Fluorescence and Glioma Heterogeneity

Study Overview
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Brief Summary
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The investigators aim to study the heterogeneity of fluorescence within malignant gliomas by sampling tissues from these variable areas within the same tumor. These tissue samples will then be subjected to pathological and biological analysis to assess proteins related to ALA metabolism and correlated with the fluorescence emitted as well as levels of protoporphyrin IX in the tissues.

Detailed Description
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Malignant gliomas are the commonest malignant brain tumors but are extremely challenging to treat. Neuro-oncology has seen little progress in its treatment despite extensive research. Extent of resection remains a very important prognostic factor in these tumors. Better the resection, better the outcomes. However resecting these tumors is not very easy primarily due to their infiltrative nature and difficulty in discerning tumor boundaries intraoperatively. Fluorescence guided resection (FGR) has recently been shown to be a very important and useful adjunct in maximizing this goal. FGR involves administration of aminolevulinic acid (ALA) to the patient prior to surgery. The ALA is converted to protoporphyrin IX (PPIX) in glioma cells. The PPIX is a fluorophore and can be visualized intraoperatively using a suitably modified microscope. Neurosurgeons can then resect the tumor radically guided by this fluorescence which is superior to the conventional microscopic resection. Selective PPIX accumulation in glioma cells is the key to the accuracy of this technique. The biological basis of selectivity of PPIX accumulation within glioma cells is however poorly understood. Various mechanisms could be involved starting from variable transport (related to blood-brain barrier properties), differential uptake (governed by active transport mechanisms) and differential metabolism within the cell. Understanding these mechanisms can lead to refinements in this strategy, overcoming its present limitations and development of methods to extend its scope.

Official Title
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Understanding the Mechanisms of ALA-induced Fluorescence in Malignant Gliomas - Exploring the Biological Basis of Tumoral Heterogeneity.

Conditions
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Malignant Gliomas

Intervention / Treatment
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* Procedure: ALA


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Per-primum glioma Adults (18-65 years) Radiologically suspected malignant gliomas Variable contrast enhancement on MRI (patchy and/or non-uniform) Eligible for surgical therapy (craniotomy NOT stereotactic biopsy ) No contraindication for surgery Exclusion Criteria: Poor general condition (KPS < 70) Prior treatment (except biopsy) Compromised renal/hepatic function Immunocompromised status Known photosensitivity / allergy to 5-ALA

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| With ALA<br>Patients with malignant glioma. 25 patients will be provided the ALA for inducing fluorescence | Procedure: ALA<br>* Prior to surgery all patients would receive freshly prepared solution of 5-ALA, 20 mg/kg bodyweight dissolved in 100 ml of potable water orally approximately 4 hours (range 4-6 hrs) before the commencement of anesthesia induction for surgery. The surgery would then be performed with the help of navigation. After craniotomy, the navigation software would be used to identify the selected target areas based on the preoperative images (MR as well as PET when available) and directed image-guided biopsies from these representative areas will be collected for histological evaluation<br>* Other names: 5- ALA;|
| Without ALA<br>5 tumor tissue samples from ACTREC tumor tissue repository will be obtained. These would be malignant gliomas or other brain tumor samples where ALA is usually not administered and will be used as controls and for calibration purposes | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Degree of fluorescence | Degree of fluorescence in different tumor regions PPIX Qualification | At the time of surgery within 72 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| High throughput proteomic screening of tissue samples | -A quantitative approach will be undertaken to compare the proteome profile | Postoperatively within 1 week of the excision | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ALA, Malignant gliomas