Radiomics-Based Machine Learning for Outcome Prediction in a Multicenter Phase II Study of Programmed Death-Ligand 1 Inhibition Immunotherapy for Glioblastoma.

BACKGROUND AND PURPOSE: Imaging assessment of an immunotherapy response in glioblastoma is challenging due to overlap in the appearance of treatment-related changes with tumor progression. Our purpose was to determine whether MR imaging radiomics-based machine learning can predict progression-free survival and overall survival in patients with glioblastoma on programmed death-ligand 1 inhibition immunotherapy. MATERIALS AND METHODS: Post hoc analysis was performed of a multicenter trial on the efficacy of durvalumab in glioblastoma (n = 113). Radiomics tumor features on pretreatment and first on-treatment time point MR imaging were extracted. The random survival forest algorithm was applied to clinical and radiomics features from pretreatment and first on-treatment MR imaging from a subset of trial sites (n = 60-74) to train a model to predict long overall survival and progression-free survival and was tested externally on data from the remaining sites (n = 29-43). Model performance was assessed using the concordance index and dynamic area under the curve from different time points. RESULTS: The mean age was 55.2 (SD, 11.5) years, and 69% of patients were male. Pretreatment MR imaging features had a poor predictive value for overall survival and progression-free survival (concordance index = 0.472-0.524). First on-treatment MR imaging features had high predictive value for overall survival (concordance index = 0.692-0.750) and progression-free survival (concordance index = 0.680-0.715). CONCLUSIONS: A radiomics-based machine learning model from first on-treatment MR imaging predicts survival in patients with glioblastoma on programmed death-ligand 1 inhibition immunotherapy.

Monitoring HPV type-specific prevalence over time through clinic-based surveillance: a perspective on vaccine effectiveness.

We investigated the feasibility of monitoring trends in prevalence of vaccine-preventable human papillomavirus (HPV) types in different clinic populations. We collected cervical specimens from women presenting to family planning, primary care, and sexually transmitted disease (STD) clinics for routine pap smears in five US cities during 2003-2005. We performed HPV genotyping and calculated annual type-specific prevalences; pre-vaccine era prevalence was highest for HPV 16 (6.0; 95% confidence interval [CI] 5.5-6.6%) and annual prevalences for vaccine-preventable types were stable, with few exceptions, after controlling for clinic type, age group, and city. With sufficient sample size and stable population characteristics, clinic-based surveillance systems can contribute to monitoring HPV vaccine impact in the cervical screening population.

Patterns and predictors of the breast cancer detection methods in women under 45 years of age (United States).

OBJECTIVES: Few studies have examined methods by which breast cancers are detected, and only one study has been published on predictors of those methods. This study examined patterns and predictors of breast cancer detection methods during 1990-1992 among women age 20-44. METHODS: In-person interview and medical record data were obtained during a population-based case-control study of 1619 women newly diagnosed with breast cancer in three areas of the United States (US). RESULTS: Seventy-one percent of the cancers were identified by self-detection, 9% by routine clinical breast exam (CBE), and 20% by routine mammography. Cancers detected by mammography and CBE, but not those detected by breast self-exam, were much more likely to be early-stage. Detection by mammography increased with age, and a history of mammography use was associated with detection by mammography or CBE. Several commonly studied predictors of screening utilization in the US population were associated with CBE detection, but were less clearly related to or unrelated to mammography detection. CONCLUSION: Findings suggest that, during the 1990s in the US, most breast cancers among women under age 45, including those age 40-44, were self-detected. Few factors other than age and prior screening are verified predictors of method of breast cancer detection.

Comparison of telephone sampling and area sampling: response rates and within-household coverage.

Random digit dialing is used frequently in epidemiologic case-control studies to select population-based controls, even when both cases and controls are interviewed face-to-face. However, concerns persist about the potential biases of random digit dialing, particularly given its generally lower response rates. In an Atlanta, Georgia, case-control study of breast cancer among women aged 20-54 years, all of whom were interviewed face-to-face, two statistically independent control groups were compared: those obtained through random digit dialing (n = 652) and those obtained through area probability sampling (n = 640). The household screening rate was significantly higher for the area sample, by 5.5%. Interview response rates were comparable. The telephone sample estimated a significantly larger percentage (by approximately 7%) of households to have no age-eligible women. Both control groups, appropriately weighted, had characteristics similar to US Census demographic characteristics for Atlanta women, except that respondents in both control groups were more educated and more likely to be married. The authors conclude that households contacted through random digit dialing are somewhat less likely to participate in the household screening process, and if they are cooperative, some households may not disclose that age-eligible women reside therein. Investigators need to develop improved methods for screening and enumerating household members in random digit dialing surveys that target a specific subpopulation, such as women.

Validation of the American Cancer Society Cancer Prevention Study II Nutrition Survey Cohort Food Frequency Questionnaire.

We assessed the validity and reproducibility of a self-administered 68-item food frequency questionnaire completed in 1992-1993 by approximately 185,000 adults. Four hundred forty-one participants completed four 24-hour dietary recall interviews over a 1-year period and a repeat administration of the food frequency questionnaire. For 20 nutrients and 10 food groups, measured nutrient intakes, but not food group intakes, were consistently lower by food frequency questionnaire than by recall. Energy-adjusted, attenuation-corrected Pearson validity correlations ranged from 0.12 to 0.80, with a median of 0.58. Reproducibility measures were generally high, with a median of 0.69. The food frequency questionnaire performed similarly to food frequency questionnaires used in other cohort studies, indicating similar ability to examine diet-disease relations.

Glutathione in human plasma: decline in association with aging, age-related macular degeneration, and diabetes.

Blood samples were analyzed for GSH and GSH redox state in 40 age-related macular degeneration (ARMD) patients (> 60 y), 33 non-ARMD diabetic patients (> 60 years), 27 similarly aged non-ARMD and nondiabetic individuals (> 60 years), and 19 younger individuals (< 60 years) without ARMD or diabetes. Results showed a significantly lower plasma GSH in older individuals (ARMD, diabetes, and controls) than in younger individuals (p < .01). Total GSH (GSHt) obtained following treatment with dithiothreitol was significantly lower only in diabetic cases (p < .05) but also approached significance for ARMD cases (p = .089). Estimation of redox potential indicated that the plasma GSH pool is considerably more oxidized in all of the older groups. Analyses of whole blood GSH showed that GSH was significantly lower in diabetic cases compared to the other groups, but did not reveal any difference associated with age or ARMD. In contrast, GSSG in whole blood was significantly higher in the older groups compared to the younger controls. The results suggest that in studies of age-related pathologies, oxidation of GSH may be a more important parameter than a decline in pool size, while in specific pathologies such as diabetes, both oxidation and a decline in pool size may be important.

Energy intake and net weight gain in pregnant women according to body mass index (BMI) status.

OBJECTIVE: To investigate whether body mass index (BMI) is related to energy intake during pregnancy, and whether BMI, energy intake and other factors are related to net weight gain. DESIGN: Longitudinal, duration of pregnancy. SUBJECTS: 156 healthy pregnant women residing in Quedlinburg county, Germany. METHODS: Weighed 7 d food records and standardized anthropometric measures in the first, second and third trimester. The analysis of variance (ANOVA) statistical technique was used to analyze differences in energy intake, net weight gain and birthweight across BMI groups, and the Cochran-Mantel Haenszel test was used to analyze food group intake by BMI group. RESULTS: Women at the highest level of BMI were significantly less often in the high energy intake category than women at the medium or low level of BMI (15% vs 36% and 48%). Net weight gain during pregnancy was independently influenced by BMI status and energy intake. Women at the highest level of BMI gained significantly less weight (4.2 kg) from first to third trimester than women at the medium or low levels of BMI (weight gains of 6.2 kg and 5.9 kg, respectively). Women with a low daily energy intake gained 4.6 kg during pregnancy, while women with medium and high energy intakes gained 6.0 kg and 6.1 kg, respectively. Examination of net weight gain simultaneously across BMI and parity groups revealed a much lower net weight gain among multigravid women at the highest BMI level (3.3 kg). Primigravid high BMI women, in contrast, gained 6.9 kg, whereas multigravid and primigravid women at medium and low BMI levels gained average of 4.8 kg and 6.5 kg, respectively. The mean birth weight in the three BMI groups did not differ and was not influenced by age, marital status, education, parity or smoking. CONCLUSION: Because other studies have shown that weight gain during pregnancy increases the risk of subsequent overweight, multigravid high BMI women may prevent an increased weight retention after pregnancy due to lower weight gain in the current gestation. A lower caloric diet may help to accomplish a lower weight gain during pregnancy in overweight women without increased risk of low birth weight infants. These findings indicate further investigation of the associations between BMI, parity and caloric intake during pregnancy are needed to increase understanding of factors affecting subsequent weight gain.

Epidemiologic studies of antioxidants and cancer in humans.

To assess whether antioxidants may reduce the risk of cancer, we reviewed the epidemiologic literature from 1985 through 1993. We assessed the separate relationships of three antioxidants (carotenoids, vitamin C, and vitamin E) with six sites of cancer (lung, upper aerodigestive tract, uterine cervix, colon, breast, prostate). This review was limited to dietary intake or serum nutrient studies that met a predefined set of methodologic standards. We judged the evidence in support of causal relationships based upon consistency of results across studies, strength of association, and evidence of a dose-response relationship. The data concerning carotenoids and lung cancer risk were most consistent (protection found in 4 of 8 diet studies and 5 of 6 serum studies), with strong associations that tended to follow a dose-response pattern. For lung cancer, there was weaker evidence of protection from vitamin C (2 of 6 diet studies) and vitamin E (3 of 4 serum studies). For upper aerodigestive tract cancers (oral cavity, pharynx, or larynx), there was evidence of a protective effect of carotenoids (3 of 4 diet studies) and vitamin C (4 of 5 diet studies). For cancer of the uterine cervix, we found suggestive evidence of protection from vitamin C (4 of 5 diet studies) and perhaps carotenoids (2 of 5 diet studies). For cancers of the colon, breast, and prostate, the current data do not support a protective effect of antioxidants. More definite conclusions about the benefits of antioxidants in cancer prevention will be derived from on-going intervention trials.

Dietary glutathione intake and the risk of oral and pharyngeal cancer.

Glutathione, a tripeptide found in a variety of foods, may function as an anticarcinogen by acting as an antioxidant and by binding with cellular mutagens. The association between dietary glutathione intake and risk of oral and pharyngeal cancer was investigated using data from 1,830 white participants (855 cases and 975 controls) in a population-based case-control study conducted in New Jersey; metropolitan Atlanta, Georgia; Los Angeles County, California; and Santa Clara and San Mateo counties, south of San Francisco-Oakland, California, during 1984-1985. The estimated relative risk of cancer among people with the highest quartile of glutathione intake from all sources was 0.5 (95% confidence interval 0.3-0.7). When analyzed by dietary source, however, glutathione intakes derived from all vegetables and from meat were not related to risk of cancer. Only glutathione derived from fruit and from vegetables commonly consumed raw was associated with reduced oral cancer risk. Relative to the lowest level of combined intake of fruit and of fruit-derived glutathione, risk of cancer decreased slightly with increasing intake of fruit glutathione. This analysis was limited, however, by the small numbers of subjects with extreme combinations of intakes. Further studies are needed to distinguish the potential effect of glutathione from that of fruit and raw vegetables per se or from the influence of other constituents in these foods.

Dietary glutathione intake in humans and the relationship between intake and plasma total glutathione level.

Glutathione may function as an anticarcinogen by acting as an antioxidant or by binding with cellular mutagens. Orally administered glutathione increases plasma glutathione levels, and plasma glutathione is also synthesized in the liver. To investigate the associations between glutathione intake and plasma glutathione level, we compared dietary intake estimates from food frequency questionnaire data and measured concentrations of plasma total glutathione and other serum antioxidants in 69 white men and women. Daily glutathione intake ranged from 13.0 to 109.9 mg (mean 34.8 mg). Fruits and vegetables were found to contribute over 50% of usual dietary glutathione intake, whereas meats contributed less than 25%. Small negative correlations were observed between dietary and plasma glutathione and, although they were usually not statistically significant, they were generally consistent by different time periods of dietary intake assessment. Adjustment for sex, age, caloric intake, and dietary intake of the sulfur-containing amino acids methionine and cystine did not alter the observed associations. The correlations appeared to be modified, however, by serum vitamin C concentration, with little or no association between dietary and plasma glutathione among those with lower levels of serum vitamin C and stronger negative correlations among those with higher serum vitamin C levels. These findings indicate that factors regulating plasma glutathione concentration are complex and not simply related to dietary glutathione intake or supply of precursor amino acids.

Plasma total glutathione in humans and its association with demographic and health-related factors.

The tripeptide glutathione is proposed to be protective against a number of chronic diseases including cardiovascular disease and cancer. However, there have been few studies of plasma glutathione levels in humans and in those studies the numbers of participants have been very small. In an exploratory analysis the determinants of plasma total glutathione (GSHt) were investigated in a group of 100 volunteers aged 18-61 years in Atlanta, Georgia, USA during June and July 1989. Data on demographic and health-related factors were collected by interview and plasma GSHt was measured using a recently modified laboratory method. The mean concentration of plasma GSHt for all 100 participants was 761 micrograms/l, with a standard deviation of 451 micrograms/l, a range of 86-2889 micrograms/l and a median of 649 micrograms/l. Men had significantly higher levels of plasma GSHt than women (924 v. 692 micrograms/l; P = 0.006). Seventh-day Adventists participating in the present study had higher plasma GSHt levels than other subgroups defined by race and/or religion. Among Seventh-day Adventists consumption of a vegetarian diet was associated with increased plasma GSHt concentration (P = 0.002). Plasma GSHt levels also appeared to vary by race, but relationships with race could not be clearly disassociated from relationships with religion. Among white participants plasma GSHt concentration decreased with age in women but increased with age in men (P = 0.05). Few other factors were associated with plasma GSHt concentration, although use of oral contraceptives (P = 0.10) was somewhat associated with decreased plasma GSHt levels. These findings suggest that plasma GSHt levels may vary with several demographic and health-related attributes and support the need for further research on this potentially important disease-preventive compound.

Epidemic poliomyelitis in The Gambia following the control of poliomyelitis as an endemic disease. I. Descriptive findings.

An epidemic of type 1 poliomyelitis involving 305 cases occurred in The Gambia (estimated 1986 population, 768,995) from May through November 1986, following a 6-year period when only five cases were reported. Cases were identified by physician reporting during the epidemic and by a national village-to-village search conducted after the epidemic. The national attack rate was 40 cases per 100,000 people. Cases lived in all parts of the country except the capital, Banjul. The peak month of the epidemic was August (139 cases). The highest attack rate by year of age was in 1-year-old children (394 cases per 100,000 persons), and 75% of cases were 3 years of age or less. A vaccination coverage survey showed that 64% (95% confidence interval 60-68) of 1- to 2-year-old children were vaccinated with at least three doses of trivalent oral polio vaccine at the beginning of the epidemic. Fifty-seven cases became paralyzed more than 2 weeks after a national mass campaign in which 95% of children 1-7 years old were reported to have received a dose of trivalent oral polio vaccine. Experience in The Gambia shows that a several-year period of excellent control of endemic poliomyelitis by a vaccination program can be followed by a major epidemic and that a mass vaccination campaign may be only partially successful in ending the epidemic.

Glutathione in foods listed in the National Cancer Institute's Health Habits and History Food Frequency Questionnaire.

Glutathione (GSH) is an antioxidant and anticarcinogen that is present in plant and animal tissues that form the bulk of the human diet. Recent studies show that GSH is absorbed intact in rat small intestine and that oral GSH increases plasma GSH concentration in humans. To provide a database for epidemiological studies of dietary intake of GSH and risk of diseases in humans, we have measured the content of GSH in the foods listed in the National Cancer Institute's Health Habits and History Questionnaire. Foods were purchased in the Atlanta area and prepared as most commonly consumed in the United States. GSH analyses were performed using a high-performance liquid chromatography technique with a method of additions to correct for losses during sample preparation. A separate set of samples was run after treatment with dithiothreitol to measure the total of GSH and its disulfide forms (GSH). The results show that dairy products, cereals, and breads are generally low in GSH; fruits and vegetables have moderate to high amounts of GSH; and freshly prepared meats are relatively high in GSH. Frozen foods generally had GSH contents similar to fresh foods, whereas other forms of processing and preservation generally resulted in extensive loss of GSH. Thus this database will allow researchers to examine the relationship between dietary GSH and risk of cancers and other diseases.