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// Anna K. Brady 1 , Jonathan D. McNeill 2 , Brendan Judy 3 , Joshua Bauml 4 , Tracey L. Evans 4 , Roger B. Cohen 4 , Corey Langer 4 , Anil Vachani 5 , Charu Aggarwal 4 1 Department of Medicine, Washington University Medical Center, St. Louis, MO, USA 2 Ruth and Raymond Perelman School of Medicine of the University of Pennsylvania, Philadelphia, PA, USA 3 Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA, USA 4 Division of Hematology and Oncology, University of Pennsylvania, Philadelphia, PA, USA 5 Division of Pulmonary, Allergy and Critical Care, University of Pennsylvania, Philadelphia, PA, USA Correspondence to: Charu Aggarwal, e-mail: Charu.Aggarwal@uphs.upenn.edu Keywords: KRAS, non-small cell lung cancer, bevacizumab Received: May 06, 2015 Accepted: August 24, 2015 Published: September 03, 2015 ABSTRACT Introduction: Mutations (MT) of the KRAS gene are the most common mutation in non-small cell lung cancer (NSCLC), seen in about 20–25% of all adenocarcinomas. Effect of KRAS MT on response to cytotoxic chemotherapy is unclear. Methods: We undertook a single-institution retrospective analysis of 93 consecutive patients with stage IV NSCLC adenocarcinoma with known KRAS and EGFR MT status to determine the association of KRAS MT with survival. All patients were treated between January 1, 2008 and December 31, 2011 with standard platinum based chemotherapy at the University of Pennsylvania. Overall and progression free survival were analyzed using Kaplan-Meier and Cox proportional hazard methods. Results: All patients in this series received platinum doublet chemotherapy, and 42 (45%) received bevacizumab. Overall survival and progression free survival for patients with KRAS MT was no worse than for patients with wild type KRAS. Median overall survival for patients with KRAS MT was 19 months (mo) vs. 15.6 mo for KRAS WT, p = 0.34, and progression-free survival was 6.2 mo in patients with KRAS MT vs. 7mo in patients with KRAS WT, p = 0.51. In multivariable analysis including age, race, gender, and ECOG PS, KRAS MT was not associated with overall survival (HR 1.12, 95% CI 0.58–2.16, p = 0.74) or progression free survival (HR 0.80, 95% CI 0.48–1.34, p = 41). Of note, receipt of bevacizumab was associated with improved overall survival only in KRAS WT patients (HR 0.34, p = 0.01). Conclusions: KRAS MT are not associated with inferior progression-free and overall survival in advanced NSCLC patients treated with standard first-line platinum-based chemotherapy.

Access to antiretroviral therapy is rapidly expanding in sub-Saharan Africa. Identifying the predictors of incomplete adherence virologic failure and antiviral drug resistance is essential to achieving long-term success. A total of 150 subjects who had received antiretroviral therapy for at least 6 months completed a structured questionnaire and adherence assessment and plasma human immunodeficiency virus (HIV) RNA levels were measured. Virologic failure was defined as an HIV RNA level > 400 copies/mL; for patients with an HIV RNA level > 1000 copies/mL genotypic antiviral drug resistance testing was performed. Predictors were analyzed using bivariable and multivariable logistic regression models. A total of 23 (16%) of 150 subjects reported incomplete adherence. Sacrificing health care for other necessities (adjusted odds ratio [AOR] 19.8; P < .01) and the proportion of months receiving self-funded treatment (AOR 23.5; P = .04) were associated with incomplete adherence. Virologic failure was identified in 48 (32%) of 150 subjects and was associated with incomplete adherence (AOR 3.6; P = .03) and the proportion of months receiving self-funded antiretroviral therapy (AOR 13.0; P = .02). Disclosure of HIV infection status to family members or others was protective against virologic failure (AOR 0.10; P = .04). Self-funded treatment was associated with incomplete adherence and virologic failure and disclosure of HIV infection status was protective against virologic failure. Efforts to provide free antiretroviral therapy and to promote social coping may enhance adherence and reduce rates of virologic failure. (authors)

7595 Background: KRAS mutations (MT) form a distinct subset of NSCLC, generally considered to have poor prognosis. Although KRAS MT is a well-establised prognostic and predictive marker in colorectal cancer, its role in NSCLC remains ambiguous. Pts with KRAS MT NSCLC do not respond well to epidermal growth factor receptor (EGFR) directed tyrosine kinase inhibitor therapy, but little is known about the ability of KRAS MT to predict outcome after first-line chemotherapy in newly diagnosed advanced or recurrent NSCLC. Methods: We analyzed outcomes of consecutive pts with newly identified Stage IV non- squamous NSCLC treated at University of Pennsylvania (Penn) between 05/2008 and 7/2010 and then compared survival based on KRAS status [MT vs wild type (WT)] using chi square, Kaplan-Meier methods, and Cox regression models. Results: Of 106 consecutive new pts with Stage IV non squamous NSCLC treated at Penn, 49 (46%) underwent molecular analysis for KRAS MT. Fifteen (34%) were KRAS MT. Of 34 KRAS WT pts, 6 were positive for EGFR MT. The median age of all 49 pts was 61 years; 83% were Caucasian, 45% male and 60% had a >10 pack year smoking history. Median duration of follow up is 16.4 mos. Majority of pts (92%) had adenocarcinoma histology. Most pts (88%) had ECOG PS 0-1 at presentation. Forty three pts received first line platinum-based combination chemotherapy (platinum and pemetrexed in 31 pts). KRAS MT was associated with smoking (p=0.04), but not with gender or age. Overall survival (OS) of pts with KRAS MT was similar to KRAS WT pts [median OS 15.6 vs. 19.0 mos; HR 1.24 (95% CI 0.57-2.67)]. Univariate analyses demonstrated superior OS among women compared to men (HR 0.40, 95% CI 0.20-0.85) in the entire pt cohort. Conclusions: In our population of stage IV non squamous NSCLC, pts with KRAS MT had similar OS to those with KRAS WT tumors. OS was slightly higher in KRAS WT pts, but this may have been confounded by the inclusion of 6 EGFR MT pts in this cohort. The potential prognostic or predictive role of KRAS MT in NSCLC pts undergoing chemotherapy requires further prospective study.

Background Childhood obesity is a growing health concern known to adversely affect quality of life in children and adolescents. The Patient Reported Outcomes Measurement Information System (PROMIS) pediatric measures were developed to capture child self-reports across a variety of health conditions experienced by children and adolescents. The purpose of this study is to begin the process of validation of the PROMIS pediatric measures in children and adolescents affected by obesity. Methods The pediatric PROMIS instruments were administered to 138 children and adolescents in a cross-sectional study of patient reported outcomes in children aged 8–17 years with age-adjusted body mass index (BMI) greater than the 85th percentile in a design to establish known-group validity. The children completed the depressive symptoms, anxiety, anger, peer relationships, pain interference, fatigue, upper extremity, and mobility PROMIS domains utilizing a computer interface. PROMIS domains and individual items were administered in random order and included a total of 95 items. Patient responses were compared between patients with BMI 85 to