New metabolic insights into the mechanism of ifosfamide encephalopathy.

Ifosfamide causes neurotoxicity, including sometimes fatal encephalopathy, in a small number of patients. Why and how this occurs is not fully understood. It is generally believed that N-dechloroethylation of ifosfamide to 2-chloroacetaldehyde is the cause.

Propranolol monotherapy in angiosarcoma - A window-of-opportunity study (PropAngio).

Background: Angiosarcoma is a rare and aggressive cancer of the endothelial cells. Propranolol, a non-selective β-blocker, was able to initiate apoptosis in angiosarcoma cell lines and its anti-tumor activity has been described in several case reports. The aim of this trial was to prospectively evaluate the anti-tumor activity of propranolol monotherapy in patients with angiosarcoma before proceeding to standard of care treatment.

Referral patterns of GIST patients: data from a nationwide study.

Background: This study compares the characteristics, referral and treatment patterns and overall survival (OS) of gastrointestinal stromal tumor (GIST) patients treated in reference and non-reference centers in the Netherlands.

Patients And Methods: This retrospective cohort study on patients diagnosed between 2016 and 2019, utilises data from the Netherlands Cancer Registry and the Dutch Nationwide Pathology Database. Patients were categorized into two groups: patients diagnosed in or referred to reference centers and patients diagnosed in non-reference centers without referral.

CYP3A4*22 Genotype-Guided Dosing of Kinase Inhibitors in Cancer Patients.

Introduction: A genetic variant explaining a part of the exposure of many kinase inhibitors (KIs) is the single nucleotide polymorphism (SNP) CYP3A4*22, resulting in less CYP3A4 enzyme activity. The primary aim of this study was to investigate if the systemic exposure is non-inferior after a dose reduction of KIs metabolized by CYP3A4 in CYP3A4*22 carriers compared to patients without this SNP (i.e.

Local treatment in metastatic GIST patients: A multicentre analysis from the Dutch GIST Registry.

Background: The added value of local treatment in selected metastatic GIST patients is unclear. This study aims to provide insight into the usefulness of local treatment in metastatic GIST by use of a survey study and retrospective analyses in a clinical database.

Methods: A survey study was conducted among clinical specialists to select most relevant characteristics of metastatic GIST patients considered for local treatment, defined as elective surgery or ablation.

Improved Efficacy of First-Line Imatinib in Advanced Gastrointestinal Stromal Tumors (GIST): The Dutch GIST Registry Data.

Background: Patients with unresectable and metastasized gastrointestinal stromal tumor (GIST) experienced a remarkable improvement of progression-free survival (PFS) and overall survival (OS) after the introduction of imatinib. Our hypothesis is that the outcomes of treatment with imatinib are even better nowadays compared with the registration trials that were performed two decades ago. To study this, we used real-life data from a contemporary registry.

Local recurrence in primary localised resected gastrointestinal stromal tumours: A registry observational national cohort study including 912 patients.

Background And Objectives: Previous literature showed a high risk of recurrence following surgical treatment in patients with gastrointestinal stromal tumours (GISTs). However, little is known about the patient- and treatment characteristics of local recurrences (LRs) in GIST patients. Therefore, this study aimed to better understand patterns of LR in surgically treated localised GIST and to describe treatment options based on our Dutch GIST Registry (DGR).

Systemic exposure of floxuridine after hepatic arterial infusion pump chemotherapy with floxuridine in patients with resected colorectal liver metastases.

Background: Floxuridine's high hepatic extraction ratio and short elimination half-life allows maximum liver exposure with minimal systemic side-effects. This study attempts to quantify the systemic exposure of floxuridine.

Methods: Patients undergoing continuous hepatic arterial infusion pump (HAIP) floxuridine after resection of colorectal liver metastases (CRLM) in two centres underwent six cycles of floxuridine at start dose 0.

Dutch Gastrointestinal Stromal Tumor (GIST) Registry Data Comparing Sunitinib with Imatinib Dose Escalation in Second-Line Advanced Non-KIT Exon 9 Mutated GIST Patients.

Background: The prognosis of patients with advanced gastrointestinal stromal tumor (GIST) has improved greatly after the introduction of imatinib. However, primary or secondary resistance to imatinib occurs in the majority of patients. Sunitinib is the standard second line treatment in exon-9 mutated GIST.

Adjuvant Imatinib in Patients with GIST Harboring Exon 9 KIT Mutations: Results from a Multi-institutional European Retrospective Study.

Purpose: The effect of high-dose imatinib (800 mg/day) on survival in the adjuvant treatment of patients with resected KIT exon 9-mutated gastrointestinal stromal tumors (GIST) is not established. Here, the association of dose and other clinicopathologic variables with survival was evaluated in a large multi-institutional European cohort.

Experimental Design: Data from 185 patients were retrospectively collected in 23 European GIST reference centers.

Early response evaluation using 18F-FDG-PET/CT does not influence management of patients with metastatic gastrointestinal stromal tumors (GIST) treated with palliative intent.

Aim: The aim of this study was to investigate the impact of F-FDG-PET/CT on treatment decision making in metastatic gastrointestinal stromal tumor (GIST) patients.

Methods: This study retrospectively evaluated F-FDG-PET/CT scans to monitor response of metastatic GIST patients treated with palliative intent. Data from the Dutch GIST Registry was used.

Location of Gastrointestinal Stromal Tumor (GIST) in the Stomach Predicts Tumor Mutation Profile and Drug Sensitivity.

Purpose: Gastrointestinal stromal tumors (GIST) commonly arise in different regions of the stomach and are driven by various mutations (most often in KIT, PDGFRA, and SDHx). We hypothesized that the anatomic location of gastric GIST is associated with unique genomic profiles and distinct driver mutations.

Experimental Design: We compared KIT versus non-KIT status with tumor location within the National Cancer Database (NCDB) for 2,418 patients with primary gastric GIST.

Clinicopathological features and treatment outcome of oesophageal gastrointestinal stromal tumour (GIST): A large, retrospective multicenter European study.

Background: Oesophageal gastrointestinal stromal tumours (GISTs) account for ≤1% of all GISTs. Consequently, evidence to guide clinical decision-making is limited.

Methods: Clinicopathological features and outcomes in patients with primary oesophageal GIST from seven European countries were collected retrospectively.

PropAngio study protocol: a neoadjuvant trial on the efficacy of propranolol monotherapy in cutaneous angiosarcoma-a proof of principle study.

Introduction: Angiosarcoma is a rare and aggressive malignancy with a high metastatic potential and recurrence rate. Despite optimal treatment with surgery, with or without radiation, the prognosis remains poor and, therefore, new treatment strategies are warranted. Recently, propranolol has effectively been repurposed for the treatment of infantile haemangioma.

Neoadjuvant Systemic Treatment of Primary Angiosarcoma.

Angiosarcoma is an extremely rare and aggressive malignancy. Standard of care of localized tumors includes surgery ± radiation. Despite this multimodal treatment, >50% of the angiosarcoma patients develop local or distant recurrent disease.

Gastrointestinal Stromal Tumours (GIST) in Young Adult (18-40 Years) Patients: A Report from the Dutch GIST Registry.

Gastrointestinal stromal tumour (GIST) is a disease of older adults and is dominated by / mutations. In children, GIST is rare, predominantly occurs in girls, has a stomach location and generally lacks / mutations. For young adults (YA), aged 18 to 40 years, the typical phenotypic and genotypic patterns are unknown.

Quality of treatment and surgical approach for rectal gastrointestinal stromal tumour (GIST) in a large European cohort.

Background: Rectal gastrointestinal stromal tumours (GISTs) are rare tumours. Variability in the management may influence outcome, but there is a lack of understanding regarding contemporary variance in care. A multicenter, international, retrospective cohort study was performed to elucidate characteristics and outcomes of rectal GIST in European practice, with particular reference to surgical approach.

Oncological Outcome After Diagnostic Biopsies in Gastrointestinal Stromal Tumors: A Retrospective Cohort Study.

Objective: To analyze whether the route of preoperative biopsy influences oncological outcome in GIST patients.

Summary Of Background Data: Preoperative biopsies are widely used for diagnosing GIST. Little is known about the risk of tumor seeding after different routes of biopsy.

Influence of the Acidic Beverage Cola on the Absorption of Erlotinib in Patients With Non-Small-Cell Lung Cancer.

Purpose: Erlotinib depends on stomach pH for its bioavailability. When erlotinib is taken concurrently with a proton pump inhibitor (PPI), stomach pH increases, which results in a clinically relevant decrease of erlotinib bioavailability. We hypothesized that this drug-drug interaction is reversed by taking erlotinib with the acidic beverage cola.