Previously, the tyrosine kinase inhibitor sunitinib failed to show clinical benefit in patients with recurrent glioblastoma. Low intratumoural sunitinib accumulation in glioblastoma patients was reported as a possible explanation for the lack of therapeutic benefit. We designed a randomized phase II/III trial to evaluate whether a high-dose intermittent sunitinib schedule, aimed to increase intratumoural drug concentrations, would result in improved clinical benefit compared to standard treatment with lomustine.
View Article and Find Full Text PDFPurpose: This study aimed to gain insight into the experiences of, and reasons for, cancer survivors participating in a primary care PA program.
Methods: We interviewed 17 patients from 11 Dutch GP practices. Patients were selected by purposive sampling based on their general practice, gender, educational level, motivation for PA, and change in PA.
Background: Standard treatment for patients with newly diagnosed glioblastoma includes surgery, radiotherapy (RT), and temozolomide (TMZ) chemotherapy (TMZ/RT→TMZ). The proteasome has long been considered a promising therapeutic target because of its role as a central biological hub in tumor cells. Marizomib is a novel pan-proteasome inhibitor that crosses the blood-brain barrier.
View Article and Find Full Text PDFPurpose: Bleomycin, etoposide, and cisplatin combination chemotherapy (BEP) improves the survival of patients with testicular cancer, but is associated with potentially life-threatening toxicities like pneumonitis and thromboembolic events. This study explored the effects of physical exercise in patients with testicular cancer during or after BEP-chemotherapy on pulmonary and vascular endothelial toxicity.
Methods: In this post hoc analysis of a multicenter randomized clinical trial (NCT01642680), patients with metastatic testicular cancer scheduled to receive BEP-chemotherapy were randomized to a 24-week exercise intervention, initiated during (group A) or after BEP-chemotherapy (group B).
RECIST 1.1 criteria are commonly used with computed tomography (CT) to evaluate the efficacy of systemic treatments in patients with neuroendocrine tumors (NETs) and liver metastases (LMs), but their relevance is questioned in this setting. We aimed to explore alternative criteria using different numbers of measured LMs and thresholds of size and density variation.
View Article and Find Full Text PDFBackground: Despite the widely acknowledged benefit of exercise for patients with cancer, little evidence on the optimal timing of exercise on adverse effects of cancer treatment is available.
Objectives: The aim of this study was to determine whether an exercise intervention initiated during chemotherapy is superior to an intervention initiated after chemotherapy for improving long-term cardiorespiratory fitness (peak oxygen uptake [VO]).
Methods: In this prospective, randomized clinical trial, patients scheduled to receive curative chemotherapy were randomized to a 24-week exercise intervention, initiated either during chemotherapy (group A) or afterward (group B).
Background: Higher levels of physical activity are associated with a lower risk of cardiovascular disease in the general population. Whether the same holds for women who underwent treatment for breast cancer is unclear.
Objectives: The aim of this study was to evaluate the association between physical activity in a typical week in the past 12 months and cardiac dysfunction in breast cancer survivors.
Background: Gastroenteropancreatic (GEP) neuroendocrine neoplasms (NENs) comprise a group of rare malignant tumours with heterogeneous behaviour. This study aimed to assess long-term survival and prognostic factors associated with survival, in order to optimise counselling.
Patients And Methods: This population-based study included all GEP-NENs diagnosed between 1989 and 2016 in the Netherlands, selected from the Netherlands Cancer Registry.
Background: Crosstalk between neoplastic and stromal cells fosters prostate cancer (PCa) progression and dissemination. Insight in cell-to-cell communication networks provides new therapeutic avenues to mold processes that contribute to PCa tumor microenvironment (TME) alterations. Here we performed a detailed characterization of PCa tumor endothelial cells (TEC) to delineate intercellular crosstalk between TEC and the PCa TME.
View Article and Find Full Text PDFBackground: In treatment of neuroendocrine neoplasms (NENs), confirmation of somatostatin receptor expression with Ga-DOTA somatostatin analogues is mandatory to determine eligibility for peptide receptor radionuclide therapy (PRRT). [F]DOPA can detect additional lesions compared to [Ga]DOTA-TOC. The aim of this study was to explore differences in tumour detection of both tracers and their relevance for selecting patients for PRRT.
View Article and Find Full Text PDFThe factors driving therapy resistance in diffuse glioma remain poorly understood. To identify treatment-associated cellular and genetic changes, we analyzed RNA and/or DNA sequencing data from the temporally separated tumor pairs of 304 adult patients with isocitrate dehydrogenase (IDH)-wild-type and IDH-mutant glioma. Tumors recurred in distinct manners that were dependent on IDH mutation status and attributable to changes in histological feature composition, somatic alterations, and microenvironment interactions.
View Article and Find Full Text PDFBackground: Surgical resection is the only potentially curative treatment for pancreatic neuroendocrine tumors. The choice for the type of procedure is influenced by the expected oncological benefit and the anticipated risk of procedure-specific complications. Few studies have focused on complications in these patients.
View Article and Find Full Text PDFIntroduction: Physical activity (PA) favourably affects various health outcomes in cancer survivors, but little is known about how to implement a PA programme in primary care. We therefore aim to implement and evaluate such a programme for cancer survivors in general practice.
Methods And Analyses: The Stimulation of Daily Activity study is an implementation study with a single-arm longitudinal design in 15 Dutch general practices.
Background: Impaired cognition can be a late effect after treatment in long-term testicular cancer (TC) survivors, negatively affecting their daily life. However, little data is available beyond 20 years post-treatment. We assessed cognitive impairment in very long-term TC survivors after CT or RT and compared the results with stage I TC survivors and controls.
View Article and Find Full Text PDFPurpose: Selinexor is an oral selective inhibitor of exportin-1 (XPO1) with efficacy in various solid and hematologic tumors. We assessed intratumoral penetration, safety, and efficacy of selinexor monotherapy for recurrent glioblastoma.
Patients And Methods: Seventy-six adults with Karnofsky Performance Status ≥ 60 were enrolled.
Purpose: Physical activity (PA) affects fatigue and mental health in cancer survivors favorably, but participation in PA interventions tends to be low. More participants may be reached by home-based PA owing to greater accessibility and self-monitoring. This systematic review therefore evaluated the effects of home-based PA of low to moderate intensity on symptoms of fatigue, depression, and anxiety among cancer survivors.
View Article and Find Full Text PDFBackground: EGFR is among the genes most frequently altered in glioblastoma, with exons 2-7 deletions (EGFRvIII) being among its most common genomic mutations. There are conflicting reports about its prognostic role and it remains unclear whether and how it differs in signaling compared with wildtype EGFR.
Methods: To better understand the oncogenic role of EGFRvIII, we leveraged 4 large datasets into 1 large glioblastoma transcriptome dataset (n = 741) alongside 81 whole-genome samples from 2 datasets.
Background: 6-[F]fluoro-L-3,4-dihydroxyphenyl alanine ([F]FDOPA) is a commonly used PET tracer for the detection and staging of neuroendocrine tumors. In neuroendocrine tumors, [F]FDOPA is decarboxylated to [F]dopamine via the enzyme amino acid decarboxylase (AADC), leading to increased uptake when there is increased AADC activity. Recently, in our hospital, a new GMP compliant multi-dose production of [F]FDOPA has been developed, [F]FDOPA-H, resulting in a higher activity yield, improved molar activity and a lower administered mass than the conventional method ([F]FDOPA-L).
View Article and Find Full Text PDFThere is no standardized treatment for grade 3 neuroendocrine tumors (G3 NETs). We aimed to describe the treatments received in patients with advanced G3 NETs and compare their efficacy. Patients with advanced digestive G3 NETs treated between 2010 and 2018 in seven expert centers were retrospectively studied.
View Article and Find Full Text PDFBackground: Adjuvant endocrine therapy (ET) in patients with breast cancer (BC) increases the risk of becoming less physically active. Physical inactivity is associated with a higher risk of treatment-related side effects and mortality. This study investigated whether supervised exercise increased the proportion of patients adhering to the national physical activity (PA) guideline during adjuvant ET in overweight or obese BC patients.
View Article and Find Full Text PDFImportance: Patients with extrapulmonary neuroendocrine carcinomas (EPNECs) receive essentially the same treatment as those with small cell lung cancer (SCLC) despite differences in origin, clinical course, and survival. This SCLC-based approach is attributable to the rarity of EPNECs, which impedes the use of randomized clinical trials. However, neuroendocrine carcinomas are becoming more common because of the increasing use of systemic cancer therapy for adenocarcinomas.
View Article and Find Full Text PDFBackground: In the EORTC 1410/INTELLANCE 2 randomised, phase II study (NCT02343406), with the antibody-drug conjugate depatuxizumab mafodotin (Depatux-M, ABT-414) in patients with recurrent EGFR-amplified glioblastoma, the primary end-point (overall survival) was not met, and the drug had ocular dose-limiting toxicity. This study reports results from the prespecified health-related quality of life (HRQoL) and neurological deterioration-free survival (NDFS) exploratory analysis.
Patients And Methods: Patients (n = 260) were randomised 1:1:1 to receive either Depatux-M 1.
Purpose: The aim of this study was to retrospectively compare 18F-FDOPA versus 68Ga-DOTATOC PET in lesion detection rates and laboratory tumor markers in patients with neuroendocrine neoplasms (NENs).
Patients And Methods: All patients with histologically proven NEN between May 2015 and February 2019 were included who underwent both 18F-DOPA and 68Ga-DOTATOC PET scans within 6 months from each other (mean, 75; median, 38; range, 2-168 days). All patients, except those with pancreatic NEN, received carbidopa before 18F-DOPA PET.