Palliation of Dysphagia from Esophageal Cancer

The prognosis of esophageal cancer is poor with a 5-year survival of 10-15%. In addition, over 50% of patients with esophageal cancer already have an inoperable disease at presentation. The majority of these patients require palliative treatment to relieve progressive dysphagia. Metal stent placement and single dose brachytherapy (intraluminal radiation) are the two most widely used palliative treatments for dysphagia from esophageal cancer, however, their relative merits are unknown. In this thesis, we present the results of the first randomized trial comparing metal stent placement with single dose brachytherapy for the palliation of dysphagia from inoperable esophageal cancer. Between December 1999 and June 2002, 209 patients with dysphagia from inoperable carcinoma of the esophagus or gastro-esophageal junction were randomized to placement of a metal stent (n=108) or single dose brachytherapy (n=101). Patients randomized to stent placement received an Ultraflex stent, patients in the brachytherapy group were treated with a single intraluminal radiation dose of 12 Gray. We compared the two treatments with respect to relief of dysphagia, complications, treatment for persistent or recurrent dysphagia, health related quality of life and costs

The yield of chest computed tomography in patients with locally advanced pancreatic cancer

Objective: To evaluate the incidence of pulmonary metastases on chest computed tomography (CT) in patients with locally advanced pancreatic cancer (LAPC). Methods: All patients diagnosed with LAPC in a single tertiary center (Erasmus MC) between October 2011 and December 2017 were reviewed. The staging chest CT scan and follow-up chest CT scans were evaluated. Pulmonary nodules were divided into three categories: apparent benign, too small to characterize, and apparent malignant. Results: In 124 consecutive patients diagnosed with LAPC, 119 (96%) patients underwent a staging chest CT scan at the initial presentation. In 88 (74%) patients no pulmonary nodules were found; in 16 (13%) patients an apparent benign pulmonary nodule was found, and in 15 (13%) patients a pulmonary nodule too small to characterize was found. Follow-up chest CT scan(s) were performed in 111 (93%) patients. In one patient with either no pulmonary nodule or an apparent benign pulmonary nodule at initial staging, an apparent malignant pulmonary nodule was found on a follow-up chest CT scan. However, a biopsy of the nodule was inconclusive. Of 15 patients in whom a pulmonary nodule too small to characterize was found at staging, 12 (80%) patients underwent a follow-up CT scan; in 4 (33%) of these patients, an apparent malignant pulmonary nodule was found. Conclusion: In patients with LAPC in whom at diagnosis a chest CT scan revealed either no pulmonary nodules or apparent benign pulmonary nodules, routine follow-up chest CT scans is not recommended. Patients with pulmonary nodules too small to characterize are at risk to develop apparent malignant pulmonary nodules during follow-up

Advances in adjuvant therapy of biliary tract cancer: an overview of current clinical evidence based on phase II and III trials

Patients with biliary tract cancer (BTC) have a high recurrence rate after complete surgical resection. To reduce the risk of recurrence and to improve survival, several chemotherapeutic agents that have shown to be active in locally advanced and metastatic BTC have been investigated in the adjuvant setting in prospective clinical trials. Based on the results of the BILCAP phase III trial, capecitabine was adapted as the standard of care by the ASCO clinical practice guideline. Ongoing randomized controlled trials mainly compare capecitabine with gemcitabine-based chemotherapy or chemoradiotherapy. This review provides an update of adjuvant therapy in BTC based on published data of phase II and III trials and ongoing randomized controlled trials (RCTs)

Implementation of contemporary chemotherapy for patients with metastatic pancreatic ductal adenocarcinoma: a population-based analysis

Background: Positive results of randomized trials led to the introduction of FOLFIRINOX in 2012 and gemcitabine with nab-paclitaxel in 2015 for patients with metastatic pancreatic ductal adenocarcinoma. It is unknown to which extent these new chemotherapeutic regimens have been implemented in clinical practice and what the impact has been on overall survival. Material and methods: Patients diagnosed with metastatic pancreatic ductal adenocarcinoma between 2007–2016 were included from the population-based Netherlands Cancer Registry. Multilevel logistic regression and Cox regression analyses, adjusting for patient, tumor, and hospital characteristics, were used to analyze variation of chemotherapy use. Results: In total, 8726 patients were included. The use of chemotherapy increased from 31% in 2007–2011 to 37% in 2012–2016 (p <.001). Variation in the use of any chemotherapy between centers decreased (adjusted range 2007–2011: 12–67%, 2012–2016: 20–54%) whereas overall survival increased from 5.6 months to 6.4 months (p <.001) for patients treated with chemotherapy. Use of FOLFIRINOX and gemcitabine with nab-paclitaxel varied widely in 2015–2016, but both showed a more favorable overall survival compared to gemcitabine monotherapy (median 8.0 vs. 7.0 vs. 3.8 months, respectively). In the period 2015–2016, FOLFIRINOX was used in 60%, gemcitabine with nab-paclitaxel in 9.7% and gemcitabine monotherapy in 25% of patients receiving chemotherapy. Conclusion: Nationwide variation in the use of chemotherapy decreased after the implementation of FOLFIRINOX and gemcitabine with nab-paclitaxel. Still a considerable proportion of patients receives gemcitabine monotherapy. Overall survival did improve, but not clinically relevant. These results emphasize the need for a structured implementation of new chemotherapeutic regimens

Conditional Survival After Resection for Pancreatic Cancer: A Population-Based Study and Prediction Model

Background: Conditional survival is the survival probability after already surviving a predefined time period. This may be informative during follow-up, especially when adjusted for tumor characteristics. Such prediction models for patients with resected pancreatic cancer are lacking and therefore conditional survival was assessed and a nomogram predicting 5-year survival at a predefined period after resection of pancreatic cancer was developed. Methods: This population-based study included patients with resected pancreatic ductal adenocarcinoma from the Netherlands Cancer Registry (2005–2016). Conditional survival was calculated as the median, and the probability of surviving up to 8 years in patients who already survived 0–5 years after resection was calculated using the Kaplan–Meier method. A prediction model was constructed. Results: Overall, 3082 patients were included, with a median age of 67 years. Median overall survival was 18 months (95% confidence interval 17–18 months), with a 5-year survival of 15%. The 1-year conditional survival (i.e. probability of surviving the next year) increased from 55 to 74 to 86% at 1, 3, and 5 years after surgery, respectively, while the median overall survival increased from 15 to 40 to 64 months at 1, 3, and 5 years after surgery, respectively. The prediction model demonstrated that the probability of achieving 5-year survival at 1 year after surgery varied from 1 to 58% depending on patient and tumor characteristics. Conclusions: This population-based study showed that 1-year conditional survival was 55% 1 year after resection and 74% 3 years after resection in patients with pancreatic cancer. The prediction model is available via www.pancreascalculator.com to inform patients and caregivers

Platelet function is disturbed by the angiogenesis inhibitors sunitinib and sorafenib, but unaffected by bevacizumab

Introduction: At the clinical introduction of antiangiogenic agents as anticancer agents, no major toxicities were expected as merely just endothelial cells (ECs) in tumors would be affected. However, several (serious) toxicities became apparent, of which underlying mechanisms are largely unknown. We investigated to what extent sunitinib (multitargeted antiangiogenic tyrosine kinase inhibitor (TKI)), sorafenib (TKI) and bevacizumab [specific antibody against vascular endothelial growth factor (VEGF)] may impair platelet function, which might explain treatment-related bleedings. Materials and methods: In vitro, the influence of sunitinib, sorafenib, and bevacizumab on platelet aggregation, P-selectin expression and fibrinogen binding, platelet–EC interaction, and tyrosine phosphorylation of c-Src was studied by optical aggregation, flow cytometry, real-time perfusion, and western blotting. Ex vivo, platelet aggregation was analyzed in 25 patients upon sunitinib or bevacizumab treatment. Concentrations of sunitinib, VEGF, and platelet and EC activation markers were measured by LC–MS/MS and ELISA. Results: In vitro, sunitinib and sorafenib significantly inhibited platelet aggregation (20 μM sunitinib: 71.3%, p < 0.001; 25 μM sorafenib: 55.8%, p = 0.042). Sorafenib and sunitinib significantly inhibited P-selectin expression on platelets. Exposure to both TKIs resulted in a reduced tyrosine phosphorylation of c-Src. Ex vivo, within 24 h sunitinib impaired platelet aggregation (83.0%, p = 0.001, N = 8). Plasma concentrations of sunitinib, VEGF, and platelet/EC activation markers were not correlated with disturbed aggregation. In contrast, bevacizumab only significantly impaired platelet aggregation in vitro at high c

Adjuvant Hepatic Arterial Infusion Pump Chemotherapy After Resection of Colorectal Liver Metastases: Results of a Safety and Feasibility Study in The Netherlands

Background: The 10-year overall survival with adjuvant hepatic arterial infusion pump (HAIP) chemotherapy after resection of colorectal liver metastases (CRLMs) was 61% in clinical trials from Memorial Sloan Kettering Cancer Center. A pilot study was performed to evaluate the safety and feasibility of adjuvant HAIP chemotherapy in patients with resectable CRLMs. Study Design: A phase II study was performed in two centers in The Netherlands. Patients with resectable CRLM without extrahepatic disease were eligible. All patients underwent complete resection and/or ablation of CRLMs and pump implantation. Safety was determined by the 90-day HAIP-related postoperative complications from the day of pump placement (Clavien–Dindo classification, grade III or higher) and feasibility by the successful administration of the first cycle of HAIP chemotherapy. Results: A total of 20 patients, with a median age of 57 years (interquartile range [IQR] 51–64) were included. Grade III or higher HAIP-related postoperative complications were found in two patients (10%), both of whom had a reoperation (without laparotomy) to replace a pump with a slow flow rate or to reposition a flipped pump. No arterial bleeding, arterial dissection, arterial thrombosis, extrahepatic perfusion, pump pocket hematoma, or pump pocket infections were found within 90 days after surgery. After a median of 43 days (IQR 29–52) following surgery, all patients received the first dose of HAIP chemotherapy, which was completed un

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

Performance-based risk-sharing agreements in renal care : current experience and future prospects

Introduction Performance-based risk-sharing agreements (PBRSAs), between payers, health care providers, and technology manufacturers can be useful when there is uncertainty about the (cost-) effectiveness of a new technology or service. However, they can be challenging to design and implement. Areas covered A total of 18 performance-based agreements were identified through a literature review. All but two of the agreements identified were pay-for-performance schemes, agreed between providers and payers at the national level. No examples were found of agreements between health care providers and manufacturers at the local level. The potential for these local agreements was illustrated by hypothetical case studies of water quality management and an integrated chronic kidney disease program. Expert opinion Performance-based risk-sharing agreements can work to the advantage of patients, health care providers, payers, and technology manufacturers, particularly if they facilitate the introduction of technologies or systems of care that might not have been introduced otherwise. However, the design, conduct, and implementation of PBRSAs in renal care pose a number of challenges. Efforts should be made to overcome these challenges so that more renal care patients can benefit from technological advances and new models of care

The bigger picture of shared decision making

Purpose: Solutions to improve the implementation of shared decision making (SDM) in oncology often focus on the consultation, with limited effects. In this study, we used a service design perspective on the care path of locally advanced pancreatic cancer (LAPC). We aimed to understand how experiences of patients, their significant others, and medical professionals over the entire care path accumulate to support their ability to participate in SDM. Participants and methods: We used qualitative interviews including design research techniques with 13 patients, 13 significant others, and 11\xc2\xa0healthcare professionals, involved in the diagnosis or treatment of LAPC. The topic list was based on the literature and an auto-ethnography of the illness trajectory by a caregiver who is also a service design researcher. We conducted a thematic content analysis to identify themes influencing the ability to participate in SDM. Results: We found four interconnected themes: (1) Decision making is an ongoing and unpredictable process with many decision moments, often unannounced. The unpredictability of the disease course, tumor response to treatment, and consequences of choices on the quality of life complicate decision making; (2) Division of roles, tasks, and collaboration among professionals and between professionals and patients and/or their significant others is often unclear to patients and their significant others; (3) It involves \xe2\x80\x9cwork\xe2\x80\x9d for patients and their significant others to obtain and understand information; (4) In \xe2\x80\x9ctheir disease journey,\xe2\x80\x9d patients are confronted with unexpected energy drains and energy boosts, that influence their level of empowerment to participate in SDM. Conclusion: The service design perspective uncovered how the stage for SDM is often set outside the consultation, which might explain the limited effect currently seen of interventions focusing on consultation itself. Our findings serve as a starting point for (re)designing care paths to improve the implementation of SDM in oncology.</p