Period 1 and estrogen receptor-beta are downregulated in Chinese colon cancers.

To investigate whether Period 1 (PER1) and Estrogen receptor-beta (ER2) are associated with occurrence and development of Chinese colorectal cancers. By using RT-quantitative PCR, tissue microarray (TMA) and immunohistochemistry, we detected mRNA levels and protein levels of PER1 and ER2 in the cancerous tissues and paired normal adjacent tissues in patients with colorectal cancer. Survival analyses were performed by the Kaplan-Meier method utilizing log-rank test and univariate and multivariate Cox proportional modeling to measure 5-year disease-free survival (DFS) and overall survival (OS). Real-time PCR showed that, the delta Ct value (tumor tissue vs. normal mucosa) of PER1 or ER2 is 8.51 ± 2.81 vs. 7.34 ± 2.08 or 12.39 ± 2.43 vs. 9.76 ± 1.75, expression of PER1 and ER2 decreased significantly in tumor tissues compared with noncancerous mucosas of patients with or without metastasis (both of P values <0.001). Spearman test revealed that PER1 and ER2 were significantly down-regulated in cancerous tissues (r=0.283; P<0.001) which was also confirmed by immunohistochemistry of specimens from 203 colon cancer patients in a TMA format. The reduction of PER1 was associated with gender and distant metastasis (P=0.037 and P<0.001, respectively) whereas the decline of ER2 was associated with age (P=0.043) by analyzing the clinical data. However, we were not capable of detecting any association between PER1 level or ER2 level and overall survival (OS) or disease free survival (DFS). It is the first observation of correlated reduction of PER1 and ER2 in Chinese colon cancers, and they do play a certain role in colorectal cancer.

Fibre intake and incident colorectal cancer depending on fibre source, sex, tumour location and Tumour, Node, Metastasis stage.

Studies on fibre intake and incident colorectal cancer (CRC) indicate inverse associations. Differences by tumour stage have not been examined. We examined associations between fibre intake and its sources, and incidental CRC. Separate analyses were carried out on the basis of sex, tumour location and the Tumour, Node, Metastasis (TNM) classification. The Malmö Diet and Cancer Study is a population-based cohort study, including individuals aged 45-74 years. Dietary data were collected through a modified diet history method. The TNM classification was obtained from pathology/clinical records and re-evaluated. Among 27 931 individuals (60% women), we found 728 incident CRC cases during 428 924 person-years of follow-up. Fibre intake was inversely associated with CRC risk (P(trend) = 0.026). Concerning colon cancer, we observed borderline interaction between fibre intake and sex (P = 0.052) and significant protective association restricted to women (P(trend) = 0.013). Intake of fruits and berries was inversely associated with colon cancer in women (P(trend) = 0.022). We also observed significant interactions between intakes of fibre (P = 0.048) and vegetables (P = 0.039) and sex on rectal cancer, but no significant associations were seen between intake of fibre, or its sources, in either of the sexes. Except for inverse associations between intake of fibre-rich cereal products and N0- and M0-tumours, we did not observe significant associations with different TNM stages. Our findings suggest different associations between fibre intake and CRC depending on sex, tumour site and fibre source. High fibre intake, especially from fruits and berries, may, above all, prevent tumour development in the colon in women. No clear differences by TNM classification were detected.

How do integrated health care systems address racial and ethnic disparities in colon cancer?

PURPOSE: Colorectal cancer (CRC) disparities have persisted over the last two decades. CRC is a complex disease requiring multidisciplinary care from specialists who may be geographically separated. Few studies have assessed the association between integrated health care system (IHS) CRC care quality, survival, and disparities. The purpose of this study was to determine if exposure to an IHS positively affects quality of care, risk of mortality, and disparities. PATIENTS AND METHODS: This retrospective secondary-data analysis study, using the California Cancer Registry linked to state discharge abstracts of patients treated for colon cancer (2001 to 2006), compared the rates of National Comprehensive Cancer Network (NCCN) guideline-based care, the hazard of mortality, and racial/ethnic disparities in an IHS versus other settings. RESULTS: More than 30,000 patient records were evaluated. The IHS had overall higher rates of adherence to NCCN guidelines. Propensity score-matched Cox models showed an independent and protective association between care in the IHS and survival (hazard ratio [HR], 0.87; 95% CI, 0.85 to 0.90). This advantage persisted across stage groups. Black race was associated with increased hazard of mortality in all other settings (HR, 1.15; 95% CI, 1.04 to 1.27); however, there was no disparity within the IHS for any minority group (P > .11 for all groups) when compared with white race. CONCLUSION: The IHS delivered higher rates of evidence-based care and was associated with lower 5-year mortality. Racial/ethnic disparities in survival were absent in the IHS. Integrated systems may serve as the cornerstone for developing accountable care organizations poised to improve cancer outcomes and eliminate disparities under health care reform.

The completeness of cancer treatment data on the National Health Collections.

The New Zealand Ministry of Health (MoH) maintains a number of National Collections, which contain data on diagnoses, procedures and service provision for patients. There are concerns that these collections may underestimate the provision of cancer treatment, but the extent to which this is true is largely unknown. In this brief report, we focus on the Auckland region to illustrate the extent to which the National Collections undercount receipt of surgery in patients with breast, colon or renal cancer, and receipt of chemo- and/or radiotherapy for breast cancer patients with regional extent of disease (all diagnosed 2006-2008). We collected treatment data from the National collections and augmented this with data from Cancer Centres, breast cancer registers, private hospitals and personal clinician databases. The National Collections were used to determine 'baseline' treatment data, and we then compared receipt of treatment to that observed on the augmented dataset. We found that the National Collections undercounted receipt of surgery by 13-19%, and receipt of chemo- or radiotherapy for breast cancer patients by 18% and 16% respectively. Our observations clearly point toward (1) a non-reporting private hospital 'effect' on surgery data completeness; and (2) underreporting of adjuvant therapy to the MoH by service providers.

Association between adherence to National Comprehensive Cancer Network treatment guidelines and improved survival in patients with colon cancer.

BACKGROUND: The objective of the current study was to examine the impact of adherence to guidelines on stage-specific survival outcomes in patients with stage III and high-risk stage II colon cancer. The National Comprehensive Cancer Network (NCCN) has established working, expert consensus, and evidence-based guidelines for organ-specific cancer care, including care of patients with colon cancer. METHODS: Patients who were diagnosed with colon adenocarcinoma between 1998 and 2002 were selected from within the National Cancer Data Base. The cohort was limited to patients who received their first course of treatment at the reporting facility. Pathologic variables, including tumor depth, lymph node status, and evidence of metastatic disease, were used to restage patients, and the patients were divided into low-risk and high-risk categories on the basis of criteria defined by the NCCN. Relative survival rates were calculated for the entire cohort, stratified according to adherence versus nonadherence to NCCN treatment guidelines. RESULTS: In univariate analysis of treatment adherence patterns for both patient subgroups (high-risk stage II and stage III), several factors were associated with a higher rate of nonadherence in both groups, including older age (P < .001); Medicaid, Medicare, or uninsured status versus private insurance (P < .001); and subsequent treatment at a facility other than the facility at which the cancer was first diagnosed (P < .001). In multivariate analysis, multiple factors were associated with differences in relative survival, although analyses that included the year of diagnosis did not demonstrate significant differences over time. CONCLUSIONS: The current study documented practice patterns in a heterogeneous population of patients with colon cancer and demonstrated a survival benefit for patients with stage III and high-risk stage II colon cancer who received treatment that adhered to NCCN guidelines. These data validate the current NCCN practice guidelines for colon cancer and support the concept of guideline-based metrics that can be compared across institutions to assess the quality of cancer care and to compare the quality of cancer care among institutions.

FOLFOX4 in the adjuvant treatment of colon cancer in Asian patients.

Colorectal cancer (CRC) is a leading cause of cancer death worldwide. Surgery is the only way to potentially cure the disease and may be accomplished in 70% to 80% of newly diagnosed cases. However, 40% to 50% of patients who undergo surgery alone ultimately relapse and die of metastatic disease. Adjuvant chemotherapy, which has been developed to reduce the recurrence of CRC, has evolved from the single agent fluorouracil (5FU) to combinations with oxaliplatin, which now have an established role in stage III CRC. FOLFOX4 has been widely used as an adjuvant treatment of CRC, including the Asia-Pacific region. Adjuvant chemotherapy for CRC has been extensively investigated in the West but whether treatment outcomes in Asian individuals vary due to racial differences is uncertain. Racial differences should be considered, and differences in outcomes have been shown in patients with non-small cell lung cancer (NSCLC) treated with epidermal growth factor receptor tyrosine kinase inhibitors. This article critically reviews the evolution of adjuvant chemotherapy in CRC and focuses on the side effects of FOLFOX4 when administered to Asian patients for the adjuvant treatment of CRC. Comparisons of the tolerability of FOLFOX4 in different races from well-designed studies conducted in the West and Asia will be reviewed.

Racial disparities in receipt and comparative effectiveness of oxaliplatin for stage III colon cancer in older adults.

BACKGROUND: African Americans in the United States have higher rates of colon cancer mortality than other races. This study examines the use of oxaliplatin, a novel chemotherapeutic agent approved in 2004, among African American and Caucasian American patients with stage III colon cancer to determine whether differential receipt or differential effectiveness of the drug may explain the racial disparity in colon cancer mortality. METHODS: The authors conducted a population-based retrospective cohort study of stage III colon cancer patients aged 65 years and older treated from 2004 through 2006 who initiated chemotherapy within 90 days of surgical resection (N = 1162) using Surveillance, Epidemiology and End Results-Medicare data. Patients receiving oxaliplatin (n = 477) were compared with those receiving 5-fluorouracil without oxaliplatin (n = 685). The authors estimated prevalence ratios and hazard ratios (HRs) using multivariate binomial regression and Cox models to evaluate racial differences in oxaliplatin receipt and survival. RESULTS: African Americans were as likely as Caucasian Americans to receive oxaliplatin (40.5 vs 41.1%; prevalence ratio, 0.90; 95% confidence interval [CI], 0.71-1.13). Oxaliplatin was associated with lower mortality compared with 5-fluorouracil (HR, 0.76; 95% CI, 0.58-1.00). This benefit appeared stronger among African Americans (HR, 0.31; 95% CI, 0.09-1.05) than Caucasian Americans (HR, 0.80; 95% CI, 0.60-1.06). CONCLUSIONS: In Medicare-insured patients receiving chemotherapy, the authors observed no meaningful racial disparities in receipt of oxaliplatin and, among those receiving it, potentially better survival among African Americans. Differential receipt and effectiveness of oxaliplatin-containing regimens does not appear to contribute to the previously documented racial disparities in colon cancer survival. Understanding reasons for potentially enhanced effectiveness among African Americans may inform efforts to resolve racial disparities in colon cancer outcomes.

Outcomes among black patients with stage II and III colon cancer receiving chemotherapy: an analysis of ACCENT adjuvant trials.

BACKGROUND: Among patients with resected colon cancer, black patients have worse survival than whites. We investigated whether disparities in survival and related endpoints would persist when patients were treated with identical therapies in controlled clinical trials. METHODS: We assessed 14,611 patients (1218 black and 13,393 white) who received standardized adjuvant treatment in 12 randomized controlled clinical trials conducted in North America for resected stage II and stage III colon cancer between 1977 and 2002. Individual patient data on covariates and outcomes were extracted from the Adjuvant Colon Cancer ENdpoinTs (ACCENT) database. The endpoints examined in this meta-analysis were overall survival (time to death), recurrence-free survival (time to recurrence or death), and recurrence-free interval (time to recurrence). Cox models were stratified by study and controlled for sex, stage, age, and treatment to determine the effect of race. Kaplan-Meier estimates were adjusted for similar covariates to control for confounding. All statistical tests were two-sided. RESULTS: Black patients were younger than whites (median age, 58 vs 61 years, respectively; P < .001) and more likely to be female (55% vs 45%, respectively; P < .001). Overall survival was worse in black patients than whites (hazard ratio [HR] of death = 1.22, 95% confidence interval [CI] = 1.11 to 1.34, P < .001). Five-year overall survival rates for blacks and whites were 68.2% and 72.8%, respectively. When subsets defined by sex, stage, and age were analyzed, overall survival was consistently worse in black patients. Recurrence-free survival was worse in black patients than whites (HR of recurrence or death = 1.14, 95% CI = 1.04 to 1.24, P = .0045). Three-year recurrence-free survival rates in blacks and whites were 68.4% and 72.1%, respectively. In contrast, recurrence-free interval was similar in black and white patients (HR of recurrence = 1.08, 95% CI = 0.97 to 1.19, P = .15). Three-year recurrence-free interval rates in blacks and whites were 71.3% and 74.2%, respectively. CONCLUSIONS: Black patients with resected stage II and stage III colon cancer who were treated with the same therapy as white patients experienced worse overall and recurrence-free survival, but similar recurrence-free interval, compared with white patients. The differences in survival may be mostly because of factors unrelated to the patients' adjuvant colon cancer treatment.

Trends in disparities in receipt of adjuvant therapy for elderly stage III colon cancer patients: the role of the medical oncologist evaluation.

BACKGROUND: Race disparities in adjuvant chemotherapy for stage III colon cancer patients have been documented, and medical oncologist evaluation is a critical step in the treatment process. Recent healthcare system and environmental changes may have reduced treatment gaps. OBJECTIVES: To examine differential rates of oncologist evaluation and conditional treatment, by race, and to determine whether changing evaluation and treatment patterns reduced disparities. RESEARCH DESIGN: Retrospective analysis of Surveillance Epidemiology and End Results-Medicare registry, enrollment, and claims data. SUBJECTS: Patients age >65, white or African American race, diagnosed with American Joint Committee on Cancer stage III colon cancer between 1997 and 2002. N = 7176. KEY MEASURES: Oncology specialty evaluation and management visit or chemotherapy claim; receipt of 5-fluorouracil based chemotherapy. Time periods are grouped into early (1997-1998), middle (1999-2000), and late (2001-2002). RESULTS: Initial adjusted oncologist evaluation rates were higher for whites compared with African American patients (58.7% vs. 42.9%), but changes over time reduced the race gap substantially. We did not find significant race-time trends in treatment rates conditional on oncologist evaluation. CONCLUSIONS: Race disparities in medical oncologist evaluations diminished over time, possibly in response to increased provider supply or changing patient and provider attitudes, but there was no parallel reduction in disparities in conditional treatment rates. Projected decreases in oncologist supply suggest the need for further research on this relationship. Research on the role of supplemental medical insurance on disparities in treatment is needed, particularly as the cost of recommended adjuvant therapy increases.

Adjuvant chemotherapy for stage III colon cancer: implications of race/ethnicity, age, and differentiation.

CONTEXT: A 1990 National Institutes of Health Consensus Conference recommended that patients with stage III colon cancer receive adjuvant chemotherapy because survival was improved in clinical trials in patients who received a 5-fluorouracil-based regimen. OBJECTIVE: To determine whether adjuvant chemotherapy is used in the community as a standard of practice that improves outcome and whether it failed to benefit any specific sets of patients. DESIGN, SETTING, AND PARTICIPANTS: Prospective data from 85 934 patients with stage III colon cancer from 560 hospital cancer registries were entered into the National Cancer Data Base between 1990 and 2002 and included standard clinical, pathological, and first course of treatment variables. MAIN OUTCOME MEASURES: Prevalence of adjuvant chemotherapy usage and 5-year survival in patients treated in US hospitals. RESULTS: Adjuvant chemotherapy use increased from 39% in 1991 to 64% in 2002 but was lower in black, female, and elderly patients. It improved 5-year survival from almost 8% in 1991 to more than 16% in 1997 compared with surgery alone. Adjuvant chemotherapy increases survival in elderly patients as much as it does in younger patients. However, the benefit of adjuvant chemotherapy in blacks and those with high-grade cancers is not as great. CONCLUSIONS: Adjuvant chemotherapy use has increased from 1990 to 2002 for patients with stage III colon cancer with an associated increase in 5-year survival of 16%. The benefit of adjuvant chemotherapy seems to be lower in black patients and high-grade cancers. Women have the same benefit but are less often treated. Elderly patients have the same benefit as younger patients but are less frequently treated. New options for adjuvant therapy in 2004-2005 may further improve the outcome of patients with stage III colon cancer.

Treatment preferences and advance care planning at end of life: the role of ethnicity and spiritual coping in cancer patients.

BACKGROUND: Although studies have reported ethnic differences in approaches to end of life, the role of spiritual beliefs is less well understood. PURPOSE: This study investigated differences between African American and White patients with cancer in their use of spirituality to cope with their cancer and examined the role of spiritual coping in preferences at end-of-life. METHODS: The authors analyzed data from interviews with 68 African American and White patients with an advanced stage of lung or colon cancer between December 1999 and June 2001. RESULTS: Similar high percentages of African American and White patients reported being "moderately to very spiritual" and "moderately to very religious." African American patients were more likely to report using spirituality to cope with their cancer as compared to their White counterparts (p = .002). Patients who reported belief in divine intervention were less likely to have a living will (p = .007). Belief in divine intervention, turning to higher power for strength, support and guidance, and using spirituality to cope with cancer were associated with preference for cardiopulmonary resuscitation, mechanical ventilation, and hospitalization in a near-death scenario. CONCLUSIONS: It was found that patients with cancer who used spiritual coping to a greater extent were less likely to have a living will and more likely to desire life-sustaining measures. If efforts aimed at improving end-of-life care are to be successful, they must take into account the complex interplay of ethnicity and spirituality as they shape patients' views and preferences around end of life.

Outcomes and toxicity in african-american and caucasian patients in a randomized adjuvant chemotherapy trial for colon cancer.

BACKGROUND: Previous studies have demonstrated that African-Americans with colon cancer have worse overall and stage-specific survival rates than Caucasians. Such differences could reflect variation in access to health care, in tumor biology, or in treatment efficacy. Little is known about potential differences in chemotherapy-related toxicities between African-Americans and Caucasians. In this study, we examined survival and toxic effects among African-American and Caucasian patients enrolled in a large, randomized phase III trial of adjuvant chemotherapy for resected colon cancer. METHODS: We analyzed data on 3380 patients (344 African-Americans and 3036 Caucasians) enrolled in a randomized trial of adjuvant 5-fluorouracil-based chemotherapy in patients with stage II (high risk) and stage III colon cancer to evaluate differences in outcomes and toxicity. We compared disease-free survival (DFS) and overall survival (OS) between African-Americans and Caucasians by the Kaplan-Meier method, computed Cox proportional hazards by multivariable analysis, and compared treatment-related toxicity rates by Fisher's exact test. All statistical tests were two-sided. RESULTS: We found no differences in DFS or OS between African-American and Caucasian patients. Five-year DFS was 57% (95% confidence interval [CI] = 52% to 62%) for African-Americans and 58% (95% CI = 56% to 60%) for Caucasians (P =.15), and 5-year OS was 65% (95% CI = 60% to 70%) for African-Americans and 66% (95% CI = 64% to 68%) for Caucasians (P =.38). On multivariable analysis, no statistically significant difference in disease recurrence or death was detected between the racial/ethnic groups (hazard ratios for African-Americans versus Caucasians: disease recurrence = 1.1, 95% CI = 0.9 to 1.3; death = 1.1, 95% CI = 0.9 to 1.3). Treatment-related toxicity differed between the African-American and Caucasian patients, with African-Americans experiencing statistically significantly lower rates of diarrhea (P<.001), nausea (P<.001), vomiting (P =.01), stomatitis (P<.001), and overall toxicity (P =.005). CONCLUSIONS: In this study of patients with similar access to health care resources and treatment with adjuvant chemotherapy, we found similar 5-year DFS and OS in African-Americans and Caucasians with stage II and III colon cancer. The two groups derived similar benefits from adjuvant chemotherapy. Moreover, African-Americans appeared to experience less treatment-related toxicity.