Translation and Validation of the Neurologic Assessment in Neuro-Oncology Scale into Indonesian (NANO-Ina).

BACKGROUND The Neurological Assessment in Neuro-Oncology (NANO) scale is a tool used to objectively assess nine clinically relevant domains of neurological function in patients with brain tumors to complement radiographic assessment and other clinician and patient-reported outcomes. Virtual visits for brain tumor patients are feasible and can improve clinical trial access for patients. The use of NANO in virtual care has not been validated, and we aim to determine whether a virtual NANO (vNANO) assessment is a feasible and reproducible alternative to in-person NANO for patients with glioblastoma. METHODS The study is a single-centre prospective study designed to evaluate and validate a modified NANO assessment for virtual visits. Instructions for the vNANO assessment were formulated and verified by 4 different neurologists including 3 neuro-oncologists and 1 expert in virtual neurological care. As part of the study design, a virtual visit is scheduled within one week of the routine standard of care in-person clinic visit and is done over Zoom for Healthcare. vNANO is performed independently using the vNANO scorecard by two providers sequentially and separately to assess inter-observer variability. Both evaluators are blinded to the MRI results to limit bias. An in-person visit is scheduled within one week of vNANO, and a NANO is performed by the same first provider to assess intra-observer variability. The duration of the virtual and in-person assessments are captured. Patients and clinicians are asked to complete a telehealth satisfaction survey at the end of the in-person visit. The primary endpoints are to demonstrate that 1) an adapted vNANO assessment is feasible and 2) to determine inter- and intra-observer concordance between in-person and vNANO. The secondary endpoint is to assess patient and clinician satisfaction with virtual versus in-person visits. RESULTS Sixty patients with glioblastoma will be enrolled in the study and accrual is ongoing at the time of submission (> 18 years old, English-speaking, KPS > 60). Preliminary results indicate that vNANO is time efficient and feasible with all patients completing the vNANO assessments without significant logistical or technological difficulties to date. CONCLUSION Our study will compare in-person and virtual NANO assessments in glioblastoma patients. If validated, vNANO may be adopted for virtual visits in the context of clinical trials for glioblastoma patients. The study is funded by the Academic Health Science Centre Alternative Funding Plan Innovation Fund.

The Macdonald criteria and the Response Assessment in Neuro-Oncology (RANO) criteria define radiologic parameters to classify therapeutic outcome among patients with malignant glioma and specify that clinical status must be incorporated and prioritized for overall assessment. But neither provides specific parameters to do so. We hypothesized that a standardized metric to measure neurologic function will permit more effective overall response assessment in neuro-oncology. An international group of physicians including neurologists, medical oncologists, radiation oncologists, and neurosurgeons with expertise in neuro-oncology drafted the Neurologic Assessment in Neuro-Oncology (NANO) scale as an objective and quantifiable metric of neurologic function evaluable during a routine office examination. The scale was subsequently tested in a multicenter study to determine its overall reliability, inter-observer variability, and feasibility. The NANO scale is a quantifiable evaluation of 9 relevant neurologic domains based on direct observation and testing conducted during routine office visits. The score defines overall response criteria. A prospective, multinational study noted a >90% inter-observer agreement rate with kappa statistic ranging from 0.35 to 0.83 (fair to almost perfect agreement), and a median assessment time of 4 minutes (interquartile range, 3-5). The NANO scale provides an objective clinician-reported outcome of neurologic function with high inter-observer agreement. It is designed to combine with radiographic assessment to provide an overall assessment of outcome for neuro-oncology patients in clinical trials and in daily practice. Furthermore, it complements existing patient-reported outcomes and cognition testing to combine for a global clinical outcome assessment of well-being among brain tumor patients.

Response assessment in neuro-oncology (RANO) criteria was established to improve the assessment of tumor response and provide guidance on the assessment of response and endpoints in neuro-oncology clinical trials. Neurologic assessment in neuro-oncology (NANO) scale is an instrument used for assessing neurological function objectively and practical in intracranial tumor patients. This study aimed to determine the association between RANO criteria with clinical outcome measured by NANO scale in intracranial tumors patients. There were 36 intracranial tumor patients that were studied in Haji Adam Malik General Hospital Medan. The RANO criteria were obtained by comparing the size of the enhanced lesion using Computed Tomography (CT) scan within an interval of a minimum of four weeks of treatment. NANO scale is a quantifiable evaluation of nine relevant neurologic domains based on examination. The NANO scale included gait, strength, ataxia, sensation, visual fields, facial strength, language, level of consciousness, and behavior as assessed domains from the medical record. We analyzed the correlation between the RANO criteria and NANO scale score using the Spearman correlation test. There were 19 males and 17 females. The mean age was 45.22±9.68 years. There were 20 patients (55.6%) with meningioma, 11 patients (30.6%) with glioma, 3 patients (8.3%) with brain metastase, and 2 patients (5.6%) with craniopharyngioma. The mean NANO scale scores for stable and progressive RANO criteria were 4.29±2.02 and 7.88±2.99, respectively. There was a significant correlation between RANO criteria and NANO scale score in patients with intracranial tumor (r = 0.468; p = 0.004). Patients with stable RANO had lower NANO scale scores indicating better response to treatment and clinical outcome.

Gamma knife treatment is a clinically effective, safe, and cost-effective adjunctive therapy for primary malignant brain tumors. For most brain metastases, radiosurgery is the treatment of choice and will result in effective tumor control in more than 90% of treated tumors.

Development of novel therapies for CNS tumors requires reliable assessment of response and progression. This requirement has been particularly challenging in neuro-oncology for which contrast enhancement serves as an imperfect surrogate for tumor volume and is influenced by agents that affect vascular permeability, such as antiangiogenic therapies. In addition, most tumors have a nonenhancing component that can be difficult to accurately quantify. To improve the response assessment in neuro-oncology and to standardize the criteria that are used for different CNS tumors, the Response Assessment in Neuro-Oncology (RANO) working group was established. This multidisciplinary international working group consists of neuro-oncologists, medical oncologists, neuroradiologists, neurosurgeons, radiation oncologists, neuropsychologists, and experts in clinical outcomes assessments, working in collaboration with government and industry to enhance the interpretation of clinical trials. The RANO working group was originally created to update response criteria for high- and low-grade gliomas and to address such issues as pseudoresponse and nonenhancing tumor progression from antiangiogenic therapies, and pseudoprogression from radiochemotherapy. RANO has expanded to include working groups that are focused on other tumors, including brain metastases, leptomeningeal metastases, spine tumors, pediatric brain tumors, and meningiomas, as well as other clinical trial end points, such as clinical outcomes assessments, seizures, corticosteroid use, and positron emission tomography imaging. In an effort to standardize the measurement of neurologic function for clinical assessment, the Neurologic Assessment in Neuro-Oncology scale was drafted. Born out of a workshop conducted by the Jumpstarting Brain Tumor Drug Development Coalition and the US Food and Drug Administration, a standardized brain tumor imaging protocol now exists to reduce variability and improve reliability. Efforts by RANO have been widely accepted and are increasingly being used in neuro-oncology trials, although additional refinements will be needed.

Tumor.

Introduction: Brain tumors have a low incidence, with only 77,000 new cases reported annually in the United States, there is limited published data on brain tumor epidemiology in Indonesia, particularly in Bali. Therefore, we conducted this study to provide data that can explain the burden of care for adult brain tumors, particularly in Bali. Methods: The study collected secondary data from medical records at Prof. Dr. I.G.N.G. Ngoerah, a tertiary hospital in Bali Province. The sample consisted of adult patients aged 18 years or older who were treated in the neurology emergency department for brain tumors between 2020 and 2022, diagnosed through imaging or histopathological examination. The sample was further divided into primary and metastatic brain tumors. Primary brain tumors were categorized based on the major classification according to the type of cell precursor, while metastatic brain tumors were grouped based on the primary source of the tumor. The collected data were presented descriptively as proportions. Results: A total of 535 subjects were included in the study, out of which 298 (55.7%) had primary brain tumors and the remaining 237 (44.29%) cases were brain metastases. The incidence rate was found to be higher among males (278 cases, 51.96%) than among females (257 cases, 48.03%). The highest incidence rate (31.77%) was observed in the age group of 51 to 60 years. Majority of primary brain tumors were classified as glioma, especially high-grade glioma, accounting for 123 cases (41.27%), followed by meningioma with 94 cases (31.54%) and low-grade glioma with 44 cases (14.76%). The majority of primary brain tumors were located in the supratentorial area, accounting for 259 cases (86.91%). Although rare, the study found a sample of 6 cases (1.76%) with primary brain tumors in both the supratentorial and infratentorial areas, consisting of meningioma, Mesenchymal, non-meningothelial tumors, and hematolymphoid tumors. The majority of patients showed clinical features of headache (68.78%), hemiparesis (51.96%), and cranial nerve palsy (51.96%). Other clinical features noted were seizure (26.72%), loss of consciousness (32.33%), vomiting (11.77%), and visual impairment (8.59%). The study revealed that lung cancer was responsible for 43.88% of brain metastasis cases, making it the most common cancer to metastasize to the brain. Conclusions: Discovering the most common type of brain tumor in emergency departments can be a vital step in understanding the characteristics of brain tumor patients. This study has revealed that primary brain tumors, particularly high-grade gliomas, are the most frequently occurring type of brain tumor in emergency departments. Not only this, but the study also found that metastatic brain tumors most often resulted from lung cancer. These findings are unique to the Indonesian context and thus provide valuable insights into the epidemiology of brain tumors in emergency settings. It is hoped that this study will encourage further research in this area, and ultimately lead to improved care for brain tumor patients in emergency departments Keywords: Brain Tumor, Primary Brain Tumor, Metastatic Brain Tumor.

PURPOSE The neurologic assessment in neuro-oncology (NANO) scale was developed as a standardized metric to objectively measure neurologic function in brain tumor patients to complement radiographic assessment in defining overall outcome. A multicenter, phase 2 study of pembrolizumab with or without bevacizumab in patients with recurrent glioblastoma incorporated the NANO scale as an exploratory endpoint. METHODS Neurologic examination was evaluated at baseline and MRI assessments using the NANO scale until patients came off study. Statistical descriptive data analysis was performed using R (version 3.4.3). Correlation analysis utilized Fisher’s exact test. RESULTS NANO compliance rate was 94% in 80 patients accrued on the study. Of the 80 patients, 7 were missing NANO at baseline visit and were excluded from analysis for NANO response criteria. Fifteen patients did not have end of treatment NANO evaluation. Of 73 patients, 35 (48%) had a normal neurologic examination at baseline by NANO. Strength and language accounted for the majority of changes in neurologic function over the course of study treatment. Eighteen patients (25%) had neurologic progression by NANO, of whom 2 did not have concurrent radiographic progression. Three patients (pembrolizumab plus bevacizumab cohort) had a neurologic response associated with stable disease on MRI. NANO assessment prior to initiation of cycle 3 correlated with RANO response (p=0.011), change in KPS (p=0.002) and dexamethasone requirement (p=0.007) while those with NANO progression at this assessment had worse overall survival (291 vs 324 days), but this trend did not achieve statistical significance (p=0.2). CONCLUSIONS Evaluation of neurologic function by NANO scale was feasible in a multicenter prospective study in patients with GBM with a high compliance rate. The NANO scale objectively tracked stable neurologic function in most patients throughout the trial period and was associated with a trend for survival.

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 outcomes. The scale has been incorporated in clinical trials, 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 glioblastoma. MATERIAL AND METHODS We report on an ongoing multi-center study of prospective NANO score collection to evaluate neurologic function in patients with glioblastoma, seen at Dana-Farber Cancer Institute (DFCI) and Sunnybrook Health Sciences Center (SHSC). Patient demographics, tumor histology, molecular status, treatment history, and progression dates are being captured. NANO score, Karnofsky performance status (KPS) 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 and subgroup analyses will be performed for specific domains of the NANO scale. Statistical analyses including descriptive data analysis and generalized linear models will be performed using R (version 3.4.3). RESULTS Since June 2020, 145 patients have been enrolled in this study across the two sites including 90 (62%) with ≥2 follow-up visits. 129 patients had baseline post-operative NANOs captured, with 45 (35%) patients having no deficits in any NANO domain at baseline. All patients with intact baseline NANO had a KPS of 80 or above. Adaptation to a virtual platform for NANO (vNANO) allowed for improved recruitment and follow-up of patients. Validation of vNANO is being performed in a subset of this population. Our interim analysis will be presented at the 2023 EANO meeting. CONCLUSION Evaluation of neurologic function by NANO is feasible in both an in-person and virtual framework in a prospective multi-center study in patients with glioblastoma. NANO is able to objectively track neurologic function throughout disease course in glioblastoma. Integration of vNANO may allow for reduced clinical visits and improve access to specialized care for patients in geographically remote locations.

A 60-year-old man developed, within a month, right thoracic pain, shortness of breath and weight loss. He had a history of working in a metallurgical company and was exposed to chemical paints. He was admitted into the emergency department and a chest computed tomography revealed a large solid mass at the left superior lung lobe, measuring 80 mm x 40 mm. A biopsy was performed and confirmed the diagnosis of Lung Adenocarcinoma. Cancer staging was performed and revealed liver, bone and brain metastases. The brain magnetic resonance imaging disclosed several metastatic lesions at the right postcentral gyrus, occipital lobes and both cerebellar hemispheres. He underwent whole brain radiation therapy and received five cycles of palliative chemotherapy (carboplatin in combination with paclitaxel, and gemcitabine in combination with cisplatin). A second biopsy was performed at the liver metastasis, to search for possible targeted therapies. The results came positive for Epidermal Growth Factor Receptor (EGFR) exon 19 deletion, and an anti-EGFR was prescribed. The patient was started on Osimertinib, 80 mg once a day. The one year follow up showed great response and good drug tolerance, with an important improvement of muscle strength, asthenia and sensory deficits. The patient became fully ambulatory with a Karnofsky Performance Status Scale score of 90 and on the Neurologic Assessment in Neuro-Oncology Scale a score of 3 out of 23. Imaging studies revealed a smaller number of brain metastatic lesions, with decreased contrast enhancement. Therefore, the patient has had a dramatic response to the targeted therapy, both clinical and imaging. Targeted therapy is a growing field in neuro-oncology, leading us to an era of personalized medicine and tailored treatments, with great improvement in overall survival and quality of life. Unfortunately, in Brazil targeted therapies are still not widely available, due to high costs.

BACKGROUND: In intracranial tumors, glucocorticoids are the main therapy to treat peritumoral edema. Neurologic Assessment in Neuro-Oncology (NANO) score is an instrument that can assess neurological function objectively and practically in patients with intracranial tumors. AIM: This study aims to determine the effect of dexamethasone administration on the NANO score of intracranial tumor patients. METHODS: This study was a pre-experimental study with a pre and post-test design at the H. Adam Malik General Hospital in Medan from March to September 2020. The study population was intracranial tumor patients. The research subject were 37 subjects taken consecutively. Treated with dexamethasone injection, then examined the NANO score before and after receiving dexamethasone injection on days 1, 2, and 3. Statistical analysis with Friedman test. RESULTS: Based on the demographic characteristics of the research subjects, the mean age was 53.29 ± 8.5 years. Most of the research subjects were male (54.1%) while female (45.9%). Most types of intracranial tumors were secondary tumors (59.5%) while primary tumors (40.5%). The significant effect of dexamethasone on NANO score in patients with intracranial tumors (p < 0.001). CONCLUSION: There is an effect of dexamethasone on the NANO score of patients with intracranial tumors.

Safety of Direct-Acting Oral Anticoagulants Versus Enoxaparin in Patients with Primary and Metastatic Brain Tumors

BACKGROUNDThe 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.METHODSWe 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).RESULTSSince 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.CONCLUSIONSEvaluation 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.

Exposure to exogenous alkylating agents, particularly N-nitroso compounds, has been associated with increased incidence of primary human brain tumors, while intrinsic risk factors are currently unknown. The DNA repair protein O6-methylguanine-DNA methyltransferase (MGMT) is a major defense against the carcinogenicity of N-nitroso compounds and other alkylators. We report here that in 55% (64/117) of cases, histologically normal brain tissue adjacent to primary human brain tumors lacked detectable MGMT activity [methyl excision repair-defective (Mer-) status]. The incidence of Mer- status in normal brain tissue from brain tumor patients was age-dependent, increasing from 21% in children 0.25-19 years of age to 75% in adults over 50. In contrast, Mer- status was found in 12% (5/43) of normal brain specimens from patients operated for conditions other than primary brain tumors and was not age-dependent. The 4.6-fold elevation in incidence of Mer- status in brain tumor patients is highly significant (chi2 = 24; p < or = 0.001). MGMT activity was independent of age in the lymphocytes of brain tumor patients and was present in lymphocytes from six of nine tumor patients whose normal brain specimen was Mer-. DNA polymerase beta, apurinic/apyrimidinic endonuclease, and lactate dehydrogenase activities were present in all specimens tested, including Mer- specimens from brain tumor patients. Our data are consistent with a model of carcinogenesis in human brain in which epigenetically regulated lack of MGMT is a predisposing factor and alkylation-related mutagenesis is a driving force.

INTRODUCTION The effectiveness of palliative care for cancer patients has already been widely recognized. However, in Japan, palliative care for brain tumor patients remains in its early stages, and related information is limited. This is because the treatment culture for brain tumors in Japan is unique, with primary brain tumors being treated by neurosurgeons and metastatic brain tumors being treated by the department of the primary tumor, making it difficult to collect comprehensive information on end-of-life care for patients with malignant brain tumors. This study investigated end-of-life care for patients with malignant brain tumors from the perspective of a palliative care unit at a single hospital in Japan. PATIENTS AND METHODS This study included 606 cancer patients who were admitted to the palliative care unit at Tsurumaki Onsen Hospital between January 2020 and December 2024 and received end-of-life care. Information was extracted from medical records and imaging tests, and a retrospective analysis was conducted. RESULTS Of the 606 patients, 71 (11.7%) had malignant brain tumors (primary malignant brain tumors and metastatic brain tumors), of which 16 (2.6%) were primary and 55 (9.1%) were metastatic. Among the 71 cases,21 patients (29.6%) presented with impaired consciousness, and 29 patients (40.8%) were unable to take oral intake. Additionally, 15 patients (2.4%) experienced seizures during hospitalization, and 12 of these were patients with malignant brain tumors. DISCUSSION The incidence of metastatic brain tumors was consistent with previous reports; however, based on the incidence rate, primary brain tumors are also frequently treated. Palliative care for common symptoms such as impaired consciousness and seizures in brain tumor patients is considered an important challenge for all of physicians treat brain tumors. CONCLUSION A Japanese palliative care unit treats more brain tumor patients than anticipated. Smoothening collaboration between neurosurgeons and palliative physicians is essential for optimizing end-of-life care.