The effects of financial incentives on diabetes prevention program attendance and weight loss among low-income patients: the We Can Prevent Diabetes cluster-randomized controlled trial.

BACKGROUND: Penetration and participation of real life implementation of lifestyle change programs to prevent type 2 diabetes has been challenging. This is particularly so among low income individuals in the United States. The purpose of this study is to examine the effectiveness of financial incentives on attendance and weight loss among Medicaid beneficiaries participating in the 12-month Diabetes Prevention Program (DPP). METHODS: This is a cluster-randomized controlled trial with two financial incentive study arms and an attention control study arm. Medicaid beneficiaries with prediabetes from 13 primary care clinics were randomly assigned to individually earned incentives (IND; 33 groups; n = 309), a hybrid of individual- and group-earned incentives (GRP; 30 groups; n = 259), and an attention control (AC; 30 groups; n = 279). Up to $520 in incentives could be earned for attaining attendance and weight loss goals over 12 months. Outcomes are percent weight loss from baseline, achieving 5% weight loss from baseline, and attending 75% of core and 75% of maintenance DPP sessions. Linear mixed models were used to examine weight change and attendance rates over the 16 weeks and 12 months. RESULTS: The percent weight change at 16 weeks for the IND, GRP, and AC participants were similar, at - 2.6, - 3.1%, and - 3.4%, respectively. However, participants achieving 5% weight loss in the IND, GRP, and AC groups was 21.5, 24.0% (GRP vs AC, P < 0.05), and 15.2%. Attendance at 75% of the DPP core sessions was significantly higher among IND (60.8%, P < 0.001) and GRP (64.0%, P < 0.001) participants than among AC (38.6%) participants. Despite substantial attrition over time, attendance at 75% of the DPP maintenance sessions was also significantly higher among IND (23.0%, P < 0.001) and GRP (26.1%, P < 0.001) participants than among AC (11.0%) participants. CONCLUSIONS: Financial incentives can improve the proportion of Medicaid beneficiaries attending the 12-month DPP and achieving at least 5% weight loss. TRIAL REGISTRATION: ClinicalTrials.gov NCT02422420 ; retrospectively registered April 21, 2015.

Phase I pharmacokinetic and pharmacodynamic study of cetuximab, irinotecan and sorafenib in advanced colorectal cancer.

Background This phase Ib study was designed to determine the maximum tolerated doses (MTD) and dose limiting toxicities (DLTs) of irinotecan and cetuximab with sorafenib. Secondary objectives included characterizing the pharmacokinetics and pharmacodynamics and evaluating preliminary antitumor activity in patients with advanced colorectal cancer (CRC). Methods Patients with metastatic, pretreated CRC were treated at five dose levels. Results Eighteen patients were recruited with median age 56.5 years. In the first five patients treated, 2 irinotecan related DLTs were observed. With reduced dose intensity irinotecan, there were no further DLTs. The most common toxicities were diarrhea, nausea/vomiting, fatigue, anorexia and rash. DLTs included neutropenia and thrombocytopenia. Two patients had partial responses (one with a KRAS mutation) and 8 had stable disease (8-36 weeks). The median progression free survival (PFS) and overall survival (OS) were 2.5 and 4.7 months respectively. Pharmacokinetic analyses suggest sorafenib and metabolite exposure correlate with OS and DLTs. Conclusions The recommended phase II dose (RP2D) is irinotecan 100 mg/m(2) i.v. days 1, 8; cetuximab 400 mg/m(2) i.v. days 1 and 250 mg/m(2) i.v. weekly; and sorafenib 400 mg orally twice daily in advanced, pretreated CRC. The combination resulted in a modest response rate.

Resident factors associated with American board of internal medicine certification exam failure.

INTRODUCTION: Performance on the certifying examinations such as the American Board of Internal Medicine Certification Exam (ABIM-CE) is of great interest to residents and their residency programs. Identification of factors associated with certification exam result may allow residency programs to recognize and intervene for residents at risk of failing. Despite this, residency programs have few evidence-based predictors of certification exam outcome. The change to pass-or-fail score reporting of the USA Medical Licensing Exam (USMLE) Step 1 removes one such predictor. MATERIALS AND METHODS: We performed a retrospective study of residents from a medium-sized internal medicine residency program who graduated from 1998 through 2017. We used univariate tests of associations between ABIM-CE result and various demographic and scholastic factors. RESULTS: Of 166 graduates, 14 (8.4%) failed the ABIM-CE on the first attempt. Failing the first attempt of the ABIM-CE was associated with older median age on entering residency (29 vs 27 years; P = 0.01); lower percentile rank on the Internal Medicine In-Training Examination (IM-ITE) in each of the first, second, and third years of training (P < 0.001 for all); and lower scores on the USMLE Steps 1, 2 Clinical Knowledge, and 3 (P < 0.05 for all). No association was seen between a variety of other scholastic or demographic factors and first-attempt ABIM-CE result. DISCUSSION: Although USMLE step 1 has changed to a pass-or-fail reporting structure, there are still other characteristics that allow residency programs to identify residents at risk of ABIM-CE first time failure and who may benefit from intervention.

Integrated preclinical and clinical development of S-trans, trans-Farnesylthiosalicylic Acid (FTS, Salirasib) in pancreatic cancer.

PURPOSE: S-trans,trans-Farnesylthiosalicylic Acid (FTS, salirasib) inhibits Ras-dependent cell growth by dislodging all isoforms of Ras, including mutant Ras, from the plasma membrane. This study evaluated the activity, safety, and toxicity of salirasib in preclinical models and patients with metastatic pancreatic adenocarcinoma (PDA). PATIENTS AND METHODS: In the preclinical study, salirasib was tested, alone and in combination with gemcitabine, in patient derived xenografts (PDX) of PDA. In the clinical study, treatment-naïve patients with advanced, metastatic PDA were treated with a standard dose schedule of gemcitabine and salirasib 200-800 mg orally (PO) twice daily (bid) for 21 days every 28 days. Tissue from preclinical models and patients' biopsies were collected pre-treatment and on Cycle (C) 1, Day (D) 9 to characterize the effect of gemcitabine and salirasib on activated Ras protein levels. Plasma samples for pharmacokinetics were collected for salirasib administered alone and in combination. RESULTS: Salirasib inhibited the growth of 2/14 PDX models of PDA and modulated Ras signaling in these tumors. Nineteen patients were enrolled. No DLTs occurred. Common adverse events included hematologic and gastrointestinal toxicities and fatigue. The median overall survival was 6.2 months and the 1 year survival 37 %. In 2 patients in whom paired tissue biopsies were available, Ras and KRas protein levels were decreased on C1D9. Salirasib exposure was not altered by gemcitabine and did not correlate with PD outcomes. CONCLUSION: The combination of gemcitabine and salirasib appears well-tolerated, with no alteration of salirasib exposure, and exerted clinical and PD activity in PDA.

Results from an experimental trial at a Head Start center to evaluate two meal service approaches to increase fruit and vegetable intake of preschool aged children.

BACKGROUND: Strategies to increase fruit and vegetable consumption of preschool aged children are needed. OBJECTIVES: Evaluate the independent effects of the following meal service strategies on intake of fruits and vegetables of preschool children: 1.) Serving fruits and vegetables in advance of other menu items as part of traditional family style meal service; and 2.) Serving meals portioned and plated by providers. METHODS: Fifty-three preschool aged children completed a randomized crossover experiment conducted at a Head Start center in Minneapolis, MN. Over a six week trial period each of the experimental meal service strategies (serving fruits and vegetable first and serving meals portioned by providers) was implemented during lunch service for two one-week periods. Two one-week control periods (traditional family style meal service with all menu items served at once) were also included over the six week trial period. Childrens lunch intake was observed as a measure of food and nutrient intake during each experimental condition. RESULTS: Fruit intake was significantly higher (p<0.01) when fruits and vegetables were served in advance of other meal items (0.40 servings/meal) compared to the traditional family style meal service control condition when they were served in tandem with other menu items (0.32 servings/meal). Intakes of some nutrients found in fruits (vitamin A and folate) were concomitantly higher. In contrast, fruit and vegetable intakes were significantly lower and energy intake significantly higher during the provider portioned compared with control condition. CONCLUSIONS: Serving fruits in advance of other meal items may be a low cost easy to implement strategy for increasing fruit intake in young children. However, serving vegetables first does not appear to increase vegetable intake. Results provide support for current recommendations for traditional family style meal service in preschool settings.

Outpatient Primary Care Practitioner Access: Gender-Based Preferences.

Background: Primary care practices are evolving under the pressure of modern-day challenges, with some clinics now introducing the choice of new nontraditional care models designed to maximize patients' needs with practitioner efficiency. These changes include team models consisting of advanced practitioners and physicians, as well as new care delivery formats such as virtual care. With a growing number of options for care, it is unclear whether patients' gender affects their visit preferences; therefore, we surveyed patients presenting to an outpatient internal medicine clinic in Arizona to understand how practice variations impact patient satisfaction of their primary care. Methods: Patients seen in an outpatient internal medicine clinic were surveyed. Multivariable models adjusting for age, marital status, education level, and income were used to evaluate gender-based care preferences. Results: Of 796 total participants (446 women, 350 men), women were more likely to prefer continuity of care with the same health care practitioner (90.2% women vs. 85.0% men, p = 0.028) and allied health staff (AHS) (36.3% women vs. 28.0% men, p = 0.0031) over convenience of appointment or quicker response time than men. However, after multivariable analysis, no statistically significant relationships remained. Discussion: Women favored both continuity of care with the same health care provider and AHS over faster access to primary care. A large majority of men had similar preferences for continuity of care. To provide the highest level of care with greatest patient satisfaction, understanding individual preferences for care delivery will be important.

The Minnesota Diabetes Plan 2015: Stemming the tide on an epidemic and improving patient care.

The Minnesota Diabetes Steering Committee, a group of experts in diabetes care and prevention from around the state, in collaboration with the Minnesota Department of Health, is working to slow the incidence of diabetes and improve the care of Minnesotans who have the disease. The steering committee has developed a new five-year diabetes plan for the state that identifies nine areas around which stakeholders will focus energy and take action. This article describes that plan.

Low awareness of overweight status among parents of preschool-aged children, Minnesota, 2004-2005.

INTRODUCTION: Many studies have found that parents of overweight children do not perceive their child to be overweight. Little is known, however, about the extent to which such misperceptions exist among parents of preschool-aged children. METHODS: We analyzed data that were collected in 2004-2005 from parents of 593 preschool-aged children in 20 child care centers in the Minneapolis-St. Paul, Minnesota, metropolitan area. Parents were asked how they would classify their preschooler's weight, and children's height and weight were measured. RESULTS: Of the predominantly white, educated sample, most parents (90.7%) of overweight preschoolers classified their child as normal weight. An even higher percentage (94.7%) of children at risk for overweight were classified as normal weight by their parents. Most parents of normal-weight children classified their child's weight as average. However, 16.0% classified their normal-weight child as underweight or very underweight. CONCLUSION: Results indicate that parents are unlikely to recognize childhood overweight among preschool-aged children, which is concerning because parents of overweight children may be unlikely to engage in obesity prevention efforts for their child if they do not recognize their child's risk status. A notable proportion of parents of normal-weight children perceived their child to be underweight, which suggests that parents of normal-weight children may be more concerned with undernutrition than overnutrition.

Leptomeningeal Carcinomatosis in Colorectal Cancer: The Mayo Clinic Experience.

BACKGROUND: Leptomeningeal metastasis (LM) is an uncommon form of metastatic disease in many cancers. There remains a paucity of literature with regard to the course and management of LM in colorectal cancers (CRCs). The aim of this study was to estimate the incidence of LM in patients with CRC seen at our institution over a 15-year period, and to describe the clinical course and outcome of these cases. METHODS: LM in CRC primary cases between 2000 and 2014 were identified in the Mayo Clinic databases. The charts were retrospectively reviewed. RESULTS: Of 17,095 CRC primaries, we identified 10 patients with LM (0.058%) in this 15-year period. Nine cases were included in the analysis. Four had metastatic disease at the time of their initial CRC diagnosis. Median overall survival after CRC diagnosis was 25.7 months (range, 4.7-74.8 months). Median time to diagnosis of LM after CRC diagnosis was 25.3 months (range, 0-68.1 months). All patients had magnetic resonance imaging findings consistent with LM: 3 patients with spinal LM, 5 patients with intracranial LM, and 1 with both. Neurologic symptoms correlated with site of the lesions, with headache, cranial nerve palsy, lower extremity weakness, and gait disturbance among the most frequently reported. However, not all patients had neurologic findings, with LM lesions found incidentally in 2 cases. Seven patients (78%) had palliative radiotherapy for LM. Three patients continued to receive systemic chemotherapy after diagnosis of LM. Median survival after LM diagnosis was 7 weeks (range, 2-39 weeks). CONCLUSIONS: LM is an exceedingly rare development in the natural course of CRC. It confers a poor prognosis with limited treatment options. At our institution, most patients had their disease addressed by palliative means, with many receiving radiotherapy to control their neurologic symptoms. Based on our series, supportive care remains a sensible approach to the management of LM in CRC.

Cost-Effectiveness of a Community-Based Diabetes Prevention Program with Participation Incentives for Medicaid Beneficiaries.

OBJECTIVE: To examine the cost-effectiveness of a community-based Diabetes Prevention Program (DPP) for Medicaid beneficiaries from the perspective of the health care sector. DATA SOURCES/STUDY SETTING: A total of 847 Medicaid enrollees at high risk for type 2 diabetes participating in a community-based DPP. STUDY DESIGN: Pre- and post clinical outcome and cost data were used as inputs into a validated diabetes simulation model. The model was used to evaluate quality-adjusted life years (QALYs) and health care costs over a 40-year time horizon from the perspective of the health care sector. DATA COLLECTION/EXTRACTION METHODS: Clinical outcome and cost data were derived from a study examining the effect of financial incentives on weight loss. PRINCIPAL FINDINGS: Study participants lost an average of 4.2 lb (p < .001) and increased high-density lipoprotein cholesterol by 1.75 mg/dl (p = .002). Intervention costs, which included financial incentives for participation and weight loss, were $915 per participant. The incremental cost-effectiveness ratio was estimated to be $14,011 per QALY but was sensitive to the time horizon studied. CONCLUSIONS: Widespread adoption of community-based DPP has the potential to reduce diabetes and cardiovascular-related morbidity and mortality for low-income persons at high risk for diabetes and may be a cost-effective investment for Medicaid programs.

Fruits and vegetables taken can serve as a proxy measure for amounts eaten in a school lunch.

This study tests the hypothesis that fruits and vegetables taken on students' lunch trays are usable proxies for fruits and vegetables eaten, and that the proxy is useful with children in the youngest school grade (ie, grade 1; ages 6 to 8 years). A total of 1,168 randomly selected students in grade 1 and grade 3 (ages 8 to 10 years) in 26 schools in the Twin Cities, MN, metropolitan area were observed before and after an intervention that was applied to 13 randomly selected schools. Trained observers recorded food quantities on a child's tray and measured food consumed during the meal. Correlations between amounts of fruits and vegetables taken and eaten ranged from 0.74 to 0.96. The median correlation in grade 1 was the same, 0.82, as in the combined sample. Food taken and food eaten as alternative response variables resulted in the same conclusions about the effects of intervention. The hypothesis is strengthened that food taken can be used as a proxy for consumption in future nutrition education research.

Association of Therapy for Autoimmune Disease With Myelodysplastic Syndromes and Acute Myeloid Leukemia.

IMPORTANCE: Therapy-related myeloid neoplasms are a potentially life-threatening consequence of treatment for autoimmune disease (AID) and an emerging clinical phenomenon. OBJECTIVE: To query the association of cytotoxic, anti-inflammatory, and immunomodulating agents to treat patients with AID with the risk for developing myeloid neoplasm. DESIGN, SETTING, AND PARTICIPANTS: This retrospective case-control study and medical record review included 40 011 patients with an International Classification of Diseases, Ninth Revision, coded diagnosis of primary AID who were seen at 2 centers from January 1, 2004, to December 31, 2014; of these, 311 patients had a concomitant coded diagnosis of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML). Eighty-six cases met strict inclusion criteria. A case-control match was performed at a 2:1 ratio. MAIN OUTCOMES AND MEASURES: Odds ratio (OR) assessment for AID-directed therapies. RESULTS: Among the 86 patients who met inclusion criteria (49 men [57%]; 37 women [43%]; mean [SD] age, 72.3 [15.6] years), 55 (64.0%) had MDS, 21 (24.4%) had de novo AML, and 10 (11.6%) had AML and a history of MDS. Rheumatoid arthritis (23 [26.7%]), psoriasis (18 [20.9%]), and systemic lupus erythematosus (12 [14.0%]) were the most common autoimmune profiles. Median time from onset of AID to diagnosis of myeloid neoplasm was 8 (interquartile range, 4-15) years. A total of 57 of 86 cases (66.3%) received a cytotoxic or an immunomodulating agent. In the comparison group of 172 controls (98 men [57.0%]; 74 women [43.0%]; mean [SD] age, 72.7 [13.8] years), 105 (61.0%) received either agent (P = .50). Azathioprine sodium use was observed more frequently in cases (odds ratio [OR], 7.05; 95% CI, 2.35- 21.13; P < .001). Notable but insignificant case cohort use among cytotoxic agents was found for exposure to cyclophosphamide (OR, 3.58; 95% CI, 0.91-14.11) followed by mitoxantrone hydrochloride (OR, 2.73; 95% CI, 0.23-33.0). Methotrexate sodium (OR, 0.60; 95% CI, 0.29-1.22), mercaptopurine (OR, 0.62; 95% CI, 0.15-2.53), and mycophenolate mofetil hydrochloride (OR, 0.66; 95% CI, 0.21-2.03) had favorable ORs that were not statistically significant. No significant association between a specific length of time of exposure to an agent and the drug's category was observed. CONCLUSIONS AND RELEVANCE: In a large population with primary AID, azathioprine exposure was associated with a 7-fold risk for myeloid neoplasm. The control and case cohorts had similar systemic exposures by agent category. No association was found for anti-tumor necrosis factor agents. Finally, no timeline was found for the association of drug exposure with the incidence in development of myeloid neoplasm.

Financial incentives for diabetes prevention in a Medicaid population: Study design and baseline characteristics.

BACKGROUND: Medicaid beneficiaries at high risk for diabetes can benefit from the Diabetes Prevention Program (DPP) lifestyle intervention. The We Can Prevent Diabetes (WCPD) trial examined whether financial incentives are more effective than no financial incentives in sustaining participation in the DPP and increasing weight loss. Here we describe the study design and baseline characteristics. METHODS: The WCPD was a 3-arm group-randomized controlled trial. Medicaid beneficiaries were aged 18 to 74years, had prediabetes or gestational diabetes, and were overweight or obese. Subjects enrolled from 13 primary care clinics into groups of 8 to 15 participants. Participants received the 12-month DPP delivered by the YMCA or trained clinic staff, free of costs. Participants from groups randomized into the intervention conditions were eligible to receive incentives up to $520 by attending sessions and meeting weight loss goals. RESULTS: The WCPD enrolled 1154 participants into 98 groups. Among the 847 attending at least one DPP session, 71.2% were women; the mean age was 48.3years; 79.3% were obese; and 87.6% entered the study with an elevated HbA1c or fasting plasma glucose. Participants' primary languages were Somali (21.0%), Hmong (3.1%), Spanish (2.2%), or English (72.4%). CONCLUSIONS: The WCPD trial demonstrated that a collaborative approach with primary care clinics and the YMCA can efficiently identify, enroll, and deliver the 12-month DPP to Medicaid beneficiaries. If the WCPD incentive arms increase attendance and weight loss, the use of financial incentives may be an avenue for engaging low-income, high-risk patients in lifestyle change.

Phase 1 Study of ABT-751 in Combination With CAPIRI (Capecitabine and Irinotecan) and Bevacizumab in Patients With Advanced Colorectal Cancer.

ABT-751 is an orally bioavailable sulfonamide with antimitotic properties. A nonrandomized phase 1 dose-escalation study of ABT-751 in combination with CAPIRI (capecitabine and irinotecan) and bevacizumab was conducted to define the maximum tolerated dose, dose-limiting toxicity (DLT), and pharmacokinetics in patients with advanced colorectal cancer. Patients were treated with ABT-751 daily for 7 days (alone) and then began 21-day cycles of treatment with ABT-751 daily and capecitabine twice daily for 14 days plus irinotecan on day 1 intravenously. Bevacizumab was added as standard of care at 7.5 mg/kg on day 1 after the first 2 dose levels. Because of intolerance to the regimen, a reduced dose of ABT-751 was also explored with reduced-dose and full-dose CAPIRI with bevacizumab. ABT-751 and irinotecan pharmacokinetics, ABT-751 glucuronidation, and protein binding were explored. Twenty-four patients were treated over 5 dose levels. The maximum tolerated dose was ABT-751 125 mg combined with full-dose CAPIRI and bevacizumab 7.5 mg/kg on day 1. DLTs were hypokalemia, elevated liver tests, and febrile neutropenia. ABT-751 is metabolized by UGT1A8 and to a lesser extent UGT1A4 and UGT1A1. Irinotecan and APC exposure were increased, SN-38 exposure was similar, and SN-38 glucuronide exposure was decreased. Clinically relevant alterations in ABT-751 and irinotecan pharmacokinetics were not observed. Despite modest efficacy, the combination of ABT-751, CAPIRI, and bevacizumab will not be studied further in colorectal cancer.

A randomized school trial of environmental strategies to encourage fruit and vegetable consumption among children.

The Cafeteria Power Plus project examined whether a cafeteria-based intervention would increase the fruit and vegetable (FV) consumption of children. Twenty-six schools were randomly assigned to either an intervention or control condition. Baseline lunch observations of a sample (N = 1668) of first- and third-grade students occurred in the spring of 2000; follow-up was in the spring of 2002. The intervention took place during two consecutive school years beginning in the fall of 2000 and consisted of daily activities (increasing the availability, attractiveness, and encouragement for FV) and special events (kick-offs, samplings, challenge weeks, theater production, and finale meal). Training of food-service staff and cook managers was ongoing throughout the intervention phase. Students in the intervention schools significantly increased their total fruit intake. Process measures indicated that verbal encouragement by food-service staff was associated with outcomes. The outcomes suggest that multicomponent interventions are more powerful than cafeteria programs alone with this age group.

Evaluation of a theater production about eating behavior of children.

This study evaluated "All's Well That Eats Well," a theater production performed in 20 schools in the Twin Cities, Minn., metropolitan area in winter 2000. The production sought to change food-related knowledge and food choices concerning fruits and vegetables among children in grades 1-6. The study used a pretest-posttest design with two randomly-assigned, sequential intervention-control groups (N = 4,093). All students completed surveys prior to and then following the theater production and the classroom and home activities. No differences existed between the groups at pretest. Significant differences occurred in food-related knowledge, food choices, and food recall from pretest to posttest for all students. Significant differences also occurred between intervention groups in food-related knowledge and food choices. The study indicates that professional theater productions in schools can create at least a short-term effect on children's nutrition knowledge and behavior.

Randomized phase III multi-institutional study of TNFerade biologic with fluorouracil and radiotherapy for locally advanced pancreatic cancer: final results.

PURPOSE: TNFerade biologic is a novel means of delivering tumor necrosis factor alpha to tumor cells by gene transfer. We herein report final results of the largest randomized phase III trial performed to date among patients with locally advanced pancreatic cancer (LAPC) and the first to test gene transfer against this malignancy. PATIENTS AND METHODS: In all, 304 patients were randomly assigned 2:1 to standard of care plus TNFerade (SOC + TNFerade) versus standard of care alone (SOC). SOC consisted of 50.4 Gy in 28 fractions with concurrent fluorouracil (200 mg/m(2) per day continuous infusion). TNFerade was injected intratumorally before the first fraction of radiotherapy each week at a dose of 4 × 10(11) particle units by using either a percutaneous transabdominal or an endoscopic ultrasound approach. Four weeks after chemoradiotherapy, patients began gemcitabine (1,000 mg/m(2) intravenously) with or without erlotinib (100 to 150 mg per day orally) until progression or toxicity. RESULTS: The analysis included 187 patients randomly assigned to SOC + TNFerade and 90 to SOC by using a modified intention-to-treat approach. Median follow-up was 9.1 months (range, 0.1 to 50.5 months). Median survival was 10.0 months for patients in both the SOC + TNFerade and SOC arms (hazard ratio [HR], 0.90; 95% CI, 0.66 to 1.22; P = .26). Median progression-free survival (PFS) was 6.8 months for SOC + TNFerade versus 7.0 months for SOC (HR, 0.96; 95% CI, 0.69 to 1.32; P = .51). Among patients treated on the SOC + TNFerade arm, multivariate analysis showed that TNFerade injection by an endoscopic ultrasound-guided transgastric/transduodenal approach rather than a percutaneous transabdominal approach was a risk factor for inferior PFS (HR, 2.08; 95% CI, 1.06 to 4.06; P = .032). The patients in the SOC + TNFerade arm experienced more grade 1 to 2 fever and chills than those in the SOC arm (P < .001) but both arms had similar rates of grade 3 to 4 toxicities (all P > .05). CONCLUSION: SOC + TNFerade is safe but not effective for prolonging survival in patients with LAPC.

Tumor engraftment in nude mice and enrichment in stroma- related gene pathways predict poor survival and resistance to gemcitabine in patients with pancreatic cancer.

PURPOSE: The goal of this study was to evaluate prospectively the engraftment rate, factors influencing engraftment, and predictability of clinical outcome of low-passage xenografts from patients with resectable pancreatic ductal adenocarcinoma (PDA) and to establish a bank of PDA xenografts. EXPERIMENTAL DESIGN: Patients with resectable PDA scheduled for resection at the Johns Hopkins Hospital were eligible. Representative pieces of tumor were implanted in nude mice. The status of the SMAD4 gene and content of tumor-generating cells were determined by immunohistochemistry. Gene expression was carried out by using a U133 Plus 2.0 array. Patients were followed for progression and survival. RESULTS: A total of 94 patients with PDA were resected, 69 tumors implanted in nude mice, and 42 (61%) engrafted. Engrafted carcinomas were more often SMAD4 mutant, and had a metastatic gene expression signature and worse prognosis. Tumors from patients resistant to gemcitabine were enriched in stroma-related gene pathways. Tumors sensitive to gemcitabine were enriched in cell cycle and pyrimidine gene pathways. The time to progression for patients who received treatment with gemcitabine for metastatic disease (n = 7) was double in patients with xenografts sensitive to gemcitabine. CONCLUSION: A successful xenograft was generated in 61% of patients attempted, generating a pool of 42 PDA xenografts with significant biological information and annotated clinical data. Patients with PDA and SMAD4 inactivation have a better engraftment rate. Engraftment is a poor prognosis factor, and engrafted tumors have a metastatic gene expression signature. Tumors from gemcitabine-resistant patients were enriched in stromal pathways.