Effect of Yoga and Mediational Influence of Fatigue on Walking, Physical Activity, and Quality of Life Among Cancer Survivors.

BACKGROUND: Cancer-related fatigue (CRF) negatively affects survivors' walking, engagement in physical activity (PA), and quality of life (QoL). Yoga is an effective therapy for treating CRF; however, evidence from large clinical trials regarding how reducing CRF through yoga influences CRF's interference with survivors' walking, engagement in PA, and QoL is not available. We examined the effects of yoga and the mediational influence of CRF on CRF's interference with walking, PA, and QoL among cancer survivors in a multicenter phase III randomized controlled trial. PATIENTS AND METHODS: Cancer survivors (n=410) with insomnia 2 to 24 months posttreatment were randomized to a 4-week yoga intervention-Yoga for Cancer Survivors (YOCAS)-or standard care. A symptom inventory was used to assess how much CRF interfered with survivors' walking, PA, and QoL. The Multidimensional Fatigue Symptom Inventory-Short Form was used to assess CRF. Two-tailed t tests and analyses of covariance were used to examine within-group and between-group differences. Path analysis was used to evaluate mediational relationships between CRF and changes in CRF's interference with walking, PA, and QoL among survivors. RESULTS: Compared with standard care controls, YOCAS participants reported significant improvements in CRF's interference with walking, PA, and QoL at postintervention (all effect size = -0.33; all P≤.05). Improvements in CRF resulting from yoga accounted for significant proportions of the improvements in walking (44%), PA (53%), and QoL (45%; all P≤.05). CONCLUSIONS: A significant proportion (44%-53%) of the YOCAS effect on CRF's interference with walking, PA, and QoL was due to improvements in CRF among cancer survivors. Yoga should be introduced and included as a treatment option for survivors experiencing fatigue. By reducing fatigue, survivors further improve their walking, engagement in PA, and QoL.

Associations Between Unprocessed Red Meat and Processed Meat With Risk of Recurrence and Mortality in Patients With Stage III Colon Cancer.

Importance: The American Cancer Society and American Institute for Cancer Research recommend that cancer survivors limit intake of red and processed meats. This recommendation is based on consistent associations between red and processed meat intake and cancer risk, particularly risk of colorectal cancer, but fewer data are available on red and processed meat intake after cancer diagnosis. Objectives: To examine whether intake of unprocessed red meat or processed meat is associated with risk of cancer recurrence or mortality in patients with colon cancer. Design, Setting, and Participants: This prospective cohort study used data from participants with stage III colon cancer enrolled in the Cancer and Leukemia Group B (CALGB 89803/Alliance) trial between 1999 and 2001. The clinical database for this analysis was frozen on November 9, 2009; the current data analyses were finalized in December 2021. Exposures: Quartiles of unprocessed red meat and processed meat intake assessed using a validated food frequency questionnaire during and 6 months after chemotherapy. Main Outcomes and Measures: Hazard ratios (HRs) and 95% CIs for risk of cancer recurrence or death and all-cause mortality. Results: This study was conducted among 1011 patients with stage III colon cancer. The median (IQR) age at enrollment was 60 (51-69) years, 442 patients (44%) were women, and 899 patients (89%) were White. Over a median (IQR) follow-up period of 6.6 (1.9-7.5) years, we observed 305 deaths and 81 recurrences without death during follow-up (386 events combined). Intake of unprocessed red meat or processed meat after colon cancer diagnosis was not associated with risk of recurrence or mortality. The multivariable HRs comparing the highest vs lowest quartiles for cancer recurrence or death were 0.84 (95% CI, 0.58-1.23) for unprocessed red meat and 1.05 (95% CI, 0.75-1.47) for processed meat. For all-cause mortality, the corresponding HRs were 0.71 (95% CI, 0.47-1.07) for unprocessed red meat and 1.04 (95% CI, 0.72-1.51) for processed meat. Conclusions and Relevance: In this cohort study, postdiagnosis intake of unprocessed red meat or processed meat was not associated with risk of recurrence or death among patients with stage III colon cancer.

Diet- and Lifestyle-Based Prediction Models to Estimate Cancer Recurrence and Death in Patients With Stage III Colon Cancer (CALGB 89803/Alliance).

PURPOSE: Current tools in predicting survival outcomes for patients with colon cancer predominantly rely on clinical and pathologic characteristics, but increasing evidence suggests that diet and lifestyle habits are associated with patient outcomes and should be considered to enhance model accuracy. METHODS: Using an adjuvant chemotherapy trial for stage III colon cancer (CALGB 89803), we developed prediction models of disease-free survival (DFS) and overall survival by additionally incorporating self-reported nine diet and lifestyle factors. Both models were assessed by multivariable Cox proportional hazards regression and externally validated using another trial for stage III colon cancer (CALGB/SWOG 80702), and visual nomograms of prediction models were constructed accordingly. We also proposed three hypothetical scenarios for patients with (1) good-risk, (2) average-risk, and (3) poor-risk clinical and pathologic features, and estimated their predictive survival by considering clinical and pathologic features with or without adding self-reported diet and lifestyle factors. RESULTS: Among 1,024 patients (median age 60.0 years, 43.8% female), we observed 394 DFS events and 311 deaths after median follow-up of 7.3 years. Adding self-reported diet and lifestyle factors to clinical and pathologic characteristics meaningfully improved performance of prediction models (c-index from 0.64 [95% CI, 0.62 to 0.67] to 0.69 [95% CI, 0.67 to 0.72] for DFS, and from 0.67 [95% CI, 0.64 to 0.70] to 0.71 [95% CI, 0.69 to 0.75] for overall survival). External validation also indicated good performance of discrimination and calibration. Adding most self-reported favorable diet and lifestyle exposures to multivariate modeling improved 5-year DFS of all patients and by 6.3% for good-risk, 21.4% for average-risk, and 42.6% for poor-risk clinical and pathologic features. CONCLUSION: Diet and lifestyle factors further inform current recurrence and survival prediction models for patients with stage III colon cancer.

Race, Income, and Survival in Stage III Colon Cancer: CALGB 89803 (Alliance).

Background: Disparities in colon cancer outcomes have been reported across race and socioeconomic status, which may reflect, in part, access to care. We sought to assess the influences of race and median household income (MHI) on outcomes among colon cancer patients with similar access to care. Methods: We conducted a prospective, observational study of 1206 stage III colon cancer patients enrolled in the CALGB 89803 randomized adjuvant chemotherapy trial. Race was self-reported by 1116 White and 90 Black patients at study enrollment; MHI was determined by matching 973 patients' home zip codes with publicly available US Census 2000 data. Multivariate analyses were adjusted for baseline sociodemographic, clinical, dietary, and lifestyle factors. All statistical tests were 2-sided. Results: Over a median follow-up of 7.7 years, the adjusted hazard ratios for Blacks (compared with Whites) were 0.94 (95% confidence interval [CI] = 0.66 to 1.35, P = .75) for disease-free survival, 0.91 (95% CI = 0.62 to 1.35, P = .65) for recurrence-free survival, and 1.07 (95% CI = 0.73 to 1.57, P = .73) for overall survival. Relative to patients in the highest MHI quartile, the adjusted hazard ratios for patients in the lowest quartile were 0.90 (95% CI = 0.67 to 1.19, P trend = .18) for disease-free survival, 0.89 (95% CI = 0.66 to 1.22, P trend = .14) for recurrence-free survival, and 0.87 (95% CI = 0.63 to 1.19, P trend = .23) for overall survival. Conclusions: In this study of patients with similar health-care access, no statistically significant differences in outcomes were found by race or MHI. The substantial gaps in outcomes previously observed by race and MHI may not be rooted in differences in tumor biology but rather in access to quality care.

Continuous versus intermittent BRAF and MEK inhibition in patients with BRAF-mutated melanoma: a randomized phase 2 trial.

Preclinical modeling suggests that intermittent BRAF inhibitor therapy may delay acquired resistance when blocking oncogenic BRAFV600 in melanoma1,2. We conducted S1320, a randomized, open-label, phase 2 clinical trial (NCT02196181) evaluating whether intermittent dosing of the BRAF inhibitor dabrafenib and the MEK inhibitor trametinib improves progression-free survival in patients with metastatic and unresectable BRAFV600 melanoma. Patients were enrolled at 68 academic and community sites nationally. All patients received continuous dabrafenib and trametinib during an 8-week lead-in period, after which patients with non-progressing tumors were randomized to either continuous or intermittent dosing of both drugs on a 3-week-off, 5-week-on schedule. The trial has completed accrual and 206 patients with similar baseline characteristics were randomized 1:1 to the two study arms (105 to continuous dosing, 101 to intermittent dosing). Continuous dosing yielded a statistically significant improvement in post-randomization progression-free survival compared with intermittent dosing (median 9.0 months versus 5.5 months, P = 0.064, pre-specified two-sided α = 0.2). Therefore, contrary to the initial hypothesis, intermittent dosing did not improve progression-free survival in patients. There were no differences in the secondary outcomes, including overall survival and the overall incidence of treatment-associated toxicity, between the two groups.

The Diet of Higher Insulinemic Potential Is Not Associated with Worse Survival in Patients with Stage III Colon Cancer (Alliance).

BACKGROUND: Hyperinsulinemia is considered to be important in the development of colon cancer, but few studies have investigated the associations of hyperinsulinemia with colon cancer survival via dietary scores. METHODS: Empirical dietary index for hyperinsulinemia (EDIH) was derived to assess the insulinemic potential of daily diets reflecting the long-term insulin exposure, with higher (more positive) scores indicating higher insulinemic diets. We prospectively estimated the HRs and 95% confidence intervals (CI) to investigate the association of EDIH with disease-free, recurrence-free, and overall survival among patients with stage III colon cancer (1999-2009) enrolled in a randomized adjuvant chemotherapy trial (CALGB 89803). RESULTS: Of 1,024 patients (median follow-up: 7.3 years), 311 died, 350 had recurrences, and 394 had events for disease-free survival. Compared with patients in the lowest quintile of EDIH, the corresponding HRs of patients in the highest quintile for disease-free survival events, cancer recurrence, and overall mortality were 0.80 (95% CI, 0.56-1.15), 0.76 (95% CI, 0.51-1.11), and 0.77 (95% CI, 0.52-1.14). CONCLUSIONS: Higher EDIH was not associated with the risk of colon cancer recurrence or mortality in this population of patients with stage III colon cancer. IMPACT: EDIH, as a measure of dietary insulinemic potential, may be associated with colon cancer risk but not survival in patients with late-stage colon cancer.

Phase III Randomized Trial of Bisphosphonates as Adjuvant Therapy in Breast Cancer: S0307.

BACKGROUND: Adjuvant bisphosphonates, when given in a low-estrogen environment, can decrease breast cancer recurrence and death. Treatment guidelines include recommendations for adjuvant bisphosphonates in postmenopausal patients. SWOG/Alliance/Canadian Cancer Trials Group/ECOG-ACRIN/NRG Oncology study S0307 compared the efficacy of three bisphosphonates in early-stage breast cancer. METHODS: Patients with stage I-III breast cancer were randomly assigned to 3 years of intravenous zoledronic acid, oral clodronate, or oral ibandronate. The primary endpoint was disease-free survival (DFS) with overall survival as a secondary outcome. All statistical tests were two-sided. RESULTS: A total of 6097 patients enrolled. Median age was 52.7 years. Prior to being randomly assigned, 73.2% patients indicated preference for oral vs intravenous formulation. DFS did not differ across arms in a log-rank test (P = .49); 5-year DFS was 88.3% (zoledronic acid: 95% confidence interval [CI] = 86.9% to 89.6%), 87.6% (clodronate: 95% CI = 86.1% to 88.9%), and 87.4% (ibandronate: 95% CI = 85.6% to 88.9%). Additionally, 5-year overall survival did not differ between arms (log rank P = .50) and was 92.6% (zoledronic acid: 95% CI = 91.4% to 93.6%), 92.4% (clodronate: 95% CI = 91.2% to 93.5%), and 92.9% (ibandronate: 95% CI = 91.5% to 94.1%). Bone as first site of recurrence did not differ between arms (P = .93). Analyses based on age and tumor subtypes showed no treatment differences. Grade 3/4 toxicity was 8.8% (zoledronic acid), 8.3% (clodronate), and 10.5% (ibandronate). Osteonecrosis of the jaw was highest for zoledronic acid (1.26%) compared with clodronate (0.36%) and ibandronate (0.77%). CONCLUSIONS: We found no evidence of differences in efficacy by type of bisphosphonate, either in overall analysis or subgroups. Despite an increased rate of osteonecrosis of the jaw with zoledronic acid, overall toxicity grade differed little across arms. Given that patients expressed preference for oral formulation, efforts to make oral agents available in the United States should be considered.

Influence of Yoga on Cancer-Related Fatigue and on Mediational Relationships Between Changes in Sleep and Cancer-Related Fatigue: A Nationwide, Multicenter Randomized Controlled Trial of Yoga in Cancer Survivors.

BACKGROUND: Cancer-related fatigue (CRF) often co-occurs with sleep disturbance and is one of the most pervasive toxicities resulting from cancer and its treatment. We and other investigators have previously reported that yoga therapy can improve sleep quality in cancer patients and survivors. No nationwide multicenter phase III randomized controlled trial (RCT) has investigated whether yoga therapy improves CRF or whether improvements in sleep mediate the effect of yoga on CRF. We examined the effect of a standardized, 4-week, yoga therapy program (Yoga for Cancer Survivors [YOCAS]) on CRF and whether YOCAS-induced changes in sleep mediated changes in CRF among survivors. STUDY DESIGN AND METHODS: Four hundred ten cancer survivors were recruited to a nationwide multicenter phase III RCT comparing the effect of YOCAS to standard survivorship care on CRF and examining the mediating effects of changes in sleep, stemming from yoga, on changes in CRF. CRF was assessed by the Multidimensional Fatigue Symptom Inventory. Sleep was assessed via the Pittsburgh Sleep Quality Index. Between- and within-group intervention effects on CRF were assessed by analysis of covariance and 2-tailed t test, respectively. Path analysis was used to evaluate mediation. RESULTS: YOCAS participants demonstrated significantly greater improvements in CRF compared with participants in standard survivorship care at post-intervention ( P < .01). Improvements in overall sleep quality and reductions in daytime dysfunction (eg, excessive napping) resulting from yoga significantly mediated the effect of yoga on CRF (22% and 37%, respectively, both P < .01). CONCLUSIONS: YOCAS is effective for treating CRF among cancer survivors; 22% to 37% of the improvements in CRF from yoga therapy result from improvements in sleep quality and daytime dysfunction. Oncologists should consider prescribing yoga to cancer survivors for treating CRF and sleep disturbance.

Dietary Insulin Load and Cancer Recurrence and Survival in Patients With Stage III Colon Cancer: Findings From CALGB 89803 (Alliance).

BACKGROUND: Evidence suggests that diets inducing postprandial hyperinsulinemia may be associated with increased cancer-related mortality. The goal of this study was to assess the influence of postdiagnosis dietary insulin load and dietary insulin index on outcomes of stage III colon cancer patients. METHODS: We conducted a prospective observational study of 1023 patients with resected stage III colon cancer enrolled in an adjuvant chemotherapy trial who reported dietary intake halfway through and six months after chemotherapy. We evaluated the association of dietary insulin load and dietary insulin index with cancer recurrence and survival using Cox proportional hazards regression adjusted for potential confounders; statistical tests were two-sided. RESULTS: High dietary insulin load had a statistically significant association with worse disease-free survival (DFS), comparing the highest vs lowest quintile (adjusted hazard ratio [HR] = 2.77, 95% confidence interval [CI] = 1.90 to 4.02, Ptrend < .001). High dietary insulin index was also associated with worse DFS (highest vs lowest quintile, HR = 1.75, 95% CI = 1.22 to 2.51, Ptrend= .01). The association between higher dietary insulin load and worse DFS differed by body mass index and was strongest among patients with obesity (HR = 3.66, 95% CI = 1.88 to 7.12, Pinteraction = .04). The influence of dietary insulin load on cancer outcomes did not differ by mutation status of KRAS, BRAF, PIK3CA, TP53, or microsatellite instability. CONCLUSIONS: Patients with resected stage III colon cancer who consumed a high-insulinogenic diet were at increased risk of recurrence and mortality. These findings support the importance of dietary management following resection of colon cancer, and future research into underlying mechanisms of action is warranted.

Associations of artificially sweetened beverage intake with disease recurrence and mortality in stage III colon cancer: Results from CALGB 89803 (Alliance).

PURPOSE: Observational studies have demonstrated increased colon cancer recurrence and mortality in states of excess energy balance, as denoted by factors including sedentary lifestyle, diabetes, increased dietary glycemic load, and increased intake of sugar-sweetened beverages. Nonetheless, the relation between artificially sweetened beverages, a popular alternative for sugar-sweetened beverages, and colon cancer recurrence and survival is unknown. METHODS: We analyzed data from 1,018 patients with stage III colon cancer who prospectively reported dietary intake during and after chemotherapy while enrolled in a National Cancer Institute-sponsored trial of adjuvant chemotherapy. Using Cox proportional hazards regressions, we assessed associations of artificially sweetened beverage intake with cancer recurrence and mortality. RESULTS: Patients consuming one or more 12-ounce servings of artificially sweetened beverages per day experienced an adjusted hazard ratio for cancer recurrence or mortality of 0.54 (95% confidence interval, 0.36 to 0.80) when compared to those who largely abstained (Ptrend = .004). Similarly, increasing artificially sweetened beverage intake was also associated with a significant improvement in both recurrence-free survival (Ptrend = .005) and overall survival (Ptrend = .02). Substitution models demonstrated that replacing a 12-ounce serving of a sugar-sweetened beverage with an isovolumetric serving of an artificially sweetened beverage per day was associated with a 23% lower risk of cancer recurrence and mortality (relative risk, 0.77; 95% confidence interval, 0.63 to 0.95; P = .02). CONCLUSION: Higher artificially sweetened beverage consumption may be associated with significantly reduced cancer recurrence and death in patients with stage III colon cancer. This association may be mediated by substitution for sugar-sweetened alternatives. Further studies are needed to confirm these findings.

Grain Intake and Clinical Outcome in Stage III Colon Cancer: Results From CALGB 89803 (Alliance).

BACKGROUND: Energy balance-related risk factors for colon cancer recurrence and mortality-type II diabetes, hyperinsulinemia, inflammation, and visceral obesity-are positively correlated with consumption of refined grains and negatively correlated with consumption of whole grains. We examined the relationship between the consumption of refined and whole grains with cancer recurrence and mortality in a cohort of patients with colon cancer. METHODS: We conducted a prospective observational study of 1024 patients with stage III colon cancer who participated in a randomized trial of postoperative chemotherapy. Patients reported consumption of refined and whole grains using a food frequency questionnaire during and six months after chemotherapy. The primary outcome was disease-free survival (DFS). Multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox regression models. All P values are two-sided. RESULTS: During a median follow-up of 7.3 years, 394 patients experienced a DFS event. The hazard ratio for DFS was 1.56 (95% CI = 1.09 to 2.24) for patients consuming three or more servings per day of refined grains compared with patients consuming less than one serving per day (Ptrend = .005). The hazard ratio for DFS was 0.89 (95% CI = 0.66 to 1.20) for patients consuming three or more servings per day of whole grains compared with patients consuming less than one serving per day (Ptrend = .54). The hazard ratio for DFS of substituting one serving per day of refined grain with one serving per day of whole grain was 0.87 (95% CI = 0.79 to 0.96, P = .007). CONCLUSIONS: The choice of grain consumed may be associated with cancer recurrence and mortality. Future studies are necessary to confirm our findings and to inform the design of randomized trials.

Association of Survival With Adherence to the American Cancer Society Nutrition and Physical Activity Guidelines for Cancer Survivors After Colon Cancer Diagnosis: The CALGB 89803/Alliance Trial.

Importance: The American Cancer Society Nutrition and Physical Activity Guidelines for Cancer Survivors (ACS guidelines) include maintaining (1) a healthy body weight; (2) physical activity; and (3) a diet that includes vegetables, fruits, and whole grains. It is not known whether patients with colon cancer who follow these guidelines have improved survival. Objective: To examine whether a lifestyle consistent with the ACS guidelines is associated with improved survival rates after colon cancer. Design, Setting, and Participants: This prospective cohort study included 992 patients with stage III colon cancer who were enrolled in the CALGB 89803 randomized adjuvant chemotherapy trial from 1999 through 2001. Data for the present study were analyzed between November 2016 and December 2017. Exposures: We assigned an ACS guidelines score for each included patient based on body mass index; physical activity; and intake of vegetables, fruits, whole grains, and red/processed meats (score range, 0-6, with higher score indicating healthier behaviors). Secondarily, we examined a score that also included alcohol intake in addition to the other factors (range, 0-8). Lifestyle was assessed during and 6 months after chemotherapy. Main Outcomes and Measures: Hazard ratios (HRs) and 95% confidence intervals (CIs) for disease-free, recurrence-free, and overall survival. Results: Of the 992 patients enrolled in the study, 430 (43%) were women, and the mean (SD) age was 59.6 (11.2) years (range, 21-85 years). Over a 7-year median follow-up, we observed 335 recurrences and 299 deaths (43 deaths without recurrence). Compared with patients with a 0 to 1 ACS guidelines score (n = 262; 26%), patients with a 5 to 6 score (n = 91; 9%) had a 42% lower risk of death during the study period (HR, 0.58; 95% CI, 0.34-0.99; P = .01 for trend) and improved disease-free survival (HR, 0.69; 95% CI, 0.45-1.06; P = .03 for trend). When alcohol consumption was included in the score, the adjusted HRs comparing patients with scores of 6 to 8 (n = 162; 16%) vs those with scores of 0 to 2 (187; 91%) were 0.49 for overall survival (95% CI, 0.32-0.76; P = .002 for trend), 0.58 for disease-free survival (95% CI, 0.40, 0.84; P = .01 for trend), and 0.64 for recurrence-free survival (95% CI, 0.44-0.94; P = .05 for trend). Conclusions and Relevance: Having a healthy body weight, being physically active, and eating a diet rich in vegetables, fruits, and whole grains after diagnosis of stage III colon cancer was associated with a longer survival. Trial Registration: clinicaltrials.gov Identifier: NCT00003835.

Nut Consumption and Survival in Patients With Stage III Colon Cancer: Results From CALGB 89803 (Alliance).

Purpose Observational studies have reported increased colon cancer recurrence and mortality in patients with states of hyperinsulinemia, including type 2 diabetes, obesity, sedentary lifestyle, and high glycemic load diet. Nut intake has been associated with a lower risk of type 2 diabetes, metabolic syndrome, and insulin resistance. However, the effect of nut intake on colon cancer recurrence and survival is not known. Patients and Methods We conducted a prospective, observational study of 826 eligible patients with stage III colon cancer who reported dietary intake on food frequency questionnaires while enrolled onto a randomized adjuvant chemotherapy trial. Using Cox proportional hazards regression, we assessed associations of nut intake with cancer recurrence and mortality. Results After a median follow-up of 6.5 years, compared with patients who abstained from nuts, individuals who consumed two or more servings of nuts per week experienced an adjusted hazard ratio (HR) for disease-free survival of 0.58 (95% CI, 0.37 to 0.92; Ptrend = .03) and an HR for overall survival of 0.43 (95% CI, 0.25 to 0.74; Ptrend = .01). In subgroup analysis, the apparent benefit was confined to tree nut intake (HR for disease-free survival, 0.54; 95% CI, 0.34 to 0.85; Ptrend = .04; and HR for overall survival, 0.47; 95% CI, 0.27 to 0.82; Ptrend = .04). The association of total nut intake with improved outcomes was maintained across other known or suspected risk factors for cancer recurrence and mortality. Conclusion Diets with a higher consumption of nuts may be associated with a significantly reduced incidence of cancer recurrence and death in patients with stage III colon cancer.

Marine ω-3 Polyunsaturated Fatty Acid and Fish Intake after Colon Cancer Diagnosis and Survival: CALGB 89803 (Alliance).

Background: Marine ω-3 polyunsaturated fatty acids (PUFAs), primarily found in dark fish, may prevent colorectal cancer progression, in part through inhibition of prostaglandin-endoperoxide synthase 2 (PTGS2). However, data in humans are limited.Methods: We examined marine ω-3 PUFAs and fish intake and survival among 1,011 colon cancer patients enrolled in Cancer and Leukemia Group B 89803 between 1999 and 2001 and followed through 2009. Diet was assessed during and 6 months after chemotherapy. We used Cox proportional hazards regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for disease-free (DFS), recurrence-free (RFS), and overall survival (OS).Results: We observed 343 recurrences and 305 deaths (median follow-up: 7 years). Patients in the highest vs. lowest quartile of marine ω-3 PUFA intake had an HR for DFS of 0.72 (95% CI, 0.54-0.97; Ptrend = 0.03). Individuals who consumed dark fish ≥1/week versus never had longer DFS (HR 0.65; 95% CI, 0.48-0.87; P-value = 0.007), RFS (HR 0.61; 95% CI, 0.46-0.86; Ptrend = 0.007), and OS (HR 0.68; 95% CI, 0.48-0.96; Ptrend = 0.04). In a subset of 510 patients, the association between marine ω-3 PUFA intake and DFS appeared stronger in patients with high PTGS2 expression (HR 0.32; 95% CI, 0.11-0.95; Ptrend = 0.01) compared with patients with absent/low PTGS2 expression (HR 0.78; 95% CI, 0.48-1.27; Ptrend = 0.35; Pinteraction = 0.19).Conclusions: Patients with high intake of marine ω-3 PUFAs and dark fish after colon cancer diagnosis may have longer DFS.Impact: Randomized controlled trials examining dark fish and/or marine ω-3 PUFA supplements and colon cancer recurrence/survival are needed. Cancer Epidemiol Biomarkers Prev; 27(4); 438-45. ©2018 AACR.

National Institute on Aging /Alzheimer's Association criteria for Mild Cognitive Impairment applied to chemotherapy treated breast cancer survivors.

BACKGROUND: In this analysis we use the National Institute on Aging/Alzheimer's Association (NIA/AA) criteria to identify Mild Cognitive Impairment (MCI) in a sample of breast cancer survivors treated with chemotherapy. METHODS: Sixty women ages 39-79 on a prospective clinical trial of donepezil were assessed at baseline using a battery of standardized/validated neurocognitive measures. Cognitive status was adjudicated to identify MCI by a panel of dementia experts. RESULTS: Fifty percent were not cognitively impaired, 43% met the NIA/AA criteria for MCI, 2% had dementia, and 5% could not be classified. DISCUSSION: In this sample, nearly half of breast cancer survivors met the NIA/AA criteria for MCI. We propose these criteria be used to define cancer-related Mild Cognitive Impairment (cMCI), providing a framework for conducting additional studies to further characterize cMCI and identify clinical, imaging, and genetic factors associated with the progression of cMCI to more advanced stages of cognitive impairment.

YOCAS©® Yoga Reduces Self-reported Memory Difficulty in Cancer Survivors in a Nationwide Randomized Clinical Trial: Investigating Relationships Between Memory and Sleep.

UNLABELLED: Background Interventions are needed to alleviate memory difficulty in cancer survivors. We previously showed in a phase III randomized clinical trial that YOCAS©® yoga-a program that consists of breathing exercises, postures, and meditation-significantly improved sleep quality in cancer survivors. This study assessed the effects of YOCAS©® on memory and identified relationships between memory and sleep. STUDY DESIGN AND METHODS: Survivors were randomized to standard care (SC) or SC with YOCAS©® . 328 participants who provided data on the memory difficulty item of the MD Anderson Symptom Inventory are included. Sleep quality was measured using the Pittsburgh Sleep Quality Index. General linear modeling (GLM) determined the group effect of YOCAS©® on memory difficulty compared with SC. GLM also determined moderation of baseline memory difficulty on postintervention sleep and vice versa. Path modeling assessed the mediating effects of changes in memory difficulty on YOCAS©® changes in sleep and vice versa. RESULTS: YOCAS©® significantly reduced memory difficulty at postintervention compared with SC (mean change: yoga=-0.60; SC=-0.16; P<.05). Baseline memory difficulty did not moderate the effects of postintervention sleep quality in YOCAS©® compared with SC. Baseline sleep quality did moderate the effects of postintervention memory difficulty in YOCAS©® compared with SC (P<.05). Changes in sleep quality was a significant mediator of reduced memory difficulty in YOCAS©® compared with SC (P<.05); however, changes in memory difficulty did not significantly mediate improved sleep quality in YOCAS©® compared with SC. CONCLUSIONS: In this large nationwide trial, YOCAS©® yoga significantly reduced patient-reported memory difficulty in cancer survivors.

Coffee Intake, Recurrence, and Mortality in Stage III Colon Cancer: Results From CALGB 89803 (Alliance).

PURPOSE: Observational studies have demonstrated increased colon cancer recurrence in states of relative hyperinsulinemia, including sedentary lifestyle, obesity, and increased dietary glycemic load. Greater coffee consumption has been associated with decreased risk of type 2 diabetes and increased insulin sensitivity. The effect of coffee on colon cancer recurrence and survival is unknown. PATIENTS AND METHODS: During and 6 months after adjuvant chemotherapy, 953 patients with stage III colon cancer prospectively reported dietary intake of caffeinated coffee, decaffeinated coffee, and nonherbal tea, as well as 128 other items. We examined the influence of coffee, nonherbal tea, and caffeine on cancer recurrence and mortality using Cox proportional hazards regression. RESULTS: Patients consuming 4 cups/d or more of total coffee experienced an adjusted hazard ratio (HR) for colon cancer recurrence or mortality of 0.58 (95% CI, 0.34 to 0.99), compared with never drinkers (Ptrend = .002). Patients consuming 4 cups/d or more of caffeinated coffee experienced significantly reduced cancer recurrence or mortality risk compared with abstainers (HR, 0.48; 95% CI, 0.25 to 0.91; Ptrend = .002), and increasing caffeine intake also conferred a significant reduction in cancer recurrence or mortality (HR, 0.66 across extreme quintiles; 95% CI, 0.47 to 0.93; Ptrend = .006). Nonherbal tea and decaffeinated coffee were not associated with patient outcome. The association of total coffee intake with improved outcomes seemed consistent across other predictors of cancer recurrence and mortality. CONCLUSION: Higher coffee intake may be associated with significantly reduced cancer recurrence and death in patients with stage III colon cancer.

Geriatric assessment-identified deficits in older cancer patients with normal performance status.

BACKGROUND: We investigated whether a brief geriatric assessment (GA) would identify important patient deficits that could affect treatment tolerance and care outcomes within a sample of older cancer patients rated as functionally normal (80%-100%) on the Karnofsky performance status (KPS) scale. METHODS: Cancer patients aged ≥65 years were assessed using a brief GA that included both professionally and patient-scored KPS and measures of comorbidity, polypharmacy, cognition, function, nutrition, and psychosocial status. Data were analyzed using descriptive statistics and multivariable logistic regression. RESULTS: The sample included 984 patients: mean age was 73 years (range: 65-99 years), 74% were female, and 89% were white. GA was conducted before (23%), during (41%), or after (36%) treatment. Overall, 54% had a breast cancer diagnosis (n = 528), and 46% (n = 456) had cancers at other sites. Moreover, 81% of participants (n = 796) had both professionally and self-rated KPS ≥80, defined as functionally normal, and those patients are the focus of analysis. In this subsample, 550 (69%) had at least 1 GA-identified deficit, 222 (28%) had 1 deficit, 140 (18%) had 2 deficits, and 188 (24%) had ≥3 deficits. Specifically, 43% reported taking ≥9 medications daily, 28% had decreased social activity, 25% had ≥4 comorbidities, 23% had ≥1 impairment in instrumental activities of daily living, 18% had a Timed Up and Go time ≥14 seconds, 18% had ≥5% unintentional weight loss, and 12% had a Mental Health Index score ≤76. CONCLUSION: Within this sample of older cancer patients who were rated as functionally normal by KPS, GA identified important deficits that could affect treatment tolerance and outcomes.

Feasibility of implementing a community-based randomized trial of yoga for women undergoing chemotherapy for breast cancer.

BACKGROUND: Treatment-related symptoms and decreased health-related quality of life (HRQoL) frequently occur during chemotherapy for breast cancer. Although research findings suggest that yoga can reduce symptoms and Improve HRQoL after treatment, potential benefits of yoga during chemotherapy have received minimal attention. OBJECTIVE: To estimate accrual, adherence, study retention, and preliminary efficacy of a yoga intervention compared with an active control group for breast cancer patients during chemotherapy. METHODS: Women with stage I-III breast cancer were recruited from 3 community cancer clinics and randomized to 10 weeks of gentle yoga or wellness education. Depressive symptoms, fatigue, sleep, and HRQoL were assessed at baseline, mid-intervention (Week 5), and after intervention (Week 10). RESULTS: 40 women aged 29-83 years (median, 48 years; 88% white) were randomized to yoga (n = 22) or wellness education (n = 18). The groups did not differ significantly on baseline characteristics, adherence, or study retention. Participant feedback was positive and comparable between groups. Meaningful within-group differences were identified For sleep adequacy and quantity in yoga participants and for somnolence in wellness-education participants. LIMITATIONS: Small sample size and lack of a usual-care control group. CONCLUSIONS: This study established Feasibility of a community-based randomized trial of yoga and an active comparison group for women undergoing chemotherapy for breast cancer. Preliminary efficacy estimates suggest that yoga improves sleep adequacy Symptom severity and interference remained stable during chemotherapy for the yoga group and snowed a trend toward increasing in the control group. The study highlighted obstacles to multisite yoga research during cancer treatment. FUNDING/SPONSORSHIP: National Cancer Institute (3U10 CA081851, PI; Shaw; R25 CA122061, PI: Avis); Translational Science Institute, Wake Forest School of Medicine.