Pediatric Brain Tumor Patients Research Articles

Comparative Analysis of Surgical Site Infections in Pediatric Brain Tumor Patients: Hygiene Practices, Risk Factors, and Implications for Healthcare Costs and Mortality

Surgical site infections (SSIs) significantly impact pediatric central nervous system tumor outcomes. We present our data of SSIs and their influence on outcomes of pediatric brain tumor patients treated between January 2011 till December 2022. This study utilized retrospective data from patients' medical records. Chi-squared test was used for correlational analysis. Independent sample t-test was used for equality of means. Linear and logistic regression was done to review impact of independent variables on dependent variable. Survival analysis was done using Kaplan–Meier curves. Between 2011 and 2022, 336 pediatric patients (202 males, 134 females) were diagnosed with brain tumors. Majority patients (279; 83%) underwent surgery (91% elective). Commonest tumor site was cerebellum (84/279; 30%). Tumor resection status was gross total resection (29/279; 46%), subtotal resection (59/279; 21%), near total resection (48/279; 17%), and partial resection (20/279; 7%); while 32/279 patients (11%) had a biopsy only. Hydrocephalus was present in 166/279 patients (59%); while majority (160/166; 96%) underwent a cerebrospinal fluid (CSF) diversion procedure. SSI developed in 23/279 patients (8%), leading to delayed postoperative management in majority (15/23; 65%). SSIs were significantly associated with lower age of presentation (p = 0.01), less duration between symptoms and diagnosis (p = 0.00), performance of CSF diversion procedure (p = 0.04), increase in hospital stay (p = 0.00), delay in postoperative management (15/23; 65%) (p = 0.01), decline in treatment completion (p = 0.01), and poor survival (p = 0.01). Majority (171/279) of patients (61%) completed treatment. The overall survival of our cohort was 84.9% with a median follow-up time of 11 (interquartile range [IQR]: 36, 1) months. Survival was significantly lower (56.5%) in patients with SSI (p = 0.01). Median time to death was 18 months. Progression-free survival was 77.4% with a median progression-free time of 8 (IQR: 28, 1) months. Median time to progression was 9 (IQR: 24, 4.5) months. The incidence of SSIs in our cohort closely resembled that of high-income countries. Risk factors for SSIs included younger age, a shorter time between symptom onset and surgery, undertaking of CSF diversion procedures. Adverse effects of SSIs included increased costs, delays in postoperative management, incomplete treatment, and higher mortality rates. This study emphasizes the substantial impact of SSIs on healthcare resources and patient well-being.

Pediatric neurosurgery training during residency in Switzerland and the need for dedicated subspecialization training

IntroductionPediatric Neurosurgery as a subspeciality started to emerge during the late 1950s, with only a few dedicated pediatric neurosurgeons in the Western world. Over the last few decades, the awareness that children require subspecialized care by dedicated pediatric neurosurgeons and an interdisciplinary team has been growing worldwide, leading to an increase in pediatric neurosurgeons. Several studies have shown that subspecialized care for pediatric patients improves outcomes and is cost-effective. This survey aims to assess the current setting of pediatric neurosurgery and training of neurosurgical residents in pediatric neurosurgery in Switzerland.MethodsWe conducted an online survey by sending e-mail invitations in 2021 to all neurosurgical residents in Switzerland. The survey included questions regarding the participants' demographics, current workplace structures, the care of specific pediatric neurosurgical pathologies, and participants’ opinions of the Swiss training program for pediatric neurosurgery and possible improvement. We defined at the beginning of the survey that a pediatric neurosurgeon is a board-certified neurosurgeon with at least one year of dedicated pediatric neurosurgical fellowship training abroad.ResultsWe received a total of 25 responses from residents, of which 20 (80%) were male. Twenty-two participants (88%) worked in one of seven major hospitals in Switzerland at the time of the survey, and four (16%) were interested in pursuing a fellowship in pediatric neurosurgery. Seven (35%) and five residents (25%) feel comfortable taking care on the ward of a craniosynostosis and hydrocephalus patient younger than 6 months, respectively. Twelve residents (60%) feel comfortable taking care of a pediatric brain tumor patient. The majority (n = 22, 88%) of all residents agree that a fellowship-trained pediatric neurosurgeon should treat children, while two (8%) residents state that any neurosurgeon with an interest in pediatric neurosurgery should be able to treat children. All residents (n = 25, 100%) agree that pediatric neurosurgery training and care in Switzerland needs to be improved.ConclusionPediatric neurosurgery training in Switzerland is rather heterogeneous and not very well structured, with varying frequencies of children-specific neurosurgical pathologies. Most residents agreed that a subspecialized pediatric neurosurgeon should oversee the care of children in neurosurgery, while all agree that pediatric neurosurgical training and care should be improved in Switzerland.

Phantosmia during proton radiation and differences in frequency of phantosmia rates based on proton craniospinal irradiation technique for pediatric brain tumor patients.

Unusual olfactory perception, often referred to as "phantosmia" or "cacosmia" has been reported during brain radiotherapy (RT), but is infrequent and does not typically interfere with the ability to deliver treatment. We seek to determine the rate of phantosmia for patients treated with proton craniospinal irradiation (CSI) and identify any potential clinical or treatment-related associations. We performed a retrospective review of 127 pediatric patients treated with CSI, followed by a boost to the brain for primary brain tumors in a single institution between 2016 and 2021. Proton CSI was delivered with passive scattering (PS) proton technique (n=53) or pencil beam scanning technique (PBS) (n=74). Within the PBS group, treatment delivery to the CSI utilized a single posterior (PA) field (n=24) or two posterior oblique fields (n=50). We collected data on phantom smell, nausea/vomiting, and the use of medical intervention. Our cohort included 80 males and 47 females. The median age of patients was 10years (range: 3-21). Seventy-one patients (56%) received concurrent chemotherapy. During RT, 104 patients (82%) developed worsening nausea, while 63 patients (50%) reported episodes of emesis. Of those patients who were awake during CSI (n=59), 17 (29%) reported phantosmia. In the non-sedated group, we found a higher rate of phantosmia in patients treated with PBS (n=16, 42%) than PS (n=1, 4.7%) (p=.002). Seventy-eight patients (61%) required medical intervention after developing nausea/vomiting or phantosmia during RT. Two patients required sedation due to the malodorous smell during CSI. We did not find any significant difference in nausea/vomiting based on treatment technique. Proton technique significantly influenced olfactory perception with greater rates of phantosmia with PBS compared to PS. Prospective studies should be performed to determine the cause of these findings and determine techniques to minimize phantosmia during radiation therapy.

Amide proton transfer weighted imaging in pediatric neuro-oncology: initial experience.

Amide proton transfer weighted (APTw) imaging enables in vivo assessment of tissue-bound mobile proteins and peptides through the detection of chemical exchange saturation transfer. Promising applications of APTw imaging have been shown in adult brain tumors. As pediatric brain tumors differ from their adult counterparts, we investigate the radiological appearance of pediatric brain tumors on APTw imaging. APTw imaging was conducted at 3 T. APTw maps were calculated using magnetization transfer ratio asymmetry at 3.5 ppm. First, the repeatability of APTw imaging was assessed in a phantom and in five healthy volunteers by calculating the within-subject coefficient of variation (wCV). APTw images of pediatric brain tumor patients were analyzed retrospectively. APTw levels were compared between solid tumor tissue and normal-appearing white matter (NAWM) and between pediatric high-grade glioma (pHGG) and pediatric low-grade glioma (pLGG) using t-tests. APTw maps were repeatable in supratentorial and infratentorial brain regions (wCV ranged from 11% to 39%), except those from the pontine region (wCV between 39% and 50%). APTw images of 23 children with brain tumor were analyzed (mean age 12 years ± 5, 12 male). Significantly higher APTw values are present in tumor compared with NAWM for both pHGG and pLGG (p< 0.05). APTw values were higher in pLGG subtype pilocytic astrocytoma compared with other pLGG subtypes (p< 0.05). Non-invasive characterization of pediatric brain tumor biology with APTw imaging could aid the radiologist in clinical decision-making.

Extra-axial desmoplastic/nodular medulloblastoma in adult mimicking cerebellar metastasis: reappraisal of this rare presentation with literature review

Introduction and importance: Medulloblastomas are the most common malignant intra-axial brain tumour in paediatric patients and represent 35–40% of posterior fossa tumour types in children between 3 and 9 years of age. Medulloblastomas may also be found in adulthood. These tumours are classified into two groups according to its molecular characteristics and histological type. The desmoplastic/nodular subtype is the second common subtype after the classic one. Only three cases of desmoplastic/nodular extra-axial medelloblastoma have been previously reported in the literature originating from to the cerebellopontine angle. Case presentation: The authors report a new case of an extra-axial desmoplastic/nodular cerebellar medulloblastoma originating outside the cerebellopontine angle and mimicking a solitary cerebellar metastasis in a 49-year-old female patient who presented for a raised intracranial pressure and cerebellar syndrome. Clinical discussion: Medulloblastoma is a malignant embryonal intra-axial tumour of the cerebellum or posterior brain stem that occurs mainly in children. Medulloblastomas may also be found in adulthood. Desmoplastic/nodular medulloblastoma is the second most common type of all medulloblastomas. The intra-axial form is always predominant. Only three cases of extra-axial desmoplastic/nodular medulloblastoma have been reported in the literature. The authors will go through the literature to dissect this rare entity. Conclusion: Although considered a common paediatric intra-axial tumour, there are increasing numbers of solitary cases reporting an extra-axial presentation in different locations of the posterior cerebral fossa even in adulthood. These rare and unusual presentations and locations may mislead the correct diagnosis and delay treatment.

Unraveling the relations between post-traumatic stress symptoms, neurocognitive functioning, and limbic white matter in pediatric brain tumor patients.

Pediatric brain tumor patients are at risk of developing neurocognitive impairments and associated white matter alterations. In other populations, post-traumatic stress symptoms (PTSS) impact cognition and white matter. This study aims to investigate the effect of PTSS on neurocognitive functioning and limbic white matter in pediatric brain tumor patients. Sixty-six patients (6-16 years) completed neuropsychological assessment and brain MRI (1-year post-diagnosis) and parents completed PTSS proxy questionnaires (CRIES-13; 1-3 months and 1-year post-diagnosis). Mean Z-scores and percentage impaired (>1SD) for attention, processing speed, executive functioning, and memory were compared to normscores (t-tests, chi-square tests). Multi-shell diffusion MRI data were analyzed for white matter tractography (fractional anisotropy/axial diffusivity). Effects of PTSS on neurocognition and white matter were explored with linear regression models (FDR correction for multiple testing), including age at diagnosis, treatment intensity, and tumor location as covariates. Neurocognition and limbic white matter associations were explored with correlations. Attention (M = -0.49, 33% impaired; P < .05) and processing speed (M = -0.57, 34% impaired; P < .05) were significantly lower than healthy peers. PTSS was associated with poorer processing speed (β = -0.64, P < .01). Treatment intensity, age at diagnosis, and tumor location, but not PTSS, were associated with limbic white matter metrics. Neurocognition and white matter metrics were not associated. Higher PTSS was associated with poorer processing speed, highlighting the need for monitoring, and timely referrals to optimize psychological well-being and neurocognitive functioning. Future research should focus on longitudinal follow-up and explore the impact of PTSS interventions on neurocognitive performance.

Patient- and xenograft-derived organoids recapitulate pediatric brain tumor features and patient treatments.

Brain tumors are the leading cause of cancer-related death in children. Experimental in vitro models that faithfully capture the hallmarks and tumor heterogeneity of pediatric brain cancers are limited and hard to establish. We present a protocol that enables efficient generation, expansion, and biobanking of pediatric brain cancer organoids. Utilizing our protocol, we have established patient-derived organoids (PDOs) from ependymomas, medulloblastomas, low-grade glial tumors, and patient-derived xenograft organoids (PDXOs) from medulloblastoma xenografts. PDOs and PDXOs recapitulate histological features, DNA methylation profiles, and intratumor heterogeneity of the tumors from which they were derived. We also showed that PDOs can be xenografted. Most interestingly, when subjected to the same routinely applied therapeutic regimens, PDOs respond similarly to the patients. Taken together, our study highlights the potential of PDOs and PDXOs for research and translational applications for personalized medicine.

Setup Uncertainty of Pediatric Brain Tumor Patients Receiving Proton Therapy: A Prospective Study.

This study quantifies setup uncertainty in brain tumor patients who received image-guided proton therapy. Patients analyzed include 165 children, adolescents, and young adults (median age at radiotherapy: 9 years (range: 10 months to 24 years); 80 anesthetized and 85 awake) enrolled in a single-institution prospective study from 2020 to 2023. Cone-beam computed tomography (CBCT) was performed daily to calculate and correct manual setup errors, once per course after setup correction to measure residual errors, and weekly after treatments to assess intrafractional motion. Orthogonal radiographs were acquired consecutively with CBCT for paired comparisons of 40 patients. Translational and rotational errors were converted from 6 degrees of freedom to a scalar by a statistical approach that considers the distance from the target to the isocenter. The 95th percentile of setup uncertainty was reduced by daily CBCT from 10 mm (manual positioning) to 1-1.5 mm (after correction) and increased to 2 mm by the end of fractional treatment. A larger variation existed between the roll corrections reported by radiographs vs. CBCT than for pitch and yaw, while there was no statistically significant difference in translational variation. A quantile mixed regression model showed that the 95th percentile of intrafractional motion was 0.40 mm lower for anesthetized patients (p=0.0016). Considering additional uncertainty in radiation-imaging isocentricity, the commonly used total plan robustness of 3 mm against positional uncertainty would be appropriate for our study cohort.

IMMU-50. DIFFERENCES IN GUT MICROBIAL COMPOSITION BETWEEN PEDIATRIC BRAIN TUMOR PATIENTS AND HEALTHY CONTROLS – THE MIMIC PROGRAM

Abstract INTRODUCTION The gut microbiome has been hypothesized to influence tumor initiation, immune evasion and treatment response in CNS tumor patients via the gut-brain axis, but data remains limited. To begin to address this question, we compared the gut microbial composition in a cohort of pediatric high-grade brain tumor patients with healthy controls. METHODS Within the MIMIC program, we prospectively collected fecal samples from 33 pediatric brain tumor patients at diagnosis and 26 pediatric healthy controls (HC) (&amp;lt; 21 years of age). Samples were analyzed using 16S rRNA amplicon sequencing of the V3-V4 region. Group differences were tested through the α- and β-diversity. Additionally, differential abundance (DA) analyses were performed. RESULTS Brain tumor patients (16 embryonal and 17 glial) significantly differed in age from HC (median 8 years vs 5 years, p&amp;lt; 0.001). Patient vs HC comparison revealed a comparable α-diversity (Shannon-index p=0.45), but significantly different β-diversity (Permanova test p=0.02). Corrected for age, DA revealed 18 genera with a significant log fold change. Twenty five of 33 brain tumor patients received dexamethasone during or prior to fecal sampling and 32 out of 33 patients received cefazolin, a first generation narrow-spectrum cephalosporin targeting mainly gram-positive bacteria, during surgery and before sample collection. Steroid use within brain tumor patients did not statistically affect α-diversity, β-diversity or DA. However, the impact of intravenously administered cefazolin during surgery on the gut microbiome in brain tumor patients remains unknown. CONCLUSION We report significant differences in gut microbial composition between pediatric brain tumor patients at diagnosis and healthy controls. DA revealed clinically relevant differences in Agathobacter , Fusicatenibacter , Eggerthella , and Hungatella. However, differences may be impacted by cefazolin administration. If and how gut microbial composition at diagnosis is associated with treatment efficacy and toxicity is subject to further research within the MIMIC program.

IMMU-51. THE LANDSCAPE OF TUMOR INFILTRATING T CELLS (TILS) OF CHILDHOOD BRAIN TUMORS

Abstract T lymphocytes have a unique ability to recognize a vast array of antigens prompt by an enormous T cell receptor (TCR) repertoire. Characterization of tumor-infiltrating T cells (TILs) and their TCRs is key to understand MHC-restricted anti-tumor immunity and for developing T cell centered immunotherapies such as adoptive cell therapy and tumor vaccines. In the current work, we investigated RNAseq data from nearly 1,000 pediatric brain tumor patients and performed the first large-scale comprehensive examination of the immunogenomic and TCR landscape of TILs across the spectrum of pediatric brain tumors. We show that the relative ratio between T cell diversity (clonality) and T cell abundance within each sample, represented by the clonal expansion index (CEI), is a strong predictor of prognosis across tumor types and molecular subtypes. Interestingly, we found that CEI was strongly associated with molecular subgroups of medulloblastoma but not with known genomic features of these subgroups. Analysis of single-cell (sc)RNAseq and scTCRseq data of TILs across several tumor types, validated clonal expansion of TILs which were frequently associated with effector-cytotoxic T cell phenotypes, whereas non-expanded TILs were associated mostly with CD4 T cell phenotypes. Investigation of T cell clones recognizing a common recurrent tumor-antigen across patients based on CDR3 homology and characteristics, reveals several T cell specificity groups which are tumor type restricted with defined HLA dominance. Using machine learning investigations of genomic profiles of the patients which contain these T cell specificity groups identified novel putative HLA-restricted tumor antigens shared across patients. Importantly, our framework grounded the foundations for developing a precision medicine approach of T cell centered immunotherapies. In all, our findings have major implications for understanding the interplay between T cell and tumor genomic, and for improving immunotherapy strategies for childhood brain tumors.

Sleep problems and impact of obstructive hydrocephalus in newly diagnosed pediatric brain tumor patients

BackgroundPediatric brain tumor patients are at risk of developing sleep problems. Previous studies were conducted in longer-term survivors or without comprehensive sleep evaluations, therefore it remains unclear whether and when problems arise. Insights can facilitate timely interventions. The aim is to examine sleep problems and contributing factors shortly after diagnosis. MethodsChildren 6–16 years with a primary brain tumor (diagnosed ≤3 months) were recruited for a prospective study. Sleep was measured at home using wrist-worn actigraphy and questionnaires (PROMIS Sleep Disturbance and Sleep Related Impairment, self- and parent-reports). Mean PROMIS scores, prevalence of sleep problems (established by cut-off scores) and actigraphic outcomes were compared to norms (t-test, chi-square, linear regression). Risk factors were explored with multivariable linear regression models. ResultsSixty-nine children (68% male, mean age 11.6 ± 2.8 years, 53 ± 28 days after diagnosis) participated. Parents reported more child sleep disturbances (mean T = 53.7, P < .01) compared to norms. Rates of self- and parent-reported severe sleep disturbances were elevated (11% versus 5% in norms, P < .04). Parents also reported higher rates of moderate child sleep disturbance (31%) and sleep related impairment (42%) than norms (25%, P < .03). Actigraphy was comparable to healthy controls. Obstructive hydrocephalus was associated with longer sleep times (B=41.04, 95%CI 11.41;70.68) and shorter time since diagnosis with self-reported sleep disturbances (B=−.11, 95%CI −0.19;−0.03). ConclusionSleep problems are more frequently reported shortly after pediatric brain tumor diagnosis, compared to healthy controls. Attention for sleep around brain tumor diagnosis and impact of obstructive hydrocephalus is important, as sleep is vital for recovery and health-related quality of life.

BIOM-56. THE PRIVATE AND RECURRING ANTIGENIC PROFILE OF MOST AGGRESIVE PEDIATRIC BRAIN TUMORS

Abstract BACKGROUND Efficient immunotherapies for pediatric brain tumors face a significant challenge in identifying tumor rejection antigens. To overcome this hurdle, we utilized a comprehensive computer algorithm called the Open Reading Frame Antigen Network (O.R.A.N.). METHODS Our focus was on expressed epitopes, including single nucleotide variations, small indels, gene fusions, novel junctions from alternative splicing, and Tumor Associated Antigens (TAAs), for antigenic epitope predictions. To ensure uniqueness, we compared immunogenic TAA epitopes against a personalized human proteomic library, ensuring they were not shared by other expressed isoforms or genes. The immunological landscape of medulloblastoma (n = 170) and DIPG (n = 30) was explored using immune deconvolution techniques combined with single-cell RNA sequencing integration. RESULTS Our hypothesis was that medulloblastomas and DIPG exhibit diverse immune profiles and express genes that are rarely found in normal tissues, making them potential targets for immunotherapy. In this study, we found that most neoantigens identified in medulloblastoma patients were unique to each individual, emphasizing the need for personalized neoantigen-based therapies. Interestingly, recurring neoantigens were predominantly present in the MB SHH subgroup, while they constituted only a small fraction of putative antigens in WNT, Group 3, and Group 4 patients. On the other hand, recurring Tumor Associated Antigens (TAAs) were more frequently expressed in the latter three molecular subgroups but not in the SHH subgroup. Thus, a combination of personalized neoantigen vaccines and targeting recurring TAAs could potentially maximize the anti-tumor effects. CONCLUSION Medulloblastoma is a disease characterized by its heterogeneity, and current standard treatments do not adequately address this aspect. In the case of DIPG, surgical resection is not a viable option due to its diffuse and infiltrative nature within the brainstem. By leveraging the power of the immune system, cellular immunotherapy holds promise in providing more targeted and personalized treatment options for pediatric brain tumor patients.

48 Longitudinal Language Outcomes in Pediatric Brain Tumor Patients Diagnosed in Early Childhood

Objective:Pediatric brain tumor (PBT) survivors are at risk for speech (e.g., articulation, prosody, fluency) and language (e.g., vocabulary, grammar, narratives, pragmatics) difficulties (Hodges et al., 2020). It is important to understand what treatment and/or demographic factors are associated with language functioning soon after diagnosis, and what factors are associated with language functioning years after treatment completion. This study characterizes longitudinal language functioning for clinically referred PBT survivors diagnosed in early childhood.Participants and Methods:Participants were 48 PBT patients (54% supratentorial, 6% disseminated), 21% with NF-1, who were diagnosed by age 6 (M = 43.2 months, SD 24.5) and received tumor-directed intervention including surgery (85%), chemotherapy (69%), and/or radiation therapy (50%). Hearing concerns existed for 29% of the patients. Age at first neuropsychological evaluation was 2-15 years (M=7.6, SD=3.63), age at second neuropsychological evaluation was 5-19 years (M=12.04, SD=3.86), with an average of 4.42 years (SD=2.37) between evaluations. Patients were 63% male, 77% White, 94% non-Hispanic, and fluent English speakers. Verbal IQ, working memory, fluencies, comprehension, memory, and parent-reported functional communication outcomes were assessed as part of comprehensive batteries. Rates of weak performance (1 SD&lt;Mean) were compared to the expected base rate of 16%.Results:Group means significantly diverged from age-expected performance by the second evaluation in all domains except semantic fluency. Weakness was identified on at least 1 verbal subtest for 79% of the sample at the first evaluation, and for 85% of the sample at the second evaluation. As a group, patients showed a significant increase in the number of weaknesses identified on performance-based measures from the first to second evaluation [t(47) = -3.60, p &lt;.001]. Over half of the sample showed an increase in the rate of verbal weaknesses identified (56.3%). Those with more weaknesses over time had lower IQ at the initial evaluation [t(36) =-2.61, p=.013]. An increase in the number of weaknesses from first to second evaluation was not associated with tumor type/location, treatment modality, or demographic variables.Conclusions:Brain tumor diagnosis in early childhood during rapid language development is associated with language impairments soon after diagnosis, and years after treatment completion. Causes for continued and increased impairment are multifactorial and risk cannot clearly be identified by demographic and treatment variables alone. Any early language weakness identification should signal need for intervention as the causes for difficulty are complex and these weaknesses are likely to persist and increase over time.

Practical adaptive skills in pediatric brain tumor survivors: the contribution of medical factors and social determinants of health

ABSTRACT Pediatric brain tumor survivors demonstrate weaknesses in adaptive functioning, most notably practical adaptive skills; however, the specific areas of weakness within practical skills are unknown. This study examined the aspects of practical adaptive functions that are most impacted in brain tumor survivors, and identified medical and socio-demographic variables that predicted outcomes. The sample included 117 pediatric brain tumor patients seen for a clinical neuropsychological evaluation and whose parents completed the Adaptive Behavior Assessment System, Second or Third Edition. T-tests compared practical adaptive skills to normative means. Correlations examined associations between medical and socio-demographic variables and each of the practical adaptive subscales (Community Use, Home Living, Health & Safety, Self-Care). Significant correlations were entered into linear regression models for each practical adaptive skill. All practical subscales were significantly below the normative mean. Community Use was positively correlated with age at diagnosis and negatively correlated with treatment burden, time since diagnosis, and neighborhood deprivation. Health and Safety was positively correlated with age at diagnosis. Home Living was positively correlated with neighborhood deprivation. Self-Care was positively correlated with age at diagnosis and parental education. Specific medical and socio-demographic factors predicted practical adaptive functioning, highlighting the importance of considering the role of medical and socio-demographic determinants of health on adaptive functioning outcomes in pediatric brain tumors.

Comparison of passive-scattered and intensity-modulated proton beam therapy of craniospinal irradiation with proton beams for pediatric and young adult patients with brain tumors

PurposeTo investigate the dose stability of craniospinal irradiation based on irradiation method of proton beam therapy (PBT).Methods and materialsTwenty-four pediatric and young adult brain tumor patients (age: 1–24 years) were examined. Treatment method was passive-scattered PBT (PSPT) in 8 patients and intensity-modulated PBT (IMPT) in 16 patients. The whole vertebral body (WVB) technique was used in 13 patients whose ages were younger than 10, and vertebral body sparing (VBS) technique was used for the remaining 11 patients aged 10 and above. Dose stability of planning target volume (PTV) against set-up error was investigated.ResultsThe minimum dose (Dmin) of IMPT was higher than that of PSPT (p = 0.01). Inhomogeneity index (INH) of IMPT was lower than that of PSPT (p = 0.004). When the irradiation field of the cervical spinal cord level (C level) was shifted, the maximum dose (Dmax) was lower in IMPT, and mean dose (Dmean) was higher than PSPT as movement became greater to the cranial–caudal direction (p = 0.000–0.043). Dmin was higher and INH was lower in IMPT in all directions (p = 0.000–0.034). When the irradiation field of the lumber spinal cord level (L level) was shifted, Dmax was lower in IMPT as movement became greater to the cranial direction (p = 0.000–0.028). Dmin was higher and INH was lower in IMPT in all directions (p = 0.000–0.022).ConclusionsThe PTV doses of IMPT and PSPT are robust and stable in both anterior–posterior and lateral directions at both C level and L level, but IMPT is more robust and stable than PSPT for cranial–caudal movements.Trial registryClinical Trial Registration number: No. 04-03.

Neurosurgical treatment of pediatric brain tumors - results from a single center multidisciplinary setup

ObjectiveThe challenge of pediatric brain tumor surgery is given due to a relative low prevalence but high heterogeneity in age, localization, and pathology. Improvements of long-term overall survival rates were achieved during the past decades stressing the importance of a multidisciplinary decision process guided by a national treatment protocol. We reviewed the entire spectrum of pediatric brain tumor surgeries from the perspective of an interdisciplinary pediatric neuro-oncology center in Germany.MethodsEvery patient who underwent brain tumor surgery from January 2010 to June 2017 in our Pediatric Neurosurgery department was retrospectively included and evaluated regarding the course of treatment. Perioperative data such as tumor localization, timing of surgery, extent of resection, neuropathological diagnosis, transfusion rates, oncologic and radiation therapy, and neurological follow-up including morbidity and mortality were evaluated.ResultsTwo hundred ninety-three pediatric brain tumor patients were applicable (age: 8.28 ± 5.62 years, 1.22:1.0 m:f). A total of 531 tumor surgical interventions was performed within these patients (457 tumor resections, 74 tumor biopsies; mean interventions per patient 1.8 ± 1.2). Due to a critical neurologic status, 32 operations (6%) were performed on the day of admission. In 65.2% of all cases, tumor were approached supratentorially. Most frequent diagnoses of the cases were glial tumors (47.8%) and embryonal tumors (17.6%). Preoperative planned extent of resection was achieved in 92.7%. Pre- and postoperative neurologic deficits resolved completely in 30.7%, whereas symptom regressed in 28.6% of surgical interventions. New postoperative neurologic deficit was observed in 10.7%, which resolved or improved in 80% of these cases during 30 days. The mortality rate was 1%.ConclusionWe outlined the center perspective of a specialized pediatric neuro-oncological center describing the heterogeneous distribution of cases regarding age-related prevalence, tumor localization, and biology, which requires a high multidisciplinary expertise. The study contributes to define challenges in treating pediatric brain tumors and to develop quality indicators for pediatric neuro-oncological surgery. We assume that an adequate volume load of patients within a interdisciplinary infrastructure is warranted to aim for effective treatment and decent quality of life for the majority of long-term surviving pediatric tumor patients.

Cognitive deficits and altered functional brain network organization in pediatric brain tumor patients.

Survivors of pediatric brain tumors experience significant cognitive deficits from their diagnosis and treatment. The exact mechanisms of cognitive injury are poorly understood, and validated predictors of long-term cognitive outcome are lacking. Resting state functional magnetic resonance imaging allows for the study of the spontaneous fluctuations in bulk neural activity, providing insight into brain organization and function. Here, we evaluated cognitive performance and functional network architecture in pediatric brain tumor patients. Forty-nine patients (7-18 years old) with a primary brain tumor diagnosis underwent resting state imaging during regularly scheduled clinical visits. All patients were tested with a battery of cognitive assessments. Extant data from 139 typically developing children were used as controls. We found that obtaining high-quality imaging data during routine clinical scanning was feasible. Functional network organization was significantly altered in patients, with the largest disruptions observed in patients who received propofol sedation. Awake patients demonstrated significant decreases in association network segregation compared to controls. Interestingly, there was no difference in the segregation of sensorimotor networks. With a median follow-up of 3.1 years, patients demonstrated cognitive deficits in multiple domains of executive function. Finally, there was a weak correlation between decreased default mode network segregation and poor picture vocabulary score. Future work with longer follow-up, longitudinal analyses, and a larger cohort will provide further insight into this potential predictor.

Seizure outcomes after resection of primary brain tumors in pediatric patients: a systematic review and meta-analysis.

Primary brain neoplasms are the most common solid tumors in pediatric patients and seizures are a common presenting symptom. Surgical intervention improves oncologic outcomes and seizure burden. A better understanding of factors that influence seizure outcomes in the surgical management of primary brain tumors of childhood can guide treatment approach thereby improving patient quality of life. We performed a systematic analysis using articles queried from PubMed, EMBASE, and Cochrane published from January 1990 to August 2022 to determine predictors of seizure outcomes in pediatric patients undergoing resection of primary brain tumors. We identified 24 retrospective cohort studies, one prospective cohort study, and one mixed retrospective and prospective study for the systematic analysis. A total of 831 pediatric patients were available for analysis. 668 (80.4%) patients achieved seizure freedom after surgery. Complete tumor resection increased the likelihood of a seizure-free (Engel I) outcome compared to subtotal resection (OR 7.1, 95% CI 2.3-21.9). Rates of Engel I seizure outcomes did not significantly differ based on factors such as age at seizure onset, duration of epilepsy, gender, tumor laterality, or age at surgery, but trended towards significance for improved outcomes in temporal lobe tumors. Primary brain tumors in the pediatric population are commonly associated with seizures. Resection of these lesions reduces seizure burden and is associated with high rates of seizure freedom. Complete resection, compared to subtotal resection, significantly increases the likelihood of seizure-free outcomes.

Health-related quality of life of pediatric brain tumor survivors after treatment in Jordan.

The number of cancer survivors and survivorship are increasing. Health-related quality of life (HRQOL) has not been widely studied in low-and-middle-income countries (LMICs). The aim of this study is to explore HRQOL of childhood brain tumor survivors and its determinants in Jordan. Health-related quality of life information was collected from 80 patients treated at the King Hussein Cancer Center and their parents using the Pediatric Quality of Life Inventory (PedsQL) Generic Core Scales questionnaire in Arabic. Multivariable linear OLS regression models were used to analyze correlates of HRQOL and compare differences between child- and parent-reported responses. Health-related quality of life scores reported by survivors and by parents were positively correlated on all subscales and total PedsQL scores (r = 0.59, P = .001). Survivors reported better HRQOL in cognitive subscale (β = 0.56, P = .03) and worse HRQOL in work subscale (β = 0.43, P = .04), but no significant differences in the physical, emotional, and social subscales and total PedsQL scores. Significant predictors of HRQOL reported by parents and by children were different. Supratentorial tumor location was associated with a 10.97-unit lower physical HRQOL score, and recurrence of tumors predicted a 17.5-unit lower total HRQOL score, indicating worse quality of life. Male gender (β = 14.9, P = .002) and diagnosis of hypopituitarism (β = 16.1, P = .03) were associated with better HRQOL. Furthermore, patients that only had radiotherapy treatment had better emotional HRQOL (β = 32.9, P = .006) compared to patients that had combined radiotherapy and chemotherapy. This study provides evidence on determinants of HRQOL of pediatric brain tumor patients in Jordan. Future studies need to capitalize on the findings of this study to institute a system for regular assessment of quality of life of pediatric cancer patients in Jordan and other countries with similar health care systems and sociocultural backgrounds.

NEIM-07 HARNESSING END-TO-END CLOUD-BASED WORKFLOWS AND MULTI-MODAL DATA ANALYTICS IN PEDIATRIC BRAIN TUMOR IMAGING AT THE CHILDREN’S BRAIN TUMOR NETWORK (CBTN)

Abstract Neuroimaging is an essential component of the standard of care in pediatric brain tumor patients. Developing efficient and agile workflows for image processing and integration of imaging with other data types to perform predictive analytics is an increasing need. At CBTN, we developed user-friendly workflows to support the entire imaging data lifecycle and to bridge access to multi-modal datasets with scalable analytics, to empower researchers to make breakthrough discoveries that will advance patient care. An automated deep learning-based brain extraction and tumor subregion segmentation model based on a multi-institutional dataset was developed that can reliably segment the treatment-naïve MRI scans of children across a variety of brain tumor histologies. This model was subsequently integrated into an end-to-end imaging pipeline for collecting, managing and analyzing clinically acquired radiology exams of the CBTN consortium with processing of 19,975 exams (1,443 subjects) to date. Critically, the constituent software tools enable the preparation of images for downstream AI analytics, from acquisition to feature extraction. A public website was also created to allow users to search and explore the dataset based on sequence labels, and clinical and imaging attributes. In addition, we established a scalable workflow and processes for de-identification, ingestion, quality control, and management of digital pathology slides for CBTN (over 8,000 slides to date). Finally, we evaluated the feasibility of interoperability between imaging (Flywheel) and molecular (CAVATICA) platforms deployed in cloud ecosystems which can allow streamlined, user-friendly workflows to ingest and harmonize files, perform cohort selection, prepare data using standard processing packages and cloud resources, and conduct analysis on extracted multi-modal feature sets. The described workflow lays the foundation for the broad use of imaging studies and access to multi-modal datasets and analytics, with the goal of empowering researchers to make breakthroughs in patient care.