bluuebunny/crossref_metadata_2025_split huggingface dataset:
CTNI-22. RETROSPECTIVE ANALYSIS OF THE COMBINED TREATMENT OF VINCRISTINE, ACNU, CARBOPLATIN AND INTERFERON-β PLUS RADIOTHERAPY (VAC-FERON-R)IN PATIENTS WITH DIFFUSE ASTROCYTOMA
Authors: Arakawa Yoshiki , Makino Yasuhide , Kawauchi Takeshi , Tanji Masaharu , Mineharu Yohei , Kanemura Yonehiro , Miyamoto Susumu 
Published: December 2020

Abstract

OBJECTIVE
Diffuse astrocytomas are classified as WHO grade II and its median overall survival (mOS) is 10 to 11 years. The efficacy of chemoradiation in the high-risk feature has been reported. The prognosis is associated with IDH and TERT promoter (TERTp) mutations. Here, we retrospectively analyzed the patients with diffuse astrocytoma treated with vincristine, ACNU, carboplatin and interferon-β plus radiotherapy (VAC-feron-R)in our institute.

PATIENTS AND METHODS
Between December 2003 to January 2016, 44 patients were diagnosed as diffuse astrocytoma with integrated diagnosis of histological and molecular analysis. The average age was 43.1 years (22–71 years). They received VAC-feron-R as initial treatment in our institute. We analyzed the IDH1/2 and the TERTp mutation using Sangar sequencing and determined the 1p/19q codeletion by the fluorescence in situ hybridization or the multiplex ligation-dependent probe amplification.

RESULTS
Median follow-up period was 76.5 months, mPFS was 126 months, mOS did not reach, and 10-year survival rate was 60%.IDH status was determined in 29 patients, 9 mutant and 20 wild types. There was no significant difference in PFS and OS between the two groups. TERTp status was determined in 18 patients with IDH wild type, 6 mutant and 12 wild types. mPFS of patients with TERTp wild type did not reach, but that with TERTp mutant type was 34.5 months (p = 0.0356).

CONCLUSION
Compared with previous clinical studies, VAC-feron-R showed a favorable clinical outcome in diffuse astrocytoma. The impact of TERTp status on prognosis was identified but not IDH status in this cohort.
CTNI-26. ACCELERATOR-BASED BNCT IN RESCUE TREATMENT OF PATIENTS WITH RECURRENT GBM: A MULTICENTER PHASE II STUDY
Authors: Miyatake Shin-Ichi , Kawabata Shinji , Goto Hiromi , Narita Yoshitaka , Suzuki Minoru , Hirose Katsumi , Takai Yoshihiro , Ono Koji , Ohnishi Takanori , Tanaka Hiroki , Kato Takahiro 
Published: December 2020

Abstract

BACKGROUND
Boron neutron capture therapy (BNCT) is tumor-selective particle　radiation and theoretically efficacious especially for tumors with infiltrative nature, such as glioblastoma (GBM). The aim of this study is to assess safety and efficacy of accelerator-based BNCT (AB-BNCT) using cyclotron-based neutron generator, BNCT30, and 10B-boronophenylalanine (borofalan(10B)) agent, SPM-011, in patients with recurrent malignant gliomas, chiefly GBM.

METHODS
The multi-institutional open-label, phase II clinical trial for recurrent 27 cases of malignant gliomas (MG) (24 cases were GBM) was conducted with above AB-BNCT system, using 500mg/kg of SPM-011 (study code, JG002). The patients were enrolled from February 2016 to June 2018. The inclusion criteria are bevacizumab-naïve MG, recurrent after standard treatment composed of XRT and chemotherapy with TMZ. Neutron-irradiation time were determined not to exceed to 8.5 Gy-Eq for scalp dose. Primary endpoint was 1-year survival rate and secondary ones were median overall survival (mOS), median progression free survival (mPFS). The results were compared to previous Japanese domestic bevacizumab trial for recurrent GBM (JO22506) which had the similar inclusion criteria with JG002.

RESULTS
1-year survival rate and mOS of recurrent GBM cases in JG002 was 79.2% (95% CI:57.0–90.8) and 18.7 months (95% CI:12.9–23.4) respectively, while those of JO22506 was 34.5% (90% CI:20.0–49.0) and 10.5 months (95% CI:8.2–12.4), respectively. Median PFS of JG002 and JO22506 were 0.9 and 3.3 months, respectively. Most important adverse event in JG002 was brain edema. Brain edema in 21 out of 27 cases was treated with bevacizumab after progress disease.

CONCLUSIONS
AB-BNCT demonstrated acceptable safety and prolonged survival for recurrent MG chiefly GBM. AB-BNCT might produce brain edema somewhat after the treatment, which might be the unavoidable adverse event of re-irradiation for recurrent MG, however that seemed to be controlled well with bevacizumab.
CTNI-51. NEUROCOGNITIVE FUNCTION (NCF) OUTCOMES OF RTOG FOUNDATION 3508: A PHASE 3 TRIAL OF ABT-414 WITH CONCURRENT CHEMORADIATION AND ADJUVANT TEMOZOLOMIDE IN PATIENTS WITH EGFR-AMPLIFIED NEWLY DIAGNOSED GBM
Authors: Wefel Jeffrey S , Won Minhee , Lassman Andrew , Stern Yaakov , Wang Tony , Aldape Kenneth , Armstrong Terri , Vogelbaum Michael , Sulman Erik , Moazami Golnaz , Macsai Marian , Gilbert Mark , Bain Earle , Blot Vincent , Gan Hui , Preusser Matthias , Ansell Peter , Samanta Suvajit , Kundu Madan , Seidel Clemens , de Vos Filip , Hsu Sigmund , Cardona Andres , Lombardi Giuseppe , Bentsion Dmitry , Peterson Richard , Gedye Craig , Lebrun-Frenay Christine , Wick Antje , Pugh Stephanie , Curran Walter , Mehta Minesh 
Published: December 2020

Abstract
RTOG 3508/AbbVie M13-813/INTELLANCE-1 was a phase 3 trial of depatuximab-mafodotin (depatux-m, formerly ABT-414) that accrued 639 patients with EGFR-amplified newly diagnosed GBM. At the pre-specified interim OS analysis, the futility criteria were met and there was no survival benefit from adding depatux-m to SOC. Pre-specified secondary NCF analyses included time to decline in verbal learning and memory as assessed by the HVLT-R Total Recall based on the reliable change index. Exploratory NCF analyses examined changes in other HVLT-R outcomes over time. As corneal epitheliopathy causing visual impairment is a known toxicity of depatux-m, NCF tests that did not depend on visual acuity were employed. NCF testing occurred at baseline, day 1 of the first cycle of adjuvant depatux-m, every other cycle (i.e., 8 weeks) thereafter, and at progression. Compliance with test completion was 95% at screening and 80%, 70%, 58%, 51%, 47% thereafter through cycle 9. The most common reasons for missing data was site error. Time to HVLT-R Total Recall decline trended worse in the depatux-m arm compared to placebo but the difference was not significant (12 month deterioration: 41.2%, 95% CI: 3.50–47.2 vs 32.4%, 95% CI: 26.6- 38.4, p=0.052). The depatux-m arm, in comparison to the placebo arm, showed greater decline from baseline on the HVLT-R at the following time points: cycle 3 (Total Recall: mean= -1.8, SD=5.7 vs mean= -0.5, SD=5.5, respectively, p=0.046; Delayed Recall: mean= -1.1, SD=3.0 vs. mean= -0.2, SD=2.7, respectively, p=0.01), cycle 7 (Total Recall: mean= -0.6, SD=5.1 vs mean= 1.4, SD=5.0, respectively, p=0.009; Delayed Recall: mean -0.6, SD=3.0 vs. mean= 0.5, SD=2.7, respectively, p=0.01), and cycle 9 (Delayed Recall: mean=-0.4, SD=2.7 vs. mean= 0.8, SD=2.4, respectively, p=0.003). Depatux-m added to concurrent chemoradiation and adjuvant temozolomide was associated with faster time to deterioration and worse episodic learning and memory over time than placebo.
CTNI-55. PREDICTIVE FACTORS FOR HIGH GRADE TRANSFORMATION IN BENIGN MENINGIOMAS
Authors: Hoon Kim Jeong , Yoo Hee Jun 
Published: December 2020

Abstract

OBJECT
Meningiomas are generally slow-growing, benign tumors, most of which are classified as WHO Grade I. Rarely, benign meningiomas may recur after surgery with transformation into WHO Grade II atypical meningiomas. As atypical meningiomas are different from benign meningiomas in terms of clinical course, and prognosis, predicting the transformation is important for patient management. The purpose of the study was to investigate the radiological and pathological factors that predict the risk of tumor progression from benign to atypical meningioma.

METHOD
All patients treated with recurrent meningiomas in whom the tumor showed histopathologically confirmed high grade transformation between 2001 and 2017 were included. To evaluate the predictors for transformation, patients’ medical records for previous benign meningioma before transformation were collected. Each patient was matched with 4 age and sex-matched controls treated with benign meningioma, and were analyzed.

RESULTS
Fourteen patients with high grade transformation were included. The median time interval of transformation was 63 months (range of 19 – 132). Multivariate analysis indicated that increased mitotic index (OR, 10.409, 95% CI, 1.297–83.549, p=0.027) was significant predictive factor of transformation. And prominent peritumoral edema (OR, 33.822, 95% CI, 0.935–223.688, p=0.054) showed relative risk for transformation.

CONCLUSION
Increased mitotic index and prominent peritumoral edema may be predictors for high grade transformation of benign meningiomas. Although these tumors do not meet the criteria for atypical meningioma, they may be required more attentive observation and management than other benign meningiomas.
CTNI-63. PROGNOSTIC FACTORS IN PATIENTS WITH BASAL GANGLIA GERM-CELL TUMORS: A RETROSPECTIVE ANALYSIS OF THE SINGLE CHINESE INSTITUTE EXPERIENCE FROM 2009 TO 2019
Authors: Hu Qingjun , Li Juan , Lai Mingyao , Zhou Cheng , Zhou Zhaoming , Shan Changguo , Cai Linbo 
Published: December 2020

Abstract

OBJECTIVE
To evaluate the clinical factors related to the prognosis of basal ganglia germ cell tumors.

METHODS
A retrospective analysis of 52 cases of the basal ganglia germ cell tumors treated from January 2009 to January 2019 in the department of oncology of Guangdong Sanjiu Brain Hospital. The median age: 12 years (range: 5–32), The median course of disease: 11.7 months (range: 1–54). Thirteen cases were diagnosed by biopsy and 39 cases were diagnosed by elevated tumor markers. There were 31 patients (59.6%) diagnosed with germinomas and 21 patients (40.4%) with non-germ germ cell tumors. Univariate and multivariate survival analysis was performed.

RESULTS
To October 15, 2019, the median follow-up time was 30.4 months (range 2–124 months). The 5-year survival rate was 85%, and the 5-year progression-free survival rate was 84%. Multivariate analysis found whether serum AFP was greater than 100mIU / ml, (with HR: 11.441,95% CI: 2.09–47.66, P = 0.005),the degree of surgical resection(with HR 5.323 (1.19–23.812), P = 0.029), PD as the effect of radiotherapy (HR: 16.53, (1.19–23.81), P = 0.001) were independent prognostic factor affecting survival.

CONCLUSION
The pathological type, degree of surgical resection, and response to initial treatment can all affect survival.
CTNI-64. MATRIX REGIMEN FOR NEWLY DIAGNOSED PRIMARY DIFFUSE B-CELL LYMPHOMA OF THE CENTRAL NERVOUS SYSTEM
Authors: Green Richard , Thornton Colleen 
Published: December 2020

Abstract
We report our experience treating 16 patients with newly diagnosed primary diffuse B-cell lymphoma of the central nervous system with the MATRix regimen as reported by Ferreri, et al in 2016. The median age was 66 years (y); 8 patients were men and 8 were women. Fourteen had cerebral mass lesions, 1 had a paraspinal mass, and 1 leptomeningeal disease. Treatment consisted of 4 cycles of rituximab 375 mg/sq m (Days 1, 6); methotrexate 3.5 g/sq m (Day 2); cytarabine 2 g/sq m every 12 h (Days 3, 4); and thiotepa 30 mg/sq m (Day 5). Patients without disease progression received carmustine 400 mg/sq m and thiotepa 4 X 5 mg/kg followed by autologous bone marrow transplantation. Four patients were switched to MATRix after 6 cycles of methotrexate and rituximab and received only 2 initial cycles including cytarabine and thiotepa. Overall, 12 patients completed initial chemotherapy. Eleven of these 12 went on to transplantation; one patient had early disease progression and did not proceed to transplantation. All 4 patients over 70 y died early after 1–2 cycles; the median age of these was 80 y, and the causes of early death were neutropenic fever, septic thrombophlebitis, and cardiac arrest. One patient who completed the entire regimen including transplantation died of fungal pneumonia; the other 11 experienced no serious acute toxicity. One patient had late disease progression; one developed symptomatic leukoencephalopathy. Nine of the 16 patients remain alive. At a median follow-up of 23 months, median time to progression was 421 days and overall survival 564 days. These preliminary data suggest that the MATRix regimen in safe and highly effective in the newly diagnosed setting. However, the high incidence of early death in patients over 70 y suggests that the regimen may be too toxic for elderly individuals.
CTNI-66. ONE-YEAR FOLLOW-UP DATA OF PHASE I/II STUDY OF TIRABRUTINIB IN PATIENTS WITH RELAPSED OR REFRACTORY PRIMARY CENTRAL NERVOUS SYSTEM LYMPHOMA
Authors: Mishima Kazuhiko , Narita Yoshitaka , Nagane Motoo , Terui Yasuhito , Arakawa Yoshiki , Yonezawa Hajime , Asai Katsunori , Fukuhara Noriko , Sugiyama Kazuhiko , Shinojima Naoki , Aoi Arata , Nishikawa Ryo 
Published: December 2020

Abstract
Primary central nervous system lymphoma (PCNSL) is known as one of the incurable brain tumors. In March 2020, Tirabrutinib (TIR), a second-generation oral Bruton’s tyrosine kinase inhibitor, was approved for the indication of relapsed or refractory PCNSL (rrPCNSL) based on the results of a phase I/II study in Japan (Trial registration: JapicCTI-173646). In this study, 44 Japanese patients with rrPCNSL were treated with TIR QD at 320 mg, 480 mg, or 480 mg in the fasted condition (480 mg fasted QD). The primary endpoint was overall response rate (ORR) assessed by an independent review committee according to International PCNSL Collaborative Group criteria. We previously reported the results of this study with data cutoff on June 13, 2019 (Nagane et al., the 61st American Society of Hematology Annual Meeting and Exposition in 2019). In the report, 17 of 44 patients were treated with TIR at 480 mg fasted QD which is an approved dose, and had ORR of 52.9%, median progression-free survival of 5.8 months, and median overall survival of not reached (median follow-up: 3.8 months). In 44 patients, ORR was similar among patients harboring either of the oncogenic mutants CARD11, MYD88, CD79B, or wild type. Throughout the whole patients, most common adverse events (AEs) at any grade were rash (32%), neutropenia (23%), leukopenia (18%), and lymphopenia (16%), and grade ≥3 AEs were neutropenia (9.1%), lymphopenia, leukopenia, and erythema multiforme (6.8% each). One patient with 480 mg QD had grade 5 AEs (pneumocystis jirovecii pneumonia and interstitial lung disease). We will present one-year follow-up data of this study at the meeting. As of data cutoff (February 25, 2020), 11 of 44 patients continued to receive TIR, including 6 patients with 480 mg fasted QD. Updated data for OS, duration of response, and time to onset of AEs will also be presented.
CTNI-71. TTFIELDS IN ROUTINE CLINICAL CARE OF NEWLY DIAGNOSED GBM PATIENTS IN GERMANY – FIRST REPORT ON THE FULLY ENROLLED TIGER STUDY POPULATION
Authors: Bähr Oliver , Tabatabai Ghazaleh , Fietkau Rainer , Goldbrunner Roland , Glas Martin 
Published: December 2020

Abstract

OBJECTIVE
Glioblastoma (GBM) is widely treated with surgery, chemoradiation and TTFields in combination with chemotherapy. Since the introduction of TTFields to first-line GBM treatment, prescribing physicians in Germany are interested to gain additional knowledge on the use in clinical practice. The TIGER study was designed to assess the therapy decision making process, safety and efficacy of TTFields in clinical routine, as well as evaluating quality of life (QoL) within 4 months after start of therapy, treatment compliance and duration.

METHODS
This multi-center prospective non-interventional study in Germany (NCT03258021) included newly diagnosed GBM patients eligible for TTFields therapy. Within the study, after receiving introduction to TTFields therapy, patients could decide for or against receiving TTFields. The study was designed to recruit 500 patients for each group, with and without TTFields. Demographic data, QoL and reasons for therapy decision 2–4 months after treatment start are assessed using the EORTC-QLQ-C30/BN-20 and a TTFields questionnaire, respectively, with 18 months follow-up.

RESULTS
At the last data cut-off (31st March, 2020), the median follow-up was 11 months (range: 0–28 months) and 581 (82%) of the 710 recruited patients in the trial had decided for TTFields therapy. According to preliminary analysis, this patient population represents a typical GBM population regarding median age (59 years, range: 19.0–85.0), gender (37 % female), median KPS (90, range: 40–100) and MGMT promoter methylation status (44% methylated). In this population 49 % received complete resection, 33 % partial resection and 19 % biopsy.

CONCLUSION
The TIGER study allows prospective and systematic analysis of TTFields treatment decision making and use of typical GBM patient population in routine clinical care. In addition, the study allows the evaluation of compliance and treatment duration. Here, we will present an updated analysis of the TIGER study.
CTNI-72. PHASE 2 STUDY OF DIANHYDROGALACTITOL (VAL-083) IN PATIENTS WITH MGMT-UNMETHYLATED, BEVACIZUMAB-NAÏVE GLIOBLASTOMA IN THE RECURRENT AND ADJUVANT SETTING
Authors: O’Brien Barbara , Penas-Prado Marta , Kamiya-Matsuoka Carlos , Weathers Shiao-Pei , Yung W K Alfred , Loghin Monica , Harrison Rebecca , Majd Nazanin , Bacha Jeffrey , Brown Dennis , Johnson Greg , Langlands John , Schwartz Richard , Kanekal Sarath , Steino Anne , Lopez Lorena , de Groot John 
Published: December 2020

Abstract
Current standard-of-care for glioblastoma (GBM) includes surgery followed by concurrent therapy with radiation and temozolomide (TMZ) followed by adjuvant TMZ. Almost all GBM patients experience recurrent/progressive disease despite upfront standard of care treatment, with a median survival after recurrence of 3–9 months. Unmethylated promoter for O6-methylguanine-DNA-methyltransferase (MGMT) is a validated biomarker for TMZ-resistance and is correlated with poor patient prognosis. VAL-083 is a bi-functional DNA-targeting agent which rapidly induces inter-strand cross-links at N7-guanine inducing double-strand breaks causing cell death and acts independent of MGMT DNA repair. This trial is an open-label two-arm biomarker-driven phase 2 clinical trial in MGMT-unmethylated bevacizumab-naïve GBM patients with either recurrent (Group 1) or newly diagnosed GBM requiring adjuvant therapy after chemo-radiation with temozolomide (Group 2). Patients receive VAL-083 IV at 30 or 40 mg/m2/d on days 1, 2, and 3 of a 21-day cycle. The primary objective of this study is to determine the effect of VAL-083 on median overall survival (mOS) in MGMT-unmethylated recurrent GBM patients (Group 1); and progression-free survival (PFS) in newly diagnosed GBM patients requiring adjuvant therapy after chemo-irradiation with temozolomide (Group 2), compared to historical controls in both groups. Tumor response will be assessed by MRI every 42 days, using RANO criteria. The initial starting dose in this study was 40 mg/m2/d on days 1, 2, and 3 of a 21-day cycle, which was subsequently reduced to 30 mg/m2/d to improve tolerance due to myelosuppression. As of June 2-2020, 35 patients with recurrent GBM (Group 1) have received 40 mg/m2/d and 39 patients have received 30 mg/m2/d VAL-083. In the adjuvant setting (Group 2), 25 patients have been enrolled (30 mg/m2/day). Enrollment, safety data and study updates will be presented at the meeting. Clinicaltrials.gov identifier: NCT02717962.
DDRE-03. INTERNATIONAL PRECLINICAL DRUG DISCOVERY AND BIOMARKER PROGRAM INFORMING AN ADOPTIVE COMBINATORIAL TRIAL FOR DIFFUSE MIDLINE GLIOMAS
Authors: Przystal Justyna , Yadavilli Sridevi , Abadi Christina Coleman , Yadav Viveka Nand , Laternser Sandra , Cosentino Chiara Cianciolo , Waszak Sebastian , Cartaxo Rodrigo , Biery Matt , Myers Carrie , Jayasekara Samantha , Olson James , Filbin Mariella , Vitanza Nicholas , Cain Jason , Koschmann Carl , Mueller Sabine , Nazarian Javad 
Published: December 2020

Abstract

INTRODUCTION
DMG-ACT (DMG- multi-arm Adaptive and Combinatorial Trial) aims to implement a highly innovative clinical trial design of combinatorial arms for patients with diffuse midline gliomas (DMGs) at all disease stages that is adaptive to pre-clinical data generated in ten collaborating institutions. Novel drug and drug combination were tested, predictive biomarkers were identified and incorporated in clinical trial design.

METHODS
In vitro (n=15) and in vivo (n=8) models of DMGs across ten institutions were used to assess single and combination treatments with ONC201, ONC206, marizomib, panobinostat, 5-Azacytidine, Val-083, GDC0084 and TAK228. In vivo drug toxicity screenings were conducted using larval zebrafish model and murine PDX models. Predictive biomarkers for ONC201 and ONC206 were identified using meta-analysis, and extensive molecular assays including CRISPR, RNAseq, FACS, and IHC.

RESULTS
Inhibitory concentrations (IC50) were established and validated multiple preclinical models. ONC201 and ONC206, ONC201 and TAK228, ONC201 and GDC0084 showed synergism. In vivo survival assays showed increased survival for: ONC201 (p=0.01), ONC206 (p=0.01), ONC201+ONC206 (p=0.02), and ONC201+panobinostat (p=0.01). Marizomib showed toxicity in murine/zebrafish PDXs models. Murine pharmacokinetic analysis showed peak brain levels of ONC201 and ONC206 above pre-clinical IC50. Molecular testing and analyses of existing drug screen across 537 cancer cell lines validated mitochondrial protease ClpP and ATF4 as ONC201/6 targets. Predictive biomarkers of response to drug were identified.

CONCLUSION
Thorough preclinical testing in a multi-site laboratory setting is feasible and identified ONC201 in combination with ONC206, TAK228 and GDC0084 as promising therapeutics for DMGs.
DDRE-05. DECREASED EXPRESSION OF DNA DAMAGE RESPONSE PATHWAYS CORRELATES WITH SYNERGISTIC ACTIVITY OF TEMOZOLOMIDE WITH ATR INHIBITORS IN GLIOBLASTOMA
Authors: Wu Shaofang , Li Xiaolong , Singh Sanjay , Koul Dimpy , Yung W K Alfred 
Published: December 2020

Abstract
The lack of knowledge about the relationship between tumor genotypes and therapeutic responses remains one of the most important gaps in enabling the development of effective targeted cancer therapies. Increasing evidence supports the notion that DNA damage response (DDR) signaling plays an important role in inducing radiation and temozolomide (TMZ) resistance in glioblastoma (GBM) and hence, it has emerged as a molecular target for therapeutic development. The cellular response to TMZ therapy is critically mediated by MGMT and DDR signaling networks that are regulated by Ataxia Telangiectasia Mutated (ATM) and Ataxia Telangiectasia and Rad3-related protein (ATR). ATR is a primary sensor of DNA damage initiating subsequent repair leading to cell survival. Here, we show that three clinical grade ATR inhibitors (Bay1895344, AZD6738 and VE-822) had similar selective sensitivity pattern across eight glioma-like stem cells (GSC) lines tested with three (GSC28, GSC11, GSC274) being the most sensitive, and three (GSC300, GSC272, and GSC20) being the most resistant cell lines. Interestingly, all three ATR inhibitors showed a significant synergism with TMZ (Combination index and Bliss model) in GSC300, GSC272, and GSC20, and antagonism in GSC28, GSC11, and GSC274. Further analysis showed that the synergistic group was resistant to single agent ATR inhibitor, whereas antagonistic group was inherently sensitive to ATR inhibitor. The synergistic response was not associated with any major genetic alterations such as MGMT status, EGFR amplification, PTEN deletion/mutation, or p53 deletion/mutation. However, GSEA analysis of baseline RNA-seq data of the 6 cell lines showed an enhanced expression of six DNA damage/repair/response pathways in the antagonistic group. It suggests that a low level of DNA damage/repair/response pathways could be a marker of synergy for TMZ with ATR inhibitors in GBM. Further studies are underway to validate this observation in more GSC lines in vitro and in vivo.