Background The incidence of T1 colorectal cancer (CRC) has increased with the implementation of CRC screening programs. It is unknown whether the outcomes and risk models for T1 CRC based on non... Show moreBackground The incidence of T1 colorectal cancer (CRC) has increased with the implementation of CRC screening programs. It is unknown whether the outcomes and risk models for T1 CRC based on non-screen-detected patients can be extrapolated to screen-detected T1 CRC. This study aimed to compare the stage distribution and oncologic outcomes of T1 CRC patients within and outside the screening program.Methods Data from T1 CRC patients diagnosed between 2014 and 2017 were collected from 12 hospitals in the Netherlands. The presence of lymph node metastasis (LNM) at diagnosis was compared between screen-detected and non-screen-detected patients using multivariable logistic regression. Cox proportional hazard regression was used to analyze differences in the time to recurrence (TTR), metastasis-free survival (MFS), cancer-specific survival (CSS), and overall survival. Additionally, the performance of conventional risk factors for LNM was evaluated across the groups.Results 1803 patients were included (1114 [62%] screen-detected), with median follow-up of 51 months (interquartile range 30). The proportion of LNM did not significantly differ between screen- and non-screen-detected patients (12.6% vs. 8.9%; odds ratio 1.41; 95%CI 0.89–2.23); a prediction model for LNM performed equally in both groups. The 3- and 5-year TTR, MFS, and CSS were similar for patients within and outside the screening program. However, overall survival was significantly longer in screen-detected T1 CRC patients (adjusted hazard ratio 0.51; 95%CI 0.38–0.68).Conclusions Screen-detected and non-screen-detected T1 CRCs have similar stage distributions and oncologic outcomes and can therefore be treated equally. However, screen-detected T1 CRC patients exhibit a lower rate of non-CRC-related mortality, resulting in longer overall survival. Show less
Background In 2014, a population-based colorectal cancer (CRC) screening programme was stepwise implemented in the Netherlands comprising faecal immunochemical testing once every 2 years, with a... Show moreBackground In 2014, a population-based colorectal cancer (CRC) screening programme was stepwise implemented in the Netherlands comprising faecal immunochemical testing once every 2 years, with a cutoff value for positivity of 47 mu g haemoglobin per g faeces. We aimed to assess CRC incidence, mortality, tumour characteristics, and treatment before and after introduction of this screening programme.Methods We did a retrospective, observational, population-based study in the Netherlands and gathered CRC incidence data from the Netherlands Cancer Registry from Jan 1, 2010, to Dec 31, 2019, in people aged 55 years or older. Patients with a CRC diagnosis between Jan 1, 2014, and Dec 31, 2018, in the Netherlands Cancer Registry were linked with the nationwide registry of histopathology and cytopathology (PALGA) to identify mode of detection (ie, screening-detected vs clinically detected). We calculated age-standardised CRC incidence rates and used data from Statistics Netherlands to calculate CRC-related mortality in 2010-19. We compared localisation, stage distribution, and treatment of screening-detected CRCs with clinically detected CRCs diagnosed in 2014-18 in patients aged 55-75 years.Findings Between Jan 1, 2010, and Dec 31, 2019, 125 215 CRCs were diagnosed in individuals aged 55 years or older and were included in the analyses for CRC incidence. Before the introduction of the screening programme, the age-standardised CRC incidence rate was 214.3 per 100 000 population in 2013 in people aged 55 years or older. After the introduction of the screening programme, this rate initially increased to 259.2 per 100 000 population in 2015, and subsequently decreased to 181.5 per 100 000 population in 2019. Age-standardised incidence rates for advanced CRCs (stage III and IV) were 117.0 per 100 000 population in 2013 and increased to 122.8 per 100 000 population in 2015; this rate then decreased to 94.7 per 100 000 population in 2018. Age-standardised CRC mortality decreased from 87.5 deaths per 100 000 population in 2010 to 64.8 per 100 000 population in 2019. Compared with clinically detected CRCs, screening-detected CRCs were more likely to be located in the left side of the colon (48.6% vs 35.2%) and to be detected at an early stage (I or II; 66. 7% vs 46.2%). Screening-detected CRCs were more likely to be treated by local excision compared with clinically detected CRCs, and this fmding persisted when stage I CRCs were analysed separately.Interpretation After introduction of this national screening programme, a decrease in overall and advanced-stage CRC incidence was observed. In view of this observation, together with the observed shift to detection at earlier stages and more screening-detected CRCs being treated by local excision, we might cautiously conclude that, in the long-term, faecal immunochemical testing-based screening could ultimately lead to a decrease in CRC-related morbidity and mortality. Copyright (C) 2021 Elsevier Ltd. All rights reserved. Show less
Vlies, E. van der; Vernooij, L.M.; Erning, F.N. van; Vink, G.R.; Bos, W.J.W.; Portielje, J.E.A.; ... ; M. los 2021
Background: Surgery is the primary treatment for non-metastatic colorectal cancer (CRC) but is omitted in a proportion of older patients. Characteristics and prognosis of non-surgical patients are... Show moreBackground: Surgery is the primary treatment for non-metastatic colorectal cancer (CRC) but is omitted in a proportion of older patients. Characteristics and prognosis of non-surgical patients are largely unknown.Objective: To examine the characteristics and survival of surgical and non-surgical older patients with non-metastatic CRC in the Netherlands.Methods: All patients aged >= 70 years and diagnosed with non-metastatic CRC between 2014 and 2018 were identified in the Netherlands Cancer Registry. Patients were divided based on whether they underwent surgery or not. Three-year overall survival (OS) and relative survival (RS) were calculated for both groups separately. Relative survival and relative excess risks (RER) of death were used as measures for cancer-related survival.Results: In total, 987/20.423 (5%) colon cancer patients and 1.459/7.335 (20%) rectal cancer patients did not undergo surgery. Non-surgical treatment increased over time from 3.7% in 2014 to 4.8% in 2018 in colon cancer patients (P = 0.01) and from 17.1% to 20.2% in rectal cancer patients (P = 0.03). 3 year RS was 91% and 9% for surgical and non-surgical patients with colon cancer, respectively. For rectal cancer patients this was 93% and 37%, respectively. In surgical patients, advanced age (>= 80 years) did not decrease RS (colon; RER 0.9 (0.7-1.0), rectum; RER 0.9 (0.7-1.1)). In non-surgical rectal cancer patients, higher survival rates were observed in patients treated with chemoradiotherapy (OS 56%, RS 65%), or radiotherapy (OS 19%, RS 27%), compared to no treatment (OS 9%, RS 10%).Conclusion: Non-surgical treatment in older Dutch CRC patients has increased over time. Because survival of patients with colon cancer is very poor in the absence of surgery, this treatment decision must be carefully weighed. (Chemo-)radiotherapy may be a good alternative for rectal cancer surgery in older frail patients. (C) 2021 Elsevier Ltd, BASO similar to The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved. Show less
BackgroundIn 2014, a population-based colorectal cancer (CRC) screening programme was stepwise implemented in the Netherlands comprising faecal immunochemical testing once every 2 years, with a... Show moreBackgroundIn 2014, a population-based colorectal cancer (CRC) screening programme was stepwise implemented in the Netherlands comprising faecal immunochemical testing once every 2 years, with a cutoff value for positivity of 47 μg haemoglobin per g faeces. We aimed to assess CRC incidence, mortality, tumour characteristics, and treatment before and after introduction of this screening programme.MethodsWe did a retrospective, observational, population-based study in the Netherlands and gathered CRC incidence data from the Netherlands Cancer Registry from Jan 1, 2010, to Dec 31, 2019, in people aged 55 years or older. Patients with a CRC diagnosis between Jan 1, 2014, and Dec 31, 2018, in the Netherlands Cancer Registry were linked with the nationwide registry of histopathology and cytopathology (PALGA) to identify mode of detection (ie, screening-detected vs clinically detected). We calculated age-standardised CRC incidence rates and used data from Statistics Netherlands to calculate CRC-related mortality in 2010–19. We compared localisation, stage distribution, and treatment of screening-detected CRCs with clinically detected CRCs diagnosed in 2014–18 in patients aged 55–75 years.FindingsBetween Jan 1, 2010, and Dec 31, 2019, 125 215 CRCs were diagnosed in individuals aged 55 years or older and were included in the analyses for CRC incidence. Before the introduction of the screening programme, the age-standardised CRC incidence rate was 214·3 per 100 000 population in 2013 in people aged 55 years or older. After the introduction of the screening programme, this rate initially increased to 259·2 per 100 000 population in 2015, and subsequently decreased to 181·5 per 100 000 population in 2019. Age-standardised incidence rates for advanced CRCs (stage III and IV) were 117·0 per 100 000 population in 2013 and increased to 122·8 per 100 000 population in 2015; this rate then decreased to 94·7 per 100 000 population in 2018. Age-standardised CRC mortality decreased from 87·5 deaths per 100 000 population in 2010 to 64·8 per 100 000 population in 2019. Compared with clinically detected CRCs, screening-detected CRCs were more likely to be located in the left side of the colon (48·6% vs 35·2%) and to be detected at an early stage (I or II; 66·7% vs 46·2%). Screening-detected CRCs were more likely to be treated by local excision compared with clinically detected CRCs, and this finding persisted when stage I CRCs were analysed separately.InterpretationAfter introduction of this national screening programme, a decrease in overall and advanced-stage CRC incidence was observed. In view of this observation, together with the observed shift to detection at earlier stages and more screening-detected CRCs being treated by local excision, we might cautiously conclude that, in the long-term, faecal immunochemical testing-based screening could ultimately lead to a decrease in CRC-related morbidity and mortality. Show less
For a nationwide real-word data study on the application of predictive mutation testing of patients with colorectal cancer (CRC) for anti-epidermal growth factor receptor (EGFR) therapy... Show moreFor a nationwide real-word data study on the application of predictive mutation testing of patients with colorectal cancer (CRC) for anti-epidermal growth factor receptor (EGFR) therapy stratification, pathology data were collected from the Dutch Pathology Registry from October 2017 until June 2019 (N=4060) and linked with the Netherlands Cancer Registry. Mutation testing rates increased from 24% at diagnosis of stage IV disease to 60% after 20-23 months of follow-up (p<0.001). Application of anti-EGFR therapy in KRAS/NRAS wild-type patients was mainly observed from the third treatment line onwards (65% vs 17% in first/second treatment line (p<0.001)). The national average KRAS/NRAS/BRAF mutation rate was 63.9%, being similar for next-generation sequencing (NGS)-based approaches and single gene tests (64.4% vs 61.2%, p=ns). NGS-based approaches detected more additional potential biomarkers, for example, ERBB2 amplifications (p<0.05). Therefore, single gene tests are suitable to stratify patients with mCRC for anti-EGFR therapy, but NGS is superior enabling upfront identification of therapy resistance or facilitate enrolment into clinical trials. Show less
Cell-free DNA in the blood provides a non-invasive diagnostic avenue for patients with cancer'. However, characteristics of the origins and molecular features of cell-free DNA are poorly understood... Show moreCell-free DNA in the blood provides a non-invasive diagnostic avenue for patients with cancer'. However, characteristics of the origins and molecular features of cell-free DNA are poorly understood. Here we developed an approach to evaluate fragmentation patterns of cell-free DNA across the genome, and found that profiles of healthy individuals reflected nucleosomal patterns of white blood cells, whereas patients with cancer had altered fragmentation profiles. We used this method to analyse the fragmentation profiles of 236 patients with breast, colorectal, lung, ovarian, pancreatic, gastric or bile duct cancer and 245 healthy individuals. A machine learning model that incorporated genome-wide fragmentation features had sensitivities of detection ranging from 57% to more than 99% among the seven cancer types at 98% specificity, with an overall area under the curve value of 0.94. Fragmentation profiles could be used to identify the tissue of origin of the cancers to a limited number of sites in 75% of cases. Combining our approach with mutation-based cell-free DNA analyses detected 91% of patients with cancer. The results of these analyses highlight important properties of cell-free DNA and provide a proof-of-principle approach for the screening, early detection and monitoring of human cancer. Show less
Braak, R.R.J.C. van den; Rijssen, L.B. van; Kleef, J.J. van; Vink, G.R.; Berbee, M.; Henegouwen, M.I.V.; ... ; PLCRC Working Grp 2018
