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The aim of this study was to compare cancer incidence rates (CIRs), between preexposure (1995-2000) and postexposure (2002-2014) periods in the entire New York City Police Department cohort exposed to the 2001 World Trade Center (WTC) disaster.CIR derived from active duty officer records, including postexposure data on retired officers.We observed 870 cancer cases in 859 officers (1995-2014), including 193 active duty cases pre-WTC and 677 cases (484 active duty, 193 retired) post-WTC. Overall, median CIR increased 1.44-fold compared with pre-WTC, with brain cancer increasing 3.27-fold, and kidney cancer increasing similarly. Thyroid cancer and non-Hodgkin's lymphoma increased 2.29 and 1.68-fold, respectively.Findings should be interpreted cautiously, given the small number of cancers at specific sites, and possibility of confounders. However, apparent increases in cancers overall, and in highlighted sites, remain of concern, underscoring the need for continued monitoring of this cohort.

Organochlorine insecticides have been studied extensively in relation to breast cancer incidence, and results from two meta-analyses have been null for late-life residues, possibly due to measurement error. Whether these compounds influence survival remains to be fully explored. We examined associations between organochlorine insecticides [p,p'-DDT (dichlorodiphenyltrichloroethane), its primary metabolite, p,p'-DDE, and chlordane] assessed shortly after diagnosis and survival among women with breast cancer. A population-based sample of women diagnosed with a first primary invasive or in situ breast cancer in 1996-1997 and with available organochlorine blood measures (n = 633) were followed for vital status through 2011. After follow-up of 5 and 15 years, we identified 55 and 189 deaths, of which 36 and 74, respectively, were breast cancer-related. Using Cox regression models, we estimated the multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for lipid-adjusted organochlorine concentrations with all-cause and breast cancer-specific mortality. At 5 years after diagnosis, the highest tertile of DDT concentration was associated with all-cause (HR = 2.19; 95% CI: 1.02, 4.67) and breast cancer-specific (HR = 2.72; 95% CI: 1.04, 7.13) mortality. At 15 years, middle tertile concentrations of DDT (HR = 1.42; 95% CI 0.99, 2.06) and chlordane (HR = 1.42; 95% CI: 0.94, 2.12) were modestly associated with all-cause and breast cancer-specific mortality. Third tertile DDE concentrations were inversely associated with 15-year all-cause mortality (HR = 0.66; 95% CI: 0.44, 0.99). This is the first population-based study in the United States to show that DDT may adversely impact survival following breast cancer diagnosis. Further studies are warranted given the high breast cancer burden and the ubiquity of these chemicals.

Patients with solid tumors are at greatest risk for dying from their cancers in the five years following diagnosis. For most malignancies, deaths from other chronic diseases begin to exceed those from cancer at some point. As little is known about the causes of death among long-term survivors of ovarian cancer, we examined causes of death by years from diagnosis.The Surveillance, Epidemiology, and End Results (SEER) database was used to identify women diagnosed with ovarian cancer between 1988 and 2012. We compared causes of death by stage, age, and interval time after diagnosis.A total of 67,385 women were identified. For stage I neoplasms, 13.6% (CI, 13.0-14.2%) died from ovarian cancer, 4.2% (CI, 3.8-4.5%) from cardiovascular disease, 3.6% (CI, 3.3-3.9%) from other causes and 2.6% (CI, 2.4-2.9%) from other tumors; ovarian cancer was the leading cause of death until 7 years after diagnosis after which time deaths are more frequently due to other causes. For those with stage III-IV tumors, 67.8% (CI, 67.3-68.2%) died from ovarian cancer, 2.8% (CI, 2.6-2.9%) from other causes, 2.3% (CI, 2.2-2.4%) from cardiovascular disease and 1.9% (CI, 1.7-2.0%) from other cancers; ovarian cancer was the most frequent cause of death in years 1-15 after which time deaths were more commonly due to other causes.The probability of dying from ovarian cancer decreases with time. Ovarian cancer remains the most common cause of death for 15 years after diagnosis in women with stage III-IV tumors.

Using a nationwide database, 4,874 patients with hypercalcemia of malignancy were identified. The in-hospital mortality rate was 6.8%. Overall, 1,971 (40.4%) patients received pamidronate and 1,399 (28.7%) received zoledronic acid during hospitalization. Calcitonin was utilized in 1,337 (27.4%) patients while glucocorticoids were administered to 1,311 (26.9%). Use of contraindicated medications was noted in 136 (2.8%) patients who received thiazide diuretics and 12 (0.2%) who received lithium. Tumor site, presence of bone metastases, and severity of illness were predictors of treatment. There was no association between treatment with bisphosphonates, calcitonin, or glucocorticoids and morbidity or mortality.

Introduction Women infected with the human immunodeficiency virus (HIV) have a higher risk of developing cervix carcinoma than do other women who are thought to be more vulnerable to acute toxicities during chemoradiation. We compared HIV-positive/HIV-negative patients with cervix carcinoma at a single institution with respect to cancer treatment toxicities. Methods and Materials Among patients with stage Ib1-IIIb invasive cervical carcinoma who received radiation or chemoradiation with curative intent, we evaluated demographic and clinical characteristics of HIV-positive and HIV-negative patients. Treatment regimens were documented and toxicities scored as per Radiation Therapy Oncology Group guidelines. We developed logistic regression models for the associations of grade 3/4 toxicities with HIV status. Results Complete data were available on 213 patients, including 36 (16.8%) who were HIV positive. More than 85% of both HIV-positive and HIV-negative patients received a minimum of 68-Gy equivalent dose in 2-Gy-fraction external beam and high-dose-rate brachytherapy. More HIV-positive than HIV-negative patients were prescribed radiation alone (38.9% vs 24.29%, P = 0.01), experienced at least 1 grade 3/4 toxicity (38.9% vs 26.6%), or developed grade 3/4 leucopenia (30.6% vs 10.2%, P = 0.003). In a multivariable model, patients who developed a grade 3/4 toxicity were 4 times as likely to have received chemotherapy (odds ratio, 4.41 [95% confidence interval, 1.76–11.1]; P = 0.023) and twice as likely to be HIV positive (odds ratio 2.16 [95% confidence interval, 0.98–4.8]; P = 0.05) as women who did not experience such toxicities. Conclusions HIV-positive patients with cervical carcinoma received adequate radiotherapy but were less likely than HIV-negative patients to complete chemotherapy. Few HIV-positive or HIV-negative patients who received radiotherapy without chemotherapy experienced grade 3/4 toxicity. However, among patients who received chemotherapy, those who were HIV positive were more likely than others to experience hematologic toxicity.

Although colonoscopy is predominant among the selection of colorectal cancer screening tests, stool testing (particularly fecal immunochemical testing) has also carved out an important niche for itself. Its simplicity and low cost make it ideal for mass population screening both in the United States and abroad, and it is an alternative choice for those reluctant to undergo endoscopy.

Background: Non-adherence to adjuvant hormonal therapy is common and has been associated with both increased copayment amount and black race. Studies suggest controlling for wealth may eliminate racial disparities for a variety of medical condition. We investigated the impact of personal finance on disparities in adherence rates. Patients and Methods: Using de-identified, integrated pharmacy and medical claims data from the Optum insurance claims database, we identified women >50 years old on hormonal therapy for early breast cancer with at least 2 mail order prescription refills between 1/1/07 and 12/31/11. Variables evaluated included demographic and clinical information, annual household income, estimated household net worth ($750,000), insurance type, and monthly copayment amounts ($20). Non-adherence was defined as a medication possession ratio Results: We identified 15,522 subjects who initiated hormonal therapy; 25% were non-adherent during the study period. Adherence was 67% with net worth $750,000 (p Conclusions: We have shown that financial factors, and in particular net worth, partially explain the lower hormone therapy adherence rate in black women compared to white women. These results suggest economic factors may contribute significantly to disparities in the quality of breast cancer care. Citation Format: Dawn L Hershman, Jennifer Tsui, Jason D Wright, Ellie J Coromilas, Wei Yann Tsai, Alfred I Neugut. Household net worth is associated with racial disparities in hormonal therapy adherence among women with early stage breast cancer [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P4-14-03.

BACKGROUND Adjuvant chemotherapy for early stage breast cancer decreases recurrence and increases survival. However, early discontinuation of chemotherapy occurs frequently and has a negative influence on patient outcomes. METHODS The Breast Cancer Quality of Care Study (BQUAL) is a prospective cohort study designed to investigate factors associated with early discontinuation of adjuvant chemotherapy among women diagnosed with non-metastatic breast cancer at three sites in the U.S between 2006 and 2010 (Columbia University Medical Center, Kaiser-Permanente of Northern California, Henry Ford Health System). Chemotherapy regimens were classified based on NCCN guidelines. Regimens were further categorized as standard and non-standard/experimental. Early discontinuation for standard treatments was defined as missing 20% of the recommended number of treatments for the prescribed regimen. We used multivariate analysis to examine the association between early discontinuation and sociodemographic factors, tumor characteristics, and baseline psychosocial factors. RESULTS Of 1157 women recruited, 478 patients initiated chemotherapy; 35 women received non-standard/experimental chemotherapy and an additional 17 did not complete all interviews and were excluded from the analysis. Of the remaining 426 patients, 59 (13.9%) did not complete the full course of prescribed chemotherapy. In multivariate analysis, compared to those who completed their full prescribed course of adjuvant chemotherapy, those who discontinued were more often >50 years of age (p=0.04). Early discontinuation of chemotherapy was less likely among Asian women (OR 0.12, 95% CI 0.01-0.96), those who held positive beliefs related to the efficacy of chemotherapy (OR 0.43, 95% CI 0.22-0.81), and those who were more optimistic (OR 0.93, 95% CI 0.86-0.99). Women prescribed chemotherapy regimens that had more cycles (>5 cycles) or contained paclitaxel/docetaxel were significantly more likely (OR 7.54, 95% CI 2.68-21.20 and OR 5.02, 95% CI 1.59-15.83, respectively) to discontinue chemotherapy treatment early than regimens with 6 or less cycles. CONCLUSIONS Women prescribed longer regimens were significantly more likely not to complete the full course. Positive beliefs about the efficacy of treatment were associated with continuation of treatment. Educational interventions focused on the importance of completing therapy may increase chemotherapy adherence. Citation Format: Alfred I Neugut, Grace C Hillyer, Lawrence W Kushi, Lois Lamerato, Jinjoo Shim, Dana H Bovberg, David Nathanson, Christine B Ambrisone, Jeanne S Mandelblatt, Carol Magai, Wei Yann Tsai, Judith S Jacobson, Dawn L Hershman. Early discontinuation of adjuvant chemotherapy in women with early stage breast cancer: The BQUAL study [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P1-11-09.

Background Polycyclic aromatic hydrocarbons (PAHs) are widespread environmental pollutants, known human lung carcinogens, and potent mammary carcinogens in laboratory animals. However, the association between PAHs and breast cancer in women is unclear. Vehicular traffic is a major ambient source of PAH exposure. Objectives Our study aim was to evaluate the association between residential exposure to vehicular traffic and breast cancer incidence. Methods Residential histories of 1,508 participants with breast cancer (case participants) and 1,556 particpants with no breast cancer (control participants) were assessed in a population-based investigation conducted in 1996–1997. Traffic exposure estimates of benzo[a]pyrene (B[a]P), as a proxy for traffic-related PAHs, for the years 1960–1995 were reconstructed using a model previously shown to generate estimates consistent with measured soil PAHs, PAH–DNA adducts, and CO readings. Associations between vehicular traffic exposure estimates and breast cancer incidence were evaluated using unconditional logistic regression. Results The odds ratio (95% CI) was modestly elevated by 1.44 (0.78, 2.68) for the association between breast cancer and long-term 1960–1990 vehicular traffic estimates in the top 5%, compared with below the median. The association with recent 1995 traffic exposure was elevated by 1.14 (0.80, 1.64) for the top 5%, compared with below the median, which was stronger among women with low fruit/vegetable intake [1.46 (0.89, 2.40)], but not among those with high fruit/vegetable intake [0.92 (0.53, 1.60)]. Among the subset of women with information regarding traffic exposure and tumor hormone receptor subtype, the traffic–breast cancer association was higher for those with estrogen/progesterone-negative tumors [1.67 (0.91, 3.05) relative to control participants], but lower among all other tumor subtypes [0.80 (0.50, 1.27) compared with control participants]. Conclusions In our population-based study, we observed positive associations between vehicular traffic-related B[a]P exposure and breast cancer incidence among women with comparatively high long-term traffic B[a]P exposures, although effect estimates were imprecise. Citation Mordukhovich I, Beyea J, Herring AH, Hatch M, Stellman SD, Teitelbaum SL, Richardson DB, Millikan RC, Engel LS, Shantakumar S, Steck SE, Neugut AI, Rossner P Jr., Santella RM, Gammon MD. 2016. Vehicular traffic–related polycyclic aromatic hydrocarbon exposure and breast cancer incidence: the Long Island Breast Cancer Study Project (LIBCSP). Environ Health Perspect 124:30–38; http://dx.doi.org/10.1289/ehp.1307736

This randomized controlled trial assessed different educational approaches for increasing colorectal cancer screening uptake in a sample of primarily non-US born urban minority individuals, over aged 50, with health insurance, and out of compliance with screening guidelines. In one group, participants were mailed printed educational material (n = 180); in a second, participants’ primary care physicians received academic detailing to improve screening referral and follow-up practices (n = 185); in a third, physicians received academic detailing and participants received tailored telephone education (n = 199). Overall, 21.5 % of participants (n = 121) received appropriate screening within one year of randomization. There were no statistically significant pairwise differences between groups in screening rate. Among those 60 years of age or older, however, the detailing plus telephone education group had a higher screening rate than the print group (27.3 vs. 7.7 %, p = .02). Different kinds of interventions will be required to increase colorectal cancer screening among the increasingly small population segment that remains unscreened. ClinicalTrials.gov Identifier: NCT02392143.

Background In laboratory experiments, ω-3 polyunsaturated fatty acids (PUFAs) reduce inflammatory eicosanoids resulting from ω-6 PUFA metabolism via competitive inhibition; and the ω-3 induced cytotoxic environment increases apoptosis and reduces cell growth in breast cancer cells. To the authors' knowledge, epidemiologic investigations regarding whether dietary ω-3 PUFA intake benefits survival following breast cancer, are limited and inconsistent.

Brachytherapy plays an important role in the treatment of cervical cancer. While small trials have shown comparable survival outcomes between high (HDR) and low-dose rate (LDR) brachytherapy, little data is available in the US. We examined the utilization of HDR brachytherapy and analyzed the impact of type of brachytherapy on survival for cervical cancer.Women with stages IB2-IVA cervical cancer treated with primary (external beam and brachytherapy) radiotherapy between 2003-2011 and recorded in the National Cancer Database (NCDB) were analyzed. Generalized linear mixed models and Cox proportional hazards regression were used to examine predictors of HDR brachytherapy use and the association between HDR use and survival.A total of 10,564 women including 2681 (25.4%) who received LDR and 7883 (74.6%) that received HDR were identified. Use of HDR increased from 50.2% in 2003 to 83.9% in 2011 (P0.0001). In a multivariable model, year of diagnosis was the strongest predictor of use of HDR. While patients in the Northeast were more likely to receive HDR therapy, there were no other clinical or socioeconomic characteristics associated with receipt of HDR. In a multivariable Cox model, survival was similar between the HDR and LDR groups (HR=0.93; 95% CI 0.83-1.03). Similar findings were noted in analyses stratified by stage and histology. Kaplan-Meier analyses demonstrated no difference in survival based on type of brachytherapy for stage IIB (P=0.68), IIIB (P=0.17), or IVA (P=0.16) tumors.The use of HDR therapy has increased rapidly. Overall survival is similar for LDR and HDR brachytherapy.

OBJECTIVE: To analyze factors associated with 30-day readmission among women who underwent hysterectomy for uterine cancer and benign indications. METHODS: We used the National Surgical Quality Improvement Project database to perform a cohort study of women who underwent hysterectomy from 2011 to 2012. Patients were stratified by surgical indication (uterine cancer or benign indications). Multivariable logistic regression models were constructed to determine factors associated with 30-day readmission. Model fit statistics were used to evaluate the importance of demographic factors, preoperative comorbidities, and postoperative complications on readmission. RESULTS: The rate of 30-day readmission was 6.1% among 4,725 women with uterine cancer and 3.4% after hysterectomy for benign gynecologic disease in 36,471 patients. In a series of multivariable models, postoperative complications including wound complications, infections, and pulmonary emboli and myocardial infarctions were the factors most strongly associated with readmission. Compared with women without a complication, complications increased the readmission rate from 2.5 to 20.3% for women with uterine cancer and from 1.5 to 15.1% for those without cancer. Among women with uterine cancer, postoperative complications explained 34.3% of the variance in readmission compared with 5.9% for demographic factors and 2.2% for preoperative comorbidities. For patients with benign diseases, complications accounted for 32.1%, preoperative conditions 1.2%, and demographic factors 2.5% of the variance in readmission. CONCLUSION: Efforts to reduce readmission should be directed at initiatives to reduce complications and improve the care of women who experience a complication. LEVEL OF EVIDENCE: II

The role of gene-specific methylation in white blood cells (WBC) as a marker of breast cancer risk is currently unclear. We determined whether promoter hypermethylation in blood DNA of candidate tumor suppressor genes frequently methylated in breast tumors can be used as a surrogate biomarker for breast cancer risk. Promoter methylation of BRCA1, CDH1 and RARβ was analyzed in WBC DNA from a population-based sample of 1,021 breast cancer patients and 1,036 controls by the MethyLight assay. Gene-specific promoter methylation in the DNA of 569 tumor tissue samples was also analyzed to determine the correlation of methylation levels with blood from the same individual. Hypermethylation of BRCA1 (OR: 1.31; 95% CI: 0.98-1.75) in WBC was associated with an increased risk of breast cancer when positive methylation was defined as ≥0.1% methylated. There was lack of concordance between tumor tissue and paired WBC DNA methylation. These results provide limited support that hypermethylation of BRCA1 in WBC DNA may be useful for determination of breast cancer risk. Additional studies with larger numbers of genes are needed to fully understand the relationship between WBC methylation and breast cancer risk.

Introduction: Little is known about how modifiable lifestyle factors interact with the epigenome to influence disease. Body mass index (BMI, weight kg/height m2) and physical activity are associated with postmenopausal breast cancer, but the mechanisms are not well-understood. We hypothesized that BMI or physical activity may modify the association between markers of global DNA methylation and postmenopausal breast cancer risk. Methods: Resources from a population-based case-control study (~1300 postmenopausal women) were used to construct logistic regression models. We explored whether the association between breast cancer and global methylation, assessed using the luminometric methylation assay (LUMA) and long interspersed elements-1 (LINE-1) methylation in white blood cell DNA, was modified by BMI or recreational physical activity (RPA). Results: The LUMA-breast cancer association was modified by BMI (multiplicative p=0.03) and RPA (p=0.004). Non-obese women in the highest quartile of LUMA experienced a greater than two-fold increased risk of postmenopausal breast cancer (BMI

Studies of vitamin D-pathway genetic variants in relation to cancer risk have been inconsistent. We examined the associations between vitamin D-related genetic polymorphisms, plasma 25-hydroxyvitamin D [25(OH)D], and breast cancer risk. In a population-based case–control study of 967 incident breast cancer cases and 993 controls, we genotyped 25 polymorphisms encoding the vitamin D receptor (VDR) gene, 1α-hydroxylase (CYP27B1), 24-hydroxylase (CYP24A1), and vitamin D-binding protein (GC) and measured plasma 25(OH)D. We used multivariable logistic regression to estimate adjusted odds ratios (ORs) and 95 % confidence intervals (CIs). Among CYP24A1 polymorphisms, rs6068816 was associated with a 72 % reduction in breast cancer risk (TT vs. CC, OR 0.28, 95 % CI 0.10–0.76; p trend = 0.01), but for rs13038432, the 46 % decrease included the null value (GG vs. AA, OR 0.54, 95 % CI 0.17–1.67; p trend = 0.03). Increased risk that included the null value was noted for CYP24A1 rs3787557 (CC vs. TT, OR 1.34, 95 % CI 0.92–1.89). The VDR polymorphism, TaqI (rs731236), was associated with a 26 % risk reduction (TT vs. CC, OR 0.74, 95 % CI 0.56–0.98; p trend = 0.01). For other polymorphisms, ORs were weak and included the null value. The inverse association for plasma 25(OH)D with breast cancer was more pronounced (OR 0.43, 95 % CI 0.27–0.68) among women with the common allele for CYP24A1, rs927650 (p for interaction on a multiplicative scale = 0.01). Breast cancer risk may be associated with specific vitamin D-related polymorphisms, particularly CYP24A1. Genetic variation in the vitamin D pathway should be considered when designing potential intervention strategies with vitamin D supplementation.

To perform a population-based analysis to compare the complications and cost of laparoscopic and robotically assisted adnexal surgery.A nationwide database was used to analyze the use and outcomes of robotically assisted adnexal surgery from 2009 to 2012. Multivariable mixed effects regression models were developed to examine predictors of use of robotic surgery. After propensity score matching, complications and cost were compared between robotically assisted and laparoscopic surgery.Eighty-seven thousand five hundred fourteen women were identified. From 2009 to 2012, performance of robotic-assisted oophorectomy increased from 3.5% (95% confidence interval [CI] 3.2-3.8%) to 15.0% (95% CI 14.4-15.6%), whereas robotically assisted cystectomy rose from 2.4% (95% CI 2.0-2.7%) to 12.9% (95% CI 12.2-13.5%). The overall complication rate was 7.1% (95% CI 4.0-10.2%) for robotically assisted compared with 6.0% (95% CI 2.9-9.1%) for laparoscopic oophorectomy (odds ratio [OR] 1.20, 95% CI 1.00-1.45; P=.052). Robotic-assisted oophorectomy was associated with a higher rate of intraoperative complications (3.4% compared with 2.1%, OR 1.60, 95% CI 1.21-2.13). The overall complication rate was 3.7% (95% CI -0.8 to 8.2%) after robotically assisted compared with 2.7% (95% CI -1.8 to 7.2%) for laparoscopic cystectomy (OR 1.38, 95% CI 0.95-1.99). The intraoperative complication rate was higher for robotically assisted cystectomy (2.0% compared with 0.9%, OR 2.40, 95% CI 1.31-4.38). Compared with laparoscopy, robotically assisted oophorectomy was associated with $2,504 (95% CI $2,356-2,652) increased total costs and robotically assisted cystectomy $3,310 (95% CI $3,082-3,581) higher costs.Use of robotically assisted adnexal surgery increased rapidly. Compared with laparoscopic surgery, robotically assisted adnexal surgery is associated with substantially greater costs and a small, but statistically significant, increase in intraoperative complications.

Higher intake of ω-3 relative to ω-6 polyunsaturated fatty acids (PUFAs) may reduce breast carcinogenesis via different metabolic pathways. The PUFA-breast cancer association remains inconclusive, thus, we hypothesized that interactions between the ratio of dietary ω-3:ω-6 intake and polymorphisms from PUFA-related metabolic pathways would help elucidate an association. Utilizing resources from the Long Island Breast Cancer Study Project, a population-based case-control study (n=1035 cases/1075 controls), we examined interactions between ω-3:ω-6 ratio and 18 polymorphisms of 15 genes. Compared to the putative lowest risk group (high ω-3:ω-6,low-risk FASL rs763110 CT/TT genotype), the odds ratio (OR) for breast cancer from unconditional logistic regression models was weakly increased for other exposure-genotype combinations (high ω-3:ω-6,high-risk FASL CC genotype, OR=1.18,95% confidence interval(CI)=0.90,1.53; low ω-3:ω-6,CT/TT genotype, OR=1.35,95%CI=1.09,1.66); but was approximately null for the putative highest risk group (low ω-3:ω-6,CC genotype; OR=1.06,95%CI=0.81,1.38). We observed an interaction between the ω-3:ω-6 ratio and FASL rs763110 on the additive scale [Relative Excess Risk Due to Interaction(RERI)=−0.47, 95%CI=−0.92,−0.02]. Interactions with other polymorphisms considered were not evident. Our findings suggest that the PUFA-breast cancer association may be modified by FASL. However, additional research is needed given this interaction may be due to chance and is inconsistent with our a priori biologic hypothesis.

Treatment selection for recurrent ovarian cancer is typically based on the duration of time between the completion of adjuvant, platinum-based therapy and the time of recurrence, the platinum free interval (PFI). We examined the use of, and outcomes associated with platinum-based chemotherapy based on the PFI in women with recurrent ovarian cancer.The Surveillance, Epidemiology, and End Results-Medicare database was used to identify women aged65years with epithelial ovarian cancer who underwent surgery and platinum-based chemotherapy and who developed a recurrence3months after the completion of adjuvant therapy. Patients were stratified by PFI into 3 groups: PFI6months, PFI 7-12months, and PFI12months. Multivariable models were used to examine predictors of use of platinum-based therapy and survival for each group.A total of 2369 patients were identified. In women with a PFI of ≤6months, treatment consisted of platinum-based combination therapy in 28.2%, single agent platinum in 5.2% and non-platinum therapy in 66.6%. Corresponding rates of these treatments among women with a PFI of 7-12months were 39.7%, 12.4% and 47.9%, respectively; the rates were 57.6%, 13.2% and 29.3% in those with a PFI of12months, respectively. Median survival was 13, 18, and 27months for patients with a PFI of ≤6months, 7-12months, and12months, respectively (P0.0001). For all three groups, platinum combination therapy was associated with decreased risk of death compared to non‑platinum based therapy.Platinum free interval is a strong predictor of survival in elderly women with recurrent ovarian cancer. There is widespread variation in treatment selection for women with recurrent ovarian cancer with many women receiving non-guideline based regimens.

Background: For patients with stages I-III colon cancer who have undergone surgical resection, guidelines recommend surveillance colonoscopy at 1 year. However, limited data exist on adherence and associated factors. We aimed to determine the rate of adherence to surveillance colonoscopy at 1 year among nonmetastatic colon cancer patients who underwent resection and factors associated with adherence. Methods: In this population-based retrospective cohort study, the Surveillance, Epidemiology, and End Results (SEER)–Medicare database was used. We identified patients with stages I-III colon cancer who underwent surgical resection and survived >3 years without recurrence (no chemotherapy after 8 months) from 2002–2011. Our primary outcome was a colonoscopy claim 10–15 months after resection. We used multivariable regression analysis to assess associations between sociodemographic and clinical factors and receipt of timely colonoscopy. Results: Among 28,732 patients who survived >3 years without recurrence, 7967 (28%) did not undergo colonoscopy; 12,033 (42%) had it at one year, with 3159 (11%) before 10 months and 5573 (19%) after 15 months. Decreased adherence was associated with older age; being male versus female; being black or Hispanic versus white; higher tumor stage; left-sided tumors versus right sided; and increased comorbidities. Chemotherapy receipt was associated with increased adherence (odds ratio 2.06; 95% confidence interval 1.88–2.24). Conclusions: In a large population-based sample of individuals aged ⩾ 65 years, only 42% of colon cancer survivors underwent 1-year surveillance colonoscopy. Demographic and clinical factors were associated with adherence.

To assess whether strict adherence to quality metrics by hospitals could explain the association between hospital volume and survival for ovarian cancer.We used the National Cancer Database to perform a retrospective cohort study of women with ovarian cancer from 2004 to 2013. Hospitals were stratified by annual case volume into quintiles (2 or less, 2.01-5, 5.01-9, 9.01-19.9, 20 cases or greater) and by adherence to ovarian cancer quality metrics into quartiles. Hospital-level adjusted 2- and 5-year survival rates were compared based on volume and adherence to the quality metrics.A total of 100,725 patients at 1,268 hospitals were identified. Higher volume hospitals were more likely to adhere to the quality metrics. Both 2- and 5-year survival increased with hospital volume and with adherence to the measured quality metrics. For example, 2-year survival increased from 64.4% (95% CI 62.5-66.4%) at low-volume to 77.4% (95% CI 77.0-77.8%) at high-volume centers and from 66.5% (95% CI 65.5-67.5%) at low-quality to 77.3% (95% CI 76.8-77.7%) at high-quality hospitals (P.001 for both). For each hospital volume category, survival increased with increasing adherence to the quality metrics. For example, in the lowest volume hospitals (two or less cases annually), adjusted 2-year survival was 61.4% (95% CI 58.4-64.5%) at hospitals with the lowest adherence to quality metrics and rose to 65.8% (95% CI 61.2-70.8%) at the hospitals with highest adherence to the quality metrics (P.001). However, lower volume hospitals with higher quality scores still had survival that was lower than higher volume hospitals.Although both hospital volume and adherence to quality metrics are associated with survival for ovarian cancer, low-volume hospitals that provide high-quality care still have survival rates that are lower than high-volume centers.

PURPOSE Breast conserving surgery (BCS) has become the preferred surgical option for the management of patients with nonmetastatic breast cancer in high-income countries. However, little is known about the distribution and determinants of BCS in low-and middle-income countries, especially those with high HIV prevalence. METHODS We compared demographic and clinical characteristics of female patients who received BCS and those who received total mastectomy (TM) for nonmetastatic invasive carcinoma of the breast in Soweto, South Africa, 2009-2011. We also developed a multivariable logistic regression model of predictors of type of surgery. RESULTS Of 445 patients, 354 (80%) underwent TM and 91 (20%) BCS. Of 373 patients screened for HIV, 59 (15.8%) tested positive. Eighty-two of 294 patients with stage I/II disease (28%), but just 9 of 151 (6%) with stage III disease had BCS (p

Purpose An estimated 5.9 million people in South Africa are infected with HIV. Because antiretroviral therapy has made infection with HIV a treatable, chronic condition, HIV-infected individuals are now surviving to middle and older age. We investigated the implications of HIV status for breast cancer in South Africa. Methods We compared clinical and demographic characteristics of women newly diagnosed with a first primary breast cancer at Tygerberg Hospital, Cape Town, South Africa, from January 2010 to December 2011 by HIV status. We then compared HIV-positive patients with HIV-negative controls, matched 2:1 on age and ethnicity, with respect to chemotherapy regimens, toxicities, completion of systemic chemotherapy, and changes in CD4 cell count. Results Of 586 women with breast cancer, 31 (5.3%) were HIV positive, 420 (71.7%) were HIV negative, and 135 (23%) were untested for HIV. Women with HIV were younger than other women (P < .001). The groups did not differ in regard to stage at presentation, histologic subtype, tumor grade, nodal involvement, or hormone receptor positivity. More than 84% of patients who initiated systemic chemotherapy, regardless of HIV status, completed it without serious toxicity. Among HIV-positive patients receiving chemotherapy, the mean baseline CD4 cell count was 477 cells/µL (standard deviation, 160 cells/µL), and the mean nadir was 333 cells/µL (standard deviation, 166 cells/µL). Conclusion HIV-infected women were younger at breast cancer diagnosis than HIV-negative women but otherwise similar in phenotype and completion of chemotherapy. Longer term follow-up is needed to evaluate the effects of HIV, antiretroviral therapy, and chemotherapy on the survival and quality of life of patients with breast cancer.

Uterine-preserving therapy with progesterone may be used in young women with endometrial cancer who desire fertility preservation. Such therapy delays definitive treatment with hysterectomy.We examined the use and safety of progestational therapy in young women with endometrial cancer. The primary outcome of the analysis was overall survival.We identified women ≤49 years of age with stage I endometrial cancer in the National Cancer Database from 2004 through 2014. Women treated with hormonal therapy with or without hysterectomy were compared to women treated with hysterectomy. After propensity score weighting, overall survival was examined using proportional hazards models.A total of 23,231 patients, including 872 (3.8%) women treated with hormonal therapy were identified. Use of hormonal therapy was 2.4% (95% confidence interval, 1.8-3.3%) in 2004 and increased over time to 5.9% (95% confidence interval, 5.0-6.9%) by 2014 (P.0001). Use of hormonal therapy decreased with older age, higher substage, and increasing grade. Black women were more likely to receive hormonal therapy while Medicaid recipients were less likely to receive hormonal therapy. The 5-year survival for patients treated with hormonal therapy was 96.4% (95% confidence interval, 94.3-98.0%) compared to 97.2% (95% confidence interval, 96.9-97.4%) for hysterectomy. In a multivariable model, women treated with hormonal therapy were 92% (hazard ratio, 1.92; 95% confidence interval, 1.15-3.19) more likely to die compared to women who underwent primary hysterectomy. When stratified by stage, hormonal therapy was associated with increased mortality in women with stage IB and I-not otherwise specified tumors but not for stage IA neoplasms.Use of progestational therapy is increasing. Its use was associated with decreased survival, particularly in women with stage IB tumors.

Background Grilled, barbecued, and smoked meat intake, a prevalent dietary source of polycyclic aromatic hydrocarbon (PAH) carcinogens, may increase the risk of incident breast cancer. However, no studies have examined whether intake of this PAH source influences survival after breast cancer. Methods We interviewed a population-based cohort of 1508 women diagnosed with first primary invasive or in situ breast cancer in 1996 and 1997 at baseline and again approximately five years later to assess grilled/barbecued and smoked meat intake. After a median of 17.6 years of follow-up, 597 deaths, of which 237 were breast cancer related, were identified. Multivariable Cox regression was used to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for mortality as related to prediagnosis intake, comparing high (above the median) to low intake, as well as postdiagnosis changes in intake, comparing every combination of pre-/postdiagnosis intake to low pre-/postdiagnosis intake. All statistical tests were two-sided. Results High prediagnosis grilled/barbecued and smoked meat intake was associated with increased risk of all-cause mortality (HR = 1.23, 95% CI = 1.03 to 1.46). Other associations were noted, but estimates were not statistically significant. These include high prediagnosis smoked beef/lamb/pork intake and increased all-cause (HR = 1.17, 95% CI = 0.99 to 1.38, Ptrend = .10) and breast cancer-specific (HR = 1.23, 95% CI = 0.95 to 1.60, Ptrend = .09) mortality. Also, among women with continued high grilled/barbecued and smoked meat intake after diagnosis, all-cause mortality risk was elevated 31% (HR = 1.31, 95% CI = 0.96 to 1.78). Further, breast cancer-specific mortality was decreased among women with any pre- and postdiagnosis intake of smoked poultry/fish (HR = 0.55, 95% CI = 0.31 to 0.97). Conclusion High intake of grilled/barbecued and smoked meat may increase mortality after breast cancer.

Whether aspirin or other nonsteroidal anti-inflammation drug (NSAID) use is associated with mortality following breast cancer remains unclear. Consideration of use patterns and interaction with obesity may help to clarify the inconsistent results. Pre-diagnosis NSAID use, weight, and height were assessed ~ 3 months after diagnosis through in-person interviews with a population-based cohort of 1,442 women with first primary breast cancer. Vital status was determined through the national death index after ~ 18 years of follow-up (N = 237/597 breast cancer-specific/all-cause deaths). We used Cox proportional hazards regression to estimate multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs). Multiplicative interaction by body mass index (BMI) was evaluated using the likelihood ratio test. Ever aspirin use was inversely associated with breast cancer-specific mortality (HR 0.87, 95% CI 0.59–1.29), but positively associated with all-cause mortality (HR 1.21, 95% CI 0.99–1.48); the CIs included the null values. The HRs, however, were more pronounced for the highest level of duration, frequency, regularity, and timing for all-cause, but not breast cancer-specific mortality. Interactions with BMI revealed no significant heterogeneity (pinteraction = 0.37 and pinteraction = 0.36, respectively). Pre-diagnosis aspirin use was not strongly associated with mortality following breast cancer. The all-cause mortality associations, however, were slightly stronger when we considered patterns of use.

Objective To examine the association of long term intake of gluten with the development of incident coronary heart disease. Design Prospective cohort study. Setting and participants 64 714 women in the Nurses’ Health Study and 45 303 men in the Health Professionals Follow-up Study without a history of coronary heart disease who completed a 131 item semiquantitative food frequency questionnaire in 1986 that was updated every four years through 2010. Exposure Consumption of gluten, estimated from food frequency questionnaires. Main outcome measure Development of coronary heart disease (fatal or non-fatal myocardial infarction). Results During 26 years of follow-up encompassing 2 273 931 person years, 2431 women and 4098 men developed coronary heart disease. Compared with participants in the lowest fifth of gluten intake, who had a coronary heart disease incidence rate of 352 per 100 000 person years, those in the highest fifth had a rate of 277 events per 100 000 person years, leading to an unadjusted rate difference of 75 (95% confidence interval 51 to 98) fewer cases of coronary heart disease per 100 000 person years. After adjustment for known risk factors, participants in the highest fifth of estimated gluten intake had a multivariable hazard ratio for coronary heart disease of 0.95 (95% confidence interval 0.88 to 1.02; P for trend=0.29). After additional adjustment for intake of whole grains (leaving the remaining variance of gluten corresponding to refined grains), the multivariate hazard ratio was 1.00 (0.92 to 1.09; P for trend=0.77). In contrast, after additional adjustment for intake of refined grains (leaving the variance of gluten intake correlating with whole grain intake), estimated gluten consumption was associated with a lower risk of coronary heart disease (multivariate hazard ratio 0.85, 0.77 to 0.93; P for trend=0.002). Conclusion Long term dietary intake of gluten was not associated with risk of coronary heart disease. However, the avoidance of gluten may result in reduced consumption of beneficial whole grains, which may affect cardiovascular risk. The promotion of gluten-free diets among people without celiac disease should not be encouraged.

Background: It has been suggested that risk in longitudinal studies may drop with time, but clear-cut documentation has been sparse. The purpose of this investigation was to determine risks at several time points in a recently completed/published longitudinal study to further evaluate this hypothesis. Methods: A population-based sample of 11,533 Bangladeshsis aged 18 to 75 was recruited and followed for 11-12 years and all-cause mortality was evaluated in those with and without baseline dyspnea. Dyspnea, the exposure, was ascertained by trained physicians by questionnaire. Kaplan-Meier survival curves and Cox Proportional Hazard models were used to determine differences between groups at 3, 6, and 11-12 years. Results: The Kaplan-Meier curves revealed a clear increase in mortality between dyspnea versus no dyspnea groups at the 3, 6, and 11.2 year time periods. The logrank test was significant with a p value less than 0.01 for all three time periods. At 3 years (3-yrs) the unadjusted hazard ratio (HR) was 3.43 (95% C.I.; 2.36 - 5.00). The 3-yrs HR adjusted for age, sex, arsenic well water concentration, education, blood pressure, BMI, and smoking was 2.58 (1.77 - 3.76)-for increased mortality in those with dyspnea versus no dyspnea. At 6-yrs, the crude and adj. HRs were 2.98 (2.28 - 3.88) and 2.23 (1.71 - 2.92), respectively. At 11.2 years, the crude and adj. HRs were 2.73 (2.27 - 3.28) and 2.10 (1.74 - 2.52) in those with dyspnea (relative to no dyspnea), respectively. Conclusions: Risk appears to drop over time in longitudinal studies of all-cause mortality, consistent with greater loss of those with the exposure relative to the unexposed. This phenomena might be expected. Therefore, longer longitudinal studies may actually underestimate and probably do not overestimate exposure risk.

Reducing delays related to inpatient chemotherapy may reduce healthcare costs. Using a national database, we identified patients with lymphoma/leukemia with ≥1 etoposide, vincristine, doxorubicin, cyclophosphamide, and prednisone (EPOCH) chemotherapy claim and evaluated chemotherapy initiation delay (ID), >1 day from admission. Standard tests/procedures prior to initiation were evaluated. Among 4453 inpatient cycles, 19.7% had ID, odds ratio 2.28 (95% confidence interval: 1.83–2.85) with cycle 1 compared to cycle 2, and mean costs were higher in patients with ID than without ID (p < .0001). Prior to cycle 1, patients were more likely to undergo routine diagnostic procedures compared to subsequent cycles. Efforts to perform routine procedures prior to admission may reduce hospital length of stay and costs.

The selective estrogen receptor modulator tamoxifen is now widely used for the treatment and prevention of breast cancer. Tamoxifen use has been associated with a variety of gynecologic problems. Despite the frequency with which hormonal therapy is used for the treatment of breast cancer, limited population-level data are available to describe the occurrence of gynecologic conditions and the use of surveillance testing in women receiving tamoxifen and aromatase inhibitors.We performed a population-based analysis among women with breast cancer receiving hormonal therapy with tamoxifen, a drug commonly used in premenopausal and sometimes postmenopausal women, to determine the frequency of gynecologic abnormalities and use of diagnostic and surveillance testing. We compared these findings to women treated with aromatase inhibitors, agents commonly used in postmenopausal women.The MarketScan database was used to identify women diagnosed with breast cancer from 2009 through 2013 who underwent mastectomy or lumpectomy. Women receiving tamoxifen (age50 vs ≥50 years) were compared to women ≥50 years of age treated with aromatase inhibitors. We examined the occurrence of gynecologic symptoms and diseases (vaginal bleeding, endometrial polyps, endometrial hyperplasia, and endometrial cancer) and gynecologic procedures and interventions (transvaginal ultrasound, endometrial biopsy, hysteroscopy/dilation and curettage, and hysterectomy). Time-dependent analyses were performed to examine symptoms and testing.A total of 75,170 women, including 15,735 (20.9%) age50 years treated with tamoxifen, 13,827 (18.4%) age ≥50 years treated with tamoxifen, and 45,608 (60.7%) age ≥50 years treated with aromatase inhibitors were identified. The cumulative incidence of any gynecologic symptom or pathologic diagnosis during the study period was 20.2%, 12.3%, and 3.5%, respectively (P.001), while the cumulative incidence of any gynecologic procedure or intervention during the study period was 34.2%, 20.9%, and 9.0%, respectively (P.0001). Among women without symptoms or pathology, interventions were performed in 20.0%, 11.0%, and 6.8%, respectively (P.0001).Compared to women taking aromatase inhibitors, gynecologic symptoms, procedures, and pathology are higher for both premenopausal and postmenopausal women with breast cancer on tamoxifen. Increased efforts to curb use of gynecologic interventions in asymptomatic women are needed.

No studies have evaluated the association between the dietary inflammatory index (DII) and colorectal adenoma recurrence. DII scores were calculated from a baseline food frequency questionnaire. Participants (n = 1727) were 40-80 years of age, enrolled in two Phase III clinical trials, who had ≥1 colorectal adenoma(s) removed within 6 months of study registration, and a follow-up colonoscopy during the trial. Multiple logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs). No statistically significant associations were found between DII and odds of colorectal adenoma recurrence [ORs (95% CIs) = 0.93 (0.73, 1.18) and 0.95 (0.73, 1.22)] for subjects in the second and third DII tertiles, respectively, compared to those in the lowest tertile (Ptrend = 0.72). No associations were found for recurrent colorectal adenoma characteristics, including advanced recurrent adenomas, large size, villous histology, or anatomic location. While our study did not support an association between a proinflammatory diet and colorectal adenoma recurrence, future studies are warranted to elucidate the role of a proinflammatory diet on the early stages of colorectal carcinogenesis.

Background: Environmental tobacco smoke (ETS) exposure is hypothesized to influence survival after breast cancer, but few studies have examined this association. Methods: A population-based cohort of women (N = 1,508) diagnosed with first primary invasive or in situ breast cancer in 1996 to 1997 was interviewed shortly after diagnosis and again approximately 5 years later to assess ETS exposure, and women were followed for more than 18 years using the National Death Index; 597 deaths (237 associated with breast cancer) were identified. Multivariable Cox regression was used to estimate adjusted HRs and 95% confidence intervals (CI) for mortality among women with breast cancer as related to at-diagnosis and at-/postdiagnosis changes in ETS exposure. Results: There was little or no association between at-diagnosis ETS exposure and all-cause (HR = 1.04; 95% CI, 0.78–1.40) or breast cancer–specific (HR = 0.98; 95% CI, 0.63–1.52) mortality. Mortality was elevated among women who reported cessation in postdiagnosis ETS exposure up to 1 year before the follow-up assessment, for all-cause (HR = 1.81; 95% CI, 0.87–3.74) and breast cancer mortality (HR = 1.89; 95% CI, 0.68–5.24); however, estimates were imprecise. Conclusions: We found little evidence of an association between at-diagnosis ETS exposure and mortality after breast cancer. Postdiagnosis cessation of ETS exposure was positively associated with mortality, although we could not rule out chance and reverse causation as possible explanations. Impact: Exposure to ETS does not appear to influence mortality after breast cancer. Cancer Epidemiol Biomarkers Prev; 26(2); 278–80. ©2016 AACR.

Cancer incidence increases with age, and as life expectancy increases, the number of elderly patients with cancer is increasing. Cancer treatments, including chemotherapy and radiotherapy, have significant short- and long-term effects on cardiovascular function. These cardiotoxic effects can be acute, such as changes in electrocardiogram (ECG), arrhythmias, ischemia, and pericarditis and/or myocarditis-like syndromes, or they can be chronic, such as ventricular dysfunction. Anticancer therapies can also have indirect effects, such as alterations in blood pressure, or can cause metabolic abnormalities that subsequently increase risk for cardiac events. In this review, we explore both observational and clinical trial evidence of cardiac risk in the elderly. In both observational and clinical trial data, risk of cardiotoxicity with anthracycline-based chemotherapy increases with age. However, it is less clear whether the association between age and cardiotoxicity exists for newer treatments. The association may not be well demonstrated as a result of under-representation of elderly patients in clinical trials and avoidance of these therapies in this population. In addition, we discuss strategies for surveillance and prevention of cardiotoxicity in the elderly. In the elderly, it is important to be aware of the potential for cardiotoxicity during long-term follow-up and to consider both prevention and surveillance of these late effects.

Despite institutional studies that suggest that radical hysterectomy for cervical cancer is well tolerated in the elderly, little population-level data are available on the procedure's outcomes in older women. We performed a population-based analysis to determine the morbidity, mortality, and resource utilization of radical hysterectomy in elderly women with cervical cancer.Patients recorded in the Nationwide Inpatient Sample with invasive cervical cancer who underwent abdominal radical hysterectomy between 1998 and 2010 were analyzed. Patients were stratified by age:50, 50-59, 60-69, and ≥70 years. We examined the association between age and the outcomes of interest using chi square tests and multivariable generalized estimating equations.A total of 8199 women were identified, including 768 (9.4%) women age 60-69 and 462 (5.6%) women ≥70 years of age. All cause morbidity increased from 22.1% in women50, to 24.7% in those 50-59 years, 31.4% in patients 60-69 years and 34.9% in women70years of age (P0.0001). Compared to women50, those70 were more likely to have intraoperative complications (4.8% vs. 9.1%, P=0.0003), surgical site complications (10.9% vs. 17.5%, P0.0001), and medical complications (9.9% vs. 19.5%, P0.0001). The risk of non-routine discharge (to a nursing facility) was 0.5% in women50 vs. 12.3% in women ≥70 (P0.0001). Perioperative mortality women ≥70 years of age was 30 times greater than that of women50 (P0.0001).Perioperative morbidity and mortality are substantially greater in elderly women who undergo radical hysterectomy for cervical cancer. Non-surgical treatments should be considered in these patients.

BACKGROUND In 2007, the Centers for Medicare and Medicaid Services stopped reimbursing for treatment of specified hospital-acquired conditions (HACs), also known as "never events." OBJECTIVE To establish benchmarks for HACs after common neurosurgical oncologic procedures. METHODS We identified adults in the Nationwide Inpatient Sample between 2002 and 2009 who underwent resection of a benign or malignant brain tumor. Baseline demographics, medical comorbidities, and hospital-level variables were assessed. A generalized estimating equation, multivariable-logistic model was used to identify predictors of HACs, mortality, prolonged hospital length of stay, and increased hospital charges. RESULTS We identified 310,133 patients undergoing surgical treatment of a cranial neoplasm; 5.4% experienced an HAC. More medical comorbidities and the presence of an immediate postoperative neurosurgical complication increased one's risk of having an HAC (odds ratios: 1.56 and 2.48, respectively; both P < .01). Patients who experienced an HAC faced increased in-hospital mortality (6.47% vs 1.53%; P < .01) and increased total hospital costs ($52,882.61 vs $25,569.45; P < .01). Patients at urban teaching hospitals and those with a high surgical volume were more likely to experience an HAC compared with those treated at rural nonteaching hospitals and those with a low surgical volume (odds ratios: 1.33 and 1.16, respectively; P < .01). CONCLUSION We found a 5.4% incidence of HACs after neurosurgical oncologic procedures, which varied based on several patient and hospital-level factors. A thorough analysis of the relationship between patient, procedure, and HAC incidence will be important to developing fair compensation practices for physicians as well as payers. Additionally, further investigation may identify opportunities for future quality improvement initiatives.

To perform an econometric analysis to examine the influence of procedure volume, variation in hospital accounting methodology, and use of various analytic methodologies on cost of robotically assisted hysterectomy for benign gynecologic disease and endometrial cancer.A national sample was used to identify women who underwent laparoscopic or robotically assisted hysterectomy for benign indications or endometrial cancer from 2006 to 2012. Surgeon and hospital volume were classified as the number of procedures performed before the index surgery. Total costs as well as fixed and variable costs were modeled using multivariable quantile regression methodology.A total of 180,230 women, including 169,324 women who underwent minimally invasive hysterectomy for benign indications and 10,906 patients whose hysterectomy was performed for endometrial cancer, were identified. The unadjusted median cost of robotically assisted hysterectomy for benign indications was $8,152 (interquartile range [IQR] $6,011-10,932) compared with $6,535 (IQR $5,127-8,357) for laparoscopic hysterectomy (P.001). The cost differential decreased with increasing surgeon and hospital volume. The unadjusted median cost of robotically assisted hysterectomy for endometrial cancer was $9,691 (IQR $7,591-12,428) compared with $8,237 (IQR $6,400-10,807) for laparoscopic hysterectomy (P.001). The cost differential decreased with increasing hospital volume from $2,471 for the first 5 to 15 cases to $924 for more than 50 cases. Based on surgeon volume, robotically assisted hysterectomy for endometrial cancer was $1,761 more expensive than laparoscopy for those who had performed fewer than five cases; the differential declined to $688 for more than 50 procedures compared with laparoscopic hysterectomy.The cost of robotic gynecologic surgery decreases with increased procedure volume. However, in all of the scenarios modeled, robotically assisted hysterectomy remained substantially more costly than laparoscopic hysterectomy.

Object Central nervous system (CNS) hemangiopericytomas are relatively uncommon and unique among CNS tumors as they can originate from or develop metastases outside of the CNS. Significant difference of opinion exists in the management of these lesions, as current treatment paradigms are based on limited clinical experience and single-institution series. Given these limitations and the absence of prospective clinical trials within the literature, nationwide registries have the potential to provide unique insight into the efficacy of various therapies. Methods The authors queried the Surveillance Epidemiology and End Results (SEER) database to investigate the clinical behavior and prognostic factors for hemangiopericytomas originating within the CNS during the years 2000–2009. The SEER survival data were adjusted for demographic factors including age, sex, and race. Univariate and multivariate analyses were performed to identify characteristics associated with overall survival. Results The authors identified 227 patients with a diagnosis of CNS hemangiopericytoma. The median length of follow-up was 34 months (interquartile range 11–63 months). Median survival was not reached, but the 5-year survival rate was 83%. Univariate analysis showed that age and radiation therapy were significantly associated with survival. Moreover, young age and supratentorial location were significantly associated with survival on multivariate analysis. Most importantly, multivariate analysis using the Cox proportional hazards model showed a statistically significant survival benefit for patients treated with gross-total resection (GTR) in combination with adjuvant radiation treatment (HR 0.31 [95% CI 0.01–0.95], p = 0.04), an effect not appreciated with GTR alone. Conclusions The authors describe the epidemiology of CNS hemangiopericytomas in a large, national cancer database, evaluating the effectiveness of various treatment paradigms used in clinical practice. In this study, an overall survival benefit was found when GTR was accomplished and combined with radiation therapy. This finding has not been appreciated in previous series of patients with CNS hemangiopericytoma and warrants future investigations into the role of upfront adjuvant radiation therapy.

BACKGROUND Observational studies comparing neoadjuvant chemotherapy to primary surgery for advanced-stage ovarian cancer are limited by strong selection bias. Multiple methods were used to control for confounding and selection bias to estimate the effect of primary treatment on survival for ovarian cancer. METHODS The Surveillance, Epidemiology, and End Results (SEER)-Medicare database was used to identify women ≥ 65 years of age with stage II-IV epithelial ovarian cancer who survived > 6 months from the date of diagnosis and received treatment from 1991 through 2007. Traditional regression analysis, propensity score-based analysis, and an instrumental variable analysis (IVA) using geographic location as an instrument were used to compare survival between neoadjuvant chemotherapy and primary surgery. RESULTS A total of 9587 patients with stage II-IV ovarian cancer were identified. Use of primary surgery decreased from 63.2% in 1991 to 49.5% by 2007, whereas primary chemotherapy increased from 19.7% in 1991 to 31.8% in 2007 (P

[][1] Joseph F. Fraumeni Jr. Photo Credit: Jonathan Newton Since its inception more than 40 years ago, the American Society for Preventive Oncology (ASPO) has made its mission impactful cancer prevention research. Its topmost recognition, the ASPO Distinguished Achievement Award

Background: Esophageal cancer remains associated with poor outcomes, yet little is known regarding factors that influence survival. Aspirin use prior to cancer diagnosis may influence outcomes. We aimed to assess the effects of prediagnosis aspirin use in patients with esophageal cancer. Methods: We conducted a prospective cohort study of newly-diagnosed esophageal cancer patients at two tertiary care centers. We assessed history of prediagnosis aspirin use, and prospectively followed patients and assessed mortality, cause of death, and development of metastases. Results: We enrolled 130 patients, the majority of whom were male (81.5%) and had adenocarcinoma (80.8%). Overall, 57 patients (43.9%) were regular aspirin users. In unadjusted analyses, we found no difference in all-cause mortality between aspirin users and nonusers. In multivariate analyses, prediagnosis aspirin use was not associated with all-cause mortality [hazard ratio (HR) 0.86, 95% confidence interval (CI) 0.48–1.57] or esophageal cancer-specific mortality (HR 1.07, 95% CI 0.52–2.21). Prediagnosis aspirin use was associated with a significantly increased risk of interval metastasis (HR 3.59, 95% CI 1.08–11.96). Conclusions: In our cohort of esophageal cancer patients, prediagnosis aspirin use was not associated with all-cause or cancer-specific mortality. However, risk of interval metastatic disease was increased among those who took aspirin regularly prediagnosis. Future studies are warranted to assess whether aspirin influences the molecular characteristics of esophageal tumors, with potential prognostic and therapeutic implications.

Small bowel adenocarcinoma is a rare disease occurring 50–100-fold less often than colorectal cancer. This commentary describes similarities and differences between the two diseases and related results of recent clinical trials.

Objective The objective of the study was to determine the rates and predictors of fertility preservation services among reproductive-aged women with common cancers in the United States. Study Design We used the MarketScan database to identify women 18–45 years of age with lung, breast, colorectal, or cervical cancer who underwent surgery and chemotherapy from 2009 through 2016. Services from 3 months before to 3 months after chemotherapy for evaluation for fertility preservation, laboratory testing for fertility evaluation, and fertility-preserving procedures were captured. Multivariable models were used to assess the factors associated with the use of fertility-preservation services. Results A total of 18,781 women, including 386 cervical, 1372 colorectal, 246 lung, and 16,777 with breast cancer, were identified. In women 18–35 years old, 11.7% underwent evaluation for fertility preservation, 13.7% underwent laboratory testing, and 6.3% pursued fertility-preserving procedures. The rates of office evaluation, laboratory testing, and performance of procedure were 3.3%, 7.5%, and 1.9 % in women aged 36–40 years and 0.5%, 7.2%, and 0.3% in those aged 41–45 years, respectively. The rate of fertility preservation evaluation rose from 1.0% in 2009 to 5.5% in 2016 (risk ratio, 4.66, 95% confidence interval, 2.38–9.11) while use of fertility-preserving procedures increased from 1.0% to 4.6% (risk ratio, 3.84, 95% confidence interval, 1.94–7.59) during the same time period. In a multivariable model, use of any fertility-preserving interventions were more common in patients with breast cancer (adjusted risk ratio, 2.30, 95% confidence interval, 1.30–4.06), those in the Northeast (adjusted risk ratio, 1.24, 95% confidence interval, 1.10–1.40), and in younger women (18–35 years) (adjusted risk ratio, 2.59, 95% confidence interval, 2.32–2.89). Conclusion Although limited by lack of information regarding cancer stage and desire for future fertility, only a small fraction of reproductive-aged female cancer patients receiving chemotherapy are evaluated in a nationwide sample for fertility preservation or undergo fertility-preserving procedures.

72 Background: In September 2018, Herbert Irving Comprehensive Cancer Center (HICCC) began using non-clinical pharmacy liaisons to oversee coordination of oral anticancer drug (OACD) prescriptions (RXs), a task previously performed by clinical staff. Liaisons interact with payers, specialty pharmacies and financial assistance (FA) groups. We assessed the impact of this strategy on time to receipt of OACDs. Methods: We collected prospective data on all new OACD RXs from HICCC’s medical oncology practice from 1/1/2018 to 9/17/2018 (pre-liaisons) and 9/17/2018 to 5/1/2019 (post-liaisons). We collected patient demographic and insurance data; date of prescription; date of drug delivery; and interactions with payers and FA groups. Federal Drug Association labels were reviewed for drug approval dates and indications. Daily drug cost was defined according to average wholesale price. We define time to receipt (TTR) as days from RX to OACD delivery and used multivariable linear regression to determine factors associated with TTR (log transformed). Results: Over the study period, we evaluated 707 RXs; 93 (13%) were never filled. Of 614 filled RXs, 350 (57%) were placed in the pre-liaison period and 264 (43%) in the post-liaison period. After introduction of liaisons, FA was pursued for more RXs (17% vs 25%, p = 0.007); there was no difference pre- and post-liaisons in patient demographics, distribution of payers, RXs needing prior authorization (PA) (76% vs 77%), off-label RXs (14% vs 16%), RXs for drugs approved < 2 years earlier (5% vs 3%) or mean daily cost ($471 vs $470). Mean TTR before and after liaisons were 11.9 and 11.6 days, respectively. Linear regression showed longer TTR was associated with commercial payers (p = 0.02), need for PA (p = 0.03), FA pursuit (p ≤ 0.0001) and daily OACD cost (p = 0.03); no association was seen with use of liaisons, patient age, off-label use or OACDs approved < 2 years earlier. Conclusions: Implementation of pharmacy liaisons to coordinate OACD prescriptions did not impact the time to OACD receipt, though liaisons were able to pursue financial assistance for more patients. Insurance and cost factors had the greatest impact on time to drug receipt. Task shifting may reduce the clerical workload for providers.

Background: Estrogen metabolites play a role in breast cancer development. Previous studies have particularly focused on the two competing metabolism pathways which yield metabolites 2-hydroxyestrone (2-OHE1) and 16-hydroxyestrone (16-OHE1). 2-OHE1 has been shown to have antiestrogenic effects, but 16-OHE1has strong estrogenic and even genotoxic activity. No study has investigated their biologically plausible role in predicting prognosis/mortality among women diagnosed with breast cancer. Methods: In the Long Island Breast Study Project, spot urine samples were obtained from 687 women diagnosed with first primary breast cancer (shortly after diagnosis) in 1996-1997. Urinary concentrations of estrogen metabolites 2-OHE1 and 16-OHE1 were measured using enzyme linked immuno-assay. Vital status was determined by the National Death Index through December 31, 2014; 244 deaths (84 breast cancer-specific and 80 cardiovascular diseases-specific) were identified. We used multivariable-adjusted Cox proportional hazards regression model to estimate hazard ratios (HRs) and 95% confidence intervals (95% CIs) for all-cause, breast cancer and cardiovascular diseases mortality as related to the two individual metabolites and their ratio (2-OHE1/16-OHE1). Multiplicative interactions with menopausal hormone therapy, body mass index, menopausal status, and breast cancer treatments were evaluated with likelihood ratio tests. Results: During a median follow-up of 18 years, urinary concentration of the 2-OHE1/16-OHE1 ratio (> median of 1.8 vs. ≤ median of 1.8) was associated with reduced risk of all-cause mortality (HR=0.74, 95% CI=0.56-0.98) among women with breast cancer. This inverse association with the 2-OHE1/16-OHE1 ratio was also observed for breast cancer mortality (HR=0.73, 95% CI=0.45-1.17) and cardiovascular diseases mortality (HR=0.76, 95% CI=0.47-1.23), although the 95%CIs included the null. The 2-OHE1/16-OHE1 ratio-mortality associations did not significantly differ by menopausal hormone therapy, body mass index, and menopausal status at the time of urine collection (Pinteration >0.05). Consistent patterns of association were not observed between the individual metabolites and mortality outcomes. Conclusion: To our knowledge, our study represents the first population-based epidemiologic evidence suggesting that the urinary concentration of the 2-OHE1/16-OHE1 ratio measured shortly after breast cancer diagnosis may be associated with improved overall mortality for breast cancer survivors. Future investigation is necessary to confirm our findings and to further understand the underlying biological mechanisms for estrogen metabolism–mortality relationships following breast cancer diagnosis. Citation Format: Tengteng Wang, Patrick B. Bradshaw, Sarah J. Nyante, Hazel B. Nichols, Patricia G. Moorman, Geoffrey C. Kabat, Susan L. Teitelbaum, Alfred I. Neugut, Marilie D. Gammon. Urinary estrogen metabolites and long-term all-cause and cause-specific mortality following breast cancer diagnosis: A population-based study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3294.