The 2016 update to the WHO Classification of Tumours of the Central Nervous System introduced molecular markers for the classification of a relatively small set of entities. Advances since then have deeply refined our understanding of tumor biology, resulting in the widespread integration of molecular markers with traditional histopathologic features in the updated 5th edition of the WHO classification.1 Increasingly, accurate diagnosis and treatment decisions rely on the timely acquisition of this information, as there are direct impacts on several aspects of patient care early in the course of treatment.2 Common examples in daily practice include decisions regarding treatment intensity and prognostication for lower histologic grade IDH-wildtype gliomas harboring molecular features that warrant rendering a diagnosis of Glioblastoma, IDH-wildtype, and the need for timely determination of MGMT promoter methylation status regarding eligibility for most clinical trials.
In anticipation of the updated WHO 2021 classification requiring next generation sequencing (NGS) for rendering integrated molecular diagnoses for many diffuse glioma types and subtypes, a new standard operating procedure (SOP) was developed at MD Anderson Cancer Center to designate procedural roles and streamline communication. This protocol was developed via collaboration between Neuro-Oncology and Neuropathology, with the goal of expediting molecular analysis. Previously, molecular testing was obtained ad hoc without a standardized process. Specifically, the process typically started after the initial diagnosis was rendered and the patient was seen by a Neuro-oncologist at postop follow-up in the clinic.
As of March 2021, upon suspicion of the diagnosis of a new or recurrent diffusely infiltrating glioma based on intra-operative sampling (“rapid frozen section”) or outside institution tissue sections, the Neuropathologist mobilizes the FastTrack Team to notify the patient’s clinical team via group email. The Neuro-oncology team then expeditiously obtains consent regarding the potential for a financial burden to the patient and places orders for NGS and MGMT analysis. Upon FastTrack Team notification of patient consent, the Neuropathologist requests preparation of the requisite number of unstained tissue sections by the Special Microtomy Laboratory based on microscopic determination of the optimal tumor tissue paraffin block, accounting for specimen quality and viable tumor percentage. Upon receipt of the sections, the Neuropathologist places the slides in a designated FastTrack box for Path Expeditors to digitally scan and then send to the Molecular Diagnostics Laboratory for molecular testing. Blood collection is coordinated for NGS testing as well, so that sequencing can occur during the surgical recovery period, and the results thus coincide with the subsequent treatment planning encounter.
From March 2021 to October 2022, 300 glioma patients underwent the FastTrack process at MD Anderson. We compared the turnaround times from 52 FastTrack cases with those from 66 Non-FastTrack cases, finding that the time from the order date to the reported result date decreased by 8.0 days for MD Anderson Solid Tumor Genomic Assay (STGA) DNA mutational profile panel, by 20.8 days for STGA RNA Fusions, and by 15.0 days for MGMT promoter methylation status (Figure 1). FastTrack had minimal impact on 1p/19q FISH testing, as it is directly ordered by the Pathologist and performed in a separate FISH laboratory. Implementation of the FastTrack protocol has ensured that most patients attending their post-operative treatment planning visit will benefit from having very timely molecular results available. A molecularly informed Neuro-oncology consultation is now regarded as a medical necessity,3 and grouping of biologically and molecularly defined entities with well-characterized natural histories is essential to the research mission of improving clinical care.4 Ongoing efforts to reduce turnaround time and provide scalable and cost-effective results remain an important endeavor.5,6 To the best of our knowledge, this is the first public report of such data, and we hope that subsequent comparison with other institutions can generate further innovation.
Figure 1.
Flowchart schematic of the FastTrack process (Panel A) and table comparing turnaround time for Non-FastTrack versus FastTrack cases (Panel B).
Acknowledgments
The authors thank Huy Nguyen, Joe Rodriguez, Mehran Taherian, Adel Abdallah for assistance with data acquisition
Contributor Information
Timothy A Gregory, Department of Neuro-Oncology, University of Texas, MD Anderson Cancer Center, Houston, TX, USA.
Garret L Williford, Department of Neuro-Oncology, University of Texas, MD Anderson Cancer Center, Houston, TX, USA.
Jacob M Maronge, Department of Biostatistics, University of Texas, MD Anderson Cancer Center, Houston, TX, USA.
Kristin Alfaro, Department of Neuro-Oncology, University of Texas, MD Anderson Cancer Center, Houston, TX, USA.
Gregory N Fuller, Department of Neuropathology, University of Texas, MD Anderson Cancer Center, Houston, TX, USA.
John de Groot, Department of Neuro-Oncology, University of Texas, MD Anderson Cancer Center, Houston, TX, USA.
Vinay K Puduvalli, Department of Neuro-Oncology, University of Texas, MD Anderson Cancer Center, Houston, TX, USA.
Leomar Y Ballester, Department of Neuropathology, University of Texas, MD Anderson Cancer Center, Houston, TX, USA.
Nazanin K Majd, Department of Neuro-Oncology, University of Texas, MD Anderson Cancer Center, Houston, TX, USA.
Funding
None.
Conflict of interest statement
The authors have no conflicts of interest to declare.
Authorship
Conceptualization and data collection: GLW, KA, JDG, and LYB. Performance of the statistical analyses: JMM. Contribution to the data analysis and significant portions of the manuscript writing: TAG, JMM, GNF, LYB, and NKM. Participation in patient care: TAG, GNF, JDG, VKP, LYB, and NKM. All authors were involved in writing, editing, and approval of the final manuscript.
Disclosures (Financial and Ethical): None.
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