Standard or high dose chemoradiotherapy, with or without the protease inhibitor nelfinavir, in patients with locally advanced pancreatic cancer: The phase 1/randomised phase 2 SCALOP-2 trial.

Background: The multi-centre two-stage SCALOP-2 trial (ISRCTN50083238) assessed whether dose escalation of consolidative chemoradiotherapy (CRT) or concurrent sensitization using the protease inhibitor nelfinavir improve outcomes in locally advanced pancreatic cancer (LAPC) following four cycles of gemcitabine/nab-paclitaxel.

Methods: In stage 1, the maximum tolerated dose (MTD) of nelfinavir concurrent with standard-dose CRT (50.4 Gy in 28 fractions) was identified from a cohort of 27 patients.

Curing Stage IV Melanoma: Where Have We Been and Where Are We?

Little more than 10 years ago, metastatic melanoma was considered to have one of the poorest cancer outcomes, associated with a median overall survival of 6-8 months. Cytotoxic chemotherapy offered modest response rates of 20%-30%, but no clear survival benefit. Patients were routinely enrolled in clinical trials as their first-line therapy in the search for effective novel therapeutics.

A three-arm randomised phase II study of the MEK inhibitor selumetinib alone or in combination with paclitaxel in metastatic uveal melanoma.

Aims: The MAPK pathway is constitutively activated in uveal melanoma (UM). Selumetinib (AZD6244, ARRY-142886), a MEK inhibitor, has shown limited activity as monotherapy in metastatic UM. Pre-clinical studies support synergistic cytotoxic activity for MEK inhibitors combined with taxanes, and here we sought to assess the clinical efficacy of combining selumetinib and paclitaxel.

A randomised phase 2 study of intermittent versus continuous dosing of dabrafenib plus trametinib in patients with BRAF mutant advanced melanoma (INTERIM).

Background: BRAF+MEK inhibitors extend life expectancy of patients with BRAF mutant advanced melanoma. Acquired resistance limits duration of benefit, but preclinical and case studies suggest intermittent dosing could overcome this limitation. INTERIM was a phase 2 trial evaluating an intermittent dosing regimen.

Comparison of three-weekly and six-weekly pembrolizumab United Kingdom prescribing practice for advanced and resected melanoma.

Background: Pembrolizumab is approved for the treatment of advanced and resected melanoma and was originally licensed as a three-weekly infusion (Q3W). In April 2019, a six-weekly infusion schedule (Q6W) was also approved. We retrospectively reviewed pembrolizumab prescribing for patients with melanoma across multiple United Kingdom (UK) centres to compare the safety and efficacy of Q6W with Q3W in real-world clinical practice.

A first census of skin cancer specialist nurses across UK secondary care trusts.

Background: Skin cancer specialist nurses (SCSNs) support patients and work alongside healthcare professionals throughout the care pathway. Skin cancer management is rapidly evolving, with increasing and more complex treatment options now available, so the need for patient support is growing. While SCSNs are a major source of that support, the provision of SCSN resource across the UK has never previously been assessed.

The impact of the COVID-19 pandemic upon pancreatic cancer treatment (CONTACT Study): a UK national observational cohort study.

Introduction: CONTACT is a national multidisciplinary study assessing the impact of the COVID-19 pandemic upon diagnostic and treatment pathways among patients with pancreatic ductal adenocarcinoma (PDAC).

Methods: The treatment of consecutive patients with newly diagnosed PDAC from a pre-COVID-19 pandemic cohort (07/01/2019-03/03/2019) were compared to a cohort diagnosed during the first wave of the UK pandemic ('COVID' cohort, 16/03/2020-10/05/2020), with 12-month follow-up.

Results: Among 984 patients (pre-COVID: n = 483, COVID: n = 501), the COVID cohort was less likely to receive staging investigations other than CT scanning (29.

Revitalising cancer clinical trials: definitely time for patient-centred reform.

Work is ongoing to recover UK clinical research capacity and capabililty post COVID-19 pandemic (https://sites.google.com/nihr.

Circulating galectin-1 delineates response to bevacizumab in melanoma patients and reprograms endothelial cell biology.

Blockade of vascular endothelial growth factor (VEGF) signaling with bevacizumab, a humanized anti-VEGF monoclonal antibody (mAb), or with receptor tyrosine kinase inhibitors, has improved progression-free survival and, in some indications, overall survival across several types of cancers by interrupting tumor angiogenesis. However, the clinical benefit conferred by these therapies is variable, and tumors from treated patients eventually reinitiate growth. Previously we demonstrated, in mouse tumor models, that galectin-1 (Gal1), an endogenous glycan-binding protein, preserves angiogenesis in anti-VEGF-resistant tumors by co-opting the VEGF receptor (VEGFR)2 signaling pathway in the absence of VEGF.

WNT5A-ROR2 axis mediates VEGF dependence of BRAF mutant melanoma.

Purpose: Despite recent advances, approximately 50% of patient with metastatic melanoma eventually succumb to the disease. Patients with melanomas harboring a BRAF mutation (BRAF) have a worse prognosis than those with wildtype (BRAF) tumors. Unexpectedly, interim AVAST-M Phase III trial data reported benefit from adjuvant anti-VEGF bevacizumab only in the BRAF group.

Tumor-Infiltrating Lymphocyte Therapy in Melanoma: Facts to the Future.

Adoptive cell therapy with tumor-infiltrating lymphocytes (TIL) is gaining momentum and demonstrating durable responses in patients with advanced melanoma. Although increasingly considered as a treatment option for select patients with melanoma, TIL therapy is not yet approved by any regulatory agency. Pioneering studies with first-generation TIL therapy, undertaken before the advent of modern melanoma therapeutics, demonstrated clinical efficacy and remarkable long-term overall survival, reaching beyond 20 months for responding patients.

The different faces of metastatic melanoma in the gastrointestinal tract.

Melanoma is the most aggressive form of skin cancer, with tendency to spread to any organ of the human body, including the gastrointestinal tract (GIT). The diagnosis of metastases to the GIT can be difficult, as they may be clinically silent for somewhile and may occur years after the initial melanoma diagnosis. CT imaging remains the standard modality for staging and surveillance of melanoma patients, and in most cases, it will be the first imaging modality to identify GIT lesions.

MRI techniques for immunotherapy monitoring.

MRI is a widely available clinical tool for cancer diagnosis and treatment monitoring. MRI provides excellent soft tissue imaging, using a wide range of contrast mechanisms, and can non-invasively detect tissue metabolites. These approaches can be used to distinguish cancer from normal tissues, to stratify tumor aggressiveness, and to identify changes within both the tumor and its microenvironment in response to therapy.

Retrospective review of outcomes associated with metastatic melanoma patients treated with 1st-line BRAF-targeted therapy.

BRAF-mutant melanoma patients can theoretically access both immunotherapy and BRAF-targeted therapy as treatment for metastatic disease. BRAF-targeted therapy is increasingly used 1st line for poorer prognostic patients, so we wanted to assess realistic expectations of these patients accessing 2nd-line immunotherapy. We conducted a retrospective review of clinical outcomes in 25 patients treated over the last 3 years with 1st-line BRAF-targeted therapy in a real-world clinical setting at a UK-based tertiary centre.

Comparative efficacy and safety of targeted therapies for BRAF-mutant unresectable or metastatic melanoma: Results from a systematic literature review and a network meta-analysis.

Background: The objective of this study was to estimate the relative efficacy and safety of targeted therapies for the treatment of metastatic melanoma using a network meta-analysis (NMA).

Methods: A systematic literature review (SLR) identified studies in Medline, Embase and Cochrane published until November 2020. Screening used prespecified eligibility criteria.

The forgotten appearance of metastatic melanoma in the small bowel.

Background: Melanoma is the most aggressive form of skin cancer, with a tendency to metastasise to any organ of the human body. While the most common body organs affected include liver, lungs, brain and soft tissues, spread to the gastrointestinal tract is not uncommon. In the bowel, it can present with a multitude of imaging appearances, more rarely as an aneurysmal dilatation.