Fluorescence and Glioma Heterogeneity (ALAglioma)

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

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.

Study Overview

• Status: Completed
• Conditions: Malignant Gliomas
• Intervention / Treatment: Procedure: ALA

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 Type: Observational
• Enrollment (Actual): 25

Contacts and Locations

Study Locations

• India
  • Maharashtra
    • Navi Mumbai, Maharashtra, India, 410210
      • Advanced Centre for Treatment, Research & Education in Cancer (ACTREC)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients with malignant glioma

Description

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 Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Other

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
With ALA; Patients with malignant glioma. 25 patients will be provided the ALA for inducing fluorescence	Procedure: ALA; 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; Other Names: 5- ALA
Without ALA; 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?

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

Collaborators and Investigators

• Sponsor: Tata Memorial Hospital
• Investigators: Principal Investigator: Aliasgar V Moiyadi, MCh DNB, neurosurgeon

Study record dates

Study Major Dates

• Study Start: May 1, 2014
• Primary Completion (Actual): July 1, 2019
• Study Completion (Actual): July 1, 2019

Study Registration Dates

• First Submitted: May 17, 2014
• First Submitted That Met QC Criteria: June 3, 2014
• First Posted (Estimate): June 4, 2014

Study Record Updates

• Last Update Posted (Actual): May 6, 2022
• Last Update Submitted That Met QC Criteria: May 2, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Keywords: ALA; Malignant gliomas
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioma
• Other Study ID Numbers: TMC- ACTREC IRB project no 139