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Kim, Yeonju, Terri Armstrong, Mark Gilbert, and Orieta Celiku. "BIOS-04. CONTACT: CLINICAL OUTCOME ASSESSMENTS TRENDS IN BRAIN CANCER TRIALS." Neuro-Oncology 24, Supplement_7 (November 1, 2022): vii21. http://dx.doi.org/10.1093/neuonc/noac209.080.
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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.
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Nomura, Keiko, Laureline Gatellier, Shuji Yamaguchi, Shigeo Kato, and Hisato Tagawa. "COT-29 The Japan Brain Tumor Alliance: Achievements in 2020–2021: highlights for neuro-oncologists and healthcare professionals." Neuro-Oncology Advances 3, Supplement_6 (December 1, 2021): vi31. http://dx.doi.org/10.1093/noajnl/vdab159.121.
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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.
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Osmanlioglu, Yusuf, Drew Parker, Steven Brem, Ali Shokoufandeh, and Ragini Verma. "NIMG-69. PERSONALIZED CONNECTOMIC SIGNATURES: BRIDGING THE GAP BETWEEN NEURO-ONCOLOGY AND CONNECTOMICS." Neuro-Oncology 22, Supplement_2 (November 2020): ii163. http://dx.doi.org/10.1093/neuonc/noaa215.682.
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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.
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Kim, Yeonju, Terri Armstrong, Mark Gilbert, and Orieta Celiku. "EPID-24. TRANSCRIPT: A cenTRAl NERVOUS SYSTEM CANCER CLINICAL tRIals PostmorTem." Neuro-Oncology 23, Supplement_6 (November 2, 2021): vi91. http://dx.doi.org/10.1093/neuonc/noab196.357.
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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.
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Rogers, Leland, Igor Barani, Marc Chamberlain, Thomas J. Kaley, Michael McDermott, Jeffrey Raizer, David Schiff, Damien C. Weber, Patrick Y. Wen, and Michael A. Vogelbaum. "Meningiomas: knowledge base, treatment outcomes, and uncertainties. A RANO review." Journal of Neurosurgery 122, no. 1 (January 2015): 4–23. http://dx.doi.org/10.3171/2014.7.jns131644.
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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.
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Grossman, Stuart A., Joy D. Fisher, Steven Piantadosi, and Henry Brem. "The New Approaches to Brain Tumor Therapy (NABTT) CNS Consortium: Organization, Objectives, and Activities." Cancer Control 5, no. 2 (March 1998): 107–14. http://dx.doi.org/10.1177/107327489800500201.
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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.
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Weinberg, Brent, Karthik Ramesh, Saumya Gurbani, Eduard Schreibmann, Lawrence Kleinberg, Hui-Kuo Shu, and Hyunsuk Shim. "NIMG-23. BRAIN TUMOR REPORTING AND DATA SYSTEM (BT-RADS) AND QUANTITATIVE TOOLS TO GUIDE ITS IMPLEMENTATION." Neuro-Oncology 21, Supplement_6 (November 2019): vi166. http://dx.doi.org/10.1093/neuonc/noz175.695.
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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.
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Senft, Christian, Marion Behrens, Irina Lortz, Katharina Wenger, Katharina Filipski, Volker Seifert, and Marie-Thérèse Forster. "The ability to return to work: a patient-centered outcome parameter following glioma surgery." Journal of Neuro-Oncology 149, no. 3 (September 2020): 403–11. http://dx.doi.org/10.1007/s11060-020-03609-2.
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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.
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Pidani, Anum Sadruddin, Amna Rehana Siddiqui, Iqbal Azam, Muhammad Shahzad shamim, Adnan Abdul Jabbar, and Shameel Khan. "Depression among adult patients with primary brain tumour: a cross-sectional study of risk factors in a low–middle-income country." BMJ Open 10, no. 9 (September 2020): e032748. http://dx.doi.org/10.1136/bmjopen-2019-032748.
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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.
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Moiyadi, Aliasgar V., and Prakash M. Shetty. "Perioperative outcomes following surgery for brain tumors: Objective assessment and risk factor evaluation." Journal of Neurosciences in Rural Practice 03, no. 01 (January 2012): 28–35. http://dx.doi.org/10.4103/0976-3147.91927.
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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.
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Ferroli, Paolo, Ignazio Gaspare Vetrano, Silvia Schiavolin, Francesco Acerbi, Costanza Maria Zattra, Marco Schiariti, Matilde Leonardi, and Morgan Broggi. "Brain Tumor Resection in Elderly Patients: Potential Factors of Postoperative Worsening in a Predictive Outcome Model." Cancers 13, no. 10 (May 12, 2021): 2320. http://dx.doi.org/10.3390/cancers13102320.
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The decision of whether to operate on elderly patients with brain tumors is complex, and influenced by pathology-related and patient-specific factors. This retrospective cohort study, based on a prospectively collected surgical database, aims at identifying possible factors predicting clinical worsening after elective neuro-oncological surgery in elderly patients. Therefore, all patients ≥65 years old who underwent BT resection at a tertiary referral center between 01/2018 and 12/2019 were included. Age, smoking, previous radiotherapy, hypertension, preoperative functional status, complications occurrence, surgical complexity and the presence of comorbidities were prospectively collected and analyzed at discharge and the 3-month follow-up. The series included 143 patients (mean 71 years, range 65–86). Sixty-five patients (46%) had at least one neurosurgical complication, whereas 48/65 (74%) complications did not require invasive treatment. Forty-two patients (29.4%) worsened at discharge; these patients had a greater number of complications compared to patients with unchanged/improved performance status. A persistent worsening at three months of follow-up was noted in 20.3% of patients; again, this subgroup presented more complications than patients who remained equal or improved. Therefore, postoperative complications and surgical complexity seem to influence significantly the early outcome in elderly patients undergoing brain tumor surgery. In contrast, postoperative complications alone are the only factor with an impact on the 3-month follow-up.
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Bartkowiak, Todd, Asa Brockman, Sierra Lima, Madeline Hayes, Caroline Roe, Justine Sinnaeve, Akshitkumar Mistry, et al. "TMIC-26. USING INTEGRATED MULTIDIMENSIONAL MASS CYTOMETRY AND MULTIPLEX IMMUNOHISTOCHEMISTRY TO INFER SPATIAL RELATIONSHIPS BETWEEN PHENOTYPICALLY DISTINCT GLIOBLASTOMA INFILTRATING IMMUNE CELLS." Neuro-Oncology 24, Supplement_7 (November 1, 2022): vii277. http://dx.doi.org/10.1093/neuonc/noac209.1070.
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Abstract Glioblastomas (GBM) account for ~60% of adult primary brain tumors. With few advances in therapeutics, median overall survival remains 15-months post-diagnosis. Immunotherapies may provide therapeutic benefit; however, no predictive immune features have informed therapeutic stratification. Radiographic tumor contact with the lateral ventricle (C-GBM) correlates with 7-months worse prognosis compared to patients with ventricle non-contacting GBM (NC-GBM), yet the influence of ventricle contact on anti-tumor immunity is unknown. This study characterized the GBM immune microenvironment and identified targetable mechanisms of immunosuppression correlating with worse outcomes in C-GBM patients.Primary glioblastoma tissue was provided with written informed consent in accordance with the Declaration of Helsinki and with approval of the Vanderbilt Institutional Review Board (IRB #131870). Seventeen patients presented with primary, IDH-wildtype C-GBM and 15 with NC-GBM. Machine learning integrated mass cytometry and matched multiplex immunohistochemistry on FFPE embedded tissue to identify phenotypic, functional, and spatial biomarkers correlating with patient outcome. C-GBM tumors were enriched in STAT3-driven CD32+CD44+HLA-DR+ monocyte-derived macrophages (MDM) compared to NC-GBM (19 ± 8% vs. 6 ± 2%; p< 0.001) and depleted in lymphocytes (2.9 ± 1% vs. 7.6 ± 2%; p< 0.001) and tissue-resident microglia (1.8 ± 0.3% vs. 7 ± 3%; p< 0.001). Exhausted T cells in C-GBM co-expressed checkpoint receptors PD-1 and TIGIT. K-means clustering identified 10 immunological niches in GBM. Macrophage-tumor niches were most common in C-GBM (17.93% of niches), followed by T cell-microglia-tumor niches (17.72%). Within NC-GBM niches, T cell-T cell interactions were more prevalent (log odds ratio = 0.90) and correlated with improved outcome.These findings suggest that factors within the periventricular space negatively influence the immune microenvironment within GBM tumors. Clinically targetable immune biomarkers were identified in C-GBM. Notably, radiologic assessment of lateral ventricle contact may guide clinical trial design for immunotherapies in neuro-oncology based on tumor proximity to the ventricle wall.
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Zarrella, Giuliana, Alice Perez, Jorg Dietrich, and Michael Parsons. "NCOG-70. RELIABILITY AND VALIDITY OF A NEW SELF-REPORT INDEX OF COGNITIVE CONCERNS IN BRAIN TUMOR PATIENTS." Neuro-Oncology 22, Supplement_2 (November 2020): ii145. http://dx.doi.org/10.1093/neuonc/noaa215.608.
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Abstract INTRODUCTION Subjective cognitive dysfunction is an important outcome measure in neuro-oncology and may provide additional information beyond performance-based neuropsychological testing. The Functional Assessment of Cancer Therapy-Brain (FACT-Br) is a frequently used quality of life (QoL) measure that includes indices of physical, emotional, social, and neurologic aspects of disease, but does not measure cognitive concerns. This study seeks to develop and validate an index of self-reported cognition derived from existing items on the FACT-Br. METHODS 145 patients (Mage=51.08, Medu=15.63) with heterogeneous brain tumor diagnoses completed neuropsychological evaluation including cognitive testing and self-report measures. Nine FACT-Br items regarding cognition were combined to form the Cognitive Index (CI). Reliability of the CI was measured with Cronbach’s alpha. Concurrent validity was assessed by correlating the CI with the Patient-Reported Outcomes Measurement Information System (PROMIS) Cognitive Abilities-8 or PROMIS Cognitive Concerns-8. Discriminant validity was assessed by correlation of the CI with other FACT-Br indices and the Beck Depression and Anxiety Inventories (BDI, BAI). RESULTS Internal consistency within the CI was high (Cronbach’s a 0.864). The CI correlated strongly with the PROMIS-Abilities (r =.680; p< 0.001) and PROMIS-Concerns (r=.780; p< 0.001) indicating high convergent validity. Moderate correlations were observed between the CI and the physical and functional subscales of the FACT (r=.453 and .555), whereas correlations with the social and emotional functioning subscales were weaker (r=.381 and .325). The FACT-Br-CI correlated strongly with BDI (r=-.622) and more weakly with the BAI (r=-.344). Consistent with prior literature, the CI showed modest correlations with neuropsychological measures, including verbal memory encoding (r=.300), verbal fluency (r=.252) and a composite measure of cognition (r=.249; all p’s< .01). CONCLUSIONS The FACT-Br-CI is a reliable and valid measure of self-reported cognition. Studies that include the FACT-Br could be retrospectively analyzed to assess self-reported cognitive outcomes, enriching the information gained from prior research.
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Lim-Fat, Mary Jane, Marie Allen, Timothy Smith, Gilbert Youssef, Brian Andersen, Oluwatosin Akintola, Tamar Berger, et al. "INNV-40. REAL WORLD INTEGRATION OF THE NEUROLOGIC ASSESSMENT IN NEURO-ONCOLOGY (NANO) SCALE IN CLINICAL PRACTICE IN PATIENTS WITH IDH-WT GBM." Neuro-Oncology 23, Supplement_6 (November 2, 2021): vi114. http://dx.doi.org/10.1093/neuonc/noab196.450.
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Abstract BACKGROUND The neurologic assessment in neuro-oncology (NANO) scale was developed as a standardized metric to objectively measure neurologic function in patients with brain tumors and complement radiographic assessment in defining overall outcome. The scale has been incorporated in clinical trials. Early data is suggestive of feasibility and that NANO contributes to overall outcome assessment. However, real-world use of the NANO scale to drive clinical-decision making and the predictive value of the NANO scale to determine overall survival remains unclear in IDH-wt GBM. METHODS We report on an ongoing study using the NANO scale to evaluate neurologic function in patients with IDH-wt GBM, seen at Dana-Farber Cancer Institute (DFCI). Patient demographics, tumor histology and molecular status, treatment history and progression dates are being captured. NANO score, as collected by a built-in scale in our institutional electronic medical record (EMR), functional status (Karnofsky performance status) and corticosteroid dose are collected at prespecified time points (prior to start of therapy, and during each subsequent MRI visit). Changes in the NANO score will be correlated to overall survival. Statistical analyses including descriptive data analysis and generalized linear models will be performed using R (version 3.4.3). RESULTS Since June 2020, 50 patients have been enrolled in this study, including 42 (84%) with ≥2 follow up visits. Study accrual was initially impacted by the COVID-19 pandemic, but adaptation to a virtual platform for NANO allowed for improved recruitment and follow up of patients. Study results will be available for discussion at the 2021 SNO conference. CONCLUSIONS Evaluation of neurologic function by NANO is feasible in a virtual framework in a prospective study in patients with GBM, aided by integration of the scale in our institutional EMR. NANO is able to objectively track neurologic function throughout disease course in IDH-wt GBM.
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Renovanz, M., J. Coburger, G. Tabatabai, F. Ringel, C. Wirtz, M. Mehdorn, and S. Goebel. "OS3.2 Relevant topics for brain tumor patients in the Distress Thermometer, first results of the HEAT study." Neuro-Oncology 21, Supplement_3 (August 2019): iii8—iii9. http://dx.doi.org/10.1093/neuonc/noz126.026.
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Abstract BACKGROUND Patient-centered assessments and disease-adjusted patient-reported outcome measures (PROMs) are crucial in neuro-oncology. The Distress Thermometer (DT) is a well-accepted screening tool for cancer patients including a numerical rating scale (1–10, cut-offs indicating relevant distress ≥4–6) and 40 items describing possible problem categories (emotional, social, physical, practical and spiritual). The aims of the first part of the “Adaption of the Distress Thermometer in patients with intracranial tumors” (HEAT) study were to evaluate the importance and relevance of items for brain tumor patients (BTP). MATERIAL AND METHODS The multicenter study included three University hospitals. After given informed consent patients were prospectively evaluated either during their hospital stay or in the outpatient setting using DT as well as the 40 item problem list. Clinical and demographic data were recorded. We performed an analysis regarding frequency of indicated topics and evaluated their relevance for patients’ psychosocial well-beings via Pearson correlations with the DT score. RESULTS Data of n = 670 patients were analyzed. Mean age was 52 years (SD = 14, range 18–81), most of the patients harbored WHO°I tumors (37%) and WHO°IV tumors (28%). Male to female ratio was 1:1, 17% were assessed preoperatively, 40% postoperatively and 43% during adjuvant therapy or follow-up. 14% of the patients faced a tumor recurrence at assessment. Mean score of DT was 5.23 (SD = 2.9, range 0–10). Applying a cut-off score ≥ 4, 61% reported distress (≥ 5: 46% and ≥ 6: 37%). Regarding the relevance of the problem list for BTP, emotional problems (e. g., anxiety, depression) were most frequently reported. A total of 14/40 (35 %) of items were endorsed by less than 10% of patients. With exception of emotional problems all areas were reflected: practical problems (e. g., problems with child care or insurance), social problems (e. g., problems with children), spiritual concerns (e. g., loss of faith), and physical problems (e. g., breathing, fever). However, some of these rarely reported problems were of relevance for patients’ psychosocial well-being as indicated by significant correlations between the respective item and the DT score. This was, for example, the case for problems with childcare (r = .106; p < .01) or breathing (r = .125; p = .001). CONCLUSION Tools developed for cancer patients do not yet perfectly reflect all needs of BTP. Based on our data, we suggest further adjustments of available tools. Yet, it should be taken into account that subgroups of BTP may require different problem lists in the DT, as we observed some topics (e.g. breathing) probably be related to BTP under chemotherapy or steroids only. Moreover, our data require cross-cultural validation as especially results regarding practical problems and insurance might differ in cultures with different social security systems.
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Walbert, Tobias, and Muhib Alam Khan. "End-of-life care in patients with primary malignant brain tumors: A systematic literature review and analysis." Journal of Clinical Oncology 31, no. 15_suppl (May 20, 2013): e20703-e20703. http://dx.doi.org/10.1200/jco.2013.31.15_suppl.e20703.
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e20703 Background: 80–85% of all adult brain tumors are high-grade glioma (HGG). HGG are typically treated with maximal surgical resection, followed by radiotherapy with concurrent and adjuvant chemotherapy. The median survival for anaplastic glioma is estimated to be 2-5 years and 15 months for patients with glioblastoma. Quality of life (QoL) has become an increasing important outcome assessed in clinical trials as well as in the standard care of brain tumor patients. Despite the inevitable disease trajectory, not much is known about symptoms and needs of brain tumor patients and their caretakers at the end of life. There appears to be a lack of published literature on this important aspect of neuro-oncology. Methods: A systematic literature search was conducted in PubMed and Cochrane covering the years between 1946 through 2012. In total, 7146 article citations were found. After first review 942 abstracts were obtained. Based on content 82 articles were examined separately by both authors and it was agreed to eliminate 67 of them because they did not include a significant number of primary brain tumor patients or the focus was not on end of life care and symptoms. Results: Only 7 of the retained articles contained specific patient data and did not just reflect opinions of authors or reviews of the topic. Only one study was performed prospectively. Three studies assessed symptom management in inpatients, 2 in outpatients and 2 in a combined setting. Studies included between 29 and 169 patients. Drowsiness and loss of consciousness was the most common symptom (85%–90%). Poor communication (64% and 90%), focal deficits (29%– 62%), seizures (3%–67%), dysphagia (10%–85%), headache (4%–62%), and fatigue (25%–67%) were also frequent. Interventions included hydration (87%-93%), urinary catheter (89%), steroids (62%-80%), anti-epileptic drugs (45%-76%), oxygen (48%), tube feeding (13%) and palliative sedation (13%). Conclusions: There is 1 prospective study and only a total of 7 studies describing detailed end of life symptoms. None of the studies addressed caregiver quality of life. More research is needed to develop purposeful interventions to address end of life symptoms and QoL in patients with HGG.
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Mora, J., O. Cruz, A. Parareda, C. de Torres, A. Guillen, R. Navarro, G. Garcia, and J. Costa. "Successful treatment of childhood astrocytomas with cisplatin and irinotecan." Journal of Clinical Oncology 25, no. 18_suppl (June 20, 2007): 9508. http://dx.doi.org/10.1200/jco.2007.25.18_suppl.9508.
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9508 Background: Childhood astrocytomas are a heterogeneous group of neoplasms for which non-surgical management is controversial. After a pilot study suggesting that irinotecan/cisplatin (I/C) may be effective for spinal cord astrocytomas in children (Mora et al, Neuro-Oncol 2007), we initiated a phase II trial for progressing astrocytomas with the aim of avoiding radiation therapy for low grade's and improve outcome for high grade's. Methods: The indication for adjuvant therapy was based upon histology, the extent of surgical resection, and the presence of clinical or neuroradiological signs of progression. Weekly Irinotecan (50 mg/m2 and 65 mg/m2 the last 2 cycles) and Cisplatin (30 mg/m2) for four consecutive weeks (1 cycle), and a total of 4 cycles was used. Results: Since 2004, 17 children aged 7m-17y were treated including 5 WHO grade I, 6 grade II, 3 grade III, and 3 non biopsied tumors: 2 intrinsic brain-stem tumors (BST) and 1 optic-pathway (OP) tumor. No patient had clinical signs of neurofibromatosis. Primary sites included 4 supratentorial, 3 BST, 3 OP, 1 cerebellar, and 6 spinal tumors. Gross total resection was performed in 1 case, subtotal in 4 and only biopsy in 9. Six patients received chemotherapy and one radiotherapy prior to the I/C regimen. Vomiting was easily controlled except for patients with BST. All but 2 patients, because of C allergy, completed the protocol with no documented ototoxic, renal, or GI side effects. Eleven (65%) pts had a complete clinical response, including 1 BST and all the spinal cord cases. Remarkably all the clinical responses were rapid, within the first 1–2 weeks of treatment. Twelve (70%) pts had a <25 [O1] % reduction of the tumor size at the end of therapy including 2 spinal cord cases that achieved complete radiological responses 10 months after the end of therapy. One BST patient progressed on therapy. Thus far, none of the low grade cases have received radiotherapy, although median f/u is only 1 year. All pts are alive and well. Conclusions: Remarkable clinicoradiological responses and avoidance of radiotherapy was obtained using the I/C regimen for childhood astrocytoma. No significant financial relationships to disclose.
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Lee, Eudocia, Ugonma Chukwueke, Shawn Hervey-Jumper, John DeGroot, Pablo Leone, Terri Armstrong, Susan Chang, et al. "INNV-33. BARRIERS TO ACCRUAL AND ENROLLMENT IN BRAIN TUMOR TRIALS." Neuro-Oncology 21, Supplement_6 (November 2019): vi137. http://dx.doi.org/10.1093/neuonc/noz175.574.
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Abstract BACKGROUND A major impediment to improving neuro-oncology outcomes is poor clinical trial accrual. METHODS We convened a multi-stakeholder group including Society for Neuro-Oncology, Response Assessment in Neuro-Oncology, patient advocacy groups, clinical trial cooperative groups, and other partners to determine how we can improve trial accrual. RESULTS We described selected factors contributing to poor trial accrual and possible solutions. We focused on patient and community factors, disparities, physician and provider factors, clinical trial factors, and site and organizational factors CONCLUSIONS We will implement strategies with the intent to double accrual to neuro-oncology trials over the next 5 years.
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Marigil, Miguel, and Mark Bernstein. "Outpatient neurosurgery in neuro-oncology." Neurosurgical Focus 44, no. 6 (June 2018): E19. http://dx.doi.org/10.3171/2018.3.focus1831.
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Technological breakthroughs along with modern application of awake craniotomy and new neuroanesthesia protocols have led to a progressive development in outpatient brain tumor surgery and improved surgical outcomes. As a result, outpatient neurosurgery has become a standard of care at the authors’ center due to its clinical benefits and impact on patient recovery and overall satisfaction. On the other hand, the financial savings derived from its application is also another favorable factor exerting influence on patients, health care systems, and society.Although validated several years ago and with recent data supporting its application, outpatient brain tumor surgery has not gained the traction that it deserves, based on scientific skepticism and perceived potential for medicolegal issues. The goal of this review, based on the available literature and the senior author’s experience in outpatient brain tumor surgery, was to evaluate the most important aspects regarding indications, clinical outcomes, economic burden, and patient perceptions.
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Lee, Eudocia Quant, Ugonma Nnenna Chukwueke, Shawn L. Hervey-Jumper, John Frederick De Groot, Jose Pablo Leone, Terri S. Armstrong, Susan Marina Chang, et al. "Barriers to accrual and enrollment in brain tumor trials." Journal of Clinical Oncology 37, no. 15_suppl (May 20, 2019): 2024. http://dx.doi.org/10.1200/jco.2019.37.15_suppl.2024.
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2024 Background: A major impediment to improving neuro-oncology outcomes is poor clinical trial accrual. Methods: We convened a multi-stakeholder group including Society for Neuro-Oncology, Response Assessment in Neuro-Oncology, patient advocacy groups, clinical trial cooperative groups, and other partners to determine how we can improve trial accrual. Results: We describe selected factors contributing to poor trial accrual and possible solutions. Conclusions: We will implement strategies with the intent to double trial accrual over the next 5 years. [Table: see text]
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Tiberi, Luca. "PDTM-35. MODELLING MEDULLOBLASTOMA WITH MOUSE MODELS AND HUMAN CEREBELLAR ORGANOIDS." Neuro-Oncology 21, Supplement_6 (November 2019): vi195. http://dx.doi.org/10.1093/neuonc/noz175.811.
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Abstract Malignant medulloblastoma (MB) is the most common brain tumor affecting children and it remains responsible for a high percentage of morbidity and mortality among cancer patients. During the past few years, studies on human MB and mouse models have uncovered the existence of four major MB groups, with specific pathological and molecular features: WNT, SHH, Group 3 and Group 4. Of the four groups, patients with Group 3 MB have the worst outcome with nearly 50% of the tumors metastatic at the time of diagnosis. Therefore, developing “humanized “ mouse model of Group3 Medulloblastoma would be of paramount importance for the identification and testing of new drugs for pediatric patients, tailored on the genetic condition of the patient itself. We performed an in-vivo screen to identify new cancer-inducing genes starting from the published genome-wide analyses of MB patients. This screen led to the identification of novel driver gene combinations required for tumorigenesis. To study Medulloblastoma in human cells, we generated human cerebellar organoids. Organoids are cellular structures that resemble whole organs and can be generated from pluripotent stem cells or isolated organ progenitors. We were able to induce cerebellar progenitors to self-form neuro-epithelial structures that mimic early human cerebellar plate, composed by cerebellar progenitors, cerebellar neurons (interneurons, Purkinje cells, and granule neurons) and glial cells. Notably, we have generated human putative iPSC-derived cancer organoids with gene combinations mimicking human Group3 MB. Indeed, organoids that mimic cancer can be used as an alternative system for drug testing that better recapitulate effects in human patients as compared to other in-vitro and in-vivo systems.
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Sul, Joohee, Paul G. Kluetz, Elektra J. Papadopoulos, and Patricia Keegan. "Clinical outcome assessments in neuro-oncology: a regulatory perspective." Neuro-Oncology Practice 3, no. 1 (December 27, 2015): 4–9. http://dx.doi.org/10.1093/nop/npv062.
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Abstract Overall survival, progression-free survival, and to a lesser extent objective response rate, have long been the most widely accepted endpoints used to evaluate clinical benefit in oncology trials. More recently, clinical outcome assessments (COAs) that measure the impact of disease and treatment on patients′ symptoms and function have been recognized as having potential to be an integral component of the risk/benefit analysis of new therapies. Although COAs have been used to evaluate cognitive and physical functioning in neurological diseases, assessing patient-centered outcomes in individuals with malignant brain tumors presents unique challenges. The approach to developing appropriate instruments to measure COAs in neuro-oncology should include identifying areas requiring new tools, reviewing existing tools that may be suitable or adapted for use in clinical trials, and engaging early with regulatory agencies to standardize a set of well-defined and reliable instruments to quantify important patient-centered outcomes.
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Millward, Christopher, Sumirat Keshwara, Abdurrahman Islim, Nisaharan Srikandarajah, Tony Marson, Paula Williamson, and Michael Jenkinson. "Development of ‘Core Outcome Sets’ for meningioma in clinical studies: The COSMIC project." Neuro-Oncology 23, Supplement_4 (October 1, 2021): iv22. http://dx.doi.org/10.1093/neuonc/noab195.055.
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Abstract Aims To date, meningioma clinical trial activity has been limited, but a number of high-quality studies are underway, with more in development. There is heterogeneity in the outcomes reported in meningioma clinical trials. The COSMIC Project will develop two ‘Core Outcome Sets’ (COS) through comprehensive, transparent, consensus methodology; to ensure outcomes relevant to key stakeholders are reported within and across future meningioma clinical studies. The first will be for use in clinical effectiveness trials (COSMIC: Intervention), the second will be for use in clinical studies of incidental meningioma (COSMIC: Observation). Method Three systematic literature reviews will be performed to generate a long-list of outcomes potentially relevant to meningioma patients, healthcare professionals, researchers, and other stakeholder groups. The first systematic review will present the outcomes reported in published and ongoing meningioma clinical effectiveness trials. The second systematic review will present patient-reported outcomes (PRO) from the measurement tools utilised in meningioma PRO studies. The third systematic review will present the outcomes reported in published and ongoing clinical studies of untreated meningioma. Outcomes will be deduplicated, unique outcomes categorised according to the taxonomy presented by COMET, and the lists combined. The long-list of outcomes will be prioritised through two, 2-round, modified eDelphi surveys including meningioma patients, healthcare professionals, researchers, and other stakeholder groups. Undecided outcomes from both eDelphi surveys will be ratified at two, one-day consensus meeting, with representation from all key stakeholder groups. Results We have formed a study advisory group with international representation from key organisations. The project already has confirmed support from the International Consortium on Meningioma (ICOM), the European Association of Neuro-Oncology (EANO), the Response Assessment in Neuro-Oncology Patient-Reported Outcome group (RANO-PRO), the Society for Neuro-Oncology (SNO), British Neuro-Oncology Society (BNOS), Society of British Neurological Surgeons (SBNS), The Brain Tumour Charity (TBTC), and Brainstrust. Conclusion Standardising minimum outcome reporting in meningioma clinical effectiveness trials and meningioma clinical studies, through the development of these two COS will ensure outcomes reported are relevant to key stakeholder groups, including patients, whilst reducing research waste for a disease with increasing clinical trial activity. We seek to raise awareness of this project and invite participation from a wide range of stakeholders to ensure that the final COS reflects the opinion of the neuro-oncology community. Registration will take place via the study website www.thecosmicproject.org between June-August 2021.
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Nejo, Takahide, Abigail Mende, and Hideho Okada. "The current state of immunotherapy for primary and secondary brain tumors: similarities and differences." Japanese Journal of Clinical Oncology 50, no. 11 (September 28, 2020): 1231–45. http://dx.doi.org/10.1093/jjco/hyaa164.
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Abstract Treatment and resolution of primary and metastatic brain tumors have long presented a challenge to oncologists. In response to the dismal survival outcomes associated with conventional therapies, various immunotherapy modalities, such as checkpoint inhibitors, vaccine, cellular immunotherapy and viral immunotherapy have been actively explored over the past couple of decades. Although improved patient survival has been more frequently noted in treatment of brain metastases, little progress has been made in improving patient survival in cases of primary brain tumors, specifically glioblastoma, which is the representative primary brain tumor discussed in this review. Herein, we will first overview the findings of recent clinical studies for treatment of primary and metastatic brain tumors with immunotherapeutic interventions. The clinical efficacy of these immunotherapies will be discussed in the context of their ability or inability to overcome inherent characteristics of the tumor as well as restricted antigen presentation and its immunosuppressive microenvironment. Additionally, this review aims to briefly inform clinicians in the field of neuro-oncology on the relevant aspects of the immune system as it pertains to the central nervous system, with special focus on the differing modes of antigen presentation and tumor microenvironment of primary and metastatic brain tumors and the role these differences may play in the efficacy of immunotherapy in eradicating the tumor.
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Pakzad-Shahabi, L., C. Cherrington, N. Brassil, P. Even, D. Gardner, W. Fulcher, K. Le Calvez, R. Mauricaite, and M. Williams. "P14.18 Patient and Public Involvement to define patient-centred outcomes from National Cancer Datasets." Neuro-Oncology 23, Supplement_2 (September 1, 2021): ii41. http://dx.doi.org/10.1093/neuonc/noab180.141.
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Abstract BACKGROUND GlioCova uses linked national cancer data on all 51 000 adult patients with a primary brain tumour in England (2013 - 2018) to understand patterns of care, treatment, and outcomes in patients with glioma (http://wwwf.imperial.ac.uk/blog/gliocova/). A key aim is the use of patient and carer input in defining patient-centered outcomes. We have held multiple Patient & Public Involvement (PPI) sessions with patients and carergivers and data analysts to understand what patient and caregivers want to know about brain tumours. MATERIAL AND METHOD We used a modified Delphi method. The online PPI sessions (Zoom) consisted of two presentations, open discussions, and Q&As. We made the sessions as interactive as possible by using Mentimeter and an interactive online white board (Explain Everything). Pre-reading material was circulated via email. Attendees (6–14 per session) covered a wide range of ages (30–75), diagnoses (GBM, recurrent gliomas, low grade gliomas, ependymoma); patients, caregivers, neuro-oncology staff, data analysts and basic scientists. Work was conducted in line with the INVOLVE PPI guidance. RESULTS We identified four questions that were of interest to patients and had correlates in the data: Patients and caregivers were also interested in the impact of diet, quality of life, social life, and exercise. However, these data cannot be answered using the current national data. CONCLUSION Our PPI work has helped us to identify and prioritise questions to ask of the data. Ongoing PPI work will provide a wider perspective and identify knowledge gaps for future research. Patients and caregivers report feeling empowered, being part of a team, feeling like they had given something back and done something meaningful for the research community and other patients. Patients and caregivers also felt that they had an enriched understanding of the data that is collected. As this process is an iterative process, we will hold more PPI sessions to identify and prioritise topics to analyse.
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Porter, Alyx B., Ugonma N. Chukwueke, Aaron G. Mammoser, Bret Friday, and Shawn Hervey-Jumper. "Delivering Equitable Care to Underserved Neuro-oncology Populations." American Society of Clinical Oncology Educational Book, no. 41 (March 2021): 38–46. http://dx.doi.org/10.1200/edbk_320803.
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It is widely recognized that subspecialized multidisciplinary care improves neuro-oncology outcomes. Optimizing patient outcomes relies on the expertise of the treating physicians, neuroradiology and neuropathology, and supportive services familiar with common neurologic syndromes that occur after brain tumor diagnosis and treatment. Despite an increasing number of providers, patient access to specialized multidisciplinary care and clinical trials remains limited. Barriers to equitable health care exist across the United States, with marginalized communities being impacted disproportionately. Such disparity causes increased morbidity and mortality for patients from backgrounds with various elements of diversity. Limited attention to this inequity has resulted in an incomplete understanding of the spectrum of experiences that patients with neuro-oncologic diseases encounter. Clinical trials represent the highest standard and quality of care in medicine, but inclusion of under-represented and underserved groups consistently lags behind counterpart participants from majority racial and ethnic groups. Through provider education as it pertains to issues from bias and health literacy to increasing clinical trial enrollment and offering opportunities through telemedicine, opportunities for improving access to high-quality neuro-oncologic care are explored.
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Dahiya, Saurabh, Hao Xie, Brian T. Hill, David Peereboom, Glen H. Stevens, Erin Murphy, Samuel Chao, John Suh, and Manmeet S. Ahluwalia. "Primary Central Nervous System Lymphoma in Elderly Patients: Clinical Outcomes and Prognosis." Blood 120, no. 21 (November 16, 2012): 5083. http://dx.doi.org/10.1182/blood.v120.21.5083.5083.
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Abstract Abstract 5083 In this retrospective study, we sought to describe the demographics, diagnoses, management, and outcomes of elderly patients with primary CNS lymphoma (PCNSL) at a single institution. Patients and Methods After obtaining IRB approval, the Cleveland Clinic Brain Tumor and Neuro-Oncology Center's database was used to identify patients with newly diagnosed PCNSL who were older than 60 years between 1986 and 2010. We excluded patients who were HIV positive or had systemic lymphoma. During individual chart review, we confirmed the diagnosis and collected information of patients' demographics, disease presentation, diagnostic procedures, initial and salvage therapy, and clinical outcome. Results A total of 84 patients were older than 60 years of age when they were diagnosed with PCNSL at our institution from 1986 to 2010. The median age was 67. 9 years (range: 60. 3–89. 2 years). The median Karnofsky performance status (KPS) of these patients at the diagnosis was 70 (range: 20–90), which stayed the same at the subsequent disease relapses. The median duration of symptoms was 1. 5 months (range: 0. 1–13 months). The initial treatment regimens included whole brain radiation therapy (WBRT), chemotherapy with or without consolidation WBRT. Five patients (6%) received WBRT alone. 43 patients (51%) received chemotherapy alone. Six patients (7%) received chemotherapy followed by consolidation WBRT. Among the patients who received chemotherapy with or without WBRT, 40 of them (48%) received methotrexate-based therapy; 9 patients (11%) received non-methotrexate-based therapy. Among the patients who received initial treatment, 20 of them (37%) achieved complete response (CR), while 19 patients (35%) had disease progression during the treatment. The median progression free survival (PFS) was 8. 0 months (95% CI 2. 7–22 months). The median overall survival (OS) was 15. 5 months (95% CI 6. 6–38. 5 months). We also compared the benefit of individual initial treatment regimens although the reason of their allocation was not determined. It turned out that patients with chemotherapy followed by consolidation WBRT had significantly higher response rate and longer survival than patients with WBRT alone (Figure 1). Unfortunately, no patient who received WBRT alone achieved CR. In addition, the methotrexate-based chemotherapy offered significantly longer PFS than non-methotrexate-based chemotherapy (P = 0. 0008). In univariate analysis, we evaluated potential prognostic factors such as gender, age, KPS, symptom duration, prior malignancy, year of diagnosis, symptoms, and multiple site involvement for response rate, PFS, and OS. Recursive partitioning analysis identified 70 years as the cutoff point for age and 70 as the cutoff point for KPS. We found that no factors can predict response to therapy. However, younger age, higher KPS, more recent diagnosis, and the presence of ocular symptoms were favorable factors for longer OS. Age is the only favorable prognostic factor for PFS, although higher KPS has a trend (P = 0. 08) toward longer PFS. When these factors were subjected to multivariable analysis, age older than 70 years and KPS less than 70 were the only poor prognostic factors for both OS and PFS. With this information in hand, we divided the patients into three prognostic groups based on the number of poor prognostic factors (Table 1). The median OS and PFS for the group with no poor prognostic factors were 65 months and 24 months, respectively. The median OS and PFS for the group with all poor prognostic factors were 1. 0 month and 0. 6 month, respectively. Conclusions Chemotherapy followed by consolidation WBRT had significantly higher response rate and longer survival than patients with WBRT alone. Age and performance status were the only independent predictor of either PFS or OS. Disclosures: No relevant conflicts of interest to declare.
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Kissoon, Trisha, Jennifer Fisher, and Sridharan Gururangan. "QOLP-11. PSYCHOSOCIAL IMPAIRMENT IN PEDIATRIC NEURO-ONCOLOGY PATIENTS AND THEIR CAREGIVERS." Neuro-Oncology 21, Supplement_6 (November 2019): vi199—vi200. http://dx.doi.org/10.1093/neuonc/noz175.831.
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Abstract BACKGROUND Complex multi-modality treatment for children with brain tumors can cause major distress for patients and caregivers. Active coordination of medical and psychosocial services can improve QoL for affected patients and their caregivers. Few studies have evaluated manifestations of psychosocial distress in pediatric neuro-oncology patients and their caregivers. OBJECTIVE We aim to describe symptoms of psychosocial impairment in children with brain tumors and their caregivers in order to identify possible actionable determinants of psychological wellness. METHODS Children older than 3 years of age diagnosed with a malignant brain tumor receiving care at a large tertiary center and their caregivers underwent psychosocial assessment using the Kessler-10 and the Pediatric Symptoms Checklist. Questionnaires were voluntarily completed at routine visits. Rates of primary outcomes, patient and caregiver distress as defined by the respective scoring scales, were calculated for both groups. Correlation between patient and caregiver distress was evaluated with a Spearman’s Rho calculation. RESULTS A total of 30 patient-caregiver dyads consented to participation and 60 total questionnaires were analyzed. Median patient age was 10 years. 80% of caregivers (N= 24/30) scored high for symptoms of psychological illness on Kessler-10 assessments. Patients exhibited substantial psychosocial impairment in physical (N= 22/30), emotional (N= 18/30), cognitive (N= 12/30), and social (N= 26/30) subdomains of the PSC. There was a significant correlation between clinical manifestations of patient and caregiver psychosocial distress, specifically with regards to symptoms of anxiety (p < 0.05) and depression (p < 0.05). CONCLUSIONS Pediatric neuro-oncology patients and caregivers report considerable levels of psychosocial impairment, particularly in physical, cognitive, emotional, and social function, as well as fatigue and insomnia. The majority of patients and caregivers exhibited coinciding symptoms, suggesting that family-based intervention may improve psychosocial stressors. This hypothesis requires future study to determine optimal timing and methods for intervention.
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Peters, Katherine, Dina Randazzo, Margaret Johnson, Jung-Young Kim, Mallika Patel, and Mary Affronti. "QOLP-24. ENGAGING PATIENTS AND CAREGIVERS TO IMPROVE THE IMPORTANCE AND QUALITY OF SUPPORTIVE CARE RESEARCH IN NEURO-ONCOLOGY." Neuro-Oncology 22, Supplement_2 (November 2020): ii180. http://dx.doi.org/10.1093/neuonc/noaa215.749.
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Abstract BACKGROUND From the time of diagnosis to end of life, patients with primary brain tumors experience challenges to maintain quality of life. While traditional research focuses on clinical trials that involve directly treating cancer, we have designed a specific research committee at our institution that promotes supportive care research to improve patients’ and caregivers’ quality of life. Past research has shown that issues key to patients and caregivers often differ from what researchers and providers might appreciate as important. Incorporating input from brain tumor patients and caregivers is vital to direct the most relevant and necessary supportive care research. METHODS As part of an IRB-approved quality improvement project, we sought the opinions of our supportive care research committee about what are the essential quality of life issues for brain tumor patients and caregivers. We polled our committee before and after a session with patients and caregivers discussing factors relevant to their quality of life. After this patient/caregiver intervention, we used a group discussion and note comparison technique to distill down key elements to advance supportive care research for this population. RESULTS Engagement of the committee included members that were neuro-oncology providers, biostatisticians, and data/regulatory/clinical trial staff. Before the intervention, common themes about key issues for patients and caregivers were comfort, pain management, counteracting side effects, cognitive issues, and financial toxicity. While similar themes emerged after the patient/caregiver intervention, the committee gleaned that aspects of communicating outcomes and support of caregivers were consistently mentioned from the discussion session with patients and caregivers. CONCLUSIONS Opinions of brain tumor patients and caregivers are crucial in driving future direction and relevance of supportive care research in neuro-oncology. Our supportive care research committee will continue to engage patients and caregivers and are planning interventions to improve communication and support for caregivers.
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Norman, Sofya, and Rupa Juthani. "COVD-27. THE COVID-19 PANDEMIC AND NEURO-ONCOLOGICAL PATIENTS." Neuro-Oncology 22, Supplement_2 (November 2020): ii26. http://dx.doi.org/10.1093/neuonc/noaa215.108.
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Abstract INTRODUCTION The Coronavirus disease 2019 (COVID-19) pandemic has uprooted healthcare systems worldwide, disrupting care and increasing dependence on alternative forms of health care delivery. It is yet to be determined how the pandemic affected neuro-oncology patient outcomes, given that the majority of even “elective” neurosurgical oncology procedures are time-sensitive. This study quantifies changes in neuro-oncological care during the height of the pandemic in New York City and investigates patient outcomes in 2020 compared to a historical control. METHODS We performed a retrospective review of patients with brain tumor diagnoses (primary or secondary) who were seen at the Weill Cornell Brain and Spine Center between March 13, 2020 and May 1, 2020. A control cohort from the corresponding time period in 2019 was also reviewed. Alterations in care, including shift from in-person to telehealth, delays in evaluation and intervention, and treatment modifications were evaluated. These variables were analyzed with respect to brain tumor control and mortality. RESULTS 114 patients from 2020 and 171 patients from 2019 were included, with no significant difference in baseline demographics between the groups. There was no significant difference in outcomes between the cohorts, despite significantly more treatment delays (p= 0.0154) and use of telehealth (p< 0.0001) in 2020. For patients treated during the pandemic in 2020, patients who experienced delays in care did not suffer from worse outcomes compared to those without delays. Patients who utilized telehealth visits had significantly more stable tumor control (P = 0.0027), consistent with appropriate use of in-person visits for patients with progression. CONCLUSION Our study showed that use of telehealth and selective alterations in neuro-oncological care during the COVID-19 pandemic did not lead to adverse patient outcomes. This suggests that adaptive physician-led changes during the pandemic were successful and effective. Further studies are needed to evaluate impact on long-term survival.
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Wang, Nancy, Justine Vanessa Cohen, Nathaniel C. Goss, Mia Bertalan, Maura C. Keeley, Daniel P. Cahill, Kevin S. Oh, and Priscilla Kaliopi Brastianos. "The impact of a dedicated multidisciplinary tumor board on care for patients with brain metastases." Journal of Clinical Oncology 37, no. 15_suppl (May 20, 2019): e13585-e13585. http://dx.doi.org/10.1200/jco.2019.37.15_suppl.e13585.
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e13585 Background: Brain metastases are the most common tumors to affect the central nervous system. Treatment options have recently evolved with the use of targeted therapies, immunotherapy, and increased clinical trials availability. We describe our institutional experience with a novel, weekly tumor board dedicated to brain metastases and its impact on treatment decisions and survival. Methods: We conducted a single institution cohort study at a large academic hospital with a dedicated center for CNS metastases. Attendance at tumor board included representatives from neuro-oncology, medical oncology, radiation oncology, neurosurgery, and neuroradiology. We prospectively gathered data on patient demographics, clinical history, and tumor board recommendations. Patients were followed to assess treatment course and survival. The Kaplan Meier method was used to calculate time to progression. Results: A total of 49 patients were presented over 2 months, with 4 patients presented twice. The median age at presentation was 63 yrs with a median ECOG of 1. The primary malignancy was 35% melanoma, 49% lung, 22% breast, the remainder other. Most patients had advanced, heavily pretreated disease: 69% had Stage IV disease at time of tumor board presentation with a median of 2 prior lines of systemic therapy, 73% had multiple brain metastases, 39% had prior surgical resection of brain metastases, and 57% had prior CNS radiation. The tumor board recommended a change in management in 26/53 case presentations: 5 surgery, 8 radiation, 9 medical therapy, 3 clinical trial, and 1 surveillance. Recommendations were followed in all except 4 cases due to patient preference and loss to follow-up. When active therapy was recommended, the median time to start was 7 days. Only 3 patients have died at a median follow-up of 62 days. 9 patients have progressed, with a median time to progression of 57 days. Conclusions: A multidisciplinary brain metastasis tumor board provides unique opportunities in the management of complex brain metastasis patients in an era of rapidly evolving therapeutic options. Additional follow-up is needed to assess long-term outcomes, and comparison to non-tumor board presented patients will be necessary.
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Piil, K., G. Locatelli, S. Laegaard Skovhus, A. Tolver, and M. Jarden. "P08.10.B Family-centred care in neuro-oncology: a longitudinal mixed-methods feasibility study." Neuro-Oncology 24, Supplement_2 (September 1, 2022): ii45. http://dx.doi.org/10.1093/neuonc/noac174.154.
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Abstract Background A diagnosis of a malignant brain tumour represents a fearful event for patients, often followed by severe physical, cognitive, emotional, and psychosocial impairments. In turn, being a family member and an informal caregiver of a person with an oncological disease is also a burdensome experience. Family and network can influence patient outcomes, and family-centred intervention may help both patients and caregivers to face illness-related issues. However, studies aiming at implementing family-centered interventions in patients with high grade glioma (HGG) and their families are scarce. Therefore, this study aims to understand how patients with HGG and their families experienced the course of illness and investigate the impact of family and network consultations (FNCs) on both of them. Material and Methods We adopted a quasi-experimental feasibility study using a longitudinal mixed-methods design. The intervention consisted of three FNCs delivered over a 1-year period. Quantitative data on physical activity level, anxiety, depression, family functioning, perceived nursing support, symptom burden and interference on daily living, caregiver burden and quality of life were collected at four time points. Qualitative data on patients’ and families’ perspectives on the intervention were explored through telephone interviews. Results A total of 21 patients with HGG and 47 family members were included in the study. Patients mean age was 66 years and they were mainly male (86%), married and living with the patient (95%), and retired (54%). Caregivers mean age was 47 years, and they were mainly female (62%), children of the cared person (47%), and employed (55%). The integration of quantitative and qualitative data showed that many variables improved over time (e.g., symptom interference in patients, family functioning in caregivers, quality of life) or remained stable (e.g., anxiety and depression), apart from physical functioning and symptom burden that worsened. Families described FNCs as a valuable strategy to holistically address the needs and concerns of the entire family and to strengthen the family dialogue and union. Conclusion FNCs can be a valuable strategy to implement family-centred care practices. However, advanced nursing competencies are required to provide optimal family-centred care. Plus, the intervention should be personalized and based on the needs of each family.
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Johnson, Margaret, Jennifer Durling, Casey B. Brown, Mustafa Khasraw, Zoey Petitt, Nicole Cort, Eric S. Lipp, et al. "NCOG-43. A RETROSPECTIVE ANALYSIS OF THE IMPACT OF THE COVID-19 INFECTION ON NEURO-ONCOLOGY CARE AND PATIENT OUTCOMES: A TWO-SITE STUDY." Neuro-Oncology 24, Supplement_7 (November 1, 2022): vii206—vii207. http://dx.doi.org/10.1093/neuonc/noac209.794.
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Abstract BACKGROUND COVID-19 radically changed neuro-oncology care. In this retrospective study, we examine the impact of COVID-19 infection on neuro-oncological care and clinical outcomes in two geographically separate populations. METHODS Descriptive statistics compared demographic and clinical history extracted from the medical records of COVID-19 positive patients with primary brain tumors treated between 3/1/2020 and 3/31/2021. All subjects were unvaccinated given our cohort pre-dates the ubiquitous availability of vaccines. Patients were treated at Washington University (WashU) in St. Louis, MO and Duke University in Durham, NC. Each site’s respective institutional review board approved the study, with a data transfer agreement in place. RESULTS We identified 62 total (WashU=13; Duke=49) subjects with positive COVID-19 infection. Patients were predominantly white (85.5%), male (56.5%), with KPS >=70 (82.3%) and never smoked (69.4%). WashU patients tended to be older with grade 4 tumors, but this was not significant. At the time of COVID infection 35.5% of patients were receiving cancer-directed therapy. Notably, 37.1% experienced delayed care due to a COVID-19 diagnosis, most often for scheduled systemic treatment or radiation treatment. A further 37.1% had an ER visit, hospitalization, or ICU stay attributed to COVID-19. Of the 17 patients who died during the study period, 4 deaths were attributed directly to COVID-19 and not to their underlying brain tumor or other cause. Finally, telehealth use differed between sites (84.6% at WashU vs 14.3% at Duke). However, this difference could not be attributed to patient age, performance status, or distance from treating institution. CONCLUSION COVID-19 infection led to treatment delays and death for a subset, but not the majority of neuro-oncology patients. Telehealth use varied between sites and was not associated with commonly held assumptions about patient distance or performance status, suggesting evolving practice norms following telehealth’s introduction. Study limitations include a small sample size
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Hardy, Sara J., Amy S. Nowacki, Mary Bertin, and Robert J. Weil. "Absence of an association between glucose levels and surgical site infections in patients undergoing craniotomies for brain tumors." Journal of Neurosurgery 113, no. 2 (August 2010): 161–66. http://dx.doi.org/10.3171/2010.2.jns09950.
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Object In select patient populations, hyperglycemia has been shown to increase the risk of surgical site infection (SSI), whereas stringent glucose control has improved outcomes. To date, no study has focused on whether SSIs in patients with brain tumors undergoing resection are associated with hyperglycemia. Methods The authors performed a retrospective chart review of patients who underwent a craniotomy after receiving a diagnosis of brain tumor. From 2001 to 2008, 2485 patients underwent a craniotomy for tumor resection at the Brain Tumor & Neuro-Oncology Center at the Cleveland Clinic. Fifty-seven of these patients (2.3%) developed SSIs postoperatively. A matched case-control study design was used, with 57 patients who developed SSIs after craniotomy (cases) matched with 57 patients who did not develop SSIs (controls). The results were analyzed using both univariate and multivariate conditional logistic regression. Results Glucose level was not a significant factor in postoperative SSI (p = 0.83) after adjusting for duration of surgery and adherence to antibiotic prophylaxis. However, duration of surgery was significantly associated with postoperative SSI (p = 0.047). Conclusions For patients who undergo craniotomy for definitive resection of a brain tumor, duration of surgery described more variation in the model to predict SSI than blood glucose levels.
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Snyder, James, Michael Wells, Laila Poisson, Steven Kalkanis, Houtan Noushmehr, and Adam Robin. "INNV-15. CLINICAL DATA THAT MATTERS: A DISTILLATION OF NEURO-ONCOLOGY CLINICAL TRIAL INCLUSION CRITERIA USING MACHINE LEARNING." Neuro-Oncology 21, Supplement_6 (November 2019): vi133. http://dx.doi.org/10.1093/neuonc/noz175.558.
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Abstract INTRODUCTION Neuro-oncologic conditions have dismal outcomes, ineffective treatments, poor access to clinical trials, and variability in care. Clinical trials do not capture a patient’s complete journey and are restricted to select populations. ‘Real-world-evidence’ (RWE) attempts to inform point of care decisions through routine collection of data with a clinical-trial-like rigor. RWE complements existing knowledge through broad patient participation, collection throughout disease course, and creation of large multidimensional datasets “knowledge network of disease” 1,2. RWE implementation is hindered by unstructured data, uncertainty of relevant features, and semantic heterogeneity. Clinical attributes were selected from trial inclusion criteria and prioritized for structuring in clinic notes for abstraction. METHOD We queried Clinicaltrials.gov from 1/1/2018-12/31/2018, refined to North America, recruiting, interventional, and adult. Meningioma, pituitary, glioblastoma, astrocytoma, oligodendroglioma, and ependymoma were chosen based on incidence3. Lymphoma and nerve sheath tumors were omitted. “Brain tumor” and “glioma” were added. ‘K-nearest-neighbor’ tokenization parsed inclusion criteria4. Document term matrix (n-gram) converted text to vectors5. A generative probabilistic model using ‘Latent Dirichlet Allocation’ plotted words into 10 clusters6. Hierarchal clustering was used to compare histology with terms. RESULTS 401 trials parsed into 3676 statements and 4008 keywords. 10 clusters of terms were similarly distributed amongst histologies, suggesting generalizability across tumor types. Cluster revealed 8 categories: 1) Time: enrollment; 2) Performance status: KPS; 3) Testing: mutations, upper limit of normal, routine hematologic laboratory assays; 4) Imaging: extent of surgery; 5) Pregnancy/childbearing; 6) Tumor grade; 7) Treatment history: recurrence, chemotherapy, radiation, time; 8) Informed consent CONCLUSIONS Dissecting the compendium of clinical trials using machine learning can identify general parameters for trial enrollment to guide RWE clinical collection. Using practical definitions of the most germane trial data, specific information can be sought after and defined to improve research quality, maximize research yields and improve patient care whilst minimizing wasted research and clinical endeavors.
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Ardhini, Rahmi, Krisna Tsaniadi Prihastomo, Dion Firli Bramantyo, Dodik Tugasworo, Retnaningsih Retnaningsih, Yovita Andhitara Andhitara, Aditya Kurnianto Kurnianto, and Jethro Budiman. "The Outcome of Surgical and Radiotherapy in Central Neurocytoma: A Case Report." Medica Hospitalia : Journal of Clinical Medicine 9, no. 3 (November 30, 2022): 373–77. http://dx.doi.org/10.36408/mhjcm.v9i3.554.
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BACKGROUND: Central neurocytoma (CN) is an infrequent and non-malignant neuro-epithelial tumor. CN is mostly found in lateral ventricle and may generate obstructive hydrocephalus. Surgical-radiation can increase patient survival and prognosis. This case report presented a rare case about 30-year-old female with CN. CASE PRESENTATION: 30-year-old female came to the hospital with severe headache and vomiting. Brain MRI showed a heterogeneous mass in right lateral ventricle causing obstructive hydrocephalus. The patient undergone partial resection. CN confirmed from histopathological analysis. Afterward, patient received 54 Gy conventional radiotherapy. 3 months after radiation, patient remain asymptomatic and no neurological deficit. Brain MRI evaluation showed slightly reduction of tumor mass (from 4,09 x 3,01 x 4,13 cm before radiation to 4,00 x 3,86 x 3,63 cm after radiation). DISCUSSION: This case report was consistent clinically, radiologically, and histopathologically with intraventricular CN. Headache and vomiting in patient due to the raised intracranial pressure from tumor mass and obstructive hydrocephalus. Headache is a significant and most frequent symptom in intraventricular tumors, may be caused by traction or compression of the pain-sensitive structures such as meningen and intracranial vasculature. Optimal management of CN still remains controversial due to their rarity. However, surgical management with gross total resection is the gold standard of treatment modality, associated with good prognosis and longer progression-free survival. CONCLUSION: Based on clinical characteristic, radiographic finding and histopathological features; this case was consistent with CN of the lateral ventricle. Surgical as the treatment option followed by radiation has led to good clinical outcome in this patient. KEYWORDS: central neurocytoma, hydrocephalus, neuro-epethelial tumor, radiotherapy
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Odom, Kristin, Brittany Cordeiro, Kathleen Wall, Claudia Chambers, Kelly Mentges, Marta Penas-Prado, Jing Wu, et al. "INNV-26. NCI-CONNECT PROGRAM PROVIDES RESOURCES TO IMPROVE CARE FOR PEOPLE WITH RARE CENTRAL NERVOUS SYSTEM (CNS) TUMORS." Neuro-Oncology 23, Supplement_6 (November 2, 2021): vi110—vi111. http://dx.doi.org/10.1093/neuonc/noab196.437.
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Abstract The National Cancer Institute Comprehensive Oncology Network Evaluating Rare CNS Tumors (NCI-CONNECT) program focuses on improving approaches to care and treatment for 12 rare CNS tumors, each with < 2,000 diagnoses per year. To reach this rare population, the primary objective was to develop a website to share educational resources that provide patients direct access to clinical care and trials. METHODS: The NCI-CONNECT website uses the Drupal platform within NCI’s framework and the content is free to syndicate. A multidisciplinary team developed tumor-specific content in English and Spanish, clinical trial information, and survivorship resources using evidence-based sources. The Central Brain Tumor Registry of the United States provided statistics on incidence and prevalence of rare tumors. Population reach was calculated using Adobe Experience Cloud website analytics. NCI-CONNECT referrals and study participation data were collected prospectively. RESULTS: The English website launched in September 2018 and visits have increased 2,384%. The Spanish website launched in March 2020 and visits have increased 1,137%. From April 2020 to March 2021, top website page views by English page views / Spanish page views / people living with this disease include oligodendroglioma (43,859 / 8,241 / 11,757), ependymoma (31,579 / 12,684 / 13,294), meningioma (30,261 / 19,507 / 2,692), medulloblastoma (28,487 / 9,999 / 3,840), diffuse midline gliomas (23,064 / 3,851 / 6,033), and pineal region tumors (19,939 / 9,973 / 1,297). Referral rates and participation have accelerated – 45% of patients visiting the Neuro-Oncology Clinic at NIH have a rare CNS tumor and 409 patients enrolled in an NCI-CONNECT study. CONCLUSION: Patient-focused websites can provide guidance to those affected by rare cancers outside of in-person health care visits. The NCI-CONNECT website is an educational and clinical resource for patients and families affected by rare CNS tumors and was created to raise awareness and improve patient outcomes.
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Lion, Alex, Saneta Maiko, Csaba Szilagyi, James Slaven, and Christina Puchalski. "QOL-48. INTERDISCIPLINARY SPIRITUAL CARE TRAINING IN PEDIATRIC NEURO-ONCOLOGY." Neuro-Oncology 22, Supplement_3 (December 1, 2020): iii439—iii440. http://dx.doi.org/10.1093/neuonc/noaa222.703.
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Abstract INTRODUCTION Pediatric neuro-oncology requires attention to not only cancer biology and therapeutics, but also to the suffering of the patient. In addressing patient suffering, consensus guidelines direct attention to the spiritual distress and resources of patients and families. A lack of training has been a key barrier to integrating this aspect of health into patient care. METHODS A neuro-oncologist and a chaplain participated in a train the trainer for the Interprofessional Spiritual Care Education Curriculum (ISPEC) through the George Washington University’s Institute for Spirituality and Health. After the train the trainer, the online curriculum was offered to interdepartmental team members, combined with in-person discussion groups, which met weekly for six sessions. A survey was given before and after the training, and Likert scores were analyzed using the Wilcoxon rank-sum non-parametric test. OUTCOMES: 17 interdisciplinary members participated in the training. These members included neuro-oncologists, neuro-surgeons, rehabilitation physicians, nurse practitioners, nurses, physical therapists, music therapists, a child life specialist, a school liaison, and a patient experience specialist. The training resulted in multiple improvements, including increased ability to identify spiritual issues (p=.0278) and increased ability to respond to these issues (p=.0056). CONCLUSION ISPEC addressed a key barrier to providing generalist spiritual care to patients with pediatric brain tumors. Diverse disciplines were represented during the training. With implementation of interdisciplinary spiritual care, outcomes that may be measured in the future include improved quality of life, patient satisfaction, and the resilience of both patients and team members.
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Lona, Andre, Alfansuri Kadri, and Irina Kemala Nasution. "Correlation between Stage and Histopathological Features and Clinical Outcomes in Patients with Glioma Tumors." Open Access Macedonian Journal of Medical Sciences 9, T3 (June 18, 2021): 262–64. http://dx.doi.org/10.3889/oamjms.2021.6296.
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BACKGROUND: Brain tumor incidence continues to increase during the last decade in several countries. Determining the response of intracranial tumors to treatment remains a major challenge in the field of neuro-oncology. Karnofsky Performance Status Scale (KPS) is a widely used method for assessing the functional status of a patient. AIM: This study aims to determine the relationship between stadium and histopathological features with clinical outcomes in patients with glioma tumors. METHODS: This was an observational analytic study with a retrospective approach at the H. Adam Malik General Hospital in Medan from September 2019 to September 2020. The study population was glioma patients. The research sample was 36 subjects taken consecutively. The independent variables of the study were stage and histopathological features, while the dependent variable of the study was KPS. Statistical analysis with Gamma test. RESULTS: Mean age was 38.11 ± 13.86 years. Most subjects were male, amounting to 20 subjects (55.6%). The most common type of glioma tumor was anaplastic astrocytoma, amounting to 8 subjects (22.2%). The highest tumor stage was a high-grade glioma, amounting to 19 subjects (52.8%), and the most histopathological features based on WHO criteria were WHO grade 3, totaling 13 subjects (36.1%). Most KPS is 80–100 with 19 subjects (52.8%). There is a significant correlation between the stage and histopathological features with KPS with a moderate correlation strength (p = 0.036; r = 0.598) (p = 0.024; r = 0.508) CONCLUSION: There is a significant correlation between stage and histopathological features with KPS with moderate correlation strength
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Body, Anjelica, Alayna Ernster, Rebecca Quinones, Phuong Deleyrolle, David Dinh Tran, Maryam Rahman, Deborah Sampson, Jennifer St. Clair, Ashley Parham Ghiaseddin, and Deidre B. Pereira. "Feasibility and acceptability of measuring psychosocial outcomes for primary brain tumor patients and caregivers in a neuro-oncology clinical setting." Journal of Clinical Oncology 40, no. 16_suppl (June 1, 2022): e24131-e24131. http://dx.doi.org/10.1200/jco.2022.40.16_suppl.e24131.
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e24131 Background: A primary brain tumor (PBT) is a distressing diagnosis that impacts the psychosocial well-being of patients and caregivers. Validated questionnaires are useful to assess PBT patient and caregiver psychosocial outcomes. However, it is unknown whether it is feasible to assess these outcomes in a routine clinical setting. This study evaluated the feasibility of assessing psychosocial outcomes for PBT patients and caregivers at the UF Health Neuro-Oncology clinic. Methods: 171 participants (100 PBT patients, 75 with malignant glioma; 71 caregivers) completed a battery of questionnaires to assess psychosocial outcomes during routine clinical appointments. At the end of the battery, a Participant Experience Form (PEF) assessed participant perceptions about the overall experience of completing the battery on a 7-point Likert Scale. Based on criteria from Bowen and colleagues (2009), feasibility and acceptability of assessment procedures were conceptualized and operationalized by assessing: Acceptability (80% of participants will have an average score ≥ 4 on the PEF); Practicality (average time of completion will be < 35 minutes); and Implementation (80% of participants will complete the entire battery). Descriptive statistics were used to assess these outcomes. Results: Patient and caregiver scores of feasibility and acceptability outcomes were as follows: Acceptability (Average PEF score: patients = 5.75 [ SD= 0.95]; caregivers = 5.96 [ SD= 0.83]); Practicality (Average time to complete (minutes): patients = 28.7 [ SD= 11.68]; caregivers = 26.0 [ SD= 12.01]); Implementation (% of participants that completed entire battery: patients = 88.0; caregivers = 84.5). Conclusions: The results indicate that assessing psychosocial outcomes in a routine clinical setting for PBT patients and caregivers was feasible, acceptable, and practical. Future research will use this battery to evaluate longitudinal psychosocial outcomes for this population in a clinical setting.
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Body, Anjelica, Alayna Ernster, Rebecca Quinones, Phuong Deleyrolle, David Dinh Tran, Maryam Rahman, Deborah Sampson, Jennifer St. Clair, Ashley Parham Ghiaseddin, and Deidre B. Pereira. "Feasibility and acceptability of measuring psychosocial outcomes for primary brain tumor patients and caregivers in a neuro-oncology clinical setting." Journal of Clinical Oncology 40, no. 16_suppl (June 1, 2022): e24131-e24131. http://dx.doi.org/10.1200/jco.2022.40.16_suppl.e24131.
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e24131 Background: A primary brain tumor (PBT) is a distressing diagnosis that impacts the psychosocial well-being of patients and caregivers. Validated questionnaires are useful to assess PBT patient and caregiver psychosocial outcomes. However, it is unknown whether it is feasible to assess these outcomes in a routine clinical setting. This study evaluated the feasibility of assessing psychosocial outcomes for PBT patients and caregivers at the UF Health Neuro-Oncology clinic. Methods: 171 participants (100 PBT patients, 75 with malignant glioma; 71 caregivers) completed a battery of questionnaires to assess psychosocial outcomes during routine clinical appointments. At the end of the battery, a Participant Experience Form (PEF) assessed participant perceptions about the overall experience of completing the battery on a 7-point Likert Scale. Based on criteria from Bowen and colleagues (2009), feasibility and acceptability of assessment procedures were conceptualized and operationalized by assessing: Acceptability (80% of participants will have an average score ≥ 4 on the PEF); Practicality (average time of completion will be < 35 minutes); and Implementation (80% of participants will complete the entire battery). Descriptive statistics were used to assess these outcomes. Results: Patient and caregiver scores of feasibility and acceptability outcomes were as follows: Acceptability (Average PEF score: patients = 5.75 [ SD= 0.95]; caregivers = 5.96 [ SD= 0.83]); Practicality (Average time to complete (minutes): patients = 28.7 [ SD= 11.68]; caregivers = 26.0 [ SD= 12.01]); Implementation (% of participants that completed entire battery: patients = 88.0; caregivers = 84.5). Conclusions: The results indicate that assessing psychosocial outcomes in a routine clinical setting for PBT patients and caregivers was feasible, acceptable, and practical. Future research will use this battery to evaluate longitudinal psychosocial outcomes for this population in a clinical setting.
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Jones, David T. W. "SL1 GENETICS OF PEDIATRIC BRAIN TUMORS: RECENT ADVANCES AND FUTURE PERSPECTIVES." Neuro-Oncology Advances 1, Supplement_2 (December 2019): ii1. http://dx.doi.org/10.1093/noajnl/vdz039.001.
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Abstract The last decade has seen a true revolution in our understanding of the oncogenic mechanisms underlying human tumors, brought about by transformative advances in the technologies available to interrogate the (epi)genetic composition of cancer cells. The dynamic pediatric neuro-oncology community has proven to be very agile in adapting to these changes, and has arguably been at the forefront of some of the most exciting new discoveries in tumor biology in recent years. For example, high-throughput genomic sequencing has revealed highly frequent mutations in histone genes in pediatric glioblastoma; highlighted an ever-expanding role for oncogenic gene fusions in multiple pediatric brain tumor types, and also shed light on novel phenotypic patterns such as chromothripsis (dramatic chromosomal shattering) and somatic hypermutation - the latter being a possible marker for response to novel immunotherapeutic approaches. Epigenetic profiling has also identified a role for ‘enhancer hijacking’ (whereby genomic rearrangement brings an active enhancer element in close proximity to a proto-oncogene) in multiple pediatric brain tumors, and is even pointing towards a fundamentally new way in which tumors may be molecularly classified. In coming years, the major challenge will be to harness the power of these discoveries to more accurately diagnose patients and to identify potential therapeutic targets in a more personalized way, so that these major biological advances can also be translated into substantial clinical benefit. Examples such as the dramatic responses observed in childhood brain tumor sufferers to BRAF V600E and NTRK inhibitors demonstrate the promise that such an approach can hold, but it will require a fundamental shift in the way that clinical trials are planned and conducted in order to optimize patient care. This talk will highlight some of the most striking developments in the field, and look at the challenges that remain before these can lead to improved patient outcomes.
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Wang, Nancy, Justine Cohen, Nathaniel Goss, Mia Bertalan, Maura Keeley, Michael Parsons, Brian Nahed, Daniel Cahill, Kevin Oh, and Priscilla Brastianos. "INNV-27. THE IMPACT OF A DEDICATED MULTIDISCIPLINARY TUMOR BOARD ON CARE FOR PATIENTS WITH BRAIN METASTASES." Neuro-Oncology 21, Supplement_6 (November 2019): vi135—vi136. http://dx.doi.org/10.1093/neuonc/noz175.568.
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Abstract Brain metastases (BM) are the most common tumors to affect the central nervous system (CNS). Treatment options have recently evolved with the use of new targeted therapies, immune checkpoint inhibitors, and increased access to clinical trials. We describe our institutional experience with a weekly tumor board dedicated to BM. METHODS We conducted a single-institution cohort study at an academic hospital. Attendance at tumor board included representatives from neuro-oncology, medical oncology, radiation oncology, neurosurgery, neuropsychology, and neuroradiology. We prospectively gathered data on patient demographics, clinical history, and tumor board recommendations. Patients were followed to assess treatment course and survival. The Kaplan Meier method was used to calculate time to progression. RESULTS A total of 49 patients were presented over 2 months. The median age at presentation was 63 yrs with a median ECOG of 1. The primary malignancy was 35% melanoma, 29% lung, 23% breast, the remainder other. Most patients had advanced, heavily pretreated disease: 69% had Stage IV disease with a median of 2 prior lines of systemic therapy, 73% had multiple BM, 39% had prior surgical resection of BM, and 57% had prior CNS radiation. Change in management was recommended in 26/53 case presentations, with active BM-directed therapy (surgery, radiation, systemic therapy) recommended in 25/26 patients. The median time to start active therapy was 7 days. Only 3 patients have died at a median follow-up of 62 days. 9 patients have progressed, with a median time to progression of 57 days. CONCLUSIONS Multidisciplinary BM tumor board provides unique opportunities in the management of complex BM patients in an era of rapidly evolving therapeutic options. Additional follow-up is needed to assess long-term outcomes.
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Wagner, T., E. Jan, S. Bley, R. Cohen, O. Furman, A. Talianski, and L. Zach. "P08.02 Israeli experience with Patient Reported Outcomes (PROs) in the field of neuro oncology - Quality of Life Assessment Metrics (QAM)." Neuro-Oncology 21, Supplement_3 (August 2019): iii37. http://dx.doi.org/10.1093/neuonc/noz126.128.
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Abstract BACKGROUND With the development of personalized medicine, it is necessary to take into consideration PROs, including quality of life (QOL) to adjust the treatment and follow up. Trends of QOL outcomes are of special interest for neuro oncologic patients in the setting of chemo-radiotherapy due to the high incidence of pseudo progression (worse MRI with no tumor progression). There are several QAM in the field of neuro oncology. We used the quality of life questionnaire (QLQ-30) for brain cancer with the QLQ-BN20 supplement, and Functional assessment of chronic illness therapy (FACIT) with the FACT-Br supplement (version 4). We looked at the level of agreement between the two assessment tools for QAM for Israeli patients with different brain tumors. MATERIAL AND METHODS Forty patients were recruited between September 2017 to May 2018 at Sheba Medical Center after local IRB approval. Patients fulfilled the two types of questionnaires at 4 time points: before radiotherapy, with radiotherapy completion, at three months follow up and before another intervention. The difference between the two metrics was measured by t-test and performed by Bland-Altman plot. The association between QAM and MRI after radiotherapy and doctor assessment was measured by Linear regression. RESULTS Forty patients completed 162 questionnaires overall (QLQ-30 and FACIT): 8 patients completed questionnaires at all 4 time points, 7 patients completed questionnaires - 3 times, 6 patients- twice, and 19 patients- once. Three patients didn’t answer FACIT questionnaires and 3 other patients didn’t answer QLQ questionnaires. Patients population included 40% (16/40) with astrocytoma [25% (4/16), 31.2% (5/16), 43.8% (7/16) of them with WHO Grade 2,3,4 respectively], 25% (10/40) with meningioma [60% (6/10), 20% (2/10), and 20% (2/10) of them with WHO Grade 1,2 and 3 respectively], 20% (8/40) with brain metastasis, and other tumors (6/40) consisted 15% of the patient population. We found a significant difference between QAM means of agreement of the two metrics used (p<0.001). There was a significant correlation between QAM and MRI after radiotherapy (p=0.013; R2=0.369 and p=0.025; R2=0.292 for QLQ and FACIT questionnaire, respectively). There was no significant correlation between physician examination and QAM metrics (p=0.880; R2=0.002 and p=0.724; R2=0.009 for QLQ and FACIT questionnaires respectively). CONCLUSION Patients’ evaluation success depends on the appropriate assessment metrics. QLQ questionnaires were a more appropriate tool in our patient population confirmed by MRI assessment compared to physicians’ evaluation. Our study shows a significant difference between two well validated tools. Further research is needed to establish the source of this difference and adjust QAM for neuro oncologic patients accordingly.
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Basu, Gargi D., Thanemozhi G. Natarajan, Szabolcs Szelinger, Candyce M. Bair, Tracey White, Janine R. LoBello, Nathan Garinger, Ahmet Kurdoglu, and Thomas Royce. "Tumor molecular profiling in advanced pediatric brain tumors." Journal of Clinical Oncology 37, no. 15_suppl (May 20, 2019): e21516-e21516. http://dx.doi.org/10.1200/jco.2019.37.15_suppl.e21516.
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e21516 Background: With the advent of high-throughput molecular profiling, clinical outcome in pediatric cancers has greatly improved due to our greater understanding of genetic origin of pediatric cancer, and availability of biomarker specific treatment options. However, pediatric brain tumors continue to be challenging in terms of therapy. The goal of this study was to evaluate the utility of integrative clinical sequencing in pediatric patients with brain tumors. Methods: Targeted exome sequencing of 562 genes in paired tumor-normal DNA was performed on 14 patients and tumor DNA and RNA was sequenced on additional 4 patients. Sequence analysis identified SNVs, indels, copy number events, fusions, alternate transcripts, breakpoints, TMB and MSI status. Clinically, actionable alterations were identified which could be targeted by FDA approved agents or clinical trials. Results: A total of 18 patients (1-17 y.o.) with low grade (n = 5) and high grade (n = 13) brain tumors were profiled. The cohort consisted of a spectrum of GBMs (45%), medulloblastomas (10%) astrocytomas (22%), and other brain tumors (23%). At least one targetable, driver alteration was identified in 83% of all patients, and 92% of high-grade patients had at least one targetable driver event. Targetable mutations were identified in histone and chromatin modifier genes like H3F3A in 3/18 cases (17%), SETD2, ARID1A, PBRM1 in 2/18 cases (11%), activation of PI3K/AKT/mTOR pathway genes in 6/18 cases (33%), DNA repair genes NBN, ATRX and BRCA2 in 3/18 cases (17%); BRAF V600E in 3 high-grade and a KIAA1549/BRAF fusion in a low-grade tumor, activation of cell cycle in 2/18 cases (11%), activation of FGFR pathway with FGFR1/TACC1 fusion and activating mutation in 2/18 cases (11%), activation of PDGFRA in 2/18 samples (11%), TP53 mutations in 4/18 cases (22%). A breakpoint translocation concurrent with LOH of PTCH1 locus was noted in a medulloblastoma patient. High TMB or MSI instability was not observed. Conclusions: Our results underline the importance of clinical sequencing in identifying targetable markers in high- risk brain tumors. Although limited by small sample size, our study highlights the need for ongoing clinical trials to integrate the genomic discoveries leading to better clinical outcomes.
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Panovska, Dena, and Frederik De Smet. "Functional Precision Oncology: The Next Frontier to Improve Glioblastoma Outcome?" International Journal of Molecular Sciences 23, no. 15 (August 3, 2022): 8637. http://dx.doi.org/10.3390/ijms23158637.
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Glioblastoma remains the most malignant and intrinsically resistant brain tumour in adults. Despite intensive research over the past few decades, through which numerous potentially druggable targets have been identified, virtually all clinical trials of the past 20 years have failed to improve the outcome for the vast majority of GBM patients. The observation that small subgroups of patients displayed a therapeutic response across several unsuccessful clinical trials suggests that the GBM patient population probably consists of multiple subgroups that probably all require a distinct therapeutic approach. Due to extensive inter- and intratumoral heterogeneity, assigning the right therapy to each patient remains a major challenge. Classically, bulk genetic profiling would be used to identify suitable therapies, although the success of this approach remains limited due to tumor heterogeneity and the absence of direct relationships between mutations and therapy responses in GBM. An attractive novel strategy aims at implementing methods for functional precision oncology, which refers to the evaluation of treatment efficacies and vulnerabilities of (ex vivo) living tumor cells in a highly personalized way. Such approaches are currently being implemented for other cancer types by providing rapid, translatable information to guide patient-tailored therapeutic selections. In this review, we discuss the current state of the art of transforming technologies, tools and challenges for functional precision oncology and how these could improve therapy selection for GBM patients.
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Levine, Adrian, Liana Nobre, Scott Milos, Anirban Das, Monique Johnson, Ben Laxer, Scott Ryall, Robert Siddaway, Uri Tabori, and Cynthia Hawkins. "IMMU-09. IMMUNOLOGICAL CHARACTERIZATION OF PEDIATRIC BRAIN TUMORS HAS CLINICAL IMPLICATIONS FOR PATIENT MANAGEMENT AND PROGNOSIS." Neuro-Oncology 24, Supplement_7 (November 1, 2022): vii133. http://dx.doi.org/10.1093/neuonc/noac209.507.
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Abstract The tumor immune microenvironment (TIME) is a growing area of interest, however, the extent of immune activation in childhood CNS tumors is unknown. Although immunotherapy has not gained success in most CNS cancers, our group described gliomas with MMRD which exhibit hypermutation and favorable responses to immune checkpoint inhibition (ICI). Therefore, detailed characterization of the CNS TIME is key for the development of novel immunotherapeutic strategies and application of existing ones in childhood brain tumors. We developed a clinical NanoString immune-oncology panel that includes markers reflecting cell types, therapeutic targets, and cellular pathways, as well as the 18-gene tumor inflammation signature (TIS), a biomarker for ICI response. We tested over 500 brain tumors, including 266 low-grade gliomas (LGG), 170 high-grade gliomas (HGG), 91 MMRD tumors, 16 ependymomas, 46 medulloblastomas, and 36 non-tumor brain samples. Overall, ependymomas and medulloblastomas had low levels of inflammation, although SHH medulloblastomas had higher inflammation than other subtypes. IDH-mutant LGG were immunologically cold, while many gliomas with pediatric-LGG mutations had high levels of inflammation, including upregulation of immune checkpoints – indicating that ICI may be an effective strategy. Interestingly, in pediatric-LGG inflammation impacted outcome in tumors with the same genetic alterations. BRAF V600E-mutant LGG exhibiting high TIS had inferior prognosis (p = 0.02), while no such relationship was observed in BRAF-fused tumors. Diffuse midline gliomas had higher inflammation than hemispheric HGG, indicating that these tumors are not immunologically cold, as has been previously reported. In MMRD tumors treated with ICI, high TIS correlated with improved survival and was independent from hypermutation and mutational burden. Furthermore, MMRD gliomas had high expression of several other immune checkpoints including LAG3, suggesting its value as an additional therapeutic target. In summary, characterization of the TIME across pediatric brain tumors provides potential prognostic clues and suggest treatment strategies for further investigation.
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Philtheos, Justine, Aram Abbasian, Brij Karmur, and Alireza Mansouri. "SCIDOT-15. DISRUPTING THE BLOOD-BRAIN BARRIER IN NEURO-ONCOLOGY: INNOVATIONS, ACHIEVEMENTS, AND LESSONS LEARNED FROM CLINICAL TRIALS." Neuro-Oncology 21, Supplement_6 (November 2019): vi274. http://dx.doi.org/10.1093/neuonc/noz175.1151.
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Abstract BACKGROUND The blood-brain barrier (BBB) presents a formidable challenge for the development of effective therapeutics in neuro-oncology. Several strategies for the disruption of the BBB have been investigated in humans. An in-depth analysis of the concepts, design, and outcomes from these trials can provide insight into optimizing strategies for safe, selective, and efficacious BBB disruption for drug delivery. METHODS The clinicaltrials.gov database was searched on June 9th, 2019 using the term blood-brain barrier. Results were screened for studies relevant to neuro-oncology. When available, linked publications were also reviewed for supplemental information. The Pubmed database was also searched for BBB disruption strategies, to identify publications not linked to a trial registry. Details regarding patient eligibility, intervention, comparators, outcomes and other design criteria were extracted. RESULTS Among 288 registered studies, 42 were relevant to neuro-oncology. Drug-based methods predominated (33/42) but there has been a surge in device-based methods with all registrations after 2015. Mannitol was the most common drug-based method (16/33, 5 Phase II), followed by RMP-7 (8/33, 3 Phase II), Ang1005 (7/33, 4 Phase II and one pending Phase III), and Regadenoson (2/33, one Phase 0 and one Phase I). MR-guided focused ultrasound was the most common device-based method (5/9), followed by MR-guide laser ablation (2/9), Sonocloud (1/9), and transcranial magnetic stimulation (1/9). All device studies have been early phase. Most early phase studies focusing on safety and tolerability met objectives. Some Phase II studies showed preliminary efficacy but control arms were lacking. Many Phase II studies have been terminated/suspended. CONCLUSIONS Diverse BBB disruption methods have been investigated and most appear to be safe and tolerable. Advanced phase studies focusing on survival differences have been limited by heterogeneous tumors and lack of control arms. Objective establishment of BBB disruption was limited. Concerted and standardized clinical trial efforts are needed.
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Harutyunyan, Martin, Lilit Sargsyan, Samvel Iskanyan, Lusine Hakobyan, Ruzanna Papyan, Gevorg Tamamyan, Karen Bedirian, et al. "LINC-14. TREATMENT OF PEDIATRIC CNS TUMORS IN ARMENIA. 10 YEARS OF EXPERIENCE IN A 29 YEARS OLD RESOURCE-LIMITED SETTING." Neuro-Oncology 22, Supplement_3 (December 1, 2020): iii381. http://dx.doi.org/10.1093/neuonc/noaa222.449.
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Abstract BACKGROUND Pediatric CNS tumors are the most common solid childhood malignancies with many challenges facing optimal outcome due to multimodality complex therapies, abandonment, and long-term morbidity. In our three-decades young, country the field of neuro-oncology is in its infancy. MATERIALS: The aim of our study is to assess incidence, epidemiology and treatment outcomes of children diagnosed and treated with CNS tumors within the last 10 years (2009–2019) in the Chemotherapy Clinic of “Muratsan” Hospital Complex of Yerevan State Medical University. RESULTS During these periods 20 patients with CNS tumors were treated in our clinic. 13 patients (65%) were diagnosed with medulloblastoma (2 patients were infants), two patients (10%) with optic pathway glioma, and 5 patients each with pilocytic astrocytoma, ATRT, ETANTR, DIPG, and glioblastoma. Five patients (3 patients with medulloblastoma, 1 patient with pilocytic astrocytoma, 1 patient with ATRT) had metastatic disease at the time of diagnosis. Seventeen patients (80%) had undergone surgery, 8 patients with medulloblastoma received chemo-RT with vincristine. Median follow up time was 15.5 months (range 5–94). Twelve patients (60%) are alive without evidence of disease. 5 patients had disease progression and three patients relapsed. From them, 3 patients died. Long-term survivors are mainly standard risk medulloblastoma patients. All medulloblastoma patients were treated according to HIT-MED guidelines. CONCLUSION Here we report about the pediatric brain tumors of one of the main pediatric oncology units in Armenia for a period of 10 years. The numbers are quite small for firm conclusions, but it shows the emerging need for further research.
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Bakhshinyan, D., T. Vijayakumar, B. Manoranjan, N. McFarlane, C. Venugopal, M. Singh, M. Qazi, P. Vora, and S. Singh. "PS1 - 169 Discovering the Treatment Refractory BTIC Population in Group 3 Medulloblastoma through Therapy Adapted Patient-Derived Human Mouse Xenograft (PDX) Model." Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques 43, S4 (October 2016): S10. http://dx.doi.org/10.1017/cjn.2016.357.
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Medulloblastoma (MB), the most common malignant pediatric brain tumor, is categorized into four molecular subgroups. Given the high rate of metastatic dissemination at diagnosis and recurrence in Group 3 MBs, these patients have the worst clinical outcome with a 5-year survivorship of approximately 50%. By adapting the existing COG (Children’s Oncology Group) Protocol for children with newly diagnosed high-risk MB, for treatment of immuno-deficient mice intracranially engrafted with human MB brain tumour initiating cells we aim to identify and characterize the treatment-refractory cell population in Group 3 MBs. Mice were sacrificed at multiple time points during the course of tumor development and therapy: (i) at engraftment; (ii) post-radiation; (iii) post-radiation and chemotherapy; and (iv) at MB recurrence. MB cell populations recovered separately from brains and spines were comprehensively profiled for gene expression analysis, stem cell and molecular features to generate a global, comparative profile of MB cells through therapy. We report a higher expression of CD133, Sox2 and Bmi1 in addition to increased self-renewal capacity following chemoradiotherapy treatment. The enrichment map constructed from global gene expression analysis showed an increase in pathways regulating self-renewal, DNA repair and chemoresistance post-therapy despite the apparent decrease in tumour size and vascularity. Additionally, from gene expression at MB recurrence, we identified a list of genes that negatively correlate with survival in patients diagnosed with Group 3 MB. A differential genomic profile of the “treatment-responsive” tumors against those that fail therapy may contribute to discovery of novel therapeutic approaches for the most aggressive subgroup of MB.