Prognostic value and kinetics of circulating endothelial cells in patients with recurrent glioblastoma randomised to bevacizumab plus lomustine, bevacizumab single agent or lomustine single agent. A report from the Dutch Neuro-Oncology Group BELOB trial

Background:Angiogenesis is crucial for glioblastoma growth, and anti-vascular endothelial growth factor agents are widely used in recurrent glioblastoma patients. The number of circulating endothelial cells (CECs) is a surrogate marker for endothelial damage. We assessed their kinetics and explored their prognostic value in patients with recurrent glioblastoma.Methods:In this side study of the BELOB trial, 141 patients with recurrent glioblastoma were randomised to receive single-agent bevacizumab or lomustine, or bevacizumab plus lomustine. Before treatment, after 4 weeks and after 6 weeks of treatment, CECs were enumerated.Results:The number of CECs increased during treatment with bevacizumab plus lomustine, but not during treatment in the single-agent arms. In patients treated with lomustine single agent, higher absolute CEC numbers after 4 weeks (log 10 CEC hazard ratio (HR) 0.41, 95% CI 0.18-0.91) and 6 weeks (log 10 CEC HR 0.16, 95% CI 0.05-0.56) of treatment were associated with improved overall survival (OS). Absolute CEC numbers in patients receiving bevacizumab plus lomustine or bevacizumab single agent were not associated wit

Targeted therapies in colorectal cancer: an integrative view by PPPM

In developed countries, colorectal cancer (CRC) is the third most common malignancy, but it is the second most frequent cause of cancer-related death. Clinicians are still faced with numerous challenges in the treatment of this disease, and future approaches which target the molecular features of the disorder will be critical for success in this disease setting. Genetic analyses of many solid tumours have shown that up to 100 protein-encoding genes are mutated. Within CRC, numerous genetic alterations have been identified in a number of pathways. Therefore, understanding the molecular pathology of CRC may present information on potential routes for treatment and may also provide valuable prognostic information. This will be particularly pertinent for molecularly targeted treatments, such as anti-vascular endothelial growth factor therapies and anti-epidermal growth factor receptor (EGFR) monoclonal antibody therapy. KRAS and BRAF mutations have been shown to predict response to anti-EGFR therapy. As EGFR can also signal via the phosphatidylinositol 3-kinase (PI3K) kinase pathway, there is considerable interest in the potential roles of members of this pathway (such as PI3K and PTEN) in predicting treatment response. Therefore, a combined approach of new techniques that allow identification of these biomarkers alongside interdisciplinary approaches to the treatment of advanced CRC will aid in the treatment decision-making process and may also serve to guide future therapeutic approaches

The Prospective Dutch Colorectal Cancer (PLCRC) cohort: real-world data facilitating research and clinical care

Real-world data (RWD) sources are important to advance clinical oncology research and evaluate treatments in daily practice. Since 2013, the Prospective Dutch Colorectal Cancer (PLCRC) cohort, linked to the Netherlands Cancer Registry, serves as an infrastructure for scientific research collecting additional patient-reported outcomes (PRO) and biospecimens. Here we report on cohort developments and investigate to what extent PLCRC reflects the “real-world”. Clinical and demographic characteristics of PLCRC participants were compared with the general Dutch CRC population (n = 74,692, Dutch-ref). To study representativeness, standardized differences between PLCRC and Dutch-ref were calculated, and logistic regression models were evaluated on their ability to distinguish cohort participants from the Dutch-ref (AU-ROC 0.5 = preferred, implying participation independent of patient characteristics). Stratified analyses by stage and time-period (2013–2016 and 2017–Aug 2019) were performed to study the evolution towards RWD. In August 2019, 5744 patients were enrolled. Enrollment increased steeply, from 129 participants (1 hospital) in 2013 to 2136 (50 of 75 Dutch hospitals) in 2018. Low AU-ROC (0.65, 95% CI: 0.64–0.65) indicates limited ability to distinguish cohort participants from the Dutch-ref. Characteristics that remained imbalanced in the period 2017–Aug’19 compared with the Dutch-ref were age (65.0 years in PLCRC, 69.3 in the Dutch-ref) and tumor stage (40% stage-III in PLCRC, 30% in the Dutch-ref). PLCRC approaches to represent the Dutch CRC population and will ultimately meet the current demand for high-quality RWD. Efforts are ongoing to improve multidisciplinary recruitment which will further enhance PLCRC’s representativeness and its contribution to a learning healthcare system

Histological subtype and systemic metastases strongly influence treatment and survival in patients with synchronous colorectal peritoneal metastases

Treatment possibilities for colorectal peritoneal metastases (PM) are increasing. It is however unclear how treatment choice and outcome are influenced by histological subtype and the presence of systemic metastases. Therefore, this study assessed the impact of histological subtype and systemic metastases on treatment choice and survival in patients with colorectal PM.This population-based study included patients with synchronous PM originating from colorectal adenocarcinoma (AC), mucinous adenocarcinoma (MC), or signet ring cell carcinoma (SRCC). Data of patients diagnosed between 2005 and 2014 were extracted from the National Cancer Registry (IKNL) of the Netherlands. Treatment strategy and survival were analyzed with logistic regression and cox proportional hazard analyses.In total, 5516 patients were included, of whom 71.8% had an AC, 21.2% an MC, and 7.0% had an SRCC. The use of cytoreduction and hyperthermic intraperitoneal chemotherapy (HIPEC) was dependent on histological subtype and the presence of systemic metastases, and increased over time, especially in AC and MC patients. The relative survival gain of CRS?+?HIPEC, corrected for systemic metastases, was comparable in AC, MC, and SRCC patients (hazard ratio: 0.17, 0.21, and 0.13, respectively). Compared to supportive care only, the absolute survival gain was 30, 35, and 18 months, respectively. Systemic therapy improved survival in all histological subtypes.Histological subtype and the presence of systemic metastases strongly influenced treatment choice and survival in patients with synchronous colorectal PM. These results can be used to optimize treatment strategy for patients with synchronous colorectal PM

Increased Survival of Patients with Synchronous Colorectal Peritoneal Metastases Receiving Preoperative Chemotherapy Before Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS?+?HIPEC) can result in long-term survival for selected patients with colorectal peritoneal metastases (PM). Most patients are additionally treated with systemic chemotherapy, but timing (adjuvant vs. preoperative) varies between treatment centers. This study aimed to compare short- and long-term outcomes for patients with synchronous colorectal PM undergoing CRS?+?HIPEC who received preoperative or adjuvant chemotherapy.This study enrolled patients with synchronous colorectal PM who underwent macroscopically complete or near complete CRS?+?HIPEC. Data were collected from a prospective database containing all patients between 2007 and 2014. Perioperative outcome and survival were compared between patients who underwent adjuvant chemotherapy (adjuvant strategy [AS]) and those who had preoperative chemotherapy followed by adjuvant systemic chemotherapy if possible (preoperative strategy [PS]).The study enrolled 91 patients, 25 (28?%) of whom received preoperative chemotherapy. The peritoneal cancer index (PCI) score was lower and the operation length shorter for the patients receiving preoperative chemotherapy (both p?=?0.02). The complication rates were comparable between the two groups. The median survival after diagnosis was 38.6?months in the AS group, whereas median survival was not reached in the PS group (p

Implementation, participation and satisfaction rates of a web-based decision support tool for patients with metastatic colorectal cancer

Objective: To examine implementation and patients’ and providers’ participation and satisfaction of a newly developed decision support tool (DST) for patients with metastatic colorectal cancer (mCRC) in palliative setting. Methods: Our DST consisted of a consultation sheet and web-based tailored information for mCRC treatment options. We conducted an implementation trajectory in 11 Dutch hospitals and evaluated implementation, participation and satisfaction rates. Results: Implementation rates fluctuated between 3 and 72 handed out (median:23) consultation sheets per hospital with patients’ login rates between 36% and 83% (median:57%). The majority of patients (68%) had (intermediate)-high participation scores. The median time spent using the DST was 38 min (IQR:18–56) and was highest for questions concerning patients’ perspective (5 min). Seventy-six% of patients were (very) satisfied. The provider DST rating was 7.8 (scale 1–10) and participation ranged between 25 and 100%. Remaining implementation thresholds included providers’ treatment preferences, resistance against shared decision-making and (over)confidence in shared decision-making concepts already in use. Conclusion: We implemented a DST with sufficient patient and oncologist satisfaction and high patient participation, but participation differed considerably between hospitals suggesting unequal adoption of our tool. Practice implications: Requirements for structural implementation are to overcome remaining thresholds and increase awareness for additional decision support

Implementation, participation and satisfaction rates of a web-based decision support tool for patients with metastatic colorectal cancer

OBJECTIVE: To examine implementation and patients' and providers' participation and satisfaction of a newly developed decision support tool (DST) for patients with metastatic colorectal cancer (mCRC) in palliative setting. METHODS: Our DST consisted of a consultation sheet and web-based tailored information for mCRC treatment options. We conducted an implementation trajectory in 11 Dutch hospitals and evaluated implementation, participation and satisfaction rates. RESULTS: Implementation rates fluctuated between 3 and 72 handed out (median:23) consultation sheets per hospital with patients' login rates between 36% and 83% (median:57%). The majority of patients (68%) had (intermediate)-high participation scores. The median time spent using the DST was 38 min (IQR:18-56) and was highest for questions concerning patients' perspective (5 min). Seventy-six% of patients were (very) satisfied. The provider DST rating was 7.8 (scale 1-10) and participation ranged between 25 and 100%. Remaining implementation thresholds included providers' treatment preferences, resistance against shared decision-making and (over)confidence in shared decision-making concepts already in use. CONCLUSION: We implemented a DST with sufficient patient and oncologist satisfaction and high patient participation, but participation differed considerably between hospitals suggesting unequal adoption of our tool. PRACTICE IMPLICATIONS: Requirements for structural implementation are to overcome remaining thresholds and increase awareness for additional decision support