Researchers at University Health Network (UHN)’s Princess Margaret Cancer Centre (PM) have developed a method to distinguish between different types of pediatric brain cancers. These findings are important for pediatric neurosurgery, as they could assist surgeons in determining the most suitable and personalized treatment strategies.
Classifying cancers into subtypes has become a key tool for determining diagnoses, prognoses, and treatment decisions. Intraoperative consultations—analysis of cancer samples during surgery— can utilize the differences in shape and structure between cancer cells and healthy cells to guide decision-making. This is often done by microscopic analysis of sections of tissue and can take up to 30 minutes to complete.
In addition, important subtypes of brain cancer have recently been identified at the molecular level. These subtypes influence prognosis and treatment decisions, prompting the need for a diagnostic strategy that considers the shape, structure, and molecular makeup of these brain tumours.
“Identifying specific molecular subtypes of brain cancer remains a challenge with existing intraoperative pathology consultation techniques,” says Dr. Arash Zarrine-Afsar, Senior Scientist at PM and senior author of the study. “These techniques do not rapidly provide molecular information during surgery to inform surgical decisions in real-time.”
A technique called Picosecond InfraRed Laser mass spectrometry (PIRL-MS) that can analyze the molecular composition of a small amount of tissue, was previously developed at UHN by Dr. Zarrine-Afsar’s lab. This technology also led to the founding of Point Surgical Inc. as a joint venture between UHN, Unity Health Toronto, and Light Matter Interaction Inc. PIRL-MS consists of a handheld probe that uses a laser beam to vaporize tumour tissue. Mass spectrometry analysis— sorting particles by mass and charge— can then identify the sample’s components in up to 10 seconds.
“In this study, we examined the utility of PIRL-MS as a rapid method for differentiating major pediatric brain cancer types of medulloblastoma, pilocytic astrocytoma, and ependymoma,” says Dr. Michael Woolman, former Doctoral Student in Dr. Zarrine-Afsar’s lab and first author of the study. “We analyzed the lipid (fat molecule) profile of patient tissue from previous surgeries and identified a range of molecular markers involved in tumour classification.”
The researchers found that PIRL-MS could identify specific molecular features unique to each cancer type, enabling precise classification. Based on this, they propose a protocol for a 10-second classification of seven types of pediatric brain cancers.
Additionally, based on a retrospective analysis of prognoses and treatments for pediatric brain cancer, the team further identified situations where PIRL-MS analysis could influence the aggressiveness of surgical intervention in a manner that could benefit the patient’s overall survival.
These findings have significant implications for pediatric neurosurgery and treatment decisions and could ultimately improve patient outcomes.
Highlighting the collaborative nature of this research, Dr. Zarrine-Afsar adds, “Without the support of Dr. James Rutka and Dr. Michael D. Taylor at the Arthur and Sonia Labatt Brain Tumour Research Centre (BTRC) and The Hospital for Sick Children, this study would not have been possible.”
Future research will further collaborative efforts between Toronto area hospitals and involve evaluating the utility of PIRL-MS in prospective patient trials.
This work was supported by the Canadian Institutes of Health Research, Canadian Cancer Society and The Princess Margaret Cancer Foundation. Dr. Arash Zarrine-Afsar is an Associate Professor at the University of Toronto.
Dr. Zarrine-Afsar, Dr. Howard Ginsberg, and Dr. Michael Woolman are inventors of PIRL-MS and are consultants with financial interest in Point Surgical Inc.
Woolman M, Kiyota T, Belgadi SA, Fujita N, Fiorante A, Ramaswamy V, Daniels C, Rutka JT, McIntosh C, Munoz DG, Ginsberg HJ, Aman A, Zarrine-Afsar A. Lipidomic-Based Approach to 10 s Classification of Major Pediatric Brain Cancer Types with Picosecond Infrared Laser Mass Spectrometry. Anal Chem. 2024 Jan 23;96(3):1019-1028. doi: 10.1021/acs.analchem.3c03156.
In neurosurgery, doctors often need to quickly (under 30 minutes) decide how much of a tumour to remove and assess the risks involved. (Getty images)