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Atherton P.J.,Alliance Statistics and Data Center | Watkins-Bruner D.W.,Emory University | Gotay C.,University of British Columbia | Moinpour C.M.,Fred Hutchinson Cancer Research Center | And 5 more authors.
Journal of Pain and Symptom Management | Year: 2015

Context Clinical trials use clinician-graded adverse events (AEs) and patient-reported outcomes (PROs) to describe symptoms. Objectives The aim of the study was to examine the agreement between PROs and AEs in the clinical trial setting. Methods Patient-level data were pooled from seven North Central Cancer Treatment Group, two Southwest Oncology Group, and three Radiation Therapy Oncology Group lung studies that included both PROs and AE data. Ten-point changes (on a 0-100 scale) in PRO scores were considered clinically significant differences (CSDs). PRO score changes were compared to AE grade (Gr) categories (2+ yes vs. no and 3+ yes vs. no) using Wilcoxon rank-sum or two-sample t-tests between Gr categories. Incidence rates and concordance of CSD in PRO scores and AE Gr categories were compiled. Spearman correlations were computed between PRO scores and AE severity. Results PROs completed by patients (n = 1013) were the Uniscale, Lung Cancer Symptom Scale (LCSS), Functional Assessment of Cancer Therapy-Lung (FACT-L), Symptom Distress Scale, and/or Functional Living Index-Cancer. Significantly worse PRO score changes were found for the FACT-L in patients with Gr 2+ AEs. Worse scores were seen for the Uniscale for patients with Gr 2+ AEs (P = 0.07) and LCSS for patients with Gr 3+ AEs (P = 0.09). Agreement between incidence of any Gr 2+ (Gr 3+) AE and a CSD in PROs ranged from 27% to 67% (36%-61%). Correlations between PRO scores and AE severity were low: -0.06 Uniscale, -0.03 LCSS, 0.10 FACT-L, -0.11 Symptom Distress Scale, and -0.51 Functional Living Index-Cancer. Conclusion These results support previous work and an a priori hypothesis that AEs and PROs measure differing aspects of the disease experience and are complementary. © 2015 American Academy of Hospice and Palliative Medicine.

McCleary N.J.,Dana-Farber Cancer Institute | Niedzwiecki D.,Duke University | Hollis D.,Duke University | Saltz L.B.,Sloan Kettering Cancer Center | And 6 more authors.
Cancer | Year: 2010

BACKGROUND: Cigarette smoking has been shown to increase the risk of developing colorectal cancer, particularly smoking early in life. Little is known about the impact of tobacco use on colon cancer recurrence among colon cancer survivors. METHODS: The authors prospectively collected lifetime smoking history from stage III colon cancer patients enrolled in a phase 3 trial via self-report questionnaires during and 6 months after completion of adjuvant chemotherapy. Smoking status was defined as never, current, or past. Lifetime pack-years were defined as number of lifetime packs of cigarettes. Patients were followed for recurrence or death. RESULTS: Data on smoking history were captured on 1045 patients with stage III colon cancer receiving adjuvant therapy (46% never smokers; 44% past; 10% current). The adjusted hazard ratio (HR) for disease-free survival (DFS) was 0.99 (95% confidence interval [CI], 0.70-1.41), 1.17 (95% CI 0.89-1.55), and 1.22 (95% CI 0.92-1.61) for lifetime pack-years 0-10, 10-20, and 20+, respectively, compared with never smoking (P = .16). In a preplanned exploratory analysis of smoking intensity early in life, the adjusted HR for 12+ pack-years before age 30 years for DFS was 1.37 (95% CI, 1.02-1.84) compared with never smoking (P = .04). The adjusted HR for DFS was 1.18 (95% CI, 0.92-1.50) for past smokers and 1.10 (95% CI, 0.73-1.64) for current smokers, compared with never smokers. CONCLUSIONS: Total tobacco usage early in life may be an important, independent prognostic factor of cancer recurrences and mortality in patients with stage III colon cancer. © 2010 American Cancer Society.

Meyerhardt J.A.,Dana-Farber Cancer Institute | Sato K.,Dana-Farber Cancer Institute | Niedzwiecki D.,Duke University | Ye C.,Duke University | And 9 more authors.
Journal of the National Cancer Institute | Year: 2012

Background The influence of glycemic load and related measures on survival among colon cancer patients remains largely unknown.MethodsWe conducted a prospective, observational study of 1011 stage III colon cancer patients reporting dietary intake during and 6 months after participation in an adjuvant chemotherapy trial. We examined the influence of glycemic load, glycemic index, fructose, and carbohydrate intakes on cancer recurrence and mortality using Cox proportional hazards regression; all tests of statistical significance were two-sided.ResultsStage III colon cancer patients in the highest quintile of dietary glycemic load experienced an adjusted hazard ratio (HR) for disease-free survival of 1.79 (95% confidence interval [CI] 1.29 to 2.48), compared with those in the lowest quintile (Ptrend across quintiles <.001). Increased glycemic load was associated with similar detriments in recurrence-free (Ptrend across quintiles <.001) and overall survival (Ptrend across quintiles <.001). These associations differed statistically significant by body mass index (BMI) (P interaction .01). Whereas glycemic load was not associated with disease-free survival in patients with BMI < 25kg/m2, higher glycemic load was statistically significant associated with worse disease-free survival among overweight or obese participants (BMI < 25kg/m2; HR 2.26; 95% CI 1.53 to 3.32; Ptrend across quintiles <.001). Increasing total carbohydrate intake was similarly associated with inferior disease-free, recurrence-free, and overall survival (Ptrend across quintiles <.001).ConclusionHigher dietary glycemic load and total carbohydrate intake were statistically significant associated with an increased risk of recurrence and mortality in stage III colon cancer patients. These findings support the role of energy balance factors in colon cancer progression and may offer potential opportunities to improve patient survival. © 2012 The Author.

Ng K.,Dana-Farber Cancer Institute | Ogino S.,Dana-Farber Cancer Institute | Ogino S.,Harvard University | Meyerhardt J.A.,Dana-Farber Cancer Institute | And 16 more authors.
Journal of the National Cancer Institute | Year: 2011

Background Although preclinical and epidemiological data suggest that statins may have antineoplastic properties, the impact of statin use on patient survival after a curative resection of stage III colon cancer is unknown. Methods We conducted a prospective observational study of 842 patients with stage III colon cancer enrolled in a randomized adjuvant chemotherapy trial from April 1999 to May 2001 to investigate the relationship between statin use and survival. Disease-free survival (DFS), recurrence-free survival (RFS), and overall survival (OS) were investigated by Kaplan-Meier curves and log-rank tests in the overall study population and in a subset of patients stratified by KRAS mutation status (n = 394), and Cox proportional hazards regression was used to assess the simultaneous impact of confounding variables. All statistical tests were two-sided. Results Among 842 patients, 134 (15.9%) reported statin use after completing adjuvant chemotherapy. DFS among statin users and nonusers was similar (hazard ratio [HR] of cancer recurrence or death = 1.04, 95% confidence interval [CI] = 0.73 to 1.49). RFS and OS were also similar between statin users and nonusers (adjusted HR of cancer recurrence = 1.14, 95% CI = 0.77 to 1.69; adjusted HR of death = 1.15, 95% CI = 0.77 to 1.71). Survival outcomes were similar regardless of increasing duration of statin use before cancer diagnosis (Ptrend =. 63,. 63, and. 59 for DFS, RFS, and OS, respectively). The impact of statin use did not differ by tumor KRAS mutation status, with similar DFS, RFS, and OS for statin use among mutant and wild-type subgroups (Pinteraction =. 84,. 67, and. 98 for DFS, RFS, and OS, respectively). Conclusion Statin use during and after adjuvant chemotherapy was not associated with improved DFS, RFS, or OS in patients with stage III colon cancer, regardless of KRAS mutation status. © The Author 2011. Published by Oxford University Press.

Ogino S.,Dana-Farber Cancer Institute | Ogino S.,Harvard University | Liao X.,Dana-Farber Cancer Institute | Imamura Y.,Dana-Farber Cancer Institute | And 17 more authors.
Journal of the National Cancer Institute | Year: 2013

Background Somatic mutations in PIK3CA (phosphatidylinositol-4,5- bisphosphonate 3-kinase [PI3K], catalytic subunit alpha gene) activate the PI3K-AKT signaling pathway and contribute to pathogenesis of various malignancies, including colorectal cancer. Methods We examined associations of PIK3CA oncogene mutation with relapse, survival, and treatment efficacy in 627 stage III colon carcinoma case subjects within a randomized adjuvant chemotherapy trial (5-fluorouracil and leucovorin [FU/LV] vs irinotecan [CPT11], fluorouracil and leucovorin [IFL]; Cancer and Leukemia Group B 89803 [Alliance]). We detected PIK3CA mutation in exons 9 and 20 by polymerase chain reaction and pyrosequencing. Cox proportional hazards model was used to assess prognostic and predictive role of PIK3CA mutation, adjusting for clinical features and status of routine standard molecular pathology features, including KRAS and BRAF mutations and microsatellite instability (mismatch repair deficiency). All statistical tests were two-sided. Results Compared with PIK3CA wild-type cases, overall status of PIK3CA mutation positivity or the presence of PIK3CA mutation in either exon 9 or 20 alone was not statistically significantly associated with recurrence-free, diseasefree, or overall survival (log-rank P > .70; P > .40 in multivariable regression models). There was no statistically significant interaction between PIK3CA and KRAS (or BRAF) mutation status in survival analysis (Pinteraction > .18). PIK3CA mutation status did not appear to predict better or worse response to IFL therapy compared with FU/LV therapy (Pinteraction > .16). Conclusions Overall tumor PIK3CA mutation status is not associated with stage III colon cancer prognosis. PIK3CA mutation does not appear to serve as a predictive tumor molecular biomarker for response to irinotecan-based adjuvant chemotherapy. © The Author 2013.

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