Objective: To investigate whether extending adjuvant temozolomide (TMZ) improved the prognosis of newly diagnosed glioblastoma (GBM) patients with different mutation statuses of O-methylguanine DNA methyltransferase (MGMT), isocitrate dehydrogenase 1 (IDH1), p53 and different expression level of Ki67.
Methods: This study was a retrospective cohort study that postoperative patients with newly diagnosed GBM who did not progress after receiving radiotherapy with concomitant and 6 cycles of adjuvant TMZ were enrolled in control group, and those received more than 6 cycles of adjuvant TMZ were incorporated in extended group. Patients were stratified by MGMT expression, IDH1 mutation, p53 mutation and expression level of Ki67. The primary endpoints were overall survival (OS) and progression-free survival (PFS).
Result: A total of 93 postoperative patients with newly diagnosed GBM were included in this study, 40 and 53 cases were included in control group and extended group, respectively. On the whole, extended adjuvant TMZ chemotherapy significantly prolonged OS and PFS of patients with newly diagnosed GBM [median OS (mOS): 29.00 months 16.70 months, < 0.001; median PFS (mPFS): 13.80 months 9.60 months, = 0.002]. The results of subgroup analysis showed that patients with methylated MGMT in extended group had significantly longer OS and PFS than those in control group; patients with IDH1 mutation benefited more from extended adjuvant TMZ chemotherapy than those with wild-type IDH1; there was no significant difference in the effect of extended TMZ chemotherapy on OS between GBM patients with wild-type p53 and those with mutant p53; compared with GBM patients with lower expression of Ki67, extended adjuvant TMZ treatment dramatically improved the OS and PFS of those with higher expression of Ki67.
Conclusion: The therapeutic schedule of extended adjuvant TMZ significantly prolonged OS and PFS of patients with newly diagnosed GBM regardless of p53 mutation status, and patients with different MGMT methylation, IDH1 mutation and Ki67 expression level benefited differently from extended adjuvant TMZ chemotherapy.
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http://dx.doi.org/10.3389/fonc.2022.1000501 | DOI Listing |
Neurooncol Adv
November 2024
Huntsman Cancer Institute, Salt Lake City, UT, USA.
Background: Glioblastoma (GBM) has a median survival of <2 years. Pexidartinib (PLX3397) is a small-molecule inhibitor of CSF1R, KIT, and oncogenic FTL3, which are implicated in GBM treatment resistance. Results from glioma models indicate that combining radiation therapy (RT) and pexidartinib reduces radiation resistance.
View Article and Find Full Text PDFMol Pharm
January 2025
Industrial Pharmacy, Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, Queens, New York 11439, United States.
Glioblastoma multiforme is the most frequently diagnosed primary malignant brain tumor. Despite multimodal therapy with surgical resection, radiation therapy, and chemotherapy, recurrence of the tumor is almost always guaranteed due to the infiltrative nature of the disease. Moreover, the blood brain barrier imparts an additional layer of complexity by impeding the delivery of therapeutic agents to the tumor, hence limiting the efficacy of systemically delivered drugs.
View Article and Find Full Text PDFNeurooncol Adv
November 2024
Radiation Oncology Research Center, Cancer Research Institute, IKHC, Tehran University of Medical Sciences, Tehran, Iran.
Background: Glioblastoma multiforme (GBM) is an aggressive brain tumor with poor survival rates despite current treatments. The standard of care (SOC) includes surgery, followed by radiotherapy plus concurrent and adjuvant chemotherapy with temozolomide (TMZ). This phase II trial assessed the safety and efficacy of neoadjuvant TMZ (nTMZ) before and during chemoradiotherapy in newly diagnosed GBM patients.
View Article and Find Full Text PDFNeurooncol Adv
November 2024
Department of Neurosurgery, Prince of Wales Hospital, Hong Kong.
Background: The optimal timing of initiating adjuvant temozolomide (TMZ) chemoradiotherapy after surgery in patients with glioblastoma is contentious. This study aimed to determine whether the timing of adjuvant treatment affects their overall survival (OS).
Methods: Consecutive adult patients with histologically-confirmed newly diagnosed glioblastoma treated with adjuvant TMZ chemoradiotherapy across all neurosurgical centers in Hong Kong between 2006 and 2020 were analyzed.
BMC Biol
November 2024
Institut de Cancérologie Strasbourg Europe (ICANS), Radiobiology Laboratory, 3 Rue de La Porte de L'Hôpital, Strasbourg, 67000, France.
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