EEG-based grading of immune effector cell-associated neurotoxicity syndrome
Abstract CAR-T cell therapy is an effective cancer therapy for multiple refractory/relapsed hematologic malignancies but is associated with substantial toxicity, including Immune Effector Cell Associated Neurotoxicity Syndrome (ICANS). Improved detection and assessment of ICANS could improve managem...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2022-11-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-022-24010-1 |
| _version_ | 1828281079353573376 |
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| author | Daniel K. Jones Christine A. Eckhardt Haoqi Sun Ryan A. Tesh Preeti Malik Syed Quadri Marcos Santana Firme Meike van Sleuwen Aayushee Jain Ziwei Fan Jin Jing Wendong Ge Fábio A. Nascimento Irfan S. Sheikh Caron Jacobson Matthew Frigault Eyal Y. Kimchi Sydney S. Cash Jong Woo Lee Jorg Dietrich M. Brandon Westover |
| author_facet | Daniel K. Jones Christine A. Eckhardt Haoqi Sun Ryan A. Tesh Preeti Malik Syed Quadri Marcos Santana Firme Meike van Sleuwen Aayushee Jain Ziwei Fan Jin Jing Wendong Ge Fábio A. Nascimento Irfan S. Sheikh Caron Jacobson Matthew Frigault Eyal Y. Kimchi Sydney S. Cash Jong Woo Lee Jorg Dietrich M. Brandon Westover |
| author_sort | Daniel K. Jones |
| collection | DOAJ |
| description | Abstract CAR-T cell therapy is an effective cancer therapy for multiple refractory/relapsed hematologic malignancies but is associated with substantial toxicity, including Immune Effector Cell Associated Neurotoxicity Syndrome (ICANS). Improved detection and assessment of ICANS could improve management and allow greater utilization of CAR-T cell therapy, however, an objective, specific biomarker has not been identified. We hypothesized that the severity of ICANS can be quantified based on patterns of abnormal brain activity seen in electroencephalography (EEG) signals. We conducted a retrospective observational study of 120 CAR-T cell therapy patients who had received EEG monitoring. We determined a daily ICANS grade for each patient through chart review. We used visually assessed EEG features and machine learning techniques to develop the Visual EEG-Immune Effector Cell Associated Neurotoxicity Syndrome (VE-ICANS) score and assessed the association between VE-ICANS and ICANS. We also used it to determine the significance and relative importance of the EEG features. We developed the Visual EEG-ICANS (VE-ICANS) grading scale, a grading scale with a physiological basis that has a strong correlation to ICANS severity (R = 0.58 [0.47–0.66]) and excellent discrimination measured via area under the receiver operator curve (AUC = 0.91 for ICANS ≥ 2). This scale shows promise as a biomarker for ICANS which could help to improve clinical care through greater accuracy in assessing ICANS severity. |
| first_indexed | 2024-04-13T08:09:50Z |
| format | Article |
| id | doaj.art-0889862c46f24d588d99f5162341e4e0 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-13T08:09:50Z |
| publishDate | 2022-11-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-0889862c46f24d588d99f5162341e4e02022-12-22T02:55:01ZengNature PortfolioScientific Reports2045-23222022-11-0112111310.1038/s41598-022-24010-1EEG-based grading of immune effector cell-associated neurotoxicity syndromeDaniel K. Jones0Christine A. Eckhardt1Haoqi Sun2Ryan A. Tesh3Preeti Malik4Syed Quadri5Marcos Santana Firme6Meike van Sleuwen7Aayushee Jain8Ziwei Fan9Jin Jing10Wendong Ge11Fábio A. Nascimento12Irfan S. Sheikh13Caron Jacobson14Matthew Frigault15Eyal Y. Kimchi16Sydney S. Cash17Jong Woo Lee18Jorg Dietrich19M. Brandon Westover20Department of Neurology, Massachusetts General Hospital (MGH)Department of Neurology, Massachusetts General Hospital (MGH)Department of Neurology, Massachusetts General Hospital (MGH)Department of Neurology, Massachusetts General Hospital (MGH)Department of Neurology, Massachusetts General Hospital (MGH)Department of Neurology, Massachusetts General Hospital (MGH)Department of Neurology, Massachusetts General Hospital (MGH)Department of Neurology, Massachusetts General Hospital (MGH)Department of Neurology, Massachusetts General Hospital (MGH)Department of Neurology, Massachusetts General Hospital (MGH)Department of Neurology, Massachusetts General Hospital (MGH)Department of Neurology, Massachusetts General Hospital (MGH)Department of Neurology, Washington University School of MedicineDepartment of Neurology, Massachusetts General Hospital (MGH)Department of Neurology, Brigham and Women’s Hospital (MGH)Department of Neurology, Massachusetts General Hospital (MGH)Department of Neurology, Massachusetts General Hospital (MGH)Department of Neurology, Massachusetts General Hospital (MGH)Harvard Medical SchoolDepartment of Neurology, Massachusetts General Hospital (MGH)Department of Neurology, Massachusetts General Hospital (MGH)Abstract CAR-T cell therapy is an effective cancer therapy for multiple refractory/relapsed hematologic malignancies but is associated with substantial toxicity, including Immune Effector Cell Associated Neurotoxicity Syndrome (ICANS). Improved detection and assessment of ICANS could improve management and allow greater utilization of CAR-T cell therapy, however, an objective, specific biomarker has not been identified. We hypothesized that the severity of ICANS can be quantified based on patterns of abnormal brain activity seen in electroencephalography (EEG) signals. We conducted a retrospective observational study of 120 CAR-T cell therapy patients who had received EEG monitoring. We determined a daily ICANS grade for each patient through chart review. We used visually assessed EEG features and machine learning techniques to develop the Visual EEG-Immune Effector Cell Associated Neurotoxicity Syndrome (VE-ICANS) score and assessed the association between VE-ICANS and ICANS. We also used it to determine the significance and relative importance of the EEG features. We developed the Visual EEG-ICANS (VE-ICANS) grading scale, a grading scale with a physiological basis that has a strong correlation to ICANS severity (R = 0.58 [0.47–0.66]) and excellent discrimination measured via area under the receiver operator curve (AUC = 0.91 for ICANS ≥ 2). This scale shows promise as a biomarker for ICANS which could help to improve clinical care through greater accuracy in assessing ICANS severity.https://doi.org/10.1038/s41598-022-24010-1 |
| spellingShingle | Daniel K. Jones Christine A. Eckhardt Haoqi Sun Ryan A. Tesh Preeti Malik Syed Quadri Marcos Santana Firme Meike van Sleuwen Aayushee Jain Ziwei Fan Jin Jing Wendong Ge Fábio A. Nascimento Irfan S. Sheikh Caron Jacobson Matthew Frigault Eyal Y. Kimchi Sydney S. Cash Jong Woo Lee Jorg Dietrich M. Brandon Westover EEG-based grading of immune effector cell-associated neurotoxicity syndrome Scientific Reports |
| title | EEG-based grading of immune effector cell-associated neurotoxicity syndrome |
| title_full | EEG-based grading of immune effector cell-associated neurotoxicity syndrome |
| title_fullStr | EEG-based grading of immune effector cell-associated neurotoxicity syndrome |
| title_full_unstemmed | EEG-based grading of immune effector cell-associated neurotoxicity syndrome |
| title_short | EEG-based grading of immune effector cell-associated neurotoxicity syndrome |
| title_sort | eeg based grading of immune effector cell associated neurotoxicity syndrome |
| url | https://doi.org/10.1038/s41598-022-24010-1 |
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