Virtual multi-institutional tumor board: a strategy for personalized diagnoses and management of rare CNS tumors.

PURPOSE: Multidisciplinary tumor boards (MTBs) integrate clinical, molecular, and radiological information and facilitate coordination of neuro-oncology care. During the COVID-19 pandemic, our MTB transitioned to a virtual and multi-institutional format. We hypothesized that this expansion would allow expert review of challenging neuro-oncology cases and contribute to the care of patients with limited access to specialized centers. METHODS: We retrospectively reviewed records from virtual MTBs held between 04/2020-03/2021. Data collected included measures of potential clinical impact, including referrals to observational or therapeutic studies, referrals for specialized neuropathology analysis, and whether molecular findings led to a change in diagnosis and/or guided management suggestions. RESULTS: During 25 meetings, 32 presenters discussed 44 cases. Approximately half (n = 20; 48%) involved a rare central nervous system (CNS) tumor. In 21% (n = 9) the diagnosis was changed or refined based on molecular profiling obtained at the NIH and in 36% (n = 15) molecular findings guided management. Clinical trial suggestions were offered to 31% (n = 13), enrollment in the observational NCI Natural History Study to 21% (n = 9), neuropathology review and molecular testing at the NIH to 17% (n = 7), and all received management suggestions. CONCLUSION: Virtual multi-institutional MTBs enable remote expert review of CNS tumors. We propose them as a strategy to facilitate expert opinions from specialized centers, especially for rare CNS tumors, helping mitigate geographic barriers to patient care and serving as a pre-screening tool for studies. Advanced molecular testing is key to obtaining a precise diagnosis, discovering potentially actionable targets, and guiding management.

Clinical impact of molecular profiling in rare brain tumors.

PURPOSE OF REVIEW: The purpose of this review is to describe the commonly used molecular diagnostics and illustrate the prognostic importance to the more accurate diagnosis that also may uncover therapeutic targets. RECENT FINDINGS: The most recent WHO Classification of Central Nervous System Tumours (2021) lists over 100 distinct tumor types. While traditional histology continues to be an important component, molecular testing is increasingly being incorporated as requisite diagnostic criteria. Specific molecular findings such as co-deletion of the short arm of chromosome 1 (1p) and long arm of chromosome 19 (19q) now define IDH-mutant gliomas as oligodendroglioma. In recent years, DNA methylation profiling has emerged as a dynamic tool with high diagnostic accuracy. The integration of specific genetic (mutations, fusions) and epigenetic (CpG methylation) alterations has led to diagnostic refinement and the discovery of rare brain tumor types with distinct clinical outcomes. Molecular profiling is anticipated to play an increasing role in routine surgical neuropathology, although costs, access, and logistical concerns remain challenging. SUMMARY: This review summarizes the current state of molecular testing in neuro-oncology highlighting commonly used and developing technologies, while also providing examples of new tumor types/subtypes that have emerged as a result of improved diagnostic precision.

Capturing evolving definitions of 12 select rare CNS tumors: a timely report from CBTRUS and NCI-CONNECT.

PURPOSE: Incidence, prevalence, and survival are population-based statistics describing cancer burden. The National Cancer Institute's (NCI) Comprehensive Oncology Network Evaluating Rare CNS Tumors (NCI-CONNECT) specializes in tumor biology and outcomes for 12 rare CNS tumor types selected for their importance in adults, research interest, or potential for targeted treatment. The aim of this study was to update incidence, prevalence, and survival statistics for these tumors. METHODS: The Central Brain Tumor Registry of the United States (CBTRUS) database, a combined dataset of Centers for Disease Control and Prevention's (CDC) National Program of Cancer Registries (NPCR) and NCI's Surveillance, Epidemiology and End Results (SEER) data, was used to calculate average annual age-adjusted incidence rates (AAAIR) per 100,000 population overall and by sex, race-ethnicity, and age for diagnosis years 2008-2019. Incidence time trends were calculated for diagnosis years 2004-2019. NPCR data were used to calculate relative survival rates. Point prevalence on December 31, 2019 was estimated using annual age-specific incidence and survival. RESULTS: AAAIR was 1.47 per 100,000 for these tumors combined, with highest incidence in ependymomas (AAAIR = 0.41/100,000). Most tumor types were more common in males, adults (ages 40 + years) or children (ages < 15 years), and non-Hispanic White individuals. Ependymomas were the most prevalent tumor type (19,320 cases) followed by oligodendrogliomas (14,900 cases). Ependymomas had the highest five-year survival (90.6%) and primary CNS sarcomas the lowest (7.7%). CONCLUSIONS: These data provide means to measure the impact of clinical care and evaluate new therapies and the evolving histopathology definitions in rare CNS tumor types.

Feasibility of a virtual reality intervention targeting distress and anxiety symptoms in patients with primary brain tumors: Interim analysis of a phase 2 clinical trial.

PURPOSE: Cancer patients experience distress and anxiety when undergoing imaging studies to monitor disease status, yet these symptoms are not always appropriately identified or well-managed. This interim analysis of a phase 2 clinical trial explored feasibility and acceptability of a virtual reality relaxation (VR) intervention for primary brain tumor (PBT) patients at the time of clinical evaluation. METHODS: English speaking, adult PBT patients with previous reports of distress and upcoming neuroimaging were recruited between March of 2021 and March 2022. A brief VR session was done within 2 weeks prior to neuroimaging with patient-reported outcomes (PROs) collected before and immediately post-intervention. Self-directed VR use over the next 1 month was encouraged with additional PROs assessments at 1 and 4 weeks. Feasibility metrics included enrollment, eligibility, attrition, and device-related adverse effects with satisfaction measured with qualitative phone interviews. RESULTS: Fifty-five patients were approached via email, 40 (73%) responded and 20 (50%) enrolled (9 declines, 11 screen fails). 65% of participants were ≤ 50 years, 50% were male, 90% were White/non-Hispanic, 85% had good KPS (≥ 90), and most were on active treatment. All patients completed the VR intervention, PROs questionnaires, weekly check-ins, and qualitative interview. Most (90%) reported frequent VR use and high satisfaction and only 7 mild AEs were recorded (headache, dizziness, nausea, neck pain). CONCLUSION: This interim analysis supports feasibility and acceptability of a novel VR intervention to target psychological symptoms for PBT patients. Trial enrollment will continue to assess for intervention efficacy. TRIAL REGISTRATION: NCT04301089 registered on 3/9/2020.

Terminal deoxynucleotidyl transferase-mediated formation of protein binding polynucleotides.

Terminal deoxynucleotidyl transferase (TdT) enzyme plays an integral part in the V(D)J recombination, allowing for the huge diversity in expression of immunoglobulins and T-cell receptors within lymphocytes, through their unique ability to incorporate single nucleotides into oligonucleotides without the need of a template. The role played by TdT in lymphocytes precursors found in early vertebrates is not known. In this paper, we demonstrated a new screening method that utilises TdT to form libraries of variable sized (vsDNA) libraries of polynucleotides that displayed binding towards protein targets. The extent of binding and size distribution of each vsDNA library towards their respective protein target can be controlled through the alteration of different reaction conditions such as time of reaction, nucleotide ratio and initiator concentration raising the possibility for the rational design of aptamers prior to screening. The new approach, allows for the screening of aptamers based on size as well as sequence in a single round, which minimises PCR bias. We converted the protein bound sequences to dsDNA using rapid amplification of variable ends assays (RAVE) and sequenced them using next generation sequencing. The resultant aptamers demonstrated low nanomolar binding and high selectivity towards their respective targets.

Phage amplification coupled with loop-mediated isothermal amplification (PA-LAMP) for same-day detection of viable Salmonella Enteritidis in raw poultry meat.

Salmonella Enteritidis is the main serotype responsible for human salmonellosis in the European Union. One of the main sources of Salmonella spp. in the food chain are poultry products, such as eggs or chicken meat. In recent years, molecular methods have become an alternative to culture dependent methods for the rapid screening of Salmonella spp. In this work, the strain S. Enteritidis S1400, and previously isolated and characterized bacteriophage PVP-SE2, were used to develop and evaluate a same-day detection method combining Phage Amplification and Loop-mediated isothermal amplification (PA-LAMP) to specifically detect viable S. Enteritidis in chicken breast. This method is based on the detection of the phage DNA rather than bacterial DNA. The virus is added to the sample during pre-enrichment in buffered peptone water, where it replicates in the presence of viable S. Enteritidis. The detection of phage DNA allows, on the one hand to detect viable bacteria, since viruses only replicate in them, and on the other hand to increase the sensitivity of the method since for each infected S. Enteritidis cell, hundreds of new viruses are produced. Two different PA-LAMP detection strategies were evaluated, a real time fluorescence and a naked-eye detection. The present method could down to 0.2 fg/µL of pure phage DNA and a concentration of viral particles of 2.2 log PFU/mL. After a short Salmonella recovery step of 3 h and a co-culture of 4 h of the samples with phage particles, both real-time fluorescence and naked-eye method showed a LoD95 of 6.6 CFU/25 g and a LoD50 of 1.5/25 g in spiked chicken breast samples. The entire detection process, including DNA extraction and LAMP analysis, can be completed in around 8 h. In the current proof-of-concept, the novel PA-LAMP obtained comparable results to those of the reference method ISO 6579, to detect Salmonella Enteritidis in poultry meat.

Dual colorimetric strategy for specific DNA detection by nicking endonuclease-assisted gold nanoparticle signal amplification.

The continuous spread of invasive alien species, as zebra mussel (Dreissena polymorpha), is a major global concern and it is urgent to stop it. Early stages of an invasion are crucial and challenging; however, detection tools based on environmental DNA analysis are promising alternatives. We present an alternative DNA target amplification strategy for signal enhancement followed by dual-mode colorimetric naked eye and optical smartphone analysis for the early detection of zebra mussel environmental DNA. Target amplification was designed based on the nicking endonuclease probe cleavage upon probe and complementary target hybridization. The cleaved/intact probe interacts with DNA-modified nanoparticles for colorimetric detection. We have demonstrated that enzyme amplification strategy enhanced 12-fold the sensitivity by naked eye detection, achieving a detection limit of ~8 nM (4.48×1010 copies) in controlled conditions, whereas target in complex environmental samples allowed the detection of 22.5 nM (1.26×1011 copies). Competitive assays also showed that the system can discriminate specific zebra mussel DNA sequences from other DNA sequences. Additionally, smartphone analysis for DNA quantification further improved the sensitivity of its detection by 130-fold, more than 2 orders of magnitude, when applied to environmental samples. The limit of detection to 0.17 nM (9.52×108 copies) is based on RGB coordinates, which is especially relevant to monitor early aggregation stages, being more accurate and reducing naked eye detection subjectivity. DNA extracted from zebra mussel meat, zebra mussel contaminated river water, and non-contaminated river water samples were successfully tested. Dual-mode colorimetric detection is useful in field analysis without the need for expensive laboratory equipment.

Dual-Mode Gold Nanoparticle-Based Method for Early Detection of Acanthamoeba.

Acanthamoeba keratitis is an aggressive and rapidly progressing ocular pathology whose main risk factor is the use of contact lenses. An early and differential diagnosis is considered the main factor to prevent the progression and improve the prognosis of the pathology. However, current diagnosis techniques require time, complex and costly materials making an early diagnosis challenging. Thus, there is a need for fast, accessible, and accurate methods for Acanthamoeba detection by practitioners for timely and suitable treatment and even for contact lens user as preventive diagnosis. Here, we developed a dual-mode colorimetric-based method for fast, visual, and accurate detection of Acanthamoeba using gold nanoparticles (AuNPs). For this strategy, AuNPs were functionalized with thiolated probes and the presence of target Acanthamoeba genomic sequences, produce a colorimetric change from red to purple. This approach allows the detection of 0.02 and 0.009 µM of the unamplified Acanthamoeba genome by the naked eye in less than 20 min and by color analysis using a smartphone. Additionally, real samples were successfully analyzed showing the potential of the technology considering the lack of point-of-care tools that are mostly needed.

Naked-eye detection strategies coupled with isothermal nucleic acid amplification techniques for the detection of human pathogens.

Nucleic acid amplification-based techniques have gained acceptance by the scientific, and general, community as reference methodologies for many different applications. Since the development of the gold standard of these techniques, polymerase chain reaction (PCR), back in the 1980s many improvements have been made, and alternative techniques emerged reporting improvements over PCR. Among these, isothermal amplification approaches resulted of particular interest as could overcome the need of specialized equipment to accurately control temperature changes, but it was after year 2000 that these techniques have flourished in a huge number of novel alternatives with many different degrees of complexities and requirements. An added value is their possibility to be combined with many different naked-eye detection strategies, simplifying the resources needed, allowing to reduce cost, and serving as the basis for novel developments of lab-on-chip systems, and miniaturized devices, for point-of-care testing. In this review, we will go over different types of naked-eye detection strategies, combined with isothermal amplification. This will provide the readers up-to-date information for them to select the most appropriate strategies depending on the particular needs and resources for their experimental setup.

The Protein-Templated Synthesis of Enzyme-Generated Aptamers.

Inspired by the chemical synthesis of molecularly imprinted polymers, we demonstrated for the first time, the protein-target mediated synthesis of enzyme-generated aptamers (EGAs). We prepared pre-polymerisation mixtures containing different ratios of nucleotides, an initiator sequence and protein template and incubated each mixture with terminal deoxynucleotidyl transferase (TdT). Upon purification and rebinding of the EGAs against the target, we observed an enhancement in binding of templated-EGAs towards the target compared to a non-templated control. These results demonstrate the presence of two primary mechanisms for the formation of EGAs, namely, the binding of random sequences to the target as observed in systematic evolution of ligands by exponential enrichment (SELEX) and the dynamic competition between TdT enzyme and the target protein for binding of EGAs during synthesis. The latter mechanism serves to increase the stringency of EGA-based screening and represents a new way to develop aptamers that relies on rational design.

Independently validated sex-specific nomograms for predicting survival in patients with newly diagnosed glioblastoma: NRG Oncology RTOG 0525 and 0825.

BACKGROUND/PURPOSE: Glioblastoma (GBM) is the most common primary malignant brain tumor. Sex has been shown to be an important prognostic factor for GBM. The purpose of this study was to develop and independently validate sex-specific nomograms for estimation of individualized GBM survival probabilities using data from 2 independent NRG Oncology clinical trials. METHODS: This analysis included information on 752 (NRG/RTOG 0525) and 599 (NRG/RTOG 0825) patients with newly diagnosed GBM. The Cox proportional hazard models by sex were developed using NRG/RTOG 0525 and significant variables were identified using a backward selection procedure. The final selected models by sex were then independently validated using NRG/RTOG 0825. RESULTS: Final nomograms were built by sex. Age at diagnosis, KPS, MGMT promoter methylation and location of tumor were common significant predictors of survival for both sexes. For both sexes, tumors in the frontal lobes had significantly better survival than tumors of multiple sites. Extent of resection, and use of corticosteroids were significant predictors of survival for males. CONCLUSIONS: A sex specific nomogram that assesses individualized survival probabilities (6-, 12- and 24-months) for patients with GBM could be more useful than estimation of overall survival as there are factors that differ between males and females. A user friendly online application can be found here- https://npatilshinyappcalculator.shinyapps.io/SexDifferencesInGBM/ .

Amplified plasmonic and microfluidic setup for DNA monitoring.

Plasmonic nanosensors for label-free detection of DNA require excellent sensing resolution, which is crucial when monitoring short DNA sequences, as these induce tiny peak shifts, compared to large biomolecules. We report a versatile and simple strategy for plasmonic sensor signal enhancement by assembling multiple (four) plasmonic sensors in series. This approach provided a fourfold signal enhancement, increased signal-to-noise ratio, and improved sensitivity for DNA detection. The response of multiple sensors based on AuNSpheres was also compared with  AuNRods, the latter showing better sensing resolution. The amplification system based on AuNR was integrated into  a microfluidic sequential injection platform and applied to the monitoring of DNA, specifically from environmental invasive species-zebra mussels. DNA from zebra mussels was log concentration-dependent from 1 to 1 × 106 pM, reaching a detection limit of 2.0 pM. In situ tests were also successfully applied to real samples, within less than 45 min, using DNA extracted from zebra mussel meat. The plasmonic nanosensors' signal can be used as a binary output (yes/no) to assess the presence of those invasive species. Even though these genosensors were applied to the monitoring of DNA in environmental samples, they potentially offer advantage in a wide range of fields, such as disease diagnostics.

Proposed Additions to the NCCN Guidelines for Adult Medulloblastoma.

Medulloblastoma is a rare brain tumor that occurs in both children and adults, with patients aged 15 to 39 years accounting for 30% of all cases. In adults, guidelines for diagnosis and treatment are often based on retrospective data and extrapolated from the pediatric experience due to limited availability of prospective trials or registries involving adults. Importantly, adult patients differ from pediatric patients in many aspects, including the molecular features of the tumor and tolerance to treatment. In 2017, the NCI was granted support from the Cancer Moonshot initiative to address the challenges and unmet needs of adults with rare central nervous system (CNS) tumors through the NCI Comprehensive Oncology Network for Evaluating Rare CNS Tumors (NCI-CONNECT). On November 25, 2019, NCI-CONNECT convened a multidisciplinary workshop on adult medulloblastoma. Working groups identified unmet needs in clinical care and research and developed specific action items, including a proposal for inclusion of new items in the NCCN Guidelines for Adult Medulloblastoma, delineated in this review along with the evidence supporting their incorporation. Recommendations included facilitating referral of patients to centers of excellence; promoting patient participation in clinical trials or registries; encouraging use of DNA methylation for confirmation of diagnosis and subgrouping; offering counseling on contraception and fertility preservation; evaluating patients for symptoms and medical management of endocrine, vision, hearing, and neurocognitive deficits; providing psychosocial support and referral to neurorehabilitation; minimizing delays in therapy; and incorporating imaging standards and criteria for progression.

The prevalence of altered body image in patients with primary brain tumors: an understudied population.

PURPOSE: Body image (BI) is an important issue for cancer patients, as patients with BI concerns are susceptible to depression, anxiety, difficulty coping, and poor quality of life (QoL). While this concern has been documented in patients with other malignancies, no data exists of this QoL issue in patients with primary brain tumors (PBT). METHODS: A cross-sectional survey of 100 PBT patients was conducted on an IRB approved prospective protocol using structured questionnaires. Participants completed the body image scale (BIS), Appearance Scheme Inventory Revised (ASI-R), MD Anderson Symptom Inventory Brain Tumor (MDASI-BT), and Patient-Reported Outcomes Measurement Information System (PROMIS) Depression, Anxiety, and Psychosocial Impact Positive measures. RESULTS: The prevalence of clinically significant body image dissatisfaction (BIS ≥ 10) was 28% (95% CI 19-37%), median BIS score was 5 (range 0-27). The median ASI-R composite score was 2.9 (range 1.5-4.7). BIS was significantly correlated with the ASI-R (r = 0.53, 95% CI 0.37 to 0.65). The mean PROMIS Depression score was 48.4 (SD = 8.9), PROMIS Anxiety score was 49.4 (SD = 9.9), and PROMIS Psychosocial Illness Impact Positive score was 48.9 (SD = 9.7). BIS was significantly correlated with age, and trended with BMI and sex. The PROMIS Psychosocial Illness Impact Positive and PROMIS Anxiety scores were the most strongly related to BIS. CONCLUSIONS: This study, the first to explore altered body image in PBT patients, revealed clinically significant body image dissatisfaction in nearly 1/3 of patients, similar to other malignancies. These findings underscore the potential contribution of disease and treatment-related body image concerns on psychosocial wellbeing in patients with PBT.

Comparative study of multiplex real-time recombinase polymerase amplification and ISO 11290-1 methods for the detection of Listeria monocytogenes in dairy products.

Dairy products have been implicated in foodborne infections caused by different bacterial pathogens. Among them, Listeria monocytogenes is of particular concern due to its ubiquity, resistance to sanitation processes and high mortality rates resulting from infection. These issues make the development of novel methods for the rapid detection of this bacterium of high interest. The evaluation of a novel multiplex real-time Recombinase Polymerase Amplification method including an internal amplification control is reported in the present work. The method performance was compared to that of the European reference method (ISO 11290-1) for the detection of the species in samples from 40 commercial products, including 14 UHT milk samples, 16 hard cheese samples, 6 infant dairy preparation samples and 4 fresh cheese samples. A limit of detection below 10 cfu/25 g or mL sample was achieved, and values higher than 90% were obtained for relative sensitivity, specificity, accuracy, positive and negative predictive values and the index (kappa) of concordance. Analysis was achieved within one working day, compared to the six days required using the ISO method. Moreover, slight modification of the ISO 11290-1 method to include secondary enrichment in half Fraser broth resulted in the confirmation of all positive samples.

Evaluation and implementation of commercial antibodies for improved nanoparticle-based immunomagnetic separation and real-time PCR for faster detection of Listeria monocytogenes.

L. monocytogenes continues to be a major health issue in Europe, as well as worldwide. Faster methods, not only for detection, but also for sample preparation are of great interest particularly for this slow-growing pathogen. Immunomagnetic separation has been previously reported to be an effective way to concentrate bacteria, and remove inhibitors. In the present study, different commercial antibodies were evaluated to select the most appropriate one, in order to develop a highly specific method. Additionally, magnetic nanoparticles, instead of microparticles, were selected due to their reported advantages (higher surface-volume ration and faster kinetics). Finally, the separation protocol, with a calculated capture efficiency of 95%, was combined with real-time PCR for highly sensitive detection of the concentrated bacteria. The optimized IMS-qPCR allowed to reduce hands-on time in the sample treatment, without affecting the overall performance of the method as a very low limit of detection was still obtained (9.7 CFU/ 25 g) with values for sensitivity, specificity, accuracy, positive and negative predictive values of 100%, resulting in a kappa index of concordance of 1.00. These results were obtained in spiked food samples of different types (chicken, fish, milk, hard and fresh cheese), further demonstrating the applicability of the optimized methodology presented.

Phase 1 lead-in to a phase 2 factorial study of temozolomide plus memantine, mefloquine, and metformin as postradiation adjuvant therapy for newly diagnosed glioblastoma.

BACKGROUND: Repurposed memantine, mefloquine, and metformin have putative anticancer activity. The objective of this phase 1 study was to determine the maximum tolerated doses (MTDs) of combinations of these agents with temozolomide (TMZ). METHODS: Adults with newly diagnosed glioblastoma who completed chemoradiation were eligible. The patients were assigned to receive doublet, triplet, or quadruplet therapy with TMZ combined with mefloquine, memantine, and/or metformin. Dose-limiting toxicities (DLTs) were determined, using a 3 + 3 study design. RESULTS: Of 85 enrolled patients, 4 did not complete cycle 1 (the DLT observation period) for nontoxicity reasons, and 81 were evaluable for DLT. The MTDs for doublet therapy were memantine 20 mg twice daily, mefloquine 250 mg 3 times weekly, and metformin 850 mg twice daily. For triplet therapy, the MTDs were memantine 10 mg twice daily, mefloquine 250 mg 3 times weekly, and metformin 850 mg twice daily. For quadruplet therapy, the MTDs were memantine 10 mg twice daily, mefloquine 250 mg 3 times weekly, and metformin 500 mg twice daily. DLTs included dizziness (memantine) and gastrointestinal effects (metformin). Lymphopenia was the most common adverse event (66%). From study entry, the median survival was 21 months, and the 2-year survival rate was 43%. CONCLUSIONS: Memantine, mefloquine, and metformin can be combined safely with TMZ in patients with newly diagnosed glioblastoma.

Progress in rare central nervous system tumors.

PURPOSE OF REVIEW: Although all primary central nervous system (CNS) tumors are rare, certain tumor types each represent less than 2% of the total and an annual incidence of about 1000 patients or less. Most of them are disproportionally diagnosed in children and young adults, but older adults can also be affected and are rarely recruited to clinical trials. Recent new molecular techniques have led to reclassification of some of these tumors and discovery of actionable molecular alterations. RECENT FINDINGS: We review recent progress in the molecular understanding and therapeutic options of selected rare CNS tumors, with a focus on select clinical trials (temozolomide and lapatinib for recurrent ependymoma; vemurafenib for BRAFV600E-mutated tumors), as well as tumor-agnostic approvals (pembrolizumab, larotrectinib) and their implications for rare CNS tumors. SUMMARY: Although rare CNS tumors are a very small fraction of the total of cancers, they represent a formidable challenge. There is a need for dedicated clinical trials with strong correlative component in patients of all ages with rare CNS tumors. Critical research questions include relevance of the selected target for specific tumor types, persistence of the actionable biomarker at recurrence, blood-brain barrier penetration, and analysis of mechanisms of primary and acquired resistance.

Neurocognitive dysfunction in adult cerebellar medulloblastoma.

OBJECTIVE: Impaired neurocognitive function (NCF) is a well-established consequence of pediatric medulloblastoma (MB) and its treatments. However, the frequency and features of neurocognitive dysfunction in adult-onset MB patients are largely unknown. METHODS: Adult patients (≥ 18 years) with MB who had received formal neurocognitive evaluation (N = 27) were identified. Demographic, medical, and treatment histories were extracted from the medical record. Lesion properties on MRI were analyzed and used to evaluate lesion-symptom mapping further. Demographically adjusted z-scores were calculated for each neurocognitive test and used to assess impairment frequency. Regression analyses were conducted to identify clinical and paraclinical factors associated with impaired NCF. RESULTS: Mean age of the patient sample was 33 years (SD = 11) at the time of MB diagnosis. Prior therapy included surgical resection (89%), radiation (70%), and chemotherapy (26%). A significant proportion of patients were impaired on tests of verbal learning and memory (32%), executive function (29%), and naming (18%). Age, education, lesion size, time from surgery, and number of chemotherapy cycles had the greatest contribution to test performance in random-forest regression models. CONCLUSION: This study identifies frequent impairment of NCF in adult patients with MB, particularly in the domains of learning and memory and executive function. Neurocognitive impairment is influenced by patients' demographic, disease, and treatment history. Further study is warranted to characterize the clinical impact of adult MB more fully.

Patients' and physicians' interpretation of chemotherapy-induced peripheral neurotoxicity.

To test if and how chemotherapy-induced peripheral neurotoxicity (CIPN) is perceived differently by patients and physicians, making assessment and interpretation challenging. We performed a secondary analysis of the CI-PeriNomS study which included 281 patients with stable CIPN. We tested: (a) the association between patients' perception of activity limitation in performing eight common tasks and neurological impairment and (b) how the responses to questions related to these daily activities are interpreted by the treating oncologist. To achieve this, we compared patients' perception of their activity limitation with neurological assessment and the oncologists' blind interpretation. Distribution of the scores attributed by oncologists to each daily life maximum limitation ("impossible") generated three groups: Group 1 included limitations oncologists attributed mainly to motor impairment; Group 2 ones mainly attributed to sensory impairment and Group 3 ones with uncertain motor and sensory impairment. Only a subset of questions showed a significant trend between severity in subjective limitation, reported by patients, and neurological impairment. In Group 1, neurological examination confirmed motor impairment in only 51%-65% of patients; 76%-78% of them also had vibration perception impairment. In Group 2, sensory impairment ranged from 84% to 100%; some degree of motor impairment occurred in 43%-56% of them. In Group 3 strength reduction was observed in 49%-50% and sensory perception was altered in up to 82%. Interpretation provided by the panel of experienced oncologists was inconsistent with the neurological impairment. These observations highlight the need of a core set of outcome measures for future CIPN trials.