Ganitumab and metformin plus standard neoadjuvant therapy in stage 2/3 breast cancer.

I-SPY2 is an adaptively randomized phase 2 clinical trial evaluating novel agents in combination with standard-of-care paclitaxel followed by doxorubicin and cyclophosphamide in the neoadjuvant treatment of breast cancer. Ganitumab is a monoclonal antibody designed to bind and inhibit function of the type I insulin-like growth factor receptor (IGF-1R). Ganitumab was tested in combination with metformin and paclitaxel (PGM) followed by AC compared to standard-of-care alone. While pathologic complete response (pCR) rates were numerically higher in the PGM treatment arm for hormone receptor-negative, HER2-negative breast cancer (32% versus 21%), this small increase did not meet I-SPY's prespecified threshold for graduation. PGM was associated with increased hyperglycemia and elevated hemoglobin A1c (HbA1c), despite the use of metformin in combination with ganitumab. We evaluated several putative predictive biomarkers of ganitumab response (e.g., IGF-1 ligand score, IGF-1R signature, IGFBP5 expression, baseline HbA1c). None were specific predictors of response to PGM, although several signatures were associated with pCR in both arms. Any further development of anti-IGF-1R therapy will require better control of anti-IGF-1R drug-induced hyperglycemia and the development of more predictive biomarkers.

Advantageous Selection, Moral Hazard, and Insurer Sorting on Risk in the U.S. Automobile Insurance Market.

This study quantifies the role of private information in automobile insurance policy choice using data on subjective beliefs, risk preference, reckless driving, the respondent's insurer and insurance policy characteristics merged with insurer-specific quality ratings distributed by independent organizations. We find a zero correlation between ex post accident risk and insurance coverage, reflecting advantageous selection in policy choice offset by moral hazard. Advantageous selection is partly attributable to insurer sorting on consumer attributes known and used by insurers. Our analysis of insurer sorting reveals that lower-risk drivers on attributes observed by insurers obtain coverage from insurers with higher-quality ratings.

Aid-assisted decision making and colorectal cancer screening: a randomized controlled trial.

BACKGROUND: Shared decision making (SDM) is a widely recommended yet unproven strategy for increasing colorectal cancer (CRC) screening uptake. Previous trials of decision aids to increase SDM and CRC screening uptake have yielded mixed results. PURPOSE: To assess the impact of decision aid-assisted SDM on CRC screening uptake. DESIGN: RCT. SETTING/PARTICIPANTS: The study was conducted at an urban, academic safety-net hospital and community health center between 2005 and 2010. Participants were asymptomatic, average-risk patients aged 50-75 years due for CRC screening. INTERVENTION: Study participants (n=825) were randomized to one of two intervention arms (decision aid plus personalized risk assessment or decision aid alone) or control arm. The interventions took place just prior to a routine office visit with their primary care providers. MAIN OUTCOME MEASURES: The primary outcome was completion of a CRC screening test within 12 months of the study visit. Logistic regression was used to identify predictors of test completion and mediators of the intervention effect. Analysis was completed in 2011. RESULTS: Patients in the decision-aid group were more likely to complete a screening test than control patients (43.1% vs 34.8%, p=0.046) within 12 months of the study visit; conversely, test uptake for the decision aid and decision aid plus personalized risk assessment arms was similar (43.1% vs 37.1%, p=0.15). Assignment to the decision-aid arm (AOR=1.48, 95% CI=1.04, 2.10), black race (AOR=1.52, 95% CI=1.12, 2.06) and a preference for a patient-dominant decision-making approach (AOR=1.55, 95% CI=1.02, 2.35) were independent determinants of test completion. Activation of the screening discussion and enhanced screening intentions mediated the intervention effect. CONCLUSIONS: Decision aid-assisted SDM has a modest impact on CRC screening uptake. A decision aid plus personalized risk assessment tool is no more effective than a decision aid alone. TRIAL REGISTRATION: This study is registered at www.clinicaltrials.govNCT00251862.

The Your Disease Risk Index for colorectal cancer is an inaccurate risk stratification tool for advanced colorectal neoplasia at screening colonoscopy.

Tailoring the use of screening colonoscopy based on the risk of advanced colorectal neoplasia (ACN) could optimize the cost-effectiveness of colorectal cancer (CRC) screening. Our goal was to assess the accuracy of the Your Disease Risk (YDR) CRC risk index for stratifying average risk patients into low- versus intermediate/high-risk categories for ACN. The YDR risk assessment tool was administered to 3,317 asymptomatic average risk patients 50 to 79 years of age just before their screening colonoscopy. Associations between YDR-derived relative risk (RR) scores and ACN prevalence were examined using logistic regression and χ(2) analyses. ACN was defined as a tubular adenoma ≥1 cm, tubulovillous or villous adenoma of any size, and the presence of high-grade dysplasia or cancer. The overall prevalence of ACN was 5.6%. Although YDR-derived RR scores were linearly associated with ACN after adjusting for age and gender (P = 0.033), the index was unable to discriminate "below average" from "above/average" risk patients [OR, 1.01; 95% confidence interval (CI), 0.75-1.37]. Considerable overlap in rates of ACN was also observed between the different YDR risk categories in our age- and gender-stratified analyses. The YDR index lacks accuracy for stratifying average risk patients into low- versus intermediate/high-risk categories for ACN.

The impact of a novel computer-based decision aid on shared decision making for colorectal cancer screening: a randomized trial.

BACKGROUND: Eliciting patients' preferences within a framework of shared decision making (SDM) has been advocated as a strategy for increasing colorectal cancer (CRC) screening adherence. Our objective was to assess the effectiveness of a novel decision aid on SDM in the primary care setting. METHODS: An interactive, computer-based decision aid for CRC screening was developed and evaluated within the context of a randomized controlled trial. A total of 665 average-risk patients (mean age, 57 years; 60% female; 63% black, 6% Hispanic) were allocated to 1 of 2 intervention arms (decision aid alone, decision aid plus personalized risk assessment) or a control arm. The interventions were delivered just prior to a scheduled primary care visit. Outcome measures (patient preferences, knowledge, satisfaction with the decision-making process [SDMP], concordance between patient preference and test ordered, and intentions) were evaluated using prestudy/poststudy visit questionnaires and electronic scheduling. RESULTS: Overall, 95% of patients in the intervention arms identified a preferred screening option based on values placed on individual test features. Mean cumulative knowledge, SDMP, and intention scores were significantly higher for both intervention groups compared with the control group. Concordance between patient preference and test ordered was 59%. Patients who preferred colonoscopy were more likely to have a test ordered than those who preferred an alternative option (83% v. 70%; P < 0.01). Intention scores were significantly higher when the test ordered reflected patient preferences. CONCLUSIONS: Our interactive computer-based decision aid facilitates SDM, but overall effectiveness is determined by the extent to which providers comply with patient preferences.

Prevalence of secondary causes of bone loss among breast cancer patients with osteopenia and osteoporosis.

PURPOSE: To determine the prevalence of secondary causes of bone loss among patients with breast cancer with osteopenia and osteoporosis. PATIENTS AND METHODS: All women referred to a bone health clinic over a 6-year period for bone evaluation were included in this retrospective study and stratified based on presence or absence of a breast cancer history. The prevalence of secondary causes of bone loss in the two groups was compared. RESULTS: Of the 238 women identified, 64 women had breast cancer. The non-breast cancer group (n = 174) was significantly older (P = .015), had a lower mean weight (P = .019), lower 25 hydroxy-vitamin D level (P = .019), and greater degree of bone loss in both the spine and hip (P < .001 and 0.004, respectively). The presence of at least one secondary cause of bone loss, excluding cancer-related therapies, was seen in 78% of the breast cancer patient group and in 77% of the non-breast cancer group (P = not significant). Newly diagnosed metabolic bone disorders were seen in 58% of the breast cancer population. The most common was vitamin D deficiency, seen in 38% of patients in the breast cancer group and 51% of patients in the non-breast cancer group. Idiopathic hypercalciuria was diagnosed in 15.6%, primary hyperparathyroidism in 1.6%, and normocalcemic hyperparathyroidism in 3.1% of the breast cancer population. CONCLUSION: A high prevalence of secondary causes of bone loss among patients with breast cancer supports a comprehensive evaluation in these patients, particularly those considering therapy with an aromatase inhibitor.

An effective educational strategy for improving knowledge, risk perception, and risk communication among colorectal adenoma patients.

BACKGROUND: We have previously shown that most adenoma patients are unaware of the personal and familial implications of their diagnosis. Our goal was to determine whether a brief, computer-based educational program (CBEP) administered alone after polypectomy, or in combination with a personalized letter (PL), was more effective than standard care (SC) for heightening awareness and improving risk communication. METHODS: Using a quasi-randomized design, adenoma-bearing subjects were assigned to the CBEP +PL (n=99), CBEP (n=96), or SC (n=120) arms. The CBEP was administered before discharge from the endoscopy unit. All subjects completed a phone survey 3 months postpolypectomy assessing knowledge, risk perception, and notification of first-degree relatives. RESULTS: Composite knowledge scores were higher (P<0.05) for the CBEP+PL group than CBEP and SC groups. Subjects in the CBEP+PL group were more likely (P<0.05) than those in the SC group to know that adenomas but not hyperplastic polyps were precancerous, that patients with adenomas were at increased risk of future adenomas, and that the siblings and children of adenoma patients may be at increased colorectal cancer risk. Subjects in the CBEP+PL group were also more likely (P<0.05) to know their polyp's histology, perceive themselves and their siblings/children to be at increased risk of colorectal neoplasia, and notify a first-degree relative. These associations remained significant after adjusting for age, sex, race/ethnicity, education, and endoscopist. No differences were observed between the CBEP and SC groups. CONCLUSIONS: The CBEP+PL intervention is an effective strategy for improving knowledge, risk perception, and risk communication among adenoma patients.

Has the surge in media attention increased public awareness about colorectal cancer and screening?

The Centers for Disease Control and Prevention's Screen for Life campaign in March 1999 followed by the creation of National Colorectal Cancer Awareness Month in March 2000 heralded a surge in media attention to promote awareness about CRC and stimulate interest in screening. Our objective was to assess whether these campaigns have achieved their goal of educating the public about CRC and screening. The study sample was comprised of mostly unscreened, average-risk, English-speaking patients aged 50-75 years seen in an urban primary care setting. Knowledge was assessed using a 12-item true/false questionnaire based primarily on the content of key messages endorsed by the National Colorectal Cancer Roundtable (Cancer 95:1618-1628, 2002) and adopted in many of the media campaigns. Multiple linear regression was performed to identify demographic correlates of knowledge. A total of 356 subjects (83% or=67%) were aware of who gets CRC, age to initiate screening, the goals of screening and potential benefits. Fewer were aware that removing polyps can prevent CRC and that both polyps and CRC may be asymptomatic. Knowledge scores were lower among Blacks and those with a high school degree or less. Race and education were independent correlates of knowledge. These data suggest that recent media campaigns have been effective in increasing public awareness about CRC risk and screening but important gaps in knowledge remain.

Patient preferences for colorectal cancer screening: how does stool DNA testing fare?

OBJECTIVE: To assess patient preferences for 1 of the recommended colorectal cancer screening options or stool DNA testing (sDNA), a novel noninvasive screening test. STUDY DESIGN: Cross-sectional survey of ambulatory-care patients in the primary care setting. METHODS: A decision aid was administered to eligible subjects, using a trained interviewer format. The decision aid described the pros and cons of colonoscopy, fecal occult blood testing (FOBT), flexible sigmoidoscopy, flexible sigmoidoscopy plus FOBT, double-contrast barium enema, and sDNA. After reviewing the decision aid, subjects were asked to identify a preferred screening option, test features influencing their choice, and level of interest in decision making. RESULTS: A total of 263 subjects completed the study. Colonoscopy (50.6%), sDNA (28.1%), and FOBT (18.3%) were preferred over the other screening options. Preferences were associated with race and education but not age, sex, or prior FOBT. Subjects who preferred colonoscopy rated accuracy as the most influential test feature, whereas those who preferred sDNA or FOBT rated concerns about discomfort or frequency of testing highest. Most subjects preferred a shared (54%) or patient-dominant (34%) decision-making process. CONCLUSIONS: Colonoscopy was the most frequently preferred screening option for average risk individuals. Noninvasive stool-based tests, particularly sDNA, were identified by most individuals who preferred an alternative to colonoscopy. These findings affirm the need to elicit patient preferences when selecting a screening option and suggest that provider-patient decision making can be tailored to include fewer options.

Screening preferences of patients at familial risk of colorectal cancer.

Our primary objective was to assess the screening preferences of patients at familial risk of colorectal cancer. Asymptomatic subjects aged 18-75 with a single first-degree relative diagnosed with colorectal cancer (n = 48) or polyps (n = 52) were asked to identify a preferred screening strategy, test features influencing their choice, and level of interest in decision-making after reviewing a decision aid describing the pros and cons of currently recommended screening tests. Although both groups preferred colonoscopy, 40% of subjects with a family history of colorectal cancer and 48% of those with a family history of polyps preferred alternative strategies. Accuracy was the most commonly identified test feature influencing test preference. Most subjects (66%) felt that selection of screening test should be a patient dominant or shared process. We conclude that patients at familial risk of colorectal cancer have distinct screening preferences that often vary from current recommendations.