scholarly journals NCOG-08. COGNITIVE DEFICITS AS A PREDICTOR OF THE COURSE OF TREATMENT IN DIFFUSE GLIOMA

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi160-vi160
Author(s):  
Suzanne IJpelaar ◽  
Emma Van Kessel ◽  
Martine Van Zandvoort ◽  
Filip De Vos ◽  
Joost Verhoeff ◽  
...  

Abstract INTRODUCTION Over half of patients with a diffuse glioma suffer from cognitive deficits in one or more domains. Cognitive functioning, especially for the domains executive functioning (EF) and memory, is an independent prognostic factor for overall survival. A possible explanation for this prognostic effect is that patients with cognitive deficits receive less intensive treatment, or do not tolerate treatment as well as other patients. METHODS Retrospective cohort study of patients with a diffuse glioma (WHO grade 2–4) who underwent an awake craniotomy, with pre-operative neuropsychological testing, followed by adjuvant radio- and/or chemotherapy. Outcome measures were (a) choice of adjuvant treatment, compared to appropriate treatment according to contemporary guidelines; (b) intensity and compliance: number of received treatment cycles, and adherence to prescribed medication; and (c) complications. Cognitive deficits (in one or more domains, Z-score < -2), as well as deficits in the domains EF and memory, were correlated to the outcome measures. RESULTS We included 187 consecutive patients. Cognitive deficits in one or more domains, EF or memory were neither associated to the choice of treatment (adherence to guidelines), nor to intensity or compliance of treatment. Having a cognitive deficit was associated with an increased risk of complications (P < .001), including severe complications (CTCAE grade 3–5, p < .05). A deficit in EF was also associated with more complications (p < .005). This risk of complications was increased for the categories of infectious, cerebral, gastro-intestinal and hematological complications. CONCLUSION Of all patients with a diffuse glioma, patients with cognitive deficits have an increased risk of complications of postoperative antineoplastic therapy. Choice of, intensity of, and compliance to treatment did not differ from cognitively intact patients. The increased risk of complications may form an explanation for the poor prognosis of glioma patients with cognitive deficits.

Cancers ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 2373
Author(s):  
Martin Kocher ◽  
Christiane Jockwitz ◽  
Philipp Lohmann ◽  
Gabriele Stoffels ◽  
Christian Filss ◽  
...  

Cognitive deficits are common in glioma patients following multimodality therapy, but the relative impact of different types and locations of treatment-related brain damage and recurrent tumors on cognition is not well understood. In 121 WHO Grade III/IV glioma patients, structural MRI, O-(2-[18F]fluoroethyl)-L-tyrosine FET-PET, and neuropsychological testing were performed at a median interval of 14 months (range, 1–214 months) after therapy initiation. Resection cavities, T1-enhancing lesions, T2/FLAIR hyperintensities, and FET-PET positive tumor sites were semi-automatically segmented and elastically registered to a normative, resting state (RS) fMRI-based functional cortical network atlas and to the JHU atlas of white matter (WM) tracts, and their influence on cognitive test scores relative to a cohort of matched healthy subjects was assessed. T2/FLAIR hyperintensities presumably caused by radiation therapy covered more extensive brain areas than the other lesion types and significantly impaired cognitive performance in many domains when affecting left-hemispheric RS-nodes and WM-tracts as opposed to brain tissue damage caused by resection or recurrent tumors. Verbal episodic memory proved to be especially vulnerable to T2/FLAIR abnormalities affecting the nodes and tracts of the left temporal lobe. In order to improve radiotherapy planning, publicly available brain atlases, in conjunction with elastic registration techniques, should be used, similar to neuronavigation in neurosurgery.


2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii168-ii168
Author(s):  
Antonio Dono ◽  
Kristin Alfaro-Munoz ◽  
Yuanqing Yan ◽  
Carlos Lopez-Garcia ◽  
Zaid Soomro ◽  
...  

Abstract In the 2016 WHO classification of CNS tumors, oligodendrogliomas are molecularly defined by IDH1 or IDH2 mutations and 1p/19q co-deletion. Some reports suggest that PI3K pathway alterations may confer increased risk of progression and poor prognosis in oligodendroglioma. However, factors that influence prognosis in molecularly defined oligodendroglioma (mOGD) have not been thoroughly studied. Also, the benefits of adjuvant radiation and temozolomide in mOGDs remain to be determined. 107 mOGDs diagnosed between 2008-2018 at the University of Texas Health Science Center at Houston (n= 39) and MD Anderson Cancer Center (n= 68) were included. A retrospective review of the demographic, clinical, histologic, molecular, and outcomes were performed. Median age at diagnosis was 37 years and 61 (57%) patients were male. There were 64 (60%) WHO Grade 2 and 43 (40%) WHO Grade 3 tumors. Ninety-five (88.8%) tumors were IDH1-mutant and 12 (11.2%) were IDH2-mutant. Eighty-two (77%) patients were stratified as high-risk: older than 40-years and/or subtotal resection (RTOG 9802). Gross-total resection was achieved in 47 (45%) patients. Treatment strategies included observation (n= 15), temozolomide (n= 11), radiation (n= 13), radiation with temozolomide (n= 62) and other (n= 6). Our results show a benefit of temozolomide vs. observation in progression-free survival (PFS). However, no benefit in PFS or overall survival (OS) was observed when comparing radiation vs. radiation with temozolomide. PIK3CA mutations were detected in 15 (14%) cases, and patients with PIK3CA-mutant mOGDs showed worse OS (10.7-years vs 15.1-years, p= 0.009). Patients with WHO Grade 3 tumors had shorter PFS but no significant difference in OS was observed compared to grade 2. Our findings suggest that mOGDs harboring PIK3CA mutations have worse OS. Except for an advantage in PFS in temozolomide treated patients, adjuvant treatment with radiation or the combination of both, showed no significant advantage in terms of OS.


Author(s):  
Annamaria Biczok ◽  
Philipp Karschnia ◽  
Raffaela Vitalini ◽  
Markus Lenski ◽  
Tobias Greve ◽  
...  

Abstract Background Prognostic markers for meningioma recurrence are needed to guide patient management. Apart from rare hereditary syndromes, the impact of a previous unrelated tumor disease on meningioma recurrence has not been described before. Methods We retrospectively searched our database for patients with meningioma WHO grade I and complete resection provided between 2002 and 2016. Demographical, clinical, pathological, and outcome data were recorded. The following covariates were included in the statistical model: age, sex, clinical history of unrelated tumor disease, and localization (skull base vs. convexity). Particular interest was paid to the patients’ past medical history. The study endpoint was date of tumor recurrence on imaging. Prognostic factors were obtained from multivariate proportional hazards models. Results Out of 976 meningioma patients diagnosed with a meningioma WHO grade I, 416 patients fulfilled our inclusion criteria. We encountered 305 women and 111 men with a median age of 57 years (range: 21–89 years). Forty-six patients suffered from a tumor other than meningioma, and no TERT mutation was detected in these patients. There were no differences between patients with and without a positive oncological history in terms of age, tumor localization, or mitotic cell count. Clinical history of prior tumors other than meningioma showed the strongest association with meningioma recurrence (p = 0.004, HR = 3.113, CI = 1.431–6.771) both on uni- and multivariate analysis. Conclusion Past medical history of tumors other than meningioma might be associated with an increased risk of meningioma recurrence. A detailed pre-surgical history might help to identify patients at risk for early recurrence.


BMJ Open ◽  
2020 ◽  
Vol 10 (11) ◽  
pp. e038829
Author(s):  
Ross McQueenie ◽  
Barbara I Nicholl ◽  
Bhautesh D Jani ◽  
Jordan Canning ◽  
Sara Macdonald ◽  
...  

ObjectiveTo investigate how the type and number of long-term conditions (LTCs) impact on all-cause mortality and major adverse cardiovascular events (MACE) in people with rheumatoid arthritis (RA).DesignPopulation-based longitudinal cohort study.SettingUK Biobank.ParticipantsUK Biobank participants (n=502 533) aged between 37 and 73 years old.Primary outcome measuresPrimary outcome measures were risk of all-cause mortality and MACE.MethodsWe examined the relationship between LTC count and individual comorbid LTCs (n=42) on adverse clinical outcomes in participants with self-reported RA (n=5658). Risk of all-cause mortality and MACE were compared using Cox’s proportional hazard models adjusted for lifestyle factors (smoking, alcohol intake, physical activity), demographic factors (sex, age, socioeconomic status) and rheumatoid factor.Results75.7% of participants with RA had multimorbidity and these individuals were at increased risk of all-cause mortality and MACE. RA and >4 LTCs showed a threefold increased risk of all-cause mortality (HR 3.30, 95% CI 2.61 to 4.16), and MACE (HR 3.45, 95% CI 2.66 to 4.49) compared with those without LTCs. Of the comorbid LTCs studied, osteoporosis was most strongly associated with adverse outcomes in participants with RA compared with those without RA or LTCs: twofold increased risk of all-cause mortality (HR 2.20, 95% CI 1.55 to 3.12) and threefold increased risk of MACE (HR 3.17, 95% CI 2.27 to 4.64). These findings remained in a subset (n=3683) with RA diagnosis validated from clinical records or medication reports.ConclusionThose with RA and other LTCs, particularly comorbid osteoporosis, are at increased risk of adverse outcomes, although the role of corticosteroids could not be evaluated in this study. These results are clinically relevant for the monitoring and management of RA across the healthcare system, and future clinical guidelines for RA should acknowledge the importance of multimorbidity.


BMC Medicine ◽  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Wolfgang Trapp ◽  
Susanne Röder ◽  
Andreas Heid ◽  
Pia Billman ◽  
Susanne Daiber ◽  
...  

Abstract Background Currently, many patients suffering from dementia do not have a diagnosis when admitted to geriatric hospitals. This is the case despite an increased risk of complications affecting the length of stay and outcome. Unfortunately, many dementia screening tests cannot be used on geriatric inpatients, who are often bedridden. Therefore, we aimed at evaluating the diagnostic accuracy of a small battery of bedside tasks that require minimal vision and fine motor skills in patients with suspected dementia. Methods In this prospective study, the Bamberg Dementia Screening Test (BDST) was administered to a consecutive series of 1295 patients referred for neuropsychological testing. The diagnosis of dementia was confirmed in 1159 and excluded in 136 patients. Sensitivity and specificity for the first subtest (ultra-short form), the first two subtests (short form), and the total score of the BDST were obtained via receiver operating characteristic curves and compared with the sensitivity and specificity values of the Mini-Mental Status Examination (MMSE). Results The overall diagnostic quality of the BDST was superior to the MMSE for mild Alzheimer’s dementia (sensitivity and specificity = .94 (95% CI .92 to .96) and .82 (95% CI .75 to .88) vs. .79 (95% CI .76 to .83) and .88 (95% CI .82 to .93)) as well as for other subtypes of mild dementia (sensitivity and specificity = .91 (95% CI .88 to .94) and .82 (95% CI .75 to .88) vs. .72 (95% CI .67 to .76) and .88 (95% CI .82 to .93)). Even the short form of the BDST was comparable to the MMSE regarding sensitivity and specificity. For moderate dementia, it was possible to identify dementia cases with sufficient and excellent diagnostic quality by using the ultra-short and the short form. Conclusions The BDST is able to detect dementia in geriatric hospital settings. If the adaptive algorithm is used, administration time can be reduced to less than 2 min in most cases. Because no test materials have to be exchanged, this test is particularly suitable for infectious environments where contact between the examiner and the person being tested should be minimized.


2021 ◽  
Vol 23 (Supplement_2) ◽  
pp. ii44-ii44
Author(s):  
A T J van der Boog ◽  
S David ◽  
A M M Steennis ◽  
T J Snijders ◽  
J W Dankbaar ◽  
...  

Abstract BACKGROUND Surgical treatment of diffuse glioma is performed to reduce tumor mass effect and to pave the way for adjuvant (chemo)radiotherapy. As a complication of surgery, ischemic lesions are often found in the postoperative setting. Not only can these lesion induce neurological deficits, but their volume has also been associated with reduced survival time. Prior studies suggest areas with a singular vascular supply to be more prone to postoperative ischemic lesions, although the precise cause is yet unknown. The aim of this study was to explore the volumetric and spatial distributions of postoperative ischemic lesions and their relation to arterial territories in glioma patients. MATERIAL AND METHODS We accessed a retrospective database of 144 adult cases with WHO grade II-IV supratentorial gliomas, who received surgery and postoperative MRI within 3 days in 2012–2014. We identified 93 patients with postoperative ischemia, defined as new confluent diffusion restriction on DWI. Ischemic lesions were manually delineated and spatially normalized to stereotaxic MNI space. Voxel-based analysis (VBA) was performed to compare presence and absence of postoperative ischemia. False positive results were eliminated by family-wise error correction. Areas of ischemia were labeled using an arterial territory map, the Harvard-Oxford cortical and subcortical atlases and the XTRACT white matter atlas. RESULTS Median volume of confluent ischemia was 3.52cc (IQR 2.15–5.94). 23 cases had only ischemic lesion in the left hemisphere, 46 in the right hemisphere and 24 bilateral. Median volume was 3.08cc (IQR 1.35–5.72) in left-sided lesions and 2.47cc (1.01–4.24) in right-sided lesions. Volume of ischemic lesions was not associated with survival after 1, 2 or 5 years. A cluster of 125.18cc was found to be significantly associated with development of postoperative ischemia. 73% of this cluster was situated in the arterial territory of the right middle cerebral artery (MCA), limited by the border of the posterior cerebral artery (PCA), and the watershed area between the right MCA and the right anterior cerebral artery (ACA). Significant areas were located in the frontal lobes, spanning into the right temporo-occipital region, and predominantly included right and left thalamus, caudate nucleus, putamen, pallidum, as well as right temporal gyri and insular cortex, and parts of the right corticospinal tract, longitudinal fasciculi and superior thalamic radiation. CONCLUSION We found slightly more and larger ischemic lesions in the right than left hemisphere after glioma resection. A statistically significant cluster of voxels of postoperative ischemia was found in the territory of the right MCA and watershed area of the right ACA. Exploration of the spatial distribution of these lesions could help elucidate their etiology and form the basis for predicting clinically relevant postoperative ischemia.


Nutrients ◽  
2018 ◽  
Vol 11 (1) ◽  
pp. 7 ◽  
Author(s):  
Gitalee Sarker ◽  
Daria Peleg-Raibstein

Ample evidence from epidemiological studies has linked maternal obesity with metabolic disorders such as obesity, cardiovascular disease, and diabetes in the next generation. Recently, it was also shown that maternal obesity has long-term effects on the progeny’s central nervous system. However, very little is known regarding how maternal overnutrition may affect, in particular, the cognitive abilities of the offspring. We reported that first-generation offspring exposed to a maternal high-fat diet (MHFD) displayed age-dependent cognitive deficits. These deficits were associated with attenuations of amino acid levels in the medial prefrontal cortex and the hippocampus regions of MHFD offspring. Here, we tested the hypothesis that MHFD in mice may induce long-term cognitive impairments and neurochemical dysfunctions in the second and third generations. We found that MHFD led to cognitive disabilities and an altered response to a noncompetitive receptor antagonist of the N-Methyl-D-aspartic acid (NMDA) receptor in adult MHFD offspring in both second and third generations in a sex-specific manner. Our results suggest that maternal overnutrition leads to an increased risk of developing obesity in subsequent generations as well as to cognitive impairments, affecting learning and memory processes in adulthood. Furthermore, MHFD exposure may facilitate pathological brain aging which is not a consequence of obesity. Our findings shed light on the long-term effects of maternal overnutrition on the development of the central nervous system and the underlying mechanisms which these traits relate to disease predisposition.


2003 ◽  
Vol 182 (5) ◽  
pp. 449-454 ◽  
Author(s):  
Anja Busse ◽  
Jeannette Bischkopf ◽  
Steffi G. Riedel-Heller ◽  
Matthias C. Angermeyer

BackgroundAlthough mild cognitive impairment is associated with an increased risk of developing dementia, there has been little work on its incidence and prevalence.AimsTo report age-specific prevalence, incidence and predictive validities for four diagnostic concepts of mild cognitive impairment.MethodA community sample of 1045 dementia-free individuals aged 75 years and over was examined by neuropsychological testing in a three-wave longitudinal study.ResultsPrevalence rates ranged from 3% to 20%, depending on the concept applied. The annual incidence rates applying different case definitions varied from 8 to 77 per 1000 person-years. Rates of conversion to dementia over 2.6 years ranged from 23% to 47%.ConclusionsMild cognitive impairment is frequent in older people. Prevalence, incidence and predictive validities are highly dependent on the diagnostic criteria applied.


2019 ◽  
Vol 4 (2) ◽  

Delirium is defined in the Diagnostic and Statistical Manual of Mental Disorders: Fifth edition (DSM-V) as a “disturbance and change in attention and awareness from baseline that develops over a short period of time, with fluctuating course” [1]. Delirium occurs as a result of factors related to primary illness, the treatment of that illness, and stressful and disorientating environment of the hospital [2]. There are limited data to describe the incidence of delirium in children hospitalized with cancer [3]. Delirium occurs frequently in adults and is an independent predictor of mortality, increased length of stay, and increased risk for long-term cognitive deficits [3]. The prevalence of delirium in hospitalized adults ages 18-56 with cancer ranges from 18%-44% [4]. Most pediatric studies on delirium focus on the critically ill child in the pediatric intensive care unit (PICU). It is estimated that the incidence of delirium in this population is as high as 29% [5].


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