Search

BackgroundObservational 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 methodsWe 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.ResultsPatients 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.ConclusionHigher 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 identifierNCT00003835.

The bone marrow transplant recipient is unique. Multiple sequelae may arise as a result of the procedure and many of these effects may be pertinent to the planning and administration of anaesthesia. The results indicate that knowledge of these idiosyncrasies accompanied by careful and directed evaluation of each patient should permit the delivery of safe anaesthesia. [ABSTRACT FROM AUTHOR]

The results of partially matched related donor (PMRD) marrow transplantation for 82 patients with leukemia are reported, including 45 who received two antigen disparate grafts. Following intensive radiochemotherapy, patients received grafts which were partially depleted of T cells by the monoclonal antibody T10B9 and complement. Actuarial probability of engraftment was 86% (95% CI = 78–93%). The median day to engraftment was similar among recipients of grafts disparate at one, two or three antigen loci. The incidence of severe (grades III and IV) acute graft-versus-host disease and extensive chronic graft-versus-host disease was 13% and 6%, respectively. The probability of disease-free survival for the entire cohort of patients is 31% at 3 years. Age 30 years, early or intermediate stage disease and a graft disparate at one or two loci predicted longer disease-free survival in multivariant analysis. Moreover, 47% of patients receiving PMRD grafts disparate at two loci who had both these favorable pre-transplant characteristics were alive and free of disease 3 years after transplantation. We believe that the utilization of PMRDs, especially those with two antigen disparate grafts, can extend allogeneic transplantation to additional leukemic patients lacking a histocompatible donor, with acceptable results. [ABSTRACT FROM AUTHOR]

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., Competing Interests: En ChengStock and Other Ownership Interests: Pfizer Fang-Shu OuConsulting or Advisory Role: SC Liver Research Consortium Leonard B. SaltzResearch Funding: Taiho Pharmaceutical Robert J. MayerConsulting or Advisory Role: Bayer Renaud WhittomConsulting or Advisory Role: AstraZenecaResearch Funding: Canadian Cancer Trials Group (Inst) Al BensonConsulting or Advisory Role: Merck Sharp & Dohme, Array BioPharma, Bristol Myers Squibb, Samsung Bioepis, Pfizer, HalioDx, AbbVie, Janssen Oncology, Natera, Apexigen, Artemida Pharma, Xencor, Therabionic, Mirati Therapeutics, Boston ScientificResearch Funding: Infinity Pharmaceuticals (Inst), Merck Sharp & Dohme (Inst), Taiho Pharmaceutical (Inst), Bristol Myers Squibb (Inst), Celgene (Inst), Rafael Pharmaceuticals (Inst), MedImmune (Inst), Xencor (Inst), Astellas Pharma (Inst), Amgen (Inst), Syncore (Inst), Elevar Therapeutics (Inst), Tyme Inc (Inst), ST Pharm (Inst), ITM Solucin (Inst) Daniel AtienzaEmployment: US Oncology Hedy KindlerHonoraria: AstraZenecaConsulting or Advisory Role: AstraZeneca, Bristol Myers Squibb, Deciphera, Novocure, Seattle Genetics, InhibrxResearch Funding: Aduro Biotech (Inst), AstraZeneca (Inst), GlaxoSmithKline (Inst), Merck (Inst), Verastem (Inst), Bristol Myers Squibb (Inst), Polaris (Inst), Deciphera (Inst), Inhibrx (Inst), Roche/Genentech (Inst), Tesaro (Inst), Macrogenics (Inst), Leap Therapeutics (Inst), Fibrogen (Inst), Vivace Therapeutics (Inst), Constellation Pharmaceuticals (Inst), Harpoon therapeutics (Inst), Bayer (Inst), Seattle Genetics (Inst), Blueprint Medicines (Inst)Travel, Accommodations, Expenses: AstraZeneca Kimmie NgConsulting or Advisory Role: Seattle Genetics, X-Biotix Therapeutics, Array BioPharma, BiomX, Bicara TherapeuticsResearch Funding: Pharmavite (Inst), Revolution Medicines (Inst), Evergrande Group (Inst), Janssen (Inst) Cary P. GrossResearch Funding: Johnson & Johnson (Inst), AstraZeneca (Inst), GenentechUncompensated Relationships: Genentech (Inst) Jeffrey A. MeyerhardtHonoraria: Cota Healthcare, Taiho PharmaceuticalResearch Funding: Boston Biomedical (Inst) Charles S. FuchsEmployment: Genentech/RocheLeadership: CytomX Therapeutics, Evolveimmune TherapeuticsStock and Other Ownership Interests: CytomX Therapeutics, Entrinsic Health, Evolveimmune Therapeutics, Roche/GenentechConsulting or Advisory Role: Sanofi, Merck, Entrinsic Health, Agios, Taiho Pharmaceutical, Genentech/Roche, CytomX Therapeutics, Unum Therapeutics, Bain Capital, Lilly, Amylin, Daiichi-Sankyo, Evolveimmune Therapeutics, AstraZeneca, AstraZenecaExpert Testimony: Lilly, AmylinNo other potential conflicts of interest were reported.

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.

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., (© The Author(s) 2021. Published by Oxford University Press.)

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., (©2020 American Association for Cancer Research.)

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., (© The Author(s) 2018. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

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., Competing Interests: I have read the journal's policy and the authors of this manuscript have the following competing interests: Dr. Ana Babic owns stock in Biogen. Dr. Emilie Zoltick owns stock in Baxter International, Bristol Myers Squibb, Cardinal Health, CVS Health, Pfizer, Shire and Zimmer Biomet. Dr. Leonard Saltz has a consulting or advisory role with Lilly and Abbvie, and has an immediate family member with a consulting or advisory role with McNeil PPC. Dr. Leonard Saltz also receives research funding from Taiho Pharmaceutical. Dr. Robert Mayer has a consulting or advisory role with CASI Pharmaceuticals and has received honoraria from Taiho Pharmaceutical. Dr. Renaud Whittom has a consulting or advisory role with Boehringer Ingelheim, Astra-Zeneca, Pfizer, and Bristol-Myers Squibb, has received honoraria from Astra-Zeneca and Astellas, receives research funding from Astellas, Genentech-Roche, and has received travel, accommodations, or other expenses from Seattle Genetics and Celgene. Dr. Alexander Hantel has received travel, accommodations or other expenses from Genentech. Dr. Al Benson has a consulting or advisory role with Genentech/Roche, Bristol-Myers Squibb, Merck Serono, Celgene, Vicus Therapeutics, Pharmacyclics, Precision Therapeutics, Taiho Pharmaceutical, Bayer, Alchemia, Infinity Pharmaceuticals, Boehringer Ingelheim, Astellas Pharma, EMD Serono, IntegraGen, Guardant Health, Opsona Therapeutics, Lexicon, Novartis, Boston Biomedical, Helsinn, Guerbet, Lilly, Spectrum Pharmaceuticals, Advanced Accelerator Applications, Bayer/Onyx, TRM Oncology, DAVA Pharmaceuticals, Sanofi, and Lilly/ImClone. Dr. Al Benson has received research funding from Gilead Sciences, Amgen, Astellas Pharma, advanced accelerator applications, Bayer/Onyx, Novartis, Alchemia, AVEO, Infinity Pharmaceuticals, Genentech/Roche, Merck Sharp & Dohme, and Taiho Pharmaceutical. Dr. Al Benson has received travel, accommodations, or other expenses from Genentech/Roche, Lilly/ImClone, Bayer, Sanofi, Spectrum Pharmaceuticals, AVEO, Gilead Sciences, Astellas Pharma, Boehringer Ingelheim, DAVAOncology, TRM Oncology, Guardant Health, Helsinn, Guerbet, and Boston Biomedical. Dr. Daniel Atienza has been employed by McKesson US Oncology. Dr. Hedy Lee Kindler has had a consulting or advisory role with Aduro Biotech, MedImmune, Bayer, Genentech/Roche, Verastem, Celgene, GlaxoSmithKline, Plexxikon, AstraZeneca, and Merck, has received research funding from Aduro Biotech, AB Science, Astellas Pharma, AstraZeneca, Bayer, Celgene, GlaxoSmithKline, Incyte, Merck, MedImmune, Verastem, Bristol-Myers Squibb, and Lilly, and has given expert testimony for Aduro Biotech. Dr. Alan Venook has had a consulting or advisory role with Gilead Sciences, has received research funding from Genentech/Roche, has received honoraria from Gilead Sciences, has received travel, accommodations, or other expenses from Genentech, and has received royalties from UpToDate for authoring and maintaining two chapters. Dr. Charles Fuchs has had a consulting or advisory role with Lilly, Sanofi, Bayer, Merck, Entrinsic Health, Five Prime Therapeutics, Agios, Gilead Sciences, Dicerna, Merrimack, Taiho Pharmaceutical, KEW Group, and Genentech/Roche. The remaining authors have declared that they have no competing interests to disclose. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

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.

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; P trend = .03) and an HR for overall survival of 0.43 (95% CI, 0.25 to 0.74; P trend = .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; P trend = .04; and HR for overall survival, 0.47; 95% CI, 0.27 to 0.82; P trend = .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.

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; P trend = 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; P trend = 0.007), and OS (HR 0.68; 95% CI, 0.48-0.96; P trend = 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; P trend = 0.01) compared with patients with absent/low PTGS2 expression (HR 0.78; 95% CI, 0.48-1.27; P trend = 0.35; P interaction = 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 ., (©2018 American Association for Cancer Research.)

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 ( P trend = .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 ( P trend = .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.

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., (© 2015 by American Society of Clinical Oncology.)

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., (©AlphaMed Press.)

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 ≥ 2 5 kg/m(2)) 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.

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., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Clinical charts from 63 consecutive highly immunocompromised haematologic patients presenting with pulmonary nodular lesions on CT scan, classified as either probable or possible invasive fungal disease (IFD) according to the revised EORTC/MSG classification, were retrospectively studied. Histopathological analysis of lung tissues, available for 23 patients, demonstrated proven IFD in 17 cases (14 invasive aspergillosis and 3 invasive zygomycosis), diffuse alveolar damage in one and organising pneumonia (OP) in five cases. In the OP cases, three of which have been defined as probable IFD according to EORTC/MSG classification, extensive immunohistochemical, molecular and immunological analyses for fungi were negative. Our case descriptions extend the notion that OP may be encountered as a distinct histopathological entity in pulmonary nodular lesions in patients with leukaemia with probable/possible IFD.

Several reports have suggested that breast cancer patients with elevated serum levels of interleukin-6 (IL-6) have a worse prognosis than patients with lower levels. We have studied IL-6 in breast cancer cell lines and have shown that autocrine production of IL-6 can confer multi-drug resistance in vitro by inducing multidrug resistance gene-1 transcription with subsequent overexpression of P-glycoprotein (PGP). Both IL-6 and PGP expression can be measured in malignant cells using immunohistochemical (IHC) techniques. We hypothesized that patients whose tumors expressed higher amounts of IL-6 or PGP would be less likely to respond to paclitaxel, an agent affected by the PGP pathway. If so, then IL-6 could serve as a predictive factor for paclitaxel sensitivity. Both IL-6 and PGP expression were measured in patients treated in a randomized trial that compared three doses of single agent paclitaxel (175, 210, and 250 mg/m(2) over 3 h every 3 weeks) in 469 women with metastatic breast cancer (CALGB 9342). No difference in complete and partial response was found among the three treatment arms. Tissue blocks in this trial were analyzed for IL-6 (154 patients) and PGP (149 patients) in paraffin-embedded sections from tumor samples; clinical characteristics of these patients were similar to the total sample of 469 patients. There were no significant differences among IL-6 or PGP scores whether measured as continuous or dichotomous variables, or by other scoring, and response to paclitaxel. In multivariate analysis neither IL-6 nor PGP was a significant predictor of time to progression or overall survival. IHC expression of IL-6 and PGP levels in tumor cells is not a predictive marker for response to paclitaxel in women with metastatic breast cancer.

Allogeneic BMT provides the best treatment currently available for long-term disease-free survival in patients with recurrent ALL. Historically, partially matched related donors provided the opportunity for treatment to a greater number of patients than matched related donors at the expense of decreased overall survival. In this study we compare the results in recurrent ALL patients transplanted with either HLA identical sibling bone marrow or partially matched related bone marrow. Thirty-two patients with relapsed ALL received partially matched bone marrows from a relative with one to three HLA, A, B and Dr antigen mismatches. Bone marrow was partially T cell-depleted with murine T10B9.1A-31 moAb. Sixteen patients with relapsed ALL received HLA-matched sibling bone marrows. All partially matched patients received additional GVHD prophylaxis with methylprednisolone in addition to anti-CD5 immunotoxin and/or CYA. All matched patients in addition to methylprednisolone received MTX and/or CYA. We observed no difference in disease-free survival between patients transplanted with partially matched bone marrow (median follow-up 1252 days, range 778-2035 days) vs those transplanted with HLA-matched bone marrow (median follow-up 1472 days, range 1165-2800 days; P = 0.48). Median survival for all patients is 38% (95% CI 24-52%) at 6 years. Patients transplanted in remission had a significant increase in disease-free survival when compared to those in relapse (P = 0.007). Our data suggest that partially matched BMTs from related donors are a comparable alternative to fully matched transplants in patients with ALL.

Granulocyte macrophage-colony-stimulating factor (GM-CSF) has shown promise as a means of alleviating leukopenia associated with a wide variety of disorders. It is currently undergoing evaluation as an adjunct to bone marrow transplantation but its use in patients with metabolic disorders, such as Hurler's syndrome (HS), has not been explored. We followed bone marrow morphology in a 2-year-old male with HS who received up to 8 micrograms/kg GM-CSF per day because of failure of allogeneic bone marrow engraftment. Both premortem and postmortem bone marrow sampling revealed almost complete replacement of the marrow space by sheets of histiocytes demonstrating metachromatic cytoplasmic granules. Such cells were present in far greater numbers than are usually seen in untreated patients with HS or patients with HS undergoing successful bone marrow transplantation without GM-CSF. Moreover, the in vitro culture of bone marrow from a second HS patient showed a GM-CSF dose-related increase in colony formation up to a dose of 250 units/ml. Microscopic examination of these colonies showed a high percentage of histiocytes identical to those seen in the patient's bone marrow. These observations suggest that caution should be exercised when considering administration of CSFs to patients with HS and similar metabolic storage diseases.

Bone marrow transplantation (BMT) has become a widely used procedure in the treatment of numerous hematological and non-hematological clinical disorders. The preparative regimen used for marrow recipients is not without risk as the immunodeficient recipient is susceptible to life-threatening infections due to the inability of the marrow to engraft properly. The monovalent cation lithium has been demonstrated to influence regenerating hematopoiesis following the use of several agents known to suppress hematopoiesis. The following report summarizes our studies which have been designed to determine the rate of hematopoietic reconstitution in lethally irradiated mice that were transplanted with bone marrow cells, harvested from either syngeneic or allogeneic donor animals, treated with lithium or phosphate buffered saline (PBS). Transplanted recipients receiving marrow cells from lithium treated donors were evaluated for their survival, peripheral blood indices and several classes of hematopoietic progenitors (granulocyte, erythroid, and megakaryocyte). Transplanted animals that received marrow cells from either syngeneic or allogeneic donors treated with lithium demonstrated greater survival, increased recovery of peripheral indices and hematopoietic progenitors compared to PBS-treated controls. These results indicate that the use of lithium to treat the donor may be an effective procedure to enhance hematopoietic recovery and engraftment in the transplanted recipient. Because of its wide-ranging effects, the use of lithium as a single agent, may be more efficacious than administering several hematopoietic growth factors in order to achieve a similar response.

Bone marrow transplantation (BMT) is discussed in terms of immunology, procedures, and complications and their treatment. Any patient with a disorder of the hematopoietic or immune system or a disease in which a transferable hematopoietic cell can supply a missing enzyme is a candidate for BMT. A priority in allogeneic BMT is the identification of a compatible donor through matching of human lymphocyte antigens (HLAs). The greater the disparity in HLAs, the greater the chance of rejection. The ideal donor is a monozygotic twin or an HLA-matched sibling, but only 30% of patients have such a donor. Before receiving the bone marrow infusion, patients must be conditioned to create space in the marrow for donor cells, suppress the immune system, and eradicate any tumor in patients with malignancies. Conditioning is achieved by the combination of total body irradiation and cyclophosphamide treatment; busulfan, etoposide, and cytarabine have also been used. For patients given unmanipulated marrow, the number of nucleated cells infused is about 3 X 10(8) per kilogram. Signs of engraftment are usually seen 14-21 days later. Toxic effects related to conditioning appear during this period and include infection, gastroenteritis, mucositis, and congestive heart failure. The most serious complication is graft-versus-host disease (GVHD), which can affect multiple organ systems. Prednisone, methylprednisolone, methotrexate, antithymocyte globulin, and cyclosporine have been used in an effort to prevent or treat GVHD. Bone marrow transplantation offers the chance of long-term survival to many patients with terminal disease, but associated morbidity and mortality rates remain high. Research is needed to address the problems of infection, leukemic relapse, and GVHD and the difficulty in obtaining and matching donors.

Interleukin-1 (IL-1), a cytokine, primarily produced by monocytes, is the molecule involved in mediating many of the body's responses associated with infection and inflammation. More recently, IL-1 has been shown to sustain elevated levels of circulating granulocytes, stimulate the production of granulocyte-macrophage colony stimulating factors (CSFs) in vitro, increase plasma levels of CSF, and act synergistically with CSFs to increase the number of granulocyte-macrophage progenitors (colony-forming units) (CFU-GM) in vitro. The purpose of this study was to investigate the effect of murine IL-1 on steady-state hematopoiesis in vivo. C3H/HeJ or its normal littermate C3H/HeN male mice were administered either murine recombinant IL-1 at 45, 50, 200, 225, or 900 units (0.0125-0.25 micrograms)/animal, or 200 units (0.05 micrograms) of semipurified IL-1 derived from P388D1 cell culture supernatants. Because one of the responses to IL-1 is increased prostaglandin (PG) production and with the known activity of PGs on hematopoiesis, additional studies incorporated the cyclooxygenase inhibitor indomethacin (IM) (10 mg/kg body weight). In order to study the effect of IL-1 in vivo on pluripotential progenitors (CFU-S), IL-1 was compared with recombinant murine GM-CSF (50, 200, and 900 units; 0.0125, 0.05, and 0.25 micrograms). Control groups consisted of animals receiving either lipopolysaccharide (0.5 mg/kg body weight) or phosphate-buffered saline where appropriate. After 24 h, animals were sacrificed, and their peripheral blood indices and stem cell content of both bone marrow and spleen were evaluated for various committed hematopoietic progenitors: CFU-GM, CFU-Meg, CFU-E, BFU-E, and CFU-DG. Circulating neutrophils were increased following IL-1; however, this increase was reduced following IM. IL-1 marrow-derived CFU-GM, CFU-E, BFU-E, and CFU-Meg were below controls. In contrast, splenic CFU-GM and CFU-Meg were significantly elevated with increasing IL-1 concentrations. Erythroid progenitors were increased following low IL-1 concentrations and reduced in animals receiving IM, thus indicating a role for prostaglandins in the mechanism of IL-1 for influencing hematopoiesis. CFU-DG were increased, however, only when animals were pretreated with IL-1 and their cells implanted into normal hosts, not when normal cells were implanted into animals pretreated with IL-1, indicating a potential target cell effect rather than an indirect, factor-related response.(ABSTRACT TRUNCATED AT 400 WORDS)

Radiation exposure to various systems can result in the development of severe toxicity, known as the acute radiation syndrome, with hematopoietic tissues being acutely susceptible to radiation-induced injury. Usually it is the degree of hematopoietic toxicity that determines the feasibility of further tumor control doses of therapy. Therefore the development of agents capable of protecting hematopoietic tissues could have important clinical applications. The cytokine interleukin-1 (IL-1) has been demonstrated to be an effective agent capable of protecting hematopoietic tissues in vivo from the toxicity associated with radiation exposure. We report here the results of studies designed to further investigate the capability of various cytokines (IL-1 and interleukins-2 and -3) to protect bone marrow-derived hematopoietic progenitors [granulocyte-macrophage and megakaryocyte colony-forming units (CFU-GM and CFU-Meg)] from radiation exposure in vitro. Only IL-1 was effective in protecting CFU-GM and CFU-Meg from radiation-induced toxicity in the range of 1-10 U/ml; however, no protection was observed when the radiation dose was greater than 300 rad. The ability of IL-1 to block radiation-induced toxicity was negated in the presence of an antibody to IL-1. These studies provide further information on the effectiveness of IL-1 in protecting in vitro hematopoietic tissues from toxicity associated with radiation exposure.