Improving Access to Palliative Care at a VHA Hospital.

OBJECTIVE: Explore veteran-specific factors impacting the acceptance of palliative care services at a Veterans Health Administration hospital. METHODS: Prospective, focused one-on-one interviews were conducted with 18 inpatient veterans with an initial consult to receive palliative care services. Domains impacting reception of outpatient palliative care management were evaluated including knowledge deficit, emotional barriers, physical barriers, psychosocial barriers, and physical support. Themes and trends from interview responses were analyzed using a qualitative directed content analysis approach. RESULTS: The following themes were discovered to influence veteran participation in outpatient palliative care: Knowledge Deficit, Environmental Factors, Positive Patient Satisfaction, Openness to Technology, and Resiliency. Characteristics of veterans interviewed included an average age of 71 with an average distance from the hospital of 59 miles. CONCLUSION: The identification of factors impacting veteran access to palliative care will be used to guide interventions and improve receipt of services. Care of seriously ill veterans may be substantially improved by facilitating access to palliative care.

Malnutrition and overall survival in older patients with cancer.

BACKGROUND & AIMS: In this study, we assessed the prevalence of malnutrition and its association with overall survival among patients with cancer aged 65 years and older. METHODS: In this retrospective cohort study, patients receiving cancer care underwent a comprehensive geriatric assessment (CGA). Malnutrition status was determined through the CGA. We used univariate and multivariable Cox regression survival analyses to assess the association between baseline malnutrition and survival. RESULTS: A total of 454 patients with cancers were included in the analysis. The median age was 78 years and men and women were equally represented. Forty-two percent (n = 190) were malnourished at baseline, and 33% died during the follow-up (range 0.2-51.1 month). Univariate analysis showed that malnutrition increased the risk of all-cause mortality in older patients with cancer (HR, 1.49; 95% CI, 1.08-2.05; p = 0.01). In the multivariate Cox regression model, malnutrition increased the risk of all-cause mortality (HR, 1.87; 95% CI, 1.10-3.17; p = 0.02) in older patients with solid tumors. However, malnutrition did not increase the risk of all-cause mortality for hematologic malignancies. CONCLUSIONS: In our study, we found that malnutrition was a risk factor for mortality in older cancer patients, especially in older patients with solid tumors. Prospective inter ventional studies are recommended.

The validity of three malnutrition screening markers among older patients with cancer.

BACKGROUND: Malnutrition is common in older adults with cancer and is associated with adverse clinical outcomes. We assessed and compared the validity of three tools commonly used to screen for malnutrition: The Mini Nutritional Assessment (MNA), weight loss and body mass index (BMI). METHODS: In this retrospective study, we reviewed patients over age 65 with a diagnosis of cancer who were treated at the MD Anderson Cancer Center between 1 January 2013 and 31 March 2017. All patients in this study were evaluated by a trained geriatrician as part of a comprehensive geriatric assessment (CGA). Malnutrition was diagnosed by both CGA and clinical examination. The sensitivity, specificity and Cohen's κ of each tool was also compared with the clinical diagnosis. RESULTS: A total of 454 older patients with cancer who had malnutrition information available were included in the analyses. The median age was 78%, and 42% (n=190) were clinically diagnosed with malnutrition at baseline. When the MNA was performed, 105 out of 352 patients (30%) were malnourished, and 122 (35%) at risk of malnutrition. Weight loss >3 kg was seen in 183 out of 359 (51%) patients, and BMI <20 kg/m2 was found in 30 of the 454 (7%) patients. MNA had the highest validity (area under curve (AUC)=0.83) and reliability (κ=0.67), weight loss had moderate validity (AUC=0.73) and reliability (κ=0.46), while BMI had the lowest validity (AUC=0.55) and reliability (κ=0.55). CONCLUSIONS: For clinical practice, MNA should be incorporated for standard assessment/screening for these older patients with cancer.

Overall survival in older patients with cancer.

OBJECTIVES: A growing number of patients with cancer are older adults. We sought to identify the predictors for overall survival (OS) in older adults with solid tumour and haematological malignancies between January 2013 and December 2016. METHODS: Retrospective cohort study. A comprehensive geriatric assessment was performed, with a median follow-up of 12.8 months. ANALYSIS: univariate and multivariate Cox proportional hazards regression analysis. RESULTS: In this study, among the 455 patients with last follow-up date or date of death, 152 (33.4%) died during the follow-up. The median follow-up is 12.8 months (range 0.2-51.1 months) and the median OS is 20.5 months (range 0.3-44.5 months). Among all older patients with cancer, predictors of OS included male gender, cancer stage, malnutrition, history of smoking, heavy alcohol use, frailty, weight loss, major depression, low body weight and nursing home residence. Traditional performance scores (Eastern Cooperative Oncology Group (ECOG) and Karnofsky Performance Scale (KPS)) were predictors of OS. Independent predictors included age >85 years and haematological malignancies. Among solid tumours (n=311) in addition to the above predictors, comorbidity, gait speed and vitamin D deficiency were associated with OS. CONCLUSIONS: We identified specific geriatric factors associated with OS in older patients with cancer, and comparable in predictive ability to traditional performance scores such as KPS and ECOG. Prospective studies will be necessary to confirm our findings.

Osteoporosis-related Vertebral Fragility Fractures: A Review and Analysis of the American Orthopaedic Association's Own the Bone Database.

STUDY DESIGN: Retrospective cohort study of the Own the Bone database which is a fracture liaison service designed to improve recognition and treatment of osteoporosis. OBJECTIVE: To use the Own the Bone (OTB) database to 1) examine the specific demographics of patients presenting with a low-energy clinical vertebral fracture (VFX) and 2) compare demographic and fracture-specific risk factors between patients with clinical VFX versus patients with nonvertebral low-energy fracture (NVFX). SUMMARY OF BACKGROUND DATA: Large database studies have described risk factors for developing VFX. It is well described that a history of previous VFX portends an increased risk of future VFX. Few studies have reported cohorts from a fracture liaison service such as the OTB initiative. METHODS: 35,039 unique cases of fragility fracture occurred between 2009 and 2016 and were included in analysis. VFX accounted for 3395 (9.9%) of the presenting fractures at OTB enrollment. The demographics, lifestyle factors, medication use, and fracture-specific data for patients in the OTB registry with vertebral fractures were summarized and then statistically compared to those with nonvertebral fragility fractures. RESULTS: The majority of VFX patients were Caucasian, postmenopausal women (74.4%). There was an increased likelihood of presenting with a vertebral fracture in patients who sustained a previous VFX after the age of 50, while patients who sustained a prior nonvertebral fracture (NVFX) were more likely to present with a subsequent NVFX. After controlling for patients with a history of fracture after the age of 50, VFX patients (vs. NVFX) were more likely to be age 70-79, class 1 obesity, with a history of taking anti-osteoporotic prescription medications. CONCLUSIONS: Multiple factors were associated with a significantly increased risk of VFX compared with NVFX. Understanding the risk factors unique to fragility VFX is a critical component for targeting "at-risk" patients and preventing future osteoporosis-related fractures and their consequences. LEVEL OF EVIDENCE: 4.

Management of Osteoporosis in Survivors of Adult Cancers With Nonmetastatic Disease: ASCO Clinical Practice Guideline.

PURPOSE: The aim of this work is to provide evidence-based guidance on the management of osteoporosis in survivors of adult cancer. METHODS: ASCO convened a multidisciplinary Expert Panel to develop guideline recommendations based on a systematic review of the literature. RESULTS: The literature search of the 2018 systematic review by the US Preventive Services Task Force in the noncancer population was used as the evidentiary base upon which the Expert Panel based many of its recommendations. A total of 61 additional studies on topics and populations not covered in the US Preventive Services Task Force review were also included. Patients with cancer with metastatic disease and cancer survival outcomes related to bone-modifying agents are not included in this guideline. RECOMMENDATIONS: Patients with nonmetastatic cancer may be at risk for osteoporotic fractures due to baseline risks or due to the added risks that are associated with their cancer therapy. Clinicians are advised to assess fracture risk using established tools. For those patients with substantial risk of osteoporotic fracture, the clinician should obtain a bone mineral density test. The bone health of all patients may benefit from optimizing nutrition, exercise, and lifestyle. When a pharmacologic agent is indicated, bisphosphonates or denosumab at osteoporosis-indicated dosages are the preferred interventions.

Malnutrition in Older Adults with Cancer.

PURPOSE OF REVIEW: Malnutrition is a common and under-recognized geriatric condition in older adults with cancer. This review describes the public health burden, malnutrition prevention, and the relationship among cancer cachexia, malnutrition, and sarcopenia. Finally, clinical practice recommendations on malnutrition and prevention are presented. RECENT FINDINGS: Advanced age and cancer stage, frailty, dementia, major depression, functional impairment, and physical performance are important risk factors for malnutrition in older adults with cancer. The Mini Nutrition Assessment (MNA), Malnutrition Universal Screening Tool (MUST), and Patient Generated Subjective Global Assessment (PG-SGA) are the most commonly used assessment tools in older adults with cancer. In addition, malnutrition is independently associated with poor overall survival and quality of life, longer hospital stays, greater hospital cost, and hospital readmission. Comprehensive malnutrition prevention is required for improving the nutrition status among older adults with cancer.

Prevalence and factors associated with malnutrition in older patients with cancer.

BACKGROUND: >60% of patients with cancer are 65 years of age and older, and malnutrition is commonly encountered in older adults. OBJECTIVE: To assess the prevalence and factors associated with malnutrition in older patients with cancer. METHODS: In this cross-sectional study, patients with cancer underwent a comprehensive geriatric assessment (CGA). Malnutrition status was diagnosed by clinical assessment including screening tools such as Mini Nutrition Assessment (MNA), weight loss, and BMI. ANALYSIS: Descriptive statistics, chi-Square and logistic regression analysis were used to assess factors associated with malnutrition. RESULTS: A total of 454 patients with malnutrition information available were included in analysis. The median age was 78, range 65-96 years and comorbid diagnoses included dementia, mild cognitive impairment, frailty, and functional impairment. A total of 41.9% (n = 190) were diagnosed with malnutrition during the CGA. In the multivariable analysis, major depression and frailty were significantly associated with malnutrition. After controlling for potential confounders, patients who had malnutrition were 2.53-times more likely to have major depression (OR = 2.53, 95% CI: 1.23-5.24, p = 0.01) and 3.82 times more likely to have frailty (OR = 3.82, 95% CI: 1.35-10.84, p = 0.01) than those without malnutrition. CONCLUSIONS: Despite significant advances in cancer and supportive care, malnutrition remains a significant and highly prevalent public health problem among older patients with cancer. Identifying factors associated with risk for malnutrition in this patient population can help develop preventive strategies as part of care. Prospective studies are recommended.

Malnutrition and overall survival in older adults with cancer: A systematic review and meta-analysis.

BACKGROUND: Some studies have shown that malnutrition is associated with increased risk of mortality in older adults with cancer. However, evidence of its effect is limited and inconsistent. To assess the effect of malnutrition on overall survival in older adults with cancer, we performed a meta-analysis of available studies. METHODS: We systematically searched MEDLINE, EMBASE, Web of Science, CINAHL, and PsycINFO for observational studies that examined the association between malnutrition and risk of mortality in older adults with cancer (≥65 years). Malnutrition is defined according to assessment and screening tools in different studies. Older adults with malnutrition were compared with those with normal nutrition for overall survival. A random-effect model was fitted to estimate the summary relative risk (RR) and 95% confidence interval (CI). Between-studies heterogeneity was measured with the I2 statistic. RESULTS: Ten studies met the inclusion criteria, and a total of 4692 older adults with cancer were included in the meta-analysis. Heterogeneity existed among the different studies (I2 = 73.7%, p < 0.01). Malnutrition was significantly positively associated with increased risk of all-cause mortality (RR: 1.73; 95% CI: 1.23-2.41) compared with those with good nutrition status. A sensitivity analysis of 2773 older adults with cancer on the malnutrition assessed by Mini Nutrition Assessment (MNA), found that malnutrition is still associated with higher risk for all-cause mortality (RR = 2.13, 95% CI: 1.34-3.39). CONCLUSION: Our meta-analysis of observational studies found a significant effect of malnutrition on overall survival in older adults with cancer.

Predicting Fracture Risk in Younger Postmenopausal Women: Comparison of the Garvan and FRAX Risk Calculators in the Women's Health Initiative Study.

BACKGROUND: Guidelines recommend fracture risk assessment in postmenopausal women aged 50-64, but the optimal method is unknown. OBJECTIVES: To compare discrimination and calibration of the Fracture Risk Assessment Tool (FRAX) and Garvan fracture risk calculator for predicting fractures in postmenopausal women aged 50-64 at baseline. DESIGN: Prospective observational study. PARTICIPANTS: Sixty-three thousand seven hundred twenty-three postmenopausal women aged 50-64 years participating in the Women's Health Initiative Observational Study and Clinical Trials. MAIN MEASURES: Incident hip fractures and major osteoporotic fractures (MOF) during 10-year follow-up. Calculated FRAX- and Garvan-predicted hip fracture and MOF fracture probabilities. KEY RESULTS: The observed 10-year hip fracture probability was 0.3% for women aged 50-54 years (n = 14,768), 0.6% for women aged 55-59 years (n = 22,442), and 1.1% for women aged 60-64 years (n = 25,513). At sensitivity thresholds ≥ 80%, specificity of both tools for detecting incident hip fracture during 10 years of follow-up was low: Garvan 30.6% (95% confidence interval [CI] 30.3-31.0%) and FRAX 43.1% (95% CI 42.7-43.5%). At maximal area under the receiver operating characteristic curve (AUC(c), 0.58 for Garvan, 0.65 for FRAX), sensitivity was 16.0% (95% CI 12.7-19.4%) for Garvan and 59.2% (95% CI 54.7-63.7%) for FRAX. At AUC(c) values, sensitivity was lower in African American and Hispanic women than among white women and lower in women aged 50-54 than those 60-64 years old. Observed hip fracture probabilities were similar to FRAX-predicted probabilities but greater than Garvan-predicted probabilities. At AUC(c) values (0.56 for both tools), sensitivity for identifying MOF was also low (range 26.7-46.8%). At AUC(c) values (0.55 for both tools), sensitivity for identifying any clinical fracture ranged from 18.1 to 34.0%. CONCLUSIONS: In postmenopausal women aged 50-64 years, the FRAX and Garvan fracture risk calculator discriminate poorly between women who do and do not experience fracture during 10-year follow-up. There is no useful threshold for either tool.

Direction of flagellum beat propagation is controlled by proximal/distal outer dynein arm asymmetry.

The 9 + 2 axoneme structure of the motile flagellum/cilium is an iconic, apparently symmetrical cellular structure. Recently, asymmetries along the length of motile flagella have been identified in a number of organisms, typically in the inner and outer dynein arms. Flagellum-beat waveforms are adapted for different functions. They may start either near the flagellar tip or near its base and may be symmetrical or asymmetrical. We hypothesized that proximal/distal asymmetry in the molecular composition of the axoneme may control the site of waveform initiation and the direction of waveform propagation. The unicellular eukaryotic pathogens Trypanosoma brucei and Leishmania mexicana often switch between tip-to-base and base-to-tip waveforms, making them ideal for analysis of this phenomenon. We show here that the proximal and distal portions of the flagellum contain distinct outer dynein arm docking-complex heterodimers. This proximal/distal asymmetry is produced and maintained through growth by a concentration gradient of the proximal docking complex, generated by intraflagellar transport. Furthermore, this asymmetry is involved in regulating whether a tip-to-base or base-to-tip beat occurs, which is linked to a calcium-dependent switch. Our data show that the mechanism for generating proximal/distal flagellar asymmetry can control waveform initiation and propagation direction.

Neurocognitive deficits in older patients with cancer.

OBJECTIVE: To assess cognitive function in older adults undergoing cancer care. MATERIALS AND METHODS: This is a cross-sectional study, in the University of Texas MD Anderson Cancer Center, in older adults undergoing cancer care. Comprehensive geriatric assessments were conducted prior to surgery, chemotherapy or allogeneic stem cell transplantation, at the Program for Healthy Aging from January 1, 2013 through March 31, 2015. Cognitive assessment was conducted through personal and family interview, and the Montreal cognitive assessment (MoCA). Functional, physical, nutritional, social support, comorbidity assessment and medication review were conducted. ANALYSIS: Patients with mild cognitive impairment (MCI) or dementia were compared to patients who were cognitively intact. RESULTS: One hundred and ninety-two patients underwent geriatric assessment, mean (±SD) age was 78 ±â€¯7 years, 121 (63%) had some degree of neurocognitive deficit, with 64 patients (33%) presenting with major neurocognitive deficit (dementia), and 57 cases (30%), minor neurocognitive deficit (MCI). Early stage dementia was evident in 50% of cases, moderate stage in 32%, and severe stage in 18%. The prevalence of dementia and MCI were higher than in the general population studies (70-79 years). Associated factors for neurocognitive deficits as compared to older patients with cancer with normal cognition, included a higher comorbidity index (p = 0.04), stroke (p = 0.03), metastatic disease (p = 0.04), and warfarin use (p = 0.03). CONCLUSION: Neurocognitive deficits (MCI and dementia) are more common in older adults with cancer. Factors associated with neurocognitive deficits include high comorbidity, stroke, warfarin use and metastatic cancer. Identification and management of these conditions is of great relevance in the course of cancer therapy.

Risk factors for falls in older patients with cancer.

OBJECTIVES: A rising number of patients with cancer are older adults (65 years of age and older), and this proportion will increase to 70% by the year 2020. Falls are a common condition in older adults. We sought to assess the prevalence and risk factors for falls in older patients with cancer. METHODS: This is a single-site, retrospective cohort study. Patients who were receiving cancer care underwent a comprehensive geriatric assessments, including cognitive, functional, nutritional, physical, falls in the prior 6 months and comorbidity assessment. Vitamin D and bone densitometry were performed. ANALYSIS: Descriptive statistics and multivariable logistic regression. RESULTS: A total of 304 patients aged 65 or above were enrolled in this study. The mean age was 78.4±6.9 years. They had haematological, gastrointestinal, urological, breast, lung and gynaecological cancers. A total of 215 patients with available information about falls within the past 6 months were included for final analysis. Seventy-seven (35.8%) patients had at least one fall in the preceding 6 months. Functional impairment (p=0.048), frailty (p<0.001), dementia (p=0.021), major depression (p=0.010) and low social support (p=0.045) were significantly associated with the fall status in the univariate analysis. Multivariate logistic regression analysis identified frailty and functional impairment to be independent risk factors for falls. CONCLUSIONS: Falls are common in older patients with cancer and lead to adverse clinical outcomes. Major depression, functional impairment, frailty, dementia and low social support were risk factors for falls. Heightened awareness and targeted interventions can prevent falls in older patients with cancer.

Fractures frequently occur in older cancer patients: the MD Anderson Cancer Center experience.

PURPOSE AND INTRODUCTION: A growing number of cancer patients are older adults aged 65 years and older. Patients with cancer are at increased risk for developing osteoporosis, falls, and fractures. We sought to identify the incidence of fractures in older adults who underwent cancer care between January 2013 and December 2015. METHODS: A comprehensive geriatric assessment was performed, and bone densitometry was measured at baseline, with a 2-year follow-up. RESULTS: In this study, among 304 patients with gastrointestinal, urologic, breast, lung, and gynecologic cancers we evaluated, and who completed the bone density testing (n = 199), 80% had osteoporosis or low bone mass (osteopenia). There was a higher prevalence of osteoporosis in cancer patients (40 vs. 16%, p = 0.05) than in population studies. Vitamin D insufficiency (< 30 ng/ml) was identified in 49% of tested cases (n = 245). Risk factors for low bone mass or osteoporosis were advanced age (p = 0.05), malnutrition (p = 0.04), and frailty (p = 0.01). Over the following 2 years (median follow-up 18 months), there was an incidence of fractures of 110 per 1000 person-years, or 2.8 times higher than reported in individuals without cancer. Risk factors for fractures included advanced age (70-79 vs. 60-69 years, p = 0.05) and frailty (p = 0.03). CONCLUSION: Most older cancer patients studied have osteoporosis or low bone mass, resulting in an almost 3-fold increase in fracture risk as compared to epidemiologic studies. Bone health issues are commonly seen in older cancer patients, we recommend universal bone density testing. The initiation of antiresorptive treatment when findings are of osteopenia or osteoporosis will reduce the risk of fractures.

Online Educational Tool to Promote Bone Health in Cancer Survivors.

Osteoporosis burden is significant in cancer survivors. Websites providing health information abound, but their development, quality, and source of information remain unclear. Our aim was to use a systematic and transparent approach to create an educational website on bone health, and to evaluate its potential to improve knowledge, self-management, and awareness in prostate cancer (PCa) and breast cancer (BCa) survivors. Guided by the Health Belief Model, we created a website using international standards and evaluated it in 10 PCa and 10 BCa survivors with self-administered questionnaire before, after, and 1 month after navigating the website. The mean scores on the knowledge questionnaire at baseline, postintervention and 1 month were, respectively, 5.1 (±2.0), 6.9 (±2.5), and 6.7 (±2.4), p < .008, in PCa and 3.4 (±2.7), 7.6 (±3.0), and 6.5 (±3.8), p  = .016, in BCa survivors. Acceptability ratings ranged from 60% to 100%. Participants found the website useful, helpful, and able to raise bone health awareness. Our website improved bone health knowledge in both PCa and BCa survivors. A systematic and transparent approach to the development of online educational websites could result in a tool capable of meeting the educational needs of targeted consumers. Cancer survivors could benefit from proven online educational tools.

Osteoporosis Risk Calculators.

Osteoporosis is a silent disease until fractures occur, patient recognition is the greatest clinical challenge. Although more than 20 million women in the US are estimated to have established osteoporosis the majority are not appropriately identified. Bone densitometry is the current gold standard for diagnosis of osteoporosis; but may not be feasible or cost-effective to recommend for all postmenopausal women. Therefore, questionnaires incorporating risk factors have been developed to aid the clinician in identifying women with osteoporosis. We will review Qfracture, CAnadian Risk for Osteoporosis Calculator (CAROC), the Simple Calculated Osteoporosis Risk Index (SCORE), the Osteoporosis Risk Assessment Index (ORAI), the Osteoporotic Self-assessment Tool (OST), ABONE, and the United States Preventive Services Task Force recommendations.

Poor prognosis of patients with triple-negative breast cancer can be stratified by RANK and RANKL dual expression.

PURPOSE: As clinical studies have correlated RANK expression levels with survival in breast cancer, and that RANK signaling is dependent on its cognate ligand RANKL, we hypothesized that dual protein expression further stratifies the poor outcome in TNBC. METHODS: RANK mRNA and protein expression was evaluated in TNBC using genomic databases, cell lines and in a tissue microarray of curated primary tumor samples derived from 87 patients with TNBC. RANK expression was evaluated either by Mann-Whitney U test on log-normalized gene expression data or by Student's t test on FACS data. Analysis of RANK and RANKL immunostaining was calculated by H-score, and correlations to clinical factors performed using χ 2 or Fisher's exact test. Associations with RFS and OS were assessed using univariate and multivariate Cox proportional hazard models. Survival estimates were generated using the Kaplan-Meier method. RESULTS: In three distinct datasets spanning 684 samples, RANK mRNA expression was higher in primary tumors derived from TNBC patients than from those with other molecular subtypes (P < 0.01). Cell surface-localized RANK protein was consistently higher in TNBC cell lines (P = 0.037). In clinical samples, TNBC patients that expressed both RANK and RANKL proteins had significantly worse RFS (P = 0.0032) and OS (P = 0.004) than patients with RANK-positive, RANKL-negative tumors. RANKL was an independent, poor prognostic factor for RFS (P = 0.04) and OS (P = 0.01) in multivariate analysis in samples that expressed both RANK and RANKL. CONCLUSIONS: RANK and RANKL co-expression is associated with poor RFS and OS in patients with TNBC.

The Association of the C-Reactive Protein Inflammatory Biomarker with Breast Cancer Incidence and Mortality in the Women's Health Initiative.

Purpose: To examine associations of prediagnosis high-sensitivity C-reactive protein (hsCRP) with breast cancer incidence and postdiagnosis survival and to assess whether associations are modified by body mass index (BMI).Methods: A prospective analysis of the Women's Health Initiative was conducted among 17,841 cancer-free postmenopausal women with baseline hsCRP measurements. Cox proportional hazards models were used to examine associations between hsCRP concentrations and (i) breast cancer risk (n cases = 1,114) and (ii) all-cause mortality after breast cancer diagnosis. HRs are per 1 SD in log hsCRP.Results: hsCRP was not associated with breast cancer risk overall [HR = 1.05; 95% confidence interval (CI), 0.98-1.12]; however, an interaction between BMI and hsCRP was observed (Pinteraction = 0.02). A 1 SD increase in log hsCRP was associated with 17% increased breast cancer risk (HR = 1.17; 95% CI, 1.03-1.33) among lean women (BMI < 25), whereas no association was observed among overweight/obese (BMI ≥ 25) women. Prediagnosis hsCRP was not associated with overall mortality (HR, 1.04; 95% CI, 0.88-1.21) after breast cancer diagnosis; however, an increased mortality risk was apparent among leaner women with higher hsCRP levels (HR, 1.39, 95% CI, 1.03-1.88).Conclusions: Prediagnosis hsCRP levels are not associated with postmenopausal breast cancer incidence or survival overall; however, increased risks are suggested among leaner women. The observed effect modification is in the opposite direction of a previous case-control study finding and warrants further investigation.Impact: Associations of higher CRP levels with incident breast cancer and survival after breast cancer may depend on BMI. Cancer Epidemiol Biomarkers Prev; 26(7); 1100-6. ©2017 AACR.

Hepatotoxicity with Vismodegib: An MD Anderson Cancer Center and Research on Adverse Drug Events and Reports Project.

BACKGROUND: On 30 January 2012, the US FDA approved vismodegib (Erivedge®, Genentech, CA, USA) for the management of both metastatic and locally advanced basal cell carcinoma. OBJECTIVE: Our objective was to identify evidence of hepatotoxicity with vismodegib in the FDA Adverse Event Reporting System (FAERS) in treated patients in two National Cancer Institute Comprehensive Cancer Centers. METHODS: FAERS was searched for reports dated 1 January 2009 through 31 December 2015 using terms including hedgehog pathway and vismodegib and hepatic-related terms such as liver, jaundice, and hepatitis, among others. Disproportionality analyses with estimates of proportional reporting ratio and empirical Bayesian geometric mean were conducted. A comprehensive literature review was conducted, and the clinical databases at the University of Texas MD Anderson Cancer Center and Robert H. Lurie Comprehensive Cancer Center of Northwestern University were searched. RESULTS: Two cases of severe liver dysfunction were published (Common Terminology Criteria for Adverse Events [CTCAE] class III), and 94 reports of adverse events (AEs) were detected in FAERS, 35 of which were serious AEs. Safety notifications related to hepatotoxicity have not been issued by the manufacturer or the FDA, although vismodegib is listed in LiverTox and the European Medicines Agency website. CONCLUSION: We identified a detectable safety signal for hepatotoxicity for vismodegib within 4 years of FDA approval. Vismodegib should be used in patients with severe liver disease only after careful consideration, and concomitant hepatotoxic medications should be avoided. Rapid dissemination of such safety concerns is expected to result in fewer serious hepatotoxic AEs and more optimal outcomes for patients with cancer receiving vismodegib.