bluuebunny/crossref_metadata_2025_split huggingface dataset:
RARE-42. PRIMARY INTRACRANIAL SARCOMA WITH DICER1-MUTATION - TREATMENT RESULTS OF A NEW MOLECULAR ENTITY
Authors: Diaz Rosdali , Mynarek Martin , Casavilca Sandro , Aptomizer Antonio Wachtel , Mora Pamela , Koelsche Christian , Von Deimling Andreas , Schüller Ulrich , Sernaque Raymundo , Sarria Gustavo , Negreiros Tatiana , Ojeda Luis , Garcia-Corrochano Pamela , Campos Danny , Ponce Jimena , Rutkowski Stefan , Garcia Juan 
Published: December 2020

Abstract

OBJECTIVE
An unexpectedly high incidence of sarcomas of the Central Nervous System (SCNS) was recently observed in Peru. We describe clinical and biological characteristics of the disease.

METHODS
Seventy pediatric patients with primary SCNS diagnosed between January 2005 and June 2018 were analyzed. DNA methylation profiling and gene panel sequencing was available from 28 and 27 tumors, respectively.

RESULTS
Median age was 6 years (range 2–17.5), 66/70 patients had supratentorial tumors, 56 patients intratumoral hemorrhage at diagnosis. Three patients fulfilled clinical criteria of NF1; 35 had café-au-lait spots and/or freckling. DNA-methylation profiling classified 28/28 as “intracranial spindle cell sarcoma with rhabdomyosarcoma-like features and DICER1 mutations”. DICER1 mutations were found in 26/27, TP53 mutations in 22/27, and RAS-pathway gene mutations (NF1, KRAS, NRAS) in 19/27 tumors, all of which were somatic (germline control available in n=19 cases). Survival was analyzed in 57 patients with non-metastatic disease who received adjuvant therapy. Two patients had metastatic disease, eleven did not receive or abandoned treatment. Two-year OS was 66.3% (95%-CI: 54–81%), 2-year PFS 51% (38–67%). PFS was highest in patients treated with postoperative ICE chemotherapy followed by radiotherapy and ICE (2y-EFS 79% [59–100%], n=18) and worse after upfront radiotherapy followed by ICE (40% [19–85%]; n=10) or VAC (50% [28–88%], n=12) and radiotherapy only (21% [6–71%], n=11; p=0.008).

CONCLUSION
Primary SCNS with DICER1 mutation have an aggressive clinical course. A combination of chemotherapy and radiotherapy seems beneficial. A link to a cancer predisposition syndrome could not be established so far.
RARE-46. A THIRTEEN YEAR PATIENT JOURNEY OF INFANT GIANT CLIVAL CHORDOMA: CASE REPORT AND LITERATURE REVIEW
Authors: Apps John , Neumann Eloise , Afshari Fardad , Solanki Guirish , English Martin 
Published: December 2020

Abstract
In 2006 we reported the youngest case of a large clival chordoma, a 15-week old baby, the second case to present without skull base involvement and the fourth case of chordoma in a patient with tuberous sclerosis. This unusually rare case (surgically un-resect able) underwent endoscopic skull-base diagnostic biopsy and a novel chemotherapy regime that aimed to control his disease[i]. Initial tumour control was achieved with chemotherapy (Ifosfamide, doxorubicin with dexrazonane, intrathecal hydrocortisone, methotrexate, cytarabine). Carboplatin and etoposide were later given for a further year. Following this, Sirolimus and imatinib were used for another twelve months due to primary tumour regrowth and three new skull-vault lesions. Sirolimus alone was continued for an additional year, but stopped due to optic neuritis. Imatinib was given until further progression two years later, leading to a change to everolimus. Surgery for the ventral foramen magnum was performed a year later. The patient received further surgery and radiotherapy for tumour recurrence. Sadly the tumour metastasised and he succumbed at age 13. Chordomas are aggressive and recur frequently. Complete primary resection followed by radiotherapy/proton beam therapy offers the best chance of cure but is not an option in infants with giant lesions, as in our case. We inform on alternative targeted treatment strategies and review the literature on these rare lesions. [i] Kambogiorgas D, St George EJ, Chapman S, English M, Solanki G: Infantile Clivus chordoma without clivus involvement: Case report and review of the literature, Childs Nerv System (2006) 22:1369–1374
RARE-52. RB1 GENE DELETIONS ARE THE NOVEL MECHANISM OF CHOROID PLEXUS TUMORS (CPT) ONCOGENESIS
Authors: Druy Alexander , Yasko Liudmila , Valiakhmetova Andge , Novichkova Galina , Papusha Liudmila 
Published: December 2020

Abstract

BACKGROUND
CPTs are known to be rare TP53-dependent neoplasms, while major molecular alterations underlying tumor progression, especially in TP53-wild type cases, are still unclear.

METHODS
18 primary CPT, including 16 choroid plexus carcinomas (CPC) and two atypical choroid plexus papillomas (CPP), were evaluated for copy number status of 87 major oncogenes and tumor suppressor genes by nCounter Cancer CNV assay by Nanostring and TP53 and RB1 by MLPA. Germline TP53 nucleotide substitutions were analyzed by Sanger sequencing.

RESULTS
Pathogenic germline TP53 variants were present in 4 cases confirming Li-Fraumeni syndrome (LFS). Two patients have somatic TP53 substitutions. Only one patient with LFS harbored somatic TP53 deletion. In 7 patients, heterozygous deletions of RB1 involving from 3 exons to the whole coding sequence detected by MLPA were discovered. All these findings were validated by nCounter CNV assay. Additionally, four patients have WT1 deletions, two patients – BRCA2, and in 1 case - NF1, concomitant with RB1 deletions in 3 cases. Interestingly, in one patient who faced a progression of CPP to CPC germline, RB1 deletion was detected, and in both subsequent tumors, the length of the deleted region progressively increased. Notably, that RB1 deletions are mostly mutually exclusive to TP53 substitutions. 3 of 4 patients with RB1 deletions having follow-up period &gt;1 year faced with tumor-related adverse events.

CONCLUSIONS
Somatic or uncommon germline RB1 heterozygous deletions have been unraveled as a novel mechanism of aggressive CPT and could be implemented in prognosis definition schemes.
RARE-56. PERITONEAL SEEDING OF A DIFFUSE LEPTOMENINGEAL GLIONEURONAL TUMOR IN A CHILD
Authors: Messiaen Julie , Uyttebroeck Anne , Depreitere Bart , Bempt Isabelle Vanden , Sciot Raf , Jacobs Sandra A 
Published: December 2020

Abstract
Diffuse leptomeningeal glioneuronal tumors (DLGNT) are rare neoplasms of the central nervous system and have been included in the 2016 update of the WHO classification. This is the first description of a DLGNT disseminating to the peritoneal cavity via a ventriculoperitoneal shunt (VPS) in a child. We describe an 11-year old girl who received a VPS for a Dandy-Walker malformation at the age of seven, and was diagnosed with a spinal pilocytic astrocytoma with leptomeningeal metastases six months later. She received chemotherapy (SIOP-LGG protocol) with partial response, and had progressive disease eight months after therapy cessation. Following a novel biopsy, the diagnosis was revised to a DLGNT, with a KIAA1549-BRAF fusion and loss of 1p. She received vinblastine, but was clinically progressive and craniospinal radiotherapy was initiated. 13 months later, she suddenly presented with ascites. The inferior vena cava was compressed due to the ascites, and an abdominal drain was placed, with massive fluid release. Abdominal MRI indicated an omental cake and peritoneal contrast enhancement. Bone metastases were suspected in the iliac and femoral bones. Anatomopathological examination of the ascites showed an atypical cell population, with irregular, hyperchromatic and enlarged nuclei resembling the primary tumor. The cells were positive for synaptophysin, MAP2 and weakly positive for S100. Pan-NTRK staining was negative. The diagnosis of a metastatic localization of the DLGNT was made, due to seeding of tumoral cells via the VPS. Treatment with a MEK-inhibitor was initiated, but was stopped due to progressive disease and she died 3 weeks later.
RARE-60. PREGNANCIES AFTER CHILDHOOD CRANIOPHARYNGIOMA – RESULTS OF KRANIOPHARYNGEOM 2000/2007
Authors: Sowithayasakul Panjarat , Boekhoff Svenja , Bison Brigitte , Müller Hermann L 
Published: December 2020

Abstract

BACKGROUND
Data on female fertility, pregnancy, and outcome of offspring after childhood-onset craniopharyngioma (CP) are rare.

STUDY DESIGN
Observational study on pregnancy rate and offspring outcome in female CP patients recruited in KRANIOPHARYNGEOM 2000/2007.

RESULTS
A total of 451 CP patients (223 female) have been recruited, and 269 (133 female) were postpubertal at study. Six of 133 female CP patients (4.5%) with median age of 14.9 years at CP diagnosis had 9 pregnancies, giving birth to 10 newborns. Three patients achieved complete surgical resections. No patient underwent postoperative irradiation. Five natural pregnancies occurred in 3 CP patients without pituitary deficiencies. Four pregnancies in 3 CP patients with hypopituitarism were achieved under assisted reproductive techniques (ART) (median 4.5 cycles, range: 3–6 cycles). Median maternal age at pregnancy was 30 years (range: 22–41 years). Six babies (60%) were delivered by caesarean section. Median gestational age at delivery was 38 weeks (range: 34–43 weeks); median birth weight was 2,920 g (range: 2,270– 3,520 g), the rate of preterm delivery was 33%. Enlargements of CP cysts occurred in 2 women during pregnancy. Other complications during pregnancy, delivery, and postnatal period were not observed.

CONCLUSIONS
Pregnancies after CP are rare and were only achieved after ART in patients with hypopituitarism. Close monitoring by an experienced reproductive physician is necessary. Due to a potentially increased risk for cystic enlargement, clinical, ophthalmological, and MRI monitoring are recommended in patients at risk. Perinatal complications, birth defects, and morbidity of mothers and offspring were not observed.
RARE-61. BODY COMPOSITION AND NUCHAL SKINFOLD THICKNESS IN PEDIATRIC BRAIN TUMOR PATIENTS
Authors: Peng Junxiang , Boekhoff Svenja , Eveslage Maria , Bison Brigitte , Sowithayasakul Panjarat , Müller Hermann L 
Published: December 2020

Abstract

BACKGROUND
Obesity, cardiovascular disease (CVD), and relapse/progression have major impact on prognosis in pediatric brain tumor (BT) patients. Cranial MRI is part of routine follow-up.

METHODS
In a cross-sectional study, we analyzed nuchal skinfold thickness (NST) on MRI performed for BT follow-up monitoring as a novel parameter for body composition (BC) and CVD in 177 BT patients (40 WHO grade 1–2 BT; 31 grade 3–4 BT; 106 craniopharyngioma (CP)), and 53 healthy controls (HC). Associations of NST with body mass index (BMI), waist-to-height ratio (WHtR), caliper-measured skinfold thickness (cSFT), and blood pressure (BP) were analysed in BT and HC.

RESULTS
CP patients showed higher BMI, WHtR, NST and cSFT when compared with BT and HC, whereas these differences were not detectable between BT and HC. However, WHO grade 1–2 BT patients were observed with higher BMI, waist circumference and triceps cSFT when compared to WHO grade 3–4 BT patients. NST showed high correlations with BMI, WHtR, and cSFT. NST, BMI and WHtR had predictive value for CVD in terms of increased BP, and in multivariate analysis, only BMI was selected for the final model resulting in an odds ratio of 1.25 (1.14–1.379). In CP patients with hypothalamic involvement/lesion or gross-total resection, rate and degree of obesity were increased.

CONCLUSIONS
As monitoring of MRI and BC play an important role in follow-up after BT, NST could serve as a novel useful parameter for assessment of BC and CVD risk in BT patients.
RONC-06. VOLUMETRIC-MODULATED ARC WHOLE-BRAIN RADIOTHERAPY FOR THE PREVENTION OF PERMANENT ALOPECIA IN PEDIATRIC PATIENTS
Authors: Uto Megumi , Umeda Katsutsugu , Arakawa Yoshiki , Takehana Keiichi , Kamitori Tatsuya , Iwai Atsushi , Kato Itaru , Saida Satoshi , Hiramatsu Hidefumi , Mineharu Yohei , Tanji Masahiro , Takita Junko , Mizowaki Takashi 
Published: December 2020

Abstract
Permanent alopecia is a grave late complication of multi-drug chemotherapy (CTx) plus cranial irradiation, reducing both patient self-esteem and quality of life in pediatric patients. We started to use craniospinal irradiation (CSI) using the volumetric-modulated arc whole-brain radiotherapy (VMAT-WBRT) in order to prevent permanent alopecia. We treated 5 pediatric patients with CSI using VMAT-WBRT, and report the initial clinical outcome. Five consecutive patients (4–11 years old) who received CSI using VMAT-WBRT from June 2015 to November 2018 were included into this study. One patient with embryonic carcinoma received radiotherapy (RT) with concurrent CTx; four patients with medulloblastoma (two patients with standard risk, and two patients with high risk) received RT followed by CTx. The prescribed doses of CSI were 23.4–35.2 Gy in 13–22 fractions, respectively. Optimization for VMAT-WBRT was performed to reduce doses to the hair follicles with keeping the dose coverage to the planning target volume. Although all patients experienced temporary alopecia, their hair fully recovered over the whole scalp within 8 months after finishing RT. One patient had disease progression after 6 months after completing CTx; this patient who was diagnosed as Group 3 subtype had diffuse meningeal dissemination confirmed with contrast enhanced spinal MRI before RT. The other four patients had no evidence of recurrence. Although CSI with VMAT-WBRT might be one of considerable options, more cases are needed to verify the efficacy to prevent permanent alopecia for pediatric patients who receive multi-drug CTx and cranial irradiation.
RONC-15. OUTCOMES OF BRAIN AND SKULL-BASE TUMOURS IN ADOLESCENTS AND YOUNG ADULTS TREATED WITH PENCIL BEAM SCANNING PROTON THERAPY
Authors: Lim Pei Shuen , Tran Sébastien , Kroeze Stephanie G C , Pica Alessia , Hrbacek Jan , Bachtiary Barbara , Walser Marc , Lomax Anthony J , Weber Damien C 
Published: December 2020

Abstract

BACKGROUND
The use of highly conformal proton therapy in adolescents and young adults (AYAs) for management of brain/skull-base tumours is becoming increasingly common. This study aims to assess the long-term clinical outcomes, prognostic factors and employment status of AYAs (15–39 years) treated with pencil-beam-scanning proton-therapy (PT).

METHODS
Between 1997–2018, 176 AYAs were treated with PT at the Paul Scherrer Institute. Median age was 30 years (range, 15–39) and the male/female ratio was 0.8.

RESULTS
After a median follow-up of 66 months (range, 12–236), 24 (13.6%) local failures and 1 (0.6%) distant failure were observed between 6 and 152 months after PT. The most common histologies treated were chordomas/chondrosarcomas (61.4%), followed by meningiomas (14.2%) and gliomas (15.3%). The 6-year local-control (LC), distant-progression-free survival and overall-survival (OS) rate was 83.2%, 97.4% and 90.2% respectively. On univariate analysis, age ≥24 years was a negative prognostic factor for LC. Recurrent disease, infratentorial tumours and low-grade-glioma histology were poor prognostic factors for both LC and OS. The 6-year ≥G3 PT-related late toxicity-free survival was 88.5%. The moderate-high grade late toxicity crude rates were 37.8% G2, 12.2% G3, 0.6% G4 and 0.6% G5. No secondary malignancies were observed. The unemployment rate was 7.3% at PT, rising to 25.3% at survivorship. High-grade(≥G3) toxicity rate in the unemployed vs employed group was 21% vs 8.5%.

CONCLUSION
PT is an effective treatment for AYAs with brain/skull-base tumours with good tumour control and acceptable long-term toxicity. Despite having satisfactory clinical outcomes, around 1 in 4 AYAs surviving brain/skull base tumours are unemployed.
RONC-22. SECOND TUMORS IN PEDIATRIC PATIENTS TREATED WITH PROTON THERAPY TO THE CENTRAL NERVOUS SYSTEM
Authors: Indelicato Daniel J , Bates James , Mailhot-Vega Raymond , Morris Christopher , Sandler Eric , Aldana Phillip , Bradley Julie 
Published: December 2020

Abstract

BACKGROUND
Previous institutional data suggests the 10-year cumulative incidence of second tumors is 3% in children treated with photon radiation for central nervous system (CNS) malignancy, with 90% of these tumors occurring in areas receiving ≤36 Gy. Comparative figures for children treated with proton therapy (PT) does not exist.

METHODS
1056 consecutive pediatric patients with a median follow-up of 5.0 years were treated between 2006–2019 with double-scattered PT to a site within the craniospinal axis. 230 patients were ≤3 years old and 14 had neurofibromatosis. A second tumor was defined as any solid neoplasm with histologic features different from the original tumor that had arisen within the irradiated volume.

RESULTS
Five patients developed second tumors resulting in a 5- and 10-year cumulative incidence of 0.2% (95% CI: 0–1.2%) and 1.6% (95% CI: 0.6%-3.9%), respectively. Of those who developed second tumors, median age at radiation was 4.3 years old (range, 2.1 to 5.1 years old) and diagnoses consisted of medulloblastoma (n=2), ependymoma (n=2), and craniopharyngioma (n=1). The second tumors included high grade gliomas (n=3) and high grade sarcoma (n=1) that occurred in regions receiving at least 54 Gy. One patient with neurofibromatosis developed both a low-grade glioma and choroidal melanoma in craniospinal irradiation regions receiving 36 Gy. Four of five patients with second tumors are alive.

CONCLUSION
The reduction in moderate-to-low dose radiation exposure from proton therapy may be associated with a decreased incidence of second tumors in children treated for CNS neoplasms. More follow-up is needed to confirm these findings.
RONC-24. PROTON THERAPY FOR PEDIATRIC EPENDYMOMA: MATURE OUTCOMES FROM THE UNIVERSITY OF FLORIDA AND MASSACHUSETTS GENERAL HOSPITAL
Authors: Indelicato Daniel J , Ioakeim-Ioannidou Myrsini , Bradley Julie , Mailhot-Vega Raymond , Morris Christopher , Tarbell Nancy , Yock Torunn , MacDonald Shannon 
Published: December 2020

Abstract

OBJECTIVE
Report long-term efficacy and toxicity of proton therapy for pediatric ependymoma.

MATERIALS AND METHODS
Between 2000–2017, 318 children with nonmetastatic grade II/III intracranial ependymoma received proton therapy at Massachusetts General Hospital and the University of Florida. Median age was 3.5 years (range, 0.7–21.3 years); 56% were male. Most (69%) tumors were in the posterior fossa and classified as WHO grade III (64%). Eighty-four percent had a gross total or near total tumor resection before radiotherapy and 30% received chemotherapy. Median radiation dose was 55.8 CGE (range, 50.4–59.4 CGE).

RESULTS
Median follow-up was 6 years (range, 0.6–19.2 years). Seven-year local control, progression-free survival, and overall survival rates were 77.1% (95% CI 71.7–81.7%), 64.4% (95% CI 58.6–69.8%), and 82% (76.9–86.2%), respectively. Subtotal resection was associated with inferior local control (60% vs 80%; p&lt;0.01), progression-free survival (49% vs 67%; p&lt;0.01), and overall survival (69% vs 84%; p&lt;0.05). Male gender was associated with inferior progression-free (59% vs 71%; p&lt;0.01) and overall survival (77% vs 89%; p&lt;0.05). Twenty patients (6.2%) require hearing aids; of these, 12/20 received cisplatin. Grade 3+ brainstem toxicity rate was 1.6% and more common in patients who received &gt;54 CGE. The rate of second malignancy was 0.9%.

CONCLUSION
Proton therapy offers commensurate disease control to modern photon therapy without unexpected toxicity. The high rate of long-term survival justifies efforts to reduce radiation exposure in this young population with brain tumors. Independent of modality, this large series confirms extent of resection as the most important modifiable factor for survival.
RONC-25. A CASE OF PEDIATRIC PONTINE GLIOMA TREATED WITH GAMMA KNIFE SURGERY
Authors: Kaneko Satoshi , Kiyokawa Juri , Hirota Shin , Murota Yasuhiro , Ishikawa Mariko , Yamaoka Hiroto , Yoshimura Masataka , Yamamoto Masaaki , Yamamoto Shinji 
Published: December 2020

Abstract

BACKGROUND
Pediatric brainstem gliomas rarely occur and are a heterogeneous group of diseases, which increases the difficulty of treatment strategy. Here, we present a case of pediatric pontine glioma treated with Gamma Knife surgery (GKS) after open biopsy. CASE DESCRIPTION: An 11-year-old boy presented with diplopia due to the left MLF syndrome. MRI showed a well-circumscribed, protruding tumor with partial gadolinium enhancement in the dorsal pons. An open biopsy was performed via the suprafacial triangle following midline suboccipital approach. Histological examinations revealed high cellularity and mild atypia. Immunohistochemistry demonstrated positive stain for GFAP and Olig2 antibodies, and negative for p53 protein. The Ki67-labeling index was 6.8%. Pyrosequence analysis indicated IDH1/2 wild type (wt), BRAF V600 wt, H3F3A K27 wt, FGFR1 wt, and TERT wt. The final diagnosis was pediatric diffuse astrocytoma, WHO grade II, pons. GKS was performed one month after the biopsy. After transient worsening of the symptom, it disappeared gradually. The tumor is stable for three years with mild shrinkage of the size. DISCUSSION: Gross total resection (GTR) of pediatric low-grade, brainstem gliomas may result in a good prognosis. However, unlike pilocytic astrocytoma, diffuse astrocytoma is not easy to perform GTR without any complications. There are some reports regarding GKS for brainstem gliomas, which prove an increase in progression free survival rate. No marked tumor regression is achieved in our case, but tumor growth is well-controlled so far.

CONCLUSION
GKS after biopsy can be a useful treatment option for pediatric low-grade brainstem gliomas.
RONC-27. PROTON THERAPY REDUCES DOSE TO CRITICAL CENTRAL NERVOUS SYSTEM STRUCTURES IN MEDULLOBLASTOMA: A DOSIMETRIC ANALYSIS OF CHILDREN’S ONCOLOGY GROUP (COG) ACNS0331
Authors: Deek Matthew , Ladra Matthew , Lin Lan , Li Yimei , Han Yuanyuan , Hardy Kristina , Michalski Jeff 
Published: December 2020

Abstract

BACKGROUND
Recently published data demonstrated proton therapy (PRT) significantly reduced cognitive decline relative to photons for pediatric medulloblastoma. These findings imply that reductions in dose to critical CNS structures during the boost phase may account for better outcomes over time. Here, we examine differences in dosimetric data for medulloblastoma patients treated on ACNS0331 with photon (Intensity Modulated Radiation Therapy, 3D-Conformal Radiation Therapy) vs PRT to identify potential structures responsible for cognitive benefit.

METHODS
COG ACNS0331 was a randomized trial examining the impact of reduced craniospinal irradiation (CSI) dose (standard vs low dose, in patients aged 3–7) and volume (whole posterior fossa vs involved field) in pediatric medulloblastoma patients. We identified 136 patients (IMRT=95, 3DCRT=28, Proton=13) enrolled on ACNS0331 with complete radiation and imaging data and re-contoured 10 critical brain structures to calculate dose.

RESULTS
Proton therapy significantly reduced the dose to critical structures. For example, temporal lobe mean dose and V30 were 30Gy/38% (PRT), 40Gy/89% (IMRT), 41Gy/84% (3DCRT)), hippocampi mean dose were 51 Gy (IMRT), 52 Gy (3DCRT), and 44Gy (PRT) and cochlear mean dose were 43 Gy (IMRT), 49 Gy (3DCRT), and 31Gy (PRT). Dose to several other critical structures were also significantly reduced including the whole brain, supratentorium, cerebellum, and pituitary.

CONCLUSIONS
Proton therapy greatly reduces dose to critical CNS structures when compared to IMRT or 3DCRT. Further studies are needed to correlate dose reductions in these structures with improved cognitive outcomes.