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Background In current practice, rates of locally recurrent rectal cancer (LRRC) are low due to the use of the total mesorectal excision (TME) in combination with various neoadjuvant treatment strategies. However, the literature on LRRC mainly consists of single- and multicenter retrospective cohort studies, which are prone to selection bias. The aim of this study is to provide a nationwide, population-based overview of LRRC after TME in the Netherlands. Patients and Methods In total, 1431 patients with nonmetastasized primary rectal cancer diagnosed in the first six months of 2015 and treated with TME were included from the nationwide, population-based Netherlands Cancer Registry. Data on disease recurrence were collected for patients diagnosed in these 6 months only. Competing risk cumulative incidence, competing risk regression, and Kaplan–Meier analyses were performed to assess incidence, risk factors, treatment, and overall survival (OS) of LRRC. Results Three-year cumulative incidence of LRRC was 6.4%; synchronous distant metastases (LRRC-M1) were present in 44.9% of patients with LRRC. Distal localization, R1–2 margin, (y)pT3-4, and (y)pN1-2 were associated with an increased LRRC rate. No differences in LRRC treatment and OS were found between patients who had been treated with or without prior n(C)RT. Curative-intent treatment was given to 42.9% of patients with LRRC, and 3-year OS thereafter was 70%. Conclusions Nationwide LRRC incidence was low. A high proportion of patients with LRRC underwent curative-intent treatment, and OS of this group was high in comparison with previous studies. Additionally, n(C)RT for primary rectal cancer was not associated with differences in treatment and OS of LRRC.

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Introduction: – This population-based study aimed to investigate incidence, risk factors, treatment, and survival of synchronous peritoneal metastases (PM) of hepatobiliary origin. Methods: – All Dutch patients diagnosed with hepatobiliary cancer between 2009 and 2018 were selected. Factors associated with PM were identified with logistic regression analyses. Treatments for patients with PM were categorized into local therapy, systemic therapy, and best supportive care (BSC). Overall survival (OS) was investigated using log-rank test. Results: – In total, 12 649 patients were diagnosed with hepatobiliary cancer of whom 8% (n = 1066) were diagnosed with synchronous PM (12% [n = 882/6519] in biliary tract cancer [BTC] vs. 4% [n = 184/5248] in hepatocellular carcinoma [HCC]). Factors that were positively associated with PM were the female sex (OR 1.18, 95% CI 1.03–1.35), BTC (OR 2.93, 95% CI 2.46–3.50), diagnosis in more recent years (2013–2015: OR 1.42, 95% CI 1.20–1.68; 2016–2018: OR 1.48, 95% CI 1.26–1.75), T3/T4 stage (OR 1.84, 95% CI 1.55–2.18), N1/N2 stage (OR 1.31, 95% CI 1.12–1.53) and other synchronous systemic metastases (OR 1.85, 95% CI 1.62–2.12). Of all PM patients, 723 (68%) received BSC only. Median OS was 2.7 months (IQR 0.9–8.2) in PM patients. Conclusion: – Synchronous PM were found in 8% of all hepatobiliary cancer patients and occurred more often in BTC than in HCC. Most patients with PM received BSC only. Given the high incidence and dismal prognosis of PM patients, extended research in hepatobiliary PM is needed to achieve better outcome in these patients.

PURPOSE: The genetic characteristics and mismatch repair (MMR) status of the primary tumor and corresponding metastases in colorectal cancer (CRC) are generally considered to be highly concordant. This implies that either the primary or metastatic tumor can be used for testing gene mutation and MMR status. However, whether this is also true for CRC and their ovarian metastases is currently unknown. Ovarian metastases generally show a poorer response to systemic therapy compared to other metastatic sites. Differences in biomarker status between primary CRC and ovarian metastases could possibly explain this difference in therapy response.METHODS: The study cohort was selected from CRC patients treated in two Dutch hospitals. Eligible patients with CRC and ovarian metastasis who were surgically treated between 2011 and 2018 were included. CRC and corresponding ovarian metastatic tissues were paired. Gene mutation status was established using next-generation sequencing, while the MMR status was established using either immunohistochemistry or microsatellite instability analysis.RESULTS: Matched samples of CRC and ovarian metastasis from 26 patients were available for analysis. A biomarker concordance of 100% was detected.CONCLUSION: Complete biomarker concordance was found between MMR proficient CRC and their matching ovarian metastasis. Biomarker testing of MMR proficient CRC tissue appears to be sufficient, and additional testing of metastatic ovarian tissue is not necessary. Differences in therapy response between ovarian metastases and other metastases from CRC are thus unlikely to be caused by differences in the genetic status.

Objective The aim of the study was to gain insight in the incidence, treatment, and survival of patients with synchronous pancreatic peritoneal metastases. Methods All patients diagnosed with pancreatic cancer between 2008 and 2018 in the Netherlands Cancer Registry were evaluated. The patients were subcategorized as (1) synchronous peritoneal metastases, (2) synchronous systemic metastases, and (3) no metastases. Results In total, 25,334 patients with pancreatic cancer were included. Among them, 3524 (14%) presented with synchronous peritoneal metastases, 10,659 (42%) with systemic metastases, and 11,151 (44%) without metastases at the time of diagnosis. The proportion of the patients diagnosed with peritoneal metastases increased over time (11%, 2008; 16%, 2018; P < 0.001). Of these patients, 964 (27%) received cancer treatment and 2560 (73%) received best supportive care. The median overall survival in patients with peritoneal metastases, systemic metastases, and without metastases was 1.9, 2.4, and 8.0 months, respectively (P < 0.001). In the patients with peritoneal metastases, the median overall survival was 5.0 months when undergoing cancer treatment and 1.3 months with best supportive care (P < 0.001). Conclusions Patients with pancreatic cancer are increasingly diagnosed with synchronous peritoneal metastases. Given the current dismal prognosis, research to improve treatment is designated for this patient category.

The reported incidence of synchronous and metachronous ovarian metastases (OM) from colorectal cancer (CRC) is approximately 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 this 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. This study included 5,253 patients with stage IV CRC that received systemic therapy. Among these patients, 161 (3%) had OM while 5,092 (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 three-year overall survival. However, the results of the present study should be interpreted with caution, due to its observational character and used selection criteria.

The reported outcomes of locoregionally recurrent colon cancer (LRCC) are poor, but the literature about LRCC is scarce and aged. Recent population-based studies to provide current insight into LRCC are warranted. This study aimed to provide an overview of the incidence, risk factors, treatment, and overall survival (OS) of patients with LRCC after curative resection of stage I-III primary colon cancer.Data on disease recurrence were collected for all patients with a diagnosis of non-metastasized primary colon cancer in the Netherlands during the first 6 months of 2015. Patients who underwent surgical resection (N = 3544) were included in this study. The 3-year cumulative incidence, risk factors, treatment, and OS for patients with LRCC were determined.The 3-year cumulative incidence of LRCC was 3.8%. Synchronous distant metastases (LRCC-M1) were diagnosed in 62.7% of the patients. The risk factors for LRCC were age of 70 years or older, pT4, pN1-2, and R1-2. Adjuvant chemotherapy was associated with a decreased risk of LRCC for high-risk stage II and stage III patients [hazard ratio (HR), 0.47; 95% confidence interval (CI) 0.31-0.93]. The median OS for the patients with LRCC was 13.1 months (95% CI 9.1-18.3 months). Curative-intent treatment was given to 22.4% of the LRCC patients, and the subsequent 3 years OS was 71% (95% CI 58-87%). The patients treated with palliative treatment and best supportive care showed 3-year OS rates of 15% (95% CI 7.0-31%) and 3.7% (95% CI 1.0-14%), respectively.The cumulative incidence of LRCC was low, and adjuvant chemotherapy was associated with a decreased risk for LRCC among targeted patients. Curative-intent treatment was given to nearly 1 in 4 LRCC patients, and the OS for this group was high.

Patient's quality of life should be included in clinical decision making regarding the administration of adjuvant chemotherapy (ACT) in stage II/III colon cancer. Therefore, quality of life, summarized as health utility (HU), was evaluated for patients treated with and without ACT. Furthermore, the role of chemotherapy–induced peripheral neuropathy (CIPN) on HU was evaluated. Patients diagnosed with stage II/III colon cancer between 2011 and 2019 and participating in the Prospective Dutch ColoRectal Cancer cohort were included (n = 914). HU scores were assessed with the EQ‐5D‐5L at baseline, 3, 6, 12, 18, and 24 months. Patients treated with ACT received mainly capecitabine and oxaliplatin (57%) or capecitabine monotherapy (40%) (average duration: 3.5 months). HU 3 to 18 months after diagnosis (potential ACT period + 12 months follow‐up) was compared between patients treated with and without ACT using a mixed model adjusted for age, sex and education level. Subsequently, the CIPN sensory, motor and autonomy scales, measured using the EORTC QLQ‐CIPN20, were independently included in the model to evaluate the impact of neuropathy. Using a mixed model, a significant difference of −0.039 (95% confidence interval: −0.062; −0.015) in HU was found between patients treated with and without ACT. Including the CIPN sensory, motor and autonomy scales decreased the difference with 0.019, 0.015 and 0.02, respectively. HU 3 to 18 months after diagnosis is significantly lower in patients treated with ACT vs without ACT. This difference is on the boundary of clinical relevance and appears to be partly related to the sensory and motor neuropathy‐related side effects of ACT., What's new? Given its potentially serious side effects, patient quality of life should be included in clinical decision‐making regarding the administration of adjuvant chemotherapy in stage II/III colon cancer. Using a mixed model which was corrected for relevant covariates, here the authors found a statistically‐significant but small decrease in HU of −0.039 during chemotherapy and the following 12 months for patients treated with adjuvant chemotherapy compared to patients without adjuvant chemotherapy. The decrease in HU, which is on the boundary of clinical relevance, appears to be partly related to sensory and motor neuropathy side effects of adjuvant chemotherapy.

Background Primary anastomosis (PA) in left-sided colorectal cancer (CRC) surgery in elderly patients is disputed. The aim of our study was to evaluate the differences in postoperative outcomes after left-sided CRC surgery in elderly patients in The Netherlands, comparing patients with PA and those who underwent end-ostomy (EO). Method Patients aged ≥ 75 years with stage I–III left-sided CRC, diagnosed and surgically treated in 2015–2017 were selected from the Netherlands Cancer Registry (n = 3286). Postoperative outcomes, short-term (30-, 60-, and 90-day) mortality and 3-year overall and relative survival were analyzed, stratified by surgical resection with PA versus EO. Propensity score matching (PSM) and multivariable logistic regression analysis were conducted. Results Patients with higher age, higher American Society of Anesthesiologists classification and higher tumor stage, a perforation, ileus or tumor located in the proximal rectum, and after open or converted surgery were more likely to receive EO. No difference in anastomotic leakage was seen in PA patients with or without defunctioning stoma (6.2% vs. 7.0%, p = 0.680). Postoperative hospital stay was longer (7.0 vs. 6.0 days, p p = 0.03) in EO patients. Sixty-day mortality (2.9% vs. 6.4%, p p p Conclusion There are significant differences between elderly patients after left-sided CRC surgery with PA versus EO in terms of postoperative length of stay, short-term survival, 3-year overall survival, and relative survival at disadvantage of EO patients. This information could be important for decision making regarding surgical treatment in the elderly.

Peritoneal metastases (PM) from lung cancer are rare and it is unknown how they affect the prognosis of patients with lung cancer. This population-based study aimed to assess the incidence, associated factors, treatment and prognosis of PM from lung cancer. Data from the Netherlands Cancer Registry were used. All patients diagnosed with lung cancer between 2008 and 2018 were included. Logistic regression analysis was performed to identify factors associated with the presence of PM. Cox regression analysis was performed to identify factors associated with the overall survival (OS) of patients with PM. Between 2008 and 2018, 129,651 patients were diagnosed with lung cancer, of whom 2533 (2.0%) patients were diagnosed with PM. The European Standardized Rate of PM increased significantly from 0.6 in 2008 to 1.4 in 2018 (p

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The aim of this study was to investigate the incidence, treatment and survival of patients with peritoneal metastases (PM) of unknown origin. All Dutch patients diagnosed in 2017 and 2018 with PM of unknown origin (PM-CUP) were evaluated. Data were extracted from the Netherlands Cancer Registry (NCR). Patients with PM-CUP were categorized into the following histological subtypes: 1) adenocarcinoma, 2) mucinous adenocarcinoma, 3) carcinoid, 4) unspecified carcinoma and 5) other. Treatments were compared between the different histological subtypes in patients with PM-CUP. Overall survival (OS) was calculated using the Kaplan–Meier method for all patients with cancer of unknown origin and between histological subtypes in patients with PM-CUP. Significant differences in OS were assessed by using the log-rank test. In total, 3026 patients were diagnosed with cancer of unknown origin, 513 (17%) among them were diagnosed with PM-CUP. Most PM-CUP patients received best supportive care only (76%), whereas 22% received systemic treatment and 4% underwent metastasectomy. Median OS was 1.1 months for all patients with PM-CUP but varied from 0.6 months to 30.5 months depending on the underlying histology. In this study, PM-CUP were diagnosed in 17% of all patients with cancer of unknown primary and the reported survival in this cohort was extremely poor. Since survival differed among histological subtypes and recently more treatment options became available for a selected group of patients with peritoneal malignancies, it is of great importance to identify the histology of the metastases and whenever possible the primary tumor.

BACKGROUND: The aim of this population-based study was to determine the prognostic value of the histologic subtypes mucinous (MAC), non-mucinous (AC) and signet ring cell (SRCC) adenocarcinoma among patients with appendiceal cancer.METHODS AND MATERIALS: Data from the Netherlands Cancer Registry (NCR) of patients with primary appendiceal adenocarcinomas with MAC, AC and SRCC histologic subtype, diagnosed between 2001 and 2015 were used (n = 675). To categorize patients according to the recent histopathological classification, the NCR was linked with the Dutch Pathology Registry (PALGA). Log-rank tests and Kaplan-Meier analyses were performed to estimate overall survival (OS), and the cox proportional hazards model was run to identify prognostic factors.RESULTS: AC was the most frequently encountered histologic subtype (50.9%), followed by MAC (35.8%) and SRCC (13.3%). In locoregional disease, histologic subtype was not a prognostic factor for OS with 5-year survival rates for patients with AC, MAC and SRCC of 60.0%, 60.5% and 69.6% respectively (p = 0.68). Metastatic disease was more common in SRCC (53.8%) than in MAC (38.8%) and AC (23.4%) (p CONCLUSION: Histologic subtype had no prognostic relevance in locoregional or systemic metastatic disease in appendiceal adenocarcinoma. In peritoneal metastases, mucinous histologic subtype was a favorable prognostic factor, compared to non-mucinous and signet ring cell subtype.

Returning patient-reported outcomes to patients might aid patients in detecting symptoms and might facilitate early intervention. This descriptive study evaluates the use of an individual feedback report on patient-reported outcomes for colorectal cancer patients and aims to assess differences in patient, tumor, and treatment characteristics and cohort retention between patients who opt and do not opt for the feedback report.Patients with colorectal cancer participating in the nationwide Prospective Dutch ColoRectal Cancer Cohort, who filled in questionnaires digitally between June 2018 and January 2019, were included. Participants were given the option to receive a feedback report at baseline, 3, 6, and 12 months. The usefulness, content, and layout of the feedback report were evaluated. Differences in patient, tumor, and treatment characteristics, patient-reported outcomes, and cohort retention at subsequent questionnaires between participants who did and did not opt for feedback were assessed.A total of 484 participants were included of whom 293 (61%) opted for feedback. The feedback report was considered useful by 92%. No differences in patient, tumor, and treatment characteristics, and patient-reported outcomes were found between participants who did and did not opt for feedback. The response rate was higher among patients who opted for feedback compared to patients who did not opt for feedback at T3 (84 vs 74%), but not at T6 and T12.The feedback report was used by 6 out of 10 patients. The feedback report was considered valuable and associated with a higher subsequent response rate.

Background This study aimed to assess the impact of open or laparoscopic resection of primary colorectal cancer (CRC) on the development of metachronous colorectal peritoneal metastases (CPM) in a population-based cohort. Materials and methods This was a retrospective, population-based study of CRC patients who underwent open or laparoscopic resection of the primary tumour in the Netherlands between January 1st and June 30th 2015. Patients with synchronous metastases were excluded. CPM were considered metachronous if diagnosed ≥ 90 days after resection of primary CRC. Multivariable cox regression analysis was performed to correct for tumour location, histology, differentiation, and stage, nodal stage, tumour perforation, primary surgery type, and unclear resection margins. Results In total, 1516 CRC patients underwent open resection and 3236 CRC patients underwent laparoscopic resection, with a 3-year cumulative incidence of metachronous CPM of 7.3% and 3.7%, respectively (p Conclusions Patients treated with open resection had a significantly higher risk to develop metachronous CPM than patients treated with laparoscopic resection. The mechanisms underlying this phenomenon remain unknown but might be related to differences in per-operative specimen handling, tumour spill, surgical trauma and pro-inflammatory response. This finding might imply the need for a personalized follow-up after primary resection of CRC.

The peritoneum is a common metastatic site in gastric cancer. This systematic review provides an overview of the incidence, risk factors and survival of synchronous peritoneal metastases from gastric cancer. A systematic search was performed to identify studies wherein the incidence, risk factors and survival of gastric cancer with peritoneal metastases were investigated. Of all 38 potentially eligible studies, 17 studies were included based on the eligibility criteria. The incidence of synchronous gastric peritoneal metastases was reviewed for population-based studies (10–21%), for observational cohort studies (2–15%) and for surgical cohort studies (13–40%). Potential risk factors for synchronous gastric peritoneal metastases were younger age, non-cardia gastric cancer, female sex, signet ring cell carcinoma, diffuse type histology or linitis plastica, T4 stage, Hispanic ethnicity and more than one metastatic location. Synchronous peritoneal metastases are commonly diagnosed in patients with gastric cancer with an incidence up to 21% in recent population-based studies. Furthermore, prognosis of patients with gastric peritoneal metastases is poor with median overall survival ranging from 2 to 9 months. The high incidence and poor prognosis require intensive research on diagnostic features and effective treatment options to improve survival.

Contains fulltext : 251536.pdf (Publisher’s version ) (Open Access) AIM: Previous studies showed that the incidence of early-onset colorectal cancer (EO-CRC, diagnosis

Background: To explore the potential value of consensus molecular subtypes (CMS) in stage II colon cancer treatment selection, we carried out an early cost-effectiveness assessment of a CMS-based strategy for adjuvant chemotherapy. Methods: We used a Markov cohort model to evaluate three selection strategies: (i) the Dutch guideline strategy (MSS+pT4), (ii) the mutation-based strategy (MSS plus a BRAF and/or KRAS mutation or MSS plus pT4), and (iii) the CMS-based strategy (CMS4 or pT4). Outcomes were number of colon cancer deaths per 1,000 patients, total discounted costs per patient (pp), and quality-adjusted life-years (QALY) pp. The analyses were conducted from a Dutch societal perspective. The robustness of model predictions was assessed in sensitivity analyses. To evaluate the value of future research, we performed a value of information (VOI) analysis. Results: The Dutch guideline strategy resulted in 8.10 QALYs pp and total costs of €23,660 pp. The CMS-based and mutation-based strategies were more effective and more costly, with 8.12 and 8.13 QALYs pp and €24,643 and €24,542 pp, respectively. Assuming a threshold of €50,000/QALY, the mutation-based strategy was considered as the optimal strategy in an incremental analysis. However, the VOI analysis showed substantial decision uncertainty driven by the molecular markers (expected value of partial perfect information: €18M). Conclusions: On the basis of current evidence, our analyses suggest that the mutation-based selection strategy would be the best use of resources. However, the extensive decision uncertainty for the molecular markers does not allow selection of an optimal strategy at present. Impact: Future research is needed to eliminate decision uncertainty driven by molecular markers.

Background As small-bowel adenocarcinoma (SBA) is scarce, no standard systemic regimen in metastatic disease has been defined. Objective To obtain insights into the use and effects of palliative chemotherapy in patients with metastatic SBA in a population-based setting. Methods Data from the Netherlands Cancer Registry of patients with metastatic SBA between 2007 and 2016 were used (n = 522). For patients treated with palliative chemotherapy, differences in treatment regimens and survival were evaluated. Results Palliative chemotherapy was received by 38% of patients (n = 199). First-line combination chemotherapy was administered to 80% of patients, mainly CAPOX/FOLFOX. Single-agent chemotherapy mostly consisted of capecitabine. Second-line treatment, mostly irinotecan-based (58%), was prescribed to 27% of patients. Age 70 years or older was an adverse predictive factor for receiving first-line combination chemotherapy (odds ratio (OR) 0.2, 95% confidence interval (CI) 0.08-0.62) and second-line therapy (OR 0.3, 95% CI 0.10-0.72). Median overall survival with palliative chemotherapy was 9.3 months, compared with 3.0 months without. In subanalyses, patients who received only first-line treatment had a median overall survival of 5.6 and 7.0 months after single-agent and combination chemotherapy, respectively. Conclusion A minority of patients were treated with palliative chemotherapy. First-line treatment consisted predominantly of oxaliplatin-based combination chemotherapy, whereas second-line treatment was mainly irinotecan-based. Population-based median overall survival for selected patients treated with chemotherapy amounted to nine months.

Introduction: The relation between the primary origin of metastasised pancreatic ductal adenocarcinoma (PDAC)—head, body or tail—metastatic patterns and outcomes has not yet been investigated in large population-based studies. Methods: Patients with metastasised PDAC at diagnosis from the Netherlands Cancer Registry were included (2005–2015). We compared number of metastatic organ sites (1, 2, ≥3) and specific metastatic organ sites (peritoneum, liver, lung and extra-regional lymph nodes) for the different primary tumour locations. Cox regression analyses were used to determine the association of tumour location and metastatic organ site(s) with overall survival. Results: Overall, we included 9952 patients with metastasised PDAC. The primary origin was head in 5644 (57%), body in 1671 (17%) and tail in 2637 (26%) patients. Differences between primary origins were the number of metastatic organ sites (proportions ≥3 sites for head: 4%, for body: 8% and for tail: 13%, p < 0.0001) and peritoneal metastases (present in 13% for head, 24% for body and 30% for tail; p < 0.0001). Median overall survival was 2.6 months for head PDAC (reference), 2.4 months for body PDAC (HR 1.02 [0.97–1.08]) and 1.9 months for tail PDAC (HR 1.20 [1.15–1.26]). Of patients with one metastatic organ site, the worst survival compared with other sites was seen with liver only metastases (2.5 months vs. 2.7–5.1 months), and the best survival for patients, with extra-regional lymph node only metastases (5.1 months). Conclusion: Metastatic patterns differ among the primary origins for PDAC with metastasised tail tumours having more metastatic sites, more often peritoneal metastases and worse survival.

Background: We aimed to evaluate the cost-effectiveness of risk-based strategies to improve the selection of surgically treated stage II colon cancer (CC) patients for adjuvant chemotherapy. Methods: Using the ‘Personalized Adjuvant TreaTment in EaRly stage coloN cancer’ (PATTERN) model, we evaluated five selection strategies: (1) no chemotherapy, (2) Dutch guideline recommendations assuming observed adherence, (3) Dutch guideline recommendations assuming perfect adherence, (4) biomarker mutation OR pT4 stage strategy in which patients with MSS status combined with a pT4 stage or a mutation in BRAF and/or KRAS receive chemotherapy assuming perfect adherence and (5) biomarker mutation AND pT4 stage strategy in which patients with MSS status combined with a pT4 stage tumor and a BRAF and/or KRAS mutation receive chemotherapy assuming perfect adherence. Outcomes were number of CC deaths per 1000 patients and total discounted costs and quality-adjusted life-years (QALYs) per patient (pp). Analyses were conducted from a societal perspective. The robustness of model predictions was assessed in sensitivity analyses. Results: The reference strategy, that is, no adjuvant chemotherapy, resulted in 139 CC deaths in a cohort of 1000 patients, 8.077 QALYs pp and total costs of €22,032 pp. Strategies 2–5 were more effective (range 8.094–8.217 QALYs pp and range 118–136 CC deaths per 1000 patients) and more costly (range €22,404–€25,102 pp). Given a threshold of €50,000/QALY, the optimal use of resources would be to treat patients with either the full adherence strategy and biomarker mutation OR pT4 stage strategy. Conclusion: Selection of stage II CC patients for chemotherapy can be improved by either including biomarker status in the selection strategy or by improving adherence to the Dutch guideline recommendations.

Background Long‐term colon cancer survivors present heterogeneous health‐related quality of life (HRQOL) outcomes. We determined unobserved subgroups (classes) of survivors with similar HRQOL patterns and investigated their stability over time and the association of clinical covariates with these classes. Materials and Methods Data from the population‐based PROFILES registry were used. Included were survivors with nonmetastatic (TNM stage I–III) colon cancer (n = 1,489). HRQOL was assessed with the Dutch translation of the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 version 3.0. Based on survivors’ HRQOL, latent class analysis (LCA) was used to identify unobserved classes of survivors. Moreover, latent transition analysis (LTA) was used to investigate changes in class membership over time. Furthermore, the effect of covariates on class membership was assessed using multinomial logistic regression. Results LCA identified five classes at baseline: class 1, excellent HRQOL (n = 555, 37.3%); class 2, good HRQOL with prevalence of insomnia (n = 464, 31.2%); class 3, moderate HRQOL with prevalence of fatigue (n = 213, 14.3%); class 4, good HRQOL with physical limitations (n = 134, 9.0%); and class 5, poor HRQOL (n = 123, 8.3%). All classes were stable with high self‐transition probabilities. Longer time since the diagnosis, no comorbid conditions, and male sex were associated with class 1, whereas older age was associated with class 4. Clinical covariates were not associated with class membership. Conclusion The identified classes are characterized by distinct patterns of HRQOL and can support patient‐centered care. LCA and LTA are powerful tools for investigating HRQOL in cancer survivors. Implications for Practice Long‐term colon cancer survivors show great heterogeneity in their health‐related quality of life. This study identified five distinct clusters of survivors with similar patterns of health‐related quality of life and showed that these clusters remain stable over time. It was also shown that these clusters do not significantly differ in tumor characteristics or received treatment. Cluster membership of long‐term survivors can be identified by sociodemographic characteristics but is not predetermined by diagnosis and treatment., Health‐related quality of life is well studied, but most studies have investigated only specific aspects of quality of life despite the vast heterogeneity of adverse effects experienced. This article focuses on heterogeneity and stability in health‐related quality of life for a cohort of long‐term survivors of colon cancer.

Purpose This population-based study determined the cumulative incidence (CI) of local, regional, and distant recurrences, examined metastatic patterns, and identified risk factors for recurrence after curative treatment for CRC. Methods All patients undergoing resection for pathological stage I–III CRC between January 2015 and July 2015 and registered in the Netherlands Cancer Registry were selected (N = 5412). Additional patient record review and data collection on recurrences was conducted by trained administrators in 2019. Three-year CI of recurrence was calculated according to sublocation (right-sided: RCC, left-sided: LCC and rectal cancer: RC) and stage. Cox competing risk regression analyses were used to identify risk factors for recurrence. Results The 3-year CI of recurrence for stage I, II, and III RCC and LCC was 0.03 vs. 0.03, 0.12 vs. 0.16, and 0.31 vs. 0.24, respectively. The 3-year CI of recurrence for stage I, II, and III RC was 0.08, 0.24, and 0.38. Distant metastases were found in 14, 12, and 16% of patients with RCC, LCC, and RC. Multiple site metastases were found often in patients with RCC, LCC, and RC (42 vs. 32 vs. 28%). Risk factors for recurrence in stage I–II CRC were age 65–74 years, pT4 tumor size, and poor tumor differentiation whereas in stage III CRC, these were ASA III, pT4 tumor size, N2, and poor tumor differentiation. Conclusions Recurrence rates in recently treated patients with CRC were lower than reported in the literature and the metastatic pattern and recurrence risks varied between anatomical sublocations.

Background:Our aim was to evaluate the cost effectiveness of 3 months’ adjuvant chemotherapy versus 6 months in high-risk (T4 stage + microsatellite stable) stage II colon cancer (CC) patients.Methods:Using the validated PATTERN Markov cohort model, which simulates the disease progression of stage II CC patients from diagnosis to death, we first evaluated a reference strategy in which high-risk patients were treated with chemotherapy for 6 months. In the second strategy, treatment duration was shortened to 3 months. Both strategies were evaluated for CAPOX (capecitabine plus oxaliplatin) and FOLFOX (fluorouracil, leucovorin and oxaliplatin). Based on trial data, we assumed that shortened treatment duration compared with a 6-month regimen was equally effective for CAPOX and less effective for FOLFOX. Adverse events were highest in the 6-month strategy. Analyses were conducted from a societal perspective using a lifelong time horizon. Outcomes were number of CC deaths per 1000 patients and total discounted costs and quality-adjusted life-years (QALYs) per patient (pp). Incremental net monetary benefit (iNMB) was calculated using a willingness-to-pay value of €50,000/QALY.Results:For CAPOX, the 6-month strategy resulted in 316 CC deaths per 1000 patients, 6.71 QALYs pp and total costs of €41,257 pp. The 3-month strategy resulted in an equal number of CC deaths, but higher QALYs (6.80 pp) and lower costs (€37,645 pp), leading to a iNMB of €8454 per person for 3 months versus 6 months. For FOLFOX, the 6-month strategy resulted in 316 CC deaths per 1000 patients, 6.71 QALYs pp and total costs of €47,135 pp. The 3-month strategy resulted in more CC deaths (393), lower QALYs (6.19 pp) and lower costs (€44,389 pp). An iNMB of −€23,189 was found for 3 months versus 6 months.Conclusion:Our findings indicate that 3 months’ adjuvant chemotherapy should be considered as standard of care in high-risk stage II CC patients for CAPOX, but not for FOLFOX.

Aim To develop a decision model for the population-level evaluation of strategies to improve the selection of stage II colon cancer (CC) patients who benefit from adjuvant chemotherapy. Methods A Markov cohort model with a one-month cycle length and a lifelong time horizon was developed. Five health states were included; diagnosis, 90-day mortality, death other causes, recurrence and CC death. Data from the Netherlands Cancer Registry were used to parameterize the model. Transition probabilities were estimated using parametric survival models including relevant clinical and pathological covariates. Subsequently, biomarker status was implemented using external data. Treatment effect was incorporated using pooled trial data. Model development, data sources used, parameter estimation, and internal and external validation are described in detail. To illustrate the use of the model, three example strategies were evaluated in which allocation of treatment was based on (A) 100% adherence to the Dutch guidelines, (B) observed adherence to guideline recommendations and (C) a biomarker-driven strategy. Results Overall, the model showed good internal and external validity. Age, tumor growth, tumor sidedness, evaluated lymph nodes, and biomarker status were included as covariates. For the example strategies, the model predicted 83, 87 and 77 CC deaths after 5 years in a cohort of 1000 patients for strategies A, B and C, respectively. Conclusion This model can be used to evaluate strategies for the allocation of adjuvant chemotherapy in stage II CC patients. In future studies, the model will be used to estimate population-level long-term health gain and cost-effectiveness of biomarker-based selection strategies.

There is an ongoing discussion regarding the impact of adjuvant chemotherapy in Stage II colon cancer. We therefore estimated adjuvant treatment effect in Stage II colon cancer using pooled disease‐free survival (DFS) data from randomized clinical trials (RCT approach) and compared this to real‐world data (RWD approach) estimates. First, we estimated the treatment effect in RCTs by (i) searching relevant trials reporting DFS data, (ii) generating patient‐level data from reported DFS data and (iii) estimating treatment effect in the patient‐level data. Second, the treatment effect was estimated in an observational cohort of 1,947 patients provided by the Netherlands Cancer Registry using three propensity score methods; matching, weighting and stratification. In the RCT approach, patient‐level data of 4,489 patients (events: 853) were generated from seven trials which compared two of the following treatment arms: control, 5FU/LV or FOLFOX. A Cox model was used to estimate a hazard ratio (HR) of 0.77 (0.43;1.10) for 5FU/LV vs. control and 0.93 (0.72;1.15) for FOLFOX vs. 5FU/LV. In the RWD approach, HRs for any adjuvant treatment vs. control were 0.95 (0.50;1.80), 0.88 (0.24;3.21) and 1.05 (0.04;2.06) using matching, weighting and stratification, respectively. There was no significant difference with the estimates from the RCT approach (interaction test, p > 0.10). The RCT data suggest a clinically relevant benefit of adjuvant chemotherapy in terms of DFS, but the estimate did not reach statistical significance. Stratified analyses are required to evaluate whether treatment effect differs in specific subgroups., What's new? There is an ongoing discussion regarding the impact of adjuvant chemotherapy in stage II colon cancer. This study presents the most recent pooled estimate based on available RCT data since 1999, resulting in a pooled hazard ratio of 0.77 (95% CI 0.43;1.10) for fluoropyrimidine compared to no treatment. Even though no significant treatment effect was found, neither in the RCT approach nor in the real‐world data approach, the RCT data suggest a clinically‐relevant benefit of adjuvant chemotherapy. To improve guidance in treatment decisions, larger sample sizes, pooling of true patient‐level data with covariate information, and subgroup specific analyses are required.

Background: Although randomized controlled trials (RCT) are the gold standard to estimate treatment effects, they are often criticized in terms of generalizability. Observational data might alleviate this problem by being readily available in large quantities. However, observational data are potentially confounded. In this methodological study we use a large-scale RCT as the gold standard to examine the performance of various statistical methods to control for potential confounding in observational data. Methods: In this paper we compare three types of methods that allow researchers to correct for such potential confounding: direct methods, inverse probability weighting (IPW) methods and doubly robust (DR) methods. We uniquely compare estimates obtained from the population-wide Netherlands Cancer Registry (NCR) on colon cancer (n=52621) with estimates obtained from a large-scale RCT. As the RCT differs from the observational data both in its sampling mechanism and in its treatment assignment mechanism, we first resample the NCR data to reflect the distribution in RCT data. Next, we correct for potential confounding using three alternative types of methods and consequentially evaluate their estimates to those obtained in the RCT. Results: We find that while all estimators qualitatively approximate to findings in the RCT, methods that can flexibly model the response (i.e., direct estimation and DR estimation) performed consistently superior to the inverse propensity score method. Subgroup analysis indicates that relatively simple models allow us to properly estimate the treatment effect. However, these simple models do not properly identify heterogeneous treatment effects in stage2 colon cancer. Careful sensitivity analysis using more flexible models demonstrates both the uncertainty and the potential heterogeneous treatment effect in stage2 cancer and provides robust estimation of treatment effect in stage3 cancer. Conclusions: Our results suggest that both the direct method and the DR method, when executed with care, can be used to reliably estimate treatment effects based on registry data. This methodological validation opens the door to more extensive use of registry data for the estimation of (individual) treatment effects. Additionally, our identification of potentially meaningful subgroups of stage2 colon cancer patients who, based on our analysis seem to benefit from chemotherapy, should be further explored.

Key PointsQuestionIs adjuvant systemic chemotherapy associated with improved overall survival compared with active surveillance in patients undergoing up-front resection of isolated synchronous colorectal peritoneal metastases? FindingsIn this Dutch nationwide propensity score-matched cohort study including 393 patients, adjuvant systemic chemotherapy was associated with improved overall survival (median, 39 months) compared with active surveillance (median, 25 months). This difference in survival rates was statistically significant. MeaningIn this study, adjuvant systemic chemotherapy was associated with improved overall survival following up-front resection of isolated synchronous colorectal peritoneal metastases; however, randomized trials are needed to address the influence of potential residual confounding and allocation bias on this association.ImportanceTo date, there are no data on the value of adjuvant systemic chemotherapy following up-front resection of isolated synchronous colorectal peritoneal metastases. ObjectiveTo assess the association between adjuvant systemic chemotherapy and overall survival following up-front resection of isolated synchronous colorectal peritoneal metastases. Design, Setting, and ParticipantsIn this population-based, observational cohort study using nationwide data from the Netherlands Cancer Registry (diagnoses between January 1, 2005, and December 31, 2017; follow-up until January 31, 2019), 393 patients with isolated synchronous colorectal peritoneal metastases who were alive 3 months after up-front complete cytoreductive surgery with hyperthermic intraperitoneal chemotherapy were included. Patients allocated to the adjuvant systemic chemotherapy group were matched (1:1) with those allocated to the active surveillance group by propensity scores based on patient-, tumor-, and treatment-level covariates. ExposuresAdjuvant systemic chemotherapy, defined as systemic chemotherapy without targeted therapy, starting within 3 months postoperatively. Main Outcomes and MeasuresOverall survival was compared between matched groups using Cox proportional hazards regression analysis adjusted for residual imbalance. A landmark analysis was performed by excluding patients who died within 6 months postoperatively. A sensitivity analysis was performed to adjust for unmeasured confounding by major postoperative morbidity. ResultsOf 393 patients (mean [SD] age, 61 [10] years; 181 [46%] men), 172 patients (44%) were allocated to the adjuvant systemic chemotherapy group. After propensity score matching of 142 patients in the adjuvant systemic chemotherapy group with 142 patients in the active surveillance group, adjuvant systemic chemotherapy was associated with improved overall survival compared with active surveillance (median, 39.2 [interquartile range, 21.1-111.1] months vs 24.8 [interquartile range, 15.0-58.4] months; adjusted hazard ratio [aHR], 0.66; 95% CI, 0.49-0.88; P=.006), which remained consistent after excluding patients who died within 6 months postoperatively (aHR, 0.68; 95% CI, 0.50-0.93; P=.02) and after adjustment for major postoperative morbidity (aHR, 0.71; 95% CI, 0.53-0.95). Conclusions and RelevanceFindings of this study suggest that in patients undergoing up-front resection of isolated synchronous colorectal peritoneal metastases, adjuvant systemic chemotherapy appeared to be associated with improved overall survival. Although randomized trials are needed to address the influence of potential residual confounding and allocation bias on this association, results of this study may be used for clinical decision-making in this patient group for whom no data are available.This cohort study compares survival with adjuvant systemic chemotherapy vs active surveillance in patients with up-front resection of isolated synchronous colorectal peritoneal metastases.

The advantage of adjuvant chemotherapy (ACT) for treating Stage III colon cancer patients is well established and widely accepted. However, many patients with Stage III colon cancer do not receive ACT. Moreover, there are controversies around the effectiveness of ACT for Stage II patients. We investigated the administration of ACT and its association with overall survival in resected Stage II (overall and stratified by low-/high-risk) and Stage III colon cancer patients in three European countries including The Netherlands (2009-2014), Belgium (2009-2013) and Sweden (2009-2014). Hazard ratios (HR) for death were obtained by Cox regression models adjusted for potential confounders. A total of 60244 resected colon cancer patients with pathological Stages II and III were analyzed. A small proportion (range 9-24%) of Stage II and over half (range 55-68%) of Stage III patients received ACT. Administration of ACT in Stages II and III tumors decreased with higher age of patients. Administration of ACT was significantly associated with higher overall survival in high-risk Stage II patients (in The Netherlands (HR; 95%CI = 0.82 (0.67-0.99), Belgium (0.73; 0.59-0.90) and Sweden (0.58; 0.44-0.75)), and in Stage III patients (in The Netherlands (0.47; 0.43-0.50), Belgium (0.46; 0.41-0.50) and Sweden (0.48; 0.43-0.54)). In Stage III, results were consistent across subgroups including elderly patients. Our results show an association of ACT with higher survival among Stage III and high-risk Stage II colon cancer patients. Further investigations are needed on the selection criteria of Stages II and III colon cancer patients for ACT.

The paucity of evidence for the optimal use of systemic therapy in elderly patients with metastatic colorectal cancer (mCRC) poses significant challenges to cancer specialists. The present population-based study provides insight into the impact of age on palliative systemic therapy in patients with metachronous metastases from CRC, in order to optimize the decision-making process.Data on the development and treatment of metachronous metastases were collected for patients with primary resected CRC diagnosed between 2003 and 2008 in the Eindhoven area of the Netherlands Cancer Registry. Patients undergoing surgery for metastases were excluded, resulting in a study population treated with palliative intent, with or without systemic therapy (n=746).385 patients received palliative systemic therapy (52%). Patients aged ≥75years were less likely to receive systemic therapy (31% ≥75years vs 73%60years) and more likely to receive single-agent chemotherapy than combination-chemotherapy. Elderly patients (≥75years) treated with capecitabine-oxaliplatin (CAPOX) received fewer cycles (51% ≤3 oxaliplatin cycles, 43% ≤3 capecitabine cycles) and lower cumulative dosages compared to patients aged75years, although initial dosages were similar. If capecitabine monotherapy (CapMono) was administered, starting dosages were 2414mg/mAge beginning at 75years significantly influenced palliative systemic therapy. Even in selected elderly patients, first-line treatment with CAPOX was associated with less cycles and lower cumulative dosages compared to younger patients. With single-agent fluoropyrimidine therapy, however, no such results were observed.

Aim of the study: Previous studies have shown that older patients benefited less than younger patients from surgical treatment for colorectal cancer (CRC). However, CRC care has advanced over time, and it is time to assess whether the difference in postoperative mortality between older and younger CRC patients is still present.Methods: Patients with primary stage I-III CRC diagnosed between 2005 and 2016 were selected from the Netherlands Cancer Registry (N = 111,778). Trends in postoperative mortality and 1-year postoperative relative survival (RS) were analysed, stratified according to age (= 75 years) and tumour location (colon versus rectum). One-year postoperative RS was analysed to correct for background mortality in the older population.Results: Between 2005 and 2016, 30-day postoperative mortality showed a stronger decrease for older patients (from 10.0% to 4.0% for colon cancer [p Conclusion: Between 2005 and 2016, differences in postoperative mortality between older and younger CRC patients decreased. One-year postoperative RS was almost equal for older and younger patients in 2015-2016. This information is crucial for shared decision-making on surgical treatment. (C) 2019 Elsevier Ltd. All rights reserved.

Background Data about the use and effectiveness of targeted therapy in metastatic small bowel adenocarcinoma (SBA) are scarce. Objective The aim of this population-based study was to obtain insights into the use and effectiveness of targeted therapy in patients with synchronous metastases of SBA. Patients and methods Data were retrieved from the Netherlands Cancer Registry. Patients treated with palliative chemotherapy and/or targeted therapy for synchronous metastatic SBA between 2007 and 2016 were included (n = 187). Differences in treatment and the subsequent effects on overall survival (OS) were evaluated. Results In first-line treatment, 25 patients (13%) received additional targeted therapy, exclusively bevacizumab, and mostly in combination with CAPOX/FOLFOX (n = 24). A primary ileal tumour was predictive for receiving bevacizumab in first-line treatment (odds ratio 3.2, 95% confidence interval (CI) 1.06-9.93). Median OS for patients in whom bevacizumab was added to first-line chemotherapy was 9.3 months, compared to 9.1 months with chemotherapy only (p = 0.85). Median OS for patients receiving first-line treatment only was 8.5 months with and 6.4 months without the addition of bevacizumab, respectively (p = 0.54). In multivariable survival analyses, the addition of bevacizumab was no prognostic factor (hazard ratio 1.01, 95% CI 0.65-1.59). Conclusions Bevacizumab was the only prescribed targeted therapy in first-line treatment. Considering the limited number of patients receiving first-line bevacizumab and the unknown reasons to prescribe additional targeted therapy, the corresponding survival rates of patients treated with and without additional bevacizumab in first-line treatment might suggest a limited clinical effect of bevacizumab in addition to first-line palliative chemotherapy on OS. Future research should focus on identifying the subgroup of patients who might benefit OR benefiting from anti-VEGF therapy in metastatic SBA.

Objective: The aim of this study is to identify doctor-related factors determining the decision-making for adjuvant chemotherapy for patients with stage III colon cancer aged >= 75 years. Materials and Methods: 21 surgeons and 15 medical oncologists from 10 community hospitals were asked to complete a short questionnaire including tick-box questions regarding motives for non-referral/non-treatment, consultation of geriatricians, chemotherapy schemes prescribed and an open question regarding tolerability of chemotherapy. Results: 29 medical specialists returned a completed questionnaire (response 81%). The motives for non-referral/non-treatment reported most often were comorbidity/bad general health condition of the patient; surgical complications; and treatment offered but refused by patient/family. 39% of the surgeons and 55% of the medical oncologists reported consultation of a geriatrician in 2-30% of their decisions. CAPOX and capecitabine were reported by medical oncologists as the most frequently prescribed regimens. Factors that influenced the decision for monotherapy or combination therapy were comorbidity; general health condition of the patient; and toxicity profile of the chemotherapeutics. In general, medical oncologists defined grade

In the era of personalized cancer medicine, identifying mutations within patient tumors plays an important role in defining high-risk stage II colon cancer patients. The prognostic role of BRAF V600E mutation, microsatellite instability (MSI) status, KRAS mutation and PIK3CA mutation in stage II colon cancer patients is not settled. We retrospectively analyzed 186 patients with stage II colon cancer who underwent an oncological resection but were not treated with adjuvant chemotherapy. KRAS mutations, PIK3CA mutation, V600E BRAF mutation and MSI status were determined. Survival analyses were performed. Mutations were found in the patients with each mutation in the following percentages: 23% (MSI), 35% (KRAS), 19% (BRAF) and 11% (PIK3CA). A trend toward worse overall survival (OS) was seen in patients with an MSI (5-year OS 74% versus 82%, adjusted hazard ratio [HR] 1.8, 95% confidence interval [CI] 0.6–4.9) and a KRAS-mutated tumor (5-year OS 77% versus 82%, adjusted HR 1.7, 95% CI 0.8–3.5). MSI and BRAF-mutated tumors tended to correlate with poorer disease-free survival (DFS) (5-year DFS 60% versus 78%, adjusted HR 1.6, 95% CI 0.5–2.1 and 5-year DFS 57% versus 77%, adjusted HR 1.1, 95% CI 0.4–2.6 respectively). In stage II colon cancer patients not treated with adjuvant chemotherapy, BRAF mutation and MSI status both tended to have a negative prognostic effect on disease-free survival. KRAS and MSI status also tended to be correlated with worse overall survival.

The course of neuropathic symptoms among elderly patients with stage III colon cancer treated with CAPOX (capecitabine, oxaliplatin), capecitabine, or no chemotherapy was investigated. A total of 117 patients (76%) selected from the Netherlands Cancer Registry completed the first questionnaire. The course of several sensory symptoms was less favorable for patients treated with chemotherapy. Moreover, CAPOX was associated with more symptoms in the toes and feet than was capecitabine.Introduction: Among the elderly, the impairment of functional capacities due to neuropathy can have a significant impact. The aim of the present study was to investigate the course of neuropathic symptoms among elderly patients with stage III colon cancer treated with CAPOX (capecitabine, oxaliplatin), capecitabine monotherapy, or no adjuvant chemotherapy. Materials and Methods: The Netherlands Cancer Registry was used to select patients with stage III colon cancer and aged >= 70 years. Questionnaires were sent after resection (T1) and 6 (T2) and 12 months (T3) later. Neuropathy was measured using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Chemotherapy- Induced Peripheral Neuropathy 20. Logistic generalized estimating equations analyses were used to evaluate the effect of chemotherapy on the course of neuropathic symptoms. Results: Of 155 eligible patients, 117 (76%) completed the T1 questionnaire, and 69 and 59 completed the T2 and T3 questionnaires, respectively. The course of the sensory symptoms tingling fingers or hands, tingling toes or feet, numbness in fingers or hands, and numbness in toes or feet was significantly unfavorable for patients treated with adjuvant chemotherapy (CAPOX or capecitabine) compared with that for patients who had not received adjuvant chemotherapy. The course of numbness in toes or feet also differed significantly between patients treated with CAPOX (T1, 7%; T2, 50%; T3, 42%) and patients treated with capecitabine (T1, 17%; T2, 31%; T3, 8%). Additionally, patients treated with capecitabine reported significantly less tingling toes or feet (T1, 6%; T2, 25%; T3, 7%) compared with patients treated with CAPOX (T1, 0%; T2, 50%; T3, 58%). Conclusion: The course of several sensory symptoms over time was less favorable for elderly patients with colon cancer treated with chemotherapy. Moreover, CAPOX was associated with more symptoms in toes and feet compared with capecitabine. It is important to inform patients of these risks to enable informed decision-making.

Item does not contain fulltext BACKGROUND & AIMS: There is controversy over the optimal management for T1 colorectal cancer (T1 CRC). This study compared initial endoscopic resection with or without additional surgery, or initial surgery for T1 CRC, and assessed risk factors for lymph node metastases (LNMs) and long-term recurrence. METHODS: We performed a registration study that included all patients diagnosed with T1 CRC from 1995 through 2011 in the southeast area of The Netherlands (n = 1315). High-risk histology (with regard to LNM) was defined as the presence of poor differentiation, lymphangio-invasion, and/or deep submucosal invasion. The primary outcome measure was the combined rate of local and distant CRC recurrence during a mean follow-up period of 6.6 years. Logistic regression and Cox proportional hazards regression analyses were performed to evaluate independent risk factors for LNM and CRC recurrence, respectively. RESULTS: Endoscopic resection was performed in 590 patients (44.9%); of these, 220 (16.7%) underwent additional surgery. Initial surgery was performed in 725 patients (55.1%). The risk of LNM was higher in T1 CRC with histologic risk factors (15.5% vs 7.1% without histologic risk factors; odds ratio, 2.21; 95% confidence interval, 1.33-3.70). Thirty-day mortality did not differ between patients who received additional surgery (0.9%) and those who underwent only endoscopic resection (1.4%; P = .631). Rates of CRC recurrence were 6.2% (9.8/1000 patient-years) after only endoscopic resection vs 6.4% (9.4/1000 patient-years) after additional surgery (P = .912), and 3.4% (5.2/1000 patient-years) after initial surgery (P = .031). In multivariate analysis, this difference was not significant. The only independent risk factor for long-term recurrence was a positive resection margin (hazard ratio, 6.88; 95% confidence interval, 2.27-20.87). CONCLUSIONS: Based on a population analysis of patients diagnosed with T1 CRC, additional surgery after endoscopic resection should be considered only for patients with high-risk histology or a positive resection margin.

Background: This study aimed to provide information on timing, anatomical location, and predictors for metachronous metastases of colorectal cancer based on a large consecutive series of non-selected patients. Methods: All patients operated on with curative intent for colorectal cancer (TanyNanyM0) between 2003 and 2008 in the Dutch Eindhoven Cancer Registry were included (N = 5671). By means of active follow-up by the Cancer Registry staff within ten hospitals, data on development of metastatic disease were collected. Median follow-up was 5.0 years. Results: Of the 5671 colorectal cancer patients, 1042 (18%) were diagnosed with metachronous metastases. Most common affected sites were the liver (60%), lungs (39%), extra-regional lymph nodes (22%), and peritoneum (19%). 86% of all metastases was diagnosed within three years and the median time to diagnosis was 17 months (interquartile range 10-29 months). Male gender (HR = 1.2, 95%CI 1.03-1.32), an advanced primary T-stage (T4 vs. T3 HR = 1.6, 95%CI 1.32-1.90) and N-stage (N1 vs. N0 HR = 2.8, 95%CI 2.42-3.30 and N2 vs. N0 HR = 4.5, 95%CI 3.72-5.42), high-grade tumour differentiation (HR = 1.4, 95%CI 1.17-1.62), and a positive (HR = 2.1, 95%CI 1.68-2.71) and unknown (HR = 1.7, 95%CI 1.34-2.22) resection margin were predictors for metachronous metastases. Conclusions: Different patterns of metastatic spread were observed for colon and rectal cancer patients and differences in time to diagnosis were found. Knowledge on these patterns and predictors for metachronous metastases may enhance tailor-made follow-up schemes leading to earlier detection of metastasized disease and increased curative treatment options. (C) 2014 Elsevier Ltd. All rights reserved.

BackgroundOlder patients who are functionally compromised or frail may be at risk for loss of quality of life (QoL) after colorectal cancer (CRC) surgery. We prospectively studied health-related QoL (HRQoL) and its association with functional dependency on multiple time points before and after CRC surgery.MethodsIncluded were patients aged 70 years and older who underwent elective CRC surgery between 2014 and 2015 in combination with an oncogeriatric care path. HRQoL (EORTC QLQ-C30 and CR38) and activities of daily living (ADL, Barthel Index) were measured at four time-points; prior to (T0) and at 3 (T3), 6 (T6), and 12 (T12) months after surgery. Functional dependency was defined as a Barthel Index ResultsResponse rate was 67% (n = 106) to two or more questionnaires; 26 (25%) patients were functionally dependent. Overall, functionally independent patients experienced a higher HRQoL than dependent patients. Compared to T0, significant and clinically relevant improvements in HRQoL after surgery were observed in functionally dependent patients: better role functioning, a higher global health, a higher summary score, less fatigue and less gastrointestinal problems (p ConclusionColorectal surgery embedded in geriatric-oncological care has a positive impact on HRQoL in older functionally dependent patients with cancer. Moderate functional dependency should not be considered a generic reason for withholding surgical treatment. Information derived from this study could be used in shared decision making.

Contains fulltext : 165695pub.pdf (Publisher’s version ) (Open Access) Regional lymph node metastases in colorectal cancer (CRC) decrease outcome. Whether nodal metastases function as a biomarker, i.e. as a sign of advanced disease, or are in fact involved in the metastatic process is unclear. We evaluated metastatic patterns of CRC according to the lymph node status of the primary tumor.A retrospective review of 1393 patients with metastatic CRC who underwent autopsy in the Netherlands was performed. Metastatic patterns of regional lymph node positive and negative CRC were compared and validated by population-based data from the Eindhoven Cancer Registry (ECR).Patients with regional lymph node positive CRC more often developed peritoneal metastases (28% vs. 21%, p=0.003) and distant lymph node metastases (25% vs. 15%, p

Item does not contain fulltext BACKGROUND: High-volume hospitals have been associated with improved patient outcomes for tumors with a relatively low incidence that require complex surgeries, such as esophageal and pancreatic cancer. The volume-outcome association for colorectal cancer is under debate. OBJECTIVE: This study investigated whether hospital volume for colorectal cancer is associated with surgical care characteristics and 5-year overall survival. DESIGN: This is a population-based study. SETTING: Data were gathered from the Netherlands Cancer Registry. Hospitals were grouped by volume for colon (/=100 resections per year) and rectum (/=40 resections per year). PATIENTS: All of the patients with primary nonmetastatic colorectal cancer who underwent resection between 2005 and 2012 were included. MAIN OUTCOME MEASURES: Differences in surgical approach, anastomotic leakage, and postoperative 30-day mortality between hospital volumes were analyzed using chi tests and multivariable logistic regression analyses. Cox proportional hazard models were used to investigate the effect of hospital volume on overall survival. RESULTS: This study included 61,394 patients with colorectal cancer. In 2012, 31 of the 91 hospitals performed less than 50 colon cancer resections per year, and 21 of the 90 hospitals performed less than 20 rectal cancer resections per year. No differences in anastomotic leakage rates between hospital volumes were observed. Only small differences between hospital volumes were revealed for conversion of laparoscopic to open resection (OR of less than 50 versus 100 or more resections per year = 1.25 (95% CI, 1.06-1.46)) and postoperative 30-day mortality (colon: OR of less than 50 versus 100 or more resections per year = 1.17 (95% CI, 1.02-1.35); rectum: OR of less than 20 versus 40 or more resections per year = 1.42 (95% CI, 1.09-1.84)). No differences in overall survival were found between hospital volumes. LIMITATIONS: Although we adjusted for several patient and tumour characteristics, data regarding comorbidity, surgeon volume, local recurrences, and specific postoperative complications other than anastomotic leakage were not available. CONCLUSIONS: In the Netherlands, no differences in 5-year survival rates were revealed between hospital volumes for patients with nonmetastatic colorectal cancer.

We sought to clarify the prognostic impact of primary tumor location in metastatic colorectal cancer (mCRC).We evaluated the association between tumor location and survival parameters in patients with previously untreated mCRC receiving first-line chemotherapy ± bevacizumab in three independent cohorts: a prospective pharmacogenetic study (PROVETTA) and two randomized phase III trials, AVF2107g and NO16966. Cancers proximal or distal of the splenic flexure were classified as right-sided or left-sided, respectively. The primary end point was overall survival (OS). Data were analyzed with Cox proportional hazards and logistic regression models. All statistical tests were two-sided.Among evaluable patients in the PROVETTA (n = 200), AVF2107g (n = 559), and NO16966 (n = 1268) studies, 72.0%, 63.1%, and 73.7% had left-sided tumors, respectively. In PROVETTA, patients with left-sided tumors had superior OS (left-sided vs right-sided: hazard ratio [HR] = .44, 95% confidence interval [CI] = .28 to .70, P.001) and progression-free survival (HR = .52, 95% CI = .36 to .75, P.001) outcomes. Multivariable analyses confirmed right-sided location as a negative prognostic variable, independent of mucinous histology and BRAF mutational status. Data from the AVF2107g (HR for OS = .55, 95% CI = .43 to .70) and NO16966 trials (HR for OS = .71, 95% CI = .62 to .82 both P.001) also showed favorable outcomes in patients with left-sided tumors. In both randomized studies, the efficacy of bevacizumab was independent of tumor location.These data demonstrate that primary tumor location is an important prognostic factor in previously untreated mCRC. Given the consistency across an exploratory set and two confirmatory phase III studies, side of tumor origin should be considered for stratification in randomized trials.

Background & Aims Controversy exists on the adequate management in case of pathologically confirmed T1 colorectal carcinoma (pT1 CRC). It is not well known whether recurrence free survival after pT1 CRC is improved by performing primary or secondary surgical resection. We aimed to compare the recurrence free survival between patients undergoing surgical resection versus endoscopic resection or transanal endoscopic microsurgery (TEM) only. Secondary aims were to identify factors associated with surgery and recurrence free survival. Methods We identified all patients diagnosed with pT1 CRC between 1995 and 2011 in the Cancer Registry of the southern part of the Netherlands. Data of these patients were linked to PALGA, the Dutch Pathology Registry. Recurrence was defined as subsequent occurrence of CRC at the same location or site of anastomosis, or distant metastasis originating from the index tumor. Surgery was defined as resection of at least a segment of the colon. Multivariable logistic regression was performed to evaluate patientand tumor characteristics associated with surgery. Cox proportional hazard regression analysis was performed to assess the effect of surgery on the risk of recurrence after adjustment for relevant patient and tumor characteristics. Results A total number of 1,965 patients with pT1 CRC were identified. We excluded 183 patients in whom prevalent CRC with tumor stage >T1 was found or in whom the pT1 stage of the index tumor could not be confirmed in PALGA. Of the remaining 1782 patients, 56% were males and mean age was 68 years (SD 11). Endoscopic resection only was performed in 510 patients (29%); TEM only in 86 patients (5%); and surgery in 1186 patients (67%), of whom 238 (20%) underwent prior endoscopic resection. Surgical resection was more often performed in younger patients (OR per 10 years increase 0.86, 95%-CI 0.78-0.95), between 1995 and 2000 (OR 1.65, 95%-CI 1.27 2.14), and in poorly differentiated (OR 1.71, 95%-CI 1.00 2.98) and right-sided tumors (OR 6.59, 95%-CI 3.95 11.00). One or more positive lymph nodes were found in 89 (8%) of 1186 patients undergoing surgery. In the endoscopic resection / TEM group, 48 recurrences (8%) were found versus 50 recurrences (4%) in the surgery group (p