Personalized Rendering of Motor System Functional Plasticity Potential to Improve Glioma Resection and Quality of Life
- Conditions
- GliomaGlioma, Malignant
- Interventions
- Drug: Up-front ChemotherapyBehavioral: Up-front Motor RehabilitationDiagnostic Test: Resting State Functional Magnetic Resonance Imaging (rs-fMRI)
- Registration Number
- NCT06381726
- Lead Sponsor
- University of Milan
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 400
Not provided
- Age <18 years
- Inability to adhere to standard study controls
- Subjects unable to understand and freely provide consent to the study
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Enhanced motor reorganization: upfront Chemotherapy Up-front Chemotherapy Temozolomide-based regimen of 6 months duration is applied. Treatment will be discontinued in case of toxicity (G2-G4). Enhanced motor reorganization: upfront Chemotherapy + Motor Rehabilitation Up-front Chemotherapy 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). Enhanced motor reorganization: upfront Chemotherapy + Motor Rehabilitation Up-front Motor Rehabilitation 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). Spontaneous motor reorganization: observation Resting State Functional Magnetic Resonance Imaging (rs-fMRI) Only neurological and neuropsychological assessment as per normal clinical routine and conventional and advanced functional, resting-state MRI acquisitions Enhanced motor reorganization: upfront Motor Rehabilitation Up-front Motor Rehabilitation 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).
- Primary Outcome Measures
Name Time Method Muscle power ARM 1: preop, 1-2 months postop, 3-4 months postop, 6-8 months postop, 12 months postop; ARM 2/3/4: before starting treatment, at 2-3 and 6-9 months during treatment, before surgery (if indicated), 1 month postop, 2-3 months postop MRC Muscle power assessment (0-5)
Motor praxia ARM 1: preop, 1-2 months postop, 3-4 months postop, 6-8 months postop, 12 months postop; ARM 2/3/4: before starting treatment, at 2-3 and 6-9 months during treatment, before surgery (if indicated), 1 month postop, 2-3 months postop ARAT test (Grasp, Grip, Pinch, each consisting of 3 items scoring 0 \[not performed, 1/2 abnormal, 3 ok\]), De Renzi test (24 complex gestures with individual scoring 0-3 \[0 no execution/always abnormal, 2/1 ok after 1 or 2 trials, 3 ok\] each evaluating one or more among finger movements \[total score 0-36\], hand movements \[total score 0-36\], hand and finger position \[total score 0-36\], sequence of movements \[total score 0-36\], meaningful gestures \[total score 0-36\], meaningless gestures \[total score 0-36\]; tool pantomime for 10 objects individual score 0 if always incorrect, 1 if correct after command repetition, 2 correct immediately, total score range 0-20)
- Secondary Outcome Measures
Name Time Method Comprehensive neuropsychological assessment ARM 1: preop, 1-2 months postop, 3-4 months postop, 6-8 months postop, 12 months postop; ARM 2/3/4: before starting treatment, at 2-3 and 6-9 months during treatment, before surgery (if indicated), 1 month postop, 2-3 months postop Language: Naming test; Fhonemic and Semantic Fluency Verbal and Spatial Memory: 15 Rey's Words; Recall Rey figure; Visuo-spatial test: Rey's Copy; Cancellation Test Attention and Executive Functions: Attentive matrice and Trail Making test For each listed test, equivalent score, from 0 to 4, is used.
Mood Disorders. HADS test (score 0-21 : 0-7= Normal; 8-21 Mood disorders
Trial Locations
- Locations (1)
IRCCS Ospedale Galeazzi Sant'Ambrogio
🇮🇹Milan, Lombardy, Italy