Emily H. Castellanos

Obese adults have visual attention bias for food cue images: evidence for altered reward system function

Background:The major aim of this study was to investigate whether the motivational salience of food cues (as reflected by their attention-grabbing properties) differs between obese and normal-weight subjects in a manner consistent with altered reward system function in obesity.Methodology/Principal Findings:A total of 18 obese and 18 normal-weight, otherwise healthy, adult women between the ages of 18 and 35 participated in an eye-tracking paradigm in combination with a visual probe task. Eye movements and reaction time to food and non-food images were recorded during both fasted and fed conditions in a counterbalanced design. Eating behavior and hunger level were assessed by self-report measures. Obese individuals had higher scores than normal-weight individuals on self-report measures of responsiveness to external food cues and vulnerability to disruptions in control of eating behavior. Both obese and normal-weight individuals demonstrated increased gaze duration for food compared to non-food images in the fasted condition. In the fed condition, however, despite reduced hunger in both groups, obese individuals maintained the increased attention to food images, whereas normal-weight individuals had similar gaze duration for food and non-food images. Additionally, obese individuals had preferential orienting toward food images at the onset of each image. Obese and normal-weight individuals did not differ in reaction time measures in the fasted or fed condition.Conclusions/Significance:Food cue incentive salience is elevated equally in normal-weight and obese individuals during fasting. Obese individuals retain incentive salience for food cues despite feeding and decreased self-report of hunger. Sensitization to food cues in the environment and their dysregulation in obese individuals may play a role in the development and/or maintenance of obesity.

Current treatment options for pancreatic carcinoma.

Pancreas cancer is a significant cause of cancer mortality; therefore, the development of early diagnostic strategies and effective treatment is essential. Improvements in imaging technology, as well as use of biomarkers such as CA 19–9, are changing the way that pancreas cancer is diagnosed and staged. Although progress in treatment for pancreas cancer has been incremental, development of combination therapies involving both chemotherapeutic and biologic agents is ongoing. This article reviews current strategies in the diagnosis and treatment of resectable and advanced pancreas cancer.

Sodium thiosulfate in the treatment of non-uremic calciphylaxis

Calciphylaxis is a metastatic calcification‐induced vasculopathy that results in the occlusion of small blood vessels. Although calciphylaxis is normally associated with end‐stage renal disease, calciphylaxis from non‐uremic origin occurs as well. While the number of reports continues to increase, a standard treatment for non‐uremic calciphylaxis has yet to be established. Sodium thiosulfate (STS), which has been proven to be effective in the treatment of uremic calciphylaxis, shows promise; however, reports of its use in non‐uremic cases are limited. We describe a case of non‐uremic calciphylaxis in a patient with normal renal and parathyroid function who had complete resolution of disease after treatment with STS, and we review similar cases in the published work. Based on the successful outcomes detailed in this case series, STS appears to be an effective therapy for non‐uremic calciphylaxis.

Driven by Mutations: The Predictive Value of Mutation Subtype in EGFR-Mutated Non-Small Cell Lung Cancer.

Abstract EGFR‐mutated NSCLC is a genetically heterogeneous disease that includes more than 200 distinct mutations. The implications of mutational subtype for both prognostic and predictive value are being increasingly understood. Although the most common EGFR mutations—exon 19 deletions or L858R mutations—predict sensitivity to EGFR tyrosine kinase inhibitors (TKIs), it is now being recognized that outcomes may be improved in patients with exon 19 deletions. Additionally, 10% of patients will have an uncommon EGFR mutation, and response to EGFR TKI therapy is highly variable depending on the mutation. Given the growing recognition of the genetic and clinical variation seen in this disease, the development of comprehensive bioinformatics‐driven tools to both analyze response in uncommon mutation subtypes and inform clinical decision making will be increasingly important. Clinical trials of novel EGFR TKIs should prospectively account for the presence of uncommon mutation subtypes in study design.

Re-Evaluating Progression in an Era of Progress: A Review of First- and Second-Line Treatment Options in Anaplastic Lymphoma Kinase-Positive Non-Small Cell Lung Cancer

UNLABELLED : The advent of crizotinib, the first small molecule inhibitor against anaplastic lymphoma kinase (ALK), has led to impressive advances in the care of patients with advanced ALK-rearranged non-small cell lung cancer. The development of second-generation ALK inhibitors, starting with the recent U.S. Food and Drug Administration approval of ceritinib, promises to expand the therapeutic landscape for this cohort of patients. With increasing use of molecularly targeted therapy options, it has been observed that disease progression in patients receiving targeted agents has a heterogeneous biology, manifesting as either oligoprogressive or widely progressive disease, which may require development of innovative treatment strategies. This review discusses the first- and second-generation ALK inhibitors approved or in clinical development, as well as the novel challenges and approaches to disease progression in patients on targeted agents. IMPLICATIONS FOR PRACTICE The identification of driver mutations in non-small cell lung cancer (NSCLC), most prominently epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK), has expanded treatment options for a significant cohort of patients. However, the success of targeted agents has brought new challenges, particularly regarding management of progression. Progression manifests heterogeneously, and management of oligoprogression may differ from diffusely progressive disease. Multiple options for treatment at progression exist, and it is becoming evident that selecting the best avenue of care requires understanding the biology and potential drivers of disease progression. This review discusses the array of treatment options available for patients with ALK-positive NSCLC, as well as evaluation and treatment of progressive disease.

Overcoming Resistance Without the Risk of Reaction: Use of Afatinib and Panitumumab in Two Cases of Epidermal Growth Factor Receptor--Mutated Non--Small-Cell Lung Cancer With T790M Mutations.

Patients with acquired resistance to first-generation EGFR TKIs, including those with the T790M mutation, may still respond to EGFR-targeted therapy. Combination afatinib and panitumumab may represent a viable therapeutic option for patients with acquired resistance to first-generation EGFR TKIs. Optimal management of LMC is an ongoing challenge, and the efficacy of targeted therapies remains undefined.

Patient Protection and Affordable Care Act Medicaid expansion and gains in health insurance coverage and access among cancer survivors: ACA Medicaid Expansion and Cancer Survivors

The Patient Protection and Affordable Care Act extends Medicaid coverage to millions of low‐income adults, including many survivors of cancer who were unable to purchase affordable health insurance coverage in the individual health insurance market.

Clinical Response to Anti–Programmed Death 1 After Response and Subsequent Progression on Anti–Programmed Death Ligand 1 Therapy

Immune checkpoint inhibitors are rapidly becominga cornerstone in the treatmentofnon–small cell lung cancer (NSCLC). The programmed death 1 (PD-1) receptor and its two ligands, programmed death ligand1(PD-L1;B7H1)andligand2(PD-L2; B7-DC), negatively regulate T-cell activation, and expression of PD-L1 by tumor cells is an important mechanism of immune evasion. Multiple agents have been developed to disrupt tumor-associated immune evasion by targeting either PD-1 or PDL1. Nivolumab and pembrolizumab, both anti– PD-1 agents approved for advanced NSCLC progressing after chemotherapy, confer an overall survival benefit and produce response rates in 16% to 23% of unselected patients with NSCLC. Food andDrugAdministrationapprovalwasalsorecently extended to pembrolizumab in the first-line setting for patients with metastatic NSCLC expressing PD-L1. Atezolizumab, an anti–PD-L1 agent, has also demonstrated an overall survival benefit and has been approved for use in the second-line setting. The growing supply of treatment options has led to new questions of optimal sequencing and choice of therapy. In particular, the utility of serial treatment with immune checkpoint inhibitors has not been established.

Abstract A77: Patterns of medical utilization, finances, health behaviors and comorbidities in older adults reporting negative versus positive net worth after a cancer diagnosis

Purpose: Financial insolvency following cancer has been linked to increased mortality; however, the individual financial factors, insurance, medical utilization, health behaviors, and comorbidities in cancer patients with a negative net worth (NNW) have not been characterized. Using the Health and Retirement Study, a national longitudinal survey of U.S. households from 1992 to 2012, we examined the effect of a cancer diagnosis on medical spending and personal finances in adults age-eligible for Medicare insurance. Demographic variables, insurance status, and measures of medical utilization, finances, and health in cancer patients reporting negative and positive net worth were assessed. Methods: Analyses were restricted to individuals age 65 years or older to reduce heterogeneity in employment and insurance status. Individual-level fixed effect panel analyses were performed to assess the effect of a cancer diagnosis on log out-of-pocket medical spending, hospitalizations, log household debt, Medicaid enrollment, and NNW. Subset analyses were performed by gender and time period (pre- and post-2002). Summary measures of cancer patients, partitioned by presence or absence of NNW, were performed on financial indices, medical utilization, health measures, and insurance. Results: A new cancer diagnosis significantly increased out-of-pocket medical spending, hospitalizations, Medicaid enrollment, and risk of NNW in all respondents, as well as household debt in males. Following a cancer diagnosis, there was a large change in medical utilization, with a 36.7% increase in log out-of-pocket medical spending and a 71.4% increase in hospitalizations (p Conclusion: A diagnosis of cancer increases out-of-pocket medical spending, hospitalizations, and financial insolvency among individuals age-eligible for Medicare insurance protection. Newly diagnosed cancer patients reporting negative net worth have multiple differences in socioeconomic status, medical utilization, and comorbidities as compared to patients with positive net worth, which may contribute to disparities in survival outcomes. Citation Format: Emily Castellanos, Michael Richards. Patterns of medical utilization, finances, health behaviors and comorbidities in older adults reporting negative versus positive net worth after a cancer diagnosis. [abstract]. In: Proceedings of the Ninth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2016 Sep 25-28; Fort Lauderdale, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2017;26(2 Suppl):Abstract nr A77.

Immunotherapy in Lung Cancer

Lung cancer has not traditionally been viewed as an immune-responsive tumor. However, it is becoming evident that tumor-induced immune suppression is vital to malignant progression. Immunotherapies act by enhancing the patients innate immune response and hold promise for inducing long-term responses in select patients with non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). Immune checkpoint inhibitors, in particular, inhibitors to cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and programmed death 1 (PD-1) and programmed death receptor ligand 1 (PD-L1) have shown promise in early studies and are currently in clinical trials in both small cell lung cancer and non-small cell lung cancer patients. Two large randomized phase III trials recently demonstrated superior overall survival (OS) in patients treated with anti-PD-1 therapy compared to chemotherapy in the second-line setting.