Multimodality treatment of colorectal peritoneal metastases:Towards evidence-based practice

This thesis focuses on patients with peritoneal metastases of colorectal cancer. Part 1 shows that the hospital of diagnosis with this disease seems to influence the probability of undergoing curative intent surgery and survival. Part 2 focuses on patients with operable peritoneal metastases undergoing curative intent surgery. Internationally, these patients increasingly receive chemotherapy before and after surgery, while nothing is known about the benefits of chemotherapy in this setting. This thesis shows that chemotherapy before and after surgery is safe, tolerable, and potentially effective. Part 3 focuses on patients with inoperable peritoneal metastases who cannot be cured. Internationally, these patients increasingly undergo PIPAC (i.e. intra-abdominal aerosol chemotherapy), while there is no available research supporting the use of PIPAC in this setting. This thesis shows that PIPAC is feasible and seems biologically active, but leads to (sometimes severe) adverse events and transient worsening of quality of life

Angular CMA: A modified Constant Modulus Algorithm providing steering angle updates

Conventional blind beamforming algorithms have no direct notion of the physical Direction of Arrival angle of an impinging signal. These blind adaptive algorithms operate by adjusting the complex steering vector in the case of changing signal conditions and directions. This paper presents Angular CMA, a blind beamforming method that calculates steering angle updates (instead of weight vector updates) to keep track of the desired signal. Angular CMA and its respective steering angle updates are particularly useful in the context of mixed-signal hierarchical arrays as means to find and distribute steering parameters. Simulations of Angular CMA show promising convergence behaviour, while having a lower complexity than alternative methods (e.g., MUSIC)

DVB-S Signal Tracking Techniques for Mobile Phased Arrays

Abstract—A system that uses adaptive beamforming techniques for mobile Digital Video Broadcasting Satellite (DVB-S) reception is proposed in this paper. The purpose is to enable DVB-S reception in moving vehicles. Phased arrays are able to electronically track the desired signal during dynamic behaviour of the vehicle the array is mounted on.\ud The proposed system uses blind beamforming to adapt the array steering vector to changing signal (conditions and) directions. Movement of the vehicle, the phased array is mounted on, leads to modulus and phase deviations at the beamformer output. An extended version of the Constant Modulus Algorithm (CMA) algorithm is used to adapt the steering vector weights to compensate for those deviations.\ud For simulation of the proposed system a model of vehicle dynamics is used to generate realistic antenna data. Simulation of the proposed system based on this antenna data shows appropriate corrections for modulus and phase deviations

F-18-fluorodeoxyglucose positron emission tomography combined with CT in critically ill patients with suspected infection

Contains fulltext : 88623.pdf (publisher's version ) (Closed access)PURPOSE: To assess the value of F-18-fluorodeoxyglucose positron emission tomography (FDG-PET) combined with CT in critically ill patients suspected of having an infection. METHODS: FDG-PET CT scans requested for evaluation of a suspected infection or inflammatory process in critically ill, mechanically ventilated patients were analyzed (blinded for the final clinical diagnosis) and compared with clinical follow-up. RESULTS: Thirty-five FDG-PET/CT scans performed in 33 ICU patients (28 adults and 5 children), median age 58 years (range 1 month-72 years), were analyzed. Twenty-one FDG-PET/CT scans were true positive. Three FDG-PET/CT scans were considered false positive, in one case leading to additional diagnostic procedures (specificity 79%). Additionally, 11 true negatives were found (sensitivity 100%), leading to an overall accuracy of 91%. CONCLUSIONS: FDG-PET/CT scanning is of additional value in the evaluation of suspected infection in critically ill patients in whom conventional diagnostics did not lead to a diagnosis. Apart from the high accuracy, in this study it appeared that, in addition to conventional diagnostic techniques that were routinely performed, a normal FDG-PET/CT ruled out important infections requiring prolonged antibiotic therapy or drainage. Since sensitivity is lower in highly metabolic active tissues (e.g., endocarditis, meningitis), the FDG-PET/CT scan is not suited to detect infections in these tissues.01 maart 201

Patient-reported outcomes during repetitive oxaliplatin-based pressurized intraperitoneal aerosol chemotherapy for isolated unresectable colorectal peritoneal metastases in a multicenter, single-arm, phase 2 trial (CRC-PIPAC)

BACKGROUND: CRC-PIPAC prospectively assessed repetitive oxaliplatin-based pressurized intraperitoneal aerosol chemotherapy (PIPAC-OX) as a palliative monotherapy (i.e., without concomitant systemic therapy in between subsequent procedures) for unresectable colorectal peritoneal metastases (CPM). The present study explored patient-reported outcomes (PROs) during trial treatment. METHODS: In this single-arm phase 2 trial in two tertiary centers, patients with isolated unresectable CPM received 6-weekly PIPAC-OX (92 mg/m(2)). PROs (calculated from EQ-5D-5L, and EORTC QLQ-C30 and QLQ-CR29) were compared between baseline and 1 and 4 weeks after the first three procedures using linear mixed modeling with determination of clinical relevance (Cohen’s D ≥ 0.50) of statistically significant differences. RESULTS: Twenty patients underwent 59 procedures (median 3 [range 1–6]). Several PROs solely worsened 1 week after the first procedure (index value − 0.10, p < 0.001; physical functioning − 20, p < 0.001; role functioning − 27, p < 0.001; social functioning − 18, p < 0.001; C30 summary score − 16, p < 0.001; appetite loss + 15, p = 0.007; diarrhea + 15, p = 0.002; urinary frequency + 13, p = 0.004; flatulence + 13, p = 0.001). These PROs returned to baseline at subsequent time points. Other PROs worsened 1 week after the first procedure (fatigue + 23, p < 0.001; pain + 29, p < 0.001; abdominal pain + 32, p < 0.001), second procedure (fatigue + 20, p < 0.001; pain + 21, p < 0.001; abdominal pain + 20, p = 0.002), and third procedure (pain + 22, p < 0.001; abdominal pain + 22, p = 0.002). Except for appetite loss, all changes were clinically relevant. All analyzed PROs returned to baseline 4 weeks after the third procedure. CONCLUSIONS: Patients receiving repetitive PIPAC-OX monotherapy for unresectable CPM had clinically relevant but reversible worsening of several PROs, mainly 1 week after the first procedure. TRIAL REGISTRATION: Clinicaltrials.gov: NCT03246321; Netherlands trial register: NL6426. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00464-021-08802-6

Towards Equal Access to Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy and Survival in Patients with Isolated Colorectal Peritoneal Metastases:A Nationwide Population-Based Study

Background: Before 2016, patients with isolated synchronous colorectal peritoneal metastases (PMCRC) diagnosed in expert centers had a higher odds of undergoing cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) and better overall survival (OS) than those diagnosed in referring centers. Nationwide efforts were initiated to increase awareness and improve referral networks. Methods: This nationwide study aimed to evaluate whether the between-center differences in odds of undergoing CRS-HIPEC and OS have reduced since these national efforts were initiated. All patients with isolated synchronous PMCRC diagnosed between 2009 and 2021 were identified from the Netherlands Cancer Registry. Associations between hospital of diagnosis and the odds of undergoing CRS-HIPEC, as well as OS, were assessed using multilevel multivariable regression analyses for two periods (2009–2015 and 2016–2021). Results: In total, 3948 patients were included. The percentage of patients undergoing CRS-HIPEC increased from 17.2% in 2009–2015 (25.4% in expert centers, 16.5% in referring centers), to 23.4% in 2016–2021 (30.2% in expert centers, 22.6% in referring centers). In 2009–2015, compared with diagnosis in a referring center, diagnosis in a HIPEC center showed a higher odds of undergoing CRS-HIPEC (odds ratio [OR] 1.64, 95% confidence interval [CI] 1.02–2.67) and better survival (hazard ratio [HR] 0.80, 95% CI 0.66–0.96). In 2016–2021, there were no differences in the odds of undergoing CRS-HIPEC between patients diagnosed in HIPEC centers versus referring centers (OR 1.27, 95% CI 0.76–2.13) and survival (HR 1.00, 95% CI 0.76–1.32). Conclusion: Previously observed differences in odds of undergoing CRS-HIPEC were no longer present. Increased awareness and the harmonization of treatment for PMCRC may have contributed to equal access to care and a similar chance of survival at a national level.</p

Towards Equal Access to Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy and Survival in Patients with Isolated Colorectal Peritoneal Metastases:A Nationwide Population-Based Study

Background: Before 2016, patients with isolated synchronous colorectal peritoneal metastases (PMCRC) diagnosed in expert centers had a higher odds of undergoing cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) and better overall survival (OS) than those diagnosed in referring centers. Nationwide efforts were initiated to increase awareness and improve referral networks. Methods: This nationwide study aimed to evaluate whether the between-center differences in odds of undergoing CRS-HIPEC and OS have reduced since these national efforts were initiated. All patients with isolated synchronous PMCRC diagnosed between 2009 and 2021 were identified from the Netherlands Cancer Registry. Associations between hospital of diagnosis and the odds of undergoing CRS-HIPEC, as well as OS, were assessed using multilevel multivariable regression analyses for two periods (2009–2015 and 2016–2021). Results: In total, 3948 patients were included. The percentage of patients undergoing CRS-HIPEC increased from 17.2% in 2009–2015 (25.4% in expert centers, 16.5% in referring centers), to 23.4% in 2016–2021 (30.2% in expert centers, 22.6% in referring centers). In 2009–2015, compared with diagnosis in a referring center, diagnosis in a HIPEC center showed a higher odds of undergoing CRS-HIPEC (odds ratio [OR] 1.64, 95% confidence interval [CI] 1.02–2.67) and better survival (hazard ratio [HR] 0.80, 95% CI 0.66–0.96). In 2016–2021, there were no differences in the odds of undergoing CRS-HIPEC between patients diagnosed in HIPEC centers versus referring centers (OR 1.27, 95% CI 0.76–2.13) and survival (HR 1.00, 95% CI 0.76–1.32). Conclusion: Previously observed differences in odds of undergoing CRS-HIPEC were no longer present. Increased awareness and the harmonization of treatment for PMCRC may have contributed to equal access to care and a similar chance of survival at a national level.</p

Consensus statement for treatment protocols in pressurized intraperitoneal aerosol chemotherapy (PIPAC)

Objectives: Safe implementation and thorough evaluation of new treatments require prospective data monitoring and standardization of treatments. Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a promising alternative for the treatment of patients with peritoneal disease with an increasing number of suggested drug regimens. The aim was to reach expert consensus on current PIPAC treatment protocols and to define the most important research topics. Methods: The expert panel included the most active PIPAC centers, organizers of PIPAC courses and principal investigators of prospective studies on PIPAC. A comprehensive literature review served as base for a two-day hybrid consensus meeting which was accompanied by a modified three-round Delphi process. Consensus bar was set at 70% for combined (strong and weak) positive or negative votes according to GRADE. Research questions were prioritized from 0 to 10 (highest importance). Results: Twenty-two out of 26 invited experts completed the entire consensus process. Consensus was reached for 10/10 final questions. The combination of doxorubicin (2.1 mg/m(2)) and cisplatin (10.5 mg/m(2)) was endorsed by 20/ 22 experts (90.9%). 16/22 (72.7%) supported oxaliplatin at 120 with potential reduction to 90 mg/m(2) (frail patients), and 77.2% suggested PIPAC-Ox in combination with 5-FU. Mitomycin-C and Nab-paclitaxel were favoured as alternative regimens. The most important research questions concerned PIPAC conditions (n=3), standard (n=4) and alternative regimens (n=5) and efficacy of PIPAC treatment (n=2); 8/14 were given a priority of &gt;= 8/10. Conclusions: The current consensus should help to limit heterogeneity of treatment protocols but underlines the utmost importance of further research

Primary tumor resection or systemic treatment as palliative treatment for patients with isolated synchronous colorectal cancer peritoneal metastases in a nationwide cohort study

Limited data are available to guide the decision-making process for clinicians and their patients regarding palliative treatment options for patients with isolated synchronous colorectal cancer peritoneal metastases (CRC-PM). Therefore, the aim of this study is to analyze the outcome of the different palliative treatments for these patients. All patients diagnosed with isolated synchronous CRC-PM between 2009 and 2020 (Netherlands Cancer Registry) who underwent palliative treatment were included. Patients who underwent emergency surgery or curative intent treatment were excluded. Patients were categorized into upfront palliative primary tumor resection (with or without additional systemic treatment) or palliative systemic treatment only. Overall survival (OS) was compared between both groups and multivariable cox regression analysis was performed. Of 1031 included patients, 364 (35%) patients underwent primary tumor resection and 667 (65%) patients received systemic treatment only. Sixty-day mortality was 9% in the primary tumor resection group and 5% in the systemic treatment group (P = 0.007). OS was 13.8 months in the primary tumor resection group and 10.3 months in the systemic treatment group (P < 0.001). Multivariable analysis showed that primary tumor resection was associated with improved OS (HR 0.68; 95%CI 0.57-0.81; P < 0.001). Palliative primary tumor resection appeared to be associated with improved survival compared to palliative systemic treatment alone in patients with isolated synchronous CRC-PM despite a higher 60-day mortality. This finding must be interpreted with care as residual bias probably played a significant role. Nevertheless, this option may be considered in the decision-making process by clinicians and their patients

Concomitant intraperitoneal and systemic chemotherapy for extensive peritoneal metastases of colorectal origin: protocol of the multicentre, open-label, phase I, dose-escalation INTERACT trial

INTRODUCTION: Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) has become standard of care for patients with peritoneal metastases of colorectal origin with a low/moderate abdominal disease load. In case of a peritoneal cancer index (PCI) score >20, CRS-HIPEC is not considered to be beneficial. Patients with a PCI >20 are currently offered palliative systemic chemotherapy. Previous studies have shown that systemic chemotherapy is less effective against peritoneal metastases than it is against haematogenous spread of colorectal cancer. It is suggested that patients with peritoneal metastases may benefit from the addition of intraperitoneal chemotherapy to systemic chemotherapy. Aim of this study is to establish the maximum tolerated dose of intraperitoneal irinotecan, added to standard of care systemic therapy for colorectal cancer. Secondary endpoints are to determine the safety and feasibility of this treatment and to establish the pharmacokinetic profile of intraperitoneally administered irinotecan. METHODS AND ANALYSIS: This phase I, '3+3' dose-escalation, study is performed in two Dutch tertiary referral centres. The study population consists of adult pa