Fluorescence and Glioma Heterogeneity

Completed

• Conditions: Malignant Gliomas
• Interventions: Procedure: ALA

• Registration Number: NCT02155452
• Lead Sponsor: Tata Memorial Hospital

Brief Summary

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

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.

Study Timeline

• Study Start: 2014-05
• Study First Submitted: 2014-05-17
• Study First Submitted QC: 2014-06-03
• Study First Posted: 2014-06-04
• Primary Completion: 2019-07
• Study Completion: 2019-07
• Status Verified: 2022-05
• Last Update Submitted: 2022-05-02
• Last Update Posted: 2022-05-06

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 25

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

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
With ALA	ALA	Patients with malignant glioma. 25 patients will be provided the ALA for inducing fluorescence

Primary Outcome Measures

Name	Time	Method
Degree of fluorescence	At the time of surgery within 72 hours	1. Degree of fluorescence in different tumor regions; 2. PPIX Qualification

Secondary Outcome Measures

Name	Time	Method
High throughput proteomic screening of tissue samples	Postoperatively within 1 week of the excision	-A quantitative approach will be undertaken to compare the proteome profile

Trial Locations

Locations (1)

Advanced Centre for Treatment, Research & Education in Cancer (ACTREC); 🇮🇳 Navi Mumbai, Maharashtra, India