Suturing Skills for Medical Students: A Systematic Review.

Aim: This systematic review aimed to identify all published evidence on teaching suturing skills for medical students. We aimed to outline significant positive teaching outcomes and devise a comprehensive framework for the optimal teaching of suturing skills for medical students.

Materials And Methods: We searched MEDLINE (via Ovid), EMBASE and SCOPUS databases until July 2019 with no language restriction using predefined 'Population, Intervention, Comparison, Outcome (PICO)' criteria.

Postoperative Morbidity After Resection of Recurrent Retroperitoneal Sarcoma: A Report from the Transatlantic Australasian RPS Working Group (TARPSWG).

Background: This study aimed to evaluate perioperative morbidity after surgery for first locally recurrent (LR1) retroperitoneal sarcoma (RPS). Data concerning the safety of resecting recurrent RPS are lacking.

Methods: Data were collected on all patients undergoing resection of RPS-LR1 at 22 Trans-Atlantic Australasian Retroperitoneal Sarcoma Working Group (TARPSWG) centers from 2002 to 2011.

Bridging the Age Gap in breast cancer: Impact of chemotherapy on quality of life in older women with early breast cancer.

Introduction: Older patients with early breast cancer (EBC) derive modest survival benefit from chemotherapy but have increased toxicity risk. Data on the impact of chemotherapy for EBC on quality of life in older patients are limited, but this is a key determinant of treatment acceptance. We aimed to investigate its effect on quality of life in older patients enrolled in the Bridging the Age Gap study.