bluuebunny/crossref_metadata_2025 huggingface dataset:
RARE-09. PRESERVATION OF ENDOCRINE FUNCTION AFTER OMMAYA RESERVOIR INSERTION IN CHILDREN WITH CYSTIC CRANIOPHARYNGIOMA
Authors: Lohkamp Laura-Nanna , Kulkarni Abhaya , Drake James , Rutka James T , Dirks Peter , Taylor Michael , Ibrahim George , Baroni Lorena , Hamilton Jill , Bartels Ute Katharina
Published: December 2020

INTRODUCTION

Children with craniopharyngiomas (CP) can be subjected to significant morbidities caused by radical surgery and/or radiation with severe long-term consequences. Ommaya reservoir Insertion (ORI) into cystic CP represents a minimally invasive procedure that aims to preserve endocrine, hypothalamic and neurocognitive function. The purpose of this study was to determine the relevance of upfront ORI (+/- intracystic treatment) for preservation of endocrine function.

METHODS

A retrospective chart review of children with CP treated at the Hospital for Sick Children between 01/01/2000 and 15/01/2020 was undertaken. Endocrine function was reviewed at the time of initial ORI or surgical resection and throughout the course of follow-up. Event free survival (EFS) was defined as the time to additional surgical resection or irradiation.

RESULTS

Fifty-five patients with sufficient endocrine follow-up data were included. The median age of diagnosis was 8.3 years (range 2.1–18.0 years), 31 were males. ORI was performed as upfront treatment in 30 patients, gross total or partial resection in 24 patients and radiation in 1 patient, respectively. Endocrine function remained stable after ORI with a median EFS of 19.2 (0 – 105.3) months while the majority of patients who underwent surgical resection had documented worsened endocrine function postoperatively (median of 0; range 0 – 29.4 months) (p< 0.001). The event most commonly related to secondary endocrine deterioration was initial or delayed surgical resection.

CONCLUSIONS

Endocrine function was preserved in patients with upfront ORI (+/- intracystic treatment). Further studies will elucidate the implications of ORI with respect to ophthalmological, vascular and neurocognitive long-term outcome.
RARE-13. INFLAMMATORY MYOFIBROBLASTIC TUMOR MIMICKING DESMOPLASTIC INFANTILE GANGLIOGLIOMA (DIG) OF THE TEMPORAL LOBE
Authors: Abukhiran Ibrahim , Lora Gino Bardi , Kirby Patricia , Shelton Julia , Shilyanski Joel , Wilson Saul , Bossler Aaron , Sato Yutaka , Bashir Amani , Sato Mariko
Published: December 2020

Inflammatory myofibroblastic tumor (IMT) is a mesenchymal neoplasm composed of fascicles of myofibroblastic spindle cells in a background of prominent inflammatory infiltrate. It is categorized as ‘intermediate, rarely metastasizing’ in the World Health Organization classification of tumors of soft tissue and bone. We present a novel case of concurrent brain and lung tumor with diagnosis of TFG-ROS1-rearranged IMT in a 14 year old female patient, in which targeted next-generation sequencing became a powerful tool for detection of genomic alterations in both lung and brain tumors. At age 9, the patient’s lung mass was incidentally found and investigated for various infectious diseases with negative result. At age 14, she presented with seizure and was noted to have a stable size lung mass and a left temporal lobe tumor. The left temporal lobe tumor showed a desmoplastic spindle cell neoplasm involving the meninges and cerebral cortex and Desmoplastic Infantile Ganglioglioma (DIG) was considered one of differentials. Subsequently, her right lung mass was resected and showed a similar spindle cell neoplasm with a background of dense fibrosis and chronic inflammation, consistent with Inflammatory Myofibroblastic Tumor. Molecular microdissection revealed that both tumors shares TFG-ROS1 fusion which is associated with (t(3;6) (q12;q22)), thus it is strongly suggestive that two tumors arose from the same origin. No predisposition syndrome was identified.
RARE-19. PEDIATRIC HIGH GRADE GLIOMA WITH DNA REPAIR PATHWAY ABERRATIONS, CLINICAL CHARACTERISTICS AND OUTCOME
Authors: Baig Muhammad , McCall David , Moss Tyler , Sandberg David , Fuller Gregory , McGovern Susan , Paulino Arnold , Najjar Amer , Chandra Joya , Khatua Soumen , Zaky Wafik
Published: December 2020

DNA mismatch repair machinery is an integral part of the human genome and its defect has been involved in tumorigenesis and treatment resistance. Heterozygous monoallelic germline loss of function in MLH-1, MSH-2, MSH-6 or PMS-2 is involved in Lynch syndrome, whereas biallelic mutations cause constitutional mismatch repair deficiency (CMMRD) which is associated with hematologic malignancies and glioblastoma. We report here the clinical characterization and molecular analyses of 7 patients who presented with gliomas and MMR machinery aberrations. Two patients had a clinical diagnosis of NF-1 with dermatologic stigmata, of whom one patient has CMMRD and the other has Lynch syndrome. Two patients had a known family history of Lynch syndrome upon their diagnosis of glioma. Three patients with high-grade glioma and negative family history, 2 had germline mutations in MMR genes, and one had numerous mutations including MMR genes with microsatellite instability. Patients were initially treated with chemotherapy and radiation for high-grade gliomas (HGG); 5/7 had progression. Median time to progression was 12 months (range: 5–52), and median time from progression to death was 7 months (range: 2–25). One patient had low-grade glioma initially but progressed to HGG and is currently on therapy. Another patient treated with temozolomide and radiation is currently receiving maintenance therapy without any disease recurrence. Although the literature data on brain tumors with MMR deficiency is limited, these consistently show that MMRD-associated gliomas are treatment-resistant and have a dismal outcome. Collaborative efforts are needed to better understand this subgroup of pediatric HGG and to define optimal treatment strategy.
RARE-26. RETROSPECTIVE ANALYSIS OF PEDIATRIC CHOROID PLEXUS TUMORS
Authors: Nakano Yoshiko , Kawamura Atsufumi , Watanabe Yuko , Saito Ryuta , Kanemori Masayuki , Kiyotani Chikako , Yamasaki Fumiyuki , Nakagawa Naoki , Gomi Akira , Nakamura Taishi , Kunihiro Noritsugu , Okada Keiko , Sakamoto Hiroaki , Kitahara Mai , Hibiya Yuko , Nobusawa Sumihito , Ichimura Koichi
Published: December 2020

BACKGROUND

Choroid plexus tumors (CPT) include choroid plexus papilloma (CPP), atypical choroid plexus papilloma (aCPP), and choroid plexus carcinoma (CPC). Because of their rarity, limited data are available on the current status of treatment and outcomes for pediatric CPTs.

METHOD

We retrospectively reviewed clinical information on patients with CPT patients aged between 0 and 30 years at diagnosis and were treated in 8 institutions in Japan.

RESULTS

Of forty-two cases initially diagnosed as CPT, 18 cases were reviewed by central pathologists. As a result, the diagnosis of CPC or aCPP in five cases were changed to other tumors including AT/RT and astroblastoma. The remaining 37 cases were subjected to analysis. Median age at diagnosis was two years (0 to 25) and the mean follow-up period was seven years. All 26 patients with CPP (n=20) or aCPP (n=6) underwent gross-total resection without adjuvant therapy. Of them 24 patients are alive without recurrence. Four patients of patients with CPC (n=11) died of cancer. Five patients including three patients experienced local relapse, achieved complete remission after resection of tumor plus chemoradiotherapy. All three patients with dissemination of CPC at diagnosis or relapse died of the disease. At least three patients were diagnosed with Li-Fraumeni syndrome: one died of medulloblastoma and one patient developed osteosarcoma.

CONCLUSION

Compared with the excellent prognosis of CPP, the survival rates for CPC, especially disseminated CPC are unsatisfactory. Our results also underline the importance of considering genetic testing of TP53 for patients with CPC.
RARE-27. DOUBLE MUTATIONS: DIFFERENT GERMLINE AND TUMOR MUTATIONS LEAD TO POOR OUTCOMES
Authors: Hemenway Molly , Nellan Anan , Foreman Nicholas , Suttman Alexandra , Schneider Kami
Published: December 2020

BACKGROUND

As genetic testing for both germline and tumor mutations has increased in completeness, complexity, and availability, more mutations and their impact on patient outcomes have been identified.

METHODS

A retrospective review of pediatric patients who have identified germline mutations and a different tumor mutation was conducted. Data collected included demographics, tumor type, germline mutation status, tumor mutation status, relapse status, and patient outcome.

RESULTS

Six patients aged 8–13 years old (median age 10 years) were identified for analysis. Four patients had pilocytic astrocytoma and two had pilomyxoid astrocytoma. One of the patients with pilocytic astrocytoma also had MPNST diagnosed very early at age 9. The combination of germline/tumor mutations is as follows: Neurofibromatosis Type I (NF1)/BRAF v600e, NF1, CHEK2/MYB-QKI, NF1, Klinefelter, ATM, MUTYH, GPC3/BRAF-KIAA fusion, NF1/BRAF-KIAA (2 patients), and Marfan’s/BRAF-KIAA. The number of relapses per patient following initial diagnosis range from 3–7 with an average of 3.3. Four of the patients are alive and on therapy, which two are deceased. The two deceased patients both had NF1/BRAF-KIAA fusions and pilocytic astrocytomas.

CONCLUSIONS

Patients with differing and compounded germline and tumor molecular genetic mutations have worse outcomes. These patients have more relapses and death when compared to those patients with one mutation, either germline or tumor. Broad molecular testing and germline testing for mutations is crucial in determining patient risk for poor outcomes.
RARE-30. A RARE CASE OF PRIMARY EWING’S SARCOMA OF THE CERVICAL SPINE
Authors: Kalra Amandeep , Neil Jayson , Mann Sarah , Giglio Pierre
Published: December 2020

Ewing sarcoma family of tumors predominantly affect the pediatric population in the long bones of the extremities or the pelvis, and only 8% of cases arise within the spine. Primary Ewing’s sarcoma of the cervical spine is extremely rare and less than 30 cases have been reported in the literature thus far. Here we present a case of primary Ewing’s sarcoma of the cervical spine in a 28-year-old female who presented with a three-month history of neck pain and right arm radiculopathy. MRI revealed a homogeneously contrast enhancing, eccentric mass with dural tail at C2-C7. After undergoing a hemilaminectomy, histopathology confirmed extraosseous Ewing’s sarcoma with CD99 positivity. A comprehensive systemic and neuraxis work-up ruled out overt metastasis. We extrapolated data from children’s cooperative group studies and IESS-II clinical trial to formulate a three phase treatment protocol as described below. To date, patient is in remission with no evidence of any residual disease in the cervical spine. In conclusion, although Primary Ewing’s sarcoma of the cervical spine is extremely rare it should be considered a differential diagnosis in patients with neck pain and a spinal mass under the age of thirty. Less than 25% of EFT’s present with overt metastasis and almost all have subclinical metastatic disease at the time of diagnosis, therefore, a comprehensive evaluation and systemic chemotherapy is recommended. We recommend a multidisciplinary approach of surgical decompression to preserve neurological functions, followed by compressed chemotherapy regimens, reevaluation for local treatment, and adjuvant chemotherapy.
RARE-32. PEDIATRIC METASTATIC SKULL BASE CHORDOMA WITH TP53 MUTATION – A CASE REPORT AND REVIEW OF THE LITERATURE
Authors: Shimada Akira , Kurozumi Kazuhiko , Kanamitsu Kiichiro , Ishida Hisashi Ishida , Fujiwara Kaori , Washio Kana Washio , Kumamoto Tadashi , Ogawa Chitose , Shin Masahiro
Published: December 2020

Chordoma is an uncommon bone tumor arising from notochordal remnant, which accounts for 1–4% of all bone malignancies. It commonly occurs along the cranial-spinal axis, and skull base is one of most frequent sites, representing 35–49% of all chordoma cases. Surgical resection is widely accepted as the first choice of treatment. There are only limited number of reports about pediatric chordoma cases, and its biological behavior including genetic backgrounds were largely unknown. Here, we present a 5 year-old girl with a large aggressive skull base chordoma of 6 cm in maximum diameter, which eventually had multiple systemic metastasis. We initially tried chemotherapy based on the protocol for the osteosarcoma, but in vain. Because the tumor was highly vascularized on angiography, after embolization of the feeding arteries and bilateral internal maxillary arteries, endoscopic endonasal surgery was performed. The tumor was sufficiently removed, achieving effective mass reduction, and the residual tumors involving the lower cranial nerves and craniocervial junction were additionally treated with Gamma Knife radiosurgery. However, one month later, it showed systemic metastasis to bilateral cervical lymph nodes and lung. We tried chemotherapy with nivolmab and imatinib for this patient, whereas they showed the partial effect. The genetic analysis revealed somatic TP53 c.569C>T, (p.P190L) mutation in chordoma specimen. In the past literature, we found only one study of the adult chordoma cases, in which majority of the patients had somatic TP53 mutation (p.P72R). Further investigation with large number of the cases is essential to clarify the molecular biology of pediatric chordomas.
RARE-34. UK CHILDREN’S CANCER AND LEUKAEMIA GROUP (CCLG): GUIDELINES FOR THE MANAGEMENT OF MENINGIOMA IN CHILDREN, TEENAGERS AND YOUNG ADULTS
Authors: Szychot Elwira , Goodden John , Gillian Whitfield , Curry Sarah
Published: December 2020

Primary tumours of the meninges are rare accounting for only 0.4–4.6% of all paediatric tumours of the central nervous system. Due to the rarity of these tumours in children, and the consequent absence of collaborative prospective trials, there is no clear consensus on how the unique characteristics of paediatric meningiomas impact clinical status, management approach, and survival. Much of the evidence and treatment recommendations for paediatric meningiomas are extrapolated from adult data. Translating and adapting adult treatment recommendations into paediatric practice can be challenging and might inadvertently lead to inappropriate management. In 2009 Traunecker et al. published guidelines for the management of intracranial meningioma in children and young people on behalf of UK Children’s Cancer and Leukaemia Group (CCLG). Ten years later we have developed the updated guidelines following a comprehensive appraisal of the literature. Complete surgical resection is the treatment of choice for symptomatic meningiomas, while radiotherapy remains the only available adjuvant therapy and may be necessary for those tumours that cannot be completely removed. However, significant advances have been made in the identification of the genetic and molecular alterations of meningioma, which has not only a potential value in development of therapeutic agents but in surveillance of childhood meningioma survivors. This guideline builds upon the CCLG 2009 guideline. We summarise recommendations for the diagnosis, treatment, surveillance and long-term follow up of children and adolescents with meningioma.
RARE-38. CLINICAL PRESENTATION OF MGA-NUTM1 FUSION TRANSCRIPT SARCOMA
Authors: Pongphitcha Pongpak , Sirachainan Nongnuch , Jinawat Artit , Boonkird Atthaporn , Puataweepong Putipun , KhongKhatithum Chaiyos , Pakakasama Samart , Anurathapan Usanarat , Songdej Duantida , Bouffet Eric , Hongeng Suradej
Published: December 2020

BACKGROUND

MGA-NUTM1 fusion gene tumor are recently described as new subtype of NUTM1-rearranged tumors. Regarding its rarity, standard treatment has not been reported. Here we described clinical presentation, radiologic finding, immunohistological profile, and treatment of a boy with MGA-NUTM1 fusion gene tumor. CASE REPORT: A 13-year-old boy with 2-month history of progressive right hemiparesis and headache. Magnetic resonance imaging (MRI) revealed 7.8 x10.6 x 8.0 cm well defined heterogeneous enhancing mass at left fronto-parietal lobe. CT chest and abdomen, bone scan, MRI spine, and CSF studies were unremarkable. He underwent craniotomy with total tumor removal. Pathology demonstrated high grade spindle cell sarcoma. The immunohistological profile was positive for BCOR, NUT1, and TEL1, but negative for CD34, STAT6, desmin, SMA, actin sarcomeric, EMA, PR, S100, SOX10, BCL 6, and SABT2. The INI-1 showed nuclear expression and Ki-67 was positive in 50% of tumor nuclei. Molecular test for MGA-NUTM1 fusion transcript was positive, while SYT-SSX1, SYT-SSX2, and SYT-SSX4 fusion transcripts were negative. Four months after operation, MRI showed newly-seen two small enhancing foci at lateral and inferior aspects of the surgical cavity. He underwent re-surgery. Then focal radiation (54Gy and boost up to 60Gy at recurrent area) to the resection cavity was decided. Post-radiation chemotherapy including ifosfamide 3 g/m2 and etoposide 150 mg/m2 on Day 1–2, and carboplatin 500 mg/m2 on Day 3, every 21–28 days was started. He has completed the first course of chemotherapy without any complication.

CONCLUSION

MGA-NUTM1 fusion CNS sarcoma is rare. Treatment may require surgery, radiation and chemotherapy.
RARE-40. CASE REPORT: LONG-TERM SURVIVOR OF A RARE, PEDIATRIC PRIMARY HISTIOCYTIC SARCOMA (HS) OF THE CENTRAL NERVOUS SYSTEM (CNS) FOLLOWING COMPLETE RESECTION, CHEMOTHERAPY AND ALLOGENEIC HEMATOPOIETIC CELL TRANSPLANTATION (ALLO-HCT)
Authors: Osorio Diana S , Abu-Arja Rolla , Abdel-Baki Mohamed S , Leonard Jeffrey R , Sribnick Eric A , Finlay Jonathan L , Ellison David W , Picarsic Jennifer , Kahwash Samir , Boue’ Daniel R
Published: December 2020

We report an unusual case of a patient with primary CNS-HS a very rare neoplasm of histiocytic lineage with usually poor prognosis. An 8 year old boy presented with a one month history of headaches, nausea and vomiting. Physical examination revealed nystagmus and dysmetria. Brain MRI revealed a localized 2.4 cm posterior fossa (cerebellar) mass with restricted diffusion. The patient underwent a gross total resection of the mass. Initial post-operative lumbar puncture was positive for rare malignant cells. Pathology showed a focally necrotic neoplasm, composed of nests and cords of large relatively uniform cells with abundant eosinophilic cytoplasm, moderately pleomorphic nuclei and numerous mitotic figures, consistent with CNS-HS with juvenile xanthogranuloma phenotype, as supported by positive IHC expression of CD163, CD68, CD14, fascin, and Factor XIIIa, while negative for CD1a, Lymphoid and Myeloid markers, and BRAFv600e mutation. He was treated with two cycles of clofarabine and cytarabine and triple intrathecal (IT) chemotherapy. He developed generalized seizures and MRI showed demyelination consistent with IT methotrexate toxicity; MTX was then discontinued. He was then given two additional cycles of cladribine and weekly intrathecal therapy prior to consolidation with an Allo-HCT using a 10/10 HLA allelic-matched unrelated donor. His conditioning regimen included total body irradiation and cyclophosphamide. He did well post-transplant with peripheral blood chimerism at 1 year showing > 95% donor cells. He remains disease-free with an excellent quality of life since August 2016. We report one of the few known survivors of this unusual and highly malignant entity.
RARE-48. CHARACTERISTICS AND OUTCOME OF DIFFUSE LEPTOMENINGEAL GLIONEURONAL TUMOR (DLGNT): A SINGLE INSTITUTION EXPERIENCE
Authors: Pickle Emily Owens , Aguilar-Bonilla Ana , Smith Amy
Published: December 2020

Diffuse leptomeningeal glioneuronal tumors (DLGNT) are rare with an unknown etiology and unestablished incidence. Most frequently reported genetic alteration is KIAA1549-BRAF fusion. We present four DLGNT cases diagnosed between 2005–2018. Patient 1 is a female who presented with a 2-year history of back pain subsequently diagnosed with pilocytic astrocytoma. Re-imaging 3 months post-resection revealed a low grade glioneuronal tumor with BRAF duplication. Patient 2 is a female who presented with recurrent vomiting, dizziness, and hydrocephalus. The patient underwent biopsy which was consistent with oligodendrogliomatosis; no genetic analysis was done. Patient 3 is a male who presented with worsening headaches and intermittent vomiting. Approximately 5 months after resection, imaging showed leptomeningeal disease and further testing revealed KIAA1549-BRAF fusion and 1p deletion. Patient 4 is a male who presented with hydrocephalus. Imaging showed disseminated leptomeningeal enhancement without a dominant mass lesion; biopsy and clinical history confirmed the diagnosis. All four patients received chemotherapy, Patients 1 and 3 underwent radiation therapy, and Patient 3 received a MEK-inhibitor to which he had a great response. However, the patient was non-compliant and had PD which continued despite re-starting therapy. Patients 1, 2, and 3 have died of progressive disease; survival was Patient 1, 276 days, Patient 2, approximately 7 years and 8 months, and Patient 3, 2 years and 11 months. Patient 4 remains alive with disease 4.5 years from diagnosis. There is much to be learned about this rare, poorly understood disease but hope for improvement through therapeutic targeting of the MAPK pathway.
RARE-50. TREATMENT RESPONSE OF CNS HIGH-GRADE NEUROEPITHELIAL TUMORS WITH MN1 ALTERATION
Authors: Baroni Lorena V , Rugilo Carlos , Lubieniecki Fabiana , Sampor Claudia , Freytes Candela , Nobre Liana , Hansford Jordan R , Malalasekera Vajiranee S , Zapotocky Michal , Dodgshun Andrew , Ramaswamy Vijay , Alderete Daniel
Published: December 2020

BACKGROUND

CNS high-grade neuroepithelial tumor with MN1 alteration (CNS HGNET-MN1) are a rare entity recently described as a high-grade tumor containing a mixture of solid and pseudopapillary patterns with MN1 rearrangement.

METHODS

CNS HGNET-MN1 patients were identified using genome wide methylation arrays across 5 institutions (the Hospital JP Garrahan, Hospital for Sick Children, the University Hospital Motol, Royal Children`s Hospital and Christchurch Hospital) and was correlated with treatment and outcome. Central imaging review with radiological features analysis was performed.

RESULTS

We identified 9 patients harboring CNS HGNET-MN1 tumors through application of the Heidelberg brain tumor classifier. Seven tumors were T supratentorial and two in the spinal cord. Median age was 5 (range 3.6–14.6). All patients had surgery (6 GTR and 3 STR) as initial management followed by radiotherapy (focal 5/CSI 1) and systemic chemotherapy in 2 patients. Four of the 9 patients relapsed by 3 years post diagnosis, with 2 local and 2 metastatic failures despite complete surgical resections and radiotherapy. Three patients died due to tumor relapse after 24 months despite upfront radiotherapy. Seven of 9 patients had an initial diagnosis of ependymoma.

CONCLUSION

Treatment of CNS HGNET-MN1 remains a major challenge with multiple failures, despite aggressive surgical resections and upfront involved field radiotherapy. Further multicenter, international prospective studies are required to determine the optimal treatment strategy for this group of tumors.
RARE-55. CHALLENGES AND SPECIFIC STRATEGIES FOR CONSTITUTIONAL MISMATCH REPAIR DEFICIENCY SYNDROME IN LOW RESOURCE SETTINGS. ON BEHALF OF THE INTERNATIONAL RRD CONSORTIUM IN LOW RESOURCE SETTINGS PANEL
Authors: Kebudi Rejin , N Nisreen Amayiri , Abedalthagafi Malak , Rana Asim Noor , Kirmani Slman , Musthaq Naureen , Lamki Zakiya Al , El Houdzi Jamilla , Yazıcı Hulya , El-Naggar S , Edwards Melissa , Bianchi Vanessa , Durno Carol , Tabori Uri , Bouffet Eric
Published: December 2020

Germline biallelic mutations in one of the mismatch repair genes (MSH2/MSH6/MLH1/PMS2 results in constitutional mismatch repair deficiency (CMMRD), a condition associated with multiple tumors arising from multiple organs during childhood, and these individuals rarely reach adulthood. The paucity of information with respect to these conditions leads to mismanagement and may be a factor in the high mortality of patients with CMMRD. Two international consortia, the European CARE4CMMRD, and the international replication repair deficiency (RRD) consortium, are addressing the many challenges associated with this condition. To address specific issues surrounding the management of CMMRD in low and middle income countries (LMIC), a multidisciplinary taskforce of 11 specialists from nine countries was formed. Preliminary conclusions are: 1) Immunohistochemistry for CMMRD should be considered for all patients with suggestive clinical features. In countries where CMMRD is common, malignant gliomas, colon cancers and T cell lymphomas should be stained routinely as the prevalence of CMMRD in these tumors can exceed 40%. 2) Temozolomide should not be used in the management of malignant glioma. By contrast, preclinical studies have suggested increased sensitivity to nitrosoureas. For the management of CMMRD related lymphoma and leukemia, mercaptopurines should not be avoided or discontinued as a part of the standard of care before more data are collected. 3) Management with checkpoint inhibitors should be limited to centers with intensive care units and expertise in complex supportive care to manage side effects of immune therapy. 4) Surveillance protocols have demonstrated long term survival benefits and should be implemented in LMIC.
RARE-57. PEDIATRIC CHORDOMA: WHOLE EXOME SEQUENCING OF 11 PEDIATRIC CHORDOMA SAMPLES
Authors: O’Halloran Katrina , Bootwalla Moiz , Merkurjev Daria , Kaneva Kristiyana , Ryutov Alex , Cotter Jennifer , Ji Jianling , Ostrow Dejerianne , Biegel Jaclyn A , Gai Xiaowu
Published: December 2020

Chordoma is a rare tumor and while SMARCB1 alterations have been observed in poorly differentiated chordomas, conventional chordomas are not well understood. We interrogated nuclear and mitochondrial genomes of 11 chordoma samples from 7 children. Frozen tumor tissue DNA was extracted and whole exome libraries generated using Agilent SureSelect Human All Exon V6 kit plus mtDNA genome capture kit. Libraries were sequenced using Illumina Nextseq 500. MuTect2, VarDict and LUBA variant callers were used with allele frequency cutoff 2%. Potential germline variants were filtered bioinformatically. In total, 656±74 high-confidence somatic variants, including 368±43 nonsynonymous variants per sample were detected. Of 2,607 combined unique nonsynonymous variants, 95% were missense. Remaining high impact variants were frameshift (37%), stop gain (39%), splice acceptor/donor (22%), start and stop loss (2%). Of the unique nonsynonymous variants, 137 fall within Cosmic Cancer Census Genes, including high impact variants in SETD2, MLLT4. No previously reported TBXT, CDKN2A, PI3K, LYST mutations identified. Tumor Mutation Burden/Megabase was 10±1. The mitochondrial analysis revealed heteroplasmic m.11727C>T MT-ND4 missense variants in three tumors resected at different time points from the same patient, and another heteroplasmic m.1023C>T rRNA mutation from the primary and recurrent tumors of another patient. Intriguingly, two Children’s Brain Tumor Tissue Consortium patients with chordoma had identical heteroplasmic m.10971G>A MT-ND4 nonsense mutations. Pediatric chordomas appear to lack somatic nuclear mutations. Observing recurrent mitochondrial mutations across multiple tumors from the same and/or different patients is striking, suggesting they may be implicated in tumorigenesis and be potential diagnostic markers.
RARE-62. VISUAL FUNCTION IN CHILDREN WITH CRANIOPHARYNGIOMA AT DIAGNOSIS: A SYSTEMATIC REVIEW
Authors: Nuijts Myrthe , Veldhuis Nienke , Stegeman Inge , van Santen Hanneke , Porro Giorgio , Imhof Saskia , van Meeteren Antoinette Schouten
Published: December 2020

Childhood craniopharyngioma is a rare and slow growing brain tumour, often located in the sellar and suprasellar region. It commonly manifests with visual impairment, increased intracranial pressure and hypothalamic and/or pituitary deficiencies. Visual impairment in childhood adversely affects a child’s daily functioning and quality of life. We systematically reviewed the literature to provide an extensive overview of the visual function in children with craniopharyngioma at diagnosis in order to estimate the diversity, magnitude and relevance of the problem of visual impairment. Of the 543 potentially relevant articles, 84 studies met our inclusion criteria. Visual impairment at diagnosis was reported in 1041 of 2071 children (50.3%), decreased visual acuity was reported in 546 of 1321 children (41.3%) and visual field defects were reported in 426 of 1111 children (38.3%). Other ophthalmological findings described were fundoscopic (32.5%) and orthoptic abnormalities (12.5%). Variations in ophthalmological testing methods and ophthalmological definitions precluded a meta-analysis. The results of this review confirm the importance of ophthalmological examination in children with craniopharyngioma at diagnosis in order to detect visual impairment and provide adequate support. Future studies should focus on long-term visual follow-up of childhood craniopharyngioma in response to different treatment strategies to provide insight in risks and ways to prevent further loss of vision.
RONC-01. PROTON BEAM THERAPY IN THE MULTIDISCIPLINARY THERAPY FOR PEDIATRIC BRAIN AND SPINAL TUMOR AT KOBE CHILDREN’S HOSPITAL WITH KOBE PROTON CENTER
Authors: Kawamura Atsufumi , Koyama Junji , Akutsu Nobuyuki , Demizu Yuske , Fukumitsu Nobuyoshi , Soejima Toshinori , Kosaka Yoshiyuki
Published: December 2020

It could be remarked that Radiotherapy (RT) has the important role for the multidisciplinary therapy to Malignant Pediatric Central Nervous System tumor. And recently among RT, Proton Beam Therapy (PBT) is expected to be effective and decrease serious late effects after RT in malignant pediatric tumor. PBT could be controlled precisely the dose and depth and spare the normal structures outside the target. Thus, PBT becomes applicable for pediatric solid tumor to insurance in April, 2016 in Japan. We have worked in closer cooperation with Hyogo Prefectural Ion Beam Medical Center and started PBT from April 2015. And from December 2017, our PBT has transferred to adjacent new medical center (Kobe Proton Center) which has the only institute that equipped the exclusive gantry for children in our country. The treated cases are 28 boys and 35 girls (age average 8.2 years oid). They are 15 Germ cell tumor, 14 Ependymoma, 13 Medulloblastoma, 4 Chordoma, 4 Atypical teratoid/rhabdoid tumor, 2 Craniopharyngioma and others. We have simulated the applications of not only broad beam but also scanned beam to limit the dose distribution and prepare for the cranio-spinal irradiation. All cases underwent magnetic resonance imaging to evaluate the results at out clinic and also the complications are assessed after treatments. The effect of PBT in this series is similar to our experience of traditional RT. There are a few controllable complications such as conventional RT. Farther more follow up is necessary to evaluate the advantage of PBT which could reduce delayed complications of RT.
RONC-04. RE-IRRADIATION AFTER TREATMENT OF MEDULLOBLASTOMA; RELAPSED CASES AND SECOND CANCER CASES
Authors: Soejima Toshinori , Fukumitsu Nobutoshi , Demizu Yusuke , Mima Masayuki , Suzuki Takeshi , Kawamura Atsufumi , Kosaka Yoshiyuki
Published: December 2020

PURPOSE

Late complications such as brainstem necrosis are great concern of re-irradiation for brain tumor. Proton beam therapy can reduce radiation dose of organs at risk such as brainstem, so is expected to reduce late complications.

PATIENTS AND METHODS

Patients with medulloblastoma treated with re-irradiation from January 2015 to February 2019 at the Kobe Children’s Hospital and the Kobe Proton Center were reviewed. There were three cases of relapsed medulloblastoma and three cases of second cancer (glioblastomas).

RESULTS

In relapsed cases, all three cases treated with 12 Gy in 8 fractions cranio-spinal irradiation followed by gamma knife radiosurgery (one) or 28.8 Gy (RBE) in 16 fractions of proton beam therapy (two). Follow-up periods were 8 to 19 months (median 12 months) and all three cases survived without relapse. In second cancer cases, all three cases were treated with 40.05 Gy per 15 fractions of radiation therapy (2 cases were treated with photon and one case with proton). However, all cases relapsed and two cases died of disease.

CONCLUSION

Twelve Gy in 8 fractions cranio-spinal irradiation followed by 28.8 Gy (RBE) in 16 fractions of proton beam therapy is thought to be useful for the relapsed case. Re-irradiation for second cancer was disappointing and further study is warranted.
RONC-13. RADIATION INDUCED BRAIN STEM GLIOMA AFTER RADIATION THERAPY FOR MIXED GERM CELL TUMOR
Authors: Yamamura Natsumi , Nonaka Masahiro , Asai Akio
Published: December 2020

We report a case of radiation-induced glioma in the pons after radiation therapy for germ cell tumor. A 17-year-old man was diagnosed as HCG and AFP secreting germ cell tumor at the age of 9. The tumor was located in the suprasellar region, which filled up most part of the third ventricle. Five courses of chemotherapy with cisplatin, etoposide, and cyclophosphamide, and whole ventricle plus local radiation therapy (total 51.2 Gy / 32Fr) were performed. After the treatment, most part of the tumor was regressed, and only small enhanced lesion remained. Six years after the treatment, he started to be ataxic, and worsened. An MRI revealed an enhanced lesion in the pons. Lesion biopsy was performed via the right cerebellar peduncle. Histopathological diagnosis confirmed the lesion was high grade glioma. He underwent extended local radiation therapy (50.4 Gy / 28 Fr) and administered temozolomide. Later, bevacizumab was added, and 3 months after treatment started, the size of the tumor was reduced and his symptoms were improving. There is no established treatment for radiation induced glioma. However, additional radiation therapy, temozolomide and bevacizumab appears to be useful to reduce tumor size and resolve the symptoms, even if it is transient.
RONC-17. STEREOTACTIC RADIOSURGERY FOR SPINE METASTASES IN PEDIATRIC MALIGNANCIES
Authors: Woodhouse Kristina , Alvarez Victor Albornoz , Boyce David , Li Jing , Yeboa Debra , Grosshans David , Briere Tina , Tatsui Claudio , Rhines Laurence , Behrang Amini , McGovern Susan , Paulino Arnold , McAleer Mary Frances , Ghia Amol
Published: December 2020

BACKGROUND

Spine stereotactic radiosurgery (SSRS) is a non-invasive technique that delivers ablative radiotherapy for optimal control of bony disease. While SSRS is known to provide excellent local control (LC) and minimal toxicity in adults, the role of SSRS in pediatrics is less clear.

PURPOSE

To evaluate SSRS in pediatric patients with spinal metastases.

METHODS

A retrospective review of patients (<18 yrs) treated with SSRS at MDACC was performed after IRB approval. Descriptive statistics were utilized for analysis.

RESULTS

From 2011–2019, 12 metastatic osseous sites (3 cervical, 4 thoracic, 5 lumbar-sacral) in 9 patients were treated. Median follow-up was 9 months (range 2–41). Six males (67%) and 3 females (33%) all KPS ≥70, received radiation to ≤3 contiguous vertebral bodies. Median age was 16 yrs (range 8–18). No patients required sedation. Histologies included 7 osteosarcomas, one rhabdomyosarcoma and one Ewing’s sarcoma. Metastatic epidural spinal cord compression scores ranged from 0 (6), 1b (3) and 3 (3). No sites had surgery prior to SSRS and one site received prior conventional radiation. SSRS doses included 24 Gy in 1 fraction (7), 24–27 Gy in 3 fractions (4) and 50 Gy in 5 fractions (1). Six-month LC was 83% with one local failure following 27 Gy. OS at 6 and 12 mo were 55% and 23%. There was no grade ≥3 acute toxicity, no radiation myelopathy or vertebral compression fractures.

CONCLUSION

In this initial report, SSRS represents a promising modality that is well tolerated and provides excellent LC. However, further follow-up is warranted in the pediatric setting.
RONC-18. ANALYSIS OF BRAIN TUMOR INDUCED BY IRRADIATION IN CHILDHOOD - A SINGLE INSTITUTIONAL ANALYSIS
Authors: Sano Takashi , Tamura Kaoru , Kuroha Masae , Sumita Kazutaka , Arai Yukika , Sugawara Takashi , Inaji Motoki , Tanaka Yoji , Nariai Tadashi , Maehara Taketoshi
Published: December 2020

BACKGROUND

Radiation-induced brain tumors are rare tumors that appear during long-term follow-up after radiation therapy. Children are at greater risk for radiation -induced brain tumors than adults. The clinical characteristics of radiation-induced brain tumor treated at our hospital were retrospectively examined.

PATIENTS AND METHODS

Clinical characteristics of seven radiation-induced brain tumors that developed in 6 patients irradiated in their childhood at our hospital were analyzed. The background disease, age at irradiation, irradiation dose, period from irradiation to onset, pathological diagnosis, and treatment for radiation-induced brain tumor were examined.

RESULTS

Background diseases for irradiation were leukemia in 3 patients, germinoma in 2, medulloblastoma in 1, and the average cranial irradiation dose was 23.2 Gy. The patients tended to be young at irradiation (2–17 yeays; median:4 years old). The time between irradiation and the onset of radiation-induced brain tumors ranged from 9.5 to 39.1 years (median:28 years). Radiation-induced brain tumors comprised 6 meningioma（grade I:5, grade II:1）and 1 high-grade gliomas. All patients underwent surgical removal of the radiation-induced brain tumors and 2 received additional irradiation. During a median of 5.3 years of follow-up after the diagnosis of radiation-induced brain tumors, 2 underwent second surgery, while the remaining 4 have no recurrence. DISCUSSION: In most cases, radiation-induced brain tumors occur for a long time after irradiation in childhood. Monitoring of radiation-induced brain tumors as well as primary tumor recurrence was considered important.
RONC-19. TWO CASES OF RE-IRRADIATION FOR LATE RECURRENT OR RADIATION-INDUCED TUMOR AFTER RADIATION THERAPY FOR PEDIATRIC BRAIN TUMORS
Authors: Mori Takashi , Yamaguchi Shigeru , Onimaru Rikiya , Hashimoto Takayuki , Aoyama Hidefumi
Published: December 2020

BACKGROUND

As the outcome of pediatric brain tumors improves, late recurrence and radiation-induced tumor cases are more likely to occur, and the number of cases requiring re-irradiation is expected to increase. Here we report two cases performed intracranial re-irradiation after radiotherapy for pediatric brain tumors. CASE 1: 21-year-old male. He was diagnosed with craniopharyngioma at eight years old and underwent a tumor resection. At 10 years old, the local recurrence of suprasellar region was treated with 50.4 Gy/28 fr of stereotactic radiotherapy (SRT). After that, other recurrent lesions appeared in the left cerebellopontine angle, and he received surgery three times. The tumor was gross totally resected and re-irradiation with 40 Gy/20 fr of SRT was performed. We have found no recurrence or late effects during the one year follow-up. CASE 2: 15-year-old female. At three years old, she received 18 Gy/10 fr of craniospinal irradiation and 36 Gy/20 fr of boost to the posterior fossa as postoperative irradiation for anaplastic ependymoma and cured. However, a anaplastic meningioma appeared on the left side of the skull base at the age of 15, and 50 Gy/25 fr of postoperative intensity-modulated radiation therapy was performed. Two years later, another meningioma developed in the right cerebellar tent, and 54 Gy/27 fr of SRT was performed. Thirty-three months after re-irradiation, MRI showed a slight increase of the lesion, but no late toxicities are observed.

CONCLUSION

The follow-up periods are short, however intracranial re-irradiation after radiotherapy for pediatric brain tumors were feasible and effective.
RONC-31. ADVANCED ECHOCARDIOGRAPHY WITH MYOCARDIAL-STRAIN-ANALYSIS DESCRIBES SUBCLINICAL CARDIAC DYSFUNCTION AFTER CRANIOSPINAL IRRADIATION (CSI) IN PEDIATRIC AND YOUNG ADULT PATIENTS WITH CENTRAL NERVOUS SYSTEM (CNS) TUMORS
Authors: Martinez Hugo , Salloum Ralph , Wright Erin , Khoury Philip , Tretter Justin , Ryan Thomas
Published: December 2020

CSI is part of the treatment of CNS tumors and is associated with cardiovascular disease; data in pediatric/young-adult patients are limited. Myocardial-strain-analysis can reveal subclinical dysfunction. Retrospective, single-center study in CNS tumor patients managed with CSI from 1986–2018. Clinical details, and echocardiography including myocardial-strain-analysis were collected at T1=first echocardiogram after CSI, and T2=most recent echocardiogram. Data are mean±standard deviation. Echocardiograms were available in 44 patients (36%female, 14±8.0years) at T1 and 39 patients (38%female, 21.0±11.3years) at T2. Standard echocardiography was normal for all subjects. At T1, global longitudinal peak systolic strain (GLS) was -16.3%±3.7% in CSI vs. -21.6%±3.5% in controls (p<0.0001); global radial peak systolic strain (GRS) was 21.5%±10.1% in CSI vs. 26.5%±7.4% in controls, and global circumferential peak systolic strain (GCS) was -19.5%±6.0% in CSI vs. -21.4%±3.4% in controls (p<0.05, both comparisons). At T2, GLS was -15.8%±5.2% in CSI vs. -21.9±3.5% in controls (p<0.0001); GRS was 22.6%±10.4% in CSI vs. 27.1±8.2% in controls (p<0.05); GCS was -20.5%±6.9% in CSI vs. -21.8±3.5% in controls (p=0.10). For 17 patients with myocardial-strain-analysis available for both time points: difference in GLS was 0.06±7.2% (p>0.95); GRS was 5.5±9.5% (p<0.05); GCS was -3.4±4.9% (p<0.05). Subclinical dysfunction is present at first echocardiogram after CSI. Myocardial impairment may recover with time, however further analysis is needed to identify risk factors and trends. These results argue for inclusion of baseline cardiovascular assessment and longitudinal follow-up in CNS tumor patients post CSI.
RONC-32. LOCAL CONTROL FOLLOWING PROTON THERAPY FOR PEDIATRIC CHORDOMA
Authors: Indelicato Daniel , Rotondo Ronny , Vega Raymond , Holtzman Adam , Looi Wen Shen , Morris Christopher , Sandler Eric , Aldana Philipp , Bradley Julie
Published: December 2020

BACKGROUND

Due to the location and high dose required for disease control, pediatric chordomas are theoretically well-suited for treatment with proton therapy, but their low incidence limits the clinical outcome data available in the literature. METHODS AND MATERIALS: Between 2008 and 2019, 29 patients with a median age of 14.8 years (range, 3.8–21.8) received proton therapy for non-metastatic chordoma at a single institution. Twenty-four tumors arose in the clivus/cervical spine region and 5 in the lumbosacral spine. Twenty-six tumors demonstrated well-differentiated histology and 3 were dedifferentiated or not otherwise specified (NOS). Approximately half of the tumors underwent specialized testing: 14 were brachyury-positive and 10 retained INI-1. Seventeen patients had gross disease at the time of radiation. The median radiation dose was 73.8 GyRBE.

RESULTS

With a median follow-up of 4.3 years (range, 1.0–10.7), the 5-year estimates of local control, progression-free survival, and overall survival rates were 85%, 82%, and 86%, respectively. Excluding 3 patients with dedifferentiated/NOS chordoma, the 5-year local control, progression-free survival, and overall survival rates were 92%, 92%, and 91%, respectively. Serious toxicities included 3 patients with hardware failure or related infection requiring revision surgery, 2 patients with hormone deficiency, and 2 patients with Eustachian tube dysfunction causing chronic otitis media.

CONCLUSION

In pediatric patients with chordoma, proton therapy is associated with a low risk of serious toxicity and high efficacy, particularly in well-differentiated tumors. Complete resection may be unnecessary for local control and destabilizing operations requiring instrumentation may result in additional complications following therapy.
SURG-04. THE APPLICATION OF EN BLOC RESECTION IN THE OPERATION OF PEDIATRIC POSTERIOR FOSSA TUMOR
Authors: Jie Ma , Mao Weiwei , Tian Shuaiwei , Wang Baocheng , Zhao Yang
Published: December 2020

OBJECTIVE

To explore the efficacy and safety of en bloc resection therapy on posterior fossa tumor in children.

METHODS

A retrospective analysis was conducted on the clinical data of 94 patients with posterior fossa tumor admitted to Department of Pediatric Neurosurgery, Xinhua Hospital Affiliated to Shanghai Jiaotong University School Of Medicine from January 2018 to December 2019. Among them, 35 cases were treated with traditional resection (control group) and 59 cases with en bloc resection (observation group). We counted the amount of blood loss and the time during tumor resection, We compare the symptoms and signs between the two groups and determine a extent of tumor resection based on microscopic observation and preoperative and postoperative imaging comparison. RESULT: The total tumor resection rate of the observation group (88.1%, 52 / 59) was significantly higher than that of the control group (62.85%, 22 / 35, P < 0.05). The average bleeding volume of 90.8ml in the observation group was significantly smaller than that of the control group (113.3ml, P < 0.05), and the average operation time of 38.6min in the observation group was shorter than that of the control group (57.4min, P < 0.05) only for tumor resection procedure.

CONCLUSION

En bloc resection technique can effectively accelerate the resection time, reduce intraoperative bleeding and improve the total resection rate of tumors in children’s posterior cranial fossa.
SURG-05. AN AWAKE SURGERY FOR A CHILD SUFFERING FROM EPILEPSY DUE TO DYSEMBRYPLASTIC NEUROEPITHELIAL TUMOR LOCATED IN THE LEFT PARIETAL LOBE
Authors: Kiyokawa Juri , Yamamoto Shinji , Murota Yasuhiro , Ishikawa Mariko , Yamaoka Hiroto , Kaneko Satoshi , Yoshimura Masataka , Hirota Shin , Inaji Motoki , Maehara Taketoshi
Published: December 2020

BACKGROUND

An awake surgery is a useful measure to remove tumors located close to eloquent areas of the brain to reduce surgical complications and maximize the resection. However, it has some disadvantages compared to surgeries under general anesthesia. Generally speaking, applying it to a child under 15 years-old (y/o) is hesitating because of anxiety, poor tolerance, failure to cooperate in tasks and so forth. Here, we present a case of a 13y/o girl who underwent an awake surgery due to dysembryplastic neuroepithelial tumor (DNT) located in the left parietal lobe. CASE PRESENTATION: She consulted our hospital for epileptic seizures. MRI showed a multilocular mass lesion in the left parietal lobe. The tumor was located in or close to eloquent areas. The epilepsy was refractory even with multiple antiepileptic drugs (AEDs). A Wada examination revealed that her speech area is on the left hemisphere. The operations were performed in two stages. Prior to the operations, we had several thought-out simulations in the operating room and ICU with her, her parents, and our staff including nurses and lab technicians. The first operation was to perform tumor biopsy and place intracranial electrodes. The histological diagnosis was DNT. Video electroencephalogram showed that the epileptogenic lesion was around the tumor. The second operation resulted in total tumor resection and reduction of paroxysmal epileptic spikes without major complications. She is seizure free for more than three years with two AEDs.

CONCLUSION

Careful preparations may enable an awake surgery even for a child under 15y/o.