Alfred I Neugut

Columbia University, New York, New York, United States

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Publications (644)

  • L. Langenhoven · P. Barnardt · A. I. Neugut · J. S. Jacobson
    Article · Mar 2016
  • [Show abstract] [Hide abstract] ABSTRACT: Objective: Extended-duration thromboprophylaxis for 4weeks after discharge has been demonstrated to reduce venous thromboembolic events (VTE) in cancer patients undergoing abdominopelvic surgery and is recommended in national guidelines. We examined the utilization and effectiveness of extended-duration low molecular weight heparin prophylaxis in high-risk cancer patients. Methods: We analyzed patients with colon, ovarian, and uterine cancer who underwent surgery from 2009 to 2013 and who were recorded in the MarketScan database. Multivariable models and propensity score analysis with inverse probability of treatment weight were developed to examine uptake and predictors of use of post-discharge low molecular weight heparin (LMWH), as well as associated adverse events (transfusion, and hemorrhage). Results: A total of 63,280 patients were identified. Use of extended-duration prophylaxis increased from 2009 to 2013 from 1.4% to 1.7% (P=0.67) for colectomy, 5.9% to 18.3% for ovarian cancer surgery (P<0.001), and 6.3% to 12.2% (P<0.001) for hysterectomy for endometrial cancer. There was no association between use of extended-duration prophylaxis and reductions in VTE for any of the procedures: colectomy (2.4% with extended-duration prophylaxis vs. 2.9% without prophylaxis, OR=0.84; 95% CI, 0.54-1.31), ovarian cancer-directed surgery (3.7% vs. 3.6%, OR=1.01; 95% CI, 0.76-1.33), hysterectomy (2.1% vs. 2.1%; OR=0.96; 95% CI, 0.67-1.38). Extended-duration prophylaxis was associated with an increased risk of adverse postoperative events: 2.20 (95% CI, 1.51-3.19) after colectomy, 1.24 (95% CI, 0.92-1.68) following ovarian cancer-directed surgery and 0.99 (95% CI, 0.66-1.48) for hysterectomy for endometrial cancer. Conclusion: Use of extended-duration thromboprophylaxis is low among high-risk cancer patients undergoing surgery.
    Article · Mar 2016 · Gynecologic Oncology
  • Ana I Tergas · Alfred I Neugut · Ling Chen · [...] · Jason D Wright
    [Show abstract] [Hide abstract] ABSTRACT: This study examines factors associated with prolonged radiation duration and its impact on survival in women with cervical cancer treated with primary chemoradiation. Women in the National Cancer Database with stage IB2-IVA cervical cancer from 2003 to 2011 who received radiation and chemotherapy were included. Of 7209 women, who met inclusion criteria, 3401 (47.1%) and 3808 (52.8%) completed radiation in ≤ 8 and > 8 weeks, respectively. There was no overall survival difference for radiation duration ≤ 8 vs. > 8 weeks. Sensitivity analyses showed that inferior overall survival is only seen with radiation duration of > 10-12 weeks.
    Article · Mar 2016 · Cancer Investigation
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    Lauren E McCullough · Jia Chen · Yoon Hee Cho · [...] · Marilie D Gammon
    [Show abstract] [Hide abstract] ABSTRACT: Mechanisms underlying the poor breast cancer prognosis among obese women are unresolved. DNA methylation levels are linked to obesity and to breast cancer survival. We hypothesized that obesity may work in conjunction with the epigenome to alter prognosis. Using a population-based sample of women diagnosed with first primary breast cancer, we examined modification of the obesity-mortality association by DNA methylation. In-person interviews were conducted approximately 3 months after diagnosis. Weight and height were assessed [to estimate body mass index (BMI)], and blood samples collected. Promoter methylation of 13 breast cancer-related genes was assessed in archived tumor by methylation-specific PCR and Methyl Light. Global methylation in white blood cell DNA was assessed by analysis of long interspersed elements-1 (LINE-1) and with the luminometric methylation assay (LUMA). Vital status among 1308 patients (with any methylation biomarker and complete BMI assessment) was determined after approximately 15 years of follow-up (N = 194/441 deaths due to breast cancer-specific/all-cause mortality). We used Cox proportional hazards regression to estimate hazard ratios (HRs) and 95 % confidence intervals (CIs) using two-sided p values of 0.05. Breast cancer-specific mortality was higher among obese (BMI ≥ 30) patients with promoter methylation in APC (HR = 2.47; 95 % CI = 1.43-4.27) and TWIST1 (HR = 4.25; 95 % CI = 1.43-12.70) in breast cancer tissue. Estimates were similar, but less pronounced, for all-cause mortality. Increased all-cause (HR = 1.81; 95 % CI = 1.19-2.74) and breast cancer-specific (HR = 2.61; 95 % CI = 1.45-4.69) mortality was observed among obese patients with the lowest LUMA levels. The poor breast cancer prognosis associated with obesity may depend on methylation profiles, which warrants further investigation.
    Full-text Article · Mar 2016 · Breast Cancer Research and Treatment
  • [Show abstract] [Hide abstract] ABSTRACT: Vehicular traffic polycyclic aromatic hydrocarbons (PAHs) have been associated with breast cancer incidence in epidemiologic studies, including our own. Because PAHs damage DNA by forming adducts and oxidative lesions, genetic polymorphisms that alter DNA repair capacity may modify associations between PAH-related exposures and breast cancer risk. Our goal was to examine the association between vehicular traffic exposure and breast cancer incidence within strata of a panel of nine biologically plausible nucleotide excision repair (NER) and base excision repair (BER) genotypes. Residential histories of 1,508 cases and 1,556 controls were assessed in the Long Island Breast Cancer Study Project between 1996 and 1997 and used to reconstruct residential traffic exposures to benzo[a]pyrene, as a proxy for traffic-related PAHs. Likelihood ratio tests from adjusted unconditional logistic regression models were used to assess multiplicative interactions. A gene-traffic interaction was evident (p=0.04) for ERCC2 (Lys751); when comparing the upper and lower tertiles of 1995 traffic exposure estimates, the odds ratio (95% confidence interval) was 2.09 (1.13, 3.90) among women with homozygous variant alleles. Corresponding odds ratios for 1960-1990 traffic were also elevated nearly 2-3-fold for XRCC1(Arg194Trp), XRCC1(Arg399Gln) and OGG1(Ser326Cys), but formal multiplicative interaction was not evident. When DNA repair variants for ERCC2, XRCC1, and OGG1 were combined, among women with 4-6 variants, the odds ratios were 2.32 (1.22, 4.49) for 1995 traffic and 2.96 (1.06, 8.21) for 1960-1990 traffic. Our study is first to report positive associations between traffic-related PAH exposure and breast cancer incidence among women with select biologically plausible DNA repair genotypes. This article is protected by copyright. All rights reserved.
    Article · Mar 2016 · International Journal of Cancer
  • Alfred I Neugut · Cary P Gross
    [Show abstract] [Hide abstract] ABSTRACT: This Viewpoint evaluates prevention as a component of cancer research.Recently, the Obama administration announced the launch of a “moonshot” approach, led by vice president Biden, to finding a cure for cancer and reducing cancer mortality in the United States. Although preliminary communications about the plan mention the development of new vaccines to prevent cancer, the moonshot approach has generally been framed as a search for a cure for cancer, with increased investment in promising therapeutic approaches such as immunotherapy and the creation and sharing of data to simplify the search for personalized medicine and genomic markers that would permit customized therapies.1
    Article · Mar 2016
  • [Show abstract] [Hide abstract] ABSTRACT: Background: Polychlorinated biphenyls (PCBs) are hypothesised to influence breast carcinogenesis due to their persistence and potential to induce oestrogenic and anti-oestrogenic effects. Whether PCBs influence survival following breast cancer is unknown. Methods: A population-based cohort of women diagnosed with first primary invasive or in situ breast cancer in 1996-1997 and with blood-measured PCBs (n=627) collected shortly after diagnosis was followed for vital status through 2011. After 5 and 15 years, we identified 54 and 187 deaths, respectively, of which 36 and 74 were breast cancer related. Using Cox regression, we estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for mortality for baseline PCB concentrations, individually and as oestrogenic (ΣGroup 1B: PCB101, PCB174, PCB177, PCB187, and PCB199), anti-oestrogenic (ΣGroup 2A: PCB66, PCB74, PCB105, and PCB118; ΣGroup 2B: PCB138 and PCB170), and cytochrome P450 enzyme-inducing (ΣGroup 3: PCB99, PCB153, PCB180, PCB183, and PCB203) groups. Results: The highest PCB174 tertile was associated with an increase in all-cause (HR=2.22, 95% CI: 1.14-4.30) and breast cancer-specific (HR=3.15, 95% CI: 1.23-8.09) mortalities within 5 years of diagnosis and remained associated with breast cancer-specific mortality (HR=1.88, 95% CI: 1.05-3.36) at 15 years. At 5 years, the highest tertile of PCB177 was positively associated with all-cause mortality (HR=2.12, 95% CI: 1.05-4.30). At 15 years, the highest tertiles of ΣGroup 2A congeners and PCB118 were inversely associated with all-cause mortality (HR=0.60, 95% CI: 0.39-0.83; HR=0.63, 95% CI: 0.43-0.92, respectively). Conclusions: In this first US study of PCBs and breast cancer survival, PCBs were associated with mortality in biologically plausible directions. The investigation of other, structurally similar, chemicals may be warranted.
    Article · Mar 2016 · European journal of cancer (Oxford, England: 1990)
  • [Show abstract] [Hide abstract] ABSTRACT: Background: Compared with non-Latino, white patients with advanced cancer, Latino patients with advanced cancer are less likely to sign do-not-resuscitate (DNR) orders, which is a form of advance care planning associated with better quality of life at the end of life (EOL). Latinos' completion of DNR orders may be more sensitive to clinical discussions regarding EOL care. The current study examined differences between Latino and white terminally ill patients with cancer with regard to the association between EOL discussions and DNR order completion. Methods: A total of 117 participants with advanced cancer (61 of whom were Latino and 56 of whom were non-Latino white individuals) were recruited between 2002 and 2008 from Parkland Hospital (a public hospital in Dallas, Texas) as part of the Coping with Cancer study, which is a large, multiinstitutional, prospective cohort study of patients with advanced cancer that is designed to examine social and psychological influences on EOL care. In structured interviews, patients reported if they had EOL discussions with their physicians, and if they completed DNR orders. Results: The association between EOL discussions and DNR order completion was significantly greater in Latino compared with white patients, adjusting for potential confounds (interaction adjusted odds ratio, 6.64; P = .041). Latino patients who had an EOL discussion were >10 times more likely (adjusted odds ratio, 10.91; P = .001) to complete a DNR order than those who had not, and were found to be equally as likely to complete a DNR order as white patients. Conclusions: Differences in the impact of EOL discussions on DNR order completion may explain Latino/non-Latino ethnic disparities in DNR order completion in EOL care, and point to a means to eliminate those disparities. Cancer 2016. © 2016 American Cancer Society.
    Article · Mar 2016 · Cancer
  • [Show abstract] [Hide abstract] ABSTRACT: Importance Despite the lack of efficacy data, robotic-assisted surgery has diffused rapidly into practice. Marketing to physicians, hospitals, and patients has been widespread, but how this marketing has contributed to the diffusion of the technology remains unknown.Objective To examine the effect of regional hospital competition and hospital financial status on the use of robotic-assisted surgery for 5 commonly performed procedures.Design, Setting, and Participants A cohort study of 221 637 patients who underwent radical prostatectomy, total nephrectomy, partial nephrectomy, hysterectomy, or oophorectomy at 1370 hospitals in the United States from January 1, 2010, to December 31, 2011, was conducted. The association between hospital competition, hospital financial status, and performance of robotic-assisted surgery was examined.Main Outcomes and Measures The association between hospital competition was measured with the Herfindahl-Hirschman Index (HHI), hospital financial status was estimated as operating margin, and performance of robotic-assisted surgery was examined using multivariate mixed-effects regression models.Results We identified 221 637 patients who underwent one of the procedures of interest. The cohort included 30 345 patients who underwent radical prostatectomy; 20 802, total nephrectomy; 8060, partial nephrectomy; 134 985, hysterectomy; and 27 445, oophorectomy. Robotic-assisted operations were performed for 20 500 (67.6%) radical prostatectomies, 1405 (6.8%) total nephrectomies, 2759 (34.2%) partial nephrectomies, 14 047 (10.4%) hysterectomies, and 1782 (6.5%) oophorectomies. Use of robotic-assisted surgery increased for each procedure from January 2010 through December 2011. For all 5 operations, increased market competition (as measured by the HHI) was associated with increased use of robotic-assisted surgery. For prostatectomy, the risk ratios (95% CIs) for undergoing a robotic-assisted procedure were 2.20 (1.50-3.24) at hospitals in moderately competitive markets and 2.64 (1.84-3.78) for highly competitive markets compared with noncompetitive markets. For hysterectomy, patients at hospitals in moderately (3.75 [2.26-6.25]) and highly (5.30; [3.27-8.57]) competitive markets were more likely to undergo a robotic-assisted surgery. Increased hospital profitability was associated with use of robotic-assisted surgery only for partial nephrectomy in facilities with medium-high (1.67 [1.13-2.48]) and high (1.50 [0.98-2.29]) operating margins. With analysis limited to patients treated at a hospital that had performed robotic-assisted surgery, there was no longer an association between competition and use of robotic-assisted surgery.Conclusions and Relevance Patients undergoing surgery in a hospital in a competitive regional market were more likely to undergo a robotic-assisted procedure. These data imply that regional competition may influence a hospital’s decision to acquire a surgical robot.
    Article · Feb 2016 · JAMA SURGERY
  • DL Hershman · LH Kushi · GC Hillyer · [...] · AI Neugut
    Article · Feb 2016 · Cancer Research
  • H Greenlee · AI Neugut · L Falci · [...] · DL Hershman
    Article · Feb 2016 · Cancer Research
  • Article · Feb 2016 · Cancer Research
  • Article · Feb 2016 · Cancer Research
  • Article · Feb 2016 · Cancer Research
  • [Show abstract] [Hide abstract] ABSTRACT: Among patients with breast and ovarian cancer, a large number for whom BRCA testing is recommended do not undergo guideline recommended testing.
    Article · Feb 2016 · American journal of obstetrics and gynecology
  • [Show abstract] [Hide abstract] ABSTRACT: Radiation therapy has long been part of the treatment of endometrial cancer. Despite the long history of radiation use, prospective trials in the U.S. and Europe have been unable to demonstrate a survival benefit with adjuvant radiotherapy compared to observation. While radiation has been associated with decreased rate of loco-regional failure, the treatment is also associated with substantial toxicity. However, a randomized trial published in 2010 demonstrated that, compared to external beam radiation therapy (EBRT), vaginal brachytherapy was less toxic and as effective in reducing loco-regional relapses.
    Article · Feb 2016 · American journal of obstetrics and gynecology
  • [Show abstract] [Hide abstract] ABSTRACT: Purpose: Despite the potential benefits of minimally invasive hysterectomy for uterine cancer, population-level data describing the procedure's safety in unselected patients are lacking. We examined the use of minimally invasive surgery and the association between the route of the procedure and long-term survival. Methods: We used the SEER-Medicare database to identify women with stage I-III uterine cancer who underwent hysterectomy from 2006 to 2011. Patients who underwent abdominal hysterectomy were compared with those who had minimally invasive hysterectomy (laparoscopic and robot-assisted). Perioperative morbidity, use of adjuvant therapy, and long-term survival were examined after propensity score balancing. Results: We identified 6,304 patients, including 4,139 (65.7%) who underwent abdominal hysterectomy and 2,165 (34.3%) who underwent minimally invasive hysterectomy; performance of minimally invasive hysterectomy increased from 9.3% in 2006 to 61.7% in 2011. Robot-assisted procedures accounted for 62.3% of the minimally invasive operations. Compared with women who underwent abdominal hysterectomy, minimally invasive hysterectomy was associated with a lower overall complication rate (22.7% v 39.7%; P < .001), and lower perioperative mortality (0.6% v 1.1%), but these women were more likely to receive adjuvant pelvic radiotherapy (34.3% v 31.3%) and brachytherapy (33.6% v 31.0%; P < .05). The complication rate was higher after robot-assisted hysterectomy compared with laparoscopic hysterectomy (23.7% v 19.5%; P = .03). There was no association between the use of minimally invasive hysterectomy and either overall (HR, 0.89; 95% CI, 0.75 to 1.04) or cancer-specific (HR, 0.83; 95% CI, 0.59 to 1.16) mortality. Conclusion: Minimally invasive hysterectomy does not appear to compromise long-term survival for women with endometrial cancer.
    Article · Feb 2016 · Journal of Clinical Oncology
  • [Show abstract] [Hide abstract] ABSTRACT: Objective: Neuroendocrine carcinomas of the cervix (NECC) are rare and thought to be aggressive. We performed a population-based analysis to examine the natural history, treatment patterns and outcomes of women with NECC compared to squamous cell carcinoma (SCCC) and adenocarcinoma (AC) of the cervix. Methods: The National Cancer Database (NCDB) was utilized to identify women with NECC, SCCC, and AC treated from 1998 to 2011. Clinical, demographic, and treatment characteristics were compared between the groups. The association between tumor histology and survival was examined using Kaplan-Meier analyses and multivariable Cox proportional hazards regression models. Results: We identified 127,332 patients, including 1,896 (1.5%) with NECC and 101,240 (79.5%) with SCCC and 24,196 (19.0%) with AC. Patients with NECC were younger, more often white, commercially insured, and diagnosed with metastatic disease at presentation compared to women with SCCC. Patients with early-stage NECC were more likely to receive adjuvant chemotherapy and radiation after surgery (P<0.05 for both). In multivariable models stratified by stage and adjusted for clinical and demographic characteristics, the risk of death was higher for patients with NECC compared to SCCC for all stages of disease: stages IB-IIA (HR=2.96; 95% CI, 2.48-3.52), stages IIB-IVA (HR=1.70; 95% CI, 1.45-1.99) and stage IVB (HR=1.14; 95% CI, 0.91-1.43). Conclusion: NECC are aggressive tumors associated with an increased risk of death. Survival is inferior for NECC compared to squamous cell tumors for women with both early and advanced stage disease.
    Article · Feb 2016 · Gynecologic Oncology
  • [Show abstract] [Hide abstract] ABSTRACT: Objective: To examine the use of periodic surveillance testing for early-stage endometrial cancer survivors. Methods: We performed a population-based analysis using the Surveillance, Epidemiology, and End Results-Medicare database, which was used to identify patients with stage I-II endometrioid endometrial cancer treated from 1992 to 2011. Three surveillance periods (7-18, 19-30, 31-42 months) after hysterectomy were examined. Use of vaginal cytology and imaging were quantified. Results: We identified 17,638 patients. From 1992 to 2011, the use of chest radiography decreased (46.3-34.2%) during the first surveillance period, whereas imaging with chest computed tomography (CT) (0.9-12.6%), abdominopelvic CT (11.7-24.8%), and positron emission tomography (0-2.9%) increased (P<.001 for all). The use of cytology increased from 68.5% in 1992 to 72.3% in 2007 and then decreased to 66.9% in 2011 (P=.02). The mean number of cytologic samples obtained per patient increased from 1.3 in 1992 to 1.6 in 2008 and then declined to 1.3 in 2011, whereas the mean per patient number of chest CTs (0.02-0.2), abdominopelvic CTs (0.2-0.4), and positron emission tomographies (0-0.03) rose from 1992 to 2011. In 2011, 49.3% underwent radiologic surveillance 7-18 months after diagnosis, whereas 11.9% underwent two or more radiologic assessments in combination with cytology. These findings were similar for surveillance periods 2 and 3. Conclusion: The use of chest radiography has decreased and use of cytology has started to decline. However, the use of more costly imaging modalities is increasing despite a lack of evidence for the efficacy of these tests for early-stage endometrial cancer survivors.
    Article · Feb 2016 · Obstetrics and Gynecology
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    [Show abstract] [Hide abstract] ABSTRACT: Background: Tobacco smoke, diet and indoor/outdoor air pollution, all major sources of polycyclic aromatic hydrocarbons (PAHs), have been associated with breast cancer. Aberrant methylation may be an early event in carcinogenesis, but whether PAHs influence the epigenome is unclear, particularly in breast tissue where methylation may be most relevant. We aimed to evaluate the role of methylation in the association between PAHs and breast cancer. Methods: In a population-based case-control study, we measured promoter methylation of 13 breast cancer-related genes in breast tumor tissue (n=765-851 cases) and global methylation in peripheral blood (1055 cases/1101 controls). PAH sources (current active smoking, residential environmental tobacco smoke (ETS), vehicular traffic, synthetic log burning, and grilled/smoked meat intake) were evaluated separately. Logistic regression was used to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CIs). Results: When comparing methylated versus unmethylated genes, synthetic log use was associated with increased ORs for CDH1 (OR=2.26, 95%CI=1.06-4.79), HIN1 (OR=2.14, 95%CI=1.34-3.42) and RARβ (OR=1.80, 95%CI=1.16-2.78) and decreased ORs for BRCA1 (OR=0.44, 95%CI=0.30-0.66). Residential ETS was associated with decreased ORs for ESR1 (OR=0.74, 95%CI=0.56-0.99) and CCND2 methylation (OR=0.65, 95%CI=0.44-0.96). Current smoking and vehicular traffic were associated with decreased ORs for DAPK (OR=0.53, 95%CI=0.28-0.99) and increased ORs for TWIST1 methylation (OR=2.79, 95%CI=1.24-6.30), respectively. In controls, synthetic log use was inversely associated with LINE-1 (OR=0.59, 95%CI=0.41-0.86). Discussion: PAH sources were associated with hypo- and hypermethylation at multiple promoter regions in breast tumors and LINE-1 hypomethylation in blood of controls. Methylation may be a potential biologic mechanism for the associations between PAHs and breast cancer incidence.
    Full-text Article · Feb 2016 · Environmental Research

Publication Stats

20k Citations

Institutions

  • 1997-2015
    • Columbia University
      • • Department of Epidemiology
      • • Mailman School of Public Health
      • • College of Physicians and Surgeons
      New York, New York, United States
  • 1985-2015
    • CUNY Graduate Center
      New York, New York, United States
  • 2000-2009
    • New York Presbyterian Hospital
      • Department of Pain Medicine
      New York City, New York, United States
  • 2005
    • University of North Carolina at Chapel Hill
      North Carolina, United States
  • 2002
    • Queen Elizabeth Dental Services Inc.
      Montréal, Quebec, Canada
  • 2001
    • Yeshiva University
      New York, New York, United States
  • 1996
    • Harvard University
      Cambridge, Massachusetts, United States
  • 1993
    • New York State
      New York City, New York, United States
  • 1988-1993
    • Rambam Medical Center
      • Department of Oncology
      H̱efa, Haifa District, Israel
  • 1992
    • Gracie Square Hospital, New York, NY
      New York City, New York, United States