Trial Title:
Sub-lobectomy for IDH Wild-type and TERT Promoter Mutant Glioblastoma
NCT ID:
NCT06368934
Condition:
Glioma
Glioblastoma
Conditions: Official terms:
Glioblastoma
Study type:
Interventional
Study phase:
N/A
Overall status:
Not yet recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Intervention model description:
Type of study: randomized parallel controlled, open-label, multicenter clinical trial.
Interventions: the intervention group was to receive frontal, temporal, parietal, and
occipital sub-lobotomies that met anatomical criteria, and the control group was to
receive imaging total resection (T1-enhanced borders) that met the Response Assessment in
Neuro-Oncology (RANO) criteria.
Randomization The control group and intervention group were equal in size. Following
intraoperative pathological diagnosis, participants were randomly assigned using a
centralized randomization system known as the Interactive Web Response System (IWRS).
Stratification factors included preoperative age brackets of [18-65] and (65-80), gender
(male or female), and tumor site in the frontal, temporal, parietal, and occipital lobes.
Primary purpose:
Treatment
Masking:
Single (Participant)
Masking description:
This study employed a single-blind approach whereby the participants were unaware of the
kind of surgical resection they were receiving.
Intervention:
Intervention type:
Procedure
Intervention name:
sub-lobectomy
Description:
Combined with previous research and our team's precise neurosurgery concept, we define
the surgical strategy based on lobectomy and further preserving the brain parenchyma in
functional areas according to anatomical landmarks and electrophysiological boundaries as
sub-lobectomy.
Arm group label:
The intervention group
Intervention type:
Procedure
Intervention name:
imaging total resection
Description:
Imaging total resection (T1-enhanced borders) will met the RANO criteria
Arm group label:
The control group
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-type/TERTp-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
tumor[1]. Treatment options are limited and often include surgical resection followed by
radiation therapy or electric field therapy[2]. 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 3.5 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 9.8 to 15.2 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 11.6 to 31.7 months)
[8]. Another study discovered that performing a sub-lobectomy on glioblastoma patients
could enhance their prognosis (median survival from 18.7 to 44.1 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 100.0% 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-type/TERTp-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-type/TERTp-mutant glioblastoma. Our study aims
to enhance the level of evidence, while also establishing a standardized surgical
strategy for glioblastoma.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Eligible patients are aged between 18 and 80, have newly diagnosed high-grade
diffuse adult-type gliomas, and have not received any other treatment besides
puncture biopsy.
2. Preoperative KPS score ≥70.
3. Enhanced MRI can be tolerated.
4. Sign the informed consent form.
5. Patients with supratentorial gliomas and lesions confined to the unilateral frontal,
temporal, parietal, and occipital lobes are included.
6. Imaging total resection can be completed after preoperative imaging evaluation.
7. The intraoperative integrative diagnosis was IDH wild-type high-grade glioma with
TERT promoter mutation.
Exclusion Criteria:
1. The tumor involves the anterior central gyrus, posterior central gyrus, nigral
gyrus, limbic lobe, corpus callosum, basal ganglia, and lateral ventricles.
2. The tumor involves 2 or more lobes of the brain;
3. Developing severe systemic diseases such as renal insufficiency, hepatic
insufficiency, cardiac insufficiency, etc.
4. Previously, the patient had experienced other types of malignant tumours.
5. Developing other brain diseases, such as Parkinson's or Alzheimer's disease.
6. Simultaneously participating in other clinical trials.
7. Expected survival is less than 3 months.
8. Not receiving Stupp protocol after surgery.
Gender:
All
Minimum age:
18 Years
Maximum age:
80 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Hushan Hospital, Fudan University
Address:
City:
Shanghai
Zip:
200040
Country:
China
Start date:
April 8, 2024
Completion date:
June 2027
Lead sponsor:
Agency:
Huashan Hospital
Agency class:
Other
Source:
Huashan Hospital
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06368934
