Abstract
BackgroundMolecular signatures are being increasingly incorporated into cancer classification systems. DNA methylation-based central nervous system (CNS) tumor classification is being recognized as having the potential to aid in cases of difficult histopathological diagnoses. Here, we present our institutional clinical experience in integrating a DNA-methylation-based classifier into clinical practice and report its impact on CNS tumor patient diagnosis and treatment.MethodsProspective case review was undertaken at CNS tumor board discussions over a 3-year period and 55 tumors with a diagnosis that was not certain to two senior neuropathologists were recommended for methylation profiling based on diagnostic needs. Tumor classification, calibrated scores, and copy number variant (CNV) plots were obtained for all 55 cases. These results were integrated with histopathological findings to reach a final diagnosis. We retrospectively reviewed each patient's clinical course to determine final neuro-pathology diagnoses and the impact of methylation profiling on their clinical management, with a focus on changes that were made to treatment decisions.ResultsFollowing methylation profiling, 46 of the 55 (84%) challenging cases received a clinically relevant diagnostic alteration, with two-thirds having a change in the histopathological diagnosis and the other one-third obtaining clinically important molecular diagnostic or subtyping alterations. WHO grading changed by 27% with two-thirds receiving a higher grade. Patient care was directly changed in 15% of all cases with major changes in clinical decision-making being made for these patients to avoid unnecessary or insufficient treatment.ConclusionsThe integration of methylation-based CNS tumor classification into diagnostics has a substantial clinical benefit for patients with challenging CNS tumors while also avoiding unnecessary health care costs. The clinical impact shown here may prompt the expanded use of DNA methylation profiling for CNS tumor diagnostics within prominent neuro-oncology centers globally.
Highlights
The classification and diagnosis of central nervous system (CNS) tumors, as with all neoplastic processes, is essential in determining optimal patient treatment decisions
This CNS tumor classifier was built based on methylation profiling of 2682 brain tumor cases across 82 different tumor subtypes and it was applied to 1104 additional cases to determine diagnostic utility
Cohort characteristics Between November 1, 2015, and September 30, 2018, a total of 1670 operative cases were reviewed at University Health Network (UHN) CNS tumor board discussions
Summary
The classification and diagnosis of central nervous system (CNS) tumors, as with all neoplastic processes, is essential in determining optimal patient treatment decisions. A recent seminal publication has demonstrated its utility in classifying CNS tumors with improved diagnostic accuracy in comparison to the standard of care histopathological analysis and single molecular tests [11] This CNS tumor classifier was built based on methylation profiling of 2682 brain tumor cases across 82 different tumor subtypes and it was applied to 1104 additional cases to determine diagnostic utility. Of these 1104 cases in their cohort, 12% received a new integrated diagnosis when methylation profiling results were added to standard of care histopathological testing. We present our institutional clinical experience in integrating a DNA-methylation-based classifier into clinical practice and report its impact on CNS tumor patient diagnosis and treatment
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