Physical activity and survival of colorectal cancer patients: Population‐based study from Germany

Increasing evidence shows physical activity to be associated with improved colorectal cancer (CRC) prognosis. However, large‐scale prospective patient cohorts, comprehensively ascertaining physical activity, comprehensively considering potential variation by CRC stage and considering specific outcome measures, are sparse. Therefore, we aimed to evaluate the association of lifetime and latest prediagnostic leisure time physical activity with relevant prognostic outcomes in a large population‐based cohort of CRC patients. 3,121 patients, diagnosed with CRC in 2003–2010 (median age: 69 years), were interviewed on sociodemographic and lifestyle factors, medication and comorbidities. Cancer recurrence, vital status and cause of death were documented over a median follow‐up time of 4.8 years. Associations between lifetime and latest prediagnostic leisure time physical activity and overall, CRC‐specific, recurrence‐free and disease‐free survival were evaluated with Cox regression. Latest but not lifetime leisure time physical activity [in metabolic task hours per week (MET‐h/wk)] was associated with decreased overall and CRC‐specific mortality (>56.2 vs. ≤13.2 MET‐h/wk: adjusted hazard ratio (aHR)_{Overall/latest} = 0.75; 95% confidence interval (CI) = 0.61–0.91; aHR_{CRC‐specific/latest} = 0.81; 95% CI = 0.64–1.02). In particular lifetime and latest walking were associated with decreased mortality (>20 vs. 0–10 MET‐h/wk of walking: aHR_{Overall/latest} = 0.66; 95% CI = 0.56–0.77; aHR_{CRC‐specific/latest} = 0.72; 95% CI = 0.60–0.87; aHR_{Overall/lifetime} = 0.78; 95% CI = 0.66–0.93; aHR_{CRC‐specific/lifetime} = 0.71; 95% CI = 0.58–0.86). Associations were particularly pronounced for lifetime walking in metastatic (stage IV) and for latest walking in nonmetastatic disease patients. Prediagnostic physical activity was associated with improved CRC prognosis. Associations might be restricted to certain activities or depend on (non)metastatic disease state. Further optimization of activity recommendations and increase of recommendation adherence may help to improve patients' prognosis.     

Impact of prediagnostic smoking and smoking cessation on colorectal cancer prognosis: a meta-analysis of individual patient data from cohorts within the CHANCES consortium

BackgroundSmoking has been associated with colorectal cancer (CRC) incidence and mortality in previous studies and might also be associated with prognosis after CRC diagnosis. However, current evidence on smoking in association with CRC prognosis is limited.Patients and methodsFor this individual patient data meta-analysis, sociodemographic and smoking behavior information of 12 414 incident CRC patients (median age at diagnosis: 64.3 years), recruited within 14 prospective cohort studies among previously cancer-free adults, was collected at baseline and harmonized across studies. Vital status and causes of death were collected for a mean follow-up time of 5.1 years following cancer diagnosis. Associations of smoking behavior with overall and CRC-specific survival were evaluated using Cox regression and standard meta-analysis methodology.ResultsA total of 5229 participants died, 3194 from CRC. Cox regression revealed significant associations between former [hazard ratio (HR) = 1.12; 95 % confidence interval (CI) = 1.04–1.20] and current smoking (HR = 1.29; 95% CI = 1.04–1.60) and poorer overall survival compared with never smoking. Compared with current smoking, smoking cessation was associated with improved overall (HR_{<10 years} = 0.78; 95% CI = 0.69–0.88; HR_{≥10 years} = 0.78; 95% CI = 0.63–0.97) and CRC-specific survival (HR_{≥10 years} = 0.76; 95% CI = 0.67–0.85).ConclusionIn this large meta-analysis including primary data of incident CRC patients from 14 prospective cohort studies on the association between smoking and CRC prognosis, former and current smoking were associated with poorer CRC prognosis compared with never smoking. Smoking cessation was associated with improved survival when compared with current smokers. Future studies should further quantify the benefits of nonsmoking, both for cancer prevention and for improving survival among CRC patients, in particular also in terms of treatment response.     

Mismatch repair status and synchronous metastases in colorectal cancer: A nationwide cohort study

The causality between the metastatic potential, mismatch repair status (MMR) and survival in colorectal cancer (CRC) is complex. This study aimed to investigate the impact of MMR in CRC on the occurrence of synchronous metastases (SCCM) and survival in patients with SCCM on a national basis. A nationwide cohort study of 6,692 patients diagnosed with CRC between 2010 and 2012 was conducted. Data were prospectively entered into the Danish Colorectal Cancer Group's database and merged with data from the Danish Pathology Registry and the National Patient Registry. Multivariable and multinomial logistic‐ and Cox‐regression and proportional excess hazards analyses were used for confounder adjustment and to adjust for the general population mortality. In total, 983 of 6,692 patients (14.7%) had dMMR and 935 (14.0%) had SCCM. dMMR was associated with a decreased risk of SCCM, adjusted Odds Ratio (aOR) = 0.54 (95% confidence interval (CI):0.40–0.70, p < 0.001). The association only applied to confined hepatic metastases (aOR = 0.30, 95%CI: 0.18–0.49, p < 0.001), whereas the presence of confined pulmonary metastases (aOR = 0.71, 95% CI: 0.39–1.29, p = 0.258) or synchronous hepatic and pulmonary metastases (aOR = 0.69, 95% CI:0.26–1.29, p = 0.436) were unaffected by MMR. MMR in patients with SCCM had no impact on survival (Cox: adjusted Hazard Ratio (aHR) = 0.76, 95% CI: 0.54–1.06, p = 0.101; Proportional excess hazards: aHR = 0.73, 95% CI: 0.50–1.07, p = 0.111) when adjusting for other prognostic factors. The metastatic pattern varied according to MMR status. MMR had no impact on survival in patients with UICC Stage IV CRC. These findings may be important for the understanding of the metastatic processes and thus for optimizing staging and treatment in CRC patients.     

Plasma miR‐122 and miR‐200 family are prognostic markers in colorectal cancer

Circulating microRNAs (miRNAs) have been proposed as minimally invasive prognostic markers for various types of cancers, including colorectal cancer (CRC), the third most diagnosed cancer worldwide. We aimed to evaluate the levels of circulating miRNAs that might serve as markers for CRC prognosis and survival. We included plasma samples of 543 CRC patients with stage I‐IV disease from a population‐based study carried out in Germany. After comprehensive evaluation of current literature, 95 miRNAs were selected and measured with Custom TaqMan® Array MicroRNA Cards. Plasma samples of non‐metastatic and metastatic colon cancer patients, each group consisting of ten patients with ‘good’ and ten patients with ‘bad’ prognosis were screened. Identified candidate miRNAs were further validated by RT‐qPCR in the whole study cohort. The association of the miRNA levels with patients' survival and the prognostic subtypes was analyzed with uni‐ and multivariate logistic regression and Cox proportional hazards regression models. Increased miR‐122 levels were associated with a ‘bad’ prognostic subtype in metastatic CRC (Odds ratio: 1.563, 95% confidence interval (CI): 1.038‐2.347) and a shorter relapse‐free survival and overall survival for non‐metastatic (Hazard ratio (HR): 1.370, 95% CI: 1.028‐1.825; HR: 1.353, 95% CI: 1.002‐1.828) and metastatic (HR: 1.264, 95% CI: 1.050‐1.520; HR: 1.292, 95% CI: 1.078‐1.548) CRC patients. Additionally, several members of the miR‐200 family showed associations with patients' prognosis and correlations to clinicopathological characteristics. The here identified miRNA markers, miR‐122 and the miR‐200 family members, could be of use in the development of a multi‐marker blood test for CRC prognosis.     

Comprehensive analysis of DNA repair gene polymorphisms and survival in patients with early stage non‐small‐cell lung cancer

This study was conducted to analyze a comprehensive panel of single nucleotide polymorphisms (SNP) in DNA repair genes to determine the relationship between polymorphisms and the survival outcome of patients with early stage non‐small‐cell lung cancer (NSCLC). Three hundred and ten consecutive patients with surgically resected NSCLC were enrolled. Forty‐eight SNP in 27 DNA repair genes were genotyped and their associations with overall survival (OS) and disease‐free survival (DFS) were analyzed. Individually, six SNP exhibited significant associations with survival outcome. When the six SNP were combined, OS and DFS decreased as the number of bad genotypes increased (P_trend < 0.0001 for both). Patients with three, and four or five bad genotypes had a significantly worse OS and DFS compared with those carrying zero or one bad genotypes (adjusted hazard ratio [aHR] for OS = 3.53, 95% confidence interval [CI] = 1.25–9.97, P = 0.02, and aHR for DFS = 3.31, 95% CI = 1.41–7.76, P = 0.006; and aHR for OS = 5.47, 95% CI = 1.87–16.00, P = 0.002, and aHR for DFS = 4.42, 95% CI = 1.82–10.74, P = 0.001, respectively). These findings suggest that the six SNP identified can be used as prognostic markers for patients with surgically resected early stage NSCLC. (Cancer Sci 2010; 101: 2436–2442)     

Racial disparities in colorectal cancer survival

BACKGROUND:

Racial/ethnic differences in colorectal cancer (CRC) survival have been documented throughout the literature. However, the reasons for these disparities are difficult to decipher. The objective of this analysis was to determine the extent to which racial/ethnic disparities in survival are explained by differences in sociodemographics, tumor characteristics, diagnosis, treatment, and hospital characteristics.

METHODS:

A cohort of 37,769 Medicare beneficiaries who were diagnosed with American Joint Committee on Cancer stages I, II, and III CRC from 1992 to 2002 and resided in 16 Surveillance, Epidemiology, and End Results (SEER) regions of the United States was identified in the SEER‐Medicare linked database. Survival was estimated using the Kaplan‐Meier method. Cox proportional hazards modeling was used to estimate hazard ratios (HRs) of mortality and 95% confidence intervals (CIs).

RESULTS:

Black patients had worse CRC‐specific survival than white patients, but the difference was reduced after adjustment (adjusted HR [aHR], 1.24; 95% CI, 1.14‐1.35). Asian patients had better survival than white patients after adjusting for covariates (aHR, 0.80; 95% CI, 0.70‐0.92) for stages I, II, and III CRC. Relative to Asians, blacks and whites had worse survival after adjustment (blacks: aHR, 1.56; 95% CI, 1.33‐1.82; whites: aHR, 1.26; 95% CI, 1.10‐1.44). Comorbidities and socioeconomic Status were associated with a reduction in the mortality difference between blacks and whites and blacks and Asians.

CONCLUSIONS:

Comorbidities and SES appeared to be more important factors contributing to poorer survival among black patients relative to white and Asian patients. However, racial/ethnic differences in CRC survival were not fully explained by differences in several factors. Future research should further examine the role of quality of care and the benefits of treatment and post‐treatment surveillance in survival disparities. Cancer 2010. © 2010 American Cancer Society.     

Association between metformin use after surgery for colorectal cancer and oncological outcomes: A nationwide register‐based study

Colorectal cancer is one of the most common malignancies in the Western world, and even after surgical removal, there is a high recurrence rate. Metformin treatment has been associated with a reduced risk of developing cancer, but whether metformin influences the risk of recurrence is unknown. The aim of our study was to examine the association between treatment with metformin and recurrence‐free, disease‐free survival and all‐cause mortality after surgery for colorectal cancer. The study was an observational register‐based study and included 25,785 patients, of which 1,116 had medically treated diabetes and 966 started metformin treatment at some point postoperatively. Diabetes was not associated with neither disease‐free (HR_adjusted = 1.09, 95% CI 0.97–1.21, p = 0.15) nor recurrence‐free survival (HR_adjusted = 1.13, 95% CI 0.95–1.35, p = 0.17). The study found no difference in regards to disease‐free or recurrence‐free survival between the metformin treated group (HR_RFS = 1.06, 95% CI 0.87–1.15, p = 0.57, HR_DFS = 1.01, 95% CI 0.89–1.15, p = 0.85) and non‐diabetic patients. Patients with diabetes had increased all‐cause mortality (HR_adjusted = 1.29, 95% CI 1.16–1.45, p < 0.0001). Metformin treatment did not affect all‐cause mortality (HR = 1.07, 95% CI 0.94–1.22, p = 0.33) compared to non‐diabetic patients. In conclusion, our study did not find an association between diabetes or metformin treatment and recurrence‐free or disease‐free survival after surgery for colorectal cancer. However, diagnosis of diabetes is associated with increased all‐cause mortality.     

The association between body mass index and postoperative complications, 30-day mortality and long-term survival in Dutch patients with colorectal cancer

IntroductionThis retrospective study aims to examine the association between body mass index (BMI) and serious postoperative complications, 30-day mortality and overall survival in colorectal cancer (CRC) patients.Materials and methodsAll CRC patients diagnosed between 2008 and 2013 in the south-eastern part of the Netherlands were included. Patients were categorized into four BMI groups: underweight (<18.5), normal weight (18.5 ≥ BMI<25), overweight (25 ≥ BMI<30), and obese (≥30).ResultsA total of 7371 CRC patients were included (underweight 133 (1.8%); normal weight 2054 (41.4%); overweight 2955 (40.1%); obesity 1229 (16.7%)). Underweight patients were more likely to have postoperative complications (18.8% vs. 11.7%, adjusted OR 1.95, 95% CI 1.08–3.49) and had a worse 30-day mortality (9.8% vs. 3.3%, adjusted OR 4.37, 95% CI 2.03–9.42) compared to normal weight patients. After stratification for stage (stage I-III and stage IV), underweight was associated with a worse overall survival in both groups compared to normal weight (stage I-III: HR 2.06, 95%CI 1.51–2.80; stage IV: HR 1.65, 95% CI 1.11–2.45). Overweight was associated with an improved overall survival compared to normal weight in both stage groups. Only in stage IV patients obesity was associated with a significant better overall survival compared to stage IV normal weight patients.ConclusionUnderweight CRC patients were more likely to have postoperative complications and a worse 30-day mortality compared to patients in other BMI categories. The underweight population also has a worse long-term survival while overweight CRC patients and obese stage IV CRC patients were associated with an improved survival compared to normal weight patients.     

Heavy smoking history interacts with chemoradiotherapy for esophageal cancer prognosis: A retrospective study

Smoking is a well‐known risk factor for esophageal cancer. However, there are few reports that directly evaluate smoking as a prognostic factor for esophageal cancer. Moreover, scarce evidence is available on whether smoking interacts with major treatment modalities of esophageal cancer. In this study we retrospectively analyzed 364 patients with esophageal squamous cell cancer who were treated between 2001 and 2005 at our institution. Background characteristics, including smoking history, were analyzed as potential prognostic factors. Of the 363 patients, 76 patients (20.9%) were non‐smokers or light smokers (non‐heavy), whereas 287 patients (79.1%) were heavy smokers. The 5‐year survival rate for non‐heavy smokers and heavy smokers was 61.8% (95% confidence interval [CI]: 49.1–72.2) vs 44.6% (95% CI: 38.2–50.9), respectively. In a multivariate Cox model (adjusted for age, gender, performance status, alcohol consumption, histology, tumor length, International Union Against Cancer [UICC] stage, and treatment), the hazard ratio for heavy smokers in comparison with non‐heavy smokers was 1.73 (95% CI: 1.12–2.68; P = 0.013). When we stratified by treatment method, heavy smoking was significantly associated with poor survival only in patients treated by chemoradiotherapy (hazard ratio, 2.43; 95% CI: 1.38–4.27; P = 0.002). More importantly, a statistically significant interaction between heavy smoking history and treatment modality was observed (P = 0.041). Our results indicated that smoking history is strongly associated with poor prognosis in patients with esophageal cancer, especially those treated by chemoradiotherapy. Further investigation is warranted to explain this different prognosis. (Cancer Sci 2010; 101: 1001–1006)     

Effect of metabolic syndrome and its components on recurrence and survival in colon cancer patients

BACKGROUND:

Although epidemiologic studies suggest that metabolic syndrome (MetS) increases the risk of colorectal cancer, its effect on cancer mortality remains controversial.

METHODS:

The authors used the Surveillance, Epidemiology, and End Results (SEER)‐Medicare linked database (1998‐2006) to conduct a retrospective cohort study of 36,079 patients with colon cancer to determine the independent effect of MetS and its components on overall survival (OS) and recurrence‐free rates (RFRs). Data on MetS and its components were ascertained from Medicare claims. OS and RFRs in patients with and without MetS and its components were compared using multivariate Cox models.

RESULTS:

MetS had no apparent effect on OS or RFR. Both elevated glucose/diabetes mellitus (DM) and elevated hypertension were associated with worse OS (adjusted hazard ratio [aHR], 1.17 [95% confidence interval, 1.13‐1.21] and 1.08 [95% confidence interval, 1.03‐1.12], respectively) and worse RFRs (aHR, 1.25 [95% confidence interval, 1.16‐1.34] and 1.22 [95% confidence interval, 1.12‐1.33], respectively). In contrast, dyslipidemia was associated with improved survival (aHR, 0.77; 95% confidence interval, 0.75‐0.80) and reduced recurrence (aHR, 0.71; 95% confidence interval, 0.66‐0.75). These effects were consistent for both men and women and were more pronounced in patients with early stage disease.

CONCLUSIONS:

MetS had no apparent effect on colon cancer outcomes, probably because of the combined adverse effects of elevated glucose/DM and hypertension and the protective effect of dyslipidemia in patients with nonmetastatic disease. The authors concluded that patients who have early stage colon cancer with elevated glucose/DM and/or hypertension may benefit from more intensive surveillance and/or broader use of adjuvant therapy and that trials to define the benefits of low‐fat diets, insulin‐lowering agents, and statins on recurrence/survival in patients with nonmetastatic colon cancer are warranted. Cancer 2013. © 2012 American Cancer Society.     

Cigarette smoking is associated with adverse survival among women with ovarian cancer: Results from a pooled analysis of 19 studies

Cigarette smoking is associated with an increased risk of developing mucinous ovarian tumors but whether it is associated with ovarian cancer survival overall or for the different histotypes is unestablished. Furthermore, it is unknown whether the association between cigarette smoking and survival differs according to strata of ovarian cancer stage at diagnosis. In a large pooled analysis, we evaluated the association between various measures of cigarette smoking and survival among women with epithelial ovarian cancer. We obtained data from 19 case‐control studies in the Ovarian Cancer Association Consortium (OCAC), including 9,114 women diagnosed with ovarian cancer. Cox regression models were used to estimate adjusted study‐specific hazard ratios (HRs), which were combined into pooled hazard ratios (pHR) with corresponding 95% confidence intervals (CIs) under random effects models. Overall, 5,149 (57%) women died during a median follow‐up period of 7.0 years. Among women diagnosed with ovarian cancer, both current (pHR = 1.17, 95% CI: 1.08–1.28) and former smokers (pHR = 1.10, 95% CI: 1.02–1.18) had worse survival compared with never smoking women. In histotype‐stratified analyses, associations were observed for mucinous (current smoking: pHR = 1.91, 95% CI: 1.01–3.65) and serous histotypes (current smoking: pHR = 1.11, 95% CI: 1.00–1.23; former smoking: pHR = 1.12, 95% CI: 1.04–1.20). Further, our results suggested that current smoking has a greater impact on survival among women with localized than disseminated disease. The identification of cigarette smoking as a modifiable factor associated with survival has potential clinical importance as a focus area to improve ovarian cancer prognosis.     

Associations of cigarette smoking and alcohol drinking with stomach cancer survival: A prospective patient cohort study in Japan

Cigarette smoking and alcohol drinking may affect the prognosis of stomach cancer, but evidence has been inconsistent. We investigated the associations between pretreatment smoking and alcohol drinking and the risk of all‐cause and stomach cancer death among 1,576 patients with histologically confirmed stomach cancer diagnosed during 1997–2010 at a single hospital in Japan. Histories of smoking and alcohol drinking were assessed using a self‐administered questionnaire. The patients were followed until December 31, 2013. The Cox proportional hazards model was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). During 9,625.1 person‐years, 670 all‐cause and 419 stomach cancer deaths were documented. Among the patients overall, ever‐drinking was significantly associated with an increased risk of all‐cause death (HR: 1.25; 95% CI: 1.03–1.51), but not stomach cancer death. Positive linear associations with the frequency of drinking (p_trend = 0.02) and the amount of alcohol consumed per day (p_trend = 0.03) were observed for the risk of all‐cause death. Ever‐smoking was not related to either the risk of all‐cause or stomach cancer death. Conversely, among the patients who underwent curative resection, a significant positive association was found between ever‐smoking and the risk of stomach cancer death (HR: 2.44; 95% CI: 1.17–5.08). A positive association was also found for earlier age at start of smoking (p_trend = 0.0046). Pretreatment smoking and alcohol drinking have significant effects on stomach cancer survival. Lifestyle adjustments throughout life may improve survival.     

Identification of polymorphisms in ultraconserved elements associated with clinical outcomes in locally advanced colorectal adenocarcinoma

BACKGROUND:

Ultraconserved elements (UCEs) are noncoding genomic sequences that completely identical among human, mouse, and rat species and harbor critical biologic functions. The authors hypothesized that single nucleotide polymorphisms (SNPs) within UCEs are associated with clinical outcomes in patients with colorectal cancer (CRC).

METHODS:

Forty‐eight SNPs within UCEs were genotyped in 662 patients with stage I through III CRC. The associations between genotypes and recurrence and survival were analyzed in patients with stage II or III CRC who received fluoropyrimidine‐based adjuvant chemotherapy using a training and validation design. The training set included 115 patients with stage II disease and 170 patients with stage III disease, and the validation set included 88 patients with stage II disease and 112 patients with stage III disease.

RESULTS:

Eight SNPs were associated with clinical outcomes stratified by disease stage. In particular, for patients with stage II CRC who had at least 1 variant allele of reference SNP sequence 7849 (rs7849), a consistent association with increased recurrence risk was observed in the training set (hazard ratio [HR], 2.39; 95% confidence interval [CI], 1.04‐5.52), in the replication set (HR, 3.70; 95% CI, 1.42‐9.64), and in a meta‐analysis (HR, 2.89; 95% CI, 1.54‐5.41). Several other SNPs were significant in the training set but not in the validation set. These included rs2421099, rs16983007, and rs10211390 for recurrence and rs6590611 for survival in patients with stage II disease; and SNPs rs6124509 and rs11195893 for recurrence in patients with stage III disease. In addition, a significant cumulative effect was observed of multiple risk genotypes and potential gene‐gene interactions on recurrence risk.

CONCLUSIONS:

To the authors' knowledge, this is the first study to evaluate the association between SNPs within UCEs and clinical outcome in patients with CRC. The results suggested that SNPs within UCEs may be valuable prognostic biomarkers for patients with locally advanced CRC who receive 5‐fluorouracil–based chemotherapy. Cancer 2012. © 2012 American Cancer Society.     

Impact of smoking on patients with stage III colon cancer

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. Cancer 2010. © 2010 American Cancer Society.     

The role of comorbidities on the uptake of systemic treatment and 3-year survival in older cancer patients

BackgroundOlder patients are notably absent from clinical trials. Thus, observational studies are the primary avenue for understanding the role of comorbidity in cancer care and survival. We examined the impact of comorbidity on systemic treatment initiation and 3-year survival in a cohort of older cancer patients.Patients and MethodsOur cohort comprised 2753 Australian veterans aged ≥65 years with full health coverage and a cancer registry notification for colorectal (CRC), breast, prostate or non-small-cell lung cancer (NSCLC). We established comorbidities based on drugs prescribed in the 6 months prior to cancer diagnosis.ResultsPatients with higher comorbidity burden were more likely to receive systemic treatment for prostate cancer [adjusted odds ratio 1.21, 95% confidence interval (CI) 1.05–1.39] but less likely for NSCLC (0.63, 95% CI 0.45–0.86). After adjusting for receipt of treatment, increased comorbidity resulted in shorter survival for CRC [adjusted hazard ratio (aHR) 1.16, 95% CI 1.07–1.26] and breast cancer (aHR 1.23, 95% CI 1.02–1.48). However, we did not demonstrate significant improvements in 3-year survival for patients receiving systemic treatment.ConclusionComorbidity influences systemic treatment uptake and adversely affects survival, with impact dependent upon comorbidity and cancer type. Clinical trials should be undertaken in older patients to better understand the risks and benefits of cancer treatments.     

Associations of alcohol intake,smoking, physical activity and obesity with survival following colorectal cancer diagnosis by stage,anatomic site and tumor molecular subtype

The influence of lifestyle factors on survival following a diagnosis of colorectal cancer (CRC) is not well established. We examined associations between lifestyle factors measured before diagnosis and CRC survival. The Melbourne Collaborative Cohort Study collected data on alcohol intake, cigarette smoking and physical activity, and body measurements at baseline (1990–1994) and wave 2 (2003–2007). We included participants diagnosed to 31 August 2015 with incident stages I–III CRC within 10‐years post exposure assessment. Information on tumor characteristics and vital status was obtained. Tumor DNA was tested for microsatellite instability (MSI) and somatic mutations in oncogenes BRAF (V600E) and KRAS. We estimated hazard ratios (HRs) for associations between lifestyle factors and overall and CRC‐specific mortality using Cox regression. Of 724 eligible CRC cases, 339 died (170 from CRC) during follow‐up (average 9.0 years). Exercise (non‐occupational/leisure‐time) was associated with higher CRC‐specific survival for stage II (HR = 0.25, 95% CI: 0.10–0.60) but not stages I/III disease (p for interaction = 0.01), and possibly for colon and KRAS wild‐type tumors. Waist circumference was inversely associated with CRC‐specific survival (HR = 1.25 per 10 cm increment, 95% CI: 1.08–1.44), independent of stage, anatomic site and tumor molecular status. Cigarette smoking was associated with lower overall survival, with suggestive evidence of worse survival for BRAF mutated CRC, but not with CRC‐specific survival. Alcohol intake was not associated with survival. Survival did not differ by MSI status. We have identified pre‐diagnostic predictors of survival following CRC that may have clinical and public health relevance.     

Colorectal signet‐ring cell carcinoma: benefit from adjuvant chemotherapy but a poor prognostic factor

Colorectal signet‐ring cell carcinoma (SRCC) has been associated with poor survival compared with mucinous adenocarcinoma (MC) and the more common adenocarcinoma (AC). Efficacy of adjuvant chemotherapy in SRCC has never been assessed. This study analyzes the prognostic impact of SRCC and determines whether colonic SRCC patients benefit from adjuvant chemotherapy equally compared with MC and AC patients. Data on 196,757 colorectal cancer (CRC) patients in the period 1989–2010 was included in this Dutch nationwide population‐based study. Five‐year relative survival estimates were calculated and multivariate relative survival analyses using a multiple regression model of relative excess risk (RER) were performed. SRCC was found in 1,972 (1.0%) patients. SRCC patients presented more frequently with stage III or IV disease than AC patients (75.2% vs. 43.6%, p < 0.0001) and SRCC was more frequently found in the proximal colon (57.7 vs. 32.0%, p < 0.0001). SRCC patients had a poor 5‐year relative survival of 30.8% (95% CI 28.1–33.6%) in the colon and 19.5% (95% CI 14.7–24.8%) in the rectum compared with 56.8% (95% CI 56.4–57.1%) and 58.5% (95% CI 57.9–59.1%) for AC. This survival difference was found in stage II, but was most prominent in stage III. Compared with AC, there was no significant interaction between SRCC and adjuvant chemotherapy (RER 1.10, 95% CI 0.81–1.51), suggesting a comparable benefit from adjuvant chemotherapy in AC and SRCC. In conclusion, the prognostic impact of SRCC is dismal in both colon and rectal cancer patients, but adjuvant chemotherapy is associated with improved survival in AC, MC, and SRCC patients.     

Long-term risk of colorectal cancer after screen-detected adenoma: Experiences from a Danish gFOBT-positive screening cohort

Fecal occult blood test (FOBT) screening for colorectal cancer (CRC) is implemented in several countries. Approximately half of all FOBT-positive persons have screen-detected adenomas. Despite removal of these, patients with large/multiple adenomas have increased risk of later developing new advanced adenomas and CRC. International guidelines exist for colonoscopic surveillance following adenoma removal. These divide patients into low-, intermediate- and high-risk groups. We followed 711 FOBT-positive patients with screening adenoma identified during population-based CRC screening in two Danish counties in 2005–2006. As reference population, we included 1,240,348 persons in the same age group from the rest of Denmark not included in the screening. We estimated the long-term CRC risk stratified by adenoma findings during screening and compared to the reference group. After 12 years follow-up, the CRC incidence among all adenoma patients was 322 cases per 100,000 person-years (95% confidence interval [CI]: 212–489) ranging from 251 (95% CI: 94–671) to 542 (95% CI: 300–978) cases per 100,000 person-years in the low- and high-risk groups, respectively. In the reference population, the CRC incidence was 244 (95% CI: 242–247) per 100,000. Patients with screen-detected high-risk adenomas after a positive FOBT had an almost doubled risk of CRC compared to the reference population (adjusted hazard ratio [aHR] 1.95, 95% CI: 1.08–3.51), and the incidence in those with no follow-up visits was over 3.6 (aHR 3.64, 95% CI: 1.82–7.29) times the incidence in the reference population. The increased CRC risk could be controlled if high-risk patients underwent follow-up colonoscopy (aHR 0.87, 95% CI: 0.28–2.69).     

Prognostic role of neutrophil‐to‐lymphocyte ratio in colorectal cancer: A systematic review and meta‐analysis

The prognostic role of inflammation index like neutrophil‐to‐lymphocyte ratio (NLR) in colorectal cancer (CRC) remains controversial. We conduct a meta‐analysis to determine the predictable value of NLR in the clinical outcome of CRC patients. The analysis was carried out based on the data from 16 studies (19 cohorts) to evaluate the association between NLR and overall survival (OS) and progression‐free survival (PFS) in patients with CRC. In addition, the relationship between NLR and clinicopathological parameters was assessed. Hazard ratio (HR) or odds ratio (OR) with its 95% confidence interval (CI) was used as the effect size estimate. Our analysis results indicated that elevated pretreatment NLR predicted poorer OS (HR: 1.813, 95% CI: 1.499–2.193) and PFS (HR: 2.102, 95% CI: 1.554–2.843) in patients with CRC. Increased NLR is also significantly associated with the poorer differentiation of the tumor (OR: 1.574, 95% CI: 1.226–2.022) and higher carcino‐embryonie antigen (CEA) level (OR: 1.493, 95% CI: 1.308–1.705). By these results, we conclude that NLR gains a prognostic value for patients with CRC. NLR should be monitored in CRC patients for rational stratification of the patients and adjusting the treatment strategy.