We described changes in treatment of colon cancer over time and the impact on survival in The Netherlands in the period 1989–2006.
All 103744 patients with invasive colon cancer during 1989–2006 in ...The Netherlands were included. Data were extracted from The Netherlands Cancer Registry. Trends in treatment over time were analysed and multivariable relative survival analysis was carried out.
The administration of adjuvant chemotherapy in stage III patients <75 years increased from 19% in 1989–1993 to 79% in 2004–2006 and from 1% to 19% in stage III patients ≥75 years. Among stage IV patients, resection rates of the primary tumour decreased from 72% to 63%, while chemotherapy administration increased from 23% to 64% in those <75 years. Survival increased from 52% to 58% in males and from 55% to 58% among females. Stage III patients with adjuvant chemotherapy exhibited a relative excess risk of 0.4 (95% confidence interval 0.4–0.4) compared with those without. Among stage IV patients, resection of primary tumour, palliative chemotherapy, and metastasectomy were important prognostic factors.
There were substantial improvements in management and survival of colon cancer from 1989 to 2006. Stage III disease patients with colon cancer experienced the largest improvement in survival, most likely related to the increased administration of adjuvant chemotherapy.
Comorbidity has large impact on colorectal cancer (CRC) treatment and outcomes and may increase as the population ages. We aimed to evaluate the prevalence and time trends of comorbid diseases in ...patients with CRC from 1995 to 2010. The Eindhoven Cancer Registry registers comorbidity in all patients with primary CRC in the South of the Netherlands. We analyzed the prevalence of serious comorbid diseases in four time frames from 1995 to 2010. Thereby, we addressed its association with age, gender and socio‐economic status (SES). The prevalence of comorbidity was registered in 27,339 patients with primary CRC. During the study period, the prevalence of comorbidity increased from 47% to 62%, multimorbidity increased from 20% to 37%. Hypertension and cardiovascular diseases were most prevalent and increased largely over time (respectively 16–29% and 12–24%). Pulmonary diseases increased in women, but remained stable in men. Average age at diagnosis increased from 68.3 to 69.5 years (p = 0.004). A low SES and male gender were associated with a higher risk of comorbidity (not changing over time). This study indicates that comorbidity among patients with CRC is common, especially in males and patients with a low SES. The prevalence of comorbidity increased from 1995 to 2010, in particular in presumably nutritional diseases. Ageing, increased life expectancy and life style changes may contribute to more comorbid diseases. Also, improved awareness among health care providers on the importance of comorbidity may have resulted in better registration. The increasing burden of comorbidity in patients with CRC emphasizes the need for more focus on individualized medicine.
What's new
Treating cancer in a patient who also has other diseases or conditions can be challenging, but is not unusual. In this study, the authors looked at comorbidity in patients with colorectal cancer over a period of 16 years, and found it increased over the time frame of the study, particularly hypertension and cardiovascular diseases. Patients with multiple conditions are less likely to respond well to treatment. These data underscore the importance of individualized treatment and awareness of other conditions that are increasingly present alongside the cancer.
Abstract
A significant proportion of colorectal cancer (CRC) patients develop peritoneal metastases (PM) in the course of their disease. PMs are associated with a poor quality of life, significant ...morbidity and dismal disease outcome. To improve care for this patient group, a better understanding of the molecular characteristics of CRC-PM is required. Here we present a comprehensive molecular characterization of a cohort of 52 patients. This reveals that CRC-PM represent a distinct CRC molecular subtype, CMS4, but can be further divided in three separate categories, each presenting with unique features. We uncover that the CMS4-associated structural protein Moesin plays a key role in peritoneal dissemination. Finally, we define specific evolutionary features of CRC-PM which indicate that polyclonal metastatic seeding underlies these lesions. Together our results suggest that CRC-PM should be perceived as a distinct disease entity.
Abstract Cancer registries must provide complete and reliable incidence information with the shortest possible delay for use in studies such as comparability, clustering, cancer in the elderly and ...adequacy of cancer surveillance. Methods of varying complexity are available to registries for monitoring completeness and timeliness. We wished to know which methods are currently in use among cancer registries, and to compare the results of our findings to those of a survey carried out in 2006. Methods In the framework of the EUROCOURSE project, and to prepare cancer registries for participation in the ERA-net scheme, we launched a survey on the methods used to assess completeness, and also on the timeliness and methods of dissemination of results by registries. We sent the questionnaire to all general registries (GCRs) and specialised registries (SCRs) active in Europe and within the European Network of Cancer Registries (ENCR). Results With a response rate of 66% among GCRs and 59% among SCRs, we obtained data for analysis from 116 registries with a population coverage of ∼280 million. The most common methods used were comparison of trends (79%) and mortality/incidence ratios (more than 60%). More complex methods were used less commonly: capture–recapture by 30%, flow method by 18% and death certificate notification (DCN) methods with the Ajiki formula by 9%. The median latency for completion of ascertainment of incidence was 18 months. Additional time required for dissemination was of the order of 3–6 months, depending on the method: print or electronic. One fifth (21%) did not publish results for their own registry but only as a contribution to larger national or international data repositories and publications; this introduced a further delay in the availability of data. Conclusions Cancer registries should improve the practice of measuring their completeness regularly and should move from traditional to more quantitative methods. This could also have implications in the timeliness of data publication.
Genomic rearrangements that give rise to oncogenic gene fusions can offer actionable targets for cancer therapy. Here we present a systematic analysis of oncogenic gene fusions among a clinically ...well-characterized, prospectively collected set of 278 primary colon cancers spanning diverse tumor stages and clinical outcomes. Gene fusions and somatic genetic variations were identified in fresh frozen clinical specimens by Illumina RNA-sequencing, the STAR fusion gene detection pipeline, and GATK RNA-seq variant calling. We considered gene fusions to be pathogenically relevant when recurrent, producing divergent gene expression (outlier analysis), or as functionally important (e.g., kinase fusions). Overall, 2.5% of all specimens were defined as harboring a relevant gene fusion (kinase fusions 1.8%). Novel configurations of
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gene fusions resulting from chromosomal translocations were identified. An R-spondin fusion was found in only one tumor (0.35%), much less than an earlier reported frequency of 10% in colorectal cancers. We also found a novel fusion involving USP9X-ERAS formed by chromothripsis and leading to high expression of ERAS, a constitutively active RAS protein normally expressed only in embryonic stem cells. This USP9X-ERAS fusion appeared highly oncogenic on the basis of its ability to activate AKT signaling. Oncogenic fusions were identified only in lymph node-negative tumors that lacked BRAF or KRAS mutations. In summary, we identified several novel oncogenic gene fusions in colorectal cancer that may drive malignant development and offer new targets for personalized therapy.
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The availability of population-based cancer registry (CR) data is paramount in the development of modern oncology. Major contributions consisted in accurately measuring cancer burden (incidence, ...survival and prevalence, beside mortality), identifying and quantifying risk factors (case control and cohort studies that, in the last two decades, included gene variant assessment) and evaluating outcomes of treatments and preventive interventions, including mass screening. Cancer registration coverage of European populations progressed slowly since 1940 and is now almost 50%. Areas lacking high-quality national population-based cancer registration still exist within large countries such as France, Italy, Romania and Spain, Germany and Poland having national plans and legislation to reach complete coverage. Depending on programme ownership, history and institutional organisation, European CRs showed huge variations in the scope (research domain), size, available resources and finally exploitation of collected data. This reflects their heterogeneous origins stemming from different professional backgrounds and healthcare systems. This review discusses not only the potential for contributing to acceleration of prevention but also the coverage expansion by and innovation of CR organizations. The latter can be attained not only by more standardisation in institutional organisation and operative methodologies but also by intensification of scientific production and risk communication. The CR's agenda should focus on cancers caused by identifiable risk factor(s) that are amenable to preventive actions, including early detection; short-term priorities usually are with tobacco, and medium-term priorities are with alcohol, occupational exposures, infection-related cancers and ultraviolet-related skin cancers, while obesity-related cancers are likely to increase gradually further in the long term.
There are profound individual differences in clinical outcomes between colorectal cancers (CRCs) presenting with identical stage of disease. Molecular stratification, in conjunction with the ...traditional TNM staging, is a promising way to predict patient outcomes. We investigated the interconnectivity between tumor stage and tumor biology reflected by the Consensus Molecular Subtypes (CMSs) in CRC, and explored the possible value of these insights in patients with stage II colon cancer.
We performed a retrospective analysis using clinical records and gene expression profiling in a meta-cohort of 1040 CRC patients. The interconnectivity of tumor biology and disease stage was assessed by investigating the association between CMSs and TNM classification. In order to validate the clinical applicability of our findings we employed a meta-cohort of 197 stage II colon cancers.
CMS4 was significantly more prevalent in advanced stages of disease (stage I 9.8% versus stage IV 38.5%, p < 0.001). The observed differential gene expression between cancer stages is at least partly explained by the biological differences as reflected by CMS subtypes. Gene signatures for stage III-IV and CMS4 were highly correlated (r = 0.77, p < 0.001). CMS4 cancers showed an increased progression rate to more advanced stages (CMS4 compared to CMS2: 1.25, 95% CI: 1.08-1.46). Patients with a CMS4 cancer had worse survival in the high-risk stage II tumors compared to the total stage II cohort (5-year DFS 41.7% versus 100.0%, p = 0.008).
Considerable interconnectivity between tumor biology and tumor stage in CRC exists. This implies that the TNM stage, in addition to the stage of progression, might also reflect distinct biological disease entities. These insights can potentially be utilized to optimize identification of high-risk stage II colon cancers.
Summary Background Skin cancer is an important, growing public health problem among white caucasians, causing a heavy burden on dermatologists and general practitioners.
Objectives To predict the ...future incidence of skin cancer in the Netherlands up to 2015.
Methods Expected numbers of skin cancer cases in the Netherlands up to 2015 were calculated by trend modelling of observed rates for melanoma and squamous cell carcinoma (SCC) between 1989 and 2000 obtained from the Netherlands Cancer Registry and for basal cell carcinoma (BCC) obtained from the Eindhoven Cancer Registry; these rates were then multiplied by the predicted age distributions. Incidence rates were fitted to four different models, and predictions were based on the best fitting model.
Results An increase of 80% in the total number of skin cancer patients is expected in the Netherlands: from 20 654 in 2000 to 37 342 in 2015. The total number of melanoma cases is expected to increase by 99%, with the largest increase for males (males aged 35–64, 111%; males aged ≥ 65, 139%). Numbers of patients with SCC will increase overall by 80%, mainly among older males and females (increase of 79%) and females aged 35–64 (increase of 93%). The number of cases of BCC will increase by 78%, with the largest increase for the combined groups, those aged 15–64 (males, 66% increase; females, 94% increase), especially for sites other than the head and neck. The contribution of demographic changes (ageing effect) was largest for males with BCC and SCC (35–44%).
Conclusions If incidence rates for skin cancers in the Netherlands continue to increase and population growth and ageing remain unabated, a rise in annual demand for care of more than 5% could occur, putting a heavy burden on general practitioners and dermatologists. In the absence of marked changes in current ultraviolet radiation exposure, these increases will probably continue after 2015.
Abstract Aim To provide insight into cancer registration coverage, data access and use in Europe. This contributes to data and infrastructure harmonisation and will foster a more prominent role of ...cancer registries (CRs) within public health, clinical policy and cancer research, whether within or outside the European Research Area. Methods During 2010–12 an extensive survey of cancer registration practices and data use was conducted among 161 population-based CRs across Europe. Responding registries (66%) operated in 33 countries, including 23 with national coverage. Results Population-based oncological surveillance started during the 1940–50s in the northwest of Europe and from the 1970s to 1990s in other regions. The European Union (EU) protection regulations affected data access, especially in Germany and France, but less in the Netherlands or Belgium. Regular reports were produced by CRs on incidence rates (95%), survival (60%) and stage for selected tumours (80%). Evaluation of cancer control and quality of care remained modest except in a few dedicated CRs. Variables evaluated were support of clinical audits, monitoring adherence to clinical guidelines, improvement of cancer care and evaluation of mass cancer screening. Evaluation of diagnostic imaging tools was only occasional. Conclusion Most population-based CRs are well equipped for strengthening cancer surveillance across Europe. Data quality and intensity of use depend on the role the cancer registry plays in the politico, oncomedical and public health setting within the country. Standard registration methodology could therefore not be translated to equivalent advances in cancer prevention and mass screening, quality of care, translational research of prognosis and survivorship across Europe. Further European collaboration remains essential to ensure access to data and comparability of the results.
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