bluuebunny/crossref_metadata_2025 huggingface dataset:
MODL-21. INTEGRATIVE APPROACHES IN FUNCTIONAL GENOMICS TO IDENTIFY GENETIC DEPENDENCIES IN PEDIATRIC BRAIN CANCER
Authors: Sun Claire , Drinkwater Caroline , Sooraj Dhanya , Bradshaw Gabrielle , Shi Claire , Fernando Dasun , Parackal Sarah , Gough Daniel , Cain Jason , Firestein Ron
Published: December 2020

The precise decoding of human genomes facilitated by the advancements in next-generation sequencing has led to a better understanding of genetic underpinnings of pediatric brain cancers. Indeed, it is now evident that tumours of the same type harbour distinct driving mutations and molecular aberrations that can result in different prognosis and treatment outcomes. The profounder insight into the the identity, amount and types of molecular aberrations has paved the way for the advent of targeted therapies in precision medicine. Nevertheless, less than 10% of pediatric cancer patients harbour actionable mutations. Strictly limited therapeutic options that are firstly available for brain cancers and secondly acceptable for children’s development further impede the breakthrough in the survival rate in pediatric brain cancers. This underscores a desperate need to delve beyond genomic sequencing to identify biomarker coupled therapies that not only featured with treatment efficacy in the central nervous system but also acceptable side effects for children. The Hudson-Monash Paediatric Precision Medicine (HMPPM) Program focuses on utilising genetic profiles of patients’ tumour models to identify new therapeutic targets and repurpose existing ones using high-throughput functional genomics screens (2220 drugs and CRISPR screen of 300 oncogenic genes). Using a large compendium of over sixty patient derived paediatric brain cancer models, we provide proof-of-concept data that shows an integrative pipeline for functional genomics with multi-omics datasets to perform genotype-phenotype correlations and, therefore, identify genetic dependencies. Herein, using several examples in ATRT, DIPG and HGG, we show how functional interrogations can better define molecular subclassification of tumours and identify unique vulnerabilities.
NFB-07. USE OF PEGYLATED INTERFERON α- 2b IN PEDIATRIC PATIENTS AFFECTED BY UNRESECTABLE PLEXIFORM NEUROFIBROMAS: MONOCENTRIC EXPERIENCE
Authors: Cacchione Antonella , Lodi Maria Chiara , Baldo Giada Del , Carai Andrea , Colafati Giovanna Stefania , Camassei Francesca Diomedi , Locatelli Franco , Mastronuzzi Angela
Published: December 2020

BACKGROUND

Neurofibromatosis type 1 (NF1) is autosomal dominant neurogenetic disorder characterized by progressive cutaneous, neurologic, skeletal, and neoplastic manifestations. Plexiform neurofibromas (PN) are one of the different types of neurofibromas that occur in these patients. Complete surgical resection is difficult due to the tumor infiltrative behavior. We evaluated pegylated interferon- α-2b (PI) in patients with unresectable progressive or symptomatic PN.

METHODS

Pediatric patients (1–21 years old) affected by unresectable PN, followed at Bambino Gesù Hospital, were treated with PI. We administered PI as a weekly subcutaneous injection at a beginning dose of 1.0 mcg/kg/wk, increased to 3.0 mcg/kg/wk if well tolerated. Paracetamol (15mg/kg) was given 30 minutes prior the dose of PI and then every 4–6 hours as needed. Patients were evaluated with Magnetic Resonance Imaging (MRI) every 12 months after treatment start in case of stable disease.

RESULTS

10 patients (3 females, 7 males) were enrolled. Median age was 12 years old. The median duration of treatment was 12,6 months. Grade 3 neutropenia (30%) and increased liver transaminases level (20%) were the most common toxicity. 6/10 patients experienced an improvement about pain. 7/10 patients showed clinical response. 1/10 patient had a radiological response at MRI, 1/10 experienced progression disease and 8/10 showed a stable disease at MRI evaluation.

CONCLUSIONS

Our study demonstrated that PI could be a suitable treatment for unresectable PN in terms of stabilization of the tumour size due to its antitumor activity although clinical response does not correlate with radiographic changes.
NURS-01. INTRACEREBROVENTRICULAR DRUG ADMINISTRATION FOR TREATMENT OF PEDIATRIC BRAIN TUMORS
Authors: Fitzgerald Caroline , Matson Kathryn
Published: December 2020

Intrathecal (IT) chemotherapy, given via lumbar puncture (LP) or an intracerebroventricular (ICV) device has become a safe and effective way to deliver chemotherapy into the cerebrospinal fluid (CSF) space. The blood brain barrier makes treating tumors with CSF dissemination difficult with systemic chemotherapy alone. IT chemotherapy is often necessary for tumors which disseminate into the CSF space including embryonal tumors and choroid plexus carcinomas. It is also used for relapsed or recurrent tumors. Giving IT chemotherapy via an ICV device instead of via an LP can be preferable as it requires no deep sedation and allows for more uniform drug distribution. Drugs given IT include methotrexate, cytarabine, hydrocortisone, etoposide, and topotecan. ICV devices can be placed in patients with adequate CSF flow and a flow study can be done if needed to confirm. Accessing the ICV device for administration of chemotherapy is typically done by a physician or nurse practitioner using sterile technique. Our institution has had success using music therapy and child life specialists for assistance with coping during the procedure as patients are awake. The procedure has few complications the most common being infection usually with skin flora. It can also cause nausea and headache. There are few long term risks.
PATH-09. SJMB12 CLINICAL TRIAL: DISCREPANCY BETWEEN LOCAL AND CENTRAL PATHOLOGY IN ASSESSING ANAPLASTIC MEDULLOBLASTOMA – REPORT FROM A SINGLE SITE EXPERIENCE
Authors: Khuong-Quang Dong-Anh , Williamson Karli , MacGregor Duncan , Orr Brent A , Gajjar Amar , Robinson Giles W , Sullivan Michael J , Hansford Jordan R
Published: December 2020

INTRODUCTION

SJMB12 is a phase 2 clinical trial led by the St. Jude Children’s Research Hospital (St. Jude) that enrolls patients with medulloblastoma based on their biological subgroup. The large cell/anaplastic (LCA) histologic variant has been identified as an important independent risk factor associated with poor outcome. However, the histologic criteria for LCA is subjective, making the distinction between anaplastic and non-anaplastic medulloblastoma difficult in some cases.

METHODS

Pathological central review was performed at St. Jude. For all patients enrolled in the study to date, concordance was assessed between the initial and central review diagnosis and histologic variant calls made at the Royal Children’s Hospital Melbourne (RCH) and at St. Jude, respectively.

RESULTS

Since the SJMB12 clinical trial opened locally in 2014, 34 patients were enrolled, and 31 were eligible for this retrospective study. A total of 12 (39%) cases with discordance were identified. The most frequent disagreement was between the designation of LCA (10 cases, 32%). In five cases the tumour was not designated as LCA variant locally. In five cases the initial designation of LCA was refuted centrally. Overall, this led to a change of treatment stratum for four patients (13%).

CONCLUSION

A high discordance rate exists between neuropathologists in the designation of LCA variant. Differences in interpretation of the subjective histologic criteria and inconsistencies in the material submitted for central review contributed to the discordance. Incorporation of more objective histologic criteria and implementation of unbiased diagnostic tools may improve the generalisability of future risk stratification.
PATH-23. ADULT SPINAL CORD ASTROBLASTOMA WITH EWSR1-BEND2 FUSION
Authors: Tsutsui Takeyoshi , Arakawa Yoshiki , Makino Yasuhide , Kataoka Hiroharu , Minamiguti Sachiko , Hirose Takanori , Nobusawa Sumihito , Nakano Yoshiko , Ichimura Koichi , Miyamoto Susumu
Published: December 2020

The most recurrent fusion of CNS high-grade neuroepithelial tumor with MN1alteration(HGNET-MN1) is MN1- BEN Domain Containing 2(BEND2) fusion. Recently, there was a report of a 3-month-old boy with spinal astroblastoma, classified as CNS HGNET-MN1 by DKFZ methylation classification but positive for EWSR1-BEND2 fusion(Yamasaki, 2019). Here, we report a 36-year old man with a spinal cord astroblastoma with EWSR1 alternation. The patient presented with back pain, gait disorder and dysesthesia in lower extremities and trunk was referred to our hospital. MRI showed intramedullary tumor in Th3-5 level, displaying low-intensity on T1 weighted image, high-intensity on T2 weighted image, and homogeneous gadolinium enhancement. Partial removal was performed with the laminectomy. The tumor extended to extramedullary and its boundary was unclear. Histological examinations showed the epithelium-like tumor cells with eosinophilic cytoplasm with high cellularity palisade, intracellar fibrosis, and mitosis. Immunohistochemical staining showed positive for Olig2, GFAP, EMA, SSTR2, S-100, but negative for p53, PgRAE1/AE3. The tumor was diagnosed as astroblastoma, and was classified as HGNET-MN1 by the DKFZ methylation classifier. However, the MN1 alternation was not detected by fluorescence in situ hybridization, instead EWSR1 and BEND2 alternations which suggested EWSR1-BEND2 fusion were detected. After radiation therapy of 54Gy/30fr with bevacizumab and temozolomide, the residual tumor reduced the size and his symptoms improved. This case provides evidence that EWSR1-BEND2 fusion is recurrent in HGNET-MN1 and, as previously reported, suggests the importance of BEND2 in this entity. These two cases suggested that it may be the BEND2 alteration that biologically defines the HGNET-MN1 subclass rather than MN1.
PATH-26. RNA SEQUENCING OF FORMALIN-FIXED PARAFFIN-EMBEDDED SPECIMENS IN DIAGNOSTIC ROUTINE IDENTIFIES CLINICALLY RELEVANT GENE FUSIONS
Authors: Stichel Damian , Schrimpf Daniel , Meyer Jochen , Wefers Annika , Sievers Philipp , Pfister Stefan M , Wick Wolfgang , Jones David T W , von Deimling Andreas , Sahm Felix
Published: December 2020

Pediatric brain tumor entities harbor a variety of gene fusions. Whilst other molecular parameters like somatic mutations and copy number alterations have become pivotal for brain tumor diagnostics, gene fusions are only less well covered by routinely applied methylation arrays or targeted next-generation sequencing of DNA. In a routine diagnostic setting we established and optimized a workflow for investigation of gene fusions in formalin-fixed paraffin-embedded (FFPE) tumor tissues by using RNA sequencing. Assessing different tools for calling fusions from raw data, we found relevant fusions in 66 out of 101 (65%) analyzed cases in a prospective cohort collected over 26 months. In 43 (43%) cases the fusions were of decisive diagnostic relevance and in 40 (40%) cases the fusion genes rendered a druggable target. Besides the relevance of pathognomonic fusions for diagnostics, especially the detection of druggable gene fusions yields direct benefit to the patients. This approach allows for an unbiased search for fusion events in the tested samples. Besides rare variants of established fusions which were not detected by prior targeted analyses, we identified previously unreported fusion events. Exemplified on KIAA1549:BRAF fusion, we in addition provide an overview of the detection accuracy of different methods, including breakpoint detection in DNA methylation array data and fusion gene detection in DNA panel sequencing data. Our data show that RNA sequencing has great diagnostic as well as therapeutic value by clinically detecting relevant alterations.
QOL-02. PERCEPTIONS OF LATE EFFECTS CARE NEEDS AMONG SURVIVORS OF PEDIATRIC BRAIN TUMOURS
Authors: Cacciotti Chantel , Fleming Adam , Tseitlin Hanna , Duckworth JoAnn , Marjerrison Stacey
Published: December 2020

OBJECTIVES

Pediatric brain tumour survivors are at risk of long-term consequences of therapy. Comprehensive late effects care may mitigate these risks, but the best care model is unclear. We sought to describe the care experience and quality of life (QOL) of pediatric brain tumour survivors at the McMaster Children’s Hospital joint adult/pediatric Neuro-Oncology clinic.

METHODS

Cross-sectional survey data were collected. Care needs were assessed with the Cancer Care Experience Questionnaire (CCEQ), Cancer Worry Scale (CWS), and Self-Management Skills Scale (SMSS). Quality of life was measured utilizing the PedsQL Brain Tumor Module. Data were analyzed descriptively.

RESULTS

Thirty-two childhood brain tumor survivors and/or their parents participated. Their malignancies included embryonal tumors (medulloblastoma/ATRT) (62%), ependymoma (22%), and germ cell tumours (16%). Among 77%, therapy included chemotherapy, surgery and radiation. Most respondents reported high quality cancer care, although some could not recall discussions of late effects risks and health promotion. Mean cancer worry scores were low (71.8 (± 28.4)). Survivors reported limited self-management skills (58.5 (±18.2)), with support required in clinic visits, arranging medical appointments, filling prescriptions and tasks of daily living. Overall median QOL scores were in the ‘good’ range (parental report 72.3 (±17.7), survivor 68.2 (±16.6)).

CONCLUSION

In comparison to other childhood cancer survivor cohorts, this group of long-term brain tumour survivors appear to have similar QOL, fewer cancer worries, and increased need for aid with self-management. Given this, along with the positive care experience reported, this clinic model of care appears to meet the needs of this population.
QOL-17. BIOLOGICAL CORRELATES OF QUALITY OF SURVIVAL AND NEUROCOGNITIVE OUTCOMES IN MEDULLOBLASTOMA; A META-ANALYSIS OF THE SIOP-UKCCSG-PNET3 AND HIT-SIOP-PNET4 TRIALS
Authors: Chevignard Mathilde , Bull Kim , Holt James , Heng Marie-Amelie , Kennedy Colin , Doz Francois , Lannering Birgitta , Rutkowski Stefan , Massimino Maura , Clifford Steven , Hicks Debbie
Published: December 2020

Relationships between biological factors (genetic, tumour molecular subgroup) and neurocognitive/Quality of Survival (QoS) outcomes in medulloblastoma survivors are emerging, based on studies of limited retrospective cohorts. Integrated investigations of the medulloblastoma late-effects pathway (considering biological, clinical and treatment factors), using larger clinically-controlled cohorts, are now essential to determine their independent significance and potential for clinical application. In a combined cohort of SIOP-UKCCSG-PNET3 and HIT-SIOP-PNET4 patients (n=150), molecular subgroup (MBWNT, MBSHH, MBGrp3, MBGrp4) was assessed against QoS measures [health status: HUI3; emotional and behavioural difficulties: SDQ; Health-related Quality of Life (HrQoL): PedsQL]. Additionally, in DNA remaining from HIT-SIOP-PNET4 (n=74), 39 candidate SNPs (involved in metabolism, DNA maintenance/repair, neural growth/repair and oxidative stress/inflammation) were genotyped by multiplexed MALDI-TOF MassArray and assessed against Wechsler Intelligence Scale (WISC) scores. Molecular subgroup was significantly associated with HrQoL and health status in univariate analyses; MBGrp4 predicted significantly worse outcomes than MBSHH and MBGrp3 (p<0.05), but not in multivariate analyses taking into consideration other significant and reported QoS predictors (e.g. treatment, gender, age). In contrast, 6 SNPs were significantly associated with ≥1 WISC domain; 4/6 showed associations across domains. 3 SNPs were independently prognostic in multivariate analyses, and further significant associations were apparent at the gene (BDNF, APOE) and pathway (folate) level. This cross-discipline, international study encompassing two medulloblastoma trials has identified relationships between molecular subgroup, genotype and survivorship outcomes. These findings now require assessment in larger series, to inform our understanding of medulloblastoma survivorship outcomes and impact future disease management strategies.
QOL-53. GENOME ASSOCIATIONS WITH NEUROCOGNITIVE OUTCOMES, CEREBRAL MICROBLEEDS (CMBS), AND BRAIN VOLUME AND WHITE MATTER (WM) CHANGES IN PEDIATRIC BRAIN TUMOR SURVIVORS
Authors: Kline Cassie , Stoller Schuyler , Byer Lennox , Edwards Caleb , Prasad Rachna , Torkildson Joseph , Gauvain Karen , Samuel David , Lupo Janine , Morrison Melanie , Tong Elizabeth , Savchuk Solomiia , Valencia Christian Rodrigo Ugaz , Rauschecker Andreas , Rudie Jeffrey , Hoffman Thomas , Dubal Dena , Fullerton Heather , Mueller Sabine
Published: December 2020

OBJECTIVE

To identify genetic predictors of neurocognition, CMBs, brain volume, and WM changes in pediatric brain tumor survivors.

METHODS

Patients were selected from an existing cohort (RadART) if they had: 1) at least one neurocognitive evaluation using computer-based CogState; 2) available DNA; 3) standard imaging. Candidate gene or genome-wide genotyping was performed on all patients. CMBs were identified using a semi-automated algorithm developed in MATLAB. Volume of T2/FLAIR WM signal abnormality was measured using a semi-automated method based on a convolutional neural network. Brain volume and cortical thickness were measured using FreeSurfer volumetric analysis. Logistic and linear regression were done to compare phenotypes with candidate genotypes. Genome-wide efficient mixed-model analysis was done to compare neurocognition and CMBs. Gene set analysis was done using https://fuma.ctglab.nl/.

RESULTS

APOE4 was a candidate variant associated with non-lobar, larger volume CMBs (p<0.05). At the GWAS-level (n=225), specific genes trended with visual memory, psychomotor function, and CMB count (p<5x10-8). Using gene set analyses, there were gene set trends seen with CMB count and psychomotor function. Small sample size and low mutant allele frequency limited reliability of these findings. Preliminary volumetric analysis show reduced volume within the right parietal, medial occipital and inferior temporal lobes with increased cortical thickness in the left occipital and medial parietal lobe in patients carrying the ApoE4 allele. WM signal assessments are ongoing.

CONCLUSION

Genetic markers may be associated with neurocognition, CMBs, brain volume and WM changes in pediatric brain tumor survivors; however, larger cohorts are needed to confirm specific gene relevance.
RARE-04. INTELLECTUAL DEVELOPMENT IN CHILDREN WITH PEDIATRIC CRANIOPHARYNGIOMA AFTER TUMOR REMOVAL
Authors: Oyoshi Tatsuki , Fujio Shingo , Higa Nayuta , Yonezawa Hajime , Yoshimoto Koji
Published: December 2020

INTRODUCTION

Intellectual assessment in children with craniopharyngioma after tumor removal is still unknown. We assessed intellectual development in children who underwent microsurgical resection in our institute over the last twelve years.

MATERIALS AND METHODS

Ten children among 41 patients with craniopharyngioma treated and followed at Kagoshima University Hospital between 2007 and 2019 were reviewed. We also assessed intellectual development in 10 years or younger children with craniopharyngioma one year after tumor removal. Intelligence was assessed using the Wechsler Intelligence Scale for Children-Fourth Edition (WISC-Ⅳ).

RESULTS

Ten children underwent microsurgical tumor removal. The mean age at surgery was 5.8 (range 1–10) years. Transcranial approach was performed in 8 children, transsphenoidal approach in two children. The mean follow up period was 110 months. Gamma knife surgery (GKS) was performed in 6 children less than 6 months after first surgery. Regional recurrences occurred in 5 children, and additional GKS was performed in four children, second microsurgical removal in one child. Severe obesity with a transient electrolyte imbalance occurred in one child. Eight children with GH deficiency underwent GH replacement therapy. Eight children were assessed working memory index (WMI), processing speed index (PSI), Perceptual reasoning index (PRI), and verbal comprehension index (VCI) using WISC 4. Each mean value of WMI, PSI, and PRI was lower than VCI, except for 2 children with normal full scale intelligence quotient.

CONCLUSION

WMI, PSI and PRI in children with intellectual disabilities were lower tendency than VCI after surgical removal of craniopharyngiomas in the present study.
RARE-36. DYSEMBRYOPLASTIC NEUROEPITHELIAL TUMORS: A REVIEW OF CLINICAL AND MOLECULAR CHARACTERISTICS, AND OUTCOME IN A PEDIATRIC POPULATION AT A SINGLE CENTER
Authors: Flores Valerie Cruz , Geller Thomas , Gomez Ignacio Gonzalez , Rodriguez Luis , Quintana Javier , Stapleton Stacie
Published: December 2020

BACKGROUND

Neuronal and mixed neuro-glial tumors of the central nervous system (CNS) are relatively rare. Dysembryoplastic neuroepithelial tumor (DNET) is a benign, rare, slow-growing tumor, but in many cases is associated with intractable epilepsy.

OBJECTIVE

To report the experience with DNET at a single free-standing children’s institution.

METHODS

A retrospective chart review of 24 patients with confirmed DNET between 2001 and 2019 was performed. Data was collected on clinical characteristics, tumor location, surgical management, histopathological and molecular findings, and outcomes.

RESULTS

Mean age at diagnosis was 10 years (range 2 to 19 years), with female predominance (54.2%). Most common presenting symptoms were seizures (79.2%) and headaches (12.5%). Location of the tumor was temporal (29.2%), frontal (25.0%), parietal (16.7%), cerebellar (12.5%) and occipital (4.2%). A gross total resection was achieved in half the cases. Recurrence occurred in 4 patients (16.7%), all of whom had subtotal resections. The average follow up since diagnosis was 4.6 years (range 0.3 to 14 years). Nineteen patients presented with seizures, of which 63.2% were seizure free after surgery. The samples with molecular genetic testing (microarrays or FISH), were all normal except one patient positive for BRAF V600E mutation.

CONCLUSIONS

This is the first and largest review of pediatric DNETs in the last 10 years. Despite majority of patients having a favorable outcome after surgery, a subset of patients remains symptomatic. As molecular mechanisms in DNET remain unknown, future aim is to describe the molecular characteristics of our DNET population, and correlate with outcomes.
RARE-44. CLINICAL CHARACTERIZATION AND OUTCOME; OUR EXPERIENCE OF CHORDOMAS IN PEDIATRIC AND YOUNG ADULTS
Authors: Gibson Amber , Baig Muhammad , Raza Shaan , Grosshans David , Zaky Wafik
Published: December 2020

Pediatric chordomas are exceedingly rare and there are limited data to guide treatment decisions. We report a retrospective analysis of 19 patients with chordomas who received treatment at our institution from 2001–2020. Of the 19 patients, 15 had clival (79%), 3 cervical and 1 sacral chordoma. There were 9 males (47%). Median age at diagnosis of 10.6 years. Eight patients had gross total (42%) and 11 (58%) had sub-total resection. As front line therapy 15 patients (79%) underwent surgery followed by radiation (1 photon and 14 proton), 3 patients (16%) received surgery and chemotherapy (anaplastic histology) and 1 patient received only surgery. For patients treated with radiation therapy the average prescribed dose was 70 Gy (range: 52–74). Post-surgery and radiation, 14 of 15 patients remained in remission. Five (26%) patients had progressive disease (PD) with median time to progression of 13 months of whom 3 died of disease at median of 18 months. Treatment of PD consisted of chemotherapy and radiation for 3, re-resection with radiation for 1 and chemotherapy alone for 1 patient. The patients with metastatic and anaplastic disease mean survival is 21 month versus 45 for the rest of the cohort. In summary, post-operative adjuvant radiation provided an overall good outcome in majority of patients. Patients with anaplastic pathology and metastasis at diagnosis had worse outcome. Those who relapsed, subsequent treatment was palliative at best with short survival. Molecular analysis is warranted in future for better disease stratification.
RARE-63. CYST WALL OF ADAMANTINOMATOUS CRANIOPHARYNGIOMA CONTAINS TUMOR CELLS THAT COULD LEAD TO RECURRENCE AFTER SURGERY
Authors: Zhao Chuan , Wang Ye , Liu Hongxing , Qi Xueling , Zhou Zhongqing , Lau Ching , Lin Zhixiong
Published: December 2020

BACKGROUND

Adamantinomatous craniopharyngioma (ACP) is the primary subtype of craniopharyngioma in children, frequently with mutations in exon 3 of the CTNNB1 gene. Most ACP consists of both a solid tumor and one or more cysts. Despite surgical resection of the solid tumor followed by radiation, recurrence involving the cystic component is common, suggesting that the cyst wall contains tumor cells. We present here conclusive molecular pathology evidence of the presence of tumor cells in the cyst wall similar to those in the solid tumor.

METHODS

We used standard H&E staining and immunohistochemistry (IHC) to compare the histopathology characteristics between the matched cyst wall and solid tumor of 11 cases of ACP as well as their CTNNB1 expression and exon 3 mutation.

RESULTS

Samples of the cyst wall and solid tumor were collected separately during the operation of 11 cases of ACP through careful dissection. The cyst wall showed the nested cell clusters and peripheral palisading epithelium which are identical to those in the solid tumor. The cyst wall and solid tumor both showed Ki67 and nuclear β-catenin expression by IHC. There is no difference in the transcription level of CTNNB1 between the cyst wall and the solid tumor, both being significantly higher than that in normal brain tissue. Exon 3 mutations of the CTNNB1 gene of the cyst wall and the solid tumor are identical in each case.

CONCLUSION

Follow-up of clinical cases suggests that tumor cells in residual cyst wall may be the cause of recurrence after surgery.
RONC-09. PSEUDOPROGRESSION AFTER PROTON THERAPY OF PEDIATRIC SPINAL PILOCYTIC ASTROCYTOMA AND MYXOPAPILLARY EPENDYMOMA
Authors: McGovern Susan , Johnson Jason , Kralik Stephen , Grosshans David , McAleer Mary Frances , Zaky Wafik , Baxter Patricia , Lin Frank , Chintagumpala Murali , Paulino Arnold
Published: December 2020

BACKGROUND

Pseudoprogression after proton therapy of CNS tumors is a challenging clinical situation. The rate of pseudoprogression after proton therapy of pediatric spinal tumors is unknown.

METHODS

Records of pediatric patients with spinal pilocytic astrocytoma (sPA; n = 9) or myxopapillary ependymoma (MPE; n = 6) with gross disease treated with proton therapy with at least 6 months of follow up from completion of proton therapy were retrospectively reviewed for demographics, treatment characteristics, and occurrence of pseudoprogression. Pseudoprogression was defined as a post-radiation increase in tumor size with subsequent decrease in size without additional tumor-directed therapy.

RESULTS

The median age at radiation for sPA patients was 10.1y (range, 7.0 – 16.2y) and 12.7y (range, 7.9 – 14.4y) for MPE patients. The median prescribed dose was 45 GyRBE (range, 39.6 – 50.4 GyRBE) for sPA patients and 50.4 GyRBE (range, 45 – 54 GyRBE) for MPE patients. One sPA patient received concurrent vincristine. Median follow up after proton therapy was 44 months (range, 9 – 99 months). Six of nine sPA patients (67%) had pseudoprogression occurring at a median of 81 days (range, 34 – 136 days) after proton therapy; no MPE patients developed pseudoprogression (0%; p < 0.03). Two sPA patients with pseudoprogression were symptomatic and improved with medical therapy.

CONCLUSION

Preliminary analysis suggests that pseudoprogression occurs frequently within 6 months after proton therapy for sPA and infrequently after proton therapy for MPE.
RONC-12. TREATMENT AGE AND NEUROCOGNITIVE OUTCOMES FOLLOWING PROTON BEAM RADIOTHERAPY FOR PEDIATRIC LOW GRADE GLIOMA
Authors: Heitzer Andrew , Kahalley Lisa , Grosshans David , Okcu M Fatih , Raghubar Kimberly , Gragert Marsha , McCurdy Mark , Warren Emily , Ris M Douglas , Paulino Arnold , Chintagumpala Murali
Published: December 2020

INTRODUCTION

Younger age at radiotherapy increases cognitive risk for patients with pediatric low grade glioma (LGG). We examined the impact of age at treatment on cognitive trajectories in LGG patients treated with proton radiotherapy (PRT) compared to patients treated without radiotherapy (surgery only; SO).

METHODS

We examined cognitive scores of 48 LGG patients on a prospective, longitudinal study. General linear mixed models evaluated change in cognitive scores over time.

RESULTS

The sample included 16 patients treated with PRT and 32 with SO (median follow-up=3.1 years, range 0.9–6.1). Median age of PRT patients was 8.2 years at diagnosis (range 1.0–14.4) and 9.4 years at PRT (range 4.2–16.7). 13 PRT patients also received surgery: 53.8% biopsy, 30.8% subtotal resection, 15.4% gross total resection. Tumor sites included: 31.2% hypothalamic/suprasellar, 25.0% optic pathway, 18.8% temporal, 25.0% other. Median age of SO patients was 8.2 years at diagnosis (range 2.9–18.6). Surgical outcomes were: 75.0% gross total resection, 21.9% biopsy/other. There were no group differences in diagnosis age, tumor volume, or shunt history (all p>0.05). Both PRT and SO groups displayed stable cognitive functioning over time (all p>0.1). Slopes (i.e., change in scores over time) did not differ between groups (all p>0.1). Age at treatment was not associated with slope or performance at last follow-up in either group (all p>0.05).

CONCLUSIONS

We observed stable cognitive functioning, independent of age at treatment, following PRT for LGG. Outcomes were similar to patients receiving surgery only. Further examination in a larger sample is warranted.
RONC-16. PROTON BEAM THERAPY FOR PATIENTS WITH INTRACRANIAL EPENDYMOMA UNDER 3 YEARS OLD: INITIAL CLINICAL OUTCOMES
Authors: Hashimoto Takayuki , Yamaguchi Shigeru , Mori Takashi , Iguchi Akihiro , Ishi Yukitomo , Motegi Hiroaki , Onimaru Rikiya , Manabe Atsushi , Shimizu Shinichi , Aoyama Hidefumi
Published: December 2020

BACKGROUND

Proton beam therapy (PBT) provides dosimetric benefits in sparing normal tissue when treating pediatric patients with brain tumors. We report the preliminary clinical outcomes of surgery and adjuvant PBT for patients under 3 years old diagnosed as intracranial ependymoma at our institute.

METHODS

This is a retrospective review of the medical records for 3 children with ependymoma in the fourth ventricle, diagnosed between March 2013 and September 2019. PBT was performed after tumor resection in all the patients.

RESULTS

Gross total resection was achieved in 2 males and 1 female patients with fourth ventricle WHO grade II to III ependymoma at 15, 18, and 37 months old. All the patients received adjuvant PBT (54.0 GyE/30 fractions) to the postoperative tumor bed under general anesthesia or sedation. PBT was acutely well tolerated, with mostly mild alopecia and skin reactions at the irradiated sites. At a median follow-up of 54 months (4–59 months) after irradiation, all the patients are alive without recurrence. No serious late adverse events were observed in any of the patients.

CONCLUSION

The number of patients in this study remains small for drawing any definite conclusion, however our preliminary results are still encouraging. Further studies of a large number of pediatric patients with long term follow-up are needed to more fully assess tumor control and late adverse events.
SURG-22. CERVICAL SPINE ANEURYSMAL BONE CYST OF A PEDIATRIC PATIENT
Authors: Almeida Carlos , Ventura Luis Marcelo , Previdelli Stephanie , Lamim Marina Lopes , Mançano Bruna Minniti , Cavalcante Carlos Bezerra , Lourenço Lucas Dias
Published: December 2020

BACKGROUND

Aneurysmal bone cysts (ABCs) are benign, expanding lesions that represent 15% of all primary spine tumors, and only 2% have been found at the cervical level. There are different therapeutic options; the most successful is complete surgical resection. Although not always possible, due to high blood loss that occurs during the procedure, a combination of surgery with other treatment modalities was used in 40% of the cases reported so far. We describe a pediatric patient that we managed with embolization plus surgery. CASE REPORT: A 5-year-old girl presented with painful torticollis associated with a left posterior cervical mass, without neurological impairment. Magnetic resonance imaging of the cervical spine showed a multiseptated bony lesion with multiple fluid levels, involving the posterior elements of C2, associated with diffuse soft tissue enhancement of the left paravertebral muscles. We proposed a multi-staged treatment with pre-operative arterial embolization followed by the posterior surgical approach. Super selective embolization of the left ascending cervical artery was performed. The right ascending cervical artery also contributed to the tumor blush, but due to its connection to the right vertebral artery and, therefore, associated with a high risk of neurological injury, we prefer not to embolize it. Two days later, we performed a posterior surgical approach, with a gross total resection of the tumor. Histological examination revealed an ABC.

CONCLUSION

An aneurysmal bone cyst is a rare cervical spine lesion that demands a multidisciplinary approach due to its locally aggressive behavior and the excessive blood loss related to surgery.
SURG-29. A SINGLE CENTRE EXPERIENCE OF USING INTRA-OPERATIVE MRI IN MANAGING PEDIATRIC CRANIAL NEURO-ONCOLOGY CASES
Authors: Ganesan Dharmendra , Bahuri Nor Faizal Ahmad , Rajagopal Revathi , PY Jasmine Loh , Mun Kein Seong , Aman Raja Rizal Azman Raja
Published: December 2020

The University of Malaya Medical Centre, Kuala Lumpur had acquired a intraoperative MRI (iMRI) brain suite via a public private initiative in September 2015. The MRI brain suite has a SIEMENS 1.5T system with NORAS coil system and NORAS head clamps in a two room solution. We would like to retrospectively review the cranial paediatric neuro-oncology cases that had surgery in this facility from September 2015 till December 2019. We would like to discuss our experience with regard to the clear benefits and the challenges in using such technology to aid in the surgery. The challenges include the physical setting up the paediatric case preoperatively, the preparation and performing the intraoperative scan, the interpretation of intraoperative images and making a decision and the utilisation of the new MRI data set to assist in the navigation to locate the residue safely. Also discuss the utility of the intraoperative images in the decision of subsequent adjuvant management. The use of iMRI also has other technical challenges such as ensuring the perimeter around the patient is free of ferromagnetic material, the process of transfer of the patient to the scanner and as a consequence increased duration of the surgery. CONCLUSION: Many elements in the use of iMRI has a learning curve and it improves with exposure and experience. In some areas only a high level of vigilance and SOP (Standard operating procedure) is required to minimize mishaps. Currently, the iMRI gives the best means of determining extent of resection before concluding the surgery.
THER-08. SGT53 – A NOVEL p53 NANOMEDICINE INDUCES SIGNIFICANT RESPONSES IN CHILDREN WITH RECURRENT MEDULLOBLASTOMA AND CHOROID PLEXUS CARCINOMA: A REPORT OF TWO CASES
Authors: Hwang Eugene , Kilburn Lindsay , Hancock Lauren , Pirollo Kathleen , Leung Chris , Packer Roger , Chang Esther
Published: December 2020

BACKGROUND

Abnormal p53 function commonly defines high-risk CNS tumors, but functional restoration has eluded investigators. SGT-53 is a targeted nanomedicine encapsulating a plasmid DNA encoding wild-type human p53 with a transferrin receptor-targeting scFv on the nanocomplex surface resulting in efficient delivery across the BBB and robust tumor binding/uptake. Data generated by collaborators demonstrated synergy with irradiation and chemotherapy. REPORT: Two children with recurrent CNS malignancies have been treated with SGT-53, each receiving greater than 50 infusions in combination with irradiation and chemotherapy with no grade 3/4 AEs positively attributed to SGT-53. The first was an 11yo male with recurrent disseminated p53+ SHH medulloblastoma, with bulky intracranial/thoracolumbar disease. He received irradiation followed by biweekly doses of SGT-53 and temozolomide, bevacizumab and irinotecan given one week out of four. This patient exhibited a complete response of all disease on his first follow-up scan 8 weeks after therapy initiation and remained in remission for 8 months. The second patient was a 3yo male with disseminated recurrent choroid plexus carcinoma. He received CSI with SGT-53, followed by SGT-53, temozolomide and irinotecan as described above, again with no related grade 3/4 AEs. He experienced a partial response to all sites of disease and completed therapy after six months, progressing 7.8 months after initiating treatment.

CONCLUSIONS

SGT-53 was well tolerated in two heavily-pretreated patients despite aggressive combinatorial strategies. The majority of the AEs experienced were mild and manageable. Each patient had significant responses, suggesting that SGT-53 should be evaluated in a clinical trial for similar patients.
A remark on renormalization group theoretical perturbation in a class of ordinary differential equations
Authors: Kuniba Atsuo
Published: December 2020

We revisit the renormalization group (RG) theoretical perturbation theory on oscillator-type second-order ordinary differential equations. For a class of potentials, we show a simple functional relation among secular coefficients of the harmonics in the naive perturbation series. It leads to an inversion formula between bare and renormalized amplitudes and an elementary proof of the absence of secular terms in all orders of the RG series. The result covers nonautonomous as well as autonomous cases and refines earlier studies, including the classic examples of Van der Pol, Mathieu, Duffing, and Rayleigh equations.
Sex estimation from morphology in living animals and dinosaurs
Authors: Motani Ryosuke
Published: December 2020

Sexual dimorphism is a prevalent feature of sexually reproducing organisms yet its presence in dinosaurs has recently been questioned. However, the inferred absence of sexual dimorphism may be a methodological artefact, rooted in the lack of systematic knowledge concerning how sexual dimorphism of living animals behaves statistically. To start building such knowledge, I re-analysed published data of 139 species of living animals that are sexually dimorphic. The previous method used for dinosaurs recognized only 5% of the living species correctly as dimorphic. This low rate is largely caused by the tilting of ordinated multivariate space due to interactions between size and shape dimorphisms, low signal/noise ratios and inclusion of outliers. The rate can be improved to 50% by modifying the method but not further, unless the information on the sex of individual specimens is used. Such information is unavailable in dinosaurs, so sexual dimorphism probably cannot be established for a large proportion of sexually dimorphic dinosaurs. At the same time, about 32% of the 139 are strongly sexually dimorphic, and can be re-sexed from shape with misclassification rates below 0.05. A reassessment of dinosaurian data suggests that sexual dimorphism likely existed at least in some species, such as Allosaurus fragilis.
Total hip replacement explained
Authors: Perkins Amanda
Published: December 2020

Nurses care for patients before, during, and after hip replacement—one of the most common joint surgeries along with knee replacement. Here's what you need to know to provide your patients with the best possible care.
Physical Activity as a Predictor of Chronic Pain Following Pediatric Spinal Surgery
Authors: Rabbitts Jennifer A. , Holley Amy L. , Zhou Chuan , Chen Lucas
Published: December 2020

Objectives:

(1) Characterize objective physical activity patterns via actigraphy over 4 months postspinal fusion surgery, and (2) examine associations between activity patterns at 2-week and chronic postsurgical pain (CPSP) status at 4 months.

Materials and Methods:

Data from 109 youth (10 to 18 y) who underwent spinal fusion surgery at a children’s hospital in the Northwestern United States were analyzed. Youth completed questionnaires and actigraphic assessment of physical activity presurgery, and 2 weeks and 4 months postsurgery.

Results:

Eighteen percent of youth developed CPSP at 4 months. Presurgery physical activity was similar for youth with and without CPSP. At 2 weeks postsurgery, daily activity levels were lower for youth who developed CPSP as compared with those who did not, including lower mean activity (168 vs. 212 counts/min, P=0.01), fewer activity bouts (n=1.7 vs. 2.6, P=0.02), and shorter bout duration (27 vs. 40 min, P=0.02). Differences in activity were maintained at 4 months such that youth with CPSP had lower mean activity (284 vs. 334 counts/min, P=0.03), as well as greater proportion time spent sedentary and lower proportion time in light activity than youth without CPSP. In adjusted models examining 2-week actigraphy as a predictor of 4-month pain status, mean activity (odds ratio=0.99, P=0.04) and number of activity bouts (odds ratio=0.79, P=0.02) were associated with subsequent CPSP status over and above 2-week pain intensity.

Discussion:

Lower activity engagement during the initial weeks following spinal fusion surgery was associated with development of CPSP, suggesting early physical activity limitations as a risk factor for CPSP in youth. Understanding recovery patterns is critical for identifying those at risk for chronic pain and implementing early interventions.
Deep Cervical Plexus Block for Neck and Shoulder Pain Due to Myofascial Pain
Authors: Naja Ahmad S. , Madi Naji , Tfayli Yehia , Ziade Fouad , Haber Georges , Kanawati Saleh , Naja Zoher
Published: December 2020

Objectives:

Myofascial pain is one of the most common causes of regional pain with no definitive treatment. This randomized clinical trial was conducted to assess the efficacy of deep cervical plexus block versus placebo injection (sham block) for the treatment of myofascial neck and shoulder pain in terms of analgesic consumption and pain during a follow-up period of 2 weeks after the block.

Materials and Methods:

Patients were randomly divided into 2 groups. Group I (block) received deep cervical plexus block and group II (placebo) received normal saline. A total of 66 patients were included in the study, 34 patients in the block group and 32 patients in the placebo group.

Results:

Two weeks after the intervention, the average pain duration was significantly lower in the block group: 1.38±1.39 versus 5.25±1.72 for the block and placebo groups, respectively (P<0.0001). Pain intensity was significantly less in the block group such that 2.9% of patients in the block group had severe pain compared with 53.1% of patients in the placebo group (P<0.0001). Two weeks after receiving the block, the mean opioid consumption calculated as tramadol equivalent was 21.1±44.2 mg compared with 166.1±118.8 mg for the block and placebo groups, respectively. Multivariate analysis showed that patients with a longer history of pain had a higher pain score after 2 weeks. The possibility of recovery is affected by pain duration as patients with a history of chronic pain were least affected by the block.

Discussion:

This technique could be an alternative to pharmacological and other nonpharmacological treatments for myofascial pain.
Statewide Severe Maternal Morbidity Review in Illinois
Authors: Geller Stacie E. , Garland Caitlin E. , Horne Ashley A.
Published: December 2020

OBJECTIVE

To address rising rates of severe maternal morbidity and persistent racial disparities, Illinois established severe maternal morbidity review in all obstetric hospitals. The purpose of this study is to describe the findings from the statewide severe maternal morbidity review in 2018.

METHODS

This is a retrospective analysis of a hospital-level severe maternal morbidity review that occurred in 2018 (n=408) compared with all 2018 Illinois live births (n=141,595), inclusive of any severe maternal morbidity cases resulting in a live birth before hospital discharge. Cases were chosen for review based on completeness of records, complexity of the case, or an assessment that cases presented opportunities for learning and quality improvement; ie, not all severe maternal morbidity cases were reviewed. We present descriptive characteristics that contributed to the severe maternal morbidity event, and health care professional, system, and patient opportunities to alter the severe maternal morbidity outcome.

RESULTS

A total of 408 severe maternal morbidity cases were reviewed. Women with severe maternal morbidity were more likely to be non-Hispanic Black, multiparous, aged 35 years or older, have public insurance, and receive inadequate prenatal care. The most common causes of severe maternal morbidity were hemorrhage (48%), and preeclampsia and eclampsia (20%). Overall, 42% of severe maternal morbidity cases had opportunities to improve care. Non-Hispanic Black women had a disproportionately high burden of severe maternal morbidity due to preeclampsia and eclampsia (31% vs 18.1%) and were more likely to need improvement in care compared with non-Hispanic White women (53% vs 39.0%). The most common opportunities to alter the severe maternal morbidity outcome were health care professional factors during the intrapartum (9%) and postpartum (10%) periods.

CONCLUSION

Standardized severe maternal morbidity review gives a fuller view of the state of maternal health and highlights opportunities to improve quality of care.
Endothelial Biomarkers Are Associated With Indirect Lung Injury in Sepsis-Associated Pediatric Acute Respiratory Distress Syndrome
Authors: Whitney Jane E. , Feng Rui , Koterba Natalka , Chen Fang , Bush Jenny , Graham Kathryn , Lacey Simon F. , Melenhorst Jan Joseph , Parikh Samir M. , Weiss Scott L. , Yehya Nadir
Published: December 2020

Objectives:

Acute respiratory distress syndrome occurring in the setting of direct versus indirect lung injury may reflect different pathobiologies amenable to different treatment strategies. We sought to test whether a panel of plasma biomarkers differed between children with sepsis-associated direct versus indirect acute respiratory distress syndrome. We hypothesized that a biomarker profile indicative of endothelial activation would be associated with indirect acute respiratory distress syndrome.

Design:

Observational cohort.

Setting:

Academic PICU.

Subjects:

Patients less than 18 years old with sepsis-associated direct (pneumonia, n = 52) or indirect (extrapulmonary sepsis, n = 46) acute respiratory distress syndrome.

Interventions:

None.

Measurements and Main Results:

Of 58 biomarkers examined, 33 differed by acute respiratory distress syndrome subtype. We used classification and regression tree methodology to examine associations between clinical and biochemical markers and acute respiratory distress syndrome subtype. The classification and regression tree model using only clinical variables (age, sex, race, oncologic comorbidity, and Pediatric Risk of Mortality-III score) performed worse than the classification and regression tree model using five clinical variables and 58 biomarkers. The best classification and regression tree model used only four endothelial biomarkers, including elevated angiopoietin-2/angiopoietin-1 ratio, vascular cell-adhesion molecule, and von Willebrand factor, to identify indirect acute respiratory distress syndrome. Test characteristics were 89% (80–97%) sensitivity, 80% (69–92%) specificity, positive predictive value 84% (74–93%), and negative predictive value 86% (76–96%).

Conclusions:

Indirect lung injury in children with acute respiratory distress syndrome is characterized by a biomarker profile indicative of endothelial activation, excess inflammation, and worse outcomes. A model using four biomarkers has the potential to be useful for more precisely identifying patients with acute respiratory distress syndrome whose pathobiology may respond to endothelial-targeted therapies in future trials.