Radiofrequency ablation and chemotherapy versus chemotherapy alone for locally advanced pancreatic cancer (PELICAN): study protocol for a randomized controlled trial

Quimioteràpia; Càncer de pàncrees localment avançat; Ablació per radiofreqüènciaQuimioterapia; Cáncer de páncreas localmente avanzado; Ablación por radiofrecuenciaChemotherapy; Locally advanced pancreatic cancer; Radiofrequency ablationBackground Approximately 80% of patients with locally advanced pancreatic cancer (LAPC) are treated with chemotherapy, of whom approximately 10% undergo a resection. Cohort studies investigating local tumor ablation with radiofrequency ablation (RFA) have reported a promising overall survival of 26–34 months when given in a multimodal setting. However, randomized controlled trials (RCTs) investigating the effect of RFA in combination with chemotherapy in patients with LAPC are lacking. Methods The “Pancreatic Locally Advanced Unresectable Cancer Ablation” (PELICAN) trial is an international multicenter superiority RCT, initiated by the Dutch Pancreatic Cancer Group (DPCG). All patients with LAPC according to DPCG criteria, who start with FOLFIRINOX or (nab-paclitaxel/)gemcitabine, are screened for eligibility. Restaging is performed after completion of four cycles of FOLFIRINOX or two cycles of (nab-paclitaxel/)gemcitabine (i.e., 2 months of treatment), and the results are assessed within a nationwide online expert panel. Eligible patients with RECIST stable disease or objective response, in whom resection is not feasible, are randomized to RFA followed by chemotherapy or chemotherapy alone. In total, 228 patients will be included in 16 centers in The Netherlands and four other European centers. The primary endpoint is overall survival. Secondary endpoints include progression-free survival, RECIST response, CA 19.9 and CEA response, toxicity, quality of life, pain, costs, and immunomodulatory effects of RFA. Discussion The PELICAN RCT aims to assess whether the combination of chemotherapy and RFA improves the overall survival when compared to chemotherapy alone, in patients with LAPC with no progression of disease following 2 months of systemic treatment.Olympus Netherlands BV supported the investigator-initiated PELICAN trial with material support by providing the RFA generators and electrodes for the study. They did not have and will not have any influence on the trial design, data collection, interpretation of the data, manuscript development, or decision to publish. Furthermore, the study protocol has undergone full external peer review and received a data management and monitoring grant from the Dutch Cancer Society (grant number 2014-7244)

Tailoring intervention procedures to routine primary health care practice; an ethnographic process evaluation

Background. Tailor-made approaches enable the uptake of interventions as they are seen as a way to overcome the incompatibility of general interventions with local knowledge about the organisation of routine medical practice and the relationship between the patients and the professionals in practice. Our case is the Quattro project which is a prevention programme for cardiovascular diseases in high-risk patients in primary health care centres in deprived neighbourhoods. This programme was implemented as a pragmatic trial and foresaw the importance of local knowledge in primary health care and internal, or locally made, guidelines. The aim of this paper is to show how this prevention programme, which could be tailored to routine care, was implemented in primary care. Methods. An ethnographic design was used for this study. We observed and interviewed the researchers and the practice nurses. All the research documents, observations and transcribed interviews were analysed thematically. Results. Our ethnographic process evaluation showed that the opportunity of tailoring intervention procedures to routine care in a pragmatic trial setting did not result in a well-organised and well-implemented prevention programme. In fact, the lack of standard protocols hindered the implementation of the intervention. Although it was not the purpose of this trial, a guideline was developed. Despite the fact that the developed guideline functioned as a tool, it did not result in the intervention being organised accordingly. However, the guideline did make tailoring the intervention possible. It provided the professionals with the key or the instructions needed to achieve organisational change and transform the existing interprofessional relations. Conclusion. As tailor-made approaches are developed to enable the uptake of interventions in routine practice, they are facilitated by the brokering of tools such as guidelines. In our study, guidelines facilitated organisational change and enabled the transformation of existing interprofessional relations, and thus made tailoring possible. The attractive flexibility of pragmatic trial design in taking account of local practice variations may often be overestimated

Radiofrequency ablation and chemotherapy versus chemotherapy alone for locally advanced pancreatic cancer (PELICAN):study protocol for a randomized controlled trial

Contains fulltext : 239066.pdf (Publisher’s version ) (Open Access)BACKGROUND: Approximately 80% of patients with locally advanced pancreatic cancer (LAPC) are treated with chemotherapy, of whom approximately 10% undergo a resection. Cohort studies investigating local tumor ablation with radiofrequency ablation (RFA) have reported a promising overall survival of 26-34 months when given in a multimodal setting. However, randomized controlled trials (RCTs) investigating the effect of RFA in combination with chemotherapy in patients with LAPC are lacking. METHODS: The "Pancreatic Locally Advanced Unresectable Cancer Ablation" (PELICAN) trial is an international multicenter superiority RCT, initiated by the Dutch Pancreatic Cancer Group (DPCG). All patients with LAPC according to DPCG criteria, who start with FOLFIRINOX or (nab-paclitaxel/)gemcitabine, are screened for eligibility. Restaging is performed after completion of four cycles of FOLFIRINOX or two cycles of (nab-paclitaxel/)gemcitabine (i.e., 2 months of treatment), and the results are assessed within a nationwide online expert panel. Eligible patients with RECIST stable disease or objective response, in whom resection is not feasible, are randomized to RFA followed by chemotherapy or chemotherapy alone. In total, 228 patients will be included in 16 centers in The Netherlands and four other European centers. The primary endpoint is overall survival. Secondary endpoints include progression-free survival, RECIST response, CA 19.9 and CEA response, toxicity, quality of life, pain, costs, and immunomodulatory effects of RFA. DISCUSSION: The PELICAN RCT aims to assess whether the combination of chemotherapy and RFA improves the overall survival when compared to chemotherapy alone, in patients with LAPC with no progression of disease following 2 months of systemic treatment. TRIAL REGISTRATION: Dutch Trial Registry NL4997 . Registered on December 29, 2015. ClinicalTrials.gov NCT03690323 . Retrospectively registered on October 1, 2018

Predicting overall survival and resection in patients with locally advanced pancreatic cancer treated with FOLFIRINOX:Development and internal validation of two nomograms

Background and Objectives Patients with locally advanced pancreatic cancer (LAPC) are increasingly treated with FOLFIRINOX, resulting in improved survival and resection of tumors that were initially unresectable. It remains unclear, however, which specific patients benefit from FOLFIRINOX. Two nomograms were developed predicting overall survival (OS) and resection at the start of FOLFIRINOX for LAPC. Methods From our multicenter, prospective LAPC registry in 14 Dutch hospitals, LAPC patients starting first-line FOLFIRINOX (April 2015-December 2017) were included. Stepwise backward selection according to the Akaike Information Criterion was used to identify independent baseline predictors for OS and resection. Two prognostic nomograms were generated. Results A total of 252 patients were included, with a median OS of 14 months. Thirty-two patients (13%) underwent resection, with a median OS of 23 months. Older age, female sex, Charlson Comorbidity Index 1, involvement of the superior mesenteric artery, celiac trunk, and superior mesenteric vein >= 270 degrees were independent factors decreasing the probability of resection (c-index: 0.79). Conclusions Two nomograms were developed to predict OS and resection in patients with LAPC before starting treatment with FOLFIRINOX. These nomograms could be beneficial in the shared decision-making process and counseling of these patients

Tailored Print Communication and Telephone Motivational Interviewing Are Equally Successful in Improving Multiple Lifestyle Behaviors in a Randomized Controlled Trial

Background: Computer tailoring and motivational interviewing show promise in promoting lifestyle change, despite few head-to-head comparative studies. Purpose: Vitalum is a randomized controlled trial in which the efficacy of these methods was compared in changing physical activity and fruit and vegetable consumption in middle-aged Dutch adults. Methods: Participants (n?=?1,629) were recruited via 23 general practices and randomly received either four tailored print letters, four motivational telephone calls, two of each type of intervention, or no information. The primary outcomes were absolute change in self-reported physical activity and fruit and vegetable consumption. Results: All three intervention groups (i.e., the tailored letters, the motivational calls, and the combined version) were equally and significantly more effective than the control group in increasing physical activity (hours/day), intake of fruit (servings/day), and consumption of vegetables (grams/day) from baseline to the intermediate measurement (week 25), follow-up 1 (week 47) and 2 (week 73). Effect sizes (Cohen's d) ranged from 0.15 to 0.18. Participants rated the interventions positively; interviews were more positively evaluated than letters. Conclusions: Tailored print communication and telephone motivational interviewing or their combination are equally successful in changing multiple behaviors. © 2010 The Author(s)

Locally advanced pancreatic cancer: Work-up, staging, and local intervention strategies

Locally advanced pancreatic cancer (LAPC) has several definitions but essentially is a nonmetastasized pancreatic cancer, in which upfront resection is considered not beneficial due to extensive vascular involvement and consequent high chance of a nonradical resection. The introduction of FOLFIRINOX chemotherapy and gemcitabine-nab-paclitaxel (gem-nab) has had major implications for the management and outcome of patients with LAPC. After 4–6 months induction chemotherapy, the majority of patients have stable disease or even tumor-regression. Of these, 12 to 35% are successfully downstaged to resectable disease. Several studies have reported a 30–35 months overall survival after resection; although it currently remains unclear if this is a result of the resection or the good response to chemotherapy. Following chemotherapy, selection of patients for resection is difficult, as contrast-enhanced computed-tomography (CT) scan is unreliable in differentiating between viable tumor and fibrosis. In case a resection is not considered possible but stable disease is observed, local ablative techniques are being studied, such as irreversible electroporation, radiofrequency ablation, and stereotactic body radiation therapy. Pragmatic, multicenter, randomized studies will ultimately have to confirm the exact role of both surgical exploration and ablation in these patients. Since evidence-based guidelines for the management of LAPC are lacking, this review proposes a standardized approach for the treatment of LAPC based on the best available evidence

Vacuum-assisted closure therapy for infected perineal wounds after abdominoperineal resection. A retrospective cohort study

INTRODUCTION: Perineal wound complications are a main problem after abdominoperineal resection (APR). There is little evidence concerning perineal wound management. This study describes and evaluates the role of vacuum-assisted closure (VAC) therapy in wound management strategies of perineal wound infections after APR. METHODS: Patients undergoing APR for malignant disease between January 2007 and January 2013 were identified retrospectively. Data regarding occurrence and management of perineal wound complications were collected. Perineal wound infections were classified into minor or major complications and time to wound healing was measured. Time to wound healing was compared between patients receiving routine care or with additional VAC therapy. RESULTS: Of 171 included patients, 76 (44.4%) had minor and 36 (21.1%) major perineal wound infections. Management of major infected perineal wounds consisted of drainage (n = 16), debridement (n = 4), drainage combined with debridement (n = 4), VAC therapy alone (n = 5), or VAC therapy combined with other treatments (n = 7). Median duration of perineal wound healing in major infected wounds was 141 days (range 17-739). Median time to wound healing was not different in patients treated with (172 days, range 23-368) or without VAC therapy (131 days, range 17-739). DISCUSSION AND CONCLUSION: In this study, VAC therapy did not shorten time to wound healing. However, prospective studies are required to investigate the role of VAC therapy in management of infected perineal wounds after APR. Up to then, wound management will remain to be based on clinical perception and 'gut-feeling'