Survival of colorectal cancer patients in Europe during the period 1978–1989

This study concerns the survival of European patients diagnosed between 1978 and 1989 with colorectal cancer. Variations in survival in relation to age, country and period of diagnosis were examined. Data from the EUROCARE study were supplied by population-based cancer registries in 17 countries to a common protocol. Five years after diagnosis, relative survival rates were 47 and 43% for cancers of the colon and rectum, respectively. Survival decreased with increasing age: the relative risk of dying for the oldest patients (75+) was 1.39 for rectum and 1.54 for colon compared with the youngest patients (15–44 years). In 1985–1989 survival from colorectal cancer differed significantly between different European countries: the Nordic countries (Denmark excluded), The Netherlands, Switzerland, France and Austria were characterised by high survival, whilst Eastern European countries, the U.K. and Denmark were characterised by low survival. There was a general improvement in survival over the period 1978–1989: from 40 to 48% for colon cancer and 38 to 46% for rectal cancer. For neither cancer site did between-country survival differences narrow over the study period. Intercountry and time differences in survival differences are probably related to stage at diagnosis and postoperative mortality.     

An evaluation and replication of miRNAs with disease stage and colorectal cancer‐specific mortality

MicroRNAs (miRNAs) have been implicated in colorectal cancer (CRC) development and associated with prognostic indicators such as disease stage and survival. Prognostic associations are often based on few individuals and imprecise. In this study, we utilize population‐based data from 1,141 CRC cases to replicate previously reported associations between 121 miRNAs and disease stage and survival. The Agilent Human miRNA Microarray V19.0 was used to generate miRNA data following a stringent quality control protocol. Assessment of survival was done using Cox Proportional Hazard models adjusting for age, disease stage and tumor molecular phenotype. Five miRNAs were associated with more advanced disease stage; hsa‐miR‐145‐5p and hsa‐miR‐31‐5p showed increased expression with more advanced tumor stage, while hsa‐miR‐200b‐3p, hsa‐miR‐215 and hsa‐miR‐451a had decreased expression with more advanced tumors. Thirteen miRNAs were associated with CRC mortality among individuals diagnosed with colon cancer while 14 were associated with CRC mortality after a diagnosis with rectal cancer. Strongest associations were observed for those miRNAs that were expressed in a small subset of tumors. Most notable associations were for hsa‐miR‐145‐3p [hazard ratio (HR) 2.94, 95% confidence interval (CI) 1.54, 5.61], and hsa‐miR‐9‐3p (HR 10.28, 95% CI 1.31, 80.84) with colon cancer and hsa‐miR‐335‐5p (HR 0.17, 95% CI 0.05, 0.54) for rectal cancer. hsa‐miR‐374a‐5p, hsa‐miR‐570‐3p and hsa‐miR‐18a‐5p significantly reduced the hazard of dying for all cases, regardless of tumor site. Our findings illustrate the need for a large sample to evaluate the association of miRNAs with survival and disease stage in order to determine associations by tumor site.     

A retrospective observational study examining the characteristics and outcomes of tumours diagnosed within and without of the English NHS Bowel Cancer Screening Programme

Background:

Colorectal cancer is common in England and, with long-term survival relatively poor, improving outcomes is a priority. A major initiative to reduce mortality from the disease has been the introduction of the National Health Service (NHS) Bowel Cancer Screening Programme (BCSP). Combining data from the BCSP with that in the National Cancer Data Repository (NCDR) allows all tumours diagnosed in England to be categorised according to their involvement with the BCSP. This study sought to quantify the characteristics of the tumours diagnosed within and outside the BCSP and investigate its impact on outcomes.

Methods:

Linkage of the NCDR and BCSP data allowed all tumours diagnosed between July 2006 and December 2008 to be categorised into four groups; screen-detected tumours, screening-interval tumours, tumours diagnosed in non-participating invitees and tumours diagnosed in those never invited to participate. The characteristics, management and outcome of tumours in each category were compared.

Results:

In all, 76 943 individuals were diagnosed with their first primary colorectal cancer during the study period. Of these 2213 (2.9%) were screen-detected, 623 (0.8%) were screening-interval cancers, 1760 (2.3%) were diagnosed in individuals in non-participating invitees and 72 437 (94.1%) were diagnosed in individuals not invited to participate in the programme due to its ongoing roll-out over the time period studied. Screen-detected tumours were identified at earlier Dukes'' stages, were more likely to be managed with curative intent and had significantly better outcomes than tumours in other categories.

Conclusion:

Screen-detected cancers had a significantly better prognosis than other tumours and this would suggest that the BCSP should reduce mortality from colorectal cancer in England.     

Progress in colorectal cancer survival in Europe from the late 1980s to the early 21st century: the EUROCARE study

Colorectal cancer (CRC) is the second most common cause of death due to cancer causing death in Europe, accounting for more than 200,000 deaths per year. Prognosis strongly depends on stage at diagnosis, and the disease can be cured in most cases if diagnosed at an early stage. We aimed to assess trends and recent developments in 5-year relative survival in European countries, with a special focus on age, stage at diagnosis and anatomical cancer subsite. Data from 25 population-based cancer registries from 16 European countries collected in the context of the EUROCARE-4 project were analyzed. Using period analysis, age-adjusted and age-specific 5-year relative survival was calculated by country, European region, stage and cancer subsite for time periods from 1988-1990 to 2000-2002. Survival substantially increased over time in all European regions. In general, increases were more pronounced in younger than in older patients, for earlier than for more advanced cancer stages and for rectum than for colon cancer. Substantial variation of CRC survival between European countries and between age groups persisted and even tentatively increased over time. There is a huge potential for reducing the burden of CRC in Europe by more widespread and equal delivery of existing options of effective early detection and curative treatment to the European population.     

Survival of Colorectal Cancer in Iran

Objective: Colorectal cancer is the fourth cause of cancer after stomach, bladder, prostate in men and secondcause after breast in women in Iran. It is estimated that 4,000 new cases occur each year with 1,150 deathsannually. The present study aimed to determine survival of colorectal cancers in Iran in a national manner.Methods and Results: The data from national cancer registry department of the Ministry of Health and MedicalEducation (MOH&ME) were used as the main source of incident colorectal cancer information in Iran fromMarch 2000 to March 2005. One and five year survival proportions were 88% and 45% for females versus 86%and 39% for men. The median overall survival for colorectal cancer in Iran was 3.5 years with a 95 % confidenceinterval of 3.2-3.8 years. The worst survival status was found for patients less than 20 and more than 80 yearsold. Conclusion: The overall 5 year survival for colorectal cancer in Iran (41%) is comparable even with somedeveloped countries but it is far from those with advanced health care systems, or community based screeningprograms. Thus at the policy level, application of an appropriate national cancer control program andmanagement guidelines should be under consideration.     

Health Insurance and Colorectal Cancer Survival in Khon Kaen,Thailand

Background: Evidence from healthcare studies demonstrates that patients’ health insurance affects serviceaccessibility and the outcome of treatment. However, assessment on how colorectal cancer survival relates to healthinsurance is limited. Objective: The study examined the association between health insurance and colorectal cancersurvival in Khon Kaen, Thailand. Methods: The retrospective cohort study was conducted with 1,931 colorectal cancerpatients from Khon Kaen cancer registry between January 1, 2003 and December 31, 2012, and was followed-up untilDecember 31, 2015. Relative survival was used to estimate the survival rate. Cox proportional hazard regression wasused to estimate the relationship between health insurance and colorectal cancer survival, represented with the hazardratio. Result: Most of the participants were males, and the median age was 62 years. The median survival time was2.25 years (95% CI: 2.00-2.51). The five-year observed survival rate and relative survival rate were 36.87 (95% CI:34.66-39.08) and, 42.28 (95% CI: 39.75-44.81), respectively. The factors that showed significant associations withpoorer survival after adjustment for gender and age were non-surgical treatments (HRadj=1.88;95%CI=1.45-2.45),advanced stage (III+IV) (HRadj=2.50; 95%CI=2.00-3.12), histological grading in poorly differentiated (HRadj=1.84;95%CI=1.32-2.56), and Universal Coverage Scheme (HRadj=1.37;95%CI=1.09-1.72). Conclusion: The survival ofcolorectal cancer patients in the Universal Coverage Scheme was likely to be poorer than in the Civil Servant MedicalBenefit Scheme. This indicates an urgent need for a national program for colorectal cancer screening in the generalpopulation and access to health insurance.     

Influence of environment and healthcare structures on the survival of patients with colorectal cancer: a French population-based study

BACKGROUND AND OBJECTIVES: Colorectal cancer is one of the highest-ranking cancers in France, both sexes combined, with 33000 new cases per year. To report on the practice and the efficiency of the healthcare system, an evaluation of the therapeutic management of colorectal cancer was carried out in the department of the Herault, in the south of France. METHODS: Cases of colorectal cancer in 1992 (344 colorectal cancer incidental cases) in the department of the Herault were reviewed. The diversity of the therapeutic choices and survival were evaluated for the different types of healthcare facilities (private hospitals, nonspecialized and specialized hospitals) and residential areas (rural, semi-urban, urban). RESULTS: Two hundred seventy-one patients with colorectal cancer (78.8%) and 234 patients with colorectal cancer (67.7%) were respectively diagnosed and treated in the private sector. Sixteen cases (23.5%) in the public sector (29.7% in the university hospital) and 24 cases (19%) in the private sector involved surgical emergencies (peritonitis, intestinal obstructions) (P = 0.003). Radiotherapy was performed in 59% of patients with rectal cancer. Preoperative radiotherapy was used primarily in specialized hospitals (80% of radiated rectal cancer; P = 0.002), as opposed to postoperative radiotherapy, which was used predominantly in private hospitals (P = 0.005). Forty-five percent of the patients with colorectal cancer who had lymph node involvement have been treated with chemotherapy. In multivariate analysis, lymph node metastasis and the presence of metastases (Dukes stage) were the most important independent pejorative prognostic factors, followed by the initial treatment in nonspecialized hospitals, complicated colorectal cancer (intestinal obstruction, peritonitis), lack of histological differentiation, and rural and urban residential areas. CONCLUSIONS: Apart from independent prognostic factors, such as parietal, ganglionic, or metastatic extensions, the lack of histological differentiation, and the complicated forms, heterogeneity and inequality persist in the distribution, treatment for, and the survival of patients with colorectal cancer based on the type of healthcare facility and the living area of this French population.     

接头蛋白DOK2在结直肠癌中的表达及临床病理学意义

目的:研究接头蛋白DOK2在结直肠癌中的表达及其临床病理学意义。方法:免疫组化检测87例结直肠癌组织中DOK2的表达,并对结直肠癌患者进行生存分析。结果:DOK2在63例（72%）结直肠癌组织中表达阴性,在正常组织中表达阳性。DOK2表达丢失与肿瘤分化程度（P=0.001）和复发（P=0.048）之间有显著相关性。COX回归分析显示,DOK2表达丢失是结直肠癌患者总体生存率（overall survival,OS）（P=0.001）和无复发生存率（recurrence-free survival,RFS）（P=0.006）的独立影响因素。Kaplan-Meier法生存分析表明,与DOK2表达阳性的患者相比,DOK2表达阴性的患者中位生存时间显著缩短（46个月vs 53个月,P＜0.001）,无复发中位生存时间也显著缩短（36个月 vs 49个月,P＜0.001）。结论:接头蛋白DOK2是结直肠癌患者预后的独立影响因素。     

Comparison of Survival between Patients with Hereditary Non Polyposis Colorectal Cancer (HNPCC) and Sporadic Cancer

Background: Hereditary non polyposis colorectal cancer (HNPCC) appears to have a better prognosis thansporadic cancer. In the present study we evaluated the clinical outcomes of HNPCC patients with their sporadiccolorectal cancer counterparts arising from the general population recorded in a population-based cancer registryin Iran. Patients and methods: The population studied consisted of 121 individuals including 61 patients withsporadic colorectal cancer and 60 with HNPCC who were followed-up between 2003 and 2008 in TaleghaniHospital Tehran. The subjects with HNPCC were screened according to Amsterdam criteria II and BethesdaGuidelines. Subjects with sporadic cancer had no familial history of colorectal cancer. Observed survival wasestimated using the Kaplan-Meier method and compared with the log rank test. Multivariate analysis wasperformed using Cox’ regression analysis. Results: In the HNPCC group, 85.0% showed tumors in the colon, vs.68.9% in the sporadic cancer group. The 5-year survival was 82.5% in the HNPCC study group compared withonly 56.4% in the sporadic colorectal cancer group (P=0.044). The age distribution at diagnosis of sporadicpatients was significantly higher than HNPCC patients (mean 50.1 years vs 44.3 years P=0.008). The hazardratio for sporadic cases was 2.93 (95% CI 1.06-8.11) compared with the HNPCC group (P=0.038). Conclusion:Our findings corroborate the results of previous studies which showed overall survival of colorectal cancer inpatients with HNPCC is better than with sporadic CRC patients.     

A propensity score-matched analysis of oncological outcome after systemic therapy for stage IV colorectal cancer: Impact of synchronous ovarian metastases

The reported incidence of synchronous and metachronous ovarian metastases (OM) from colorectal cancer (CRC) is ~3.4%. OM from CRC are often considered sanctuary sites due to their lower sensitivity to systemic treatment. It has thus been hypothesized that the presence of OM decreases overall survival. Therefore, the purpose of our study was to evaluate the impact of synchronous OM on overall survival in female patients with stage IV CRC treated with systemic therapy alone with palliative intent. The present study used data from the Netherlands Cancer Registry and included female CRC patients with synchronous systemic metastases who were treated with systemic therapy between 2008 and 2018. A subsample was created using propensity score matching to create comparable groups. Propensity scores were determined using a logistic regression model in which the dependent variable was the presence of OM and the independent variables were the variables that differed significantly between both groups. Our study included 5253 patients with stage IV CRC that received systemic therapy. Among these patients, 161 (3%) had OM while 5092 (97%) had extra-ovarian metastases only. Three-year overall survival rates did not show a significant difference between patients with OM compared to patients without ovarian metastases. Moreover, the propensity score-matched analysis showed that the presence of OM in patients treated with systemic therapy for stage IV CRC disease was not associated with decreased 3-year overall survival. However, the results of the present study should be interpreted with caution, due to its observational character and used selection criteria.     

Modification to Systemic Anticancer Therapy at the Start of the COVID-19 Pandemic and its Overall Impact on Survival Outcomes in Patients with Colorectal Cancer

BackgroundSince the beginning of the COVID-19 pandemic, multiple changes to the provision of cancer care has been introduced to maximize patient safety and protect staff. We aimed to identify factors influencing clinicians’ decision on treatment modification during the initial phase of the pandemic, and to assess its impact on outcomes in patients with colorectal cancer.Patients and MethodsElectronic records of patients seen in a large United Kingdom tertiary cancer center was reviewed. The frequency and type of changes to systemic anticancer therapy , as well as the factors predicting clinicians’ decision were assessed.ResultsA total of 418 patients; mean age 63 ± 12 years and 57% male were included. More than half of the patients had modification to their treatment; with treatment delay (21%) or cancellation (10%), being the most common. Majority of patients on neoadjuvant treatment (97%) proceeded with treatment, with some form of treatment modification in 20%. Half of patients on adjuvant treatment had their treatment plan modified. Overall, a change in treatment was more likely in older patients (OR 1.028 [95% CI 1.010-1.047]; P = .002), and in patients who had already received higher number of cycles of systemic anticancer therapy (OR 1.040 [95% CI 1.016-1.065]; P = .001). A change in treatment was less likely further out of the first national lockdown (OR 0.837 [95% CI 0.758-0.925]; P < .001). Patients on third-line treatment were most likely to have alterations to their treatment plan (69%, n=33/48).ConclusionDuring the first wave of COVID-19 in the United Kingdom, clinicians adapted clinical practice in accordance to local and national guidance, especially amongst older patients and those on third-line treatment. Further real-world data are needed to document the important impact of changes to treatment on outcomes in patients with cancer.     

DEK 的表达与结直肠癌患者预后的相关性研究

目的：采用免疫组化技术,分析DEK基因在结直肠癌患者中的表达情况及其与预后的相关性。方法：运用免疫组化SP法,检测DEK基因在169例结直肠癌患者肿瘤组织及癌旁组织中的表达情况,并运用统计分析软件分析DEK表达水平与结直肠癌患者预后的相关性。结果：DEK的表达率在结直肠癌组织（85／169,50．30％）明显高于癌旁正常组织（28／169,16．57％）,差异具有统计学意义（P〈0．01）。DEK在肿瘤组织中的表达情况与病人年龄、性别、肿瘤分化程度、TNM分期及肿瘤大小等因素无相关性,与总生存率（OS）显著相关（P〈0．05）。结论：DEK表达水平与结直肠癌预后密切相关,DEK高表达的结直肠癌患者预后较差。     

Colorectal cancer survival in the Nordic countries and the United Kingdom: excess mortality risk analysis of 5 year relative period survival in the period 1999 to 2000

A deficit in colorectal cancer survival in Denmark and in the UK compared to Sweden, Norway and Finland was found in the EUROCARE studies. We set out to explore if these differences still exist. Patients diagnosed with colorectal cancer as their first invasive cancer at age 15-89 in the period 1994-2000 were identified using data from 11 cancer registries in the UK and from four Nordic countries. Five-year relative period survival using deaths in 1999-2000 following cancers diagnosed in 1994-2000 was analysed with excess mortality risk modelling. Follow-up time since diagnosis with age as an effect-modifier in the first half year was the most important factor with the highest excess risk of death immediately after diagnosis and with higher age and decreasing with length of follow-up. Variations between countries were bigger in the first half year following diagnosis than in the interval 0.5-5 years with about 30% higher risk in UK and Denmark. The differences between countries are still substantial and the order has not changed, even if the five year relative survival has improved since the EUROCARE studies. Patient management, diagnostics, and comorbidity likely explain the excess deaths in UK and Denmark during the first 6 months. The effect of stage and quality of management and treatment should be examined in population based studies with detailed patient information. Use of more detailed age-intervals than conventionally applied in survival studies proved to be important in statistical modelling and is recommended for future studies.     

Survival Rate of Colorectal Cancer in Iran: A Systematic Review and Meta-Analysis

Background: Different studies have been conducted to estimate the survival rate of colorectal cancer in Iran butthere is no overall estimate of the survival rate. The aim of this study was to calculate the pooled 1, 3, and 5-year survivalrate of the patients with colorectal cancer in Iran. Methods: To retrieve relevant studies, we conducted a systematicsearch in Iranian databases, including Iran Medex, Magiran, SID, and international databases such as Medlin/PubMed,Scopus, and Google scholar using “Colorectal Neoplasms” and “Survival Rate” as keywords up to December 1st, 2017.We used random effect model to estimate pooled 1, 3, and 5-year survival rates of the patients with colorectal cancerin Iran. To assess the heterogeneity, we used Chi-squared test at the 5 % significance level (p <0.05) and I2 Index. Weused meta-regression and subgroup analysis to find a potential source of heterogeneity. Results: After a systematicsearch, 196 articles were found, of the 38 studies met the eligibility criteria and are included in our meta-analysis. Thepooled 1, 3, and 5-year survival rates in patient with colorectal cancer were 0.84 (95% CI: 0.81-0.87), 0.64 (95%CI:0.59-0.70), and 0.54 (95%CI: 0.49-0.58) respectively. The 5-year survival rate in the subgroup of women was 0.5(0.44-0.56) and in male subgroup was 0.44 (0.40-0.48). In a subgroup of the tumor site, the 5-year survival rate in coloncancer was 0.6 (0.49-0.75) and rectum cancer was 0.54 (0.36-0.69). In multivariable models, there was a significantassociation between years of study and 5-year survival rate as a source of heterogeneity (β = 18.9, P=0.01). Conclusion:According to the results of this study, women had a better survival rate than men, and according to the tumor site, the5-year survival rate in colon cancer was better than the rectum cancer.     

A long non-coding RNA signature to improve prognosis prediction of colorectal cancer

Increasing evidence suggests long non-coding RNAs (lncRNAs) are frequently aberrantly expressed in cancers, however, few related lncRNA signatures have been established for prediction of cancer prognosis. We aimed to develop a lncRNA signature to improve prognosis prediction of colorectal cancer (CRC). Using a lncRNA-mining approach, we performed lncRNA expression profiling in large CRC cohorts from Gene Expression Ominus (GEO), including {"type":"entrez-geo","attrs":{"text":"GSE39582","term_id":"39582"}}GSE39582 test series(N=436), internal validation series (N=117); and two independent validation series {"type":"entrez-geo","attrs":{"text":"GSE14333","term_id":"14333"}}GSE14333 (N=197) and {"type":"entrez-geo","attrs":{"text":"GSE17536","term_id":"17536"}}GSE17536(N=145). We established a set of six lncRNAs that were significantly correlated with the disease free survival (DFS) in the test series. Based on this six-lncRNA signature, the test series patients could be classified into high-risk and low-risk subgroups with significantly different DFS (HR=2.670; P<0.0001). The prognostic value of this six-lncRNA signature was confirmed in the internal validation series and another two independent CRC sets. Gene set enrichment analysis (GSEA) analysis suggested that risk score positively correlated with several cancer metastasis related pathways. Functional experiments demonstrated three dysregulated lncRNAs, {"type":"entrez-nucleotide","attrs":{"text":"AK123657","term_id":"34529258"}}AK123657, {"type":"entrez-nucleotide","attrs":{"text":"BX648207","term_id":"34367366"}}BX648207 and {"type":"entrez-nucleotide","attrs":{"text":"BX649059","term_id":"34368231"}}BX649059 were required for efficient invasion and proliferation suppression in CRC cell lines. Our results might provide an efficient classification tool for clinical prognosis evaluation of CRC.     

Do metastatic colorectal cancer patients who present with late relapse after curative surgery have a better survival?

Background:

Patients who relapse after potentially curative surgery for colorectal cancer tend to relapse within 5 years. There is, however, a group of patients who relapse beyond 5 years after resection and this late relapsing group may have a different behaviour and prognosis.

Methods:

We analysed data from a prospective population-based registry to compare the characteristics and survival of relapsed patients with metachronous mCRC. Patients were categorised into relapse at <2, 2–5 and >5 years following their initial surgery. Univariate log-rank tests and multivariate Cox regression was performed to determine whether time to relapse (TTR) and other factors were associated with overall survival (OS).

Results:

A total of 750 metachronous mCRC patients were identified. In all, 56% relapsed ⩽2 years, 32.4% at 2–5 years and 11.6% >5 years. Median survival time from the time of diagnosis of mCRC for the three groups was 17.6, 26.1 and 27.5 months, respectively. Short TTR (<2 years) was significantly associated with survival (HR=0.75, 95% confidence interval (CI)=0.60–0.93 and HR=0.73, 95% CI=0.53–1.01, respectively, for 2–5 and >5 years vs <2 years, P<0.05). However, there was no significant difference in survival between patients who relapsed at 5 years or later compared with those who relapsed between 2 and 5 years (HR=0.98, 95% CI=0.69–1.38, P=0.90).

Conclusion:

TTR within 2 years is an independent predictor of shorter survival time for mCRC patients who experience a relapse. These data do not support the hypothesis that patients who have late relapse late (>5 years) have a ‘better'' biology or survival compared with patients with a TTR of 2–5 years.     

A Q-TWiST analysis comparing panitumumab plus best supportive care (BSC) with BSC alone in patients with wild-type KRAS metastatic colorectal cancer

Background:

Panitumumab+best supportive care (BSC) significantly improved progression-free survival (PFS) vs BSC alone in patients with chemo-refractory wild-type KRAS metastatic colorectal cancer (mCRC). We applied the quality-adjusted time without symptoms of disease or toxicity (Q-TWiST) analysis to provide an integrated measure of clinical benefit, with the objective of comparing quality-adjusted survival between the two arms. As the trial design allowed patients on BSC alone to receive panitumumab after disease progression, which confounded overall survival (OS), the focus of this analysis was on PFS.

Methods:

For each treatment group, the time spent in the toxicity (grade 3 or 4 adverse events; TOX), time without symptoms of disease or toxicity (TWiST), and relapse (after disease progression; REL) states were estimated by the product-limit method, and adjusted using utility weights derived from patient-reported EuroQoL 5-dimensions measures. Sensitivity analyses were performed in which utility weights (varying from 0 to 1) were applied to time in the TOX and REL health states.

Results:

There was a significant difference between groups favouring panitumumab+BSC in quality-adjusted PFS (12.3 weeks vs 5.8 weeks, respectively, P<0.0001) and quality-adjusted OS (P=0.0303).

Conclusion:

In patients with chemo-refractory wild-type KRAS mCRC, panitumumab+BSC significantly improved quality-adjusted survival compared with BSC alone.