bluuebunny/crossref_metadata_2025_split huggingface dataset:
GCT-25. INNOVATIVE, INTENSIVE IRRADIATION-AVOIDING/MINIMIZING CHEMOTHERAPY FOR HIGH-RISK PRIMARY CENTRAL NERVOUS SYSTEM (CNS) MIXED MALIGNANT GERM CELL TUMORS (HR-MMGCT): A PILOT STUDY AND PROPOSED MULTI-NATIONAL PROSPECTIVE TRIAL
Authors: Finlay Jonathan L , Abu-Arja Mohammad H , Abu-Arja Rolla , Auletta Jeffery , AbdelBaki Mohamed S , Osorio Diana S , Conley Suzanne , Shatara Margaret , Boué Daniel R , Pierson Christopher R , Rusin Jerome , Martin Lisa , Jones Jeremy , Palmer Joshua D , Vatner Ralph , Drapeau Annie , Sribnick Eric , Leonard Jeffrey R 
Published: December 2020

Abstract

BACKGROUND
About one-third of children with primary CNS MMGCT experience incomplete responses to initial induction chemotherapy prior to irradiation, many of whom will subsequently relapse. Such high-risk patients are variably defined as having initial alpha-fetoprotein (AFP) elevations exceeding 1,000ng/mL, predominant histopathologies of malignant non-germinomatous GCT and incomplete responses to induction chemotherapy. Drugs targeting GCT-specific molecular markers have been identified for non-germinomatous GCT elements but have yet to be incorporated into prospective clinical trials. Four children with clearly identified HR-MMGCT characteristics have been treated on an innovative pilot regimen incorporating intensified chemotherapy and molecularly targeted agents, with avoidance or minimization of irradiation.

METHODS
Four children (two with pure suprasellar embryonal carcinoma (EC) - one with Down syndrome and the other with pre-diagnosis cognitive dysfunction; one with initial serum AFP exceeding 7,000ng/mL and yolk sac tumor (YST)+EC+Teratoma pathology; one with initial serum AFP exceeding 1,000ng/mL) were treated with 3 cycles of “standard” induction chemotherapy (ACNS1123), followed by 1–3 transplant cycles (thiotepa/carboplatin) each with complete radiographic and tumor marker responses. Two children with pure EC subsequently received six cycles of brentuximab-vedotin without irradiation and remain disease-free off therapy for 2–4 years. One child with YST+EC+Teratoma has subsequently received reduced dose craniospinal irradiation and pineal region boost, and will receive oral everolimus, erlotinib, palbocyclib and intravenous brentuximab-vedotin. The fourth child with YST+MT will commence everolimus, erlotinib and palbocyclib without irradiation.

CONCLUSION
This treatment strategy for HR-MMGCT patients provides preliminary tolerance and response data justifying extension to a multi-center trial.
GCT-27. CLINICAL FEATURES AND PROGNOSTIC FACTORS OF NONGERMINOMATOUS GERM CELL TUMORS IN 111 CONSECUTIVE PATIENTS IN A SINGLE INSTITUTION: IMPACT OF IRRADIATION AND CHEMOTHERAPY CYCLES ON SURVIVAL
Authors: Wen Lei , Li Juan , Hu Qingjun , Lai Mingyao , Zhou Cheng , Zhen Junjie , Shan Changguo , Hong Weiping , Luo Rishun , Zhang Yangqiong , Zhang Xing , Wang Lichao , Cai Linbo 
Published: December 2020

Abstract

BACKGROUND
Limited data is available in intracranial nongerminomatous germ cell tumors (NGGCTs) in Chinese population. Here we aimed to retrospectively assess the clinical-pathological and prognostic factors of NGGCTs in a single large institution in China.

METHODS
From June 2003 to December 2018, 111 consecutive NGGCTs were treated in Guangdong Sanjiu Brain Hospital, China.

RESULTS
The median follow-up was 36.2 months (range, 1.2 to 131.2 months). Three-year EFS and OS for 111 NGGCTs patients were 78.5%±4.5% and 82.8%±4.0%, respectively. 98 patients received CSI plus boost yielded better survival than those who received reduced-volume radiotherapy or no radiotherapy (3y OS, 86.7% vs. 51.4%, p=0.007). Patients had at least four cycles of chemotherapy were strongly associated with improved 3-year OS, compared to those received less than 4 cycles (94.1% vs. 63.6%, p＜0.001). There was no significant difference in survival of patients stratified by age, surgery, hydrocephalus, as well as tumor diameter. Multivariate analysis identified chemotherapy cycles less than 4 was the only prognostic factor that conferring a worse OS (p=0.003). Patients both received CSI and at least 4 courses of chemotherapy were correlated with lower incidence of relapse (p=0.044).

CONCLUSIONS
Multimodal approach including CSI and enough courses of chemotherapy was effective and should be recommended for the treatment of newly diagnosed NGGCTs in Chinese population.
GCT-28. RECURRENCE PATTERN AND SURVIVAL FOR RELAPSED INTRACRANIAL NON-GERMINOMATOUS GERM CELL TUMORS: A SINGLE-INSTITUTION EXPERIENCE
Authors: Wen Lei , Zhou Zhaoming , Hu Qingjun , Li Juan , Lai Mingyao , Zhou Cheng , Shan Changguo , Zhen Junjie , Hong Weiping , Zhang Xing , Zhang Yangqiong , Luo Rishun , Wang Lichao , Cai Linbo 
Published: December 2020

Abstract

PURPOSE
Intracranial non-germinomatous germ cell tumors (NGGCTs) have lower overall survival than germinoma because relatively higher recurrence usually occurs after first line therapy.

METHODS
Between January 2003 and December 2018, 111 consecutive patients diagnosed with NGGCTs reviewed. Those who progressed after first line therapy were included in this study. Data of first line treatment, salvage treatment, clinicopathological features and survival were collected and analyzed.

RESULTS
Totally, thirty patients (30/111, 27.0%) relapsed in our cohort, including 19 patients with accurate relapse information detail, and 11 patients who died of disease progression during follow up but without exact time and site of relapse. The median OS from diagnosis of the disease was 49.2 months (95% CI: 14.1 to 84.3 months) and 3-year OS was 54.3%. Patients who received both CSI and chemotherapy relapsed less than those who received reduced volume of radiotherapy or only CSI or only chemotherapy (22.5% vs. 45.5%, p=0.034). Of 19 patients who had detail information of recurrence time and site, the median time from diagnosis of disease to relapse was 9.5 months (2.2 to 72.1 months). Regarding to recurrence site, most patients relapsed in primary site (10/19, 52.6%) or distant intracranial (6/19, 31.6%). The recurrence site of other 3 patients were spinal (n=1), ventricular (n=1) and peritoneal (n=1).

CONCLUSION
Protracted follow-up is recommended because late recurrence is not uncommon. Primary tumor site and distant intracranial are the most prevalent relapsed location. Patients who relapsed could benefited from both CSI and salvage chemotherapy.
GCT-37. PREVALENCE OF AUTISM SPECTRUM DISORDER AND OTHER NEURODEVELOPMENTAL DISORDERS IN PEDIATRIC PATIENTS WITH INTRACRANIAL GERM CELL TUMORS
Authors: Liu Kevin X , Sethi Roshan V , Pulsifer Margaret B , D’Gama Alissa M , Lavally Beverly , Tarbell Nancy J , Yock Torunn I , MacDonald Shannon M 
Published: December 2020

Abstract

PURPOSE/OBJECTIVE(s)
Intracranial germ cell tumors (IGCTs) are rare tumors of the central nervous system with peak incidence around puberty. Due to the developmental origins of IGCTs, we investigated the prevalence of neurodevelopmental disorders (NDDs), including autism spectrum disorder (ASD), in our retrospective institutional cohort of patients diagnosed with IGCTs.

MATERIALS/METHODS
A retrospective review of medical records was conducted for 105 patients who were diagnosed with IGCTs and treated at Massachusetts General Hospital between 1998 and 2016. All patients with ASD had thorough neuropsychological assessment at the time of radiotherapy that confirmed their diagnoses.

RESULTS
Median age at diagnosis was 12.8 years (range: 4.3–21.6) and median follow-up time was 4.7 years (range: 0.4–15.8). Seventeen patients with IGCTs were diagnosed with NDDs prior to cancer diagnoses, including five patients with ASD, and three patients with chromosomal abnormalities, including one patient with Down syndrome. Interestingly, four of five patients with ASD developed pure germinomas, giving an ASD prevalence rate of 6.5% and 2.3% in the pure germinoma and NGGCT cohorts, respectively. All other patients had no known diagnoses of NDDs.

CONCLUSIONS
Our study found 17 patients with IGCTs were diagnosed with NDDs prior to their cancer diagnoses. An ASD prevalence of 6.5% in the pure germinoma cohort is more than three-fold greater than the national prevalence, suggesting there may be an association between ASD and pure germinomas. Future prospective studies with larger cohorts are still needed to examine associations between NDDs and ASD and IGCTs.
GCT-60. DEVELOPMENT OF MICROBLEEDING AFTER PROTON THERAPY FOR PATIENTS WITH GERM CELL TUMOR
Authors: Kohzuki Hidehiro , Muroi Ai , Mizumoto Masashi , Sakurai Hideaki , Ishikawa Eiichi , Matsumura Akira 
Published: December 2020

Abstract

BACKGROUND
Proton therapy has been increasingly used to treat pediatric brain tumor. However, there were few reports about radiation-induced cerebral microbleeds(CMBs) and cavernous malformation among these patients. Here we evaluate the incidence and risk factor of CMBs with MR imaging.

MATERIAL AND METHOD
We retrospectively identified patients with germ cell tumor treated with whole ventricle irradiation of 30.6 Gy using proton therapy at the Tsukuba University Hospital between 2004 and 2017. CMBs were characterized by examination of MR imaging scan including susceptibility-weighted imaging and T2* weighed gradient-recalled echo sequence.

RESULT
The mean age at the time of proton therapy was 14.5 years. The median follow-up duration was 62.3 months. Three patients were treated by local boost in addition to whole ventricle irradiation. CMBs were found in 78% at 5 years, and 88% at 10 years from irradiation. Over 80% of CMBs occurred in area of the brain exposed to 30 Gy.

CONCLUSION
This study indicated over 30 Gy irradiation may become a risk factor for development of CMBs. Although the correlation between development of CMBs and cognitive function, proton therapy might have an advantage to reduce late sequelae with decreasing irradiating dose to surrounding normal brain tissue.
GCT-63. STEREOTACTIC RADIOSURGERY FOR RESIDUAL LESIONS OF PINEAL NON-GERMINOMATOUS GERM CELL TUMORS AFTER CONVENTIONAL RADIOTHERAPY: A RETROSPECTIVE STUDY
Authors: Lai Mingyao , Li Juan , Hu Qingjun , Zhou Zhaoming , Wen Lei , Zhou Cheng , Shan Changguo , Cai Linbo 
Published: December 2020

Abstract

OBJECTIVE
To explore the efficacy and safety of SRS for residual lesions of NGGCTs after conventional RT.

METHODS
The clinical data of patients with iGCT who were admitted to Department of Oncology, Guangdong Sanjiu Brain Hospital between January 1, 2008 and December 30, 2019 were gathered. Those who were pathologically or clinically diagnosed with NGGCTs, with lesions located at pineal region, limited stage and residual lesions (with a maximum diameter&gt;10mm) of pineal NGGCTs after RT with a total dose of 50-54Gy/25-30f, were eligible for the study. Several indexes such as local control rate, PFS, OS and treatment-related toxicity were analyzed.

RESULTS
A total of 27 patients were included; all were male, with a median age of 16 years (range 8–31 years). The patients were followed-up to December 30, 2019, but there were 2 cases lost to follow-up. The median follow-up time was 34 months (range 8–142 months). After a month of treatment with SRS, the ORR and DCR were 71.4% and 95.2%, respectively. During follow-up, 5 cases had radiographic progressions, including 3 cases combined with increased AFP which were diagnosed with local recurrence and 2 cases diagnosed with GTS；The 3y-PFS and OS were 85.2% and 88.0%.no acute radiation response was found after treatment with SRS, and only one patient had brain neurotoxicity.

CONCLUSION
SRS for residual lesions of NGGCTs after RT is proved to be safe and feasible, with well tolerance, which is beneficial for the improvement of local control and the prolongation of survival.
GCT-64. TREATMENT RESULTS IN CHILDREN WITH LOCALIZED CNS NGGCT
Authors: Vilesova Irina , Tarasova Ekaterina , Valiakhmetova Andge , Salnikova Ekaterina , Pshonkin Alexey , Novichkova Galina , Karachunsky Alexander , Papusha Ludmila 
Published: December 2020

Abstract

BACKGROUND/OBJECTIVES
Treatment of children with CNS NGGCT remains challenge: 5y OS is 60 – 80%; relapses are very aggressive.

DESIGN/METHODS
Between 2003 and 2019, 14 children (median age 10.5, range 4 – 16 years) with localized intracranial NGGCT were treated with RT after induction chemotherapy (focal – 4, WVI+boost – 6, WBI+boost – 3, CSI+boost – 1). Tumor markers were elevated in 13 patients: 6 – AFP, 5 – HCG, 2 – both. One patient with level of HCG 72049 IU/l in serum and 121451 IU/l in CSF received 4 cycles of PEI + CSI 30 Gy with boost 54Gy.

RESULTS
At a median follow-up of 4,7 years (range 1 – 16,25 years), 12 patients are alive. 5-year PFS and OS are 77,1% and 85,7%, respectively. Two patients (both AFP and HCG) progressed during RT (1 – focal, 1 – WBI+boost), both died. Two patients with high level of HCG recurred after therapy (WVI+boost – 1, focal – 1), both are alive. The first of them at recurrence (mts of lateral ventricle) received 4 cycles of PEI and RT (WBI+boost). The second patient had level of HCG 620IU/l and initially received focal irradiation 54Gy. At recurrence with distant spinal mts he received HD-CHT with auto-SCT, surgical resection of residual tumor and CSI with boost.

CONCLUSIONS
Good results of treatment of localized CNS NGGCT with CSI, WBI or WVI in compare with focal RT show advantages of extended irradiation field. CSI should be considered for patients with extremely high levels of tumor markers and respectively poor prognostic histology.
GCT-74. RETROSPECTIVE LITERATURE REVIEW OF CENTRAL NERVOUS SYSTEM (CNS) GERM CELL TUMORS (GCTs) IN PATIENTS WITH DOWN SYNDROME (DS)
Authors: Harris Micah K , Lamb Margaret , Stanek Joseph R , Finlay Jonathan L , AbdelBaki Mohamed S 
Published: December 2020

Abstract

BACKGROUND
A standard-of-care has not been established for the management of DS patients who develop primary CNS GCTs – the most common CNS neoplasm in DS – despite being more susceptible to treatment-related adverse events.

METHODS
A review of the English-language medical literature between 1960 and 2020 was conducted.

RESULTS
Thirty-one cases of CNS GCTs in DS patients (median nine-years-old; 21 males) were reported; the majority (23/31) originated from East Asia. Twelve had germinomas (39%), 12 had non-germinomatous germ cell tumors (NGGCTs) (39%), and seven had teratomas (22%). Four patients (13%) died from tumor progression (one germinoma versus three teratoma). Seven patients (23%) died from treatment-related complications (four germinoma versus three NGGCT). Of the germinoma patients, two died from chemotherapy-related sepsis, one from post-surgery cardiopulmonary failure, and one from Moyamoya following radiation-therapy (RT) only. Of the NGGCT patients, one died from chemotherapy-related sepsis, one from post-surgical infection, and one from pneumonia following surgery/chemotherapy/RT. Three-year overall survival (OS) was 58.1% for all patients, 52.5% for germinoma, 64.8% for NGGCT, and 60% for teratoma. Three-year OS for patients who received RT or chemotherapy was 63.6% and 59.6% respectively. Twenty patients (65%) remain alive (seven germinoma versus nine NGCCT versus four teratoma). Ten patients (32%) experienced serious treatment-related complications (five germinoma versus five NGGCT).

CONCLUSIONS
Patients with DS and CNS GCTs are at an increased risk of treatment-related complications. Therefore, a different therapeutic approach may need to be considered for this patient population in order to mitigate the treatment-related complications and long-term neurocognitive sequelae.
GCT-76. 24Gy WHOLE VENTRICULAR RADIOTHERAPY ALONE IS SUFFICIENT FOR DISEASE CONTROL IN LOCALISED GERMINOMA IN CR AFTER INITIAL CHEMOTHERAPY – EARLY RESULTS OF THE SIOP CNS GCT II STUDY
Authors: Calaminus Gabriele , Bison Brigitte , Faure-Conter Cecile , Frappaz Didier , Peyrl Andreas , Gerber Nicolas , Müller Jans-Enno , Thankamma Ajithkumar , Mitra Dipayan , Cross Justin , Pietsch Torsten , Smith Colin , Solem Kristin , Devenney Irene , Garre Maria Luisa , Brisse Herve , Zimmermann Martin , Kortmann Rolf-Dieter , Alapetite Claire , Nicholson James 
Published: December 2020

Abstract
SIOP CNS GCT II aimed to establish if 24Gy Whole Ventricular Radiotherapy (WVRT) in localised germinoma is sufficient for tumour control. After central review of radiological response after ‘CarboPEI’ chemotherapy, patients in complete remission (CR) were consolidated with 24Gy WVRT. Between 2/2012 and 7/2018, 182 patients from 8 European countries with histologically-confirmed fully-staged localised germinoma were registered. 70 patients were in CR after chemotherapy, 98 in partial remission (PR), seven had stable disease, two progressive disease, and in five no response data were documented. Of the 70 patients in CR, 58 received 24Gy WVRT alone; two of these relapsed, one local and one disseminated, two and six years after diagnosis. Of the 98 patients in PR after chemotherapy, 86 received 24Gy WVRT and 16Gy boost, of which five relapsed (three local, two distant) 12–24 months from diagnosis. Twelve patients in each of the CR/PR groups received non-protocol or undocumented radiotherapy fields/doses. Median follow-up was 3.7 years. Event-free survival (EFS) for patients in CR and with WVRT only (n=58) was 98% at 4 years. 4-years EFS of patients with PR and WVRT 24Gy and 16Gy tumor boost (n=86) was 95%. Localised germinoma in CR after chemotherapy had an excellent outcome with 24Gy WVRT alone; 24GY WVRT can therefore be considered standard consolidation treatment in this group. International consensus on radiological response criteria is of utmost importance to avoid over- and undertreatment of such patients and to pave the way for further treatment reduction in this group of patients.
HGG-01. ENTRECTINIB IN RECURRENT OR REFRACTORY SOLID TUMORS INCLUDING PRIMARY CNS TUMORS: UPDATED DATA IN CHILDREN AND ADOLESCENTS
Authors: Robinson Giles , Desai Ami , Basu Ellen , Foster Jennifer , Gauvain Karen , Sabnis Amit , Shusterman Suzanne , Macy Margaret , Mease Luke , Yoon Janet , Cash Thomas , Abdelbaki Mohamed , Nazemi Kellie , Pratilas Christine , Weiss Brian , Chohan Saibah , Cardenas Alison , Hutchinson Katherine , Bergthold Guillaume , Gajjar Amar 
Published: December 2020

Abstract
STARTRK-NG (phase 1/2) is evaluating entrectinib, a CNS-penetrant oral, TRK/ROS1/ALK tyrosine kinase inhibitor, in patients &lt;21 years with recurrent/refractory solid tumors, including primary CNS tumors. After determining the recommended dose, 550mg/m2/day, in all-comers, expansion cohorts with gene-fusion-positive CNS/solid tumors (NTRK1/2/3, ROS1) are being enrolled. As of 5Nov2019 (data cut-off), 39 patients (4.9m–20y; median 7y) have been evaluated for response, classified as complete (CR) or partial response (PR), stable (SD) or progressive disease (PD) using RANO (CNS), RECIST (solid tumors), or Curie score (neuroblastoma). Responses in patients with fusion-positive tumors were Investigator-assessed (BICR assessments are ongoing) and occurred at doses ≥400mg/m2. Best responses in fusion-positive CNS tumors (n=14) were: 4 CR (GKAP1-NTRK2, ETV6-NTRK3 [n=2], EML1-NTRK2); 5 PR (KANK1-NTRK2, GOPC-ROS1, ETV6-NTRK3, TPR-NTRK1, EEF1G-ROS1); 3 SD (BCR-NTRK2, ARHGEF2-NTRK1, KIF21B-NTRK1); 2 PD (PARP6-NTRK3, EML4-ALK); and in fusion-positive solid tumors (n=8) were: 3 CR (ETV6-NTRK3 [n=2], DCTN1-ALK); 5 PR (EML4-NTRK3, TFG-ROS1 [n=3], KIF5B-ALK). Responses (Investigator-assessed) in non-fusion tumors (n=17) were: 1 CR (ALK F1174L mutation), 3 SD, 10 PD, 3 no data/unevaluable. The objective response rate (CR+PR/total) in patients with fusion-positive tumors was 77% (17/22) versus 6% (1/17) in those with non-fusion tumors. All 39 patients experienced ≥1 adverse event (AE); the most frequent AEs included weight gain and anemia (both 48.7%); increased ALT, increased AST, cough and pyrexia (all 46.2%); increased creatinine and vomiting (both 43.6%); and bone fractures (n=10, in 9 patients). Entrectinib has produced striking, rapid, and durable responses in solid tumors with target gene fusions, especially high-grade CNS neoplasms.
HGG-11. HIGH-GRADE GLIOMAS IN ADOLESCENTS AND YOUNG ADULTS HIGHLIGHT HISTOMOLECULAR DIFFERENCES WITH THEIR ADULT AND PAEDIATRIC COUNTERPARTS
Authors: Roux Alexandre , Pallud Johan , Saffroy Raphaël , Edjlali-Goujon Myriam , Debily Marie-Anne , Boddaert Nathalie , Sanson Marc , Puget Stéphanie , Knafo Steven , Adam Clovis , Faillot Thierry , Cazals-Hatem Dominique , Mandonnet Emmanuel , Polivka Marc , Dorfmüller Georges , Dauta Aurélie , Desplanques Mathilde , Gareton Albane , Pages Mélanie , Tauziède-Espariat Arnault , Grill Jacques , Bourdeaut Franck , Doz François , Dhermain Frédéric , Mokhtari Karima , Chrétien Fabrice , Figarella-Branger Dominique , Varlet Pascale 
Published: December 2020

Abstract

BACKGROUND
Considering that paediatric high-grade gliomas (HGGs) are biologically distinct from their adult counterparts, the objective of this study was to define the landscape of HGGs in adolescents and young adults (AYAs).

METHODS
We performed a multicentric retrospective study of 112 AYAs from adult and paediatric Ile-de-France neurosurgical units, treated between 1998 and 2013 to analyse their clinicoradiological and histomolecular profiles. The inclusion criteria were age between 15 and 25-years, histopathological HGG diagnosis, available clinical data, pre-operative and follow-up MRI. MRI and tumoral samples were centrally reviewed. Immunohistochemistry and complementary molecular techniques such as targeted/next generation sequencing, whole exome sequencing and DNA-methylation analyses were performed to achieve an integrated diagnosis according to the 2016 WHO classification.

RESULTS
Based on 80 documented AYA patients, HGGs constitute heterogeneous clinicopathological and molecular groups, with a predominant representation of paediatric-subtypes (Histone H3-mutants, 40%) but also adult-subtypes (IDH-mutants, 28%) characterized by the rarity of oligodendrogliomas, IDH-mutant and 1p/19q co-deleted and the relative high frequency of “rare adult IDH mutations” (20%). H3G34-mutants (14%) represent the most specific subgroup in AYAs. In the H3K27-mutant subgroup, the non-brainstem diffuse midline gliomas are more frequent (66.7%) than diffuse intrinsic pontine gliomas (23.8%), contrary to children. We found that WHO grade has no prognostic value, but molecular subgrouping has major prognostic importance.

CONCLUSIONS
HGGs in AYAs could benefit from a more personalized neuro-oncological management, driven by molecular subtyping rather than age group. Collaborative efforts are needed from paediatric and adult neuro-oncology teams to improve the management of HGGs in AYAs.