Resources for the practice of pediatric neuro-oncology in Mexico: a cross-sectional evaluation.

Background: The evaluation of existing resources and services is key to identify gaps and prioritize interventions to expand care capacity for children with central nervous system (CNS) tumors. We sought to evaluate the resources for pediatric neuro-oncology (PNO) in Mexico. Methods: A cross-sectional online survey with 35 questions was designed to assess PNO resources and services, covering aspects including number of patients, infrastructure, human resources, and diagnostic and treatment time intervals. The survey was distributed to the members of the Mexican Association of Pediatric Oncology and Hematology (AMOHP) who belong to the nation's many different health systems. Results: Responses were obtained from 33 institutions, distributed throughout the country and part of the many health systems that exist in Mexico. Twenty-one (64%) institutions had less than 10 new cases of pediatric CNS tumors per year. Although 30 (91%) institutions saw pediatric patients up to the age of 18 years, 2 (6%) had a cutoff of 15 years. Twenty-four (73%) institutions had between 1 and 3 pediatric oncologists providing care for children with CNS tumors. Six (18%) institutions did not have a neurosurgeon, while 19 (57%) institutions had a pediatric neurosurgeon. All centers had a pathology department, but 13 (39%) institutions only had access to basic histopathology. Eleven (33%) institutions reported histopathological diagnoses within one week, but 3 (9%) took more than 4 weeks. Radiotherapy for pediatric CNS tumors was referred to outside centers at 18 (55%) institutions. All centers had access to conventional cytotoxic chemotherapy, but only 6 (18%) had access to targeted therapy. Eighteen (55%) respondents estimated a survival rate of less than 60%. Fifteen (45%) centers attributed the main cause of mortality to non-tumor related factors, including infection and post-surgical complications. Conclusions: This is the first national assessment of the resources available in Mexico for the treatment of CNS tumors. It shows disparities in resource capacity and a lack of the specific and efficient diagnoses that allow timely initiation of treatment. These data will enable the prioritization of collaborative interventions in the future.

To scan or not to scan? A retrospective cohort study analysing the efficacy of routine post-operative CT after brain biopsy.

PURPOSE: Postoperative management following elective cranial surgery, particularly after biopsy procedures, varies significantly across neurosurgical centres. Routine postoperative head CT scans, traditionally performed to detect complications such as intracranial bleeding or cerebral oedema, lack substantial evidence supporting their necessity. METHODS: This study is a retrospective cohort analysis conducted at a regional neurosurgical department of 236 patients who underwent brain biopsies between 2018 and 2022. Patient data, including demographics, surgical details, and postoperative outcomes, were collected and analysed. The outcomes investigated were the incidence and impact of postoperative CT scans on time to discharge, management changes, and the influence of preoperative anticoagulation. RESULTS: Out of 236 patients, 205 (86.86%) underwent postoperative CT scans. There was no significant relationship between postoperative hematoma, as detected on a CT scan, and neurological deficit (p = 0.443), or between preoperative anticoagulation and postoperative bleeding on CT scans (p = 0.464). Patients who had postoperative CT scans had a significantly longer length of stay (LOS) compared to those who did not (p < 0.001). Intraoperative bleeding was a predictor of hematoma on postoperative CT (p = 0.017) but not of postoperative neurological deficit. The routine postoperative CT scan showed limited predictive value for symptomatic deficits, with a positive predictive value of 6.67% and a negative predictive value of 96.88%. CONCLUSIONS: Routine postoperative CT scans after brain biopsies do not significantly impact management or improve patient outcomes but are associated with longer hospital stays. CT scans should be reserved for patients showing clinical signs of complications rather than used as a routine procedure after a brain biopsy.

Imaging meningioma biology: Machine learning predicts integrated risk score in WHO grade 2/3 meningioma.

Background: Meningiomas are the most common primary brain tumors. While most are benign (WHO grade 1) and have a favorable prognosis, up to one-fourth are classified as higher-grade, falling into WHO grade 2 or 3 categories. Recently, an integrated risk score (IRS) pertaining to tumor biology was developed and its prognostic relevance was validated in a large, multicenter study. We hypothesized imaging data to be reflective of the IRS. Thus, we assessed the potential of a machine learning classifier for its noninvasive prediction using preoperative magnetic resonance imaging (MRI). Methods: In total, 160 WHO grade 2 and 3 meningioma patients from 2 university centers were included in this study. All patients underwent surgery with histopathological workup including methylation analysis. Preoperative MRI scans were automatically segmented, and radiomic parameters were extracted. Using a random forest classifier, 3 machine learning classifiers (1 multiclass classifier for IRS and 2 binary classifiers for low-risk and high-risk prediction, respectively) were developed in a training set (120 patients) and independently tested in a hold-out test set (40 patients). Results: Multiclass IRS classification had a test set area under the curve (AUC) of 0.7, mostly driven by the difficulties in clearly separating medium-risk from high-risk patients. Consequently, a classifier predicting low-risk IRS versus medium-/high-risk showed a very high test accuracy of 90% (AUC 0.88). In particular, "sphericity" was associated with low-risk IRS classification. Conclusion: The IRS, in particular molecular low-risk, can be predicted from imaging data with high accuracy, making this important prognostic classification accessible by imaging.

"Not me!" a qualitative, vignette-based study of nurses' and physicians' reactions to spiritual distress on neuro-oncological units.

PURPOSE: People with primary malignant brain tumors experience serious health-related suffering caused by limited prognosis and high symptom burden. Consequently, neuro-oncological healthcare workers can be affected emotionally in a negative way. The aim of this study was to analyze the attitudes and behavior of nurses and physicians when confronted with spiritual distress in these patients. METHODS: Neurospirit-DE is a qualitative vignette-based, multicenter, cross-sectional online survey that was conducted in Bavaria, Germany. Reflexive thematic analysis was used for data analysis. RESULTS: A total of 143 nurses and physicians working in neurological and neurosurgical wards in 46 hospitals participated in the survey. The participants questioned if the ability to provide spiritual care can be learned or is a natural skill. Spiritual care as a responsibility of the whole team was highlighted, and the staff reflected on the appropriate way of involving spiritual care experts. The main limitations to spiritual care were a lack of time and not viewing spiritual engagement as part of the professional role. Some were able to personally benefit from spiritual conversations with patients, but many participants criticized the perceived emotional burden while expressing the imminent need for specific training and team reflection. CONCLUSIONS: Most neuro-oncological nurses and physicians perceive spiritual care as part of their duty and know how to alleviate the patient's spiritual distress. Nonetheless, validation of spiritual assessment tools for neuro-oncology and standardized documentation of patients' distress, shared interprofessional training, and reflection on the professional and personal challenges faced when confronted with spiritual care in neuro-oncology require further improvement and training.

Translation and validation of the Neurological Assessment in Neuro-Oncology scale to Brazilian Portuguese.

Introduction: The Neurological Assessment for Neuro-Oncology (NANO) scale was elaborated to assess neurologic function in integration with radiological criteria to evaluate neuro-oncological patients in clinical setting and enable the standardization of neurological assessment in clinical trials. The objective of this study is the translation to Brazilian Portuguese and transcultural adaptation of NANO scale in patients with the diagnosis of glioblastoma, brain metastasis and low-grade glioma. Methods: Patients with diagnosis of glioblastoma, brain metastasis, and low-grade glioma were prospectively evaluated between July 2019 and July 2021. The process of translating and cross-culturally adapting the NANO scale included: translation from English to Portuguese, synthesis and initial revision by an expert committee, back-translation from Portuguese to English, a second revision by the expert committee, and the application of the NANO scale. Regarding the reliability of the NANO scale, Cronbach's alpha was employed to measure the internal consistency of all scale items and assess the impact of item deletion. Additionally, Spearman's correlation test was used to evaluate the convergent validity between the NANO scale and Karnofsky Performance Scale (KPS). Results: One hundred and seventy-four patients were evaluated. A statistically significant inverse relation (p < 0.001) between KPS and NANO scale was founded. The Cronbach's alpha values founded for NANO scale were 0.803 for glioblastoma, 0.643 for brain metastasis, and 0.482 for low grade glioma. Discussion: The NANO scale Brazilian Portuguese version proves to be reproducible and valid to evaluate neuro-oncological patients with glioblastoma and brain metastasis, presenting a strong correlation with KPS scale. Further studies are warranted to assess the validity and reliability of the scale in patients diagnosed with low-grade glioma.

A prospective clinical study of the influence of oral protein intake on [18F]FET-PET uptake and test-retest repeatability in glioma.

BACKGROUND: O-(2-[18F]fluoroethyl)-L-tyrosine positron emission tomography ([18F]FET PET) scanning is used in routine clinical management and evaluation of gliomas with a recommended 4 h prior fasting. Knowledge of test-retest variation of [18F]FET PET imaging uptake metrics and the impact of accidental protein intake can be critical for interpretation. The aim of this study was to investigate the repeatability of [18F]FET-PET metrics and to assess the impact of protein-intake prior to [18F]FET PET scanning of gliomas. RESULTS: Test-retest variability in the non-protein group was good with absolute (and relative) upper and lower limits of agreement of + 0.15 and - 0.13 (+ 9.7% and - 9.0%) for mean tumour-to-background ratio (TBRmean), + 0.43 and - 0.28 (+ 19.6% and - 11.8%) for maximal tumour-to-background ratio (TBRmax), and + 2.14 cm3 and - 1.53 ml (+ 219.8% and - 57.3%) for biological tumour volume (BTV). Variation was lower for uptake ratios than for BTV. Protein intake was associated with a 27% increase in the total sum of plasma concentration of the L-type amino acid transporter 1 (LAT1) relevant amino acids and with decreased standardized uptake value (SUV) in both healthy appearing background brain tissue (mean SUV - 25%) and in tumour (maximal SUV - 14%). Oral intake of 24 g of protein 1 h prior to injection of tracer tended to increase variability, but the effects on derived tumour metrics TBRmean and TBRmax were only borderline significant, and changes generally within the variability observed in the group with no protein intake. CONCLUSION: The test-retest repeatability was found to be good, and better for TBRmax and TBRmean than BTV, with the methodological limitation that tumour growth may have influenced results. Oral intake of 24 g of protein one hour before a [18F]FET PET scan decreases uptake of [18F]FET in both tumour and in healthy appearing brain, with no clinically significant difference on the most commonly used tumour metrics.

Recurrent Glioblastoma-Molecular Underpinnings and Evolving Treatment Paradigms.

Glioblastoma is the most common and lethal central nervous system malignancy with a median survival after progression of only 6-9 months. Major biochemical mechanisms implicated in glioblastoma recurrence include aberrant molecular pathways, a recurrence-inducing tumor microenvironment, and epigenetic modifications. Contemporary standard-of-care (surgery, radiation, chemotherapy, and tumor treating fields) helps to control the primary tumor but rarely prevents relapse. Cytoreductive treatment such as surgery has shown benefits in recurrent glioblastoma; however, its use remains controversial. Several innovative treatments are emerging for recurrent glioblastoma, including checkpoint inhibitors, chimeric antigen receptor T cell therapy, oncolytic virotherapy, nanoparticle delivery, laser interstitial thermal therapy, and photodynamic therapy. This review seeks to provide readers with an overview of (1) recent discoveries in the molecular basis of recurrence; (2) the role of surgery in treating recurrence; and (3) novel treatment paradigms emerging for recurrent glioblastoma.

Advancing presurgical non-invasive molecular subgroup prediction in medulloblastoma using artificial intelligence and MRI signatures.

Global investigation of medulloblastoma has been hindered by the widespread inaccessibility of molecular subgroup testing and paucity of data. To bridge this gap, we established an international molecularly characterized database encompassing 934 medulloblastoma patients from thirteen centers across China and the United States. We demonstrate how image-based machine learning strategies have the potential to create an alternative pathway for non-invasive, presurgical, and low-cost molecular subgroup prediction in the clinical management of medulloblastoma. Our robust validation strategies-including cross-validation, external validation, and consecutive validation-demonstrate the model's efficacy as a generalizable molecular diagnosis classifier. The detailed analysis of MRI characteristics replenishes the understanding of medulloblastoma through a nuanced radiographic lens. Additionally, comparisons between East Asia and North America subsets highlight critical management implications. We made this comprehensive dataset, which includes MRI signatures, clinicopathological features, treatment variables, and survival data, publicly available to advance global medulloblastoma research.

Brain tumor surgery guided by navigated transcranial magnetic stimulation mapping for arithmetic calculation.

OBJECTIVE: The onco-functional balance represents the primary goal in neuro-oncology. The increasing use of navigated transcranial magnetic stimulation (nTMS) allows the noninvasive characterization of cortical functional anatomy, and its reliability for motor and language mapping has previously been validated. Calculation and arithmetic processing has not been studied with nTMS so far. In this study, the authors present their preliminary data concerning nTMS calculation. METHODS: The authors designed a monocentric prospective study, adopting an internal protocol to use nTMS for preoperative planning, including arithmetic processing. When awake surgery was possible, according to the patients' conditions, nTMS points were used to guide direct cortical stimulation (DCS), i.e., the gold standard for cortical mapping. Navigated TMS-based tractography was used for surgical planning. Statistical analyses on the nTMS and DCS points were performed. RESULTS: From February 2021 to October 2023, 61 procedures for nTMS calculation mapping were performed. The clinical evaluation, including pre- and postoperative evaluations (3 months after surgery), demonstrated a good clinical outcome with preservation of arithmetic function and recovery (92.8% of patients). Between the awake and asleep surgery groups, the postoperative clinical results were comparable at the 3-month follow-up, with > 90% of the patients achieving improved calculation function. The surgical strategy adopted was aimed at sparing nTMS positive points in asleep procedures, whereas nTMS and DCS positive points were not removed in awake procedures. Overall, 62% of the positive points for calculation functions were exposed by craniotomy and 85% were spared during surgery. None of the patients developed nTMS-related seizures. Diffusion tensor imaging fiber tracking based on nTMS positive points for calculation was used. The white matter fiber tracts involved in calculation functions were the arcuate fasciculus (56%) and frontal aslant tract (22%). When nTMS and DCS points were compared in awake surgery (n = 10 patients), a sensitivity of 31.71%, specificity of 85.76%, positive predictive value of 22.41%, negative predictive value of 90.64%, and accuracy of approximately 69% were achieved. CONCLUSIONS: Based on the authors' preliminary data, nTMS can be an advantageous tool to study cognitive functions, aimed at minimizing neurological impairment. The postoperative clinical outcome for patients who underwent operation with nTMS was very good. Considering these results, nTMS has proved to be a feasible method to map cognitive areas including those for calculation functions. Further analyses are needed to validate these data. Finally, other cognitive functions (e.g., visuospatial) may be explored with nTMS.

"Life Gets Turned Upside-Down " Opportunities to Improve Palliative Care for High-Grade Glioma.

CONTEXT: Early palliative care referral is recommended broadly in oncology. Yet, few patients with high-grade gliomas (HGG) - highly aggressive brain tumors - receive specialty palliative care consultation. OBJECTIVES: To delineate unique needs of HGG patients relative to other oncology patients according to perceptions of a diverse sample of US palliative medicine physicians and neuro-oncologists in each of the eight domains of palliative care; and to describe contrasts between physician specialties on indications for and timing of specialty palliative care referrals in HGG. METHODS: Between September 2021 and May 2023, we conducted semi-structured, 40-minute interviews with ten palliative medicine physicians and ten neuro-oncologists. Participants were recruited via purposive sampling for diversity in geographic setting, years in practice, and practice structure. Interviews were audio-recorded, professionally transcribed, and coded by two investigators. Data were analyzed thematically using a qualitative, phenomenological approach. RESULTS: The palliative care needs of HGG relative to other cancers across palliative care domains are distinguished by poor prognosis, physical and cognitive deficits, and neuropsychiatric symptoms. Themes on indications for palliative care referral differed between neuro-oncologists and palliative physicians. Neuro-oncologists favored selective referral for clinical indications such as high non-neurologic symptom burden requiring time-intensive management. Palliative physicians favored early referral of most HGG patients, to allow for maximal benefit across HGG trajectory. CONCLUSION: Patients with HGG have unique palliative care needs that affect palliative care delivery across care domains. Bidirectional education, enhanced collaboration, and consensus guidelines may help overcome barriers to specialty palliative care referral.

Expertise in surgical neuro-oncology. Results of a survey by the EANS neuro-oncology section.

Introduction: Technical advances and the increasing role of interdisciplinary decision-making may warrant formal definitions of expertise in surgical neuro-oncology. Research question: The EANS Neuro-oncology Section felt that a survey detailing the European neurosurgical perspective on the concept of expertise in surgical neuro-oncology might be helpful. Material and methods: The EANS Neuro-oncology Section panel developed an online survey asking questions regarding criteria for expertise in neuro-oncological surgery and sent it to all individual EANS members. Results: Our questionnaire was completed by 251 respondents (consultants: 80.1%) from 42 countries. 67.7% would accept a lifetime caseload of >200 cases and 86.7% an annual caseload of >50 as evidence of neuro-oncological surgical expertise. A majority felt that surgeons who do not treat children (56.2%), do not have experience with spinal fusion (78.1%) or peripheral nerve tumors (71.7%) may still be considered experts. Majorities believed that expertise requires the use of skull-base approaches (85.8%), intraoperative monitoring (83.4%), awake craniotomies (77.3%), and neuro-endoscopy (75.5%) as well as continuing education of at least 1/year (100.0%), a research background (80.0%) and teaching activities (78.7%), and formal interdisciplinary collaborations (e.g., tumor board: 93.0%). Academic vs. non-academic affiliation, career position, years of neurosurgical experience, country of practice, and primary clinical interest had a minor influence on the respondents' opinions. Discussion and conclusion: Opinions among neurosurgeons regarding the characteristics and features of expertise in neuro-oncology vary surprisingly little. Large majorities favoring certain thresholds and qualitative criteria suggest a consensus definition might be possible.

Surgical treatment of orbital tumors in a single center: Analysis and results.

Background: Orbital tumors, arising within the bony orbit and its contents, present diverse challenges due to their varied origins and complex anatomical context. These tumors, classified as primary, secondary, or metastatic, are further subdivided into intraconal and extraconal based on their relationship with the muscle cone. This classification significantly influences surgical approach and management. This study highlights surgical experiences with orbital tumors, underscoring the importance of tailored surgical approaches based on the lesion's site and its proximity to the optic nerve. Methods: This retrospective study at the National Institute of Cancer's Head and Neck Department (2005-2014) analyzed 29 patients with orbital tumors treated with surgery, radiotherapy, chemotherapy, or combinations of them. Patient demographics, tumor characteristics, and treatment responses were evaluated using computed tomography (CT), magnetic resonance imaging, and positron emission tomography-CT imaging. Malignant tumors often required orbital exenteration and reconstruction, highlighting the study's commitment to advancing orbital tumor treatment. Results: 29 patients (18 females and 11 males, age 18-88 years, mean 53.5 years) with orbital tumors exhibited symptoms such as decreased vision and exophthalmos. Tumors included primary lesions like choroidal melanoma and secondary types like epidermoid carcinoma. Treatments varied, involving a multidisciplinary team for surgical approaches like exenteration, with follow-up from 1 to 9 years. Radiotherapy and chemotherapy were used for specific cases. Conclusion: Our study underscores the need for a multidisciplinary approach in treating orbital tumors, involving various surgical specialists and advanced technologies like neuronavigation for tailored treatment. The integration of surgery with radiotherapy and chemotherapy highlights the effectiveness of multidimensional treatment strategies.

A neuropsychological profile for high-grade primary central nervous system neuroendocrine tumor (CNS NET): a single-case study.

Objective: Neuroendocrine tumors (NETs) are neoplasms that primarily occur in the lungs, appendix, small intestine, pancreas, and rectum, and typically metastasize to the liver or lymph nodes. However, in rare cases NETs can originate in the central nervous system (CNS). Understanding primary CNS NET neuropsychological manifestations aids in recommendations for neurocognitive follow-up, treatment and lifestyle planning, and future research. Method: Given the dearth of neuropsychological research for CNS NETs, we present a case seen in a 43-year-old woman. Results: Initial and 8-month follow-up neuropsychological evaluations of the patient revealed a Major Neurocognitive Disorder where the pattern of findings was consistent with tumor location and additional treatment-related factors. Reliable change indices at her re-evaluation revealed declines in verbal and visual memory, with statistical, yet not clinical, improvements in different domains. Follow-up monitoring of comprehensive care continued to occur after neuropsychological evaluations. Conclusions: This case study assists in the characterization of initial and follow-up neuropsychological presentation of a primary CNS NET, where evaluations helped inform clinical care and functional recommendations. This case demonstrates the importance for neuropsychologists to have awareness of various conditions, even rare conditions, which can inform a systematic approach to research and clinical care with neuro-oncological populations.

Optical Methods for Brain Tumor Detection: A Systematic Review.

Background: In brain tumor surgery, maximal tumor resection is typically desired. This is complicated by infiltrative tumor cells which cannot be visually distinguished from healthy brain tissue. Optical methods are an emerging field that can potentially revolutionize brain tumor surgery through intraoperative differentiation between healthy and tumor tissues. Methods: This study aimed to systematically explore and summarize the existing literature on the use of Raman Spectroscopy (RS), Hyperspectral Imaging (HSI), Optical Coherence Tomography (OCT), and Diffuse Reflectance Spectroscopy (DRS) for brain tumor detection. MEDLINE, Embase, and Web of Science were searched for studies evaluating the accuracy of these systems for brain tumor detection. Outcome measures included accuracy, sensitivity, and specificity. Results: In total, 44 studies were included, covering a range of tumor types and technologies. Accuracy metrics in the studies ranged between 54 and 100% for RS, 69 and 99% for HSI, 82 and 99% for OCT, and 42 and 100% for DRS. Conclusions: This review provides insightful evidence on the use of optical methods in distinguishing tumor from healthy brain tissue.

Rapid identification of pediatric brain tumors with differential mobility spectrometry.

Introduction: Brain tumors are a major source of disease burden in pediatric population, with the most common tumor types being pilocytic astrocytoma, ependymoma and medulloblastoma. In every tumor entity, surgery is the cornerstone of treatment, but the importance of gross-total resection and the corresponding patient prognosis is highly variant. However, real-time identification of pediatric CNS malignancies based on the histology of the frozen sections alone is especially troublesome. We propose a novel method based on differential mobility spectrometry (DMS) analysis for rapid identification of pediatric brain tumors. Methods: We prospectively obtained tumor samples from 15 pediatric patients (5 pilocytic astrocytomas, 5 ependymomas and 5 medulloblastomas). The samples were cut into 36 smaller specimens that were analyzed with the DMS. Results: With linear discriminant analysis algorithm, a classification accuracy (CA) of 70% was reached. Additionally, a 75% CA was achieved in a pooled analysis of medulloblastoma vs. gliomas. Discussion: Our results show that the DMS is able to differentiate most common pediatric brain tumor samples, thus making it a promising additional instrument for real-time brain tumor diagnostics.

The Potential of Nano Pharmaceuticals to Change the Paradigm of Brain Tumor Therapy: A State-of-the-Art Review.

Central nervous system tumors are abnormal proliferations of neuronal cells within the brain and spinal cord. They can be primary or secondary and place a heavy financial, psychological, and physical burden on individuals. The highly selective blood-brain barrier, which only permits specific molecules to flow into the brain parenchyma, inhibits the efficacy of pharmacological medicines. Treatment options include surgery, chemoradiotherapy, and targeted therapy. Despite advances in therapy over the past few decades, the overall morbidity and mortality rates are still high, emphasizing the need for improved therapeutic choices to improve survival and quality of life further. Nano pharmaceuticals have demonstrated encouraging outcomes in in vivo trials using microscopic particles to enhance bioavailability and selectivity. The most successful clinical results to date have been achieved by liposomes, extracellular vesicles, and biomimetic nanoparticles; nevertheless, clinical trials are required to confirm their safety, efficacy, affordability, longterm impact, and success in patients from various demographics. Nano pharmaceuticals have the potential to change the paradigm of therapy for brain tumors, allowing better outcomes as primary and adjunctive therapy.

Towards Consistency in Pediatric Brain Tumor Measurements: Challenges, Solutions, and the Role of AI-Based Segmentation.

MR imaging is central to the assessment of tumor burden and changes over time in neuro-oncology. Several response assessment guidelines have been set forth by the Response Assessment in Pediatric Neuro-Oncology (RAPNO) working groups in different tumor histologies; however, the visual delineation of tumor components using MRIs is not always straightforward, and complexities not currently addressed by these criteria can introduce inter- and intra-observer variability in manual assessments. Differentiation of non-enhancing tumor from peritumoral edema, mild enhancement from absence of enhancement, and various cystic components can be challenging; particularly given a lack of sufficient and uniform imaging protocols in clinical practice. Automated tumor segmentation with artificial intelligence (AI) may be able to provide more objective delineations, but rely on accurate and consistent training data created manually (ground truth). Herein, this paper reviews existing challenges and potential solutions to identifying and defining subregions of pediatric brain tumors (PBTs) that are not explicitly addressed by current guidelines. The goal is to assert the importance of defining and adopting criteria for addressing these challenges, as it will be critical to achieving standardized tumor measurements and reproducible response assessment in PBTs, ultimately leading to more precise outcome metrics and accurate comparisons among clinical studies.