bluuebunny/crossref_metadata_2025_split huggingface dataset:
GCT-06. DIAGNOSIS OF A RARE CASE OF RECURRENT GERM CELL TUMOR BY CSF PLACENTAL ALKALINE PHOSPHATASE PRESENTING WITH DIFFUSE INTRAAXIAL ABNORMALITY IN THE LOWER BRAINSTEM
Authors: Yamada Hiroki , Abiko Tomohiro , Fujiwara Hirokazu , Yoshida Kazunari , Sasaki Hikaru 
Published: December 2020

Abstract

INTRODUCTION
Germ cell tumors in the central nervous system (CNS) typically arise either at suprasellar and/or pineal region, and occasionally at basal ganglia. We report a case of diagnostically challenging, recurrent germ cell tumor presented with diffuse intraaxial abnormality in and across the lower brainstem, which was diagnosed by the elevated placental alkaline phosphatase (PLAP) level in cerebrospinal fluid (CSF). CASE DESCRIPTION: A 28-year-old man had been treated by chemoradiotherapy at the previous hospital for bifocal suprasellar and pineal lesions with the provisional diagnosis of germinoma without histological confirmation. Three years later, he presented with progressive weakness of bilateral extremities for weeks. Magnetic resonance imaging showed a diffuse, bilaterally symmetric high intensity lesion on T2-weighted image with slight contrast enhancement across the ventral side of the medulla oblongata to the upper cervical spinal cord. Serum and CSF hCG, hCG-β, and AFP were all negative. Since the image findings were atypical for recurrent germ cell tumor, some kind of myelitis was initially suspected. Therefore, steroid pulse therapy was administered. However, the patient’s symptom was still gradually progressing. Then, the CSF PLAP turned out to be positive, indicating the recurrence of germinoma. Accordingly, platinum-based chemotherapy was administered, and the imaging findings, patient’s symptoms, and CSF PLAP began to improve. The patient is to be treated with radiotherapy following chemotherapy.

CONCLUSION
We report a rare case of CNS germ cell tumor that presented with diffuse intraaxial lesion in the lower brainstem in which examination of CSF PLAP was extremely useful.
GCT-18. CLINICAL FEATURES OF GERM CELL TUMORS IN CHILDREN
Authors: Higa Nayuta 
Published: December 2020

Abstract

INTRODUCTION
Here, we discuss the presentation, histology, therapy, and outcome of germ cell tumors in children.

METHODS
Treatment outcome and management was assessed for children diagnosed with germ cell tumors from 2007 to 2017 at Kagoshima University.

RESULTS
Twenty-six patients (20 boys, 6 girls) with a mean age of 11.5 ± 4.9 years were included in this study. Patient tumor types included: germinoma (n = 19); immature teratoma (n = 3); yolk sac tumor (n = 3); choriocarcinoma (n = 1); embryonal carcinoma (n = 1). The most common patient clinical features were headache and vomiting associated with hydrocephalus. The median follow-up period was 96.5 months. Tumor location was pineal (n=9), bifocal (n=6), suprasellar (n = 5), basal ganglia (n=2), frontal lobe (n=2), and cerebellum (n=2). Surgical procedures included stereotactic biopsy (n=13), endoscopic third ventriculostomy and biopsy (n=8), and tumor decompression (n=5). All patients with germ cell tumors underwent adjuvant chemotherapy and radiation therapy; patients with germinoma or immature teratoma were still alive, while patients with embryonal carcinoma, yolk sac tumor, or choriocarcinoma had poor prognosis with a median survival of 16 months.

CONCLUSIONS
Patients with germinoma had a relatively good prognosis, while patients with embryonal carcinoma, yolk sac tumor, or choriocarcinoma had a poor prognosis. A multidisciplinary approach including surgical strategy based on location, appropriate radiation planning, and chemotherapy is needed for effective treatment and improved outcomes.
GCT-30. TREATMENT OF PRIMARY INTRACRANIAL GERM CELL TUMORS: SINGLE INSTITUTION EXPERIENCE OF 74 CASES WITHOUT HISTOLOGICAL CONFIRMATION
Authors: Guo Chengcheng , Yang Qunying , Wang Jian , Mou Yonggao , Chen Zhongping 
Published: December 2020

Abstract

BACKGROUND AND OBJECTIVE
Primary intracranial germ cell tumors (PIGCTs) are a group of heterogeneous tumors. It is very difficult to treat those patients without pathological diagnosis. This study retrospectively analyzed the clinical data and outcomes of patients with clinically diagnosed (without histologically confirmed) PIGCTs in SunYat-sen University Cancer Center.

METHODS
Patients who were clinically diagnosed as PIGCTs without histological diagnosis through surgical resection or biopsy were included in this study. Patients were analyzed for clinical characteristics, treatment patterns, outcomes and adverse effects.

RESULTS
From May 2002 to July 2014, 74 patients clinically diagnosed with PIGCTs received chemotherapy and/or radiotherapy at the Sun Yat-sen University Cancer Center. The median age was 16.5 years old (4–45 years old, majority was teenagers). The most of tumors were found in male, and located in the pineal and suprasellar regions. When the patients were grouped into diagnostic chemotherapy group (57 cases), diagnostic radiotherapy group (5 cases) and gamma knife radiosurgery group (12 cases) based on their initial anti-tumor therapy. The 5-year survival rates were 84.3%, 75.0% and 75.0%, respectively. There was a trend that the chemotherapy group got a better survival. Patients were allocated to secretory tumor group (49 cases) and non-secretory tumor group (25 cases) based on their levels of tumor makers (α-FP and β-hCG). The 5- year survival rates were 80% and 77.8% (P value = 0.966), respectively.

CONCLUSION
Clinical diagnosed PIGCT (without histological confirmation) patients may obtain good responses when receiving comprehensive treatments of chemotherapy combined with radiotherapy.
GCT-34. ELUCIDATION OF THE MECHANISMS OF TUMORIGENESIS IN INTRACRANIAL GERM CELL TUMOR BY WHOLE GENOME SEQUENCE
Authors: Yamagishi Yuki , Takami Hirokazu , Narushima Daichi , Matsushita Yuko , Sugihara Eiji , Nishikawa Ryo , Kato Mamoru , Ichimura Koichi ,   Intracranial Germ Cell Tumor Genetic Analysis Consortium
Published: December 2020

Abstract
Intracranial germ cell tumors (iGCT) are heterogenous group of primary brain tumors that consist of various subtype, and driver genetic alterations in iGCTs remain largely unknown. We have previously reported in a study of whole exome sequence that iGCTs frequently harbored mutations in the KIT gene and its downstream MAPK/PI3K pathway, regardless of tumor subtype. However, no mutations were detected in about one-quarter of germinomas and half of non-germinomatous germ cell tumors. A genome-wide methylation profiling revealed that only germinomas exhibited extreme DNA hypomethylation among iGCTs. Moreover, in mixed iGCT tumors which contained more than one tumor subtypes, each component exhibited distinct methylation status depending on the subtype, while they shared the same mutations. These data suggested that not only mutations in the coding region as previously reported, but also genetic alterations in regulatory regions including promoters and enhancers as well as non-coding RNA genes may be involved in the tumorigenesis of iGCTs. In order to comprehensively search for driver gene alterations, we performed whole genome sequence in 18 paired tumor blood samples from iGCT tumors (16germinomas and two yolk sac tumors (YST)) registered in the Intracranial Germ Cell Tumor Genome Analysis Consortium. In a preliminary analysis of four cases, YSTs harbored a significantly higher number of structural abnormalities, compared with germinomas. Of note, 62 structural abnormalities were clustered within the small genomic region of 95Mb at 1q21-44 in one YST case, suggesting a possibility of chromothripsis. A full analysis of somatic alterations is underway and will be reported.
GCT-40. PROGNOSTIC FACTORS FOR PATIENTS WITH RELAPSED CENTRAL NERVOUS SYSTEM (CNS) NON-GERMINOMATOUS GERM CELL TUMORS (NGGCTs)
Authors: Abu-Arja Mohammad H , Osorio Diana S , Stanek Joseph R , Finlay Jonathan L , AbdelBaki Mohamed S 
Published: December 2020

Abstract

BACKGROUND
Patients with relapsed CNS NGGCTs experience poor outcomes. Our aim to explore prognostic factors that may guide future clinical trials.

METHODS
A review of clinical trials that included patients with relapsed CNS NGGCTs was performed.

RESULTS
Seventy-four patients were identified; only 14 patients (19%) were long-term survivors. Patients who relapsed &gt;24 months after initial diagnosis had a survival rate of 47% compared with 15% of patients who relapsed in &lt;24 months after initial diagnosis (p= 0.015). Patient with serum/cerebrospinal fluid (CSF) alpha-fetoprotein (AFP) level &lt;25 ng/ml at relapse had a survival rate of 40% compared with 0% among patients with serum/CSF AFP level &gt;25 ng/ml at relapse (p= 0.0015). Patients who achieved complete response/continued complete response (CR/CCR) by the end of therapy had a survival rate of 59% compared with 3% among patients who had less than CR/CCR by the end of therapy (p= 0.0001). Patients who received marrow-ablative chemotherapy followed by autologous hematopoietic cell rescue (HDCx/AuHCR) at relapse had a survival rate of 33% compared with 9% of patients who did not receive HDCx/AuHCR at relapse (p=0.056). The extent of surgical resection, receiving radiotherapy, and beta-human chorionic gonadotropin levels at relapse were not statistically associated with improved outcomes.

CONCLUSION
Timing of relapse (&gt;24 months after initial diagnosis), serum/CSF AFP &lt;25 ng/ml at relapse, achieving CR/CCR after treatment were associated with a positive impact on survival. Receiving HDCx/AuHCR at relapse was associated with an improved outcome trend among the patients.
GCT-41. RESPONSE-BASED RADIATION THERAPY IN PATIENTS WITH NEWLY DIAGNOSED CENTRAL NERVOUS SYSTEM LOCALIZED GERMINOMA: A CHILDREN’S ONCOLOGY GROUP (COG) PROSPECTIVE PHASE 2 CLINICAL TRIAL
Authors: Bartels Ute , Fangusaro Jason , Shaw Dennis , Bhatia Aashim , Omar-Thomas Arzu , Wu Shengjie , MacDonald Shannon , Murphy Erin , Souweidane Mark , Fouladi Maryam , Gajjar Amar , Dhall Girish , Khatua Soumen 
Published: December 2020

Abstract

BACKGROUND
The objective of stratum 2 of COG ACNS1123 was to evaluate children and young adults (3–21 years) with localized central nervous system (CNS) germinoma and investigate whether simplified pre-irradiation chemotherapy followed by response based dose-reduced whole ventricular irradiation (WVI) would maintain a high progression-free survival (PFS) while reducing long term treatment burden.

METHODS
Pre-irradiation chemotherapy consisted of 4 cycles of carboplatin and etoposide every 21 days followed by response-based irradiation (XRT). Patients with a complete response (CR) to pre-XRT chemotherapy received 18Gy WVI + 12Gy boost to the tumor bed. Patients with partial response (PR) but less than 1.5 cm residual proceeded to 24Gy WVI + 12Gy boost. All patients were also enrolled on COG ALTE07C1 to prospectively evaluate and longitudinally model the cognitive, social and behavioral functioning.

RESULTS
During a total accrual time of 45.5 months from 05/2012 to 06/2018, 137 eligible patients were enrolled. Median age was 14.09 years (4.95–21.46), 73% were male, and 45.26% had elevated βhCG in serum and/or cerebrospinal fluid. Twenty-nine patients (21.17%) did not have tissue biopsy. Eleven patients underwent second-look surgery; 7 had mature teratoma and 4 had non-viable tumor. Eighty-one patients (59.13%) had a CR. There were 4 relapses in patients receiving 18Gy WVI + boost, but no deaths. No unexpected treatment-related events were observed. The estimated 3-year PFS was 94.4 ±2.7% among 74 evaluable subjects.

CONCLUSION
This study shows promise in XRT reduction for patients with localized CNS germinoma and CR. Long-term survival outcomes and ALTE07C1 data are being evaluated.
GCT-44. A CASE OF INTRACRANIAL GERMINOMA WHICH RECURRED IN THE SPINAL CORD 13 YEARS AFTER THE INITIAL TREATMENT
Authors: Murota Yasuhiro , Kiyokawa Juri , Ishikawa Mariko , Yamaoka Hiroto , Kaneko Satoshi , Yoshimura Masataka , Hirota Shin , Yamamoto Shinji 
Published: December 2020

Abstract

BACKGROUND
Central nervous system germinoma occurs most often in early teens, accounting for 15% of childhood brain tumors. Here, we report a case of germinoma which recurred in the spinal cord 13 years after complete remission. CASE DESCRIPTION: A 15-year-old boy presented with diabetes insipidus (DI). MRI showed a pineal gland tumor and ventriculomegaly. Biopsy was performed and the histological examinations revealed PLAP and c-kit positive pure germinoma. Ki67 LI was 64.4%. Gamma knife radiosurgery and 3 courses of ICE chemotherapy brought disappearance of the tumor. However, it recurred in lateral ventricles. Forty-Gray whole brain radiation resulted in complete remission of the tumor. For the sake of DI treatment and MRI examinations, he kept periodical visit to our hospital. Thirteen years later, when he was 28y/o, he complained paresthesia in the right upper extremity. MRI demonstrated gadolinium-enhance mass lesion in the cervical spinal cord. Recurrence of the tumor and multiple sclerosis were the principal differential diagnosis. Pulse steroid therapy did not make any change, and radiation therapy to the cervical spinal cord led to tumor disappearance. Nevertheless, the tumor recurred on the dorsal medulla oblongata one and a half years later. Biopsy of the tumor clarified that the tumor was germinoma. ICE chemotherapy which was limited to three courses due to severe bone marrow suppression was carried out. MRI proved no enhanced mass lesion in the central nervous system.

DISCUSSION
Germinoma may recur even after long period of remission, demonstrating that long-term follow-up is indispensable.
GCT-47. TREATMENT STRATEGIES FOR GIANT IMMATURE TERATOMAS IN INFANTS
Authors: Miwa Tomoru , Kono Maya , Shima Haruko , Shimada Hiroyuki , Yoshida Kazunari 
Published: December 2020

Abstract

INTRODUCTION
Immature teratomas are the most frequent fetal brain tumors and show a poor prognosis. At onset, the tumor is often already giant with deep origins such as suprasellar or pineal region, and easy bleeding is also considered to be a cause of poor prognosis. On the other hand, it is also known that the prognosis is improved in total removal cases.

METHODS
We investigated the best treatment strategy based on two cases of total removal of giant immature teratomas in infants.

RESULTS
1.5 month after birth at onset (median), maximum diameter of 75 mm (median). A giant tumor centered around the third ventricle with hydrocephalus. First, biopsy (+septostomy) was performed using an endoscope. The tumor showed easily bleeding. In addition, external ventricular drainage was taken out of the lower abdomen subcutaneously by long tract. After chemotherapy (carboplatin and etoposide), tumor removal was performed by using drainage tract. Both cases showed not easily bleeding at that time and the tumor was safely removed. Regarding the deep blind spot, using a flexible endoscope was effective. They showed no recurrence after total removal (median 50 months).

DISCUSSION
There have been reports of cases in which chemotherapy for immature teratomas suppressed tumor growth and reduced bleeding and safely removed totally. In infants giant immature teratomas, chemotherapy before tumor removal can be expected to reduce bleeding, and further increase body weight during that period. In addition, long-term placement of ventricular drainage by long tract during the chemotherapy can prevent brain development delay due to hydrocephalus.
GCT-51. IMMUNE CHECKPOINT MOLECULES AND TUMOR INFILTRATING LEUKOCYTES IN THE TUMOR MICROENVIRONMENT ARE ASSOCIATED WITH THE GROWTH OF INTRACRANIAL GERMINOMAS
Authors: Nishimoto Masaaki , Ohara Kentaro , Kamamoto Dai , Tamura Ryota , Miwa Tomoru , Yoshida Kazunari , Sasaki Hikaru 
Published: December 2020

Abstract
The role of immune checkpoint molecules and the tumor immune microenvironment in the development of intracranial germ cell tumors remains unclear. In the present study, we investigated the expression of immune checkpoint molecules, as well as the number of tumor-infiltrating lymphocytes (TILs), in intracranial germinomas to determine whether there were any correlations between the statuses of these immune-related molecules/cells and clinical manifestations in patients with germinoma. The 8 patients were categorized based on the duration between symptom onset and pathological diagnosis into the long-term onset (LTO) group (&gt; 1 year of symptoms, 3 patients) and the short-term onset (STO) group (&lt; 1 year of symptoms, 5 patients). Compared with STO tumors, LTO tumors were significantly associated with a lower ratio of programed cell death ligand-1 (PD-L1)–positive tumor cells (p = 0.012), higher number of infiltrating CD3- and CD8-positive lymphocytes (p = 0.016, 0.003, respectively), and lower ratio of programed cell death-1 (PD-1)–positive cells per CD8–positive lymphocytes (p = 0.047). LTO germinomas were significantly smaller in size than STO tumors and tended to be present in patients with atypical tumor location. Our data suggest that the tumor immune microenvironment, including PD-1/PD-L1 signaling, is associated with the growth of intracranial germinomas. Immune checkpoint inhibitors might be a reasonable treatment option for recurrent germinomas or as replacement for radiotherapy in patients with intracranial germinomas.
GCT-56. ACUTE MYELOID LEUKEMIA FOLLOWING CHEMORADIOTHERAPY FOR INTRACRANIAL GERMINOMA: A CASE REPORT
Authors: Nakaya Masato , Koda Yuya , Yamaguchi Kentaro , Yoshida Kazunari , Sasaki Hikaru 
Published: December 2020

Abstract

INTRODUCTION
Therapy-related acute myeloid leukemia (t-AML) is known as　possible complication of chemotherapy, especially topoisomerase Ⅱ　inhibitor,　alkylating agents, and platinum agents. Although there are many reports of therapy-related leukemia associated with gonadal germ cell tumor, few cases have been reported on central nervous system (CNS) germ cell tumor. CASE REPORT: A 35-year old gentleman presented with diplopia. CT and MR imaging showed enhancing nodules on his right hypothalamus and around fourth ventricle, and differential diagnoses included sarcoidosis and germinoma. Biopsy for fourth ventricle lesion was performed via transvermian approach, and histopathological diagnosis was germinoma. He was treated by 3 cycles of CARE chemotherapy (carboplatin and etoposide) followed by craniospinal irradiation (CSI, 24Gy). After completion of chemoradiotherapy, he was followed up every half year by MRI, and there had been no evidence of tumor recurrence. Two years after chemoradiotherapy, however, the patient presented with bleeding tendency, which led to the diagnosis of AML. Based on the history of chemoradiotherapy and the presence of t(16;21)(q24; q22), t-AML was diagnosed. Complete remission was successfully achieved by chemotherapy consisting of idarubicin and cytarabine.

DISCUSSION
t-AML was diagnosed after chemoradiotherapy in a patient with CNS germinoma probably due to the administration of　topoisomerase II inhibitor, etoposide. The prognosis of t-AML is known to be poorer as compared with de novo AML. Therefore, intensive therapy such as allogeneic stem cell transplantation should be considered in younger patients.

CONCLUSION
A possibility of t-AML should be kept in mind following chemotherapy for CNS germ cell tumors.
GCT-62. DISSECTING INTRATUMORAL HETEROGENEITY OF CENTRAL NERVOUS SYSTEM GERM CELL TUMORS BY SINGLE-CELL RNA-SEQUENCING
Authors: Nakano Tomoyuki , Matsushita Yuko , Onuki Ritsuko , Shiokawa Daisuke , Imamura Kiyomi , Horiuchi Terumi , Uchida Eita , Kimura Yui , Ihara Satoshi , Suzuki Tomonari , Tsurubuchi Takao , Ishikawa Eiichi , Nakamura Taishi , Yoshida Makiko , Kawamura Atsufumi , Fukuoka Kohei , Jun Kurihara , Miyakita Yasuji , Narita Yoshitaka , Kobayashi Keiichi , Nagane Motoo , Takami Hirokazu , Nishikawa Ryo , Kato Mamoru , Suzuki Yutaka , Ichimura Koichi 
Published: December 2020

Abstract

BACKGROUND
Central nervous system germ cell tumor (CNSGCT) is a rare pediatric brain tumor. However, they are found at a relatively high incidence in East Asia. Germinoma is sensitive toward radiotherapy and chemotherapy; however, non-germinoma GCTs (NGGCT) often show poor response. Some cases are a mixture of germinoma and NGGCT (mixed GCT), and they sometimes change histological subtypes at recurrence. Previous report demonstrated that a germinoma and NGGCT component within the same mixed GCT tissue shared the same gene mutation, whereas the genome-wide methylation profiles were distinct from each other. The methylation profiles of germinoma was similar to the primordial germ cells (PGC) at the migration phase, supporting a model that PGC is the cell of origin for CNSGCT. However, tumor heterogeneity hinder information of the mixed bulk RNA-sequence data, causing difficulty in elucidating the mechanism of tumor development. The purpose of this study was to investigate the tumor cells subpopulations at the resolution of individual cells by single-cell RNA-seq.

RESULTS
Fresh surgical tumor tissue was immediately dissociated mechanically and enzymatically. Tumor cells are separated from CD45-labelled lymphocytes by FACS, and libraries were generated by Chromium Single cell 3’ Reagent Kit. Total of 11 tumor samples were collected and sequenced. Unsupervised Clustering showed individual clusters. One of the clusters had high expression of Oct-4, which is a marker of germinoma. The other clusters showed different subtypes of cells representing the heterogeneity of CNSGCT. Further analysis including a pseudo-time course analysis is underway to identify the lineage of tumor cell development.
GCT-66. FINAL REPORT OF THE PROSPECTIVE NEXT/CNS-GCT-4 CONSORTIUM TRIAL (GemPOx FOLLOWED BY MARROW-ABLATIVE CHEMOTHERAPY) IN PATIENTS WITH REFRACTORY/RECURRENT CNS GERM CELL TUMORS
Authors: Shatara Margaret , Blue Megan , Stanek Joseph R , Liu Allison Y , Osorio Diana S , AbdelBaki Mohamed S , Prevedello Daniel , Puduvalli Vinay , Giglio Pierre , Gardner Sharon , Allen Jeffrey , Wong Kenneth E , Dhall Girish , Finlay Jonathan L 
Published: December 2020

Abstract

BACKGROUND
We report the responses, toxicities and long-term outcomes of gemcitabine, paclitaxel and oxaliplatin (GemPOx) regimen administered, in responsive patients, prior to single cycle marrow-ablative chemotherapy (thiotepa, etoposide and carboplatin) with autologous hematopoietic progenitor cell rescue (HDCx+AuHPCR).

METHODS
Since December 2009, 11 recurrent/refractory patients (10 MMGCT, 1 germinoma; 10 males; mean age 16.5 years, range 7–46 years) have been treated with up to four cycles of gemcitabine (800mg/M2), paclitaxel (170mg/M2) and oxaliplatin (100mg/M2) administered on one day at 14 days intervals.

RESULTS
All 11 patients were enrolled on a prospective multi-center trial, which was closed in October 2019. Three patients achieved complete remissions (tumor marker and/or imaging studies), five achieved partial remissions, two developed disease progression (PD), and one was withdrawn after one cycle for severe paclitaxel neurotoxicity followed by rapid tumor progression and death. One patient with PD after one cycle had pathologically-confirmed metastatic transformation to pure embryonal rhabdomyosarcoma, and rapidly expired. A second patient, with pure pineal choriocarcinoma, progressed after the second GemPOx cycle, ultimately died of tumor progression. Eight of the 11 responsive patients subsequently underwent HDCx+AuHPCR; five of these received some form of radiotherapy. Seven patients (six MMGCT, one germinoma) are alive and disease-free without recurrence for a mean of 94 months (range 74–118 months) since completion of therapy.

CONCLUSION
GemPOx is an effective re-induction regimen for patient with recurrent CNS germ cell tumors, with acceptable toxicities; when followed by marrow-ablative chemotherapy and subsequent irradiation/re-irradiation, the regimen produces encouraging long-term disease-free survival.