Personalized Rendering of Motor System Functional Plasticity Potential to Improve Glioma Resection and Quality of Life

University of Milan

Status: Enrolling

Conditions: Glioma; Glioma, Malignant

Treatments: Drug: Up-front Chemotherapy; Diagnostic Test: Resting State Functional Magnetic Resonance Imaging (rs-fMRI); Behavioral: Up-front Motor Rehabilitation

Study type: Interventional

Funder types: Other

Identifiers

NCT06381726

Progetto AIRC IG-2022 ID 27184

Details and patient eligibility

About

Background Lower-grade-gliomas affect young patients, thus the longest progression-free-survival (PFS) with a high level quality of life is crucial. Surgery most significantly impacts on tumor natural history, postponing recurrence, improving symptoms, decreasing the need of adjuvant therapies, with extent of resection, gross-total and supra-total (GTR and STR), strongly associating with longest PFS. Achievement of GTR or STR depends on the degree of functional reorganization induced by glioma. Consequently, a successful treatment fostering neural circuit reorganization before surgery, would increase the chance of GRT/STR.

Hypothesis The plastic potential of motor system suggests that reorganization of circuits controlling hand movements could be presurgically fostered in LGG patients by enhancing plasticity with up-front motor-rehabilitation and/or by decreasing tumor infiltration with up-front chemotherapy. Advanced neuroimaging allows to infer the neuroplasticity potential. Intraoperative assessment of the motor circuits functionality will validate reliability of preoperative analyses.

Aims The project has 4 aims, investigating: A) the presurgical functional (FC) and structural (SC) connectomics of the hand-motor network to picture the spontaneous reorganization and the influence of clinical, imaging and histomolecular variables; B) the dynamic of FC and SC after tumor resection; C) changes in FC and SC maps after personalized upfront motor rehabilitation and/or chemotherapy; D) the effect of FC and SC upfront treatment on the achievement of GTR/STR preserving hand dexterity.

Experimental Design Resting-state fMRI and diffusion-MRI will provide FC and SC maps pre- and post-surgery; personalized up-front motor rehabilitation and/or chemotherapy will be administered; Intraoperative brain mapping procedures will generate data to validate the maps.

Expected Results

1. Provide a tool to render the motor functional reorganization predictive of surgical outcome.
2. Identify demographic, clinical and imaging variables associated with functional reorganization.
3. Describe the gain induced by up-front treatment.
4. Distinguish "patterns" predicting chance for GTR/STR from "patterns" suggesting need for up-front treatment.

Impact On Cancer Results will increase the achievement of GTR/STR, preserving motor integrity, with dramatic impact on LGGs natural history.

Enrollment: 400 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria (ARM 1):

• Patients signing informed consent for participation in the study
• Males and females
• Age ≥ 18 years
• Patients with lower-grade gliomas with involvement of the motor pathways who are candidates for surgery

Inclusion Criteria (ARM 2/3/4):

• Patients signing informed consent for participation in the study
• Males and females
• Age ≥ 18 years
• Patients with lower-grade gliomas treated over two years with tumors only biopsied and/or partially resected and eligible for second surgery

Exclusion Criteria:

• Age <18 years
• Inability to adhere to standard study controls
• Subjects unable to understand and freely provide consent to the study

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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400 participants in 4 patient groups

Spontaneous motor reorganization: observation

Active Comparator group

Description:

Only neurological and neuropsychological assessment as per normal clinical routine and conventional and advanced functional, resting-state MRI acquisitions

Treatment:

Diagnostic Test: Resting State Functional Magnetic Resonance Imaging (rs-fMRI)

Enhanced motor reorganization: upfront Motor Rehabilitation

Experimental group

Description:

Patients submitted to motor rehabilitation program aimed at learning unimanual and bimanual coordinated sequences, along with personalized exercise according to tumor location (frontal vs parietal). For 6 months each patient will perform the motor training program in outpatient training session, checked by a physiotherapist for corrected execution at home 3 times/week, and is assessed for the correct training execution and progresses in training sessions each month, by physical therapists at the Rehabilitation Unit and on a weekly schedule by on-line distant monitoring (telemedicine).

Treatment:

Behavioral: Up-front Motor Rehabilitation

Enhanced motor reorganization: upfront Chemotherapy

Experimental group

Description:

Temozolomide-based regimen of 6 months duration is applied. Treatment will be discontinued in case of toxicity (G2-G4).

Treatment:

Drug: Up-front Chemotherapy

Enhanced motor reorganization: upfront Chemotherapy + Motor Rehabilitation

Experimental group

Description:

Temozolomide-based regimen of 6 months duration is applied. Treatment will be discontinued in case of toxicity (G2-G4). Patients will also be submitted to motor rehabilitation program aimed at learning unimanual and bimanual coordinated sequences, along with personalized exercise according to tumor location (frontal vs parietal). For 6 months each patient will perform the motor training program in outpatient training session, checked by a physiotherapist for corrected execution at home 3 times/week, and is assessed for the correct training execution and progresses in training sessions each month, by physical therapists at the Rehabilitation Unit and on a weekly schedule by on-line distant monitoring (telemedicine).

Treatment:

Drug: Up-front Chemotherapy

Behavioral: Up-front Motor Rehabilitation