Добірка наукової літератури з теми "Neuro-oncology, brain tumor, clinical outcome, patient-centred"

Abstract BACKGROUND Clinical outcome assessments (COAs) are a key component of patient-centered assessment of net clinical benefit in trials. In neuro-oncology, unique symptoms, treatment-related toxicities, and overall poor prognosis further necessitate a focus on symptom management and quality of life. We conducted a computational survey of trends of COA use in past and ongoing neuro-oncology trials. METHODS Neuro-oncology trials on ClinicalTrials.gov were identified using primary malignant CNS tumor terms. Instrument names from PROQOLID (n= 2695) were used to determine COA use. Regression and interrupted time-series analyses assessed chronological and design-related trends. RESULTS Among 3584 adult neuro-oncology studies, 20% reported using a specific COA instrument: 21% among (n= 3038) interventional and 16% among (n= 524) observational trials. Among interventional studies, most trials used one instrument (91%) as a secondary outcome (81%). 269 unique COAs were reported overall, most frequently patient-reported (72%) and clinician-reported outcomes (44%) indicated for general neoplasms (59%), all conditions (30%), and brain tumors (21%). Most commonly used instruments among treatment-focused trials (n= 523 reporting COAs) included Performance Status (KPS 18%, ECOG 9%), EORTC QLQ-C30 and QLQ-BN20 (9%), and MMSE (7%). Among supportive care studies (n= 47), HADS (13%), FACT-Br (11%), and KPS (11%) were most frequent. COAs use was more likely in phase 3 versus early phase 1 and phase 1 (OR= 0.12 [(95% CI:) 0.02-0.42]; OR= 0.22 [0.09-0.52]) but not versus phase 2 (OR= 0.60 [0.26-1.36]), and was more likely in supportive care trials (versus diagnostics and prevention: OR= 0.10 [0.01-0.65]; OR= 0.05 [0.00-0.79]). The rate of COA use increased linearly over time (1998-2020; β= 1.1 [0.8–1.4]), with no significant changes surrounding individual regulatory events. CONCLUSION A growing proportion of neuro-oncology trials specified COA use, reflecting positive changes toward patient-centered drug evaluation. Further investigation of COA use by phase and trial focus may inform future trial design.

Abstract Brain tumors are a major shock at diagnosis for patients and their families, and the journey is hectic, impacted in various and complex ways, including acute and chronic episodes. The Japan Brain Tumor Alliance is a non-profit organisation, established in 2006 to support patients and their families. As our key activity, JBTA offers nation-wide patient support through patient-gathering meetings with and without health care professionals to openly share needs, issues and concerns, partly summarized and shared in the scientific field (Gatellier, 2021, OT Journal, vol 55 no.3, 257–259; Gatellier, 2021, MASCC Annual Meeting). JBTA actively collaborates with the International Brain Tumor Alliance, with recent outcome of an international survey featuring the brain-tumor patient and caregiver experience during COVID-19 pandemic (Voisin et al., 2020, Neuro-oncology advances, 2(1), vdaa104). As part of collaboration with healthcare professionals in 2020–21, JBTA achievements include the review of clinical guidelines (as part of Patient and Public Involvement activity), information-sharing events with the Japan Clinical Oncology Group and the seminar with a group including occupational therapists. In addition, to highlight patients’ needs and priorities to the neuro-oncology community, since March 2020, JBTA shares the Japanese translation of the monthly IBTA e-newsletter broadcasting the latest and most relevant scientific, community information and brain tumor-related events around the world to healthcare professionals and brain tumor patients and families in Japan. These enlightening events place JBTA in an ideal position to lead research in the direction most meaningful to brain tumor patients.

Abstract PURPOSE Connectomics has led to significant neuroscientific findings within the last two decades, eventually making impact in the clinics. Neuro-oncology can benefit immensely from connectomics in evaluating structural connectivity of brains with tumor for pre- and post-treatment planning, as a tumor connectome along with derived network measures will make it possible to determine the cognitive effects of treatment and quantify the effect of surgery on quality of life. However, generating connectomes in the presence of tumor is a challenging task. Specifically, registration of an atlas to the brain, which is essential in parcellating the brain into regions of interest, fails around the tumor due to mass effect and infiltration related distortions which are not present in the atlas that comes from a healthy brain. We aim to tackle this problem by introducing a novel atlas registration method. METHOD Although tumor deforms the geometrical shape of its surrounding regions, it does not violate the connectivity of displaced cortical voxels to the rest of the brain. Leveraging this fact, we represent the brain as an annotated graph with nodes representing ROIs encoding geometric features of regions and weighted edges representing the connectivity between regions. In encoding the surroundings of the tumor into the graph, we subsample the region into smaller patches to represent the area with multiple nodes. We then calculate many-to-one graph matching between the graphs of a tumor patient and a healthy control to associate surroundings of tumor with healthy ROIs. OUTCOME A tumor connectome showing how the connectivity is morphed around the tumor, which can further be extended to creating connectomes of recurrence. CLINICAL IMPLICATIONS Use of connectomes can revolutionize neuro-oncology by helping surgeons in estimating structural, functional, and behavioral outcomes of resection prior to surgery and in predicting recovery after the surgery, potentially suggesting subject specific treatment plans.

Abstract BACKGROUND Despite the growing number of neuro-oncology clinical trials, there have been limited advances in the treatment of malignant primary central nervous system tumors. We surveyed the landscape of past, ongoing, and planned trials to assess trends in their interventions, outcomes, and design considerations to guide future studies. METHODS Data on interventional trials on ClinicalTrials.gov were accessed programmatically using AACT and R. Neuro-oncology trials were isolated using primary malignant brain tumor classification terms. Instrument names from PROQOLID were used to identify clinical outcome assessment (COA) use. Linear regression was used to assess chronological trends; power analyses utilized CBTRUS survival rates among trials investigating overall survival. RESULTS We identified 3039 interventional brain tumor trials that started between 1966 and 2025. Trials were most frequently phase II (43%), completed (40%), non-blinded (92%), single-group assignment (65%), non-randomized (51%) studies targeting glioblastoma (45%). Planned outcomes were reported by 93% of trials; this included adverse event or toxicity (54%), overall/x-year survival (44%), progression free survival (43%), maximum tolerated dose (16%), and objective response rate (14%). Evaluating the anticipated and actual trial enrollment, we estimate that only 10% and 8% of trial arms, respectively, were sufficiently powered to assess overall survival endpoints. 21% of trials mentioned the use of a COA (first trial initiated in 1992), majority of which were patient-reported outcomes. Among these, 25% and 58% reported COA as a primary or secondary outcome, respectively. The rate of COA use increased linearly over time at 1.1%/year but remained less than 5 trials per year until 2003. Ongoing work is investigating treatment mechanisms of actions and evidence of preclinical efficacy among brain tumor studies. CONCLUSIONS Low randomization rates and underpowered trial design may impede interpretability of efficacy. Increasing trends in COA use suggests cumulative influence of advocacy efforts to holistically evaluate net clinical benefit of interventions.

Evolving interest in meningioma, the most common primary brain tumor, has refined contemporary management of these tumors. Problematic, however, is the paucity of prospective clinical trials that provide an evidence-based algorithm for managing meningioma. This review summarizes the published literature regarding the treatment of newly diagnosed and recurrent meningioma, with an emphasis on outcomes stratified by WHO tumor grade. Specifically, this review focuses on patient outcomes following treatment (either adjuvant or at recurrence) with surgery or radiation therapy inclusive of radiosurgery and fractionated radiation therapy. Phase II trials for patients with meningioma have recently completed accrual within the Radiation Therapy Oncology Group and the European Organisation for Research and Treatment of Cancer consortia, and Phase III studies are being developed. However, at present, there are no completed prospective, randomized trials assessing the role of either surgery or radiation therapy. Successful completion of future studies will require a multidisciplinary effort, dissemination of the current knowledge base, improved implementation of WHO grading criteria, standardization of response criteria and other outcome end points, and concerted efforts to address weaknesses in present treatment paradigms, particularly for patients with progressive or recurrent low-grade meningioma or with high-grade meningioma. In parallel efforts, Response Assessment in Neuro-Oncology (RANO) subcommittees are developing a paper on systemic therapies for meningioma and a separate article proposing standardized end point and response criteria for meningioma.

Background: Despite advances in neuro-imaging, neurosurgery, radiation therapy, and chemotherapy, limited progress has been made in the treatment of patients with high-grade astrocytomas. The National Cancer Institute has attempted to speed advances in this field by funding CNS consortia to conduct innovative clinical trials in this patient population since 1994. Methods: The NABTT CNS Consortium is composed of a consortium headquarters and nine member institutions with outstanding multidisciplinary expertise, clinical and laboratory research capabilities, and access to large numbers of patients with brain tumors. Results: The objectives of the NABTT Consortium are to improve the therapeutic outcome for adults with primary brain tumors, to conduct basic science and clinical research, and to improve the care and quality of life of adults with primary brain tumors. NABTT's clinical studies have discovered important drug interactions between anticonvulsant and antineoplastic agents, defined the activity of paclitaxel and 9-aminocamptothecin in glioblastoma multiforme, tested a novel dose escalation strategy for brain tumor trials, and established new protocol “classes” to expedite and standardize clinical research in this field. Conclusions: Significant progress in the care of patients with primary brain tumors is likely to result from the highly focused and multidisciplinary efforts of the NIH-funded CNS consortia.

Abstract Glioblastoma is the most aggressive primary adult brain tumor, with median survival of 15 months despite surgery and chemoradiation. MRI is used to guide treatment decisions, but imaging interpretation is challenging because of subtle findings with overlap between treatment effect and disease progression. The most frequently used quantitative brain tumor assessment metric is the Response Assessment in Neuro-Oncology (RANO), but this scoring system requires manual delineation 2-D metrics which can be subjective and is not directly tied to patient management decisions. The Brain Tumor Reporting and Data System (BT-RADS) is a novel, management-based reporting system developed by the Emory brain tumor team to improve quantitation and reduce bias in imaging assessment. BT-RADS scoring incorporates quantitative volumetric changes in contrast-enhanced T1-weighted (CE-T1w) and fluid attenuation inversion recovery (FLAIR) MRI, patient medications, clinical outcome, and treatment dates, and has been aligned closely with management decisions. To improve repeatability and reliability of scoring, we have begun to develop a cloud platform to help physicians utilizing BT-RADS. Longitudinal MRI data from each patient are automatically co-registered using rigid registration and aligned using trilinear interpolation, enabling voxel-to-voxel comparisons across multiple scans. The platform implements a semi-automated algorithm to segment tumor volumes using curvature flow, thresholding, and morphological filtering which expedites clinical review, as physicians simply edit and confirm segmentation accuracy rather than manual segmenting and measuring 2D images. Additionally, radiation dose maps can be overlaid on clinical images to determine what may be treatment effect and in-field vs. out-of-field recurrence. A secure web interface allows easy use by the entire treatment team, e.g. in a “tumor board” setting. Future plans include incorporating clinical and genomic data and fully automating tumor segmentation. The goal of this work is to provide more quantitative and objective follow-up metrics that can guide clinical decision making in glioblastoma patients.

Abstract Background With refinements in diagnosis and therapy of gliomas, the importance of survival time as the sole outcome parameter has decreased, and patient-centered outcome parameters have gained interest. Pursuing a profession is an indispensable component of human happiness. The aim of this study was to analyze the professional outcomes besides their neuro-oncological and functional evaluation after surgery for gliomas in eloquent areas. Methods We assessed neuro-oncological and functional outcomes of patients with gliomas WHO grades II and III undergoing surgery between 2012 and 2018. All patients underwent routine follow-up and adjuvant treatment. Treatment and survival parameters were collected prospectively. Repercussions of the disease on the patients’ professional status, socio-economic situation, and neurocognitive function were evaluated retrospectively with questionnaires. Results We analyzed data of 58 patients with gliomas (WHO II: 9; III: 49). Median patient age was 35.8 years (range 21–63 years). Awake surgery techniques were applied in 32 patients (55.2%). Gross total and subtotal tumor resections were achieved in 33 (56.9%) and 17 (29.3%) patients, respectively, whereas in 8 patients (13.8%) resection had to remain partial. Most patients (n = 46; 79.3%) received adjuvant treatment. Median follow up was 43.8 months (range 11–82 months). After treatment 41 patients (70.7%) were able to resume a working life. Median time until returning to work was 8.0 months (range 0.2–22.0 months). To be younger than 40 at the time of the surgery was associated with a higher probability to return to work (p < .001). Multivariable regression analysis showed that patient age < 40 years as well as occupational group and self-reported fatigue were factors independently associated with the ability to return to work. Conclusion The ability to resume professional activities following brain tumor surgery is an important patient-oriented outcome parameter. We found that the majority of patients with gliomas were able to return to work following surgical and adjuvant treatment. Preservation of neurological function is of utmost relevance for individual patients´ quality of life.

ObjectiveThe prevalence of depression among patients with primary brain tumour ranges from 15% to 40% globally. Several individual and clinical factors contribute to the development of depression. However, their association with depression in Pakistani setting has not yet been assessed. Thus, we aim to study the factors associated with depression among adult patients with primary brain tumour at a tertiary care hospital in Karachi, Pakistan.Study designA prospective cross-sectional study.SettingThis study was conducted at a tertiary care hospital of Karachi, Pakistan.ParticipantsThis study included 132 patients with confirmed diagnosis of primary brain tumour (initially diagnosed on MRI of the brain with contrast and later confirmed on histology of surgical specimen) in various stages of treatment.Primary outcomeThe primary outcome of this study was to assess depression and its associated factors among adult patients with primary brain tumour. Depression was assessed using a validated screening tool Patient Health Questionnaire-9 (PHQ-9). Scores of 10–27 on PHQ-9 were indicative of screen positive for depressive symptoms. A set of the structured pre-tested questions was used to evaluate patient-related, tumor-related and treatment-related factors.ResultsFifty-one (39%, CI: 33.33–46.94) patients in our study screened positive for depressive symptoms on PHQ-9. There was a significant association between depressive symptoms and Karnofsky Performance Scores (KPS) (prevalence ratio: 3.25 and CI: 1.87–5.62) after controlling covariates. Propensity scores predicted a positive association between KPS (functional status) and unemployment, treatment stage, and tumour recurrence. Tumor-related and treatment-related factors including tumour grade, location, type and hemispheric lateralisation were found insignificant.ConclusionDepression is common in patients with primary brain tumour. Impaired functional status has a direct impact on depression in these patients. Incorporating the psychosocial domain earlier in the course of treatment needs to be considered for better neuro-oncology management of patients with primary brain tumour.

ABSTRACT Background: Perioperative outcomes following surgery for brain tumors are an important indicator of the safety as well as efficacy of surgical intervention. Perioperative morbidity not only has implications on direct patient care, but also serves as an indicator of the quality of care provided, and enables objective documentation, for comparision in various clinical trials. We document our experience at a tertiary care referral, a dedicated neuro-oncology center in India. Materials and Methods: One hundred and ninety-six patients undergoing various surgeries for intra-axial brain tumors were analyzed. Routine microsurgical techniques and uniform antibiotic policy were used. Navigation/ intraoperative electrophysiological monitoring was not available. The endpoints assessed included immediate postoperative neurological status, neurological outcome at discharge, regional complications, systemic complications, overall morbidity, and mortality. Various risk factors assessed included clinico-epidemiological factors, tumor-related factors, and surgery-related factors. Univariate and multivariate analysis were performed. Results: Median age was 38 years. 72% had tumors larger than 4 cm. Neurological morbidity, and regional and systemic complications occurred in 16.8, 17.3, and 10.7%, respectively. Overall, major morbidity occurred in 18% and perioperative mortality rate was 3.6%. Although a few of the known risk factors were found to be significant on univariate analysis, none achieved significance on multivariate analysis. Conclusions: Our patients were younger and had larger tumors than are generally reported. Despite the unavailability of advanced intraoperative aids we could achieve acceptable levels of morbidity and mortality. Objective recording of perioperative events is crucial to document outcomes after surgery for brain tumors.

Brain tumors, independently from histology, share a similar progressive growth pattern that often requires multiple treatment modalities. Surgery, radiotherapy, chemotherapy and medications are often administered in close proximity to one another or, sometimes, contemporaneously. For that reason, the assessment of the effectiveness of any single treatment is extremely difficult. Brain tumors are a rare cancer but they are among the most devastating forms of cancer and afflict the very core of the person. Optimizing the life style of patients should become essential and on a par with the life prolongation goal of anti-cancer therapy. A potential solution to this problem is a patient-centered approach to different tumor types and treatments in which the comprehensive patient assessment is included in the outcome set. Traditionally, clinical trials of treatments for gliomas have relied on measures such as the reduction in tumor size, or on time-dependent metrics including the progression-free survival and the overall survival. The procedure used to evaluate of treatment effects by means of these measures can be complemented by the assessment of clinical outcomes such as measurements of the functional or symptomatic effects of the condition on the person. Unfortunately, the most commonly reported outcome measures are not necessarily the most appropriate. They are often selected and motivated since they are widely cited in the literature; this is an incorrect approach on a scientific ground and also precludes new and more effective instruments to be introduced and accepted. The instruments currently used in neuro-oncology are influenced by notions anchored to the type of treatment (such as chemotherapy or radiotherapy) rather than to tumor and, particularly, to patient characteristics. The utility of patient-reported outcome data can be maximized with standardization of methods to assess, analyze, interpret and report results. Nevertheless, neuro-oncological guidelines do not mention instruments and parameters but rather generically prescribe “neurological monitoring”. A paradox is that, while new therapies and diagnostics are improving survival rates, much remains unknown about the patient clinical conditions and performance at an instrumental level. However, in the last years, a growing interest on cognitive response in clinical trials has been observed and the cognitive performance is now considered as an important patient-related outcome to assess response to treatments. Tracking symptoms and function can inform clinicians about whether a treatment results in measurable benefits or adverse effects to patients. 6 We should not forget that patients want to live longer, but they also want to continue to function as well as possible for as long as possible. This research. arose from the considerations set forth above. The aim of the thesis is to provide an overview of the clinical outcome assessment of patients with brain tumors. The thesis analyzes the role of the assessment in collecting information about the direct impact of neoplastic invasion of the cerebral parenchyma and in monitoring the effects of therapies. This thesis is composed of three different studies. The first study describes the characteristics of clinical trials on gliomas and the outcome profile (objective, endpoints, domains, categories and instruments), since the 1990 (the advent of evidence based medicine) to 2019. The second study describes the neuropsychological tests mainly used in the brain tumor clinical trials published over the last 30 years and tries to evaluate the methodological quality of studies on measurement properties by means of the COSMIN checklist. Finally, the third study focuses on the neuropsychological assessment of language in multilingual people. Due to the increasingly widespread integration, this has become a crucial issue in neuro-oncology, especially in the perioperative evaluation of patients undergoing surgical treatment for brain cancer. The aim is to verify to what extent the variables that affect linguistic processing in multilingual speakers have been considered during planning and decision making in awake surgery for brain tumors.