A better understanding of transcriptional evolution of IDH-wild-type glioblastoma may be crucial for treatment optimization. Here, we perform RNA sequencing (RNA-seq) (n = 322 test, n = 245... Show moreA better understanding of transcriptional evolution of IDH-wild-type glioblastoma may be crucial for treatment optimization. Here, we perform RNA sequencing (RNA-seq) (n = 322 test, n = 245 validation) on paired primary-recurrent glioblastoma resections of patients treated with the current standard of care. Transcriptional subtypes form an interconnected continuum in a two-dimensional space. Recurrent tumors show preferential mesenchymal progression. Over time, hallmark glioblastoma genes are not significantly altered. Instead, tumor purity decreases over time and is accompanied by co-increases in neuron and oligodendrocyte marker genes and, independently, tumor-associated macrophages. A decrease is observed in endothelial marker genes. These composition changes are confirmed by single-cell RNA-seq and immunohistochemistry. An extracellular matrix-associated gene set increases at recurrence and bulk, single-cell RNA, and immunohistochemistry indicate it is expressed mainly by pericytes. This signature is associated with significantly worse survival at recurrence. Our data demonstrate that glioblastomas evolve mainly by microenvironment (re-)organization rather than molecular evolution of tumor cells. Show less
Joode, K. de; Taal, W.; Snijders, T.J.; Hanse, M.; Koekkoek, J.A.F.; Hoop, E.O. de; ... ; DOCC Investigators 2021
Introduction Routine assessment of patient-reported outcomes (PROs) in oncology has shown to improve the quality of the delivered care and to prolong survival. However, for successful... Show moreIntroduction Routine assessment of patient-reported outcomes (PROs) in oncology has shown to improve the quality of the delivered care and to prolong survival. However, for successful implementation of routine assessment of PROs, more knowledge on their usability in clinical practice is needed. Objective This study aimed to cross-sectionally assess the perspective of patients and clinicians on the practicality of routinely measuring PROs in clinical practice for glioma patients. Methods Semistructured interviews were conducted evaluating the role of healthcare professionals (HCP) in discussing results of PRO measures (PROMs), and the preferred topics, methods and frequency of PRO assessment. Glioma patients, their proxies and HCPs involved in the treatment of glioma patients from eight centres in the Netherlands were included. Results Twenty-four patients, 16 proxies and 35 HCPs were interviewed. The majority of patients, proxies and HCPs (92%, 81% and 80%, respectively) were willing to discuss PRO results during consultations. Although HCPs prefer that results are discussed with the nurse specialist, only one-third of patients/proxies agreed. Functioning of daily life was considered important in all three groups. Most participants indicated that discussion of PROM results should take place during standard follow-up visits, and completed at home about 1 week in advance. On group level, there was no preference for administration of questionnaires on paper or digitally. Lastly, all centres had staff available to send questionnaires on paper. Conclusion This study shows that routine assessment of PROs is desired by patients, proxies and HCP's in neuro-oncological care in Dutch hospitals. Show less
Gehring, K.; Stuiver, M.M.; Visser, E.; Kloek, C.; Bent, M. van den; Hanse, M.; ... ; Sitskoorn, M.M. 2020
Background. Patients with glioma often suffer from cognitive deficits. Physical exercise has been effective in ameliorating cognitive deficits in older adults and neurological patients. This pilot... Show moreBackground. Patients with glioma often suffer from cognitive deficits. Physical exercise has been effective in ameliorating cognitive deficits in older adults and neurological patients. This pilot randomized controlled trial (RCT) explored the possible impact of an exercise intervention, designed to improve cognitive functioning in glioma patients, regarding cognitive test performance and patient-reported outcomes (PROs).Methods. Thirty-four clinically stable patients with World Health Organization grades II/III glioma were randomized to a home-based remotely coached exercise group or an active control group. Patients exercised 3 times per week for 20-45 minutes, with moderate to vigorous intensity, during 6 months. At baseline and immediate follow-up, cognitive performance and PROs were assessed with neuropsychological tests and questionnaires, respectively. Linear regression analyses were used to estimate effect sizes of potential between-group differences in cognitive performance and PROs at 6 months.Results. The exercise group (n = 21) had small- to medium-sized better follow-up scores than the control group (n = 11) on several measures of attention and information processing speed, verbal memory, and executive function, whereas the control group showed a slightly better score on a measure of sustained selective attention. The exercise group also demonstrated small- to medium-sized better outcomes on measures of self-reported cognitive symptoms, fatigue, sleep, mood, and mental health-related quality of life.Conclusions. This small exploratory RCT in glioma patients provides a proof of concept with respect to improvement of cognitive functioning and PROs after aerobic exercise, and warrants larger exercise trials in brain tumor patients. Show less
Draaisma, K.; Chatzipli, A.; Taphoorn, M.; Kerkhof, M.; Weyerbrock, A.; Sanson, M.; ... ; French, P. 2017
