Use of the Decipher genomic classifier among men with prostate cancer in the United States.

BACKGROUND: Management of localized or recurrent prostate cancer since the 1990s has been based on risk stratification using clinicopathological variables, including Gleason score, T stage (based on digital rectal exam), and prostate-specific antigen (PSA). In this study a novel prognostic test, the Decipher Prostate Genomic Classifier (GC), was used to stratify risk of prostate cancer progression in a US national database of men with prostate cancer. METHODS: Records of prostate cancer cases from participating SEER (Surveillance, Epidemiology, and End Results) program registries, diagnosed during the period from 2010 through 2018, were linked to records of testing with the GC prognostic test. Multivariable analysis was used to quantify the association between GC scores or risk groups and use of definitive local therapy after diagnosis in the GC biopsy-tested cohort and postoperative radiotherapy in the GC-tested cohort as well as adverse pathological findings after prostatectomy. RESULTS: A total of 572 545 patients were included in the analysis, of whom 8927 patients underwent GC testing. GC biopsy-tested patients were more likely to undergo active active surveillance or watchful waiting than untested patients (odds ratio [OR] =2.21, 95% confidence interval [CI] = 2.04 to 2.38, P < .001). The highest use of active surveillance or watchful waiting was for patients with a low-risk GC classification (41%) compared with those with an intermediate- (27%) or high-risk (11%) GC classification (P < .001). Among National Comprehensive Cancer Network patients with low and favorable-intermediate risk, higher GC risk class was associated with greater use of local therapy (OR = 4.79, 95% CI = 3.51 to 6.55, P < .001). Within this subset of patients who were subsequently treated with prostatectomy, high GC risk was associated with harboring adverse pathological findings (OR = 2.94, 95% CI = 1.38 to 6.27, P = .005). Use of radiation after prostatectomy was statistically significantly associated with higher GC risk groups (OR = 2.69, 95% CI = 1.89 to 3.84). CONCLUSIONS: There is a strong association between use of the biopsy GC test and likelihood of conservative management. Higher genomic classifier scores are associated with higher rates of adverse pathology at time of surgery and greater use of postoperative radiotherapy.In this study the Decipher Prostate Genomic Classifier (GC) was used to analyze a US national database of men with prostate cancer. Use of the GC was associated with conservative management (ie, active surveillance). Among men who had high-risk GC scores and then had surgery, there was a 3-fold higher chance of having worrisome findings in surgical specimens.

Morbidity and Mortality Differences Between Hematopoietic Cell Transplantation Survivors and Other Cancer Survivors.

Purpose To compare the risks of serious health outcomes among hematopoietic cell transplantation (HCT) survivors versus a matched population of patients with cancer who did not undergo HCT, where the primary difference may be exposure to HCT. Methods Two-year HCT survivors treated at a comprehensive cancer center from 1992 through 2009 who were Washington State residents (n = 1,792; 52% allogeneic and 90% hematologic malignancies) were frequency matched by demographic characteristics and underlying cancer diagnosis (as applicable) to non-HCT 2-year cancer survivors, using the state cancer registry (n = 5,455) and the general population (n = 16,340) using driver's license files. Late outcomes for all three cohorts were ascertained from the state hospital discharge and death registries; subsequent cancers were ascertained from the state cancer registry. Results After median follow-up of 7.1 years, HCT survivors experienced significantly greater rates of hospitalization compared with matched non-HCT cancer survivors (280 v 173 episodes per 1,000 person-years, P < .001) and greater all-cause mortality (hazard ratio [HR], 1.1; 95% CI, 1.01 to 1.3). HCT survivors had more hospitalizations or death with infections (10-year cumulative incidence, 31% v 22%; HR, 1.4; 95% CI, 1.3 to 1.6) and respiratory complications (cumulative incidence, 27% v 20%; HR, 1.4; 95% CI, 1.2 to 1.5). Risks of digestive, skin, and musculoskeletal complications also were greater among HCT versus non-HCT cancer survivors. The two groups had similar risks of circulatory complications and second cancers. Both HCT and non-HCT cancer survivors had significantly greater 10-year cumulative incidences of all major organ-system outcomes versus the general population. Conclusion History of HCT was associated with late morbidity and mortality among cancer survivors. In particular, clinicians who care for HCT survivors should be aware of their high rates of late respiratory and infectious complications.

Hospital volume is associated with survival but not multimodality therapy in Medicare patients with advanced head and neck cancer.

BACKGROUND: Given the complexity of management of advanced head and neck squamous cell carcinoma (HNSCC), this study hypothesized that high hospital volume would be associated with receiving National Comprehensive Cancer Network (NCCN) guideline therapy and improved survival in patients with advanced HNSCC. METHODS: The Surveillance, Epidemiology, and End Results (SEER)-Medicare database was used to identify patients with advanced HNSCC. Treatment modalities and survival were determined using Medicare data. Hospital volume was determined by the number of patients with HNSCC treated at each hospital. RESULTS: There were 1195 patients with advanced HNSCC who met inclusion criteria. In multivariable analyses, high hospital volume was not associated with receiving multimodality therapy per NCCN guidelines (odds ratio = 1.02, 95% confidence interval = 0.66-1.60), but showed a nearly significant inverse association with survival in a model adjusted for National Cancer Institute-designated cancer center status, age, sex, race, socioeconomic status, marital status, comorbidity, year of diagnosis, tumor site, and tumor stage (hazard ratio = 0.85, 95% confidence interval = 0.69-1.04). CONCLUSIONS: Medicare patients with advanced HNSCC treated at high-volume hospitals were not more likely to receive NCCN guideline therapy, but had nearly statistically significant better survival, when compared with patients treated at low-volume hospitals. These results suggest that features of high-volume hospitals other than delivery of NCCN guideline therapy influence survival. Cancer 2013. © 2013 American Cancer Society.

Vitamin or mineral supplement intake and the risk of head and neck cancer: pooled analysis in the INHANCE consortium.

To investigate the potential role of vitamin or mineral supplementation on the risk of head and neck cancer (HNC), we analyzed individual-level pooled data from 12 case-control studies (7,002 HNC cases and 8,383 controls) participating in the International Head and Neck Cancer Epidemiology consortium. There were a total of 2,028 oral cavity cancer, 2,465 pharyngeal cancer, 874 unspecified oral/pharynx cancer, 1,329 laryngeal cancer and 306 overlapping HNC cases. Odds ratios (OR) and 95% confidence intervals (CIs) for self reported ever use of any vitamins, multivitamins, vitamin A, vitamin C, vitamin E, and calcium, beta-carotene, iron, selenium and zinc supplements were assessed. We further examined frequency, duration and cumulative exposure of each vitamin or mineral when possible and stratified by smoking and drinking status. All ORs were adjusted for age, sex, race/ethnicity, study center, education level, pack-years of smoking, frequency of alcohol drinking and fruit/vegetable intake. A decreased risk of HNC was observed with ever use of vitamin C (OR = 0.76, 95% CI = 0.59-0.96) and with ever use of calcium supplement (OR = 0.64, 95% CI = 0.42-0.97). The inverse association with HNC risk was also observed for 10 or more years of vitamin C use (OR = 0.72, 95% CI = 0.54-0.97) and more than 365 tablets of cumulative calcium intake (OR = 0.36, 95% CI = 0.16-0.83), but linear trends were not observed for the frequency or duration of any supplement intake. We did not observe any strong associations between vitamin or mineral supplement intake and the risk of HNC.

Neither antioxidants nor genistein inhibit the progression of established atherosclerotic lesions in older apoE deficient mice.

Supplements and diets enriched in antioxidants and soy isoflavones are purported to reduce cardiovascular disease risk. Many experimental studies have demonstrated inhibitory effects of antioxidants and soy isoflavones on the development of fatty streaks in animal models. However, it is still unknown whether antioxidants and isoflavones have comparable inhibitory effects on the progression of advanced stages of atherosclerosis. This is an important question because clinical trials in humans have not supported a cardio-protective role for antioxidants or isoflavones. Thus, we examined the effects of antioxidants and genistein on the progression and composition of established, advanced atherosclerotic lesions in the innominate arteries (IA) of older apolipoprotein E-deficient (apoE(-/-)) mice. Thirty-week-old male apoE(-/-) mice were fed chow with or without genistein (0.27%, w/w) for 6, 12 and 24 weeks. Twenty-week-old male apoE(-/-) mice were fed chow with or without a cocktail of antioxidants (vitamin E 0.2%, w/w; vitamin C 0.05%, w/w; and beta carotene 0.5%, w/w) for 10, 16, and 22 weeks. There were no significant differences in total plasma cholesterol, body weight, average lesion or medial area, or changes in lesion composition with either treatment in comparison to control mice.

Lignan and isoflavone excretion in relation to uterine fibroids: a case-control study of young to middle-aged women in the United States.

BACKGROUND: Uterine fibroids are hormonally responsive; estradiol and progesterone stimulate their growth, and gonadotrophin-releasing hormone agonists shrink them. Phytoestrogens, including isoflavones and lignans, can act as weak estrogens or antiestrogens. OBJECTIVE: The objective of this case-control study was to evaluate the relation between uterine fibroid risk and phytoestrogen exposure. DESIGN: Two overnight urine collections (48 h apart) from 170 uterine fibroid cases and 173 controls were analyzed for isoflavonoids (ie, daidzein, genistein, equol, and O-desmethylangolensin) and lignans (enterodiol and enterolactone). Logistic regression was used to determine associations between the mean excretion of the 2 collections and the risk of uterine fibroids. RESULTS: Unadjusted isoflavone excretion did not differ significantly between cases and controls (2.33 +/- 5.82 and 2.60 +/- 5.90 nmol/mg Cr, respectively; P = 0.68), but cases excreted significantly less lignans than did controls (2.86 +/- 3.45 and 4.57 +/- 6.67 nmol/mg Cr, respectively; P < 0.01). The trend for a reduced risk of uterine fibroids with increasing quartiles of lignan excretion was significant (odds ratio for highest versus lowest quartile = 0.31; 95% CI: 0.17, 0.58; P for trend < 0.01). When adjusted for age, BMI, race, family history of uterine fibroids, and isoflavone excretion, this trend remained but was attenuated (P = 0.07). CONCLUSIONS: Our findings suggest a modest inverse association between lignan excretion and uterine fibroid risk. Whether this relation represents an effect of lignans per se or of other constituents of lignan-containing foods on the development of uterine fibroids remains to be determined. No association was found between isoflavone excretion and uterine fibroids; however, the intake of soy foods, the primary source of isoflavones, was low in this population.

Postmenopausal bone mineral density in relation to soy isoflavone-metabolizing phenotypes.

OBJECTIVES: Intestinal bacterial metabolize the soy isoflavone daidzein to O-desmethylangolensin (O-DMA) or equol. Some individuals do not excrete O-DMA or equol after soy consumption, suggesting they do not harbor bacteria capable of producing these metabolites. The aim of this study was to evaluate bone mineral density (BMD) in relation to presence of these urinary metabolites. METHODS: BMD, determined by whole-body dual X-ray absorptiometry scan, was age-adjusted and evaluated in relation to O-DMA-producer and equol-producer phenotypes in 92 postmenopausal women, aged 50-75 years. Women consumed supplemental soy foods (daidzein source) for 3 days and collected a first-void urine sample on the fourth day in order to determine metabolic phenotypes. RESULTS: In O-DMA producers (n=76) compared to O-DMA non-producers (n=16), greater total, leg and head BMD (p<0.05) were observed. Total BMD among the O-DMA producers (geometric mean=1.04 g/cm2) was 6% greater than total BMD among the O-DMA non-producers (geometric mean=0.98 g/cm2). Total and site-specific BMD did not differ between equol producers (n=24) and non-producers (n=68) (p>0.05). In exploratory analyses, among regular soy consumers, spinal BMD was 20% lower among the equol producers than non-producers, whereas, among soy non-consumers, no such difference was observed (p-interaction<0.05). Among equol producers, circulating estrone and free estradiol concentrations were inversely or not associated with total BMD, whereas, among equol non-producers, these hormones were positively associated (p-interaction<0.05). CONCLUSIONS: Our results provide evidence that intestinal bacterial composition may influence BMD in postmenopausal women. Further studies characterizing associations of intestinal bacterial profiles with BMD are warranted.

High concordance of daidzein-metabolizing phenotypes in individuals measured 1 to 3 years apart.

Particular intestinal bacteria are capable of metabolizing the soya isoflavone daidzein to equol and/or O-desmethylangolensin (O-DMA), and the presence of these metabolites in urine after soya consumption are markers of particular intestinal bacteria profiles. Prevalences of equol producers and O-DMA producers are approximately 30-50 % and 80-90 %, respectively, and limited observations have suggested that these daidzein-metabolizing phenotypes are stable within individuals over time. Characterizing stability of these phenotypes is important to understand their potential as markers of long-term exposure to particular intestinal bacteria and their associations with disease risk. We evaluated concordance within an individual for the equol-producer and O-DMA-producer phenotypes measured at two time points (T1, T2), 1-3 years apart. Phenotypes were ascertained by analysing equol and O-DMA using GC-MS in a spot urine sample collected after 3 d soya (source of daidzein) supplementation. In ninety-two individuals without recent (within 3 months before phenotyping) or current antibiotics use, 41 % were equol producers at T1 and 45 % were equol producers at T2, and 90 % were O-DMA producers at T1 and 95 % were O-DMA producers at T2. The percentage agreement for the equol-producer phenotype was 82 and for the O-DMA-producer phenotype was 89. These results indicate that these phenotypes are stable in most individuals over time, suggesting that they provide a useful biomarker for evaluating disease risk associated with harbouring particular intestinal bacteria responsible for, or associated with, the metabolism of the soya isoflavone daidzein.

Sex differences in motives for use of complementary and alternative medicine among cancer patients.

CONTEXT: There is evidence that the prevalence of complementary and alternative medicine (CAM) use is increasing especially among women. However, little is known about why there are sex differences in the use of CAM. OBJECTIVE: This study investigated sex differences in motivations for use of CAM among adult cancer patients. DESIGN: A population-based telephone survey of CAM use. SETTINGS AND PARTICIPANTS: 178 male and 178 female cancer patients randomly selected from a statewide Cancer Surveillance System in Washington State. MAIN OUTCOME MEASURES: Demographics, complementary and alternative medicine use, lifestyle changes and four psychosocial variables: desire for personal control; internal locus of control; symptom distress; and perceived health status. RESULTS: Overall, 81.5% of women and 59.0% of men used some type of CAM. After adjusting for age and income, the relative odds that an alternative therapy user was female was 2.2 (95% CI 1.4-3.3)for alternative dietary supplements, 5.0 (95% CI 2.3-11.2) for categories of alternative providers, 2.2 (95% CI 1.2-4.2) for focused mental therapies and 1.4 (95% CI 0.9-2.2) for lifestyle changes. CAM use was positively associated with desire for personal control among both men and women (P = 0.05). However, the association of two factors, dissatisfaction with a conventional provider and cancer-related symptom distress with alternative dietary supplement use, was only modestly different for men and women (P < 0.10 for interaction). High cancer related symptom distress score and dissatisfaction with a conventional provider predicted increased dietary supplement use for men, but decreased dietary supplement use for women. CONCLUSIONS: Clinicians should be aware that men and women differ considerably in their use of CAM, which may reflect differences in their psychological needs as they cope with their cancer diagnosis and treatment.

Mammographic density in relation to daidzein-metabolizing phenotypes in overweight, postmenopausal women.

Circulating hormones are associated with mammographic density, an intermediate marker of breast cancer risk. Differences in circulating hormones, including estrone and testosterone, have been observed in premenopausal women based on their capacity to metabolize daidzein, an isoflavone found predominantly in soybeans. Equol and O-desmethylangolensin (O-DMA) are products of intestinal bacterial metabolism of daidzein. There is interindividual variability in the capacity to produce daidzein metabolites; individuals can be equol producers or non-producers and O-DMA producers or non-producers. We tested the hypothesis that daidzein-metabolizing phenotypes are associated with mammographic density. Participants were recruited from among 92 sedentary, postmenopausal women, ages 50 to 75 years, who participated in a 1-year physical activity intervention. Pre-intervention mammographic density was determined using a computer-assisted, gray-scale thresholding technique. Fifty-five of these women consumed supplemental soy protein (>10 mg daidzein/d) for 3 days and collected a first-void urine sample on the fourth day to determine daidzein-metabolizing phenotypes. Equol and O-DMA concentrations were measured using gas chromatography-mass spectrometry. Associations between daidzein-metabolizing phenotypes and percent mammographic density were adjusted for age, maximum adult weight, gravidity, family history of breast cancer, and serum follicle-stimulating hormone and free testosterone concentrations. Mammographic density was 39% lower in equol producers compared with non-producers (P = 0.04). O-DMA producers had mammographic density 69% greater than non-producers (P = 0.05). These results suggest that particular intestinal bacterial profiles are associated with postmenopausal mammographic density, and these associations are not entirely explained by differences in reproductive or anthropometric characteristics or circulating hormones.

Changes in diet, physical activity, and supplement use among adults diagnosed with cancer.

OBJECTIVE: To investigate the prevalence and predictors of changes in diet, physical activity, and dietary supplement use among cancer patients. Design/subjects Telephone interviews of a population-based sample of 126 breast, 114 prostate, and 116 colorectal cancer patients from the state of Washington. ANALYSIS: Logistic regression was used to estimate the odds ratio as a measure of the association of participant characteristics with lifestyle changes in the 12 months before the interview. RESULTS: Overall, 66.3% of patients reported making lifestyle changes: 40.4% made one or more dietary changes, 20.8% added new physical activity, and 48.0% started taking new dietary supplements. Compared with men, women were 2.2 times more likely to take new dietary supplements (P <.01). Compared with patients aged 35 to 59, those aged 60 to 69 and 70 or older were statistically significantly less likely to make dietary changes (odds ratio = 0.39 and 0.54, respectively) or to take new supplements (odds ratio = 0.42 and 0.69, respectively). Compared with patients who received only one medical treatment, those receiving three or more treatments were more likely to make dietary changes (odds ratio = 2.6) or to start new physical activity (odds ratio = 3.0). Patients diagnosed 12 to 24 months before the interview were as likely to report making lifestyle changes as those diagnosed within one year of the interview. Having a stronger desire for personal control or internal locus of control predicted use of new dietary supplements (P for trend <.05 for both). Applications/conclusions Cancer survivors are likely to be making lifestyle changes and represent a group that could benefit from counseling on diet and physical activity.

Types of alternative medicine used by patients with breast, colon, or prostate cancer: predictors, motives, and costs.

OBJECTIVE: Assess predictors and costs of various types of alternative medicine used by adult patients with cancer. DESIGN, LOCATION, SUBJECTS: Telephone survey of 356 patients with colon, breast, or prostate cancer identified from the population-based Cancer Surveillance System of western Washington. RESULTS: Overall, 70.2% of patients used at least one type of alternative medicine, with 16.6% seeing alternative providers, 19.1% using mental/other therapy, and 64.6% taking dietary supplements. Compared to males, females were five times more likely to see an alternative provider and about twice as likely to use mental therapies or supplements (p < 0.05 for all). Older patients were less likely to use mental/other therapy. Higher education (but not income) was associated with use of all types of alternative medicine. Patients with multiple medical treatments were two times more likely to take dietary supplements compared to patients having only surgery (p < 0.01). Varying by the type of alternative therapy, 83%-97% of patients reported that they used alternative medicine for general health and well-being while 8% to 56% reported use for treatment of cancer. Almost all patients reported that the alternative therapy improved their well-being. Expenditures for alternative medicine averaged $68 per user per year, but ranged from $4 to $14,659. CONCLUSIONS: Given the high prevalence of use and that patients believed that alternative medicine improved their well-being, clinicians should show an open mind toward these treatment choices and encourage frank discussion. Familiarity and some knowledge regarding use of alternative medicine is important in cases where interactions between conventional and alternative medicine may occur. It is also important to identify potential patient needs for mental health support beyond conventional care and support patients who want to make healthful lifestyle changes. Longitudinal investigations are urgently needed to investigate associations of alternative medicine use with survival and quality of life in patients with cancer.