System Tumors In Children Research Articles

Investigation of the Relationship between CMYC Gene Polymorphisms and Glioma Susceptibility in Chinese Children

Glioma is a common central nervous system tumors in children. CMYC has a range of functions that are disrupted in various tumor cells, and may contribute to the occurrence and development of glioma. Two CMYC single nucleotide polymorphisms (rs4645943C>T and rs2070583 A>G) were genotyped in 190 cases and 248 controls from Wenzhou and Guangzhou hospitals. After adjusting for age and sex, odds ratio and 95% confidence interval values were calculated by logistic regression to evaluate the correlation between CMYC gene polymorphisms and glioma risk; no significant associations were detected. These results require future validation in a larger sample cohort.

Perceived Barriers to the Time to Diagnosis of Central Nervous System Tumors in Children: Surveying the Perspectives From the Frontline.

Perceived Barriers to the Time to Diagnosis of Central Nervous System Tumors in Children: Surveying the Perspectives From the Frontline.

Diagnostic accuracy of image-guided core needle biopsy of non-central nervous system tumors in children.

Core needle biopsies (CNB) are less invasive, cause less morbidity, and have lower costs than open biopsies (OB). However, the number of studies reporting CNB accuracy in pediatric tumors is limited and series are small. The aim of this study is to investigate if CNB diagnosis is concordant with the final diagnosis in pediatric solid non-central nervous system (CNS) tumors. Data from all patients treated in a single center between November 2014 and December 2019 were collected from the national pathology database and from local medical records. Data collection included age, sex, CNB diagnosis, final diagnosis, number of cores obtained, number of cores used for histology, cumulative core length, greatest dimension of the lesion, lesion volume, and complications. Out of 361 CNB, 95.6% (345/361) provided a diagnosis. A resection or follow-up biopsy was performed in 201 cases. The final diagnosis was concordant with the CNB in 100% (201/201) of cases. The age, number of cores used for histology, and the greatest dimension of the lesion did not significantly differ between diagnostic and nondiagnostic CNB. The cumulative core length of diagnostic CNB was significantly higher than in the nondiagnostic group (24.72mm vs. 13.37mm, p-value .022). Complications occurred in 2.1% (7/337) of CNB procedures. Molecular analysis was successful in 228/233 (98%) of cases in which it was performed. CNB diagnosis is highly concordant with the final diagnosis and the diagnostic rate is high. The complication rate in CNB is low.

Association of HMGA2 Polymorphisms with Glioma Susceptibility in Chinese Children.

BackgroundGlioma is a malignant central nervous system tumor in children, with poor outcomes and prognosis. HMGA2 is a proto-oncogene with increased expression in various malignancies.MethodsWe explored the association of HMGA2 polymorphisms with glioma susceptibility in Chinese children using a case-control study (191 cases, 248 controls). HMGA2 single nucleotide polymorphisms (rs6581658 A>G; rs8756 A>C; rs968697 T>C) were genotyped using PCR-based TaqMan.ResultsIncreased glioma susceptibility was associated with rs6581658 A>G; AG (adjusted odds ratio (OR) = 1.71, 95% confidence interval (CI) = 1.13–2.58, P = 0.010) or GG (adjusted OR = 3.12, 95% CI = 1.26–7.74, P = 0.014) genotype carriers had significantly raised glioma risk compared with AA genotype carriers. The rs6581658 AG/GG (adjusted OR = 1.85, 95% CI = 1.25–2.73, P = 0.002) and AA/GG (adjusted OR = 2.58, 95% CI = 1.05–6.33, P = 0.038) genotypes were associated with an increased risk of glioma relative to the AA genotype. Subjects with 2–3 risk genotypes had a significantly elevated risk (adjusted OR = 1.93, 95% CI = 1.31–2.84, P = 0.001) relative to those with 0–1 risk genotype.ConclusionHMGA2 rs6581658 A>G is associated with glioma susceptibility in Chinese children.

Atypical Teratoid/Rhabdoid Tumor (AT/RT) With Molecular Features of Pleomorphic Xanthoastrocytoma.

Atypical teratoid/rhabdoid tumor (AT/RT) is a highly malignant central nervous system tumor predominantly occurring in infants that may also arise in older children and adults. Rare secondary AT/RT developing from other tumors such as pleomorphic xanthoastrocytoma (PXA) are on record, but AT/RT presenting with molecular features of PXA have not been described. Here, we report 3 malignant central nervous system tumors in children (10, 13, and 18 y old). All tumors were located in the temporal lobe. In 2 cases, there was no history of a low-grade precursor lesion; in 1 case anaplastic PXA had been diagnosed 3 months earlier. Histopathologically, all tumors were composed of RT cells and showed frank signs of malignancy as well as loss of nuclear SMARCB1/INI1 protein expression. Two cases displayed homozygous deletions of the SMARCB1 region while the third case showed an exon 7 mutation (c.849_850delGT; p.Met283Ilefs*77). Of note, DNA methylation profiles did not group with AT/RT or other tumor entities using the Heidelberg Brain Tumor Classifier (version v11b4). By unsupervised t-distributed stochastic neighbor embedding analysis and hierarchical clustering analysis, however, all tumors clearly grouped with PXA. Genome-wide copy number analysis revealed homozygous CDNK2A/B deletions and gains of whole chromosome 7. BRAF V600E mutations could be demonstrated in all cases. In conclusion, the possibility of AT/RT with molecular features of PXA needs to be taken into account and warrants molecular characterization of AT/RT especially in older children. Since treatments targeting mutated BRAF are available, identification of such cases may also have therapeutic consequences.

Development of a prognostic model based on an immunogenomic landscape analysis of medulloblastoma.

Medulloblastoma (MB) is one of the most common central nervous system tumors in children. At present, the vital role of immune abnormalities has been proved in tumorigenesis and progression. However, the immune mechanism in MB is still poorly understood. In the present study, 51 differentially expressed immune-related genes (DE-IRGs) and 226 survival associated immune-related genes (Sur-IRGs) were screened by an integrated analysis of multi-array. Moreover, the potential pathways were enriched by functional analysis, such as ‘cytokine–cytokine receptor interaction’, ‘Ras signaling pathway’, ‘PI3K-Akt signaling pathway’ and ‘pathways in cancer’. Furthermore, 10 core IRGs were identified from DE-IRGs and Sur-IRGs. And the potential regulatory mechanisms of core IRGs were also explored. Additionally, a new prognostic model, including 7 genes (HDGF, CSK, PNOC, S100A13, RORB, FPR1, and ICAM2) based on IRGs, was established by multivariable COX analysis. In summary, our study revealed the underlying immune mechanism of MB. Moreover, we developed a prognostic model associated with clinical characteristics and could reflect the infiltration of immune cells.

Adverse cutaneous effects of mitogen-activated protein kinase inhibitors in children.

Mitogen-activated protein kinase inhibitors (MEKi) are currently used for the treatment of central nervous system tumors in children and have shown promising results. Cutaneous adverse effects are among the most common toxicities described in adults, but few studies exist in pediatric patients. We aimed to describe the cutaneous adverse effects associated with MEKi in pediatric patients. A retrospective study was carried out at our pediatric hospital in Barcelona, Spain, in patients undergoing treatment with MEKi. Sixty-one children between 1 and 18years of age were included. All patients developed cutaneous toxicity. Eczema, hair abnormalities, oral aphthae, and paronychia were among the most common cutaneous side effects. Recognizing skin toxicity in pediatric patients under treatment with MEKi is essential to establishing appropriate education and therapy, thereby improving treatment tolerability and minimizing avoidable interruptions in treatment.

The Treatment Outcomes in Children with Medulloblastoma

Background: Medulloblastoma is the most common central nervous system tumor in childhood. This study aims to evaluate the clinical features, treatments, and outcomes of pediatric patients diagnosed with medulloblastoma Materials and Method:Between 2006 and 2019, the medical records of children with medulloblastoma were reviewed retrospectively. Patients who died after surgery, before chemotherapy or radiotherapy were not included in the survival analysis Results: During the study period, 38 children were diagnosed with medulloblastoma. Twenty-one of the patients were male (55.3%) and 17 were female (44.7%). The ages of the children ranged from 3 months to 17 years (median age 8 years). The ages of five patients were under 3 years (13.1%). The most common complaints were headache (n: 26, 68.4%), imbalance (n: 21, 55.3%), and vomiting (n: 20, 52.6%). The mass sizes ranged between 3 and 6 cm in 32 patients (84.2%). At the time of diagnosis, 5 patients had seeding metastasis (13.1%). The most commonlyused chemotherapy protocol included vincristine, cisplatin, etoposide (60.5%). Five patients died after surgery without any chemotherapy or radiotherapy. Of the 33 patients included in the life analysis, 12 died (36.4%). Follow-up times ranged from 2 months to 14 years (median, 44 months). The overall survival rate was 59.1%. Eight patients had relapsed (24.2%). Late relapse was detected in 3 of the relapsed patients (relapse times were the 91st, 69th, and 72nd months). Conclusions: It is possible to achieve satisfactory treatment results in children with medulloblastoma using international treatment guidelines and recommendations, with an experienced professional team dedicated to pediatric neurooncology.

Central nervous system tumors in children: trends of the past decade

The article presents the current state of the domestic children’s neuro-oncological system; also it highlights the main development trends over the past decade. The authors summarize, analyze and compare data on the prevalence of malignant neoplasms of the central nervous system in children in the Republic of Tatarstan with the data of large-scale multicenter studies. The article presents the age-sex, histological and molecular structure of the central nervous system tumors through the prism of the new World Health Organization classification dd 2016, which determines the trends in the development of future systems for recording, diagnosis, treatment and rehabilitation of children with brain and spinal tumors.

Identification of genetic alterations in childhood and adolescence glioblastoma (GBM) using next generation sequencing strategy.

e14547 Background: Glioblastoma (GBM) is the most aggressive brain malignancy with a heterogeneity molecular profile and accounts for no more than 3-5% of Central Nervous System tumors in children. Despite its rarity, pediatric GBM pertain different molecular genetics, outcome and effectiveness to therapies and remains an equally lethal tumor in children. Identification of genetic alterations in GBM of childhood and adolescence is important to refine molecular classification, define prognosis and therapeutic strategies. We aimed to detect and investigate molecular changes with potential prognostic marker and therapeutic target in GBM, using next generation sequencing (NGS) strategy. Methods: We selected 41 GBM samples from patients treated at Pediatric Oncology Institute/GRAACC. NGS was performed to identified genetic alterations in tumor samples using Oncomine Childhood Cancer Research Assay (OCCRA) panel, specific genetic panel for childhood and adolescence neoplasms. Results: We selected 41 GBM samples and identified 33 mutated genes. The most commonly detected genetic alterations were involving TP53, PDGFRA, PIK3CA, NF1, MYC, MET and genes with histone-related functions, including H3F3A and ATRX. Mutations in H3F3A K28M, ATRX and TP53 were most recurrent. ATRX alterations, either nonsense substitution or frameshift deletion, were exclusively found in patients with H3F3A K28M mutations. TP53 loss-of-function was exclusive in 9 of 41 (22%) tumors. In 7 of 9 cases (78%) harboring both H3F3A and TP53 mutations, patients died due to disease progression . In these patients, H3F3A-TP53 mutation is suggested to be unfavorable prognostic factor. Copy number alterations were found in 30% of GBM cases and PDGFRA-amplifications were the most frequent. PDGFRA-amplification was exclusively found in patients with H3F3A K28M mutations and 75% of these patients did not survived longer than two years. Conclusions: Molecular profiling based on NGS genetic panel, specific for pediatric tumors, can provide information about potential prognostic biomarkers for GBM of childhood and adolescence. Thus, wider understanding about GBM biologic heterogeneity may lead to personalized therapeutic strategies for pediatric patients.

COT-14 CLINICAL FEATURES OF PEDIATRIC CENTRAL NERVOUS SYSTEM TUMORS

INTRODUCTIONHere,we discuss the presentation,histology,therapy,and outcome of central nervous system tumors in children.METHODSTreatment outcome and management was assessed for children diagnosed with central nervous tumors from 2007 to 2017 at Kagoshima University.RESULTSEight-eight patients (56 boys,32 girls) with a mean age of 10.3 years were included in this study. Patient tumor types included: germ cell tumor (n = 26); medulloblastoma (n = 16); pilocytic astrocytoma (n = 8); glioblastoma (n = 8); ependymoma (n = 6,1 with grade 2,5 with grade 3); hemangioblastoma,schwannoma,and ganglioglioma (n = 3 each); SEGA,pilomyxoid astrocytoma,and diffuse astrocytoma (n = 2 each),and anaplastic astrocytoma,PPTID,PNET,PXA,DIA,central neurocytoma,astroblastoma,meningioma,and choroid plexus papilloma (n = 1 each). The most common patient clinical features were headache and vomiting associated with hydrocephalus. The median follow-up period was 61 months. All patients with germ cell tumors underwent adjuvant chemotherapy and radiation therapy (RT); patients with germinoma or immature teratoma were still alive,while patients with embryonal carcinoma,yolk sac tumor,or choriocarcinoma had poor prognosis with a median survival of 16 months. For cases of ependymoma,three patients received ICE chemotherapy and RT,and two patients received RT alone; median survival time was 31 months. For high grade glioma,seven patients received temozolomide and RT,and two patients received temozolomide alone; median survival time was 13 months.CONCLUSIONSPatients with germ cell tumors had a relatively good prognosis,while patients with ependymoma or high grade glioma had a poor prognosis. As treatment strategies for ependymoma and high grade glioma are currently limited,it is necessary to evaluate treatment options in consideration of clinical course and quality of life,in addition to histologic and genetic findings.

Optic Pathway Glioma in Type 1 Neurofibromatosis: Review of Its Pathogenesis, Diagnostic Assessment, and Treatment Recommendations.

Type 1 neurofibromatosis (NF1) is a dominantly inherited condition predisposing to tumor development. Optic pathway glioma (OPG) is the most frequent central nervous system tumor in children with NF1, affecting approximately 15–20% of patients. The lack of well-established prognostic markers and the wide clinical variability with respect to tumor progression and visual outcome make the clinical management of these tumors challenging, with significant differences among distinct centers. We reviewed published articles on OPG diagnostic protocol, follow-up and treatment in NF1. Cohorts of NF1 children with OPG reported in the literature and patients prospectively collected in our center were analyzed with regard to clinical data, tumor anatomical site, diagnostic workflow, treatment and outcome. In addition, we discussed the recent findings on the pathophysiology of OPG development in NF1. This review provides a comprehensive overview about the clinical management of NF1-associated OPG, focusing on the most recent advances from preclinical studies with genetically engineered models and the ongoing clinical trials.

Functional outcome of the low vision aids for visual impairment secondary to central nervous system tumors in children.

To assess functional outcomes of optical low vision aids (LVAs) for pediatric visual impairment due to central nervous system (CNS) tumors. A prospective case study was conducted on 15 children with history of CNS tumors with mean age of 10.47±1.85y. Lighthouse distance, near visual acuity tests, cycloplegic refraction, reading speed measurement and visual field examination were done. Prescription of far and near LVAs followed by training sessions. LVPrasad-functional vision questionnaire was done to evaluate performance. Visual impairment was moderate (13.3%), severe (73.3%), profound (6.7%) and near blindness in 6.7%. Telescopes prescribed in 33.4%, video magnifier in 46.7%. Questionnaire scores were significantly improved for distant rather than near tasks (P≤0.05) after training. LVAs rehabilitation is an effective method of improving vision in pediatric visual defects secondary to CNS tumors.

Medulloblastoma in childhood: What effects on neurocognitive functions?

PuposeMedulloblastoma is the most common primary malignant central nervous system tumor in childhood, accounting for 16–25% of cases (1). New treatment approaches have led to improved survival rates; however toxicities are still a major concern. Patients and methodsParticipants were selected from the records of patients who were treated with craniospinal irradiation for medulloblastoma. Between January 2008 and December 2012, 62 patients were diagnosed with medulloblastoma at the national institute of oncology Rabat, 27 patients were still alive at the time of the study, of which n=16 patients were included in the study. The mean age of patients at the time of the study was 9.6 years. All children were treated with radiation therapy and chemotherapy, according to standard protocols. Median follow-up between treatment and evaluation was 4 years. All the children were assessed with the Wechsler Intelligence Scale for Children - fourth Edition (WISC-IV) three to five years after completion of radiotherapy. The test was administered by two well-trained psychologists in a distraction-free environment. The scoring was then reviewed by a psychologist from Brooklyn College. ResultsThe mean standard score Full-Scale Intelligence Quotient (FSIQ) (M=63, SD=12.6) was found to be in the extremely low range and in the 1st percentile rank (PR), compared to the general population. All the measured primary index scales were below typical performance: verbal comprehension (M=67.7, SD=13.1), perceptual reasoning (M=63.5, SD=13.8) and processing speed (M=62.7, SD=15.5) were all found to be in the extremely low range, while xorking memory (M=75.5, SD=10.8) was found to be in the borderline range compared to the general population. To identify factors influencing the results, we performed both univariate and multivariate analyses. Age at the time of radiotherapy, initial clinical stage, total cranial radiotherapy dose, socioeconomic status, and the time of evaluation were identified as significantly impacting cognitive scores in the univariate analysis. In the multivariate analysis, only age at the time of radiotherapy and initial clinical stage remained factors significantly impacting cognitive outcomes with P=0.001 and P<0.001 respectively. ConclusionOur study is evidence that tremendous efforts are still to be made in low-income countries to correctly measure neurocognitive dysfunction in medulloblastoma survivors and to prepare those patients to a typical life after the completion of treatment.

Hospital admission for neurologic disorders among 5-year survivors of noncentral nervous system tumors in childhood: A cohort study within the Adult Life after Childhood Cancer in Scandinavia study.

Large, comprehensive studies of the risk for neurologic disorders among long-term survivors of noncentral nervous system (CNS) childhood cancers are lacking. Thus, the aim of our study was to assess the lifetime risk of Nordic non-CNS childhood cancer survivors for neurologic disorders. We identified 15,967 5-year survivors of non-CNS childhood cancer diagnosed in Denmark, Iceland, Finland and Sweden in 1943-2008, and 151,118 matched population comparison subjects. In-patient discharge diagnoses of neurologic disorders were used to calculate relative risks (RRs) and absolute excess risks (AERs). A neurologic disorder was diagnosed in 755 of the survivors while 370 were expected, yielding a RR of 2.0 (95% confidence interval (CI) 1.9-2.2). The highest risks were found among survivors of neuroblastoma (4.1; 95% CI 3.2-5.3) and leukemia (2.8; 95% CI 2.4-3.2). The AER decreased from 331 (278-383) excess neurologic disorders per 100,000 person-years 5-9 years after diagnosis to 82 (46-118) ≥ 20 years after diagnosis. Epilepsy was the most common diagnosis (n = 229, 1.4% of all survivors), and significantly increased risks were seen among survivors of eight out of 12 types of childhood cancer. Survivors of neuroblastoma had remarkably high risks (RR ≥ 10) for hospitalization for paralytic syndromes and hydrocephalus, while survivors of leukemia had additional high risks for dementia and encephalopathy. In conclusion, survivors of non-CNS childhood cancer are at high risk for neurologic disorders, especially within the first decade after diagnosis. Therefore, intensive follow-up to identify those who require close management is needed.

Diagnostic delay and morbidity of central nervous system tumors in children and young adults: a pediatric hospital experience.

For children with central nervous system (CNS) tumors, survival rates remain significantly lower than other childhood malignancies with a substantial increase in disability of survivors. Given this, it is imperative that these children are identified at the earliest sign of symptom onset. Our institution aimed to identify diagnostic delays, morbidity and mortality, and specific barriers that may exist within our specific healthcare system that result in diagnostic delay. A retrospective chart review was performed of newly diagnosed CNS tumors between January 1, 2008 and December 31, 2017. 235 patient cases were reviewed, 34 (14.5%) of which had an associated tumor predisposition syndrome. Median age at the time of diagnosis was 9years (range 1day to 25years), with median number of days from symptom onset to definitive diagnosis of 42days (interquartile range 14-120days). Delays longer than 60days occurred in 95 (47.5%) patients. The 10year relative survival rate for all tumors was 86.8%. Our institution had a shorter interval from symptom onset to diagnosis than currently reported in the literature, as well as a decrease in associated morbidity. In addition, for those with longer delays, we were able to characterize the etiology and barriers leading to these delays. With these identified, we are able to utilize this knowledge to further improve education and awareness in community members and healthcare professionals to continue to improve the time to diagnosis in the future.

Synergistic activity of BET inhibitor MK-8628 and PLK inhibitor Volasertib in preclinical models of medulloblastoma

Medulloblastoma is the most prevalent central nervous system tumor in children. Targeted treatment approaches for patients with high-risk medulloblastoma are needed as current treatment regimens are not curative in many cases and cause significant therapy-related morbidity. Medulloblastoma harboring MYC amplification have the most aggressive clinical course and worst outcome. Targeting the BET protein BRD4 has significant anti-tumor effects in preclinical models of MYC-amplified medulloblastoma, however, in most cases these are not curative. We here assessed the therapeutic efficacy of the orally bioavailable BRD4 inhibitor, MK-8628, in preclinical models of medulloblastoma. MK-8628 showed therapeutic efficacy against in vitro and in vivo models of MYC-amplified medulloblastoma by inducing apoptotic cell death and cell cycle arrest. Gene expression analysis of cells treated with MK-8628 showed that anti-tumor effects were accompanied by significant repression of MYC transcription as well as disruption of MYC-regulated transcriptional programs. Additionally, we found that targeting of MYC protein stability through pharmacological PLK1 inhibition showed synergistic anti-medulloblastoma effects when combined with MK-8628 treatment. Thus, MK-8628 is effective against preclinical high-risk medulloblastoma models and its effects can be enhanced through simultaneous targeting of PLK1.

BRAF V600E Inhibitor (Vemurafenib) for BRAF V600E Mutated Low Grade Gliomas.

Low-grade gliomas (LGG) are the most common central nervous system tumors in children. Prognosis depends on complete surgical resection. For patients not amenable of gross total resection (GTR) new approaches are needed. The BRAF mutation V600E is critical for the pathogenesis of pediatric gliomas and specific inhibitors of the mutated protein, such as Vemurafenib, are available. We investigated the safety and efficacy of Vemurafenib as single agent in pediatric patients with V600E+ LGG. From November 2013 to May 2018, 7 patients have been treated in our Institution; treatment was well-tolerated, the main concern being dermatological toxicity. The best responses to treatment were: 1 complete response, 3 partial responses, 1 stable disease, only one patient progressed; in one patient, the follow-up is too short to establish the clinical response. Two patients discontinued treatment, and, in both cases, immediate progression of the disease was observed. In one case the treatment was discontinued due to toxicity, in the other one the previously assessed BRAF V600E mutation was not confirmed by further investigation. Two patients, after obtaining a response, progressed during treatment, suggesting the occurrence of resistance mechanisms. Clinical response, with improvement of the neurologic function, was observed in all patients a few weeks after the therapy was started. Despite the limitations inherent to a small and heterogeneous cohort, this experience, suggests that Vemurafenib represents a treatment option in pediatric patients affected by LGG and carrying BRAF mutation V600E.

402P - Adult medulloblastoma: An oncology radiation therapy department experience with 22 cases

Background: Medulloblastoma is the most common central nervous system tumor in children. However, the occurrence in adults is rare and accounts for about 1% - 2%. The objective of this study is to define the clinical characteristic of this entity and therapeutic results. Methods: We retrospectively evaluated the treatment data of 22 adult patients (≥18 years) treated for medulloblatoma from 1993 to 2013 in our department. Median follow up was 161.5 months [58; 296 months]. Results: Male female ratio was 2.14 :1. Median age was 25 years [18 ; 57]. Eight patients (36%) had cerebellar hemispheric tumors, nine cases (41%) occur in the vermis and five patients (23%) had an hemispheric-vermian localisation. Twenty one patients (95%) underwent macroscopically total exicision. Sixteen patients (73%) had classic form; five patients had desmoplastic (23%) type and one patient had extensive nodularity type. Patients were stratified into standard and high risk in 14 and 5 cases respectively. The risk couldn’t be identified for 3 patients. Among patients in the high-risk group, four received a cisplatin/etoposide chemotherapy before radiation. All patients had craniospinal radiotherapy. The mean interval between surgery and the begining of radiation therapy was 107 days. Craniospinal dose range between 30Gy and 36Gy. The dose in the posterior fossa was respectively 54Gy and 64Gy in 18 (82%) and 4 (18%) cases. The 5 year overall survival was 63%. Conclusions: There are differences between pediatric and adult patients with medulloblastoma in terms of clinical and pathological characteristic. Ultimately, prospective trials including adult patient with medulloblastoma are needed to optimize the management of this rare and complex disease. Legal entity responsible for the study: Kallel Mouna. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.

Diffusion profiling of tumor volumes using a histogram approach can predict proliferation and further microarchitectural features in medulloblastoma.

Medulloblastomas are the most common central nervous system tumors in childhood. Treatment and prognosis strongly depend on histology and transcriptomic profiling. However, the proliferative potential also has prognostical value. Our study aimed to investigate correlations between histogram profiling of diffusion-weighted images and further microarchitectural features. Seven patients (age median 14.6years, minimum 2years, maximum 20years; 5 male, 2 female) were included in this retrospective study. Using a Matlab-based analysis tool, histogram analysis of whole apparent diffusion coefficient (ADC) volumes was performed. ADC entropy revealed a strong inverse correlation with the expression of the proliferation marker Ki67 (r = - 0.962, p = 0.009) and with total nuclear area (r = - 0.888, p = 0.044). Furthermore, ADC percentiles, most of all ADCp90, showed significant correlations with Ki67 expression (r = 0.902, p = 0.036). Diffusion histogram profiling of medulloblastomas provides valuable in vivo information which potentially can be used for risk stratification and prognostication. First of all, entropy revealed to be the most promising imaging biomarker. However, further studies are warranted.