Michael Messino

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 geriatric assessment in community oncology clinics.

OBJECTIVE Emerging results support the value of geriatric assessment (GA) in determining the risk and benefits of cancer treatment in older adults. A brief GA tool consisting of valid and reliable measures has been developed; however, little data exist on the ability to perform the GA in community oncology clinics. The objective of this study was to determine the feasibility of performing the GA in the community. MATERIALS AND METHODS Patients aged ≥65 were eligible. The GA included a health care provider assessment of performance status, cognitive function, a Timed Up and Go test, and a self-administered patient questionnaire that evaluated measures of functional status, comorbidity, psychological state, social support, and nutritional status. RESULTS From 2009 to 2013, 1088 patients were assessed including 339 (31%) from seven community clinics across North Carolina. The median amount of time to complete the patient-report portion of the GA was 19min in the academic center versus 22min in the community. The median amount of time to complete the entire GA was 23min in the academic center and 30min in community settings. Significantly more patients in the community required assistance completing the questionnaire (24% vs. 14%); however, most patients required no assistance (76%). CONCLUSION A brief GA can be performed in community oncology clinics. The time to complete the professional assessments and patient self-assessments were similar in both settings. Future studies are planned to determine if such assessments can improve cancer care for older patients.

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.

Sugar-Sweetened Beverage Intake and Cancer Recurrence and Survival in CALGB 89803 (Alliance)

Background In colon cancer patients, obesity, sedentary lifestyle, and high dietary glycemic load have been associated with increased risk of cancer recurrence. High sugar-sweetened beverage intake has been associated with obesity, diabetes, and cardio-metabolic diseases, but the influence on colon cancer survival is unknown. Methods We assessed the association between sugar-sweetened beverage consumption on cancer recurrence and mortality in 1,011 stage III colon cancer patients who completed food frequency questionnaires as part of a U.S. National Cancer Institute-sponsored adjuvant chemotherapy trial. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated with Cox proportional hazard models. Results Patients consuming ≥2 servings of sugar-sweetened beverages per day experienced an adjusted HR for disease recurrence or mortality of 1.67 (95% CI, 1.04–2.68), compared with those consuming <2 servings per month (P trend = 0.02). The association of sugar-sweetened beverages on cancer recurrence or mortality appeared greater among patients who were both overweight (body mass index ≥25 kg/m2) and less physically active (metabolic equivalent task-hours per week <18) (HR = 2.22; 95% CI, 1.29–3.81, P trend = 0.0025). Conclusion Higher sugar-sweetened beverage intake was associated with a significantly increased risk of cancer recurrence and mortality in stage III colon cancer patients.

Impact of Physical Activity After Cancer Diagnosis on Survival in Patients With Recurrent Colon Cancer: Findings From CALGB 89803/Alliance

BACKGROUND The impact of physical activity on survival outcomes in patients with recurrent colon cancer has not been studied. We tested the association between the level of postdiagnosis physical activity and survival outcomes of patients with recurrent colon cancer. PATIENTS AND METHODS We conducted a prospective observational study of 237 patients with stage III colon cancer who had recurrence of disease. Physical activity was measured approximately 6 months after the completion of therapy (14 months after surgical resection) but before detection of recurrent disease. The primary end point of the study was survival time after recurrence. RESULTS The hazard ratio comparing patients who reported at least 18 metabolic equivalent task (MET) hours per week of physical activity with those engaging in < 3 MET hours per week was 0.71 (95% confidence interval, 0.46-1.11). Increasing total MET hours of physical activity per week was associated with a borderline statistical significance trend for improved survival after recurrence (P = .052). The benefit of physical activity on survival was not significantly modified by sex, body mass index (BMI), number of positive lymph nodes, age, baseline performance status, adjuvant chemotherapy regimen, or recurrence-free survival period. CONCLUSION To our knowledge, this is the first study investigating the association of physical activity with survival outcome of patients with recurrent colon cancer. Although the association exceeded our predefined P trend < .05 for statistical significance, these findings warrant further studies of physical activity in patients with recurrent colorectal cancer.

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

Predicted vitamin D status and colon cancer recurrence and mortality in CALGB 89803 (Alliance)

Background Observational studies suggest that higher levels of 25-hydroxyvitamin D3 (25(OH)D) are associated with a reduced risk of colorectal cancer and improved survival of colorectal cancer patients. However, the influence of vitamin D status on cancer recurrence and survival of patients with stage III colon cancer is unknown. Patients and methods We prospectively examined the influence of post-diagnosis predicted plasma 25(OH)D on outcome among 1016 patients with stage III colon cancer who were enrolled in a National Cancer Institute-sponsored adjuvant therapy trial (CALGB 89803). Predicted 25(OH)D scores were computed using validated regression models. We examined the influence of predicted 25(OH)D scores on cancer recurrence and mortality (disease-free survival; DFS) using Cox proportional hazards. Results Patients in the highest quintile of predicted 25(OH)D score had an adjusted hazard ratio (HR) for colon cancer recurrence or mortality (DFS) of 0.62 (95% confidence interval [CI], 0.44-0.86), compared with those in the lowest quintile (Ptrend = 0.005). Higher predicted 25(OH)D score was also associated with a significant improvement in recurrence-free survival and overall survival (Ptrend = 0.01 and 0.0004, respectively). The benefit associated with higher predicted 25(OH)D score appeared consistent across predictors of cancer outcome and strata of molecular tumor characteristics, including microsatellite instability and KRAS, BRAF, PIK3CA, and TP53 mutation status. Conclusion Higher predicted 25(OH)D levels after a diagnosis of stage III colon cancer may be associated with decreased recurrence and improved survival. Clinical trials assessing the benefit of vitamin D supplementation in the adjuvant setting are warranted. 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.

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.