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AJNR. American Journal of Neuroradiology Jun 2024Radiographic assessment plays a crucial role in the management of patients with central nervous system (CNS) tumors, aiding in treatment planning and evaluation of... (Review)
Review
Radiographic assessment plays a crucial role in the management of patients with central nervous system (CNS) tumors, aiding in treatment planning and evaluation of therapeutic efficacy by quantifying response. Recently, an updated version of the Response Assessment in Neuro-Oncology (RANO) criteria (RANO 2.0) was developed to improve upon prior criteria and provide an updated, standardized framework for assessing treatment response in clinical trials for gliomas in adults. This article provides an overview of significant updates to the criteria including (1) the use of a unified set of criteria for high and low grade gliomas in adults; (2) the use of the post-radiotherapy MRI scan as the baseline for evaluation in newly diagnosed high-grade gliomas; (3) the option for the trial to mandate a confirmation scan to more reliably distinguish pseudoprogression from tumor progression; (4) the option of using volumetric tumor measurements; and (5) the removal of subjective non-enhancing tumor evaluations in predominantly enhancing gliomas (except for specific therapeutic modalities). Step-by-step pragmatic guidance is hereby provided for the neuroradiologist and imaging core lab involved in operationalization and technical execution of RANO 2.0 in clinical trials, including the display of representative cases and in-depth discussion of challenging scenarios.ABBREVIATIONS: BTIP = Brain Tumor Imaging Protocol; CE = Contrast-Enhancing; CNS = Central Nervous System; CR = Complete Response; ECOG = Eastern Cooperative Oncology Group; HGG = High-Grade Glioma; IDH = Isocitrate Dehydrogenase; IRF = Independent Radiologic Facility; LGG = Low-Grade Glioma; KPS = Karnofsky Performance Status; MR = Minor Response; mRANO = Modified RANO; NANO = Neurological Assessment in Neuro-Oncology; ORR = Objective Response Rate; OS = Overall Survival; PD = Progressive Disease; PFS = Progression-Free Survival; PR = Partial Response; PsP = Pseudoprogression; RANO = Response Assessment in Neuro-Oncology; RECIST = Response Evaluation Criteria In Solid Tumors; RT = Radiation Therapy; SD = Stable Disease; Tx = Treatment.
PubMed: 38926092
DOI: 10.3174/ajnr.A8396 -
Anticancer Research Jul 2024Glioblastoma multiforme (GBM) is one of the most lethal types of brain cancer with a median survival of only 12 months due to its aggressiveness and lack of effective...
BACKGROUND/AIM
Glioblastoma multiforme (GBM) is one of the most lethal types of brain cancer with a median survival of only 12 months due to its aggressiveness and lack of effective treatment options. Astrocytomas and oligodendrogliomas are classified as low-grade gliomas (LGG) and have the potential to progress into secondary GBM. YAP1 and TAZ are transcriptional co-activators of the hippo pathway and play an important role in tumorigenesis by controlling cell proliferation and differentiation. The aim of this study was to analyze whether YAP1 and TAZ influence the survival in patients with astrocytoma and oligodendroglioma.
PATIENTS AND METHODS
A total of 22 patient samples of astrocytoma and 11 samples of oligodendroglioma were analyzed using real-time PCR. We utilized open-access data from The Cancer Genome Atlas (TCGA) focusing on "brain lower grade glioma". mRNA expression rates were used to validate our findings on survival analysis.
RESULTS
Expression of YAP1 was twice as high in astrocytoma than in oligodendroglioma, whereas there was no difference in TAZ. In oligodendrogliomas, the expression of TAZ was higher in relapsed than in primary tumors. Patients with astrocytoma having a high YAP1 expression had a significantly shorter overall survival than patients with lower expression (median survival 161 vs. 86 months, p=0.0248). These findings were validated with survival analysis of TCGA data.
CONCLUSION
High YAP1 expression shows a high correlation with poorer overall survival in LGG. YAP1 has higher levels of expression in astrocytomas than in oligodendrogliomas.
Topics: Humans; YAP-Signaling Proteins; Astrocytoma; Adaptor Proteins, Signal Transducing; Female; Male; Transcription Factors; Brain Neoplasms; Middle Aged; Adult; Neoplasm Grading; Oligodendroglioma; Phosphoproteins; Aged; Prognosis; Gene Expression Regulation, Neoplastic; Biomarkers, Tumor; Transcriptional Coactivator with PDZ-Binding Motif Proteins; Trans-Activators; Young Adult
PubMed: 38925840
DOI: 10.21873/anticanres.17113 -
Anticancer Research Jul 2024Many patients with glioblastoma experience an intracerebral recurrence and require a personalized treatment. This study aimed to facilitate this approach by identifying...
BACKGROUND/AIM
Many patients with glioblastoma experience an intracerebral recurrence and require a personalized treatment. This study aimed to facilitate this approach by identifying prognostic factors for progression-free survival (PFS) and overall survival (OS).
PATIENTS AND METHODS
In 102 patients with recurrent glioblastoma following primary treatment with resection or biopsy plus adjuvant chemoradiation, 11 characteristics were retrospectively investigated regarding PFS and OS.
RESULTS
In the multivariate analyses, Karnofsky performance score (KPS) 90-100 at the time of recurrence (p=0.032), maximum cumulative diameter of recurrent lesions ≤40 mm (p=0.002), resection of recurrent glioblastoma (p=0.025), and systemic therapy for recurrent glioblastoma (p=0.025) were significantly associated with improved PFS. In addition, KPS 90-100 (p=0.024), maximum cumulative diameter ≤40 mm (p=0.033), and systemic therapy (p=0.006) were significantly associated with better OS.
CONCLUSION
Our study identified high Karnofsky Performance Status (KPS 90-100), maximum cumulative diameter of recurrent glioblastoma lesions ≤40 mm, and systemic therapy for recurrent glioblastoma as independent predictors of overall survival (OS) and progression-free survival (PFS). These independent prognostic factors may help select the most suitable treatment for individual patients with recurrent glioblastoma, potentially improving patient outcomes.
Topics: Humans; Glioblastoma; Male; Female; Middle Aged; Neoplasm Recurrence, Local; Aged; Prognosis; Brain Neoplasms; Progression-Free Survival; Adult; Retrospective Studies; Karnofsky Performance Status; Aged, 80 and over
PubMed: 38925836
DOI: 10.21873/anticanres.17119 -
Anticancer Research Jul 2024Glioblastoma is an incurable cancer with limited treatment options and a low survival rate. Temozolomide is the standard marketed small-molecule agent for glioblastoma...
BACKGROUND/AIM
Glioblastoma is an incurable cancer with limited treatment options and a low survival rate. Temozolomide is the standard marketed small-molecule agent for glioblastoma therapy; therefore, we aimed to find new drugs among the marketed medicines for brain diseases because of their cerebral migratory property and found lomerizine, used for the treatment of migraine.
MATERIALS AND METHODS
We evaluated the effect of lomerizine and its metabolites against U251 glioblastoma cells and temozolomide-resistant cells, T98G and GB-1, caused by the expression of O(6)-methylguanine-DNA methyltransferase or P-glycoprotein, compared with temozolomide, and combined with it. The mechanism of action was investigated using inhibitors of necrosis or apoptosis.
RESULTS
Lomerizine and its metabolite (M6) inhibited the proliferation of glioblastoma cells with greater potency and efficacy than temozolomide, including against temozolomide-resistant cells. The effects of lomerizine and M6 on glioblastoma were mainly attributed to the inhibition of proliferation because cells were not rescued by cell death inhibitors, such as necrosis or apoptosis inhibitors, although they were slightly rescued by necrostatin-1. Additionally, lomerizine and M6 combined with temozolomide were more effective at inhibiting the proliferation of U251 and GB-1 cells at some doses than single treatments.
CONCLUSION
Lomerizine has been used for migraine treatment because of its brain-penetrating properties without serious side-effects; thus, it might potentially be expected to be used alone for glioblastoma, including temozolomide-resistant glioblastoma, or in combination with temozolomide.
Topics: Humans; Glioblastoma; Cell Line, Tumor; Cell Proliferation; Apoptosis; Temozolomide; Piperazines; Drug Resistance, Neoplasm; Brain Neoplasms; Dacarbazine
PubMed: 38925834
DOI: 10.21873/anticanres.17106 -
International Journal of Biological... Jun 2024As a clinical anti-glioma agent, the therapeutic effect of carmustine (BCNU) was largely decreased because of the drug resistance mediated by O-alkylguanine-DNA...
As a clinical anti-glioma agent, the therapeutic effect of carmustine (BCNU) was largely decreased because of the drug resistance mediated by O-alkylguanine-DNA alkyltransferase (AGT) and the blood-brain barrier (BBB). To overcome these obstacles, we synthesized a BCNU-loaded hypoxia/esterase dual stimulus-activated nanomicelle, abbreviated as T80-HACB/BCNU NPs. In this nano-system, Tween 80 acts as the functional coating on the surface of the micelle to facilitate transport across the BBB. Hyaluronic acid (HA) with active tumor-targeting capability was linked with the hypoxia-sensitive AGT inhibitors (O-azobenzyloxycarbonyl group) via an esterase-activated ester bond. The obtained T80-HACB/BCNU NPs had an average particle size of 232.10 ± 10.66 nm, the zeta potential of -18.13 ± 0.91 mV, and it showed high drug loading capacity, eximious biocompatibility and dual activation of hypoxia/esterase drug release behavior. The obtained T80-HACB/BCNU NPs showed enhanced cytotoxicity against hypoxic T98G and SF763 cells with IC at 132.2 μM and 133.1 μM, respectively. T80 modification improved the transportation of the micelle across an in vitro BBB model. The transport rate of the T80-HACB/Cou6 NPs group was 12.37 %, which was 7.6-fold (p<0.001) higher than the micelle without T80 modification. T80-HACB/BCNU NPs will contribute to the development of novel CENUs chemotherapies with high efficacy.
PubMed: 38925197
DOI: 10.1016/j.ijbiomac.2024.133404 -
Computers in Biology and Medicine Jun 2024The CUSP9 protocol is a polypharmaceutical strategy aiming at addressing the complexity of glioblastoma by targeting multiple pathways. Although the rationale for this...
The CUSP9 protocol is a polypharmaceutical strategy aiming at addressing the complexity of glioblastoma by targeting multiple pathways. Although the rationale for this 9-drug cocktail is well-supported by theoretical and in vitro data, its effectiveness compared to its 511 possible subsets has not been comprehensively evaluated. Such an analysis could reveal if fewer drugs could achieve similar or better outcomes. We conducted an exhaustive in vitro evaluation of the CUSP9 protocol using COMBImageDL, our specialized framework for testing higher-order drug combinations. This study assessed all 511 subsets of the CUSP9v3 protocol, in combination with temozolomide, on two clonal cultures of glioma-initiating cells derived from patient samples. The drugs were used at fixed, clinically relevant concentrations, and the experiment was performed in quadruplicate with endpoint cell viability and live-cell imaging readouts. Our results showed that several lower-order drug combinations produced effects equivalent to the full CUSP9 cocktail, indicating potential for simplified regimens in personalized therapy. Further validation through in vivo and precision medicine testing is required. Notably, a subset of four drugs (auranofin, disulfiram, itraconazole, sertraline) was particularly effective, reducing cell growth, altering cell morphology, increasing apoptotic-like cells within 4-28 h, and significantly decreasing cell viability after 68 h compared to untreated cells. This study underscores the importance and feasibility of comprehensive in vitro evaluations of complex drug combinations on patient-derived tumor cells, serving as a critical step toward (pre-)clinical development.
PubMed: 38925084
DOI: 10.1016/j.compbiomed.2024.108748 -
Drug Resistance Updates : Reviews and... Jun 2024Despite aggressive treatment, the recurrence of glioma is an inevitable occurrence, leading to unsatisfactory clinical outcomes. A plausible explanation for this...
AIMS
Despite aggressive treatment, the recurrence of glioma is an inevitable occurrence, leading to unsatisfactory clinical outcomes. A plausible explanation for this phenomenon is the phenotypic alterations that glioma cells undergo aggressive therapies, such as TMZ-therapy. However, the underlying mechanisms behind these changes are not well understood.
METHODS
The TMZ chemotherapy resistance model was employed to assess the expression of intercellular adhesion molecule-1 (ICAM1) in both in vitro and in vivo settings. The potential role of ICAM1 in regulating TMZ chemotherapy resistance was investigated through knockout and overexpression techniques. Furthermore, the mechanism underlying ICAM1-mediated TMZ chemotherapy resistance was examined using diverse molecular biological methods, and the lipid raft protein was subsequently isolated to investigate the cellular subcomponents where ICAM1 operates.
RESULTS
Acquired TMZ resistant (TMZ-R) glioma models heightened production of intercellular adhesion molecule-1 (ICAM1) in TMZ-R glioma cells. Additionally, we observed a significant suppression of TMZ-R glioma proliferation upon inhibition of ICAM1, which was attributed to the enhanced intracellular accumulation of TMZ. Our findings provide evidence supporting the role of ICAM1, a proinflammatory marker, in promoting the expression of ABCB1 on the cell membrane of TMZ-resistant cells. We have elucidated the mechanistic pathway by which ICAM1 modulates phosphorylated moesin, leading to an increase in ABCB1 expression on the membrane. Furthermore, our research has revealed that the regulation of moesin by ICAM1 was instrumental in facilitating the assembly of ABCB1 exclusively on the lipid raft of the membrane.
CONCLUSIONS
Our findings suggest that ICAM1 is an important mediator in TMZ-resistant gliomas and targeting ICAM1 may provide a new strategy for enhancing the efficacy of TMZ therapy against glioma.
PubMed: 38924997
DOI: 10.1016/j.drup.2024.101112 -
The New England Journal of Medicine Jun 2024
Topics: Glioblastoma; Humans; Brain Neoplasms; T-Lymphocytes; Immunotherapy, Adoptive; Receptors, Chimeric Antigen
PubMed: 38924746
DOI: 10.1056/NEJMc2405721 -
The New England Journal of Medicine Jun 2024
Topics: Glioblastoma; Humans; Immunotherapy, Adoptive; Brain Neoplasms; T-Lymphocytes; Receptors, Chimeric Antigen; Male
PubMed: 38924745
DOI: 10.1056/NEJMc2405721 -
Annals of Clinical and Translational... Jun 2024The molecular era of glioma diagnosis and treatment has arrived, and a single rapid histopathology is no longer sufficient for surgery. This study sought to present an...
OBJECTIVE
The molecular era of glioma diagnosis and treatment has arrived, and a single rapid histopathology is no longer sufficient for surgery. This study sought to present an automatic integrated gene detection system (AIGS), which enables rapid intraoperative detection of IDH/TERTp mutations.
METHODS
A total of 78 patients with gliomas were included in this study. IDH/TERTp mutations were detected intraoperatively using AIGS in 41 of these patients, and they were guided to surgical resection (AIGS detection group). The remaining 37 underwent histopathology-guided conventional surgical resection (non-AIGS detection group). The clinical utility of this technique was evaluated by comparing the accuracy of glioma subtype diagnosis before and after TERTp mutation results were obtained by pathologists and the extent of resection (EOR) and patient prognosis for molecular pathology-guided glioma surgery.
RESULTS
With NGS/Sanger sequencing and chromosome detection as the gold standard, the accuracy of AIGS results was 100%. And the timing was well matched to the intraoperative rapid pathology report. After obtaining the TERTp mutation detection results, the accuracy of the glioma subtype diagnosis made by the pathologists increased by 19.51%. Molecular pathology-guided surgical resection of gliomas significantly increased EOR (99.06% vs. 93.73%, p < 0.0001) and also improved median OS (26.77 vs. 13.47 months, p = 0.0289) and median PFS (15.90 vs. 10.57 months, p = 0.0181) in patients with glioblastoma.
INTERPRETATION
Using AIGS intraoperatively to detect IDH/TERTp mutations to accurately diagnose glioma subtypes can help achieve maximum safe resection of gliomas, which in turn improves the survival prognosis of patients.
PubMed: 38924338
DOI: 10.1002/acn3.52138