Racial Disparity in Adherence to Endocrine Therapy among Women with Early-Stage Hormone Receptor Positive Breast Cancer: An Analysis of Arkansas All-Payers Claims Database.

Introduction/background: To assess racial/ethnic disparities in endocrine therapy (ET) adherence among women with breast cancer.

Materials And Methods: A retrospective cohort study of Arkansas All-Payer Claims Database (APCD) linked to Arkansas Cancer Registry (ACR). Women with stages 0-3 HR+ breast cancer diagnosed in 2013-2017 were followed from cancer diagnosis for a year to determine ET initiation.

Consistency Between State's Cancer Registry and All-Payer Claims Database in Documented Radiation Therapy Among Patients Who Received Breast Conservative Surgery.

Purpose: Arkansas is one of only four known states that have linked All-Payer Claims Database (APCD) to state's cancer registry (Arkansas Cancer Registry [ACR]). We evaluated the reporting consistency of radiation therapy (RT) between the two sources.

Methods: Women age ≥ 18 years diagnosed in 2013-2017 with early-stage hormone receptor-positive breast cancer who received breast-conserving surgery were identified.

Immune adverse events (irAEs) with adjuvant ipilimumab in melanoma, use of immunosuppressants and association with outcome: ECOG-ACRIN E1609 study analysis.

Background: The impact of immune-related adverse events (irAEs) occurring from adjuvant use of immunotherapy and of their management on relapse-free survival (RFS) and overall survival (OS) outcomes is currently not well understood.

Patients And Methods: E1609 enrolled 1673 patients with resected high-risk melanoma and evaluated adjuvant ipilimumab 3 mg/kg (ipi3) and 10 mg/kg (ipi10) versus interferon-α. We investigated the association of irAEs and of use of immunosuppressants with RFS and OS for patients treated with ipilimumab (n=1034).

Association of DNA-Methylation Profiles With Immune Responses Elicited in Breast Cancer Patients Immunized With a Carbohydrate-Mimicking Peptide: A Pilot Study.

Immune response to a given antigen, particularly in cancer patients, is complex and is controlled by various genetic and environmental factors. Identifying biomarkers that can predict robust response to immunization is an urgent need in clinical cancer vaccine development. Given the involvement of DNA methylation in the development of lymphocytes, tumorigenicity and tumor progression, we aimed to analyze pre-vaccination DNA methylation profiles of peripheral blood mononuclear cells (PBMCs) from breast cancer subjects vaccinated with a novel peptide-based vaccine referred to as P10s-PADRE.

Phase III Study of Adjuvant Ipilimumab (3 or 10 mg/kg) Versus High-Dose Interferon Alfa-2b for Resected High-Risk Melanoma: North American Intergroup E1609.

Purpose: Phase III adjuvant trials have reported significant benefits in both relapse-free survival (RFS) and overall survival (OS) for high-dose interferon alfa (HDI) and ipilimumab at 10 mg/kg (ipi10). E1609 evaluated the safety and efficacy of ipilimumab at 3 mg/kg (ipi3) and ipi10 versus HDI.

Patients And Methods: E1609 was a phase III trial in patients with resected cutaneous melanoma (American Joint Committee on Cancer 7th edition stage IIIB, IIIC, M1a, or M1b).

In vivo liquid biopsy using Cytophone platform for photoacoustic detection of circulating tumor cells in patients with melanoma.

Most cancer deaths arise from metastases as a result of circulating tumor cells (CTCs) spreading from the primary tumor to vital organs. Despite progress in cancer prognosis, the role of CTCs in early disease diagnosis is unclear because of the low sensitivity of CTC assays. We demonstrate the high sensitivity of the Cytophone technology using an in vivo photoacoustic flow cytometry platform with a high pulse rate laser and focused ultrasound transducers for label-free detection of melanin-bearing CTCs in patients with melanoma.

Germline Genetic Variants in GATA3 and Breast Cancer Treatment Outcomes in SWOG S8897 Trial and the Pathways Study.

Introduction: GATA3 is a critical transcription factor in maintaining the differentiated state of luminal mammary epithelial cells. We sought to determine the prognostic and predictive roles of GATA3 genotypes for breast cancer.

Patients And Methods: Twelve single nucleotide polymorphisms (SNPs) were genotyped in 2 breast cancer cohorts, including the SWOG S8897 trial where patients were treated with adjuvant chemotherapy (CAF [cyclophosphamide, doxorubicin, 5-fluorouracil] vs.

Targeting tumor-associated carbohydrate antigens: a phase I study of a carbohydrate mimetic-peptide vaccine in stage IV breast cancer subjects.

Tumor-associated carbohydrate antigens (TACAs) support cell survival that could be interrupted by anti-TACA antibodies. Among TACAs that mediate cell survival signals are the neolactoseries antigen Lewis Y (LeY) and the ganglioside GD2. To induce sustained immunity against both LeY and GD2, we developed a carbohydrate mimicking peptide (CMP) as a surrogate pan-immunogen that mimics both.

Clinical characteristics, molecular profile and outcomes of myeloid sarcoma: a single institution experience over 13 years.

Background: Myeloid sarcoma (MS) is characterized by extramedullary infiltration by immature myeloid cells. Owing to rarity of this disease, the clinical features and overall outcomes are yet to be clarified.

Objective: To define clinical characteristics, epidemiology, pathologic findings, treatment options and outcomes in MS.

Immune surveillance in melanoma: From immune attack to melanoma escape and even counterattack.

Pharmacologic inhibition of the cytotoxic T lymphocyte antigen 4 (CTLA4) and the programmed death receptor-1 (PD1) has resulted in unprecedented durable responses in metastatic melanoma. However, resistance to immunotherapy remains a major challenge. Effective immune surveillance against melanoma requires 4 essential steps: activation of the T lymphocytes, homing of the activated T lymphocytes to the melanoma microenvironment, identification and episode of melanoma cells by activated T lymphocytes, and the sensitivity of melanoma cells to apoptosis.

Managing Expectations in the Transition to Proof of Concept Studies.

Background: As we move away from the traditional chemotherapy era to targeted therapy, the validity of old assessment paradigms associated with therapeutics are being raised in the context of immunotherapy. The old paradigm required elaborating on the toxicity assessment, with no expectation of efficacy in early phase trials. Safety data from Phase 1 and 2 studies with many immunotherapeutics show limited toxicities and draw attention to the need to demonstrate efficacy in the early evaluation of new agents.

Germline Genetic Variants in TEK, ANGPT1, ANGPT2, MMP9, FGF2 and VEGFA Are Associated with Pathologic Complete Response to Bevacizumab in Breast Cancer Patients.

Background: We previously reported improved pathologic complete response (pCR) in a prospective phase II study using neoadjuvant bevacizumab in combination with chemotherapy compared to chemotherapy alone in breast cancer patients (41% vs. 25%, p = 0.0291).

Harnessing benefit from targeting tumor associated carbohydrate antigens.

Integrating additive or synergistic antitumor effects that focus on distinct elements of tumor biology are the most rational strategies for cancer treatment. Treatments for breast cancer have increased overall survival, but remain limited by lack of efficacy in a subset of breast cancer patients. The real challenge is to define what elements of tumor biology make the most sense to be integrated.

Role of EZH2 histone methyltrasferase in melanoma progression and metastasis.

There is accumulating evidence that the histone methyltransferase enhancer of zeste homolog 2 (EZH2), the main component of the polycomb-repressive complex 2 (PRC2), is involved in melanoma progression and metastasis. Novel drugs that target and reverse such epigenetic changes may find a way into the management of patients with advanced melanoma. We provide a comprehensive up-to-date review of the role and biology of EZH2 on gene transcription, senescence/apoptosis, melanoma microenvironment, melanocyte stem cells, the immune system, and micro RNA.

Pre-diagnosis blood glucose and prognosis in women with breast cancer.

Background: The effect of moderately elevated blood glucose levels among non-diabetic subjects on cancer prognosis is not well described. The goal of this study was to examine the association of elevated random blood glucose (RBG) levels in non-diabetic breast cancer patients with overall survival (OS) and time to tumor recurrence (TTR).

Results: Forty-nine deaths and 32 recurrences occurred among 148 eligible study subjects during 855.

Human papillomavirus type 16 viral load is decreased following a therapeutic vaccination.

In the dose-escalation phase of a Phase I clinical trial in which six subjects each were vaccinated with PepCan at the 50, 100, 250, and 500 μg per peptide dose, the 50 μg dose showed the best histological regression rate. Ten additional subjects were vaccinated at this dose in the final dose phase. As with the dose-escalation phase, no dose-limiting toxicities were observed.

Ipilimumab-Induced Gastrointestinal Toxicities: A Management Algorithm.

Ipilimumab is a cytotoxic T-lymphocyte-associated antigen-4-blocking monoclonal antibody, which has shown a significant survival benefit in metastatic melanoma patients. Despite being a promising therapy for a disease with an otherwise rather dismal prognosis, it is associated with several immune-related adverse effects (IRAE) mainly targeted toward the digestive tract, skin, liver, and hypothalamic-pituitary axis. Ipilimumab-induced gastrointestinal toxicity (IGT) include diarrhea (~44 %), colitis (~18 %), bowel perforation (<1 %), and pancreatitis (<1.

A phase I dose-escalation clinical trial of a peptide-based human papillomavirus therapeutic vaccine with skin test reagent as a novel vaccine adjuvant for treating women with biopsy-proven cervical intraepithelial neoplasia 2/3.

: Non-surgical treatments for cervical intraepithelial neoplasia 2/3 (CIN2/3) are needed as surgical treatments have been shown to double preterm delivery rate. The goal of this study was to demonstrate safety of a human papillomavirus (HPV) therapeutic vaccine called PepCan, which consists of four current good-manufacturing production-grade peptides covering the HPV type 16 E6 protein and skin test reagent as a novel adjuvant. : The study was a single-arm, single-institution, dose-escalation phase I clinical trial, and the patients (n = 24) were women with biopsy-proven CIN2/3.

Rituximab and intermediate-purity plasma-derived factor VIII concentrate (Koate®) as adjuncts to therapeutic plasma exchange for thrombotic thrombocytopenic purpura in patients with an ADAMTS13 inhibitor.

Thrombotic thrombocytopenic purpura (TTP) results from a congenital or acquired deficiency of the von Willebrand factor (vWF)-cleaving protease ADAMTS13. The disease can be fatal and hence treatment should be initiated promptly. Therapeutic plasma exchange (TPE) remains the standard treatment along with adjunct therapies including steroids and immunosuppressive drugs.

Cancer survivorship training: a pilot study examining the educational gap in primary care medicine residency programs.

Background: Cancer survivors need high-quality follow-up care that addresses long-term problems related to cancer and their treatment. With growing numbers of cancer patients transitioning from oncological treatment to survivorship care, primary care physicians (PCPs) will play a major role in the delivery of survivorship care.

Objective: This pilot study was undertaken to provide initial insights into internal medicine (IM) and family medicine (FM) residents' educational experience, training, and preparedness for practice as healthcare providers of adult cancer survivors (ACS).

Merkel Cell Carcinoma: Epidemiology, Target, and Therapy.

Merkel cell carcinoma (MCC) is an aggressive neuroendocrine tumor of the skin with a rising incidence. MCC has metastatic potential regardless the size of the primary tumor and a 5-year disease associated mortality rate is 46 %. Surgery and radiation are the mainstays of management for primary MCC.

High-circulating Tie2 Is Associated With Pathologic Complete Response to Chemotherapy and Antiangiogenic Therapy in Breast Cancer.

Introduction: Vascular endothelial growth factor (VEGF) is a central mediator of angiogenesis in breast cancer. Research in antiangiogenic cancer treatment has been marked by the development of the monoclonal antibody bevacizumab, which targets VEGF in many solid tumors. As patients do not equally benefit from bevacizumab, it has become necessary to define the profile of patients who will benefit from the drug.

Treatment of metastatic melanoma with pazopanib: A report of five patient cases.

Metastatic melanoma has a median length of survival after diagnosis of 6-9 months. Unfortunately, the National Comprehensive Cancer Network clinical practice guidelines for treating stage IV, unresectable, metastatic melanoma are limited with regard to treatment options. Pazopanib (Votrient™) is FDA-approved for advanced soft tissue sarcoma and advanced renal cell carcinoma.