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

Comparison of dose metrics between automated and manual radiotherapy planning for advanced stage non-small cell lung cancer with volumetric modulated arc therapy

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The Prognostic Relevance of Histological Subtype in Patients With Peritoneal Metastases From Colorectal Cancer: A Nationwide Population-Based Study

Item does not contain fulltextBACKGROUND: With evolving treatment possibilities for peritoneal metastases (PM) from colorectal cancer (CRC), adequate prognostication and patient selection for treatment becomes increasingly important. We investigated the prognostic relevance of commonly identified histological subtypes in PM of CRC (adenocarcinoma [AC], mucinous AC [MC], and signet-ring cell carcinoma [SC]), which is currently unclear. PATIENTS AND METHODS: This study involved 4277 patients diagnosed with synchronous PM from CRC between 2005 and 2012 in The Netherlands. Kaplan-Meier analysis and log-rank testing were performed to estimate survival. Subsequently a Cox proportional hazard model was used to calculate hazard ratios for the risk of death. RESULTS: Most of the CRC patients were diagnosed with AC (n = 3008; 70%), whereas MC and SC were found in 958 (22%) and 311 (7%) patients, respectively. SC was associated with the highest risk of death in colon and rectal cancer, with median survival rates of respectively, 6.6 and 6.9 months. For MC, median survival varied from 10.9 months in colon and 9.8 months in rectal cancer (P > .05). In colon cancer, MC was associated with a significantly lower risk of death compared with AC (hazard ratio, 0.9; 95% confidence interval, 0.79-0.95). In rectal cancer, no such effect was observed. AC was associated with a significantly poorer survival rate in the case of primary colonic tumor localization (7.4 months in colon vs. 10.9 months in rectal cancer). CONCLUSION: Histological subtype is an important prognostic factor in patients with synchronous PM of colorectal origin. This knowledge will aid clinicians in counseling of patients and clinical decision-making regarding possible treatment options

Increase in the incidence of synchronous and metachronous peritoneal metastases in patients with colorectal cancer: A nationwide study

Introduction: – To investigate the incidence of, factors associated with, and differences between synchronous and metachronous colorectal peritoneal metastases (CPM) in a population-based cohort. Methods: – Data from the Netherlands Cancer Registry were used. All patients diagnosed with colorectal cancer (CRC) between 1 January and June 30, 2015 were evaluated for synchronous or metachronous CPM (diagnosis ≤90 or >90 days after surgery for primary CRC), and survival in 2019 (median follow-up 38.4 months). Results: – Of 7233 included patients, 409 (5.7%) were diagnosed with synchronous CPM. Factors associated with synchronous CPM were mucinous (OR 2.72 [1.90–3.90]) or signet ring cell (SRC) histology (OR 6.58 [3.66–11.81]), T4 (OR 4.82 [3.68–6.32]), N1 (OR 1.66 [1.20–2.30]), or N2 stage (OR 3.27 [2.36–4.52]), and synchronous systemic metastases (SM) (OR 3.13 [2.37–4.14]). After surgery for primary CRC, 326 patients developed metachronous CPM after a median time of 14.7 months (3-year cumulative incidence: 5.5%). Factors associated with metachronous CPM were younger age (HR 1.63 [1.10–2.42]), mucinous (HR 1.84 [1.20–2.82]) or SRC histology (HR 2.43 [1.11–5.32]), T4 (HR 2.77 [2.07–3.70]), N1 (HR 2.90 [2.18–3.85]), N2 (HR 3.19 [2.26–4.50]), and synchronous SM (HR 1.95 [1.43–2.66]). Conclusion: – This population-based study found the highest incidence of CPM currently reported in literature and a strong association between the presence of synchronous SM and both synchronous and metachronous CPM. These findings may contribute to a tailored approach in the follow-up after primary CRC surgery and guide future clinical trials investigating new strategies regarding risk-reduction or early detection of metachronous CPM

Preoperative Chemoradiotherapy Versus Immediate Surgery for Resectable and Borderline Resectable Pancreatic Cancer: Results of the Dutch Randomized Phase III PREOPANC Trial

PURPOSE Preoperative chemoradiotherapy may improve the radical resection rate for resectable or borderline resectable pancreatic cancer, but the overall benefit is unproven.PATIENTS AND METHODS In this randomized phase III trial in 16 centers, patients with resectable or borderline resectable pancreatic cancer were randomly assigned to receive preoperative chemoradiotherapy, which consisted of 3 courses of gemcitabine, the second combined with 15 x 2.4 Gy radiotherapy, followed by surgery and 4 courses of adjuvant gemcitabine or to immediate surgery and 6 courses of adjuvant gemcitabine. The primary end point was overall survival by intention to treat.RESULTS Between April 2013 and July 2017, 246 eligible patients were randomly assigned; 119 were assigned to preoperative chemoradiotherapy and 127 to immediate surgery. Median overall survival by intention to treat was 16.0 months with preoperative chemoradiotherapy and 14.3 months with immediate surgery (hazard ratio, 0.78; 95% CI, 0.58 to 1.05; P = .096). The resection rate was 61% and 72% (P = .058). The R0 resection rate was 71% (51 of 72) in patients who received preoperative chemoradiotherapy and 40% (37 of 92) in patients assigned to immediate surgery (P < .001). Preoperative chemoradiotherapy was associated with significantly better disease-free survival and locoregional failure-free interval as well as with significantly lower rates of pathologic lymph nodes, perineural invasion, and venous invasion. Survival analysis of patients who underwent tumor resection and started adjuvant chemotherapy showed improved survival with preoperative chemoradiotherapy (35.2 v 19.8 months; P = .029). The proportion of patients who suffered serious adverse events was 52% versus 41% (P = .096).CONCLUSION Preoperative chemoradiotherapy for resectable or borderline resectable pancreatic cancer did not show a significant overall survival benefit. Although the outcomes of the secondary end points and predefined subgroup analyses suggest an advantage of the neoadjuvant approach, additional evidence is required.Surgical oncolog

Neoadjuvant Chemoradiotherapy Versus Upfront Surgery for Resectable and Borderline Resectable Pancreatic Cancer: Long-Term Results of the Dutch Randomized PREOPANC Trial

PURPOSE The benefit of neoadjuvant chemoradiotherapy in resectable and borderline resectable pancreatic cancer remains controversial. Initial results of the PREOPANC trial failed to demonstrate a statistically significant overall survival (OS) benefit. The long-term results are reported. METHODS In this multicenter, phase III trial, patients with resectable and borderline resectable pancreatic cancer were randomly assigned (1:1) to neoadjuvant chemoradiotherapy or upfront surgery in 16 Dutch centers. Neoadjuvant chemoradiotherapy consisted of three cycles of gemcitabine combined with 36 Gy radiotherapy in 15 fractions during the second cycle. After restaging, patients underwent surgery followed by four cycles of adjuvant gemcitabine. Patients in the upfront surgery group underwent surgery followed by six cycles of adjuvant gemcitabine. The primary outcome was OS by intention-to-treat. No safety data were collected beyond the initial report of the trial. RESULTS Between April 24, 2013, and July 25, 2017, 246 eligible patients were randomly assigned to neoadjuvant chemoradiotherapy (n = 119) and upfront surgery (n = 127). At a median follow-up of 59 months, the OS was better in the neoadjuvant chemoradiotherapy group than in the upfront surgery group (hazard ratio, 0.73; 95% CI, 0.56 to 0.96; P = .025). Although the difference in median survival was only 1.4 months (15.7 months v 14.3 months), the 5-year OS rate was 20.5% (95% CI, 14.2 to 29.8) with neoadjuvant chemoradiotherapy and 6.5% (95% CI, 3.1 to 13.7) with upfront surgery. The effect of neoadjuvant chemoradiotherapy was consistent across the prespecified subgroups, including resectable and borderline resectable pancreatic cancer. CONCLUSION Neoadjuvant gemcitabine-based chemoradiotherapy followed by surgery and adjuvant gemcitabine improves OS compared with upfront surgery and adjuvant gemcitabine in resectable and borderline resectable pancreatic cancer