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 normalweight 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 nonfood 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.

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.

Bristol-Myers Squibb, and Genentech. JAS is a compensated member of the advisory boards of Bristol-Myers Squibb, Pfizer, Array, Genentech, Incyte, and Curis and has received research support from Pfizer, Bristol-Myers Squibb, and Curis. PBF receives research funding from Incyte. JMB, MES, MVE, VS, and DBJ are coauthors on a patent pending for use of MHC-II to predict responses from immunotherapy (15/376,276). RSD, DMS, DBJ, and JMB are coauthors on a patent pending for use of FCRL6 antibodies for cancer therapy (62/584,458). JB and JYK are employees of Navigate BioPharma Services and receive compensation as such.

IMPORTANCE Tumor mutational burden (TMB) is a potential biomarker associated with response to immune checkpoint inhibitor therapies. The prognostic value associated with TMB in the absence of immunotherapy is uncertain. OBJECTIVE To assess the prevalence of high TMB (TMB-H) and its association with overall survival (OS) among patients not treated with immunotherapy with the same 10 tumor types from the KEYNOTE-158 study. DESIGN, SETTING, AND PARTICIPANTS This retrospective cohort study evaluated the prognostic value of TMB-H, assessed by Foundation Medicine (FMI) and defined as at least 10 mutations/ megabase (mut/Mb) in the absence of immunotherapy. Data were sourced from the deidentified Flatiron Health-FMI clinicogenomic database collected up to July 31, 2018. Eligible patients were aged 18 years or older with any of the following solid cancer types: anal, biliary, endometrial, cervical, vulvar, small cell lung, thyroid, salivary gland, mesothelioma, or neuroendocrine tumor. Patients with microsatellite instability-high tumors were excluded from primary analysis. For OS analysis, patients were excluded if immunotherapy started on the FMI report date or earlier or if patients died before January 1, 2012, and patients were censored if immunotherapy was started later than the FMI report date. Data were analyzed from November 2018 to February 2019. MAIN OUTCOMES AND MEASURES Overall survival was analyzed using the Kaplan-Meier method and Cox proportional hazards model, adjusting for age, sex, cancer types, practice type, and albumin level. RESULTS Of 2589 eligible patients, 1671 (64.5%) were women, and the mean (SD) age was 63.7 (11.7) years. Median (interquartile range) TMB was 2.6 (1.7-6.1) mut/Mb, and 332 patients (12.8%) had TMB-H (Ն10 mut/Mb). Prevalence of TMB-H was highest among patients with small cell lung cancer (40.0%; 95% CI, 34.7%-45.6%) and neuroendocrine tumor (29.3%; 95% CI, 22.8%-36.6%) and lowest was among patients with mesothelioma (1.2%; 95% CI, 0.3%-4.4%) and thyroid cancer (2.7%; 95% CI, 1.2%-5.7%). Adjusted hazard ratio for OS of patients not treated with immunotherapy with TMB-H vs those without TMB-H was 0.94 (95% CI, 0.77-1.13). Comparable results were observed when including patients with high microsatellite instability tumors and calculating OS from first observed antineoplastic treatment date.

9084 Background: Immune checkpoint inhibitors are active for patients with stage IV NSCLC who have progressed following platinum-based chemotherapy. We evaluated responses to chemotherapy in patients who had progressed on a checkpoint inhibitor. Methods: Eligible patients were adults with NSCLC who received salvage chemotherapy following PD-1/PD-L1 inhibitors (cases) versus no PD-1/PD-L1 inhibitors (controls). CT-imaging was done within 4 weeks of initiation of salvage chemotherapy and every 6 weeks thereafter. Revised RECIST guidelines were used to define response. Clinical and imaging data were abstracted from review of electronic medical records. Multivariate logistic regression analysis was used to calculate probability of response. Results: Three-hundred and fifty patients’ charts were reviewed and 82 patients met eligibility criteria. Among evaluable patients, 46 were males. Sixty-seven patients were cases versus 15 controls. Fifty-six patients received nivolumab, 7 pembrolizumab and 4 atezolizumab. Sixty-three (77%) had adenocarcinoma, 18 (22%) squamous cell carcinoma and 1 (1%) large cell carcinoma. The mean number of chemotherapy regimens prior to salvage chemotherapy was 2.37 (95% C.I. 2.10-2.64)) in cases versus 1.93 (95% C.I: 1.32-2.54) in controls. Salvage drugs included docetaxel (62%), pemetrexed (20%), gemcitabine (12%), paclitaxel (6%). Eighteen (27%) cases had partial response to chemotherapy versus 1(7%) controls. Fifteen (22%) cases had progressive disease versus 6 (40%) controls. Thirty-four (51%) cases had stable disease versus 8 (53%) controls. The odd ratio for achieving a partial response was 0.30 (95% CI: 0.18 to 0.50, P = 0.000). In multiple logistic regression model, age, gender, number of prior chemotherapy regimens, tumor histology, smoking status, different salvage chemotherapy regimens were not associated with the likelihood of achieving a partial response. Conclusions: The odds of achieving a partial response to salvage chemotherapy were more than 3 times higher inpatients with prior exposure to PD-1/PD-L1 inhibitors. Ongoing investigations include the duration of response as well as evaluation of toxicity.

Liquid biopsy and comprehensive genomic profiling (CGP) of circulating tumor DNA (ctDNA) are increasingly used for detection of targetable genomic alterations (GA) in non-small cell lung cancer (NSCLC). To examine the clinical outcomes for patients following CGP using liquid biopsy versus tissue biopsy, receipt of matched targeted therapy post-CGP and associated outcomes were evaluated in the real-world setting. Methods: 6491 patients with NSCLC and liquid biopsy (N = 937 tests) and/or tissue (N = 5582 tests) CGP were included in a de-identified commercial clinico-genomic database. Targetable GAs included National Comprehensive Cancer Network NSCLC guideline biomarkers. Clinical characteristics, real-world progression, and real-world response (rwR) were obtained via technology-enabled abstraction of clinician notes and radiology/pathology reports. Results: At the time of liquid biopsy CGP, 53% (496/937) of patients were documented to have received ≥1 line of prior therapy (tissue CGP: 13%, 735/5582). 90% (832/928) of liquid biopsy cases had evidence of ctDNA. A targetable GA was detected in 20% (188/937) of liquid biopsy and 22% (1215/5582) of tissue CGP cases. Use of matched targeted therapy overall was similar post-liquid biopsy or post-tissue CGP but varied considerably across emerging (25%, 79/317) versus standard of care (SOC) (74%, 475/640) GA. Real-world-progression free survival for patients receiving SOC first line matched targeted therapy administered following liquid biopsy (n = 33) and tissue (n = 229) CGP were similar (13.8 vs 10.6 months; aHR = 0.68 [0.36-1.26]). Among patients evaluated for rwR, overall response rate (partial/complete response) to matched targeted therapy post-liquid biopsy CGP was 75% (39/52) versus 66% post-tissue CGP (254/385, P = 0.51). Conclusion: Retrospective analysis of real-world clinico-genomic data demonstrated that clinical outcomes on matched targeted therapy were similar following liquid biopsy and tissue CGP in NSCLC, which suggests routine clinical use of liquid biopsy CGP can reliably guide therapy selection.Comprehensive Cancer Network (NCCN) NSCLC clinical practice guidelines additionally suggest testing for emerging biomarkers including RET rearrangement, MET exon 14 skipping mutation or amplification, HER2 mutation and tumor mutational burden (TMB) [1][2][3][4]. Beyond genomic biomarkers, immunohistochemical staining for PD-L1 status can guide immunotherapy options [1,5].Testing for targetable genomic alterations (GA) in NSCLC has traditionally been performed on tissue biopsy or surgical specimens. However, such testing may not always be possible due to lack of an

Objective To determine the association of caregiving task burden and patient symptom burden with psychological distress among caregivers of head and neck cancer (HNC) patients. Methods Adults with HNC and their primary caregivers were included. Patient symptom burden was assessed with the Vanderbilt Head and Neck Symptom Survey‐2.0. Caregiving task burden was quantified as task number and task difficulty/distress using the HNC Caregiving Task Inventory. Psychological distress was measured with the Profile of Mood States—Short Form. Two‐step clustering analysis was conducted for patient symptom burden, caregiving task burden, and psychological distress. Associations of the resultant clusters of task burden and patient symptoms with caregiver distress were tested using logistic regressions. Results Eighty‐nine HNC caregivers and 84 patients were included. Among patients, two clusters of symptom burden were found (51% mod‐high, 49% low). Among caregivers, two clusters of caregiving task burden (40% mod‐high, 60% low) and caregiver psychological distress (40% mod‐high, 60% low) were found. Caregivers with mod‐high task numbers and task difficulty/distress reported higher levels of psychological distress. After controlling for caregiver number of tasks, respective difficulty/distress, and patient symptom burden, caregiver perceived task difficulty/distress had the strongest association with caregiver psychological distress (adjusted OR = 3.83; 95% CI, 1.0‐14.64; P = 0.049). Conclusions Psychological distress in HNC caregivers is associated with caregiving task burden, with caregivers experiencing high task difficulty/distress at greatest risk. Further study of the caregiver and task characteristics leading to psychological distress should inform supportive interventions for HNC patients and caregivers.

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.