Prospective Validation of Molecular Prognostic Markers in Cutaneous Melanoma: A Correlative Analysis of E1690.

To validate the prognostic impact of combined expression levels of three markers (SPP1, RGS1, and NCOA3) in melanoma specimens from patients enrolled in the E1690 clinical trial of high-dose or low-dose IFNα-2b versus observation. Tissue was available from 248 patients. Marker expression was determined by digital imaging of immunohistochemically stained slides.

Collaborative Care in Melanoma: The Essential Role of the Nurse .

This article provides perspective from medical oncologists on the importance of this supplement from the Melanoma Nursing Initiative. The authors (a) delineate the challenges inherent in addressing adverse event (AE) management with newer melanoma therapies, particularly in the community setting; (b) illustrate how advanced practice providers with extensive clinical trial experience in melanoma are in a key position to set the agenda and educate colleagues on best practices in AE management; and

Adjuvant interferon-α for the treatment of high-risk melanoma: An individual patient data meta-analysis.

Background: Many randomised trials assessing interferon-α (IFN-α) as adjuvant therapy for high-risk malignant melanoma have been undertaken. To better assess the role of IFN-α, an individual patient data (IPD) meta-analysis of these trials was undertaken.

Methods: IPD was sought from all randomised trials of adjuvant IFN-α versus no IFN-α for high-risk melanoma.

The effector AvrRxo1 phosphorylates NAD in planta.

Gram-negative bacterial pathogens of plants and animals employ type III secreted effectors to suppress innate immunity. Most characterized effectors work through modification of host proteins or transcriptional regulators, although a few are known to modify small molecule targets. The Xanthomonas type III secreted avirulence factor AvrRxo1 is a structural homolog of the zeta toxin family of sugar-nucleotide kinases that suppresses bacterial growth.

Interferon-γ Drives T Fragility to Promote Anti-tumor Immunity.

Regulatory T cells (T) are a barrier to anti-tumor immunity. Neuropilin-1 (Nrp1) is required to maintain intratumoral T stability and function but is dispensable for peripheral immune tolerance. T-restricted Nrp1 deletion results in profound tumor resistance due to T functional fragility.

Immune Correlates of GM-CSF and Melanoma Peptide Vaccination in a Randomized Trial for the Adjuvant Therapy of Resected High-Risk Melanoma (E4697).

E4697 was a multicenter intergroup randomized placebo-controlled phase III trial of adjuvant GM-CSF and/or a multiepitope melanoma peptide vaccine for patients with completely resected, high-risk stage III/IV melanoma. A total of 815 patients were enrolled from December 1999 to October 2006 into this six-arm study. GM-CSF was chosen to promote the numbers and functions of dendritic cells (DC).

Identifying baseline immune-related biomarkers to predict clinical outcome of immunotherapy.

As cancer strikes, individuals vary not only in terms of factors that contribute to its occurrence and development, but as importantly, in their capacity to respond to treatment. While exciting new therapeutic options that mobilize the immune system against cancer have led to breakthroughs for a variety of malignancies, success is limited to a subset of patients. Pre-existing immunological features of both the host and the tumor may contribute to how patients will eventually fare with immunotherapy.

Safety and efficacy of the antiganglioside GD3 antibody ecromeximab (KW2871) combined with high-dose interferon-α2b in patients with metastatic melanoma.

This study evaluated the safety and clinical benefit of ecromeximab (KW2871) combined with high-dose interferon-α2b (HDI) in patients with metastatic melanoma. We also carried out pharmacokinetic and immune monitoring studies of this combination. This was an open-label, phase 1/2 study of ecromeximab plus HDI in patients with measurable metastatic melanoma.

Genetic and Epigenetic Alterations of TERT Are Associated with Inferior Outcome in Adolescent and Young Adult Patients with Melanoma.

Progression of melanoma to distant sites in adolescents and young adults (AYAs) is not reliably predicted by clinicopathologic criteria. TERT promoter mutations when combined with BRAF/NRAS mutations correlate with adverse outcome in adult melanoma. To determine the prognostic value of TERT alterations in AYA melanoma, we investigated the association of TERT promoter mutations, as well as promoter methylation, an epigenetic alteration also linked to TERT upregulation, with TERT mRNA expression and outcome using a well-characterized cohort of 27 patients with melanoma (ages 8-25, mean 20).

A phase 2 trial of dasatinib in patients with locally advanced or stage IV mucosal, acral, or vulvovaginal melanoma: A trial of the ECOG-ACRIN Cancer Research Group (E2607).

Background: KIT-directed tyrosine kinase inhibitors such as imatinib have demonstrated benefits in KIT-mutant (KIT+) mucosal, acral, vulvovaginal, and chronically sun-damaged (CSD) melanoma. Dasatinib has superior preclinical activity in comparison with other tyrosine kinase inhibitors against cells with the most common KIT mutation, exon 11 . The ECOG-ACRIN E2607 trial assessed dasatinib in patients with these melanoma subtypes.

A Large Skin Cancer Screening Quality Initiative: Description and First-Year Outcomes.

Importance: The lack of prospective randomized clinical trials demonstrating that full-body skin examination (FBSE) reduces melanoma morbidity or mortality has prompted an "I" rating from the United States Preventive Services Task Force for population-based skin cancer screening. More data on these screening programs are needed.

Objectives: To describe a skin cancer screening quality initiative in a large health care system and to determine if the intervention was associated with screening of a demographically higher-risk population than previous screening programs and if melanoma incidence and thickness differed in screened vs unscreened patients.

The HDAC inhibitor AR42 interacts with pazopanib to kill trametinib/dabrafenib-resistant melanoma cells in vitro and in vivo.

Studies focused on the killing of activated B-RAF melanoma cells by the histone deacetylase (HDAC) inhibitor AR42. Compared to other tumor cell lines, PDX melanoma isolates were significantly more sensitive to AR42-induced killing. AR42 and the multi-kinase inhibitor pazopanib interacted to activate: an eIF2α-Beclin1 pathway causing autophagosome formation; an eIF2α-DR4/DR5/CD95 pathway; and an eIF2α-dependent reduction in the expression of c-FLIP-s, MCL-1 and BCL-XL.

Phase III Randomized Study of 4 Weeks of High-Dose Interferon-α-2b in Stage T2bNO, T3a-bNO, T4a-bNO, and T1-4N1a-2a (microscopic) Melanoma: A Trial of the Eastern Cooperative Oncology Group-American College of Radiology Imaging Network Cancer Research Group (E1697).

Purpose To test the efficacy of 4 weeks of intravenous (IV) induction with high-dose interferon (IFN) as part of the Eastern Cooperative Oncology Group regimen compared with observation (OBS) in patients with surgically resected intermediate-risk melanoma. Patients and Methods In this intergroup international trial, eligible patients had surgically resected cutaneous melanoma in the following categories: (1) T2bN0, (2) T3a-bN0, (3) T4a-bN0, and (4) T1-4N1a-2a (microscopic). Patients were randomly assigned to receive IFN α-2b at 20 MU/m/d IV for 5 days (Monday to Friday) every week for 4 weeks (IFN) or OBS.

Comparison of prognostic indices in patients who undergo melanoma brain metastasis radiosurgery.

OBJECTIVE The goal of this study was to use 4 prognostic indices to compare survival times of patients who underwent Gamma Knife stereotactic radiosurgery (SRS) to treat melanoma brain metastases. METHODS The authors analyzed 422 consecutive patients (1440 brain metastases) who underwent Gamma Knife SRS. The median total brain tumor volume was 4.

Evaluation of the effectiveness of music therapy in improving the quality of life of palliative care patients: a randomised controlled pilot and feasibility study.

Background: Music therapy is frequently used as a palliative therapy. In consonance with the goals of palliative care, the primary aim of music therapy is to improve people's quality of life by addressing their psychological needs and facilitating communication. To date, primarily because of a paucity of robust research, the evidence for music therapy's effectiveness on patient reported outcomes is positive but weak.

Contemporary experience with high-dose interleukin-2 therapy and impact on survival in patients with metastatic melanoma and metastatic renal cell carcinoma.

High-dose interleukin-2 (HD IL-2) was approved for treatment of metastatic renal cell carcinoma (mRCC) in 1992 and for metastatic melanoma (mM) in 1998, in an era predating targeted therapies and immune checkpoint inhibitors. The PROCLAIM registry was established to collect and analyze data for patients treated with HD IL-2 in the current era. This analysis includes 170 patients with mM and 192 patients with mRCC treated between 2005 and 2012 with survival data current as of July 27, 2015.

A retrospective analysis of High-Dose Interleukin-2 (HD IL-2) following Ipilimumab in metastatic melanoma.

Background: High dose interleukin-2 (HD IL-2) can induce durable responses in a subset of patients leading to long-term survival. Immune checkpoint blockade (ICB) has demonstrated similarly durable responses in a larger proportion of patients. However, not all patients respond to immune checkpoint blockade and subsequent therapeutic options need to be explored.

A novel microflow LC-MS method for the quantitation of endocannabinoids in serum.

Endocannabinoids (ECs) represent a class of endogenous, small molecules that bind and activate the G-protein coupled EC receptors. They are involved in a variety of fundamental biological processes and are associated with many disease states. Endocannabinoids are often present in complex matrices and at low concentrations, complicating their measurement.

Non-targeted Metabolomics in Diverse Sorghum Breeding Lines Indicates Primary and Secondary Metabolite Profiles Are Associated with Plant Biomass Accumulation and Photosynthesis.

Metabolomics is an emerging method to improve our understanding of how genetic diversity affects phenotypic variation in plants. Recent studies have demonstrated that genotype has a major influence on biochemical variation in several types of plant tissues, however, the association between metabolic variation and variation in morphological and physiological traits is largely unknown. Sorghum bicolor (L.

Dietary supplementation with rice bran or navy bean alters gut bacterial metabolism in colorectal cancer survivors.

Scope: Heat-stabilized rice bran (SRB) and cooked navy bean powder (NBP) contain a variety of phytochemicals that are fermented by colonic microbiota and may influence intestinal health. Dietary interventions with these foods should be explored for modulating colorectal cancer risk.

Methods And Results: A randomized-controlled pilot clinical trial investigated the effects of eating SRB (30 g/day) or cooked navy bean powder (35 g/day) on gut microbiota and metabolites (NCT01929122).

Melanoma and immunotherapy bridge 2015 : Naples, Italy. 1-5 December 2015.

MELANOMA BRIDGE 2015 KEYNOTE SPEAKER PRESENTATIONS Molecular and immuno-advances K1 Immunologic and metabolic consequences of PI3K/AKT/mTOR activation in melanoma Vashisht G. Y. Nanda, Weiyi Peng, Patrick Hwu, Michael A.

Downstream consequences of melanoma screening in a community practice setting: First results.

Background: Population-based screening for the early detection of melanoma holds great promise for reducing melanoma mortality, but evidence is needed to determine whether benefits outweigh risks. Skin surgeries and dermatology visits after screening were assessed to indicate potential physical, psychological, and financial consequences.

Methods: Targeted primary care providers (PCPs) at the University of Pittsburgh Medical Center were trained to detect early melanoma using the INFORMED (INternet course FOR Melanoma Early Detection) program.

IFN-λ cancer immunotherapy: new kid on the block.

Interferon-lambda (IFN-λ) is a new IFN type, related to IFN-α, that is commonly used in the clinic. However, significant side effects accompanying IFN-α treatment limit enthusiasm for IFN-α. In this review, we discuss the current landscape of IFN-α use in oncology and describe the biologic characteristics of IFN-λ.