bluuebunny/crossref_metadata_2025_split huggingface dataset:
CTNI-70. RADIOTHERAPY QUALITY ASSURANCE IN THE ROAM/EORTC1308 ATYPICAL MENINGIOMA RANDOMISED CONTROLLED TRIAL: PROSPECTIVE REVIEW IMPROVES RADIOTHERAPY QUALITY AND CONSISTENCY
Authors: Jenkinson Michael , Mayles Helen , Weber Damien , Haylock Brian ,   ROAM/EORTC1308 Trial Management Group
Published: November 2023

Abstract

OBJECTIVE
ROAM/1308 is an international randomised controlled phase III trial comparing radiotherapy (60Gy in 30 fractions) to observation following complete surgical resection of atypical meningioma. We embedded prospective radiotherapy quality assurance (RTQA) within the trial with the aim of ensuring consistent radiotherapy planning and delivery.

METHODS
The radiotherapy protocol described the consensus contouring/planning guidelines. Pre-trial assessment included benchmark cases (outlining/planning) and a technology ‘Dummy Run’. Individual case reviews were undertaken. Non-conformities were classed as ‘major’ (undertreatment of dural margins/over treatment of brain or organs at risk) or ‘minor’ (for education). Resubmissions were mandated for all major non-conformities. All plans were approved before radiotherapy delivery.

RESULTS
The UK RTQA group coordinated European sites. The Australian RTQA group (TROG) reviewed their sites and provided all data to the UK for review. Four radiation oncologists reviewed contours and physicists/dosimetrists reviewed plans. All sites (20 UK, 25 EORTC, 11 TROG) undertook the benchmark/’Dummy Run’ cases prior to opening. Resubmissions were: UK (1 contour, 0 plans), EORTC (2 contours, 6 plans) and TROG (1 contour, 3 plans). Trial communications and outlining workshops were used to provide feedback. Radiotherapy was delivered to 30, 26 and 7 patients at 11 UK, 12 EORTC and 5 TROG sites, respectively. Overall, 25 (40%) patient cases needed resubmitting: 23 (37%) sets of outlines (2 cases twice) and 9 (14%) treatment plans (1 plan twice).

CONCLUSIONS
Prospective quality assurance and case review are essential to ensure consistent high-quality radiotherapy and benchmark/’Dummy Run’ alone is not sufficient. RTQA should be used for future trials in rare tumours where centres may only treat a few patients. The consistent high-quality radiotherapy in ROAM/EORTC1308 ensures the primary outcome (progression free survival: to report 2026) will be a robust assessment and any difference between treatment arms cannot be attributed to variation in radiotherapy planning or delivery.
CTNI-75. EFFICACY AND SAFETY OF LAROTRECTINIB IN PATIENTS WITH TROPOMYOSIN RECEPTOR KINASE (TRK) FUSION PRIMARY CENTRAL NERVOUS SYSTEM (CNS) TUMORS: AN UPDATED ANALYSIS
Authors: Perreault Sébastien , Doz François , Geoerger Birgit , Italiano Antoine , Lassen Ulrik , Nilsson Anna , Nysom Karsten , Spano Jean-Philippine , Norenberg Ricarda , Bernard-Gauthier Vadim , de la Cuesta Esther , Drilon Alexander , Laetsch Theodore , van Tilburg Cornelis 
Published: November 2023

Abstract

BACKGROUND
Larotrectinib is a highly selective TRK inhibitor approved for tumor-agnostic use in patients with various tumor types, including primary CNS tumors. Here, we report the independent central review and updated data on patients with TRK fusion-positive primary CNS tumors.

METHODS
Patients with TRK fusion primary CNS tumors enrolled in two clinical trials (NCT02637687, NCT02576431) were included. Responses were independent review committee (IRC)-assessed.

RESULTS
As of July 2022, 41 patients were eligible for response assessment by IRC. The median age at enrollment was 11 years (range 1-79). Tumor histologic groups included: high-grade glioma (HGG; n=25), low-grade glioma (LGG; n=9), and other (n=7). Sixteen (39%) patients had received ≥ 2 prior systemic therapies. For all patients, objective response rate (ORR) was 22% (95% CI 11–38): one complete response, eight partial response, 20 stable disease, and 12 progressive disease. For pediatric patients (n=28), the ORR was 29% (95% CI 13–49). For pediatric patients with HGG and LGG, ORRs were 14% (95% CI 2–43) and 57% (95% CI 18–90), respectively. The disease control rates at 24 weeks were 54% (95% CI 37–69) and 71% (95% CI 51–87) for all patients and pediatric patients, respectively. Medians for time to response, duration of response, progression-free survival, and overall survival (OS) were 1.9 months, 12.2 months (95% CI 3.7–not estimable), 11.1 months (95% CI 3.6–19.8), and not reached, respectively. The 48-month OS rate was 52%. Treatment duration ranged from 1 to 50+ months. Treatment-related adverse events (TRAEs) were mostly Grade 1/2. No patients discontinued treatment due to TRAEs.

CONCLUSION
Larotrectinib demonstrated rapid, durable responses and a manageable safety profile in patients with TRK fusion primary CNS tumors. This supports the wider adoption of next-generation sequencing panels that include NTRK gene fusions when testing patients with CNS tumors.
CTNI-76. EFFICACY OF BRAF INHIBITOR PLIXORAFENIB (FORE8394) IN RECURRENT, PRIMARY CENTRAL NERVOUS SYSTEM TUMORS (PCNST)
Authors: de la Fuente Macarena , Butowski Nicholas , Taylor Jennie , Yaeger Rona , Tsai Frank Yung-Chin , Janku Filip , Allen Carl , Ammakkanavar Natraj , Michelson Glenn , Jiang Ping , Paz Michael , Tussay-Lindenberg Alexia , Wang Kongming , Shepherd Stacie Peacock , Kline Irina , Sherman Eric , Rodon Jordi 
Published: November 2023

Abstract
Plixorafenib, a selective potent BRAFi, is uniquely designed to disrupt BRAF dimers and evade paradoxical MAPK pathway activation. Thus, it inhibits both V600 and non-V600 BRAF alterations and may be less prone to toxicities and resistance typical of approved BRAFi. An approved BRAFi, when used with MEKi, has ORR 33% with mDOR 13.6=months and ORR=50% with DOR of 6-29 months in V600+ HGG and LGG, respectively (dabrafenib US Prescribing Information, 2023). Phase 1/2a is a single-arm study (NCT02428712) in patients (n=113) with BRAF-altered advanced tumors to assess safety, PK, and efficacy of oral plixorafenib 900-3600 mg/day alone or with cobicistat (CYP3A4/P-gp inhibitor). Symptomatic TEAEs (rash, pyrexia, myalgia) were low grade and infrequent relative to approved BRAFi. This pre-specified analysis (31Mar2023) was in MAPKi-naïve adults with BRAFV600+ PCNST. 22 patients with PCNST received plixorafenib: 9 LGG, 1 glioneuronal tumor (LGG/GNT; 5 V600+), 12 HGG (10 V600+). Treatment-emergent AEs (TEAEs, ≥ 20%) were limited to LFT changes, G1 increased creatinine, fatigue, headache, and nausea. Only one G3 event (increased ALT) occurred at the RP2D (n=7) showing better tolerability than dabrafenib. 10 BRAFV600+ MAPKi-naïve adults with PCNST (median age 45 yrs, 6 females, 9 non-Hispanic) were efficacy evaluable: 6 HGG (4 glioblastoma, 1 epithelioid glioblastoma, 1 anaplastic astrocytoma); 4 LGG/GNT (1 each: ganglioglioma, pilocytic astrocytoma, xanthoastrocytoma, neuroepithelial tumor). Prior anti-cancer treatments included surgery (8/10), radiotherapy (8/10), and systemic therapy (8/10, including temozolomide [n=8], bevacizumab [n=2], carboplatin [n=1], dendritic cell vaccine [n=1]). 1 was treatment-naïve (unresectable; declined radiation/chemotherapy). ORR=60% (6/10) including HGG=67% (4/6), LGG/GNT=50% (2/4); median time to response=1.94 months; 4/6 responders with DOR &gt; 9 months; mPFS=34.1 months; median follow-up=10.3 months; 4/10 ongoing. Plixorafenib has a benign safety profile and leads to a high ORR and durable response in MAPKi-naïve BRAFV600+ PCNST. A phase 2 study is ongoing to confirm these findings (NCT05503797).
CTNI-81. REAL-WORLD TREATMENT RESULTS OF RELAPSED PRIMARY CENTRAL NERVOUS SYSTEM LYMPHOMA TREATED BY MEDICAL THERAPIES
Authors: Nagane Motoo , Sasaki Nobuyoshi , Yamagaishi Yuki , Saito Kuniaki , Kobayashi Keiichi , Nakatomi Hirofumi 
Published: November 2023

Abstract
Recurrence of primary central nervous system lymphoma (PCNSL) is a condition which often leads to morbidity and mortality. Consensus regarding the optimal treatment regimen for relapsed PCNSL has not been achieved due to the rarity of the disease. In this study, we conducted a retrospective, single-institution study to investigate real world treatment results of relapsed PCNSL treated by several medical therapeutic regimens. Relapsed PCNSL patients treated at the authors’ institution were identified, and progression-free survival (PFS), overall survival (OS) were analyzed among patients treated by medical therapies. Patients treated by radiotherapy, treated for intraocular or systemic relapses, or best supportive care, were excluded from the survival analysis. 83 patients with first, 44 with second, 25 with third relapse were identified. Upon each relapse, number of patients who received medical therapies for CNS lesions, radiotherapy, treatment for intraocular or systemic relapse, and best supportive care were 48 (57.8%), 5(6%), 4(4.8%), 26(31.3%) (first relapse), 31(70.5%), 3(6.8%), 1(2.3%), 9(20.5%) (second relapse), 13(52.0%), 0, 1(4%), 11(44.0%) (third relapse), respectively. A total of 101 CNS relapses were treated by medical therapies, and PFS (months), OS (months) of the four groups of treatments (rituximab, methotrexate, procarbazine and vincristine [R-MPV], methotrexate [MTX], tirabrutinib, and others) were as follows. PFS: 13.0, 4.5, 2.7, 3.0, and OS: 70.0, 26.4, 51.2, 9.7 (all relapse). PFS: 12.7, 7.0, 3.0, 3.2, and OS: 58.9, 33.1, not reached(n/r), 16.1 (first relapse). PFS: 34.3, 3.9, 25.3, 1.5, and OS: n/r, 28.1, 25.5, 7.5 (second relapse). PFS: 10.1, 3.9, 2.4, 2.9, and OS: 14.9, 22.3, n/r, 8.1 (third relapse). In relapsed PCNSL, favorable PFS was observed in patients treated by R-MPV. Favorable OS was also observed in tirabrutinib, which might suggest that tirabrutinib failure were effectively salvaged by R-MPV. R-MPV might confer better prognosis in relapsed PCNSL.
CTNI-85. GBM AGILE PLATFORM TRIAL FOR NEWLY DIAGNOSED AND RECURRENT GBM: RESULTS OF FIRST EXPERIMENTAL ARM, REGORAFENIB
Authors: Wen Patrick , Alexander Brian , Berry Donald , Buxton Meredith , Cavenee Webster , Colman Howard , de Groot John , Ellingson Benjamin , Gordon Gary , Hyddmark Emma , Khasraw Mustafa , Lim Michael , Mellinghoff Ingo , Mikkelsen Tom , Perry James , Powell Ashley , Sulman Erik , Tanner Kirk , Weller Michael , Yung W K Alfred , Blondin Nicolas , Brenner Andrew , Butt Omar , de la Fuente Macarena , Drappatz Jan , Iwamoto Fabio , Kim Lyndon , Lee Eudocia , Mantica Megan , Nabors Burt , Newton Herbert , Schiff David , Walbert Tobias , Weathers Shiao-Pei , Cloughesy Timothy , Lassman Andrew 
Published: November 2023

Abstract
GBM AGILE (NCT03970447;https://www.gcaresearch.org/research/gbm-agile) is a phase 3 Bayesian adaptive platform trial that efficiently tests multiple arms against common control, with 6 arms included to date. Primary endpoint is overall survival (OS). Stage 1 experimental arms are adaptively randomized against other arms. Demonstrated efficacy in stage 1 leads to fixed randomization stage 2. Stages 1 and 2 are combined for registration. Control randomization is fixed. Regorafenib, a multikinase-inhibitor, entered into GBM AGILE as the first arm and therefore was equally randomized against control. Regorafenib showed OS benefit in recurrent disease (RD) in randomized phase 2 REGOMA trial. METHODS: Patient subtypes in GBM AGILE are newly diagnosed unmethylated (NDU), RD, and—not considered for regorafenib—ND methylated (NDM). Arm indications (signatures) are combinations of subtypes. Control is temozolomide (ND) and lomustine (RD). Efficacy is assessed by OS hazard ratio(HR), arm/control. Efficacy is demonstrated when Bayesian probability of benefit (HR&lt; 1.00) ≥ 98% (roughly analogous P-value: 0.02). Futility occurs at any monthly analysis when Bayesian predictive power (PP) is &lt; 25% for all signatures. Follow-up continues for 12 months after arm’s accrual stops. RESULTS: for regorafenib: When PP for all 3 pre-defined signatures was &lt; 25%, regorafenib’s accrual was stopped for futility. Regorafenib/control sample sizes were 49/51, 126/128, 175/179 for signatures NDU, RD, and both. Respective PPs: 0.138, 0.030, 0.025—none close to 0.25. Respective mean HRs: 1.26, 1.25, 1.23. Probabilities of benefit (HR&lt; 1.00): 0.35, 0.18, 0.17. At final analysis, mean HRs were 1.07, 1.12, 1.10 with final probabilities of benefit (HR&lt; 1.00) equal to 0.43, 0.24, 0.24—none close to 0.98. CONCLUSION: GBM AGILE efficiently and compellingly addressed regorafenib’s role in GBM, in RD and NDU. These findings are germane as they fail to confirm the REGOMA results in RD. GBM AGILE continues to efficiently assess other therapies, including utilizing concurrent and previously accrued controls.
DNAR-03. A ROLE FOR THE INTERACTION BETWEEN DNA-DEPENDENT PROTEIN KINASE (DNA-PK) AND TAZ IN INDUCING GLIOMA STEM-LIKE CELL (GSC) RADIO-RESISTANCE
Authors: Tang Tiffany , Katayama Hiroshi , Bhat Krishna 
Published: November 2023

Abstract
Glioblastoma (GBM) is a primary brain tumor that is virtually incurable. Previous studies have shown that glioma stem-like cells (GSCs) are a particularly resistant subpopulation of GBM. Thus, a greater understanding of the mechanisms underlying therapy resistance in GSCs is required. TAZ is a transcriptional cofactor highly expressed in about 70% of GBMs. TAZ and its paralog YAP are oncogenic drivers of brain tumor progression. Our group has shown that GSCs overexpressing TAZ undergo a proneural to mesenchymal subtype transition, which is accompanied by aggressive phenotypes such as increased grade and treatment resistance in GSC xenografts. However, the molecular mechanisms of TAZ-mediated cell fate transition and GBM treatment resistance remain elusive. Previously, our group identified a novel interaction between DNA-dependent protein kinase (DNA-PK) and TAZ in response to exposure to ionizing radiation (IR) in GSCs. Here, we extend our previous findings by contextualizing the significance of this novel interaction in altering sensitivity to IR in GSCs. We demonstrate that prolonged culture of GSCs treated with etoposide increases TAZ expression. Furthermore, si-RNA knockdown of TAZ increases the number of γH2AX foci post-IR. Intriguingly, knocking down both TAZ/YAP does not increase the number of γH2AX foci post-IR in comparison to single knockdown of TAZ. Additionally, DNA-PK inhibitor treatment in GSCs reduces the half-life of TAZ. In contrast, GSCs treated with IR increases the half-life of TAZ compared to mock-irradiated cells. A combination of IR and DNA-PK inhibitor treatment in GSCs reduces the half-life of TAZ compared to GSCs treated with IR and DMSO, implicating the role of the recruitment of TAZ to DNA damage breaks and its resulting interactions with DNA-PK to induce radio-resistance. Overall, this study reports how interaction of DNA-PK with TAZ globally induces a GSC radio-resistant phenotype, highlighting the potential role of TAZ as a therapeutic target for GBM.
DDEL-02. CLINICAL BENEFIT OF BEVACIZUMAB AND IRINOTECAN (BEV+IRI) IN PATIENTS WITH RELAPSED/REFRACTORY GLIOBLASTOMA (R/RGBM) AND ITS POTENTIAL PREDICTORS
Authors: Park Ji Hyun , Cho Kyung Rae 
Published: November 2023

Abstract
BACKGROUND/AIM: Bevacizumab-containing chemotherapy constitutes an important salvage treatment for recurrent/refractory glioblastoma(r/rGBM). Patients and methods: We retrospectively collected the data of r/rGBM patients treated with the combination of bevacizumab and irinotecan (BEV+IRI) as their salvage treatment from July 2013 and December 2021 in Konkuk Medical Center of Korea. Patients with available results from molecular diagnostic tests were eligible, and markers of interest were examined including the presence of MGMT methylation, IDH1/2 mutation, or 1p/19q co-deletion. Efficacy of BEV+IRI and its potential biomarker was explored. RESULTS: Among 21 patients, 38.1% demonstrated European Cooperative Oncology Group-Performance scale (ECOG-PS) ≥3. The majority (71.4%) received BEV+IRI as their second-line chemotherapies, and the median dose was 5 (range=1-25). Objective response rate (ORR) was 33.3% and disease-control rate (DCR) was 85.7%. Irrespective of objective response, early clinical response was achieved in 14(66.7%) patients. During the median follow-up of 16.4 months for survivors, median progression-free survival (PFS) and overall survival (OS) were 3.6 and 6.8 months, respectively. ECOG PS≥3 and TP53 loss were independent predictors of an unfavorable OS, while prompt clinical improvement could predict favorable OS. Any molecular aberration was associated with OS or PFS in the study. CONCLUSION: Salvage BEV+IRI treatment in r/rGBM conferred comparable clinical benefit. ECOG PS ≥3, TP53 loss, and lack of prompt clinical improvement after the treatment were significantly associated with an unfavorable OS.
DDDR-11. IDENTIFYING NEW VULNERABILITIES TO TARGET PEDIATRIC LOW-GRADE GLIOMA
Authors: Borgenvik Anna , Misek Sean , Maile Jens , Novikov Dana , Bahadur Sher , Apfelbaum April , Morin Eric , Condurat Alexandra , Gonzales Elizabeth , Zhou Kevin , Goodale Amy , Abid Tanaz , Kalani Zohra , Piccioni Federica , Ligon Keith , Beroukhim Rameen , Persky Nicole , Jones David , Root David , Bandopadhayay Pratiti 
Published: November 2023

Abstract
Pediatric low-grade gliomas (pLGGs) are the most common solid tumors in children and are associated with devastating lifelong morbidities and mortality. Recent genomic profiling efforts have revealed that these tumors are largely driven by single-driver events that activate MAPK signaling. These insights have led to early clinical trials evaluating the role of MAPK inhibitors for these children with promising initial results. However, pLGGs are not cured by MAPK inhibitors, and tumors often rapidly rebound upon cessation of treatment. Therefore, continuous dosing of these inhibitors is required throughout a child’s development–often with significant and potentially permanent toxicities. In addition, 30-40% of tumors do not respond to MAPK inhibition, indicating primary resistance. We hypothesized that pediatrlc low-grade gliomas may also harbor additional dependencies beyond the MAPK pathway that may represent potential therapeutic targets. To address this, we generated isogenic neural stem cell models that expressed pLGG relevant oncogenes (BRAF family members, FGFR family members and MYB transcription factors, and subjected them to genome-scale CRISPR-cas9 screens. Compared to vector controls, pLGG models exhibited genetic dependencies on pathways that included regulators of cell-cycle and differentiation, in addition to genes involved in regulating the mTOR and MAPK pathways. Cell lines expressing MYB family transcription factors also harbored dependencies on genes involved in the DREAM complex. Together, these genes and pathways represent potential targets for combination treatments with MAPK pathway inhibitors for the treatment of pediatric low-grade gliomas.
DDDR-18. SINGLE-CELL FUNCTIONAL GENOMIC ANALYSIS OF PHARMACOLOGIC RESPONSES IN NF1 MUTANT GLIOBLASTOMA REVEALS DISTINCT MECHANISMS OF ACTION FOR MEK AND SHP2 INHIBITION
Authors: Pan Sixuan , Liu John , Mirchia Kanish , Payne Emily , Pak Joanna , Seo Kyounghee , Ozawa Tomoko , Raleigh David , Berger Mitchel , Abate Adam , Vasudevan Harish 
Published: November 2023

Abstract

BACKGROUND
Glioblastomas harbor recurrent mutations in NF1 that activate Ras/Raf/MEK signaling, motivating pharmacologic approaches targeting downstream (MEK) or upstream (SHP2) of Ras signaling. However, the mechanisms underlying therapeutic response remain unclear. Here, we integrate genome wide CRISPRi screens and single cell sequencing in cell lines and mouse xenografts to identify functional genomic mechanisms underlying responses to the MEK inhibitor selumetinib or the SHP2 inhibitor RMC-4550.

METHODS
Human NF1 mutant GBM43 cells expressing CRISPRi machinery were used for CRISPRi screens with selumetinib or RMC-4550. Intracranial xenografts were established with GBM43 cells and treated with selumetinib or RMC-4550. Tumor growth kinetics were measured with bioluminescent imaging.

RESULTS
Genome-wide CRISPRi screens with selumetinib or RMC-4550 in NF1 mutant human GBM43 cells identified 39 genes (14 sensitivity, 25 resistance) mediating selumetinib response and 327 genes (51 sensitivity, 276 resistance) mediating RMC-4550 response. While both selumetinib and RMC-4550 hits were enriched for components of Ras/Raf/MEK, hits sensitizing RMC-4550 response were uniquely enriched for PI3K signaling and focal adhesion components while hits mediating resistance were enriched for cell cycle genes. In NF1 mutant GBM43, RMC-4550 significantly reduced tumor volume (p=0.02) while selumetinib did not. Single cell RNA-sequencing (scRNA-seq) analysis of 90,782 tumor cells from NF1 mutant GBM43 xenografts treated with selumetinib or RMC-4550 identified 12 clusters across all samples. RMC-4550, but not selumetinib, resulted in significant depletion of cells expressing an epithelial-mesenchymal transition (EMT) signature marked by expression of focal adhesion genes mediating RMC-4550 sensitivity, suggesting this signature comprises a distinct mechanism of action in response to RMC-4550 but not selumetinib.

CONCLUSIONS
In NF1 mutant glioblastoma in vitro and in vivo models, cellular response to both upstream (SHP2) and downstream (MEK) inhibition are mediated by Ras/Raf/MEK signaling while RMC-4550 alone uniquely regulates a focal adhesion network associated with EMT and demonstrates improved efficacy in vivo.
DDDR-21. A TEMOZOLOMIDE-INDUCED LONG NONCODING RNA, LINC02454, REGULATES CHEMOSENSITIVITY IN GLIOBLASTOMA VIA MODULATION OF CXCR4
Authors: Yuan Edith , Tsung Kathleen , Han Jane , Lu Wange , Attenello Frank 
Published: November 2023

Abstract

INTRODUCTION
Chemoresistance is one of the primary factors influencing the poor prognosis in glioblastoma (GBM) patients. Long noncoding RNAs (lncRNAs) are a novel class of RNAs representing up to 80% of the genome, and noted to induce profound alterations in transcriptional regulation and phenotype, including chemotherapy response. We therefore set out to identify novel lncRNAs induced by chemotherapy that regulate GBM chemosensitivity. We further evaluated the mechanism by which a candidate chemoresistance-associated lncRNA exerts function.

METHODS
We evaluated gene expression following temozolomide treatment in multiple glioma lines (via RNA-seq). Candidate lncRNAs demonstrating significant expression upon TMZ treatment were assessed for association with patient survival. We further evaluated the effect of knockdown of candidate lncRNAs upon resulting TMZ sensitivity and downstream gene expression.

RESULTS
Linc02454 was among the most highly upregulated genes following TMZ treatment. Linc02454 resides on chromosome 12q14 within a locus of genes amplified in 10% of GBM patients. Elevated linc02454 expression was associated with decreased survival in TCGA data, while linc02454 knockdown reduced in vitro GBM cell viability in response to TMZ. RNA-seq identified CXC-chemokine receptor 4 (CXCR4) among the most heavily downregulated genes following lncRNA knockdown. Finally, TMZ induces similar increases in linc02454 and CXCR4, while CXCR4 KD chemosensitivity phenotypes closely parallel linc02454 KD phenotypes.

CONCLUSION
TMZ-induced increases in long noncoding RNAs, particularly in linc02454, regulate expression of well-known and previously targeted chemokines, including CXCR4. Subsequent studies, evaluating the manner by which chemotherapy increases linc02454, and the manner by which linc02454 affects CXCR4 and treatment sensitivity may improve GBM temozolomide sensitivity.