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  • 1
    In: Annals of Surgery, Ovid Technologies (Wolters Kluwer Health), Vol. 278, No. 2 ( 2023-08), p. 260-266
    Abstract: To describe outcome after pancreatic surgery in the first 6 years of a mandatory nationwide audit. Background: Within the Dutch Pancreatic Cancer Group, efforts have been made to improve outcome after pancreatic surgery. These include collaborative projects, clinical auditing, and implementation of an algorithm for early recognition and management of postoperative complications. However, nationwide changes in outcome over time have not yet been described. Methods: This nationwide cohort study included consecutive patients after pancreatoduodenectomy (PD) and distal pancreatectomy from the mandatory Dutch Pancreatic Cancer Audit (January 2014–December 2019). Patient, tumor, and treatment characteristics were compared between 3 time periods (2014–2015, 2016–2017, and 2018–2019). Short-term surgical outcome was investigated using multilevel multivariable logistic regression analyses. Primary endpoints were failure to rescue (FTR) and in-hospital mortality. Results: Overall, 5345 patients were included, of whom 4227 after PD and 1118 after distal pancreatectomy. After PD, FTR improved from 13% to 7.4% [odds ratio (OR) 0.64, 95% confidence interval (CI) 0.50–0.80, P 〈 0.001] and in-hospital mortality decreased from 4.1% to 2.4% (OR 0.68, 95% CI 0.54–0.86, P =0.001), despite operating on more patients with age 〉 75 years (18%–22%, P =0.006), American Society of Anesthesiologists score ≥3 (19%–31%, P 〈 0.001) and Charlson comorbidity score ≥2 (24%–34%, P 〈 0.001). The rates of textbook outcome (57%–55%, P =0.283) and major complications remained stable (31%–33%, P =0.207), whereas complication-related intensive care admission decreased (13%–9%, P =0.002). After distal pancreatectomy, improvements in FTR from 8.8% to 5.9% (OR 0.65, 95% CI 0.30–1.37, P =0.253) and in-hospital mortality from 1.6% to 1.3% (OR 0.88, 95% CI 0.45–1.72, P =0.711) were not statistically significant. Conclusions: During the first 6 years of a nationwide audit, in-hospital mortality and FTR after PD improved despite operating on more high-risk patients. Several collaborative efforts may have contributed to these improvements.
    Type of Medium: Online Resource
    ISSN: 0003-4932
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2023
    detail.hit.zdb_id: 2002200-1
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  • 2
    In: British Journal of Surgery, Oxford University Press (OUP), Vol. 110, No. 10 ( 2023-09-06), p. 1374-1380
    Abstract: Guidelines suggest that the serum carbohydrate antigen (CA19-9) level should be used when deciding on neoadjuvant treatment in patients with resectable and borderline resectable pancreatic ductal adenocarcinoma (hereafter referred to as pancreatic cancer). In patients with resectable pancreatic cancer, neoadjuvant therapy is advised when the CA19-9 level is ‘markedly elevated’. This study investigated the impact of baseline CA19-9 concentration on the treatment effect of neoadjuvant chemoradiotherapy (CRT) in patients with resectable and borderline resectable pancreatic cancers. Methods In this post hoc analysis, data were obtained from two RCTs that compared neoadjuvant CRT with upfront surgery in patients with resectable and borderline resectable pancreatic cancers. The effect of neoadjuvant treatment on overall survival was compared between patients with a serum CA19-9 level above or below 500 units/ml using the interaction test. Results Of 296 patients, 179 were eligible for analysis, 90 in the neoadjuvant CRT group and 89 in the upfront surgery group. Neoadjuvant CRT was associated with superior overall survival (HR 0.67, 95 per cent c.i. 0.48 to 0.94; P = 0.019). Among 127 patients (70, 9 per cent) with a low CA19-9 level, median overall survival was 23.5 months with neoadjuvant CRT and 16.3 months with upfront surgery (HR 0.63, 0.42 to 0.93). For 52 patients (29 per cent) with a high CA19-9 level, median overall survival was 15.5 months with neoadjuvant CRT and 12.9 months with upfront surgery (HR 0.82, 0.45 to 1.49). The interaction test for CA19-9 level exceeding 500 units/ml on the treatment effect of neoadjuvant CRT was not significant (P = 0.501). Conclusion Baseline serum CA19-9 level defined as either high or low has prognostic value, but was not associated with the treatment effect of neoadjuvant CRT in patients with resectable and borderline resectable pancreatic cancers, in contrast with current guideline advice.
    Type of Medium: Online Resource
    ISSN: 0007-1323 , 1365-2168
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2023
    detail.hit.zdb_id: 2006309-X
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  • 3
    In: British Journal of Surgery, Oxford University Press (OUP), Vol. 109, No. 1 ( 2021-12-17), p. 96-104
    Abstract: Venous resection of the superior mesenteric or portal vein is increasingly performed in pancreatic cancer surgery, whereas results of studies on short- and long-term outcomes are contradictory. The aim of this study was to evaluate the impact of the type of venous resection in pancreatoduodenectomy for pancreatic cancer on postoperative morbidity and overall survival. Methods This nationwide retrospective cohort study included all patients who underwent pancreatoduodenectomy for pancreatic cancer in 18 centres (2013–2017). Results A total of 1311 patients were included, of whom 17 per cent underwent wedge resection and 10 per cent segmental resection. Patients with segmental resection had higher rates of major morbidity (39 versus 20 versus 23 per cent, respectively; P  & lt; 0.001) and portal or superior mesenteric vein thrombosis (18 versus 5 versus 1 per cent, respectively; P  & lt; 0.001) and worse overall survival (median 12 versus 16 versus 20 months, respectively; P  & lt; 0.001), compared to patients with wedge resection and those without venous resection. Multivariable analysis showed patients with segmental resection, but not those who had wedge resection, had higher rates of major morbidity (odds ratio = 1.93, 95 per cent c.i. 1.20 to 3.11) and worse overall survival (hazard ratio = 1.40, 95 per cent c.i. 1.10 to 1.78), compared to patients without venous resection. Among patients who received neoadjuvant therapy, there was no difference in overall survival among patients with segmental and wedge resection and those without venous resection (median 32 versus 25 versus 33 months, respectively; P = 0.470), although there was a difference in major morbidity rates (52 versus 19 versus 21 per cent, respectively; P  = 0.012). Conclusion In pancreatic surgery, the short- and long-term outcomes are worse in patients with venous segmental resection, compared to patients with wedge resection and those without venous resection.
    Type of Medium: Online Resource
    ISSN: 0007-1323 , 1365-2168
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2021
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  • 4
    In: BMC Cancer, Springer Science and Business Media LLC, Vol. 21, No. 1 ( 2021-12)
    Abstract: Neoadjuvant therapy has several potential advantages over upfront surgery in patients with localized pancreatic cancer; more patients receive systemic treatment, fewer patients undergo futile surgery, and R0 resection rates are higher, thereby possibly improving overall survival (OS). Two recent randomized trials have suggested benefit of neoadjuvant chemoradiotherapy over upfront surgery, both including single-agent chemotherapy regimens. Potentially, the multi-agent FOLFIRINOX regimen (5-fluorouracil with leucovorin, irinotecan, and oxaliplatin) may further improve outcomes in the neoadjuvant setting for localized pancreatic cancer, but randomized studies are needed. The PREOPANC-2 trial investigates whether neoadjuvant FOLFIRINOX improves OS compared with neoadjuvant gemcitabine-based chemoradiotherapy and adjuvant gemcitabine in resectable and borderline resectable pancreatic cancer patients. Methods This nationwide multicenter phase III randomized controlled trial includes patients with pathologically confirmed resectable and borderline resectable pancreatic cancer with a WHO performance score of 0 or 1. Resectable pancreatic cancer is defined as no arterial and ≤ 90 degrees venous involvement; borderline resectable pancreatic cancer is defined as ≤90 degrees arterial and ≤ 270 degrees venous involvement without occlusion. Patients receive 8 cycles of neoadjuvant FOLFIRINOX chemotherapy followed by surgery without adjuvant treatment (arm A), or 3 cycles of neoadjuvant gemcitabine with hypofractionated radiotherapy (36 Gy in 15 fractions) during the second cycle, followed by surgery and 4 cycles of adjuvant gemcitabine (arm B). The primary endpoint is OS by intention-to-treat. Secondary endpoints include progression-free survival, quality of life, resection rate, and R0 resection rate. To detect a hazard ratio of 0.70 with 80% power, 252 events are needed. The number of events is expected to be reached after inclusion of 368 eligible patients assuming an accrual period of 3 years and 1.5 years follow-up. Discussion The PREOPANC-2 trial directly compares two neoadjuvant regimens for patients with resectable and borderline resectable pancreatic cancer. Our study will provide evidence on the neoadjuvant treatment of choice for patients with resectable and borderline resectable pancreatic cancer. Trial registration Primary registry and trial identifying number: EudraCT: 2017–002036-17 . Date of registration: March 6, 2018. Secondary identifying numbers: The Netherlands National Trial Register – NL7094 , NL61961.078.17, MEC-2018-004.
    Type of Medium: Online Resource
    ISSN: 1471-2407
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
    detail.hit.zdb_id: 2041352-X
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  • 5
    In: BMC Cancer, Springer Science and Business Media LLC, Vol. 22, No. 1 ( 2022-12-29)
    Abstract: Significant comorbidities, advanced age, and a poor performance status prevent surgery and systemic treatment for many patients with localized (non-metastatic) pancreatic ductal adenocarcinoma (PDAC). These patients are currently treated with ‘best supportive care’. Therefore, it is desirable to find a treatment option which could improve both disease control and quality of life in these patients. A brief course of high-dose high-precision radiotherapy i.e. stereotactic ablative body radiotherapy (SABR) may be feasible. Methods A nationwide multicenter trial performed within a previously established large prospective cohort (the Dutch Pancreatic cancer project; PACAP) according to the ‘Trial within cohorts’ (TwiCs) design. Patients enrolled in the PACAP cohort routinely provide informed consent to answer quality of life questionnaires and to be randomized according to the TwiCs design when eligible for a study. Patients with localized PDAC who are unfit for chemotherapy and surgery or those who refrain from these treatments are eligible. Patients will be randomized between SABR (5 fractions of 8 Gy) with ‘best supportive care’ and ‘best supportive care’ only. The primary endpoint is overall survival from randomization. Secondary endpoints include preservation of quality of life (EORTC-QLQ-C30 and -PAN26), NRS pain score response and WHO performance scores at baseline, and, 3, 6 and 12 months. Acute and late toxicity will be scored using CTCAE criteria version 5.0: assessed at baseline, day of last fraction, at 3 and 6 weeks, and 3, 6 and 12 months following SABR. Discussion The PANCOSAR trial studies the added value of SBRT as compared to ‘best supportive care’ in patients with localized PDAC who are medically unfit to receive chemotherapy and surgery, or refrain from these treatments. This study will assess whether SABR, in comparison to best supportive care, can relieve or delay tumor-related symptoms, enhance quality of life, and extend survival in these patients. Trial registration Clinical trials, NCT05265663 , Registered March 3 2022, Retrospectively registered.
    Type of Medium: Online Resource
    ISSN: 1471-2407
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 2041352-X
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  • 6
    In: BMC Cancer, Springer Science and Business Media LLC, Vol. 23, No. 1 ( 2023-01-20)
    Type of Medium: Online Resource
    ISSN: 1471-2407
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2023
    detail.hit.zdb_id: 2041352-X
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  • 7
    In: Annals of Surgery, Ovid Technologies (Wolters Kluwer Health)
    Abstract: To develop a prediction model for long-term (≥5 years) disease-free survival (DFS) after resection of pancreatic ductal adenocarcinoma (PDAC). Summary Background Data: Despite high recurrence rates, approximately 10% of patients have long-term DFS after PDAC resection. A model to predict long-term DFS may aid individualized prognostication and shared decision-making. Methods: This nationwide cohort study included all consecutive patients who underwent PDAC resection in the Netherlands (2014-2016). The best performing prognostic model was selected by Cox-proportional hazard analysis and Akaike’s Information Criterion, presented by hazard ratio’s (HR) with 95% confidence interval (CI). Internal validation was performed, and discrimination and calibration indices were assessed. Results: 836 patients with a median follow-up of 67 months (interquartile range 51-79) were analyzed. Long-term DFS was seen in 118 patients (14%). Factors predictive of long-term DFS were low preoperative carbohydrate antigen 19-9 (logarithmic; HR1.21; 95%CI 1.10-1.32), no vascular resection (HR1.33; 95%CI 1.12-1.58), T1 or T2 tumor stage (HR1.52; 95%CI 1.14-2.04, and HR1.17; 95%CI 0.98-1.39, respectively), well/moderate tumor differentiation (HR1.44; 95%CI 1.22-1.68), absence of perineural and lymphovascular invasion (HR1.42; 95%CI 1.11-1.81 and HR1.14; 95%CI 0.96-1.36, respectively), N0 or N1 nodal status (HR1.92; 95%CI 1.54-2.40, and HR1.33; 95%CI 1.11-1.60, respectively), R0 resection margin status (HR1.25; 95%CI 1.07-1.46), no major complications (HR1.14; 95%CI 0.97-1.35) and adjuvant chemotherapy (HR1.74; 95%CI 1.47-2.06). Moderate performance (concordance index 0.68) with adequate calibration (slope 0.99) was achieved. Conclusions: The developed prediction model, readily available at www.pancreascalculator.com, can be used to estimate the probability of long-term disease-free survival after resection of pancreatic ductal adenocarcinoma.
    Type of Medium: Online Resource
    ISSN: 0003-4932
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2023
    detail.hit.zdb_id: 2002200-1
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  • 8
    In: Trials, Springer Science and Business Media LLC, Vol. 21, No. 1 ( 2020-12)
    Abstract: 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.
    Type of Medium: Online Resource
    ISSN: 1745-6215
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2020
    detail.hit.zdb_id: 2040523-6
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  • 9
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 16 ( 2020-06-01), p. 1763-1773
    Abstract: 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 × 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.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2020
    detail.hit.zdb_id: 2005181-5
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  • 10
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 41, No. 16_suppl ( 2023-06-01), p. 4152-4152
    Abstract: 4152 Background: Implementation of new treatment strategies in cancer care is often inadequate and slow. We aimed to implement best practices in pancreatic cancer care using a nationwide stepped wedge design and assess the impact on overall survival. Methods: Nationwide multicenter stepped-wedge cluster randomized controlled trial comparing implementation of best practices with usual care (May 22, 2018 – May 29, 2020). Best practices included adequate use of perioperative and palliative chemotherapy, pancreatic enzyme replacement therapy (PERT), and metal biliary stents. The 6-week implementation period in all 17 Dutch pancreatic centers and their regional referral networks included monitoring, return visits, and provider feedback in combination with education and reminders. Primary outcome was one-year overall survival for all disease stages and secondary outcomes included guideline compliance and quality of life. Results: Overall, 5580 patients diagnosed with pancreatic cancer were included; 2939 after implementation of best practices versus 2641 before. One-year survival did not differ among the groups (HR 0.98, 95 CI 0.88-1.08). Overall use of perioperative chemotherapy (neoadjuvant and adjuvant) did not significantly differ, but use of palliative chemotherapy significantly increased (23.9% to 30.3%, OR 1.38, 95 CI 1.10-1.74). Also the use of PERT (34.2% to 45.2%, OR 1.64, 95 CI 1.28-2.11); and metal biliary stents (74.1.% to 83.3%, OR 1.78, 95 CI 1.13-2.08) significantly increased. The Global Health Score did not differ (AUC 43.8 to 42.7, median difference -1.12, 95 CI -3.13-0.80, n=655). Conclusions: This nationwide population-based trial to enhance implementation of best practices in pancreatic cancer care showed successful implementation of most best practices, but no increase in one-year survival and quality of life. Clinical trial information: NCT03513705 .
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2023
    detail.hit.zdb_id: 2005181-5
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