CONNEctome-guided Navigation for Eloquent-area Tumor Surgery Trial (CONNECT Trail)

A Prospective, Randomized, Controlled Superiority Trial of Connectome-Guided Navigation-Assisted Microsurgical Resection for Functional Preservation in Eloquent-Area Brain Tumors

This study is designed for patients with brain tumors located in eloquent brain areas involved in language, motor, or major functional brain networks. The purpose of the study is to determine whether connectome-guided navigation-assisted microsurgical resection can better preserve neurological function after surgery than conventional tractography-guided surgery.

Participants who meet the study criteria will be assigned to one of two surgical planning strategies. In the experimental group, patients will undergo preoperative diffusion tensor imaging and resting-state functional MRI for individualized brain network reconstruction, and these data will be integrated with intraoperative navigation and neurophysiological monitoring to guide the resection boundary. In the control group, surgery will be guided by conventional DTI tractography-assisted navigation.

The main outcome is the rate of postoperative functional preservation. Other outcomes include extent of tumor resection, postoperative complications, time to neurological recovery, overall survival, and quality of life. Patients will be evaluated before surgery and followed after surgery with clinical examinations, neurological assessments, and MRI at prespecified time points.

Study Overview

• Status: Recruiting
• Conditions: Brain Neoplasms; Eloquent Area Brain Tumors
• Intervention / Treatment: Procedure: Connectome-Guided Navigation-Assisted Microsurgical Resection; Procedure: Conventional DTI Tractography-Guided Tumor Resection

Detailed Description

This is a prospective, randomized, controlled superiority trial designed to evaluate whether connectome-guided navigation-assisted microsurgical resection improves postoperative functional preservation in patients with tumors located in eloquent brain regions when compared with conventional tractography-guided surgery.

Brain tumors involving language areas, motor areas, or key large-scale functional networks present a major surgical challenge because maximal resection must be balanced against preservation of neurological function. Conventional neuronavigation based mainly on structural landmarks or tractography may be insufficient to fully characterize the topological relationship between the tumor and critical functional networks. This study therefore applies a connectome-informed surgical strategy that integrates preoperative structural and functional imaging with intraoperative guidance to support individualized surgical planning and functional protection.

Eligible patients are those with brain tumors involving language, motor, or major functional network regions, including the default mode network, central executive network, dorsal attention network, and ventral attention network, with Karnofsky Performance Status of at least 70 and preoperative MRI evidence of a spatial relationship between the tumor and major white matter tracts. Patients with non-neoplastic lesions, multifocal tumors, incomplete evaluation data, pregnancy-related conditions, or extensive adhesion to multiple key network nodes are excluded.

Participants are randomized in a 1:1 ratio to the experimental group or the control group. The experimental intervention includes preoperative DTI and resting-state functional MRI-based brain network reconstruction, intraoperative real-time navigation, electrophysiological monitoring, and resection planning based on network-informed boundaries. The control intervention consists of conventional DTI tractography-guided tumor resection.

The primary endpoint is postoperative functional preservation. Secondary endpoints include extent of resection, postoperative complication rate, time to neurological recovery, overall survival, progression-related outcomes, and quality of life. Exploratory analyses will assess postoperative dynamic changes in brain networks and functional compensation mechanisms using multimodal MRI data, including resting-state functional MRI and diffusion imaging.

Study assessments are performed at baseline, within 24 to 72 hours after surgery, and during postoperative follow-up at 1 month, 3 months, 6 months, and 1 year. MRI is used to evaluate extent of resection, while neurological examinations, performance scales, and clinical rating instruments are used to assess functional outcomes over time. Quality of life is assessed using validated cancer-related instruments during follow-up.

The planned total sample size is 200 participants, with 100 patients in each group, based on a superiority design using postoperative functional preservation as the primary endpoint. Data will be analyzed using predefined statistical methods, including descriptive statistics, between-group comparisons, survival analysis, and modeling of factors associated with postoperative neurological impairment.

• Study Type: Interventional
• Enrollment (Estimated): 200
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Fengchun Mu; Phone Number: +8618888294650; Email: alicemfc@163.com

Study Locations

• China
  • Beijing, China, 100021
    • Recruiting
    • National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
    • Contact: Ming Yang, M.D.; Phone Number: +8613810655237; Email: yangming@cicams.ac.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Patients clinically diagnosed with brain tumors involving language areas, motor areas, or major functional brain networks, including the default mode network, central executive network, dorsal attention network, or ventral attention network.
2. Karnofsky Performance Status (KPS) score of 70 or higher.
3. Preoperative MRI demonstrating a spatial relationship between the tumor and major white matter tracts, such as the corticospinal tract or arcuate fasciculus.
4. No other neurological disease or underlying condition that may cause neurological dysfunction.
5. No prior treatment for a brain tumor in the same region, such as radiotherapy.
6. Tumor not extensively adherent to multiple critical network nodes.
7. Planned craniotomy for tumor resection and provision of written informed consent by the patient or legally authorized representative.

Exclusion Criteria:

1. Pathologically or clinically suspected non-neoplastic brain lesion.
2. Multifocal tumors.
3. Incomplete evaluation data.
4. Withdrawal from the study by the patient or legally authorized representative for any reason.
5. Pregnancy, lactation, possibility of pregnancy, or planned pregnancy.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Connectome-Guided Surgery Group; Participants in this arm will undergo connectome-guided navigation-assisted microsurgical resection. The surgical strategy includes preoperative diffusion tensor imaging and resting-state functional MRI-based brain network reconstruction, integrated with intraoperative neuronavigation and neurophysiological monitoring to guide resection boundaries and optimize postoperative functional preservation.	Procedure: Connectome-Guided Navigation-Assisted Microsurgical Resection; Microsurgical resection of eloquent-area brain tumors guided by preoperative diffusion tensor imaging and resting-state functional MRI-based brain network reconstruction. The intervention integrates connectome-informed surgical planning, intraoperative neuronavigation, and neurophysiological monitoring to define individualized resection boundaries with the goal of maximizing tumor removal while preserving neurological function.; Other Names: Brain network-guided surgery; Connectome-guided surgery; DTI and rs-fMRI-guided tumor resection
Active Comparator: Conventional Tractography-Guided Surgery Group; Participants in this arm will undergo conventional DTI tractography-guided microsurgical resection using standard surgical planning and navigation procedures. This group serves as the comparator for evaluating postoperative functional preservation and extent of resection.	Procedure: Conventional DTI Tractography-Guided Tumor Resection; Microsurgical resection of eloquent-area brain tumors guided by conventional diffusion tensor imaging tractography-assisted navigation according to standard surgical planning procedures. This intervention serves as the comparator for evaluation of postoperative functional preservation, extent of resection, and other clinical outcomes.; Other Names: Conventional tractography-guided surgery; DTI-guided microsurgical resection; Standard tractography-assisted tumor resection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Postoperative Functional Preservation Rate	The proportion of participants with preservation of neurological function at 6 months after surgery compared with baseline, based on neurological examination and protocol-specified functional assessments.	6 months after surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Extent of Resection	Extent of tumor resection assessed on postoperative contrast-enhanced brain MRI performed within 24 to 72 hours after surgery.	Within 24 to 72 hours after surgery
Incidence of Postoperative Complications	The incidence of surgery-related postoperative complications, including new or worsened neurological deficits, intracranial hemorrhage, brain edema, seizures, intracranial infection, deep vein thrombosis, and other protocol-defined adverse events.	Within 30 days after surgery

Collaborators and Investigators

• Sponsor: Cancer Institute and Hospital, Chinese Academy of Medical Sciences

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2025
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2028

Study Registration Dates

• First Submitted: June 14, 2026
• First Submitted That Met QC Criteria: June 14, 2026
• First Posted (Actual): June 18, 2026

Study Record Updates

• Last Update Posted (Actual): June 18, 2026
• Last Update Submitted That Met QC Criteria: June 14, 2026
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: Diffusion tensor imaging; Resting-state fMRI; Microsurgical resection; Intraoperative neurophysiological monitoring; Connectome-guided surgery; Eloquent area brain tumor; Brain network navigation; DTI tractography; Functional preservation
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms by Site; Neoplasms; Nervous System Neoplasms; Central Nervous System Neoplasms; Brain Neoplasms; Investigative Techniques; Diagnostic Techniques and Procedures; Diagnosis; Tomography; Diagnostic Imaging; Diagnostic Techniques, Neurological; Neuroimaging; Magnetic Resonance Imaging; Diffusion Magnetic Resonance Imaging; Diffusion Tensor Imaging
• Other Study ID Numbers: NCC-020019; 2024-I2M-3-014 (Other Grant/Funding Number: CAMS Medical Innovation Fund)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No