Ano-uro-genital mucosal melanoma UK national guidelines.

Ano-uro-genital (AUG) mucosal melanomas are rare cancers associated with poor outcomes and limited evidence-based management. The United Kingdom AUG mucosal melanoma guideline development group used an evidence-based systematic approach to make recommendations regarding the diagnosis, treatment and surveillance of patients diagnosed with AUG mucosal melanomas. The guidelines were sent for international peer review, and are accredited by The National Institute for Health and Clinical Excellence (NICE).

Real-world experience with pembrolizumab toxicities in advanced melanoma patients: a single-center experience in the UK.

Aim: We aimed to characterize the safety profile of pembrolizumab in advanced melanoma patients at our center to better reflect 'real-world' data on anti-PD-1 inhibitors.

Materials & Methods: At our institution, 58 ipilimumab-naive and 30 ipilimumab-treated patients with advanced melanoma who have received pembrolizumab between June 2014 and June 2017 were included for analysis.

Results: Incidence of any-grade and grade 3/4 toxicities were 81.

Pembrolizumab-induced Sarcoid-like Reactions during Treatment of Metastatic Melanoma.

Pembrolizumab is a programmed cell death protein 1, or PD-1, inhibitor therapy immunotherapy for patients with advanced melanoma. This report discusses a series of documented cases of sarcoid-like reactions associated with this therapy. Three patients with malignant melanoma developed metastatic disease and were treated with pembrolizumab immunotherapy.

Managing side effects of cancer immunotherapy for the acute physician.

Immunotherapy is a novel type of anti-cancer treatment that works by upregulating the host's immune system to fight against cancer cells. Landmark immunotherapy trials have demonstrated improvements in response rates and survival compared to cytotoxic chemotherapy. Specific immunotherapies known as checkpoint inhibitors are now routinely used in a range of cancers including melanoma, lung, renal and urological cancers.

Adjuvant bevacizumab in patients with melanoma at high risk of recurrence (AVAST-M): preplanned interim results from a multicentre, open-label, randomised controlled phase 3 study.

Background: Bevacizumab, a monoclonal antibody that targets VEGF, has shown restricted activity in patients with advanced melanoma. We aimed to assess the role of bevacizumab as adjuvant treatment for patients with resected melanoma at high risk of recurrence. We report results from the preplanned interim analysis.

Detection of PIK3CA mutations in circulating free DNA in patients with breast cancer.

Somatic mutations in PIK3CA (encoding a class I phosphoinositide 3 kinase (PI3K) subunit) modulate PI3K signalling to influence tumour behaviour and occur in up to 40% of breast cancers. Inhibitors of PI3K signalling are entering clinical trials, but the impact of PIKC3A mutation on tumour response has yet to be clarified. This study investigated the potential utility of circulating free DNA (cfDNA) as a source for PIK3CA mutation detection in patients with breast cancer.

Circulating tumour-derived predictive biomarkers in oncology.

Molecular characterization of tumour material will become increasingly important in selecting patients for clinical trials and offering appropriate treatment for patients in clinical practice. Recent advances in the field have indicated that the molecular characteristics of a tumour can be determined from circulating tumour cells and circulating tumour DNA; thus, a simple blood sample could provide these data in a simple, convenient and efficient manner. This article discusses progress towards guiding treatment decisions through measuring tumour-derived factors in the circulation.

Isolation and extraction of circulating tumor DNA from patients with small cell lung cancer.

There is no consensus on the optimal protocol for isolation of circulating tumor DNA. We report our comparison of several extraction methods and variables that may affect yield, quality, and contamination of tumor DNA. DNA was extracted from the plasma and serum of five healthy volunteers by means of four different commercially available kits and DNA yield was quantified by real-time PCR.

Multiplexed assays for detection of mutations in PIK3CA.

Background: Mutations in the PIK3CA gene (phosphoinositide-3-kinase, catalytic, alpha polypeptide) have recently been described in a number of cancers, and their detection is currently limited because of the low sensitivity of conventional sequencing techniques.

Methods: We combined Amplification Refractory Mutation System (ARMS; AstraZeneca) allele-specific PCR and Scorpions (DxS) to develop assays for tumor-borne PIK3CA mutations and used real-time PCR to develop high-throughput multiplexed assays for the most commonly reported PIK3CA mutants (H1047L, H1047R, E542K, E545K).

Results: These assays were more sensitive than sequencing and could detect 5 copies of mutant DNA in proportions as low as 0.

DNA methylation in circulating tumour DNA as a biomarker for cancer.

Free circulating DNA, which is thought to be derived from the primary tumour, can be detected in the blood of patients with cancer. Detection of genetic and epigenetic alteration in this tumour DNA offers a potential source of development of prognostic and predictive biomarkers for cancer. One such change is DNA methylation of the promotor region of tumour suppressor genes.

Metastatic colorectal cancer: current systemic treatment options.

The treatment of colorectal cancer has become increasingly complex over recent years. With the emergence of new chemotherapy drugs and targeted agents, there has been great improvement in the prognosis of patients with metastatic colorectal cancer. This review summarises the evidence supporting the use of combination chemotherapy with oxaliplatin and/or irinotecan with fluorouracil (5-FU) for the treatment of colorectal cancer and outlines the pivotal trials.

Novel therapies for the treatment of small-cell lung cancer: a time for cautious optimism?

Small-cell lung cancer accounts for up to one-fifth of all lung cancers diagnosed. While the response rates to chemotherapy are high, ultimately the majority of patients will relapse and die from their disease. Long-term outcomes are poor.

Anti-angiogenic therapy in the treatment of advanced renal cell cancer.

Metastatic renal cell cancer is associated with a poor prognosis and is resistant to traditional chemotherapy agents. The majority of tumours are associated with inactivation of the von Hippel-Lindau gene and subsequent overexpression of proangiogenic factors, including vascular endothelial growth factor (VEGF). Drugs targeting these pathways have undergone clinical testing in renal cell cancer with encouraging results.

Second-line treatment of postmenopausal women with advanced breast carcinoma.

Breast cancer is the most prevalent cancer in women and, currently, there is no standard of care for the treatment of metastatic disease. Treatment options are based on a number of tumor- and patient-related factors. This review explores some of these options, including the use of hormonal manipulation in the treatment of hormone-positive disease, current chemotherapy options and the use of targeted therapies, such as trastuzumab.