Treatment of Stage III Resectable Melanoma-Adjuvant and Neoadjuvant Approaches.

Patients with stage III resectable melanoma carry a high risk of melanoma recurrence that ranges from approximately 40% to 90% at 5 years following surgical management alone. Postoperative systemic adjuvant therapy targets residual micrometastatic disease that could be the source of future recurrence and death from melanoma. Randomized phase III adjuvant trials reported significant improvements in overall survival with high-dose interferon α in 2 of 3 studies (compared with observation and GMK ganglioside vaccine) and with anti-cytotoxic T-lymphocyte antigen 4 ipilimumab at 10 mg/kg compared with placebo and ipilimumab 3 mg/kg compared with high-dose interferon α.

Updates in Risk Stratification in Myelodysplastic Syndromes.

Risk stratification plays an essential role in treatment planning in myelodysplastic syndromes. For decades, the International Prognostic Scoring System and its revised version have provided unified consensus for clinical trial enrollment and design. These models relied on laboratory and cytogenetic data to estimate prognosis and dictate treatment paradigms.

The Impaired Anesthesia Provider: Strategies to Prevent, Recognize, and Treat Substance Use Disorder within the Workplace.

The development of a substance use disorder within an anesthesia provider is complex and multifactorial. Substance use disorder is considered the number one occupational hazard for anesthesia professionals, and it is estimated that 10%-15% of anesthesia providers will experience a substance use disorder. High stress levels within the workplace environment contribute to the risk of an anesthesia professional developing a substance use disorder.

Overall Survival with Durvalumab after Chemoradiotherapy in Stage III NSCLC.

Background: An earlier analysis in this phase 3 trial showed that durvalumab significantly prolonged progression-free survival, as compared with placebo, among patients with stage III, unresectable non-small-cell lung cancer (NSCLC) who did not have disease progression after concurrent chemoradiotherapy. Here we report the results for the second primary end point of overall survival.

Methods: We randomly assigned patients, in a 2:1 ratio, to receive durvalumab intravenously, at a dose of 10 mg per kilogram of body weight, or matching placebo every 2 weeks for up to 12 months.

Landscape of EGFR-Dependent and -Independent Resistance Mechanisms to Osimertinib and Continuation Therapy Beyond Progression in -Mutant NSCLC.

Purpose: Osimertinib was initially approved for T790M-positive non-small cell lung cancer (NSCLC) and, more recently, for first-line treatment of -mutant NSCLC. However, resistance mechanisms to osimertinib have been incompletely described.

Experimental Design: Using cohorts from The University of Texas MD Anderson Lung Cancer Moonshot GEMINI and Moffitt Cancer Center lung cancer databases, we collected clinical data for patients treated with osimertinib.

Preclinical testing of 5-amino-1-((1R,2S,3S,4R)-2,3-dihydroxy-4-methylcyclopentyl)-1H-imidazole-4-carboxamide: a potent protein kinase C-ι inhibitor as a potential prostate carcinoma therapeutic.

Protein kinase C-iota (PKC-ι) is an oncogene overexpressed in many cancer cells including prostate, breast, ovarian, melanoma, and glioma. Previous in-vitro studies have shown that 5-amino-1-((1R,2S,3S,4R)-2,3-dihydroxy-4-methylcyclopentyl)-1H-imidazole-4-carboxamide (ICA-1s), a PKC-ι specific inhibitor, is effective against some cancer cell lines by decreasing cell growth and inducing apoptosis. To assess ICA-1s as a possible therapeutic, in-vivo studies using a murine model were performed.

Transitioning Patients With Iron Overload From Exjade to Jadenu.

Iron overload is a concern for patients who require chronic transfusions as a result of inherited or acquired anemias, including sickle cell disease, thalassemia, and myelodysplastic syndromes. Iron chelation therapy (ICT) is the primary treatment for iron overload in these patients. The ICT deferasirox, which has been available as an oral dispersible tablet for liquid suspension, is now also available as a once-daily, film-coated tablet (FCT).

Identification and Management of Gene Carriers Detected Through Multigene Panel Testing.

Objectives: The increasing use of multigene panel tests may reveal an unexpected pathogenic variant in the tumor protein p53 () gene among individuals who do not meet clinical criteria for Li-Fraumeni syndrome (LFS). Among a registry-based sample of individuals with a pathogenic (P) or likely pathogenic (LP) variant in , we sought to characterize the original clinical context in which genetic testing was performed, the personal and family history and whether they met clinical LFS criteria, and the follow-up care following diagnosis among those in whom this information was available.

Methods: Among individuals with multigene panel testing (inclusive of the gene) who were part of either the Inherited Cancer Registry or the Vanderbilt Hereditary Cancer Registry protocols and were confirmed to have a P/LP variant in , pedigree was reviewed to characterize personal and family history, including original clinical context for genetic testing and whether they met clinical diagnostic criteria for .

Emerging Therapeutic Strategies in Breast Cancer.

The field of medical oncology is experiencing a period of rapid evolution owing to advances in the fields of genomics, tumor biology, and immunology. These disciplines have provided valuable insights into the heterogeneity between breast tumors, key oncogenic drivers, and the role of the immune system in the natural history of breast cancer. This knowledge is translating into many novel therapeutic strategies using personalized medicines, targeted drug delivery systems, and immunomodulatory agents in the treatment of both the early and metastatic stages of the disease.

Treatment of the Pregnant Patient with Breast Cancer.

Pregnancy-associated breast cancer is defined as invasive breast cancer diagnosed during gestation, within 1 year postpartum, or during lactation. Of particular interest is the treatment of invasive breast cancer during gestation; standard treatment protocols must take into account the health of the fetus. This article reviews the literature and emerging data regarding the treatment of pregnancy-associated breast cancer.

Durvalumab after Chemoradiotherapy in Stage III Non-Small-Cell Lung Cancer.

Background: Most patients with locally advanced, unresectable, non-small-cell lung cancer (NSCLC) have disease progression despite definitive chemoradiotherapy (chemotherapy plus concurrent radiation therapy). This phase 3 study compared the anti-programmed death ligand 1 antibody durvalumab as consolidation therapy with placebo in patients with stage III NSCLC who did not have disease progression after two or more cycles of platinum-based chemoradiotherapy.

Methods: We randomly assigned patients, in a 2:1 ratio, to receive durvalumab (at a dose of 10 mg per kilogram of body weight intravenously) or placebo every 2 weeks for up to 12 months.

Single Institution Review of Patients With Prior Breast Augmentation Undergoing Breast Conservation Therapy for Breast Cancer.

Background: Increasing number of patients with preexisting breast implants desire breast conservation therapy for breast cancer. There is paucity of comparative data on tumor margins and re-excisions in these patients. High re-excision rates up to 25% have been reported in breast conservation therapy patients; efforts to obtain cosmesis and avoid implant rupture might increase this further.

Nivolumab versus Docetaxel in Advanced Squamous-Cell Non-Small-Cell Lung Cancer.

Background: Patients with advanced squamous-cell non-small-cell lung cancer (NSCLC) who have disease progression during or after first-line chemotherapy have limited treatment options. This randomized, open-label, international, phase 3 study evaluated the efficacy and safety of nivolumab, a fully human IgG4 programmed death 1 (PD-1) immune-checkpoint-inhibitor antibody, as compared with docetaxel in this patient population.

Methods: We randomly assigned 272 patients to receive nivolumab, at a dose of 3 mg per kilogram of body weight every 2 weeks, or docetaxel, at a dose of 75 mg per square meter of body-surface area every 3 weeks.

The influence of dermatologist and primary care physician visits on melanoma outcomes among Medicare beneficiaries.

Background: Ambulatory visits to dermatologists and primary care physicians (PCPs) may improve melanoma outcomes through early detection. We sought to measure the effect of dermatologist and PCP visits on melanoma stage at diagnosis and mortality.

Methods: We used data from the database linking Surveillance Epidemiology and End Results (SEER) and Medicare data (1994 to 2005) to examine patterns of dermatologist and PCP ambulatory visits before diagnosis for 18,884 Medicare beneficiaries with invasive melanoma or unknown stage at diagnosis.

From modules to medicine: How modular domains and their associated networks can enable personalized medicine.

Unveiling of cancer genomes is unleashing new therapeutic strategies for cancer. With cancer parts lists in hand, new approaches to personalized medicine can be developed by understanding the assembly of cancer machines using modular domains in proteins and their associated networks. Using the Src-homology-2 (SH2) domain as an example, new profiling approaches can discern global patterns of tyrosine phosphorylation in cancer cells that can enable molecular cancer medicine.

Clinical and imaging surveillance following breast cancer diagnosis.

Breast cancer is the most common malignancy affecting women worldwide. Women have a 1 in 8 lifetime risk of breast cancer. Breast conservation therapy (BCT) is the most common method of definitive treatment.

Positive regulatory domain I (PRDM1) and IRF8/PU.1 counter-regulate MHC class II transactivator (CIITA) expression during dendritic cell maturation.

Dendritic cells (DCs) are key mediators of immune function through robust and tightly regulated presentation of antigen in the context of the MHC Class II. MHC Class II expression is controlled by the transactivator CIITA. CIITA expression in conventional DCs is uniquely dependent on an uncharacterized myeloid cell-specific promoter, CIITApI.

A pilot study of preoperative gefitinib for early-stage lung cancer to assess intratumor drug concentration and pathways mediating primary resistance.

Background: Targeted agents such as tyrosine kinase inhibitors have been extensively studied in preclinical systems and in advanced-stage patients. Little is known about levels of kinase inhibitors found in tumors as opposed to plasma. Similarly, effects of inhibitors on tumor signaling pathways in patient-based materials are unclear.

Immunomodulatory drugs in the treatment of myelodysplastic syndromes.

Purpose Of Review: The aim of this article is to discuss the proposed mechanisms of action, clinical trial data, and clinical implications for use of the immunomodulatory drugs in the treatment of myelodysplastic syndrome.

Recent Findings: The immunomodulatory drugs are a novel, nonteratogenic class of thalidomide analogues that are more potent and less toxic than the parent compound. Lenalidomide, a second generation immunomodulatory drug, has shown substantial remitting activity in myelodysplastic syndrome that is karyotype-dependent.

The role of lenalidomide in the treatment of patients with chromosome 5q deletion and other myelodysplastic syndromes.

Purpose Of Review: The aim of this article is to discuss the relevant pathobiologic effects of lenalidomide and the most recent clinical evidence to support its use in patients with myelodysplastic syndrome.

Recent Findings: Lenalidomide is an immunomodulatory agent with biological activity in several hematologic malignancies, including myelodysplastic syndrome. The precise mechanism yielding benefit in patients with myelodysplastic syndrome and 5q- syndrome is not clear, but various molecular and pathogenic targets have been identified.

Involvement of the SH3 domain in Ca2+-mediated regulation of Src family kinases.

When cells are treated with Ca(2+) and Ca(2+)-ionophore, c-Src kinase activity increases, whereas c-Yes kinase activity decreases. This opposite modulation can be reproduced in an in vitro reconstitution assay and is dependent on Ca(2+) and on soluble factors present in cell lysates. Since c-Src and c-Yes share a high degree of homology, with the exception of their N-terminal "unique" domains, their activity was thought to be coordinately regulated.

Activated epidermal growth factor receptor-Stat-3 signaling promotes tumor survival in vivo in non-small cell lung cancer.

Purpose: Signal transducers and activators of transcription 3 (Stat3), a member of the STAT family of transcription factors, regulates multiple oncogenic pathways, including pathways regulating tumor cell survival. We evaluated Stat3 activation in early stage non-small cell lung cancers (NSCLC) and how this relates to upstream epidermal growth factor receptor (EGFR) activation, tumor apoptosis, and prognosis.

Experimental Design: High-density tissue microarrays using tissues from 176 surgically resected NSCLC were evaluated for expression of phosphorylated Stat3 (pStat3) and epidermal growth factor receptor (pEGFR) along with tumor apoptosis.

Mutagenesis of Glycine 179 modulates both catalytic efficiency and reduced pyridine nucleotide specificity in cytochrome b5 reductase.

Cytochrome b5 reductase (cb5r), a member of the ferredoxin:NADP+ reductase family of flavoprotein transhydrogenases, catalyzes the NADH-dependent reduction of cytochrome b5. Within this family, a conserved "GxGxxP" sequence motif has been implicated in binding reduced pyridine nucleotides. However, Glycine 179, a conserved residue in cb5r primary structures, precedes this six-residue "180GxGxxP185" motif that has been identified as binding the adenosine moiety of NADH.

The efficacy and safety of pain management before and after implementation of hospital-wide pain management standards: is patient safety compromised by treatment based solely on numerical pain ratings?

Unlabelled: Inadequate analgesia in hospitalized patients prompted the Joint Commission on Accreditation of Healthcare Organizations in 2001 to introduce standards that require pain assessment and treatment. In response, many institutions implemented treatment guided by patient reports of pain intensity indexed with a numerical scale. Patient safety associated with treatment of pain guided by a numerical pain treatment algorithm (NPTA) has not been examined.

Small tumor size and limited smoking history predicts activated epidermal growth factor receptor in early-stage non-small cell lung cancer.

Study Objective: Epidermal growth factor receptor (EGFR) signaling has been implicated in the pathogenesis of bronchial dysplasia and overt non-small cell lung cancer (NSCLC). We hypothesized that assaying for EGFR activity using an antibody that recognizes phosphorylated EGFR (pEGFR) may identify a subset of patients whose tumor cells are dependent on EGFR signaling. We also hypothesized that EGFR activity may be prognostic for early-stage NSCLC.