Impact of time interval between multidisciplinary team meeting and intended pancreatoduodenectomy on oncological outcomes

Background: Dutch guidelines indicate that treatment of pancreatic head and periampullary malignancies should be started within 3 weeks of the multidisciplinary team (MDT) meeting. This study aimed to assess the impact of time to surgery on oncological outcomes. Methods: This was a retrospective population-based cohort study of patients with pancreatic head and periampullary malignancies included in the Netherlands Cancer Registry. Patients scheduled for pancreatoduodenectomy and who were discussed in an MDT meeting from May 2012 to December 2016 were eligible. Time to surgery was defined as days between the final preoperative MDT meeting and surgery, categorized in tertiles (short interval, 18 days or less; intermediate, 19–32 days; long, 33 days or more). Oncological outcomes included overall survival, resection rate and R0 resection rate. Results: A total of 2027 patients were included, of whom 677, 665 and 685 had a short, intermediate and long time interval to surgery respectively. Median time to surgery was 25 (i.q.r. 14–36) days. Longer time to surgery was not associated with overall survival (hazard ratio 0⋅99, 95 per cent c.i. 0⋅87 to 1⋅13; P = 0⋅929), resection rate (relative risk (RR) 0⋅96, 95 per cent c.i. 0⋅91 to 1⋅01; P = 0⋅091) or R0 resection rate (RR 1⋅01, 0⋅94 to 1⋅09; P = 0⋅733). Patients with pancreatic ductal adenocarcinoma and a long time interval had a lower resection rate (RR 0⋅92, 0⋅85 to 0⋅99; P = 0⋅029). Discussion: A longer time interval between the last MDT meeting and pancreatoduodenectomy did not decrease overall survival

Surveillance for pancreatic cancer in high-risk individuals leads to improved outcomes: a propensity score-matched analysis

BACKGROUND & AIMS: Recent pancreatic cancer surveil-lance programs of high-risk individuals have reported improved outcomes. This study assessed to what extent outcomes of pancreatic ductal adenocarcinoma (PDAC) patients with a CDKN2A/p16 pathogenic variant diagnosed under surveillance are better as compared with patients with PDAC diagnosed outside surveillance.METHODS: In a pro-pensity score matched cohort using data from the Netherlands Cancer Registry, we compared resectability, stage, and survival between patients diagnosed under sur-veillance with non-surveillance patients with PDAC. Survival analyses were adjusted for potential effects of lead time.RESULTS: Between January 2000 and December 2020, 43,762 patients with PDAC were identified from the Netherlands Cancer Registry. Thirty-one patients with PDAC under surveillance were matched in a 1:5 ratio with 155 non surveillance patients based on age at diagnosis, sex, year diagnosis, and tumor location. Outside surveillance, 5.8% of the patients had stage I cancer, as compared with 38.7% of surveillance patients with PDAC (odds ratio [OR], 0.09; 95% confidence interval [CI], 0.04-0.19). In total, 18.7% of non surveillance patients vs 71.0% of surveillance patients un- derwent a surgical resection (OR, 10.62; 95% CI, 4.56-26.63). Patients in surveillance had a better prognosis, reflected by 5-year survival of 32.4% and a median overall survival of 26.8 months vs 4.3% 5-year survival and 5.2 months median overall survival in non-surveillance patients (hazard ratio, 0.31; 95% CI 0.19-0.50). For all adjusted lead times, survival remained significantly longer in surveillance patients than non-surveillance patients.CONCLUSION: Surveillance for PDAC in carriers of a CDKN2A/p16 pathogenic variant results in earlier detection, increased resectability, and improved survival as compared with non-surveillance patients with PDAC

Treatment and survival of resected and unresected distal cholangiocarcinoma: a nationwide study

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 regres

Real-world evidence of adjuvant gemcitabine plus capecitabine vs gemcitabine monotherapy for pancreatic ductal adenocarcinoma

The added value of capecitabine to adjuvant gemcitabine monotherapy (GEM) in pancreatic ductal adenocarcinoma (PDAC) was shown by the ESPAC-4 trial. Real-world data on the effectiveness of gemcitabine plus capecitabine (GEMCAP), in patients ineligible for mFOLFIRINOX, are lacking. Our study assessed whether adjuvant GEMCAP is superior to GEM in a nationwide cohort. Patients treated with adjuvant GEMCAP or GEM after resection of PDAC without preoperative treatment were identified from The Netherlands Cancer Registry (2015-2019). The primary outcome was overall survival (OS), measured from start of chemotherapy. The treatment effect of GEMCAP vs GEM was adjusted for sex, age, performance status, tumor size, lymph node involvement, resection margin and tumor differentiation in a multivariable Cox regression analysis. Secondary outcome was the percentage of patients who completed the planned six adjuvant treatment cycles. Overall, 778 patients were included, of whom 21.1% received GEMCAP and 78.9% received GEM. The median OS was 31.4 months (95% CI 26.8-40.7) for GEMCAP and 22.1 months (95% CI 20.6-25.0) for GEM (HR: 0.71, 95% CI 0.56-0.90; logrank P = .004). After adjustment for prognostic factors, survival remained superior for patients treated with GEMCAP (HR: 0.73, 95% CI 0.57-0.92, logrank P = .009). Survival with GEMCAP was superior to GEM in most subgroups of prognostic factors. Adjuvant chemotherapy was completed in 69.5% of the patients treated with GEMCAP and 62.7% with GEM (P = .11). In this nationwide cohort of patients with PDAC, adjuvant GEMCAP was associated with superior survival as compared to GEM monotherapy and number of cycles was similar.Surgical oncolog

Impact of nationwide enhanced implementation of best practices in pancreatic cancer care (PACAP-1):a multicenter stepped-wedge cluster randomized controlled trial

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. 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

Nationwide trends in incidence, treatment and survival of colorectal cancer patients with synchronous metastases

Item does not contain fulltextThe aim of this study was to determine trends in incidence, treatment and survival of colorectal cancer (CRC) patients with synchronous metastases (Stage IV) in the Netherlands. This nationwide population-based study included 160,278 patients diagnosed with CRC between 1996 and 2011. We evaluated changes in stage distribution, location of synchronous metastases and treatment in four consecutive periods, using Chi square tests for trend. Median survival in months was determined, using Kaplan-Meier analysis. The proportion of Stage IV CRC patients (n = 33,421) increased from 19 % (1996-1999) to 23 % (2008-2011, p < 0.001). This was predominantly due to a major increase in the incidence of lung metastases (1.7-5.0 % of all CRC patients). During the study period, the primary tumor was resected less often in Stage IV patients (65-46 %) and the use of systemic treatment has increased (29-60 %). Also an increase in metastasectomy was found in patients with one metastatic site, especially in patients with liver-only disease (5-18 %, p < 0.001). Median survival of all Stage IV CRC patients increased from 7 to 12 months. Especially in patients with metastases confined to the liver or lungs this improvement in survival was apparent (9-16 and 12-24 months respectively, both p < 0.001). In the last two decades, more lung metastases were detected and an increasing proportion of Stage IV CRC patients was treated with systemic therapy and/or metastasectomy. Survival of patients has significantly improved. However, the prognosis of Stage IV patients becomes increasingly diverse

Palliative resection of the primary tumor is associated with improved overall survival in incurable stage IV colorectal cancer: A nationwide population-based propensity-score adjusted study in the Netherlands

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

Centralization of esophagectomy for cancer: How far should we go?

Development and application of statistical models for medical scientific researc

Re-resection in Incidental Gallbladder Cancer: Survival and the Incidence of Residual Disease

Contains fulltext : 219889pub.pdf (publisher's version ) (Open Access)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 re-resected 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 re-resection, 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 analysis. Predictive factors for the presence of RD were pT3 stage (HR 25.3; p = 0.003) and pN1 stage (HR 23.0; p = 0.022). CONCLUSION: Re-resection for iGBC is associated with improved survival but remains infrequently used and is often performed after the optimal timing interval. RD is the only significant prognostic factor for survival after re-resection and can be predicted by pT and pN stages

Nationwide outcomes in patients undergoing surgical exploration without resection for pancreatic cancer

Contains fulltext : 177836.pdf (publisher's version ) (Closed access)BACKGROUND: Despite improvements in diagnostic imaging and staging, unresectable pancreatic cancer is still encountered during surgical exploration with curative intent. This nationwide study investigated outcomes in patients with unresectable pancreatic cancer found during surgical exploration. METHODS: All patients diagnosed with primary pancreatic (adeno)carcinoma (2009-2013) in the Netherlands Cancer Registry were included. Predictors of unresectability, 30-day mortality and poor survival were evaluated using logistic and Cox proportional hazards regression analysis. RESULTS: There were 10 595 patients with pancreatic cancer during the study interval. The proportion of patients undergoing surgical exploration increased from 19.9 to 27.0 per cent (P < 0.001). Among 2356 patients who underwent surgical exploration, the proportion of patients with tumour resection increased from 61.6 per cent in 2009 to 71.3 per cent in 2013 (P < 0.001), whereas the contribution of M1 disease (18.5 per cent overall) remained stable. Patients who had exploration only had an increased 30-day mortality rate compared with those who underwent tumour resection (7.8 versus 3.8 per cent; P < 0.001). In the non-resected group, among those with M0 (383 patients) and M1 (435) disease at surgical exploration, the 30-day mortality rate was 4.7 and 10.6 per cent (P = 0.002), median survival was 7.2 and 4.4 months (P < 0.001), and 1-year survival rates were 28.0 and 12.9 per cent, respectively. Among other factors, low hospital volume (0-20 resections per year) was an independent predictor for not undergoing tumour resection, but also for 30-day mortality and poor survival among patients without tumour resection. CONCLUSION: Exploration and resection rates increased, but one-third of patients who had surgical exploration for pancreatic cancer did not undergo resection. Non-resectional surgery doubled the 30-day mortality rate compared with that in patients undergoing tumour resection