bluuebunny/crossref_metadata_2025_split huggingface dataset:
GCT-21. CENTRAL NERVOUS SYSTEM GERMINOMA - PONDERING THE NEXT STEPS
Authors: AbdelBaki Mohamed S , Bartels Ute 
Published: December 2020

Abstract
Central nervous system germinoma (CNS) represents one successful example where the introduction of chemotherapy into the treatment allowed significant and meaningful reductions in the volume and dose of radiation therapy while maintaining excellent outcomes. However, the long-term toxicities and morbidities of the current therapies, in addition to their substantial negative impact on the social wellbeing of germinoma patients, should clearly indicate that the current achievements are not enough. While stepwise cutback of the radiation therapy needs to be commended, real progress must be achieved in the exploration and investigation of biological and molecular markers. Furthermore, the differences that still exist between the several working groups around the globe in determining the tumor marker cut-offs that help diagnose these tumors illustrate their shortcomings, and therefore the need for newer and more reliable methods. Additionally, efforts should focus on the inclusion of metastatic and basal ganglia/thalamic germinomas in future prospective clinical trials given the lack of evidence on the best treatment strategy for these patients. A comprehensive review of all major CNS germinoma clinical trials will be presented aiming to lay a foundation for researchers and clinicians alike who are currently working on designing innovative approaches for this group of patients. This review also details the current issues of debate, and provides suggestions which may assist in the design of future prospective clinical trials for children with CNS germinomas.
GCT-22. PROTEIN DEUBIQUITINATION PATHWAY IS A NOVEL THERAPEUTIC TARGET AGAINST MALIGNANT NON-GERMINOMATOUS CNS GERM CELL TUMORS
Authors: Tomiyama Arata , Uchida Eita , Wada Kojiro , Ichimura Koichi 
Published: December 2020

Abstract
Central nervous system germ cell tumors (CNSGCTs) are rare intracranial neoplasm usually developed in adolescents and young adults. However, in East Asia including Japan, incidence of CNSGCTs is considerably higher compare with other regions of the world. Whereas germinomas generally respond to chemo-radiotherapy well, malignant subtypes of non-germinomatous germ cell tumors (NGGCT) are refractory, and development of novel therapy against NGGCTs is urgently needed. To develop a new therapeutic strategy against aggressive NGGCTs, we have investigated novel molecular targets for NGGCT treatment. We screened a total of 120 CNSGCT tumor tissues (including 55 NGGCT), which were registered to the Intracranial Germ Cell Tumor Consortium (iGCT), and discovered multiple mutations of a molecule that regulates protein ubiquitination and degradation specifically in NGGCT cases (5 of 55 cases; 1 immature teratoma, 3 mixed gem cell tumors, and 1 embryonal carcinoma). An in vitro ubiquitination assay revealed the mutations of this molecule discovered in NGGCT cases were loss of function mutations. Reduced expression of this molecule by knockdown in an established human seminoma cell line Tcam2 or a human yolk sac tumor cell line YST1, which was recently established in our institute, resulted in enhanced proliferation as well as upregulation of MEK-ERK activation. Importantly, treatment of these two GCT cell lines with reduced expression of this molecule by MEK inhibitor trametinib suppressed augmented proliferation of these cells. Taken together, these results suggest that protein ubiquitination-related pathways as well as MEK-ERK cascade may serve as a novel therapeutic target against NGGCTs.
GCT-23. MULTI-INSTITUTIONAL ANALYSIS OF TREATMENT MODALITIES IN BASAL GANGLIA AND THALAMIC GERMINOMA
Authors: Graham Richard T , Abu-Arja Mohammad H , Stanek Joseph , Bartels Ute , Cappellano Andrea , Chi Susan , Cooney Tabitha , Dhall Girish , Finlay Jonathan L , Fisher Michael J , Friedman Gregory , Gajjar Amar , Gauvain Karen , Hoffmann Lindsey M , Hukin Juliette , Margol Ashley , Mueller Sabine , Navalkele Pournima , Ronsley Rebecca , Villeneuve Stephanie , Yeo Kee Kiat , Su Jack M , Gottardo Nicholas G , Allen Jeffrey , Packer Roger , AbdelBaki Mohamed 
Published: December 2020

Abstract

BACKGROUND
Central nervous system (CNS) germinomas are radiotherapy (RT)-sensitive tumors with excellent survival. Current treatment strategies combine chemotherapy with RT to reduce the field and dose of RT. There is no standard treatment for germinomas originating in the basal ganglia/thalami (BGTG) given their rarity and poorly-defined imaging characteristics. Craniospinal (CSI), whole brain (WBI), whole ventricle (WVI), and focal RT have been previously utilized; however, the optimal strategy remains unclear.

METHODS
Retrospective multi-institutional analysis was conducted across 18 institutions in four countries.

RESULTS
For 46 cases with non-metastatic BGTG, the event-free survival (EFS) was 86.9% at both 5 and 10 years, while overall survival (OS) was 100%, and 95.7% respectively at 5 and 10 years. Median RT dose and range for the various treatment volumes were as follows: CSI (n=10): 2340 cGy (1980–3060 cGy), WBI (n=8): 2340 (1800–3000 cGy), WVI (n=14): 2340 cGy (1800–2550 cGy), focal (n=9): 3600 cGy (3060–5400 cGy). There was no statistically significant difference in the EFS based on RT modality (p=0.57), but EFS for subjects with CSI and WBI were both 100%. The three subjects who received chemotherapy alone had significantly lower EFS than those who received chemotherapy and RT (p=0.001), but were salvageable with RT.

CONCLUSION
In the largest study to date for BGTG, there were no significant differences in outcomes between patients who received CSI, WBI, WVI or focal RT. This group of patients should be included in future prospective clinical trials, and a more limited RT field may be considered.
GCT-29. DOES TUMOUR MARKER DECLINE PREDICT OUTCOME IN INTRACRANIAL NON-GERMINOMATOUS GERM CELL TUMOURS (NGGCTs)?
Authors: Conter Cecile Faure , Lardy-Cleaud Audrey , Murray Matthew , Nicholson James , Guerrini-Rousseau Lea , Palenzuela Gilles , Alapetite Claire , Garre Maria Louise , Kortmann Rolf , Saran Frank , Ajithkumar Thankamma , Pietsch Torsten , Vasiljevic Alexandre , Ricardi Umberto , Timmermann Beate , Muller Jans Enno , Calaminus Gabriele 
Published: December 2020

Abstract

INTRODUCTION
The prognostic impact of tumour marker (TM) decline rate has been demonstrated for extracranial poor prognostic non-seminomatous/germinomatous germ cell tumours (NGGCT). The current series aimed to assess if this finding can be applied to intracranial primaries.

METHODS
Patients were retrieved from the SIOP-CNS-GCT-96 database. They were selected if they had i/assessable values of serum alpha-fetoprotein (AFP) and/or human chorionic gonadotropin (HCG) before and 18 to 28 days after the first course of chemotherapy and ii/ available data for outcome. Decline rate was calculated using a logarithmic transformation and expressed as time to normalization (TTN) as published by Fizazi (JCO 2004). TTN≤ 9 weeks for AFP and ≤ 6 weeks for HCG were considered as favourable decline rate. Prognostic impact of TTN on outcomes was assessed using the log-rank test.

RESULTS
Out of 149 patients with NGGCT, 59 were evaluable for both HCG and AFP TTN of whom 44 (74%) had a favourable decline rate. After a median follow-up of 88 months (2–251), 20 relapses and 15 deaths occurred. The 5-year PFS rates were 72% and 60% in patients who had a favourable and an unfavourable TTN, respectively (p=0.15). The 5-year OS rates were 77 % and 69%, respectively (p=0.66). Separate analysis of TTN based only on AFP or only on HCG gave similar results.

CONCLUSION
Despite the use of a methodology similar to that used in extracranial NGGCT, no significant impact of serum TM decline on prognosis was observed, but insufficient statistical power cannot be ruled out.
GCT-33. A PHASE 2 TRIAL OF RESPONSE-BASED RADIATION THERAPY FOR PATIENTS WITH LOCALIZED CENTRAL NERVOUS SYSTEM GERM CELL TUMORS: A CHILDREN’S ONCOLOGY GROUP (COG) STUDY. IMPACT OF RAPID CENTRAL RADIOTHERAPY REVIEW ON RADIOTHERAPY QUALITY AND PATTERN OF FAILURE FOR NON-GERMINOMATOUS GERM CELL TUMORS
Authors: Murphy Erin S , Dhall Girish , Fangusaro Jason , Bartels Ute , Fouladi Maryam , Shaw Dennis , Khatua Soumen , Panigraphy Ashok , Souweidane Mark , Gajjar Amar , Williams-Hughes Chris , Onar Arzu , Wu Shengjie , Haas-Kogan Daphne , MacDonald Shannon 
Published: December 2020

Abstract

BACKGROUND
COG ACNS 1123 tested reduced radiotherapy (RT) for non-metastatic, non-germinomatous germ cell tumor (NGGCT) patients. The impact of central review on quality of RT and pattern of failure for NGGCT patients is evaluated.

METHODS
Patients who achieved a complete response (CR) or partial response (PR) to induction chemotherapy were eligible for reduced dose and field RT of 30.6 Gy whole ventricular field (WVI) and 54 Gy tumor-bed total dose. An online contouring atlas was available. Within three days of RT start, WVI plans were submitted for rapid central review. Within one week of RT completion, the complete RT record was submitted. Brain and spine MRIs of relapsed patients were centrally reviewed.

RESULTS
Between 5/2012–9/2016, 107 eligible patients were accrued and 70 met reduced RT criteria. Rapid RT review was performed for 49 (70%) of 70 patients. Forty-four (89.8%) required no modification. All modifications were completed and plans became compliant. Final central review was performed for 66 evaluable patients: 62 (94%) were per protocol; there were 2 major (1 dose and 1 target) and 2 minor deviations. Eight patients progressed; none had deviations. Median time to progression was 3.54 months (range: 1.7–19.1) from RT start. All failures had a spine component; two also had cranial component: one local progression (within the RT boost volume) and one leptomeningeal disease.

CONCLUSION
Providing an online contouring atlas and performing a rapid central review lead to high quality radiotherapy on this prospective trial. The deviations did not contribute to the pattern of failure.
GCT-49. EVALUATION OF THE PERIOPERATIVE AND POSTOPERATIVE COURSE OF SURGERY OF PINEAL GERMINOMA ACCORDING TO THE SIOP CNS GCT 96 TRIAL
Authors: Shabo Ehab , Czech Thomas , Nicholoson James C , Mallucci Conor , Sarikaya-Seiwert Sevgi , Guerini-Rousseau Lea , Piatelli Gianluca , Murray Matthew C , Faure-Conter Cecile , Calaminus Gabriele 
Published: December 2020

Abstract

INTRODUCTION
CNS germinoma, being marker-negative, are diagnosed by surgical biopsy. Here we evaluate the perioperative status and postoperative complications of patients with pineal germinoma who underwent a primary biopsy or resection, treated according to SIOP CNS GCT 96.

METHODS
235 patients with histologically conﬁrmed germinoma were registered, of which 113 were pineal: 55 were biopsied and 58 underwent primary resection. Initial symptoms, tumour size, complications and neurological status were assessed. 111 patients were evaluable.

RESULTS
Pure germinoma was present in 101 patients; 10 had additional teratoma components. The main clinical symptoms at diagnosis were headache (n=98), hydrocephalus (n=93), double vision (n=62), Parinaud syndrome (n=57) and papilloedema (n=44). Tumour size was documented in 81 patients (&lt;2cm, n=14; 2-3cm, n=35; ≥3cm, n=32). 17 patients underwent primary total resection, 14 subtotal resection &gt;50%, 26 subtotal resection &lt;50%, 39 stereotactic biopsy, 11 endoscopic biopsy, 2 open biopsy and 2 not documented. The postoperative neurological status after resection was improved in 23 patients, unchanged in 27, deteriorated in 6 and not documented in one. Clinical status after biopsy improved in 26 patients, was unchanged in 15, deteriorated in 2 and not documented in 11. Postoperatively, 16/57 patients after resection and 5/54 after biopsy developed complications (Parinaud syndrome, double vision and hydrocephalus).

CONCLUSION
Although surgical techniques have improved within recent decades, these results support the practice of biopsy over resection for histological confirmation of germinoma arising at the pineal site. Supported in part by German Cancer Aid.
GCT-58. BRAZILIAN CENTRAL NERVOUS SYSTEM GERM CELL TUMOR CONSORTIUM PROTOCOL
Authors: Cappellano Andréa M , Silva Nasjla S , Mançano Bruna , Almeida Daniela B , Cavalheiro Sergio , Dastoli Patricia A , Silva Frederico A , Epelman Sidnei , Aguiar Simone S , Finlay Jonathan L 
Published: December 2020

Abstract

INTRODUCTION
Primary central nervous system (CNS) germ cell tumors (GCT) account for 2–3% brain tumors children/adolescents in Western hemisphere. The report aim is to present the results of a Brazilian CNSGCT consortium protocol.

METHODS
Since 2013, 45 patients with histologic and/or tumor marker (TM) diagnosis of germinoma with/without HCGβ levels≤200mIU/ml (n=33), four between 100-200mIU/ml and NGGCT (n=12), received carboplatin/etoposide/cyclophosphamide (4–6 cycles), followed by 18Gy ventricular field irradiation and primary site(s) boost. Autologous bone marrow transplant (ABMT) was conducted for NGGCT low responders.

RESULTS
Mean age 12.9 years (4.7-20y), 34 males. Diagnosis was made by TM (n=9), surgery (n=19), both (n=15). Two bifocal cases, (-)TM were treated as germinoma. Primary tumor location was pineal (n=20), suprasellar (n=13), bifocal (n=11) and basal ganglia/thalamus (n=1). Fourteen had ventricular/spinal spread. Second-look surgery occurred in 5 patients. For the germinoma group, 26 achieved complete response (CR) after chemotherapy, seven showed residual teratoma/scar. For the NGGCT after 2/4 cycles, four patients showed CR, 2 failure/progression and 6 partial response (4 (-)TM). Two were submitted to ABMT. Radiotherapy was performed as described, except in three. One recurrence to date. Two patients died (endocrinologic complications/progression). Toxicity was mostly grade ¾ neutropenia/thrombocytopenia during chemotherapy. At a median follow-up of 38 months, OS was 100% for Germinoma and 85% NGGCT.

CONCLUSION
The treatment is tolerable and VFI dose reduction to 18Gy seems to preserve efficacy. Further follow-up is warranted to assess the NG group and the slow-responder patients.
GCT-69. VOLUMETRIC CHANGE BEFORE CHEMORADIOTHERAPY AND INFLUENCE OF DIAGNOSTIC RADIATION EXPOSURE IN INTRACRANIAL GERMINOMAS
Authors: Kagawa Naoki , Hirayama Ryuichi , Yokota Chisato , Chiba Yasuyoshi , Fujimoto Yasunori , Nakagawa Tomoyoshi , Umehara Toru , Kijima Noriyuki , Kinoshita Manabu , Kishima Haruhiko 
Published: December 2020

Abstract

BACKGROUND
Spontaneous regression in intracranial germ cell tumors has been reported in some literatures, but the mechanism has not been well known. We retrospectively measured the tumor volume before chemoradiotherapy and analyzed factors that influence reduction of tumor volume.

PATIENTS AND METHODS
Plural MRI scans were done before the first course of chemotherapy regimen in 27 patients with primary intracranial germinomas. Their age ranged from 8 to 31 years. 35 lesions from them were enrolled and included 13 pineal, 4 neurohypophyseal, 4 basal ganglia, 4 bifocal type, and 2 multiple lesions. All regions were verified as pure germinoma or HCG-producing germinoma by histopathological examination. Tumor volume of 35 lesions was analyzed by volumetric assessment based on MRI. Ratio of volumetric change between the first MRI and the scan immediately before chemotherapy was defined as shrinking rate (%). Period between disease onset and the first chemotherapy was 20 to 47 days. Diagnostic radiation dose was calculated in each case.

RESULTS
Initial tumor volume ranged from 0.962 to 72.356 cubic centimeters (mean: 8.27). Diagnostic radiation dose: 40.5 to 910.1 mGy. Shrinking rate ranged from -57.8 to 85.4% (mean: 30.8). In 10 regions, shrinking rate was within 30%. Shrinking rate was significant positively influenced by diagnostic radiation dose (p&lt;0.05) and negatively influenced by initial volume (p&lt;0.05). But, other factors such as age, sex, histopathological parameters did not influence tumor shrinkage.

CONCLUSION
This study shows that the volume of intracranial germ cell tumors is changing dynamically before chemoradiotherapy in many cases. Diagnostic exposure to low-dose radiation influences tumor shrinkage of intracranial germinomas.
GCT-70. INTRACRANIAL GROWING TERATOMA SYNDROME IN CHILDREN
Authors: Febres Maria Carter , Bruggers Carol S , Zhou Holly , Perry Arie , Kestle John , Whipple Nicholas 
Published: December 2020

Abstract
Germ cell tumors account for less than 5% of all intracranial malignancies in children. Intracranial growing teratoma syndrome (GTS) is a rare pathophysiologic process characterized by growth of mature teratoma elements of a non-germinomatous germ cell tumor (NGGCT) during or following treatment with chemotherapy, in addition to normalization of or declining AFP/βHCG of the cerebral spinal fluid (CSF)/serum. A 13-year-old male presented with headache, emesis, and diplopia. MRI of the brain/spine revealed a localized 3.1 x 3.1 x 3.2 cm pineal tumor. Biopsy confirmed NGGCT (germinoma, immature and mature teratoma). Serum AFP (227ng/ul) and βHCG (12 IU/L) and CSF AFP (21ng/ul) and βHCG (31 IU/L) were elevated. Prior to cycle two of chemotherapy, he developed unstable gait and moderate hearing loss. Repeat MRI brain demonstrated tumor enlargement (4.4 x 5.2 x 5.1 cm) and obstructive hydrocephalus, although serum AFP/βHCG had normalized. Gross total resection of tumor confirmed GTS, without residual immature/malignant elements. Following six cycles of multiagent chemotherapy (carboplatin, etoposide, ifosfamide) and proton beam craniospinal irradiation (36 Gy with 18 Gy boost), he remains free of disease at eleven months since diagnosis. The pathogenesis of GTS remains unclear. Care must be taken to avoid misdiagnosing GTS as progressive NGGCT, as treatment and prognosis differ significantly. Second-look surgery, with a goal of complete resection, should be considered in cases of NGGCT when residual tumor grows during or following therapy, as this may represent GTS. Although histologically benign, GTS can be fatal. In patients with GTS, complete resection is usually curative.
GCT-71. SIOP STRATEGY TREATMENT FOR CENTRAL NERVOUS SYSTEM GERM CELL TUMORS IN A MIDDLE INCOME COUNTRY
Authors: Oller Agustina , Sampor Claudia , Baroni Lorena , Freytes Candela , Ponce Nicolas Fernandez , Villanueva Gabriela , Alderete Daniel 
Published: December 2020

Abstract

BACKGROUND/OBJECTIVES
Central nervous system (CNS) germ cell tumors (GCTs) represent 3% of primary paediatric brain tumours in occident. They can be divided into major groups including germinomas and nongerminomatous GCTs (NGGCTs). The aim is to describe demographic characteristics, Event Free Survival (EFS) and Overall Survival (OS) in patients with GCTs treated at Oncology Unit of Garrahan Hospital (HG).

DESIGN/METHODS
Retrospective analysis of patients with GCTs admitted between September 1st,2000 to September 1st,2019. Variables analysed: age, localization, treatment, relapse and death. Patients were treated per SIOP-CNSGCTs protocol. For statically analysis SPSS (IBM), for EFS/OS Kaplan-Meyer, Long-rank for significance.

RESULTS
Fifty-seven patients were included, comprising 38 Germinomas and 19 NGGCTS. Median age was 146 months (range 11–228). Primary site in localized Germinomas were pineal (16p), suprasellar (7p) and bifocal (7p). Five-year EFS and OS of 100% and 88.5%, respectively. Four patients presented metastatic disease, with an EFS and OS of 60.9% and 66.6%. Tumor site in localized NGGCT were pineal(8p) and suprasellar(5p). Five-year EFS was 81.8% and OS was 80.2%. No patients presented metastatic disease. All patients with high-risk tumor markers at diagnosis relapsed. No significative differences were found in OS neither EFS between groups (Germinomas OS5y 90% vs NGGCTs 74.6%p=0.19[CI95%0.0786–1.689]), (Germinomas EFS5y 78.9% vs NGGCTs5y 81.8%p=0.85[CI95%0.3046–4.230). Global OS and EFS5y was 83% and 72.9%.

CONCLUSION
OS of our cohort is lower than what has been shown in current literature. This result may be related to the lack of resources and lower social economic status in our population.
HGG-02. ADOLESCENT AND YOUNG ADULT (AYA) GLIOMA WITH BRAF V600E-MUTANTATION
Authors: Kimura Yui , Ishi Yukitomo , Watanabe Yuko , Nakano Yoshiko , Yamaguchi Shigeru , Narita Yoshitaka , Ichimura Koichi 
Published: December 2020

Abstract

BACKGROUND
Biological features of pediatric glioma differ significantly from those of adult glioma, and limited data are available on those of AYA patients. Here, we focused on AYA patients with glioma, especially those harboring BRAF V600E mutation, and investigated their clinical and genetic features. METHOD: We retrospectively analyzed AYA patients with brain tumors harboring BRAF V600E, who were treated in two hospitals in Japan.

RESULTS
Clinical information was available for 14 patients. The median age at diagnosis was 25 years (range: 15–38). Five patients were diagnosed with glioblastoma (GBM), including one epithelioid type. These patients were over 25. Although one patient with GBM died of the disease 6.9 years after initial diagnosis, the remaining patients were alive. Two patients were alive without recurrence at 38 and 51 months after the treatment. The patient with epithelioid glioblastoma experienced early recurrence. The remaining nine patients (64%) were diagnosed with low-grade glioma, including ganglioglioma, pilocytic astrocytoma, diffuse astrocytoma, oligodendroglioma, pleomorphic xanthoastrocytoma, and polymorphous low-grade neuroepithelial tumor of the young. No patients died of the disease, and four patients are alive without recurrence after initial operation without adjuvant treatment. Two patients are (epithelioid glioblastoma and ganglioglioma) currently undergoing treatment with a BRAF inhibitor for recurrent tumors.

DISCUSSION
Although the number of this study is limited, our study suggested that the prognosis of AYA patients with BRAF-V600E positive GBM may not be as dismal as that of children or adults.
HGG-05. REGRESSION OF RECURRENT GLIOBLASTOMA AFTER BORON NEUTRON CAPTURE THERAPY AND CHIMERIC ANTIGEN RECEPTOR T-CELL THERAPY IN A CHILD
Authors: Chen Hsin-Hung , Chen Yi-Wei 
Published: December 2020

Abstract
A 6 y/o girl with recurrent multifocal glioblastoma received 3 times of boron neutron capture therapy (BNCT) and chimeric antigen receptor (CAR)–engineered T cells targeting the tumor-associated antigen HER2. Multiple infusions of CAR T cells were administered over 30 days through intraventricular delivery routes. It was not associated with any toxic effects of grade 3 or higher. After BNCT and CAR T-cell treatment, regression of all existing intracranial lesions were observed, along with corresponding increases in levels of cytokines and immune cells in the cerebrospinal fluid, but new lesions recurred soon after the treatment. This clinical response continued for 14 months after the initiation of first recurrence.