Background: Population-based data on distal cholangiocarcinoma (DCC) from the Western world are not available, albeit essential to identify areas for improvement. This study investigated the incidence, treatment and outcomes, including time trends and predictors for survival, in a nationwide cohort of DCC. Methods: This is a retrospective cohort study of patients diagnosed with DCC (2009-2016) derived from the Netherlands Cancer Registry. Overall survival (OS) and its predictors were analyzed using Kaplan-Meier and Cox regression analysis. Time trends (2009-2012 versus 2013-2016) were assessed. Results: Overall, 1338 patients with DCC were included, with 1-, 3-and 5-year OS of 46%, 18%, and 11%. Incidence of DCC was 0.55-0.90 per 100.000 per year. Median OS was 10.4 months across all stages; 21.9 months for resected (n ¼ 620, 46.3%), 6.7 months for unresected nonmetastatic (n ¼ 445, 33.3%), and 3.6 months for metastatic DCC (n ¼ 273, 20.4%) (p < .001). After resection, 30-day mortality was 4.8% and 90-day mortality 7.7%. Patients with metastatic DCC who received chemotherapy (n ¼ 78, 28.6%) had a median OS of 8.2 versus 2.8 months for those not treated (p < .001). Over time, resection rates (53.6% to 61.7%, p ¼ .008) and use of palliative chemotherapy in metastatic DCC (22.3% to 32.9%, p ¼ .05) increased, without improvement in OS (10.3 vs 10.6 months, p ¼ .55). Independent poor prognostic factors for OS in resected disease were increasing age, pT3/T4 stage, higher lymph node ratio, poor differentiation, and R1 resection. Conclusions: In a nationwide cohort of DCC, resection rates and the use of chemotherapy increased whereas OS remained stable at 10.4 months.

Adjuvant chemotherapy after pancreatoduodenectomy for pancreatic cancer is currently considered standard of care. In this nationwide study, we investigated which characteristics determine the likelihood of receiving adjuvant chemotherapy and its effect on overall survival. The data were obtained from the Netherlands Cancer Registry. All patients alive 90 days after pancreatoduodenectomy for M0‐pancreatic cancer between 2008 and 2013 in the Netherlands were included in this study. The likelihood to receive adjuvant chemotherapy was analyzed by multilevel logistic regression analysis and differences in time‐to‐first‐chemotherapy were tested for significance by Mann–Whitney U test. Overall survival was assessed by Kaplan–Meier method and Cox regression analysis. Of the 1195 patients undergoing a pancreatoduodenectomy for pancreatic cancer, 642 (54%) patients received adjuvant chemotherapy. Proportions differed significantly between the 19 pancreatic centers, ranging from 26% to 74% (P < 0.001). Median time‐to‐first‐chemotherapy was 6.7 weeks and did not differ between centers. Patients with a higher tumor stage, younger age, and diagnosed more recently were more likely to receive adjuvant treatment. The 5‐year overall survival was significantly prolonged in patients treated with adjuvant chemotherapy—23% versus 17%, log‐rank = 0.01. In Cox regression analysis, treatment with adjuvant chemotherapy significantly prolonged survival compared with treatment without adjuvant chemotherapy. The finding that elderly patients and patients with a low tumor stage are less likely to undergo treatment needs further attention, especially since adjuvant treatment is known to prolong survival in most of these patients.

As the value of palliative primary tumor resection in stage IV colorectal cancer (CRC) is still under debate, the purpose of this population-based study was to investigate if palliative primary tumor resection as the initial treatment after diagnosis was associated with improved overall survival. All patients with stage IV colorectal adenocarcinoma (2008-2011) were selected from the Netherlands Cancer Registry, and patients undergoing treatment with curative intent (i.e., metastasectomy, radiofrequency ablation and/or hyperthermic intraperitoneal chemotherapy), or best supportive care were excluded. After propensity score matching, a multivariable Cox proportional hazard model was performed to determine the association between treatment strategy and mortality. From a total group of 10,371 patients with stage IV CRC, 2,746 patients (26%) underwent an elective palliative resection of the primary tumor, whether or not followed by systemic therapy, and 3,345 patients (32%) were initially treated with palliative systemic therapy. After propensity score matching, median overall survival in these groups was 17.2 months (95% CI 16.3-18.1) and 11.5 months (95% CI 11.0-12.0), respectively. In Cox regression analysis, primary tumor resection was significantly associated with improved overall survival (hazard ratio of death = 0.44 [95% CI 0.35-0.55], p < 0.001). This large population-based study shows an overall survival benefit for patients with incurable stage IV CRC who underwent primary tumor resection as the initial treatment after diagnosis, compared to patients who started systemic therapy with the primary tumor in situ. This result is an argument in favor of resection of the primary tumor, even when patients have little to no symptoms.

Background. Re-resection for incidental gallbladder cancer (iGBC) is associated with improved survival but little is known about residual disease (RD) and prognostic factors. In this study, survival after re-resection, RD, and prognostic factors are analyzed. Methods. Patients with iGBC were identified from the Netherlands Cancer Registry, and pathology reports of reresected patients were reviewed. Survival and prognostic factors were analyzed. Results. Overall, 463 patients were included; 24% (n = 110) underwent re-resection after a median interval of 66 days. RD was present in 35% of patients and was most frequently found in the lymph nodes (23%). R0 resection was achieved in 93 patients (92%). Median overall survival (OS) of patients without re-resection was 13.7 (95% confidence interval [CI] 11.6-15.6), compared with 52.6 months (95% CI 36.3-68.8) in re-resected patients (p \ 0.001). After re-resection, median OS was superior in patients without RD versus patients with RD (not reached vs. 23.1 months; p \ 0.001). In patients who underwent reresection, RD in the liver (hazard ratio [HR] 5.54; p \ 0.001) and lymph nodes (HR 2.35; p = 0.005) were the only significant prognostic factors in multivariable Electronic supplementary material The online version of this article (

Background: Periampullary adenocarcinoma consists of pancreatic adenocarcinoma (PDAC), distal cholangiocarcinoma (DC), ampullary cancer (AC), and duodenal adenocarcinoma (DA). The aim of this study was to assess treatment modalities and overall survival by tumor origin.Methods: Patients diagnosed with non-metastatic periampullary cancer in 2012-2018 were identified from the Netherlands Cancer Registry. OS was studied with Kaplan-Meier analysis and multivariable Cox regression analyses, stratified by origin.Results: Among the 8758 patients included, 68% had PDAC, 13% DC, 12% AC, and 7% DA. Resection was performed in 35% of PDAC, 56% of DC, 70% of AC, and 59% of DA. Neoadjuvant and/or adjuvant therapy was administered in 22% of PDAC, 7% of DC, 7% of AC, and 12% of DA. Three-year OS was highest for AC (37%) and DA (34%), followed by DC (21%) and PDAC (11%). Adjuvant therapy was associated with improved OS among PDAC (HR = 0.62; 95% CI 0.55-0.69) and DC (HR = 0.69; 95% CI 0.48-0.98), but not AC (HR = 0.87; 95% CI 0.62-1.22) and DA (HR = 0.85; 95% CI 0.48-1.50). Conclusion:This retrospective study identified considerable differences in treatment modalities and OS between the four periampullary cancer origins in daily clinical practice. An improved OS after adjuvant chemotherapy could not be demonstrated in patients with AC and DA. Q4

Impact of nationwide enhanced implementation of best practices in pancreatic cancer care (PACAP-1): a multicenter stepped-wedge cluster randomized controlled trial Abstract Background: Pancreatic cancer has a very poor prognosis. Best practices for the use of chemotherapy, enzyme replacement therapy, and biliary drainage have been identified but their implementation in daily clinical practice is often suboptimal. We hypothesized that a nationwide program to enhance implementation of these best practices in pancreatic cancer care would improve survival and quality of life.(Continued on next page) Methods/design: PACAP-1 is a nationwide multicenter stepped-wedge cluster randomized controlled superiority trial. In a per-center stepwise and randomized manner, best practices in pancreatic cancer care regarding the use of (neo)adjuvant and palliative chemotherapy, pancreatic enzyme replacement therapy, and metal biliary stents are implemented in all 17 Dutch pancreatic centers and their regional referral networks during a 6-week initiation period. Per pancreatic center, one multidisciplinary team functions as reference for the other centers in the network. Key best practices were identified from the literature, 3 years of data from existing nationwide registries within the Dutch Pancreatic Cancer Project (PACAP), and national expert meetings. The best practices follow the Dutch guideline on pancreatic cancer and the current state of the literature, and can be executed within daily clinical practice. The implementation process includes monitoring, return visits, and provider feedback in combination with education and reminders. Patient outcomes and compliance are monitored within the PACAP registries. Primary outcome is 1-year overall survival (for all disease stages). Secondary outcomes include quality of life, 3-and 5-year overall survival, and guideline compliance. An improvement of 10% in 1-year overall survival is considered clinically relevant. A 25-month study duration was chosen, which provides 80% statistical power for a mortality reduction of 10.0% in the 17 pancreatic cancer centers, with a required sample size of 2142 patients, corresponding to a 6.6% mortality reduction and 4769 patients nationwide. Discussion: The PACAP-1 trial is designed to evaluate whether a nationwide program for enhanced implementation of best practices in pancreatic cancer care can improve 1-year overall survival and quality of life. Trial registration: ClinicalTrials.gov, NCT03513705. Trial opened for accrual on 22th May 2018.Note: the numbers in curly brackets in this protocol refer to SPIRIT checklist item numbers. The order of the items has been modified to group similar items (see http://www.equa tor-network.org/reporting-guidelines/spirit-2013-statementdefining-standard-protocol-items-for-clinical-trials/). Title {1}Impact of nationwide enhanced implementation of best practices in pancreatic cancer care (PACAP-1): a multicenter stepped-wedge cluster randomized controlled trial Trial registration {2a and 2b}. Trial open for accr...

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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.