Associations between nutritional factors and chemotherapy toxicity in older adults with solid tumors.

BACKGROUND: Nutritional status can directly affect morbidity and mortality in older adults with cancer. This study evaluated the association between pretreatment body mass index (BMI), albumin level, and unintentional weight loss (UWL) in the prior 6 months and chemotherapy toxicity among older adults with solid tumors. METHODS: This was a secondary analysis of a prospective, multicenter study involving chemotherapy-treated patients 65 years old or older. Geriatric assessment, BMI, albumin level, and UWL data were collected before treatment. Multivariable logistic regression models evaluated the associations between nutritional factors and the risk of grade 3 or higher (grade 3+) chemotherapy toxicity. RESULTS: Seven hundred fifty patients with a median age of 72 years (range, 65-94 years) and mostly stage IV disease were enrolled. The median pretreatment BMI and albumin values were 26 kg/m2 (range, 15.1-52.1 kg/m2 ) and 3.9 mg/dL (range, 1.0-5.0 mg/dL), respectively. Nearly 50% of the patients reported UWL, with 17.6% reporting >10% UWL. Multivariable analysis revealed no association between >10% UWL and a risk for grade 3+ chemotherapy toxicity (adjusted odds ratio [AOR], 0.87; P = .58). Multivariable analysis showed a trend toward an association between a BMI ≥ 30 kg/m2 and a decreased risk of grade 3+ chemotherapy toxicity (AOR, 0.65; P = .06), whereas a low albumin level (≤3.6 mg/dL) was associated with a higher risk of grade 3+ chemotherapy toxicity (AOR, 1.50; P = .03). An analysis of the joint effect of BMI and albumin demonstrated the lowest risk of grade 3+ chemotherapy toxicity among patients with high BMIs (≥30 kg/m2 ) and normal albumin levels (AOR, 0.41; P = .008). CONCLUSIONS: Among older adults with solid tumors, higher BMIs and normal albumin levels are associated with a lower risk of grade 3+ chemotherapy toxicity. Additional research is warranted to define the clinical significance of nutritional markers and to inform future interventions.

Lung Cancer in Nonelderly Patients: Facility and Patient Characteristics Associated With Not Receiving Treatment.

BACKGROUND: In elderly patients with lung cancer, race/ethnicity is associated with not receiving treatment; however, little attention has been given to nonelderly patients (aged ≤65 years) with a range of disease stages and histologies. Nonelderly patients with lung cancer have superior survival at NCI-designated Comprehensive Cancer Centers (CCCs), although the reasons remain unknown. PATIENTS AND METHODS: A retrospective cohort study was conducted in 9,877 patients newly diagnosed with small cell or non-small cell lung cancer (all stages) between ages 22 and 65 years and reported to the Los Angeles County Cancer Surveillance Program registry between 1998 and 2008. Multivariable logistic regression examined factors associated with nontreatment. RESULTS: In multivariable analysis, race/ethnicity was associated with not receiving cancer treatment (black: odds ratio [OR], 1.22; P=.004; Hispanic: OR, 1.17; P=.04), adjusting for patient age, sex, disease stage, histology, diagnosis year, distance to treatment facility, type of facility (CCC vs non-CCC), and insurance status. With inclusion of socioeconomic status (SES) in the model, the effect of race/ethnicity was no longer significant (black: OR, 1.02; P=.80; Hispanic: OR, 1.00; P=1.00). Factors independently associated with nontreatment included low SES (OR range, 1.37-2.15; P<.001), lack of private insurance (public: OR, 1.71; P<.001; uninsured: OR, 1.30; P<.001), and treatment facility (non-CCC: OR, 3.22; P<.001). CONCLUSIONS: In nonelderly patients with lung cancer, SES was associated with nontreatment, mitigating the effect of race/ethnicity. Patients were also at higher odds of nontreatment if they did not have private insurance or received cancer care at a non-CCC facility. These findings highlight the importance of understanding how both patient-level factors (eg, SES, insurance status) and facility-level factors (eg, treatment facility) serve as barriers to treatment of nonelderly patients with lung cancer.

Subcortical brain iron deposition and cognitive performance in older women with breast cancer receiving adjuvant chemotherapy: A pilot MRI study.

As the number of older adults in the U.S. increases, so too will the incidence of cancer and cancer-related cognitive impairment (CRCI). However, the exact underlying biological mechanism for CRCI is not yet well understood. We utilized susceptibility-weighted imaging with quantitative susceptibility mapping, a non-invasive MRI-based technique, to assess longitudinal iron deposition in subcortical gray matter structures and evaluate its association with cognitive performance in women age 60+ with breast cancer receiving adjuvant chemotherapy and age-matched women without breast cancer as controls. Brain MRI scans and neurocognitive scores from the NIH Toolbox for Cognition were obtained before chemotherapy (time point 1) and within one month after the last infusion of chemotherapy for the patients and at matched intervals for the controls (time point 2). There were 14 patients age 60+ with breast cancer (mean age 66.3 ±â€¯5.3 years) and 13 controls (mean age 68.2 ±â€¯6.1 years) included in this study. Brain iron increased as age increased. There were no significant between- or within- group differences in neurocognitive scores or iron deposition at time point 1 or between time points 1 and 2 (p > 0.01). However, there was a negative correlation between iron in the globus pallidus and the fluid cognition composite scores in the control group at time point 1 (r = -0.71; p < 0.01), but not in the chemotherapy group. Baseline iron in the putamen was negatively associated with changes in the oral reading recognition scores in the control group (r = 0.74, p < 0.01), but not in the chemotherapy group. Brain iron assessment did not indicate cancer or chemotherapy related short-term differences, yet some associations with cognition were observed. Studies with larger samples and longer follow-up intervals are warranted.

Adolescents and Young Adults with Acute Lymphoblastic Leukemia and Acute Myeloid Leukemia: Impact of Care at Specialized Cancer Centers on Survival Outcome.

Background: Adolescents and young adults (AYA; 15-39 years) with acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) experience inferior survival when compared with children. Impact of care at NCI-designated Comprehensive Cancer Centers (CCC) or Children's Oncology Group sites (COG) on survival disparities remains unstudied.Methods: Using the Los Angeles cancer registry, we identified 1,870 ALL or AML patients between 1 and 39 years at diagnosis. Cox regression analyses assessed risk of mortality; younger age + CCC/COG served as the referent group. Logistic regression was used to determine odds of care at CCC/COG, adjusting for variables above.Results: ALL outcome: AYAs at non-CCC/COG experienced inferior survival (15-21 years: HR = 1.9, P = 0.005; 22-29 years: HR = 2.6, P < 0.001; 30-39 years: HR = 3.0, P < 0.001). Outcome at CCC/COG was comparable between children and young AYAs (15-21 years: HR = 1.3, P = 0.3; 22-29 years: HR = 1.2, P = 0.2) but was inferior for 30- to 39-year-olds (HR = 3.4, P < 0.001). AML outcome: AYAs at non-CCC/COG experienced inferior outcome (15-21 years: HR = 1.8, P = 0.02; 22-39 years: HR = 1.4, P = 0.06). Outcome at CCC/COG was comparable between children and 15- to 21-year-olds (HR = 1.3, P = 0.4) but was inferior for 22- to 39-year-olds (HR = 1.7, P = 0.05). Access: 15- to 21-year-olds were less likely to use CCC/COG than children (P < 0.001). In 22- to 39-year-olds, public/uninsured (ALL: P = 0.004; AML<0.001), African American/Hispanics (ALL: P = 0.03), and 30- to 39-year-olds (ALL: P = 0.03) were less likely to use CCC/COG.Conclusions: Poor survival in AYAs with ALL and AML is mitigated by care at CCC/COG. Barriers to CCC/COG care include public/uninsured, and African American/Hispanic race/ethnicity.Impact: Care at CCC/COG explains, in part, inferior outcomes in AYAs with ALL and AML. Key sociodemographic factors serve as barriers to care at specialized centers. Cancer Epidemiol Biomarkers Prev; 26(3); 312-20. ©2017 AACR.

Impact of care at comprehensive cancer centers on outcome: Results from a population-based study.

BACKGROUND: Rigorous processes ensure quality of research and clinical care at National Cancer Institute-designated comprehensive cancer centers (NCICCCs). Unmeasurable elements of structure and process of cancer care delivery warrant evaluation. To the authors' knowledge, the impact of NCICCC care on survival and access to NCICCCs for vulnerable subpopulations remain unstudied. METHODS: The current study's population-based cohort of 69,579 patients had newly diagnosed adult-onset (aged 22-65 years) cancers reported to the Los Angeles County cancer registry between 1998 and 2008. Geographic information systems were used for geospatial analysis. RESULTS: With regard to overall survival across multiple diagnoses, patients not receiving their first planned treatment at NCICCCs experienced poorer outcomes compared with those treated at NCICCCs; differences persisted on multivariable analyses after adjusting for clinical and sociodemographic factors (hepatobiliary: hazard ratio [HR], 1.5; 95% confidence interval [95% CI], 1.4-1.7 [P<.001]; lung: HR, 1.4; 95% CI, 1.3-1.6 [P<.001]; pancreatic: HR, 1.5; 95% CI, 1.3-1.7 [P<.001]; gastric: HR, 1.3; 95% CI, 1.1-1.7 [P = .01]; breast: HR, 1.3; 95% CI, 1.1-1.5 [P<.001]; and colorectal: HR, 1.2; 95% CI, 1.0-1.4 [P = .05]). With regard to barriers to care, multivariable analyses revealed that a lower likelihood of treatment at NCICCCs was associated with race/ethnicity (African-American: OR range across diagnoses: 0.4-0.7 [P<.03]; Hispanic: OR range, 0.5-0.7 [P<.04]); lack of private insurance (public: OR range, 0.6-0.8 [P<.004]; uninsured: OR range, 0.1-0.5 [P<.04]); less than high socioeconomic status (high-middle: OR range, 0.4-0.7 [P<.02]; middle: OR range, 0.3-0.5 [P<.001]; and low: OR range, 0.2-0.6 [P<.01]), and residing >9 miles from the nearest NCICCC (OR range, 0.5-0.7 [P<.02]). CONCLUSIONS: Among individuals aged 22 to 65 years residing in Los Angeles County with newly diagnosed adult-onset cancer, those who were treated at NCICCCs experienced superior survival compared with those treated at non-NCICCC facilities. Barriers to care at NCICCCs included race/ethnicity, insurance, socioeconomic status, and distance to an NCICCC.

Impact of treatment site in adolescents and young adults with central nervous system tumors.

BACKGROUND: Adolescents and young adults (AYAs; aged 15-39 years) have inferior survival in comparison with younger (aged 0-14 years) cancer patients. Impact of care at specialized centers such as National Cancer Institute-designated Comprehensive Cancer Centers (NCICCC) for AYAs of all ages or the Children's Oncology Group (COG) for AYAs aged 15 to 21 years with central nervous system (CNS) tumors remains unstudied. METHODS: We constructed a cohort of 560 children and 784 AYAs with CNS tumors reported to the Los Angeles cancer registry from 1998 to 2008. Cox and logistic regression models were used, with two-sided P values from Wald χ(2) tests. RESULTS: In Cox regression analysis restricted to World Health Organization (WHO) grade II tumors, patients of all ages saw worse outcome if not treated at NCICCC/COG sites (non-NCICCC/COG vs NCICCC/COG: hazard ratio [HR] =1.73; 95% confidence interval [CI] = 1.09 to 2.72). Furthermore, the worse outcome for AYAs compared with children (HR = 1.90; 95% CI = 1.21 to 2.98; P = .005) was abrogated (HR = 1.35; 95% CI = 0.79 to 2.29; P = .27) by care at NCICCC/COGs. Those less likely to receive care at NCICCC/COG sites included young AYAs (aged 15-21 years vs children: odds ratio [OR] = 0.23; 95% CI = 0.11 to 0.48; P < .001) and older AYAs (aged 22-39 years) with low socioeconomic status (OR = 0.39; 95% CI = 0.17 to 0.89; P = .02), public/no insurance (OR = 0.30; 95% CI = 0.12 to 0.71; P < .01), and distance to care greater than 5 miles (OR = 0.29; 95% CI = 0.15 to 0.57; P < .001). CONCLUSIONS: Population-based data reveal that care at NCICCC/COG sites mitigates inferior outcome in AYAs with WHO grade II CNS tumors compared with children. Compared with children, AYAs are less likely to receive care at NCICCC/COGs. Insurance, socioeconomic status, and distance serve as barriers to care at NCICCCs for older AYAs.

Coffee intake and risk of colorectal cancer among Chinese in Singapore: the Singapore Chinese Health Study.

We prospectively investigated whether coffee consumption was associated with decreased risk of colorectal cancer and whether cigarette smoking and stage of disease modify the association in the Singapore Chinese Health Study. During the first 12 years of follow-up, 961 colorectal cancer cases occurred in the cohort of over 60,000 middle-aged or older Chinese men and women living in Singapore. Baseline dietary exposures were assessed through in-person interviews using a validated food frequency questionnaire. The relation between coffee consumption and colorectal cancer risk was assessed by proportional hazards (Cox) regression. No overall association between coffee intake and colorectal cancer was observed. However, in analysis by subsite and stage restricted to ever smokers, the coffee-colon cancer association became statistically significant for advanced disease (P for trend = 0.01). The hazard ratio was 0.56 (95% confidence interval = 0.35-0.90) for advanced colon cancer in drinkers of 2 or more cups per day compared with those who drank no coffee or less than 1 cup per day. Although there is a null association between coffee intake and risk of colorectal cancer overall, coffee may protect against smoking related advanced colon cancer.

Green tea and black tea consumption in relation to colorectal cancer risk: the Singapore Chinese Health Study.

The relationships between green tea and black tea consumption and colorectal cancer risk were examined within the Singapore Chinese Health Study, a prospective cohort study of diet and cancer involving >60,000 men and women. Intake of green tea and black tea was assessed through in-person interviews. Incident cancer cases and deaths among cohort members were identified through record linkage of the cohort database with respective databases from the nationwide Singapore Cancer Registry and the Singapore Registry of Births and Deaths. The proportional hazard regression method was used to examine the associations between intake of green and black tea separately and colorectal cancer risk with adjustment for potential confounders. After an average of 8.9 years of follow-up, 845 colorectal cancer cases were identified. Subjects who drank green tea exhibited a statistically non-significant increase in risk [relative risk (RR) = 1.12, 95% confidence interval (CI) = 0.97-1.29] relative to non-drinkers of green tea. This risk increase was mainly confined to men (RR = 1.31, 95% CI = 1.08-1.58); the comparable RR in women was 0.89 (95% CI = 0.71-1.12). In men, the green tea-colorectal cancer association was noted mainly in those with advanced disease (Duke C or D) (RR = 1.53, 95% CI = 1.19-1.97), and the association was dose dependent (P for trend = 0.0002). This latter association was especially strong within the colon subsite (RR = 1.75, 95% CI = 1.24-2.46; P for trend < 0.0001). Irrespective of gender, intake of black tea was not associated with risk of colorectal cancer (RR = 0.92, 95% CI = 0.79-1.07) in this Asian population.

Green tea intake, ACE gene polymorphism and breast cancer risk among Chinese women in Singapore.

Experimental and epidemiological data have implicated a potential chemoprotective role of green tea polyphenols and a potential enhancing role of angiotensin II in the development of breast cancer in humans. Angiotensin II is converted from its precursor by angiotensin-converting enzyme (ACE). Women with low-activity genotype of the ACE gene had a reduced risk of breast cancer compared with those possessing high-activity ACE genotype. Experimental data showed that green tea polyphenols could inhibit angiotensin II-induced reactive oxygen species production. We reasoned that if this is one of the mechanisms by which green tea polyphenols protect against human breast cancer, then their effect should be more prominent among women possessing high-activity ACE genotype than women with low-activity ACE genotype. In other words, we predict a stronger inverse green tea-breast cancer association among the former versus the latter subgroup of women. To test this hypothesis, we conducted a nested case-control study involving 297 incident breast cancer cases and 665 control subjects within the Singapore Chinese Health Study. There was no association between intake frequencies of green tea and risk of breast cancer among all women or those with low-activity ACE genotype. Among women with high-activity ACE genotype, however, intake frequency of green tea was associated with a statistically significant decrease in risk of breast cancer (P for trend=0.039); the odds ratio (95% confidence interval) was 0.33 (0.13-0.82) for women drinking green tea at least monthly and 0.29 (0.10-0.79) for those drinking green tea at least weekly compared with non-drinkers. There was a statistically significant interaction effect between green tea intake and ACE genotype on risk of breast cancer (P for interaction=0.01). Black tea intake was unrelated to breast cancer risk irrespective of the ACE genotype. The findings of the present study highlight the importance of genetically determined factors in evaluating the role of green tea intake in the development of breast cancer.

Marine n-3 fatty acid intake, glutathione S-transferase polymorphisms and breast cancer risk in post-menopausal Chinese women in Singapore.

We have previously found marine n-3 fatty acids to be inversely related to post-menopausal breast cancer in Chinese women from Singapore. Post-menopausal women with high [quartiles 2-4 (Q2-Q4)] versus low [quartile 1 (Q1)] intake exhibited a statistically significant reduction in risk of breast cancer after adjustment for potential confounders [relative risk (RR) = 0.66, 95% confidence interval (CI) = 0.50, 0.87]. Experimental studies have demonstrated a direct role for the peroxidation products of marine n-3 fatty acids in breast cancer protection. There is a suggestion that the glutathione S-transferases (GSTs) may be major catalysts in the elimination of these beneficial by-products. Therefore, we hypothesized that individuals possessing the low activity genotypes of GSTM1, GSTT1 and/or GSTP1 (i.e. the GSTM1 null, GSTT1 null and GSTP1 AB/BB genotypes, respectively) may exhibit a stronger marine n-3 fatty acid-breast cancer association than their high activity counterparts. The Singapore Chinese Health Study is a prospective investigation involving 35,298 middle-aged and older women, who were enrolled between April 1993 and December 1998. In this case-control analysis, nested within the Singapore Chinese Health Study, we compared 258 incident breast cancer cases with 670 cohort controls. Overall, breast cancer risk was unrelated to GSTM1 and GSTP1 genotypes. However, the GSTT1 null genotype was associated with a 30% reduced risk of breast cancer [odds ratio (OR) = 0.71, 95% CI = 0.52, 0.96]. Among women with high activity GST genotypes (i.e. GSTM1 positive, GSTT1 positive and GSTP1 AA), no marine n-3 fatty acid-breast cancer relationships were observed in either pre-menopausal or post-menopausal women at baseline. However, post-menopausal women possessing the combined GSTM1 null and GSTP1 AB/BB genotypes showed a statistically significant reduction in risk after adjustment for potential confounders (Q2-Q4 versus Q1, OR = 0.36, 95% CI = 0.14, 0.94). A similar relationship was observed among women with the combined GSTT1 null and GSTP1 AB/BB genotypes (OR = 0.26, 95% CI = 0.08, 0.78).

Urinary tea polyphenols in relation to gastric and esophageal cancers: a prospective study of men in Shanghai, China.

Experimental studies have shown that tea and tea polyphenols have anticarcinogenic properties. There have been no prospective investigations examining the relationship between tea polyphenols and cancer risk using validated biomarkers. In the present study, a nested case-control study design was used to investigate the association between prediagnostic urinary tea polyphenol markers and subsequent risk of gastric and esophageal cancers. One hundred and ninety incident cases of gastric cancer and 42 cases of esophageal cancer occurring in members of the Shanghai Cohort (18 244 men aged 45-64 years at recruitment with up to 12 years of follow-up) were compared with 772 cohort control subjects. The control subjects were individually matched to the index cases by age, month and year of sample collection, and neighborhood of residence (case-control ratio = 1:3 for gastric cancer, 1:5 for esophageal cancer). Urinary tea polyphenols, including epigallocatechin (EGC) and epicatechin (EC), and their respective metabolites 5-(3',4',5'-trihydroxyphenyl)-gamma-valerolactone (M4) and 5-(3',4'-dihydroxyphenyl)-gamma-valerolactone (M6), were measured in all study subjects by means of a validated assay. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated from logistic regression models. After exclusion of cases diagnosed under 4 years follow-up, urinary EGC positivity showed a statistically significant inverse association with gastric cancer (OR = 0.52, 95% CI = 0.28-0.97) after adjustment for Helicobactor pylori seropositivity, smoking, alcohol drinking, and level of serum carotenes. The protective effect was primarily seen among subjects with low (below population median) serum carotenes. The odds ratio for EGC positivity was 0.49 (95% CI = 0.26-0.94) among subjects with low serum carotenes while the corresponding odds ratio among subjects with higher levels of serum carotenes was 1.02 (95% CI = 0.46-2.28). Similar tea polyphenol-cancer risk associations were observed when the gastric cancer and esophageal cancer sites were combined. The present study provides direct evidence that tea polyphenols may act as chemopreventive agents against gastric and esophageal cancer development.