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BACKGROUND: Since 2016, staging laparoscopy has been implemented in the diagnostic workup of patients with gastric cancer. Staging laparoscopy aims to detect incurable disease (peritoneal metastases and irresectable tumors) and to prevent futile laparotomies. METHODS: In this population-based nationwide study, we sought patient- and tumor characteristics associated with undergoing a staging laparoscopy. Additionally, we analyzed the prevalence of synchronous peritoneal metastases, the outcome of the staging laparoscopy and its clinical impact on treatment decisions. All patients diagnosed with non-cardia gastric cancer from the Netherlands Cancer Registry between 2016 and 2021 were included. RESULTS: Alongside tumor characteristics, patient characteristics such as younger age, absence of comorbidities and lower WHO performance status were associated with performing a staging laparoscopy. In the study period, an increase in the proportion of patients who underwent a staging laparoscopy was observed, from 19.6% in 2016 to 32.3% in 2021 (p-value<0.001). In the same period, the prevalence of synchronous peritoneal metastases increased from 25% to 31%. In 37.6% of the patients who had the outcome of their staging laparoscopy reported, had incurable disease diagnosed during staging laparoscopy. Significantly less of these patients were treated with triplet regimens as compared to patients with a negative staging laparoscopy (18.5 vs. 76.3%; p-value<0.001). CONCLUSION: The implementation of staging laparoscopy in gastric cancer patients paralleled the increase in diagnosis of incurable disease and a decrease in the application of triplet systemic therapies in these patients.
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BACKGROUND: Disease recurrence remains one of the biggest concerns in patients after resection of pancreatic ductal adenocarcinoma (PDAC). Despite (neo)adjuvant systemic therapy, most patients experience local and/or distant PDAC recurrence within 2 years. High-level evidence regarding the benefits of recurrence-focused surveillance after PDAC resection is missing, and the impact of early detection and treatment of recurrence on survival and quality of life is unknown. In most European countries, recurrence-focused follow-up after surgery for PDAC is currently lacking. Consequently, guidelines regarding postoperative surveillance are based on expert opinion and other low-level evidence. The recent emergence of more potent local and systemic treatment options for PDAC recurrence has increased interest in early diagnosis. To determine whether early detection and treatment of recurrence can lead to improved survival and quality of life, we designed an international randomized trial. METHODS: This randomized controlled trial is nested within an existing prospective cohort in pancreatic cancer centers in the Netherlands (Dutch Pancreatic Cancer Project; PACAP) and the United Kingdom (UK) (Pancreas Cancer: Observations of Practice and survival; PACOPS) according to the "Trials within Cohorts" (TwiCs) design. All PACAP/PACOPS participants with a macroscopically radical resection (R0-R1) of histologically confirmed PDAC, who provided informed consent for TwiCs and participation in quality of life questionnaires, are included. Participants randomized to the intervention arm are offered recurrence-focused surveillance, existing of clinical evaluation, serum cancer antigen (CA) 19-9 testing, and contrast-enhanced computed tomography (CT) of chest and abdomen every three months during the first 2 years after surgery. Participants in the control arm of the study will undergo non-standardized clinical follow-up, generally consisting of clinical follow-up with imaging and serum tumor marker testing only in case of onset of symptoms, according to local practice in the participating hospital. The primary endpoint is overall survival. Secondary endpoints include quality of life, patterns of recurrence, compliance to and costs of recurrence-focused follow-up, and the impact on recurrence-focused treatment. DISCUSSION: The RADAR-PANC trial will be the first randomized controlled trial to generate high level evidence for the current clinical equipoise regarding the value of recurrence-focused postoperative surveillance with serial tumor marker testing and routine imaging in patients after PDAC resection. The Trials within Cohort design allows us to study the acceptability of recurrence-focused surveillance among cohort participants and increases the generalizability of findings to the general population. While it is strongly encouraged to offer all trial participants treatment at time of recurrence diagnosis, type and timing of treatment will be determined through shared decision-making. This might reduce the potential survival benefits of recurrence-focused surveillance, although insights into the impact on patients' quality of life will be obtained. TRIAL REGISTRATION: Clinicaltrials.gov, NCT04875325 . Registered on May 6, 2021.
Subject(s)
Carcinoma, Pancreatic Ductal , Neoplasm Recurrence, Local , Pancreatectomy , Pancreatic Neoplasms , Quality of Life , Randomized Controlled Trials as Topic , Humans , Carcinoma, Pancreatic Ductal/surgery , Carcinoma, Pancreatic Ductal/mortality , Carcinoma, Pancreatic Ductal/diagnostic imaging , Carcinoma, Pancreatic Ductal/pathology , Carcinoma, Pancreatic Ductal/blood , Pancreatic Neoplasms/surgery , Pancreatic Neoplasms/pathology , Pancreatectomy/adverse effects , Time Factors , Prospective Studies , Multicenter Studies as Topic , Treatment Outcome , Predictive Value of Tests , Netherlands , United Kingdom , Research Design , Early Detection of Cancer/methodsABSTRACT
BACKGROUND: Distinguishing postoperative fibrosis from isolated local recurrence (ILR) after resection of pancreatic ductal adenocarcinoma (PDAC) is challenging. A prognostic model that helps to identify patients at risk of ILR can assist clinicians when evaluating patients' postoperative imaging. This nationwide study aimed to develop a clinically applicable prognostic model for ILR after PDAC resection. PATIENTS AND METHODS: An observational cohort study was performed, including all patients who underwent PDAC resection in the Netherlands (2014-2019; NCT04605237). On the basis of recurrence location (ILR, systemic, or both), multivariable cause-specific Cox-proportional hazard analysis was conducted to identify predictors for ILR and presented as hazard ratios (HRs) with 95% confidence intervals (CIs). A predictive model was developed using Akaike's Information Criterion, and bootstrapped discrimination and calibration indices were assessed. RESULTS: Among 1194/1693 patients (71%) with recurrence, 252 patients (21%) developed ILR. Independent predictors for ILR were resectability status (borderline versus resectable, HR 1.42; 95% CI 1.03-1.96; P = 0.03, and locally advanced versus resectable, HR 1.11; 95% CI 0.68-1.82; P = 0.66), tumor location (head versus body/tail, HR 1.50; 95% CI 1.00-2.25; P = 0.05), vascular resection (HR 1.86; 95% CI 1.41-2.45; P < 0.001), perineural invasion (HR 1.47; 95% CI 1.01-2.13; P = 0.02), number of positive lymph nodes (HR 1.04; 95% CI 1.01-1.08; P = 0.02), and resection margin status (R1 < 1 mm versus R0 ≥ 1 mm, HR 1.64; 95% CI 1.25-2.14; P < 0.001). Moderate performance (concordance index 0.66) with adequate calibration (slope 0.99) was achieved. CONCLUSIONS: This nationwide study identified factors predictive of ILR after PDAC resection. Our prognostic model, available through www.pancreascalculator.com , can be utilized to identify patients with a higher a priori risk of developing ILR, providing important information in patient evaluation and prognostication.
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BACKGROUND: Surgical resection followed by adjuvant mFOLFIRINOX (5-fluorouracil with leucovorin, irinotecan, and oxaliplatin) is currently the standard of care for patients with resectable pancreatic cancer. The main concern regarding adjuvant chemotherapy is that only half of patients actually receive adjuvant treatment. Neoadjuvant chemotherapy, on the other hand, guarantees early systemic treatment and may increase chemotherapy use and thereby improve overall survival. Furthermore, it may prevent futile surgery in patients with rapidly progressive disease. However, some argue that neoadjuvant therapy delays surgery, which could lead to progression towards unresectable disease and thus offset the potential benefits. Comparison of perioperative (i.e., neoadjuvant and adjuvant) with (only) adjuvant administration of mFOLFIRINOX in a randomized controlled trial (RCT) is needed to determine the optimal approach. METHODS: This multicenter, phase 3, RCT will include 378 patients with resectable pancreatic ductal adenocarcinoma with a WHO performance status of 0 or 1. Patients are recruited from 20 Dutch centers and three centers in Norway and Sweden. Resectable pancreatic cancer is defined as no arterial contact and ≤ 90 degrees venous contact. Patients in the intervention arm are scheduled for 8 cycles of neoadjuvant mFOLFIRINOX followed by surgery and 4 cycles of adjuvant mFOLFIRINOX (2-week cycle of oxaliplatin 85 mg/m2, leucovorin 400 mg/m2, irinotecan 150 mg/m2 at day 1, followed by 46 h continuous infusion of 5-fluorouracil 2400 g/m2). Patients in the comparator arm start with surgery followed by 12 cycles of adjuvant mFOLFIRINOX. The primary outcome is overall survival by intention-to-treat. Secondary outcomes include progression-free survival, resection rate, quality of life, adverse events, and surgical complications. 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 the inclusion of 378 patients in 36 months, with analysis planned 18 months after the last patient has been randomized. DISCUSSION: The multicenter PREOPANC-3 trial compares perioperative mFOLFIRINOX with adjuvant mFOLFIRINOX in patients with resectable pancreatic cancer. TRIAL REGISTRATION: Clinical Trials: NCT04927780. Registered June 16, 2021.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols , Pancreatic Neoplasms , Humans , Irinotecan/therapeutic use , Oxaliplatin/therapeutic use , Leucovorin/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Pancreatic Neoplasms/drug therapy , Pancreatic Neoplasms/surgery , Fluorouracil/therapeutic use , Neoadjuvant Therapy/methods , Chemotherapy, Adjuvant , Adjuvants, Immunologic/therapeutic use , Randomized Controlled Trials as Topic , Multicenter Studies as Topic , Pancreatic NeoplasmsABSTRACT
BACKGROUND: As part of a randomized phase II trial in patients with isolated resectable colorectal peritoneal metastases (CPMs), the present study compared patient-reported outcomes (PROs) of patients treated with perioperative systemic therapy versus cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) alone. Also, PROs of patients receiving perioperative systemic therapy were explored. PATIENTS AND METHODS: Eligible patients were randomized to perioperative systemic therapy (experimental) or CRS-HIPEC alone (control). PROs were assessed using EORTC QLQ-C30, QLQ-CR29, and EQ-5D-5L questionnaires at baseline, after neoadjuvant treatment (experimental), and at 3 and 6 months postoperatively. Linear mixed modeling was used to compare five predefined PROs (visual analog scale, global health status, physical functioning, fatigue, C30 summary score) between arms and to longitudinally analyze PROs in the experimental arm. RESULTS: Of 79 analyzed patients, 37 (47%) received perioperative systemic therapy. All predefined PROs were comparable between arms at all timepoints and returned to baseline at 3 or 6 months postoperatively. The experimental arm had worsening of fatigue [mean difference (MD) + 14, p = 0.001], loss of appetite (MD + 15, p = 0.003), hair loss (MD + 18, p < 0.001), and loss of taste (MD + 27, p < 0.001) after neoadjuvant treatment. Except for loss of appetite, these PROs returned to baseline at 3 or 6 months postoperatively. CONCLUSIONS: In patients with resectable CPM randomized to perioperative systemic therapy or CRS-HIPEC alone, PROs were comparable between arms and returned to baseline postoperatively. Together with the trial's previously reported feasibility and safety data, these findings show acceptable tolerability of perioperative systemic therapy in this setting.
Subject(s)
Colorectal Neoplasms , Hyperthermia, Induced , Peritoneal Neoplasms , Humans , Hyperthermic Intraperitoneal Chemotherapy , Peritoneal Neoplasms/secondary , Colorectal Neoplasms/pathology , Cytoreduction Surgical Procedures , Combined Modality Therapy , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Patient Reported Outcome Measures , Survival RateABSTRACT
BACKGROUND: The mean incidence of ovarian metastases (OM) in patients with colorectal cancer (CRC) is 3.4%. The 5-year survival of these patients, even when operated with curative intent, is remarkably low. The lifetime risk of ovarian cancer is approximately 1.3%. Prophylactic salpingo-oophorectomy (PSO, or surgical removal of the ovaries and fallopian tubes) could reduce the number of CRC patients that develop OM after removal of the primary tumor, as well as preventing the occurrence of primary ovarian cancer. Recently, the care pathway for CRC has been changed in several hospitals in line with the updated Dutch guideline. The possibility of PSO is now discussed with postmenopausal CRC patients in these hospitals. The aims of the current study are firstly to estimate the incidence of OM and primary ovarian cancer in postmenopausal patients with CRC, and secondly to evaluate the effect of PSO in these patients. METHODS: An information bulletin and decision guide on this topic was implemented in several Dutch hospitals in 2020. Post-decision outcomes will be collected prospectively. The study population consists of postmenopausal (≥ 60 years of age) patients that are operated with curative intent for CRC. Based on their own preference, patients will be divided into two groups: those who choose to undergo PSO and those who do not. The main study parameters are the reduction in incidence of ovarian malignancies (metastatic or primary) following PSO, and the number needed to treat (NNT) by PSO to prevent one case of ovarian malignancy. DISCUSSION: This will be the first study to evaluate the effect of PSO in postmenopausal CRC patients that is facilitated by an altered CRC care pathway. The results of this study are expected to provide relevant information on whether PSO adds significant value to postmenopausal patients with CRC. TRIAL REGISTRATION: International Clinical Trials Registry Platform, NL7870. Registered on 2019 July 12. URL of trial registry record: https://trialsearch.who.int/Trial2.aspx?TrialID=NL7870 . PROTOCOL VERSION: 1.0, date 2021 June 8.
Subject(s)
Colorectal Neoplasms , Ovarian Neoplasms , Female , Humans , Colorectal Neoplasms/complications , Colorectal Neoplasms/pathology , Colorectal Neoplasms/surgery , Ovarian Neoplasms/prevention & control , Ovarian Neoplasms/epidemiology , Ovariectomy , Postmenopause , Salpingo-oophorectomyABSTRACT
BACKGROUND AND PURPOSE: Previous studies indicated that approximately 3.4% of female colorectal cancer (CRC) patients are at increased risk of developing ovarian metastases (OM). It has been suggested that young women more frequently develop this form of metastatic disease. METHODS: This study evaluated, in 6 Dutch hospitals, the proportion of young women with CRC who developed OM. RESULTS: In a cohort of 200 young (age ≤ 55) women with CRC, the proportion of patients diagnosed with synchronous or metachronous OM was calculated. This study revealed that 5% (n = 10) of young female CRC patients developed ovarian metastases resulting in a 5-year overall survival rate of approximately 40%. Furthermore, six patients had concurrent peritoneal metastases, five patients had bilateral ovarian metastases, and five patients had synchronous metastases, while the median time of the occurrence of metachronous metastases (n = 5) was 19 months. CONCLUSION: This retrospective multicenter cohort study indicates that 5% of young women with CRC either present with or develop OM. This result appears to be clinically relevant and demonstrates the need for improved surveillance for young women diagnosed with CRC.
Subject(s)
Colorectal Neoplasms , Cohort Studies , Colorectal Neoplasms/pathology , Female , Humans , Prognosis , Retrospective Studies , Survival RateABSTRACT
BACKGROUND: With the introduction of cytoreductive surgery with intraperitoneal chemotherapy and the development of new systemic anti-cancer agents, the treatment of colorectal cancer (CRC) patients with peritoneal metastases has changed. Real-world data on the treatment of elderly patients and their clinical outcomes is lacking. METHODS: All CRC patients diagnosed with synchronous peritoneal metastases (SPM) during 2008-2019 (n = 7,748) were identified from the Netherlands Cancer Registry. Trends in treatment and postoperative mortality were described by age category (<70, 70-74, 75-79, ≥80 years) and period of diagnosis (2008-2013, 2014-2019). Kaplan-Meier curves were constructed, and log-rank tests were performed to evaluate differences in overall survival (OS). RESULTS: With increasing age, less patients received multimodality treatment and systemic treatment. Of the patients aged <70 years, 38% underwent multimodality treatment and 35% palliative systemic therapy, declining to 4% and 12% in patients ≥80 years. A large and increasing proportion of elderly patients did not receive cancer-directed treatment, this increased from 32% in 2008-2013 to 41% in 2014-2019 in 75-79 years old patients and from 52% to 65% in ≥80 years old. Postoperative mortality decreased in all age categories over time, OS remained stable. The median OS of elderly patients ranged from 8 months in 70-74 years old to 3 months in patients aged ≥80 years. DISCUSSION: Age strongly affects treatment of patients with SPM, with a large and increasing proportion of elderly patients not receiving cancer-directed treatment. Their prognosis remains very poor. There is a need for therapeutic options that are well tolerable for elderly patients.
Subject(s)
Colorectal Neoplasms , Hyperthermia, Induced , Peritoneal Neoplasms , Aged , Humans , Aged, 80 and over , Child, Preschool , Child , Peritoneal Neoplasms/secondary , Colorectal Neoplasms/pathology , Cytoreduction Surgical Procedures , Peritoneum/pathology , Combined Modality Therapy , Survival RateABSTRACT
BACKGROUND AND PURPOSE: Women with colorectal cancer (CRC) are at risk not only of developing ovarian metastases, but also of developing a primary ovarian malignancy. Several earlier studies have in fact shown a link between the development of primary ovarian cancer and CRC. The purpose of this study was therefore to determine the risk of developing a primary ovarian cancer in women with prior CRC compared to the general population. METHODS: Data from the Netherlands Cancer Registry were used. All women diagnosed with invasive CRC between 1989 and 2017 were included. Standardized incidence ratios (SIRs) and absolute excess risks (AERs) per 10,000 person-years were calculated. RESULTS: During the study period, 410 (0.3%) CRC patients were diagnosed with primary ovarian cancer. Women with CRC had a 20% increased risk of developing ovarian cancer compared to the general population (SIR = 1.2, 95% CI: 1.1-1.3). The AER of ovarian cancer was 0.9 per 10,000 person-years. The risk was especially increased within the first year of a CRC diagnosis (SIR = 3.3, 95% CI: 2.8-3.8) and in women aged ≤ 55 years (SIR = 2.0, 95% CI: 1.6-2.6). CONCLUSION: This study found a slightly increased risk of primary ovarian cancer in women diagnosed with CRC compared to the general population. However, this may be partly attributable to surveillance or detection bias. Nevertheless, our findings could be helpful for patient counseling, as CRC patients do not currently receive information concerning the increased risk of ovarian cancer.
Subject(s)
Colorectal Neoplasms , Neoplasms, Second Primary , Ovarian Neoplasms , Colorectal Neoplasms/complications , Colorectal Neoplasms/epidemiology , Female , Humans , Incidence , Neoplasms, Second Primary/epidemiology , Ovarian Neoplasms/epidemiology , Registries , Risk FactorsABSTRACT
BACKGROUND: This study aimed to describe the treatment of metachronous colorectal cancer metastases in a recent population-based cohort. METHOD: Patients with stage I-III colorectal cancer (CRC), diagnosed between January 1st and June 30th, 2015 who were surgically treated with curative intent were selected from the Netherlands Cancer Registry. Follow-up was at least 3 years after diagnosis of the primary tumour. Treatment of metachronous metastases was categorized into local treatment, systemic treatment, and best supportive care. Overall survival was estimated using Kaplan-Meier method. RESULTS: Out of 5412 patients, 782 (14%) developed metachronous metastases, of whom 393 (50%) underwent local treatment (LT) with or without systemic therapy, 30% of patients underwent only systemic therapy (ST) and 19% only best supportive care (BSC). The most common metastatic site was the liver (51%) followed by lungs (33%) and peritoneum (22%). LT rates were 69%, 66%, and 44% for liver-only, lung-only and, peritoneal-only metastases respectively. Patients receiving LT and ST were significantly younger than patients receiving LT alone, while patients receiving BSC were significantly older than the other groups (p < 0.001). Patients with liver-only or lung-only metastases had a 3-year OS of 50.2% (43.3-56.7 95% CI) and 61.5% (50.7-70.6 95% CI) respectively. Patients with peritoneal-only disease had a lower 3-year OS, 18.1% (10.1-28.0 95% CI). CONCLUSION: Patients with metastases confined to the liver and lung have the highest rates of local treatment for metachronous metastatic colorectal cancer. The number of patients who underwent local treatment is higher than reported in previous Dutch and international studies.
Subject(s)
Colonic Neoplasms , Colorectal Neoplasms , Liver Neoplasms , Lung Neoplasms , Rectal Neoplasms , Colorectal Neoplasms/pathology , Humans , Liver Neoplasms/secondary , Lung Neoplasms/secondary , Lung Neoplasms/therapy , Netherlands/epidemiology , PrognosisABSTRACT
BACKGROUND: This study aims to assess the impact of nationwide centralization of surgery on travel distance and travel burden among patients with oesophageal, gastric, and pancreatic cancer according to age in the Netherlands. As centralization of care increases to improve postoperative outcomes, travel distance and experienced burden might increase. MATERIALS AND METHODS: All patients who underwent surgery between 2006 and 2017 for oesophageal, gastric and pancreatic cancer in the Netherlands were included. Travel distance between patient's home address and hospital of surgery in kilometres was calculated. Questionnaires were used to assess experienced travel burden in a subpopulation (n = 239). Multivariable ordinal logistic regression models were constructed to identify predictors for longer travel distance. RESULTS: Over 23,838 patients were included, in whom median travel distance for surgical care increased for oesophageal cancer (n = 9217) from 18 to 28 km, for gastric cancer (n = 6743) from 9 to 26 km, and for pancreatic cancer (n = 7878) from 18 to 25 km (all p < 0.0001). Multivariable analyses showed an increase in travel distance for all cancer types over time. In general, patients experienced a physical and social burden, and higher financial costs, due to traveling extra kilometres. Patients aged >70 years travelled less often independently (56% versus 68%), as compared to patients aged ≤70 years. CONCLUSION: With nationwide centralization, travel distance increased for patients undergoing oesophageal, gastric, and pancreatic cancer surgery. Younger patients travelled longer distances and experienced a lower travel burden, as compared to elderly patients. Nevertheless, on a global scale, travel distances in the Netherlands remain limited.
Subject(s)
Cost of Illness , Digestive System Surgical Procedures , Esophageal Neoplasms/surgery , Health Services Accessibility , Pancreatic Neoplasms/surgery , Stomach Neoplasms/surgery , Surgical Oncology/organization & administration , Travel , Age Factors , Aged , Female , Health Expenditures , Hospital Planning , Hospitals , Hospitals, High-Volume , Hospitals, Low-Volume , Humans , Logistic Models , Male , Middle Aged , Multivariate Analysis , Netherlands , Referral and Consultation , Surveys and QuestionnairesABSTRACT
BACKGROUND: Despite the fact that primary percutaneous catheter drainage has become standard practice, some patients with pancreatic fistula after pancreatoduodenectomy ultimately undergo a relaparotomy. The aim of this study was to compare completion pancreatectomy with a pancreas-preserving procedure in patients undergoing relaparotomy for pancreatic fistula after pancreatoduodenectomy. METHODS: This retrospective cohort study of nine institutions included patients who underwent relaparotomy for pancreatic fistula after pancreatoduodenectomy from 2005-2018. Furthermore, a systematic review and meta-analysis were performed according to the PRISMA guidelines. RESULTS: From 4877 patients undergoing pancreatoduodenectomy, 786 (16 per cent) developed a pancreatic fistula grade B/C and 162 (3 per cent) underwent a relaparotomy for pancreatic fistula. Of these patients, 36 (22 per cent) underwent a completion pancreatectomy and 126 (78 per cent) a pancreas-preserving procedure. Mortality was higher after completion pancreatectomy (20 (56 per cent) versus 40 patients (32 per cent); P = 0.009), which remained after adjusting for sex, age, BMI, ASA score, previous reintervention, and organ failure in the 24 h before relaparotomy (adjusted odds ratio 2.55, 95 per cent c.i. 1.07 to 6.08). The proportion of additional reinterventions was not different between groups (23 (64 per cent) versus 84 patients (67 per cent); P = 0.756). The meta-analysis including 33 studies evaluating 745 patients, confirmed the association between completion pancreatectomy and mortality (Mantel-Haenszel random-effects model: odds ratio 1.99, 95 per cent c.i. 1.03 to 3.84). CONCLUSION: Based on the current data, a pancreas-preserving procedure seems preferable to completion pancreatectomy in patients in whom a relaparotomy is deemed necessary for pancreatic fistula after pancreatoduodenectomy.
Subject(s)
Drainage/methods , Laparotomy/methods , Pancreatectomy/methods , Pancreatic Fistula/surgery , Pancreaticoduodenectomy/adverse effects , Postoperative Complications/surgery , Cohort Studies , Global Health , Humans , Incidence , Intraoperative Period , Multicenter Studies as Topic , Pancreatic Fistula/epidemiology , Pancreatic Fistula/etiology , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Reoperation , Survival Rate/trendsABSTRACT
BACKGROUND: Postoperative pancreatic fistula (POPF) remains the main cause of morbidity in patients after distal pancreatectomy. The objective of this study was to investigate whether an absorbable fibrin sealant patch could prevent POPF after distal pancreatectomy. METHODS: A multicentre, patient-blinded, parallel-group randomized superiority trial was performed in seven Dutch hospitals. Allocation was done using a computer-generated randomization list with a 1 : 1 allocation ratio and concealed varying permuted block sizes. Pancreatic stump closure with a fibrin patch was compared with standard treatment in patients undergoing distal pancreatectomy. The primary endpoint was the development of grade B/C POPF. A systematic review and meta-analysis was performed which combined the present findings with all available evidence. RESULTS: Between October 2010 and August 2017, 247 patients were enrolled. Fifty-four patients (22.2 per cent) developed a POPF, 25 of 125 patients in the patch group versus 29 of 122 in the control group (20.0 versus 23.8 per cent; P = 0·539). No related adverse effects were observed. In the meta-analysis, no significant difference was seen between the patch and control groups (19.7 versus 22.0 per cent; odds ratio 0.89, 95 per cent c.i. 0.60 to 1.32; P = 0·556). CONCLUSION: Application of a fibrin patch to the pancreatic stump does not reduce the incidence of POPF in distal pancreatectomy. Future studies should focus on alternative fistula mitigation strategies, considering pancreatic neck thickness and duct size as risk factors. Trial registration number NL5876 (Netherlands Trial Registry).
Subject(s)
Fibrin Tissue Adhesive , Pancreatic Fistula , Humans , Fibrin Tissue Adhesive/therapeutic use , Multicenter Studies as Topic , Pancreas/surgery , Pancreatectomy/adverse effects , Pancreatic Fistula/etiology , Pancreatic Fistula/prevention & control , Randomized Controlled Trials as TopicABSTRACT
BACKGROUND: This study aimed to compare treatment strategies and survival of patients with synchronous colorectal peritoneal metastases (CPM) and patients with metachronous CPM in a nationwide cohort. METHODS: All patients from the Netherlands Cancer Registry with synchronous or metachronous CPM whose primary colorectal cancer (CRC) was diagnosed between 1 January and 30 June 2015 were included in the study. Treatments were categorized as (A) cytoreductive surgery and hyperthermic intraperitoneal chemotherapy [CRS-HIPEC]; (B) palliative treatment; or (C) best supportive care. Overall survival (OS) for all the patients and disease-free survival (DFS) for those who underwent CRS-HIPEC were compared between the two groups. RESULTS: Of 7233 patients, 743 had a diagnosis of CPM, including 409 patients with synchronous CPM and 334 patients with metachronous CPM. The median OS was 8.1 months for the patients with synchronous CPM versus 12 months for the patients with metachronous CPM (p = 0.003). After multivariable correction, OS no longer differed between the patients with synchronous CPM and those with metachronous CPM (HR 1.03 [0.83-1.27]). The patients with metachronous CPM more often underwent CRS-HIPEC than the patients with synchronous CPM (16 % vs 8 %; p = 0.001). The two groups did not differ statistically in terms of DFS and OS (median DFS, 21.5 vs 14.1 months, respectively; p = 0.094; median OS, 37.8 vs. 35.8 months, respectively; p = 0.553). CONCLUSION: This population-based study showed that survival for the patients with synchronous CPM and patients with metachronous CPM did not significantly differ. This suggests that a similar prognosis may be expected for patients selected for treatment regardless of the onset of CPM.
Subject(s)
Colorectal Neoplasms , Hyperthermia, Induced , Peritoneal Neoplasms , Colorectal Neoplasms/therapy , Combined Modality Therapy , Cytoreduction Surgical Procedures , Humans , Peritoneal Neoplasms/therapy , Prognosis , Survival RateABSTRACT
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.
Subject(s)
Pancreatic Neoplasms , Radiofrequency Ablation , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Humans , Multicenter Studies as Topic , Netherlands , Pancreatic Neoplasms/drug therapy , Pancreatic Neoplasms/surgery , Progression-Free Survival , Radiofrequency Ablation/adverse effects , Randomized Controlled Trials as TopicABSTRACT
BACKGROUND: Selecting patients with peritoneal metastases from colorectal cancer (CRCPM) who might benefit from cytoreductive surgery followed by hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) is challenging. Computed tomography generally underestimates the peritoneal tumor load. Diagnostic laparoscopy is often used to determine whether patients are amenable for surgery. Magnetic resonance imaging (MRI) has shown to be accurate in predicting completeness of CRS. The aim of this study is to determine whether MRI can effectively reduce the need for surgical staging. METHODS: The study is designed as a multicenter randomized controlled trial (RCT) of colorectal cancer patients who are deemed eligible for CRS-HIPEC after conventional CT staging. Patients are randomly assigned to either MRI based staging (arm A) or to standard surgical staging with or without laparoscopy (arm B). In arm A, MRI assessment will determine whether patients are eligible for CRS-HIPEC. In borderline cases, an additional diagnostic laparoscopy is advised. The primary outcome is the number of unnecessary surgical procedures in both arms defined as: all surgeries in patients with definitely inoperable disease (PCI > 24) or explorative surgeries in patients with limited disease (PCI < 15). Secondary outcomes include correlations between surgical findings and MRI findings, cost-effectiveness, and quality of life (QOL) analysis. CONCLUSION: This randomized trial determines whether MRI can effectively replace surgical staging in patients with CRCPM considered for CRS-HIPEC. TRIAL REGISTRATION: Registered in the clinical trials registry of U.S. National Library of Medicine under NCT04231175 .