Benign Brain Tumor, Malignant Brain Tumor
Conditions
Keywords
Brain Tumor, Brain Tumor Surgery, Cancer Surgery, Brain Tumor Resection, Biopsy, Digital Biopsy, Frozen Section
Brief summary
Intra-operative evaluation of residual brain tumor currently relies on frozen-section histopathology, which typically requires 20-30 minutes for tissue processing and interpretation, prolonging operative time and increasing staffing demands. Confocal Laser Fluorescence Microscopy (cCeLL - Ex vivo) acquires real-time, high-resolution fluorescence images of resected tissue and therefore may serve as a rapid alternative or adjunct to frozen sections. This prospective, multi-center study was designed to systematically assess the clinical performance of cCeLL - Ex vivo during brain-tumor surgery.
Detailed description
Primary Objective Demonstrate non-inferiority of cCeLL - Ex vivo versus frozen-section histopathology in terms of clinical sensitivity and specificity for intra-operative brain-tumor diagnosis. Secondary Objectives Compare diagnostic turnaround time between cCeLL - Ex vivo and frozen section. Evaluate tumor-type classification accuracy for each modality. Determine the average number of images required for definitive cCeLL - Ex vivo interpretation. Quantify overall diagnostic performance of cCeLL - Ex vivo using the area under the ROC curve (AUC).
Interventions
DIAGNOSTIC_TESTcCeLL - Ex vivo
Neoplastic brain tissue biopsied from participant will be visualized, and images will be captured using cCeLL - Ex vivo.
Sponsors
Unity Health Toronto
Korea University Anam Hospital
Samsung Medical Center
Seoul National University Hospital
VPIX Medical
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Masking description
This trial employed an assessor-blinded design. Specifically, the pathologist who interpreted the cCeLL - Ex vivo images had no access to the patient's clinical information, frozen section results, or permanent section results. By ensuring that the individual responsible for cCeLL - Ex vivo image interpretation was blinded to other diagnostic data, the study minimized bias in determining sensitivity and specificity outcomes.
Intervention model description
* All enrolled participants were assigned to the same intervention (i.e., cCeLL - Ex vivo), with no separate control group or comparator. * The study's primary purpose was to evaluate the diagnostic performance (sensitivity, specificity) of the investigational device in a single cohort of participants undergoing brain tumor resection.
Eligibility
Sex/Gender
ALL
Age
19 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Specimens and images used in this study must meet all of the following criteria: 1. Tissue obtained from male or female patients aged 19 years or older. 2. Tissue collected from patients scheduled for neurosurgical resection of a suspected brain tumor. 3. Tissue obtained from patients capable of understanding and signing the informed consent form.
Exclusion criteria
Specimens and images that meet any of the following criteria will be excluded from the study: 1. Emergency cases where informed consent could not be obtained before surgery. 2. Specimens with significant hemorrhage, affecting image quality. 3. Small biopsy specimens that do not meet the required size for imaging. 4. Poor-quality images that do not meet study criteria, including: * Low-quality cCeLL - Ex vivo images. * Non-diagnostic cCeLL - Ex vivo images of the tumor core. 5. Cases deemed inappropriate for the study by the principal investigator or study staff due to ethical concerns or potential impact on study results. 6. Patients undergoing multiple surgeries at the same site.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Sensitivity for Tumor Detection (Specimen-level) | From neurosurgical resection to permanent pathology (≈ 4 weeks) | The diagnostic results of cCeLL - Ex vivo imaging interpretation by experts and frozen section examination for 283 tumor specimens are presented below. |
| Clinical Specificity for Tumor Detection (Specimen-level) | From neurosurgical resection to permanent pathology (≈ 4 weeks) | The diagnostic results of cCeLL - Ex vivo imaging interpretation by experts and frozen section examination for 39 normal specimens are as follows |
Countries
Canada, South Korea
Participant flow
Recruitment details
Recruitment Status: Completed / Enrolled: 285 patients, 358 specimens, drop-out 36 speciments Study Start: Jan 1, 2023 , Primary y Completion: Nov 27, 2024 First enrollment: Korea: Jan 1, 2023 Canada: Jul 5, 2024 Enrollment ended: Korea: Nov 27, 2024 / Canada: Oct 18, 2024 Analyzed: 322 specimens Study Completion Date (database lock and QC): 31 Dec 2024
Pre-assignment details
This was a single-group, assessor-blinded study with no randomization or run-in period. Adults (≥19) with suspected brain tumors who consented were enrolled. A total of 285 Patient at four sites (three in Korea, one in Canada) joined; Each could yield up to three specimens, resulting in 322 analyzable samples. No comparator was used, so all proceeded to cCeLL - Ex vivo. No extra screening or washout was performed.
Participants by arm
| Arm | Count |
|---|---|
| CeLL - Ex Vivo Imaging All resected brain-tumor specimens were imaged in the operating room with cCeLL - Ex vivo, a confocal laser fluorescence endomicroscope that captures real-time, sub-cellular resolution images. Blinded expert pathologists interpreted the images on a secure workstation. | 271 |
| CeLL - Ex Vivo Imaging All resected brain-tumor specimens were imaged in the operating room with cCeLL - Ex vivo, a confocal laser fluorescence endomicroscope that captures real-time, sub-cellular resolution images. Blinded expert pathologists interpreted the images on a secure workstation. | 322 |
| Total | 593 |
Baseline characteristics
| Characteristic | CeLL - Ex Vivo Imaging |
|---|---|
| Age, Continuous | 55.6 years STANDARD_DEVIATION 14.6 |
| Baseline Number of Tissue Specimens Collected for cCeLL - Ex vivo Imaging | 322 Specimens |
| Sex: Female, Male Female | 154 Participants |
| Sex: Female, Male Male | 117 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 285 |
| other Total, other adverse events | 0 / 285 |
| serious Total, serious adverse events | 0 / 285 |
Outcome results
Primary
Clinical Sensitivity for Tumor Detection (Specimen-level)
The diagnostic results of cCeLL - Ex vivo imaging interpretation by experts and frozen section examination for 283 tumor specimens are presented below.
Time frame: From neurosurgical resection to permanent pathology (≈ 4 weeks)
Population: Both tumor and non-tumor specimens were collected from 19 participants.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| cCeLL - Ex vivo and Frozen Section | Clinical Sensitivity for Tumor Detection (Specimen-level) | cCeLL - Ex vivo | 96.05 Percentage of tumor specimens (%) |
| cCeLL - Ex vivo and Frozen Section | Clinical Sensitivity for Tumor Detection (Specimen-level) | Frozen section | 94.81 Percentage of tumor specimens (%) |
Comparison: We performed a paired comparison within the same participant population, evaluating both cCeLL - Ex vivo and Frozen Section on each specimen.p-value: <0.4049McNemar
Primary
Clinical Specificity for Tumor Detection (Specimen-level)
The diagnostic results of cCeLL - Ex vivo imaging interpretation by experts and frozen section examination for 39 normal specimens are as follows
Time frame: From neurosurgical resection to permanent pathology (≈ 4 weeks)
Population: Both tumor and non-tumor specimens were collected from 19 participants.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| cCeLL - Ex vivo and Frozen Section | Clinical Specificity for Tumor Detection (Specimen-level) | cCeLL - Ex vivo | 78.57 Percentage of normal specimens (%) |
| cCeLL - Ex vivo and Frozen Section | Clinical Specificity for Tumor Detection (Specimen-level) | Frozen Section | 67.86 Percentage of normal specimens (%) |
Comparison: We performed a paired comparison within the same participant population, evaluating both cCeLL - Ex vivo and Frozen Section on each specimen.p-value: <0.307595% CI: [-0.1628, 0.0557]McNemar