Ignite Creation Date:
2024-05-06 @ 8:23 PM
Last Modification Date:
2024-10-26 @ 3:27 PM
Study NCT ID:
NCT06368934
Status:
NOT_YET_RECRUITING
Last Update Posted:
2024-04-16
First Post:
2024-02-27
Brief Title:
Sub-lobectomy for IDH Wild-type and TERT Promoter Mutant Glioblastoma
Sponsor:
Huashan Hospital
Organization:
Huashan Hospital
Study Overview
Official Title:
Sub-lobectomy for IDH Wild-type and TERT Promoter Mutant Glioblastoma A Prospective Interventional Multicenter Randomized Controlled Trial
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-04
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Glioblastoma is recognized as the most common and aggressive form of primary malignant brain tumor with treatment options that are limited and prognosis that is extremely poor showing median progression-free survival of 12 months and median overall survival of less than 18 months Surgical resection plays a critical role in the treatment with the extent of resection significantly impacting patient outcomes Historical approaches to surgical resection have evolved moving from radical strategies to more conservative ones that aim to preserve normal brain function while removing the tumor as completely as possible Recent studies have suggested that increasing the extent of surgical resection particularly along the T2 FLAIR border rather than the traditional T1-enhanced border can significantly improve patient prognosis There is however a lack of consensus on the optimal surgical approach and the heterogeneity of tumors presents challenges in standardizing surgical strategies Extended resection has been shown to prolong survival and novel intraoperative molecular diagnostics have emerged to improve accuracy in tumor classification and prognosis Building on these advancements a multicenter prospective randomized controlled trial is proposed to evaluate the efficacy of sub-lobectomy in treating IDH wild-typeTERTp-mutant glioblastoma aiming to improve evidence levels and establish standardized surgical practices for this devastating disease
Detailed Description:
Glioblastoma is the most prevalent and aggressive type of primary malignant brain tumor1 Treatment options are limited and often include surgical resection followed by radiation therapy or electric field therapy2 Prognosis is very poor with median progression-free survival of only 12 months and median overall survival of less than 18 months The 5-year survival rate is a mere 12 3
Surgical resection is fundamental to treating patients with glioblastoma and the extent of resection directly impacts patient prognosis 4 Professor William Stewart Halsted a renowned surgeon historically championed radical surgical resection as a means of controlling tumours 5 Nevertheless the majority of neurosurgeons disagreed with this view because of the disruption to normal brain function caused by extreme surgery However in 1928 Professor Walter Dandy reported five patients with gliomas who underwent right hemispherectomy 6 These patients showed no significant neurological impairment except for left hemiparesis Even though no grave complications arise from the complete resection of the nondominant hemisphere it did not seem to enhance the patients prognosis either Only one out of these five patients survived for 35 years and eventually all of them passed away due to gliomas After this the radical surgical strategy of enlarging the resection margin around gliomas was challenged and neurosurgeons aimed to achieve total resection of imaging gliomas based on the principle of removing tumour tissue with an abnormal signal on MRI while preserving normal brain function
Notably with respect to the complete surgical removal of glioblastoma the T1-enhanced borders of MRI imaging were commonly used as a criterion in the past However various retrospective studies reveal that increasing the extent of surgical resection significantly improves patient prognosis median survival from 98 to 152 months 7 However a recent study conducted retrospectively discovered that resection along the T2 FLAIR border advanced the prognosis of patients with glioblastoma even further compared to resection along the T1 enhancing border median survival from 116 to 317 months 8 Another study discovered that performing a sub-lobectomy on glioblastoma patients could enhance their prognosis median survival from 187 to 441 months in comparison to T2 FLAIR border resection as long as normal brain function is not affected 9 Nonetheless there remains a lack of consensus in the academic community regarding the optimal surgical resection strategy for glioblastoma patients such as T1 enhancing border T2 FLAIR border sub-lobectomy In addition the significant heterogeneity in tumour location size infiltration extent and anatomical proximity across different patients makes it difficult to standardise imaging border resection as an individualised surgical approach This places greater demands on the surgical capabilities and knowledge of clinicians in clinical settings Furthermore it also introduces multiple confounding factors that hinder the advancement of interventional clinical research
Therefore we have thoroughly reviewed recent studies to investigate the prognosis of glioblastoma patients following extended resection The majority of studies analyzed the prognostic benefits of extended resection beyond T1 enhancement compared to gross total tumor resection while a few studies evaluated the difference between sub-lobectomy and gross total tumor resection Extended resection beyond the T1 enhancement region was discovered to prolong the survival of glioblastoma patients with the prognostic benefits of sub-lobectomy proving significantly pronounced and not associated with further neurological impairment 9 Previous studies have several limitations Firstly they are predominantly retrospective leading to issues with selection bias and retrospective memory bias among other factors Furthermore many of these studies lack a balanced control group Secondly factors such as a small number of patient cases short follow-up time and poor quality control of follow-up have also contributed to their low level of evidence 10 Furthermore the classification for glioblastoma were updated in 2021 Patients with gliomas who were included in these studies also await further evaluation to clarify their diagnosis
Previous studies on the correlation between surgical resection and prognosis of glioblastoma were retrospective due to the absence of molecular pathology Intraoperative frozen pathology cannot provide real-time diagnosis of glioblastoma Therefore molecular testing is crucial for accurate staging and diagnosis According to the 5th edition of World Health Organization Central Nervous System tumors classification patients diagnosed with glioblastoma IDH wild-type had IDH wild-type adult diffuse glioma accompanied by tissue necrosis vascular hyperplasia TERT promoter mutation 7-10 or epidermal growth factor receptor EGFR amplification 17 TERT promoter mutation which is the most frequent hotspot mutation observed in glioblastomas is present in almost 80 of patients with glioblastoma mutations 18 We have conducted a range of innovative studies regarding intraoperative rapid integrated diagnosis of gliomas Our works include ①simplified integrated diagnostic system for human gliomas that is based on a combination of IDH TERT and histopathology ②We have also developed an accurate method for detecting IDH and TERT mutations through the use of locked nucleic acid-amplification refractory mutation system fluorescence polymerase chain reaction PCR ③We have optimized the DNA extraction process and reduced the detection cycle as well ④Conducting multi-center prospective clinical trials to verify the feasibility of intraoperative rapid molecular testing In summary through combining intraoperative frozen pathology our technique allows for precise diagnosis of glioblastoma IDH wild-type with TERT promoter mutations within 35 minutes intraoperatively with a sensitivity and specificity of 1000 when compared with postoperative sequencing data Furthermore our prior retrospective study found that a higher degree of surgical resection greatly improved the prognosis of glioblastoma with IDH wild-typeTERTp-mutated and that sub-lobectomy conferred a more significant prognostic benefit
Therefore building on previous work and knowledge in our field we will conduct a multicenter prospective randomized controlled trial to evaluate the efficacy of sub-lobectomy in the treatment of IDH wild-typeTERTp-mutant glioblastoma Our study aims to enhance the level of evidence while also establishing a standardized surgical strategy for glioblastoma
Surgical resection is fundamental to treating patients with glioblastoma and the extent of resection directly impacts patient prognosis 4 Professor William Stewart Halsted a renowned surgeon historically championed radical surgical resection as a means of controlling tumours 5 Nevertheless the majority of neurosurgeons disagreed with this view because of the disruption to normal brain function caused by extreme surgery However in 1928 Professor Walter Dandy reported five patients with gliomas who underwent right hemispherectomy 6 These patients showed no significant neurological impairment except for left hemiparesis Even though no grave complications arise from the complete resection of the nondominant hemisphere it did not seem to enhance the patients prognosis either Only one out of these five patients survived for 35 years and eventually all of them passed away due to gliomas After this the radical surgical strategy of enlarging the resection margin around gliomas was challenged and neurosurgeons aimed to achieve total resection of imaging gliomas based on the principle of removing tumour tissue with an abnormal signal on MRI while preserving normal brain function
Notably with respect to the complete surgical removal of glioblastoma the T1-enhanced borders of MRI imaging were commonly used as a criterion in the past However various retrospective studies reveal that increasing the extent of surgical resection significantly improves patient prognosis median survival from 98 to 152 months 7 However a recent study conducted retrospectively discovered that resection along the T2 FLAIR border advanced the prognosis of patients with glioblastoma even further compared to resection along the T1 enhancing border median survival from 116 to 317 months 8 Another study discovered that performing a sub-lobectomy on glioblastoma patients could enhance their prognosis median survival from 187 to 441 months in comparison to T2 FLAIR border resection as long as normal brain function is not affected 9 Nonetheless there remains a lack of consensus in the academic community regarding the optimal surgical resection strategy for glioblastoma patients such as T1 enhancing border T2 FLAIR border sub-lobectomy In addition the significant heterogeneity in tumour location size infiltration extent and anatomical proximity across different patients makes it difficult to standardise imaging border resection as an individualised surgical approach This places greater demands on the surgical capabilities and knowledge of clinicians in clinical settings Furthermore it also introduces multiple confounding factors that hinder the advancement of interventional clinical research
Therefore we have thoroughly reviewed recent studies to investigate the prognosis of glioblastoma patients following extended resection The majority of studies analyzed the prognostic benefits of extended resection beyond T1 enhancement compared to gross total tumor resection while a few studies evaluated the difference between sub-lobectomy and gross total tumor resection Extended resection beyond the T1 enhancement region was discovered to prolong the survival of glioblastoma patients with the prognostic benefits of sub-lobectomy proving significantly pronounced and not associated with further neurological impairment 9 Previous studies have several limitations Firstly they are predominantly retrospective leading to issues with selection bias and retrospective memory bias among other factors Furthermore many of these studies lack a balanced control group Secondly factors such as a small number of patient cases short follow-up time and poor quality control of follow-up have also contributed to their low level of evidence 10 Furthermore the classification for glioblastoma were updated in 2021 Patients with gliomas who were included in these studies also await further evaluation to clarify their diagnosis
Previous studies on the correlation between surgical resection and prognosis of glioblastoma were retrospective due to the absence of molecular pathology Intraoperative frozen pathology cannot provide real-time diagnosis of glioblastoma Therefore molecular testing is crucial for accurate staging and diagnosis According to the 5th edition of World Health Organization Central Nervous System tumors classification patients diagnosed with glioblastoma IDH wild-type had IDH wild-type adult diffuse glioma accompanied by tissue necrosis vascular hyperplasia TERT promoter mutation 7-10 or epidermal growth factor receptor EGFR amplification 17 TERT promoter mutation which is the most frequent hotspot mutation observed in glioblastomas is present in almost 80 of patients with glioblastoma mutations 18 We have conducted a range of innovative studies regarding intraoperative rapid integrated diagnosis of gliomas Our works include ①simplified integrated diagnostic system for human gliomas that is based on a combination of IDH TERT and histopathology ②We have also developed an accurate method for detecting IDH and TERT mutations through the use of locked nucleic acid-amplification refractory mutation system fluorescence polymerase chain reaction PCR ③We have optimized the DNA extraction process and reduced the detection cycle as well ④Conducting multi-center prospective clinical trials to verify the feasibility of intraoperative rapid molecular testing In summary through combining intraoperative frozen pathology our technique allows for precise diagnosis of glioblastoma IDH wild-type with TERT promoter mutations within 35 minutes intraoperatively with a sensitivity and specificity of 1000 when compared with postoperative sequencing data Furthermore our prior retrospective study found that a higher degree of surgical resection greatly improved the prognosis of glioblastoma with IDH wild-typeTERTp-mutated and that sub-lobectomy conferred a more significant prognostic benefit
Therefore building on previous work and knowledge in our field we will conduct a multicenter prospective randomized controlled trial to evaluate the efficacy of sub-lobectomy in the treatment of IDH wild-typeTERTp-mutant glioblastoma Our study aims to enhance the level of evidence while also establishing a standardized surgical strategy for glioblastoma
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None