Glioma, Glioma, Malignant
Conditions
Keywords
Glioma, Neurosurgery, Chemotherapy, Neoadjuvant, Motor Rehabilitation, Magnetic Resonance Imaging, Diffusion Magnetic Resonance Imaging, Resting State Functional Magnetic Resonance Imaging, Functional Magnetic Resonance Imaging, Functional Connectomics, Structural Connectomics, Neuronal Plasticity, Higher Nervous Activity, Neurological Rehabilitation, Antineoplastic Protocols
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.
Interventions
DIAGNOSTIC_TESTResting State Functional Magnetic Resonance Imaging (rs-fMRI)
rs-fMRI + neurological and neuropsychological evaluation at preoperative timepoint and 1-2 months postop, 3-4 months postop, 6-8 months postop, 12 months postop
BEHAVIORALUp-front Motor Rehabilitation
personalized motor rehabilitation for 6 months + rs-fMRI + neurological and neuropsychological evaluation before starting motor rehabilitation, at 2-3 months during rehabilitation, 6-9 months during rehabilitation, before surgery (if surgery indicated by tumour board), 1 month postop, 2-3 months postop
DRUGUp-front Chemotherapy
Temozolomide at either 6 cycles consisting of 150-200 mg per square meter for 5 days during each 28-day cycle, or metronomic schedule, + rs-fMRI + neurological and neuropsychological evaluation before starting motor rehabilitation, at 2-3 months during rehabilitation, 6-9 months during rehabilitation, before surgery (if surgery indicated by tumour board), 1 month postop, 2-3 months Post
Sponsors
University of Turin, Italy
University of Milan
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Patients immediately candidate for resection will be assessed neurologically, neuropsychologically and by functional MRI. Extent of resection will be assessed on \<48hrs and 2-month MRI. Neurological and neuropsychological assessment will be performed during regular follow-up. Patients not requiring an adjuvant treatment according to tumor board meeting will be submitted to functional MRI at 4-8 and 12 months from surgery. Patients not immediately eligible for resection will be submitted to biopsy for histomolecular definition. Patients not requiring radiation therapy will be submitted to neurological, neuropsychological, and functional MRI evaluation. Upon clinical context, patients will undergo motor rehabilitation and/or chemotherapy. After 3-6 months, patients will undergo functional MRI and evaluated for surgery. Neurological and neuropsychological evaluation will be performed at treatment initiation, every month during treatment, at admission for surgery and 1 month after surgery.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Countries
Italy
Contacts
Primary ContactLorenzo Bello, MD
Outcome results
None listed