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  1. Article ; Online: Using machine learning to predict outcomes following carotid endarterectomy.

    Li, Ben / Beaton, Derek / Eisenberg, Naomi / Lee, Douglas S / Wijeysundera, Duminda N / Lindsay, Thomas F / de Mestral, Charles / Mamdani, Muhammad / Roche-Nagle, Graham / Al-Omran, Mohammed

    Journal of vascular surgery

    2023  Volume 78, Issue 4, Page(s) 973–987.e6

    Abstract: Objective: Prediction of outcomes following carotid endarterectomy (CEA) remains challenging, with a lack of standardized tools to guide perioperative management. We used machine learning (ML) to develop automated algorithms that predict outcomes ... ...

    Abstract Objective: Prediction of outcomes following carotid endarterectomy (CEA) remains challenging, with a lack of standardized tools to guide perioperative management. We used machine learning (ML) to develop automated algorithms that predict outcomes following CEA.
    Methods: The Vascular Quality Initiative (VQI) database was used to identify patients who underwent CEA between 2003 and 2022. We identified 71 potential predictor variables (features) from the index hospitalization (43 preoperative [demographic/clinical], 21 intraoperative [procedural], and 7 postoperative [in-hospital complications]). The primary outcome was stroke or death at 1 year following CEA. Our data were split into training (70%) and test (30%) sets. Using 10-fold cross-validation, we trained six ML models using preoperative features (Extreme Gradient Boosting [XGBoost], random forest, Naïve Bayes classifier, support vector machine, artificial neural network, and logistic regression). The primary model evaluation metric was area under the receiver operating characteristic curve (AUROC). After selecting the best performing algorithm, additional models were built using intra- and postoperative data. Model robustness was evaluated using calibration plots and Brier scores. Performance was assessed on subgroups based on age, sex, race, ethnicity, insurance status, symptom status, and urgency of surgery.
    Results: Overall, 166,369 patients underwent CEA during the study period. In total, 7749 patients (4.7%) had the primary outcome of stroke or death at 1 year. Patients with an outcome were older with more comorbidities, had poorer functional status, and demonstrated higher risk anatomic features. They were also more likely to undergo intraoperative surgical re-exploration and have in-hospital complications. Our best performing prediction model at the preoperative stage was XGBoost, achieving an AUROC of 0.90 (95% confidence interval [CI], 0.89-0.91). In comparison, logistic regression had an AUROC of 0.65 (95% CI, 0.63-0.67), and existing tools in the literature demonstrate AUROCs ranging from 0.58 to 0.74. Our XGBoost models maintained excellent performance at the intra- and postoperative stages, with AUROCs of 0.90 (95% CI, 0.89-0.91) and 0.94 (95% CI, 0.93-0.95), respectively. Calibration plots showed good agreement between predicted and observed event probabilities with Brier scores of 0.15 (preoperative), 0.14 (intraoperative), and 0.11 (postoperative). Of the top 10 predictors, eight were preoperative features, including comorbidities, functional status, and previous procedures. Model performance remained robust on all subgroup analyses.
    Conclusions: We developed ML models that accurately predict outcomes following CEA. Our algorithms perform better than logistic regression and existing tools, and therefore, have potential for important utility in guiding perioperative risk mitigation strategies to prevent adverse outcomes.
    MeSH term(s) Humans ; Endarterectomy, Carotid/adverse effects ; Risk Assessment ; Bayes Theorem ; Treatment Outcome ; Risk Factors ; Stroke/diagnosis ; Stroke/etiology ; Machine Learning ; Retrospective Studies
    Language English
    Publishing date 2023-05-20
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 605700-7
    ISSN 1097-6809 ; 0741-5214
    ISSN (online) 1097-6809
    ISSN 0741-5214
    DOI 10.1016/j.jvs.2023.05.024
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  2. Article ; Online: The Cost of Caring: Compassion Fatigue among Peer Overdose Response Workers in British Columbia.

    Mamdani, Zahra / McKenzie, Sophie / Ackermann, Emma / Voyer, Rayne / Cameron, Fred / Scott, Tracy / Pauly, Bernie / Buxton, Jane A

    Substance use & misuse

    2022  Volume 58, Issue 1, Page(s) 85–93

    Abstract: Background: ...

    Abstract Background:
    MeSH term(s) Humans ; Compassion Fatigue ; British Columbia ; Quality of Life/psychology ; Burnout, Professional/psychology ; Mental Health ; Empathy ; Drug Overdose ; Surveys and Questionnaires
    Language English
    Publishing date 2022-11-25
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1310358-1
    ISSN 1532-2491 ; 1082-6084
    ISSN (online) 1532-2491
    ISSN 1082-6084
    DOI 10.1080/10826084.2022.2148481
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  3. Article ; Online: Xylitol for the prevention of acute otitis media episodes in children aged 1-5 years: a randomised controlled trial.

    Persaud, Navindra / Azarpazhooh, Amir / Keown-Stoneman, Charles / Birken, Catherine S / Isaranuwatchai, Wanrudee / Maguire, Jonathon L / Mamdani, Muhammad / Allen, Christopher / Mason, Dalah / Kowal, Christine / Jaleel, Mateenah / Bazeghi, Farnaz / Thorpe, Kevin E / Laupacis, Andreas / Parkin, Patricia C

    Archives of disease in childhood

    2024  Volume 109, Issue 2, Page(s) 121–124

    Abstract: Objective: To investigate the regular use of xylitol, compared with sorbitol, to prevent acute otitis media (AOM), upper respiratory tract infections (URTIs) and dental caries.: Design: Blinded randomised controlled trial with a 6-month study period.! ...

    Abstract Objective: To investigate the regular use of xylitol, compared with sorbitol, to prevent acute otitis media (AOM), upper respiratory tract infections (URTIs) and dental caries.
    Design: Blinded randomised controlled trial with a 6-month study period.
    Setting: Enrolment took place at 11 primary care practices in Ontario, Canada.
    Patients: Children aged 1-5 years who did not use xylitol or sorbitol at enrolment.
    Interventions: Children were randomly assigned to use a placebo syrup with sorbitol or xylitol syrup two times per day for 6 months.
    Main outcome measures: Primary outcome was the number of clinician-diagnosed AOM episodes over 6 months. Secondary outcomes were caregiver-reported URTIs and dental caries.
    Results: Among the 250 randomised children, the mean (SD) age was 38±14 months and there were 124 girls (50%). There were three clinician-diagnosed AOM episodes in the 125 placebo group participants and six in the 125 xylitol group participants (OR 2.04; 95% CI 0.43, 12.92; p=0.50). There was no difference in number of caregiver-reported URTI episodes (rate ratio (RR) 0.88; 95% CI 0.70, 1.11) between the placebo (4.2 per participant over 6 months; 95% CI 3.6, 5.0) and xylitol (3.7; 95% CI 3.2, 4.4) groups. Dental caries were reported for four participants in the placebo group and two in the xylitol group (OR 0.42; 95% CI 0.04, 3.05; p=0.42). In a post-hoc analysis of URTIs during the COVID-19 pandemic, the rate among the 59 participants receiving placebo was 2.3 per participant over 6 months (95% CI 1.8, 3.0) and for the 55 receiving xylitol, 1.3 over 6 months (95% CI 0.92, 1.82; RR 0.56; 95% CI 0.36, 0.87). The most common adverse event was diarrhoea (28% with placebo; 34% with xylitol).
    Conclusions: Regular use of xylitol did not prevent AOM, URTIs or dental caries in a trial with limited statistical power. A post-hoc analysis indicated that URTIs were less common with xylitol exposure during the COVID-19 pandemic, but this finding could be spurious.
    Trial registration number: NCT03055091.
    MeSH term(s) Female ; Humans ; Acute Disease ; COVID-19/epidemiology ; Dental Caries/epidemiology ; Dental Caries/prevention & control ; Ontario/epidemiology ; Otitis Media/epidemiology ; Otitis Media/prevention & control ; Pandemics ; Sorbitol ; Xylitol/therapeutic use ; Infant ; Child, Preschool ; Male
    Chemical Substances Sorbitol (506T60A25R) ; Xylitol (VCQ006KQ1E)
    Language English
    Publishing date 2024-01-22
    Publishing country England
    Document type Randomized Controlled Trial ; Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 524-1
    ISSN 1468-2044 ; 0003-9888 ; 1359-2998
    ISSN (online) 1468-2044
    ISSN 0003-9888 ; 1359-2998
    DOI 10.1136/archdischild-2023-325565
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Preferences and Attitudes of Cardiologists in Management of Patients with Cancer.

    Azar, Ibrahim / Wang, Stephani / Dhillon, Vikram / Kenitz, Jacqueline / Lombardo, Dawn / Deano, Roderick / Mahmood, Syed / Mamdani, Hirva / Shields, Anthony F / Philip, Philip Agop / Stellini, Michael / Schulman-Marcus, Joshua

    Palliative medicine reports

    2022  Volume 3, Issue 1, Page(s) 279–286

    Abstract: ... To our knowledge, there are no current U.S. data examining how the presence and extent of cancer influence ... based survey of cardiologists was conducted at five U.S. institutions investigating how the extent ...

    Abstract Background: With recent improvements in survival of cancer patients and common use of high-value care at end of life, the management of cardiovascular disease (CVD) in patients with cancer is increasingly important. To our knowledge, there are no current U.S. data examining how the presence and extent of cancer influence cardiologists' decision making for common cardiovascular conditions.
    Methods: An anonymous online vignette-based survey of cardiologists was conducted at five U.S. institutions investigating how the extent of gastrointestinal and thoracic malignancies (prior/localized, metastatic) would influence treatment recommendations for atrial fibrillation (AF), aortic stenosis, unstable angina (UA), and obstructive coronary artery disease (CAD).
    Results: Thirty-three percent (86/259) of cardiologists completed the survey between September and November 2019. Participants were 67% male, 51% below age 40, and 58% had five or more years of clinical experience. Majority of cardiologists practiced at teaching hospitals (72%) and were noninterventional (63%). Cardiologists were more likely to recommend procedural interventions for patients with localized cancer than for those with metastatic disease: AF (left atrial appendage occlusion: 20% vs. 8%), atrial stenosis (aortic valve repair: 83% vs. 11%), UA (left heart catheter: 70% vs. 27%), and obstructive CAD (percutaneous coronary intervention: 81% vs. 38%). In patients with metastatic cancer, most cardiologists sought an oncology (82%) or a palliative care (69%) consultation. However, a persistent trend of undertreatment in patients with localized cancers and overtreatment in patients with end-of-life disease was apparent.
    Conclusions: Cardiologists were less likely to recommend invasive cardiovascular therapies to patients with metastatic cancer. This preference pattern likely reflects the influence of comorbidities and quality of life expectation on cardiologists' treatment recommendations but may also be related to the stigma of advanced cancer. Better communication between cardiologists and oncologists is necessary to provide a personalized care of patients with cancer and CVD that would maximize treatment benefit with least morbidity.
    Language English
    Publishing date 2022-11-21
    Publishing country United States
    Document type Journal Article
    ISSN 2689-2820
    ISSN (online) 2689-2820
    DOI 10.1089/pmr.2022.0014
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Using intervention mapping to develop 'ROSE': an intervention to support peer workers in overdose response settings.

    Mamdani, Zahra / McKenzie, Sophie / Cameron, Fred / Knott, Mike / Conway-Brown, Jennifer / Scott, Tracy / Buxton, Jane A / Pauly, Bernie

    BMC health services research

    2021  Volume 21, Issue 1, Page(s) 1279

    Abstract: ... for Organizational support, S for Skill development and E for Everyone. The ROSE model aims to facilitate cultural ...

    Abstract Background: Peer workers (those with lived/living experience of substance use working in overdose response settings) are at the forefront of overdose response initiatives in British Columbia (BC). Working in these settings can be stressful, with lasting social, mental and emotional impacts. Peer workers have also been disproportionately burdened by the current dual public health crises characterized by the onset of the COVID-19 pandemic and rise in illicit drug overdose deaths. It is therefore critical to develop supports tailored specifically to their realities.
    Methods: We used the six steps outlined in the Intervention Mapping (IM) framework to identify needs of peer workers and design an intervention model to support peer workers in overdose response settings.
    Results: Eight peer-led focus groups were conducted in community settings to identify peer workers' needs and transcripts were analyzed using interpretive description. The strategies within the intervention model were informed by organizational development theory as well as by lived/living experience of peer workers. The support needs identified by peer workers were categorized into three key themes and these formed the basis of an intervention model titled 'ROSE'; R stands for Recognition of peer work, O for Organizational support, S for Skill development and E for Everyone. The ROSE model aims to facilitate cultural changes within organizations, leading towards more equitable and just workplaces for peer workers. This, in turn, has the potential for positive socio-ecological impact.
    Conclusions: Centering lived/living experience in the intervention mapping process led us to develop a framework for supporting peer workers in BC. The ROSE model can be used as a baseline for other organizations employing peer workers.
    MeSH term(s) COVID-19 ; Drug Overdose/epidemiology ; Drug Overdose/prevention & control ; Humans ; Pandemics ; Peer Group ; SARS-CoV-2 ; Substance-Related Disorders/epidemiology
    Language English
    Publishing date 2021-11-27
    Publishing country England
    Document type Journal Article
    ISSN 1472-6963
    ISSN (online) 1472-6963
    DOI 10.1186/s12913-021-07241-2
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  6. Article ; Online: Developing and validating natural language processing algorithms for radiology reports compared to ICD-10 codes for identifying venous thromboembolism in hospitalized medical patients.

    Verma, Amol A / Masoom, Hassan / Pou-Prom, Chloe / Shin, Saeha / Guerzhoy, Michael / Fralick, Michael / Mamdani, Muhammad / Razak, Fahad

    Thrombosis research

    2021  Volume 209, Page(s) 51–58

    Abstract: Background: Identifying venous thromboembolism (VTE) from large clinical and administrative databases is important for research and quality improvement.: Objective: To develop and validate natural language processing (NLP) algorithms to identify VTE ... ...

    Abstract Background: Identifying venous thromboembolism (VTE) from large clinical and administrative databases is important for research and quality improvement.
    Objective: To develop and validate natural language processing (NLP) algorithms to identify VTE from radiology reports among general internal medicine (GIM) inpatients.
    Methods: This cross-sectional study included GIM hospitalizations between April 1, 2010 and March 31, 2017 at 5 hospitals in Toronto, Ontario, Canada. We developed NLP algorithms to identify pulmonary embolism (PE) and deep venous thrombosis (DVT) from radiologist reports of thoracic computed tomography (CT), extremity compression ultrasound (US), and nuclear ventilation-perfusion (VQ) scans in a training dataset of 1551 hospitalizations. We compared the accuracy of our NLP algorithms, the previously-published "simpleNLP" tool, and administrative discharge diagnosis codes (ICD-10-CA) for PE and DVT to the "gold standard" manual review in a separate random sample of 4000 GIM hospitalizations.
    Results: Our NLP algorithms were highly accurate for identifying DVT from US, with sensitivity 0.94, positive predictive value (PPV) 0.90, and Area Under the Receiver-Operating-Characteristic Curve (AUC) 0.96; and in identifying PE from CT, with sensitivity 0.91, PPV 0.89, and AUC 0.96. Administrative diagnosis codes and the simple NLP tool were less accurate for DVT (ICD-10-CA sensitivity 0.63, PPV 0.43, AUC 0.81; simpleNLP sensitivity 0.41, PPV 0.36, AUC 0.66) and PE (ICD-10-CA sensitivity 0.83, PPV 0.70, AUC 0.91; simpleNLP sensitivity 0.89, PPV 0.62, AUC 0.92).
    Conclusions: Administrative diagnosis codes are unreliable in identifying VTE in hospitalized patients. We developed highly accurate NLP algorithms to identify VTE from radiology reports in a multicentre sample and have made the algorithms freely available to the academic community with a user-friendly tool (https://lks-chart.github.io/CHARTextract-docs/08-downloads/rulesets.html#venous-thromboembolism-vte-rulesets).
    MeSH term(s) Algorithms ; Cross-Sectional Studies ; Hospitalization ; Humans ; International Classification of Diseases ; Natural Language Processing ; Ontario ; Pulmonary Embolism/diagnostic imaging ; Radiology ; Venous Thromboembolism/diagnostic imaging
    Language English
    Publishing date 2021-11-27
    Publishing country United States
    Document type Journal Article
    ZDB-ID 121852-9
    ISSN 1879-2472 ; 0049-3848
    ISSN (online) 1879-2472
    ISSN 0049-3848
    DOI 10.1016/j.thromres.2021.11.020
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  7. Article ; Online: Identification of potential blood biomarkers associated with suicide in major depressive disorder.

    Mamdani, Firoza / Weber, Matthieu D / Bunney, Blynn / Burke, Kathleen / Cartagena, Preston / Walsh, David / Lee, Francis S / Barchas, Jack / Schatzberg, Alan F / Myers, Richard M / Watson, Stanley J / Akil, Huda / Vawter, Marquis P / Bunney, William E / Sequeira, Adolfo

    Translational psychiatry

    2022  Volume 12, Issue 1, Page(s) 159

    Abstract: ... in total). Samples were collected from MDD patients who died by suicide (MDD-S), MDDs who died ... platform. In blood, we identified 14 genes which significantly differentiated MDD-S versus MDD-NS. The top ... Additionally, four genes showed significant changes in brain and blood between MDD-S and MDD-NS; SOX9 was ...

    Abstract Suicides have increased to over 48,000 deaths yearly in the United States. Major depressive disorder (MDD) is the most common diagnosis among suicides, and identifying those at the highest risk for suicide is a pressing challenge. The objective of this study is to identify changes in gene expression associated with suicide in brain and blood for the development of biomarkers for suicide. Blood and brain were available for 45 subjects (53 blood samples and 69 dorsolateral prefrontal cortex (DLPFC) samples in total). Samples were collected from MDD patients who died by suicide (MDD-S), MDDs who died by other means (MDD-NS) and non-psychiatric controls. We analyzed gene expression using RNA and the NanoString platform. In blood, we identified 14 genes which significantly differentiated MDD-S versus MDD-NS. The top six genes differentially expressed in blood were: PER3, MTPAP, SLC25A26, CD19, SOX9, and GAR1. Additionally, four genes showed significant changes in brain and blood between MDD-S and MDD-NS; SOX9 was decreased and PER3 was increased in MDD-S in both tissues, while CD19 and TERF1 were increased in blood but decreased in DLPFC. To our knowledge, this is the first study to analyze matched blood and brain samples in a well-defined population of MDDs demonstrating significant differences in gene expression associated with completed suicide. Our results strongly suggest that blood gene expression is highly informative to understand molecular changes in suicide. Developing a suicide biomarker signature in blood could help health care professionals to identify subjects at high risk for suicide.
    MeSH term(s) Amino Acid Transport Systems/metabolism ; Biomarkers/metabolism ; Brain/metabolism ; Calcium-Binding Proteins ; Depressive Disorder, Major/psychology ; Humans ; Prefrontal Cortex/metabolism ; Suicide/psychology
    Chemical Substances Amino Acid Transport Systems ; Biomarkers ; Calcium-Binding Proteins ; SLC25A26 protein, human
    Language English
    Publishing date 2022-04-14
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2609311-X
    ISSN 2158-3188 ; 2158-3188
    ISSN (online) 2158-3188
    ISSN 2158-3188
    DOI 10.1038/s41398-022-01918-w
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  8. Article ; Online: AutoScribe: Extracting Clinically Pertinent Information from Patient-Clinician Dialogues.

    Khattak, Faiza Khan / Jeblee, Serena / Crampton, Noah / Mamdani, Muhammad / Rudzicz, Frank

    Studies in health technology and informatics

    2019  Volume 264, Page(s) 1512–1513

    Abstract: We present AutoScribe, a system for automatically extracting pertinent medical information from dialogues between clinicians and patients. AutoScribe parses the dialogue and extracts entities such as medications and symptoms, using context to predict ... ...

    Abstract We present AutoScribe, a system for automatically extracting pertinent medical information from dialogues between clinicians and patients. AutoScribe parses the dialogue and extracts entities such as medications and symptoms, using context to predict which entities are relevant, and automatically generates a patient note and primary diagnosis.
    MeSH term(s) Databases, Factual ; Humans ; Physician-Patient Relations
    Language English
    Publishing date 2019-07-09
    Publishing country Netherlands
    Document type Journal Article
    ISSN 1879-8365
    ISSN (online) 1879-8365
    DOI 10.3233/SHTI190510
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  9. Article ; Online: Vision Transformer-based Decision Support for Neurosurgical Intervention in Acute Traumatic Brain Injury: Automated Surgical Intervention Support Tool.

    Smith, Christopher W / Malhotra, Armaan K / Hammill, Christopher / Beaton, Derek / Harrington, Erin M / He, Yingshi / Shakil, Husain / McFarlan, Amanda / Jones, Blair / Lin, Hui Ming / Mathieu, François / Nathens, Avery B / Ackery, Alun D / Mok, Garrick / Mamdani, Muhammad / Mathur, Shobhit / Wilson, Jefferson R / Moreland, Robert / Colak, Errol /
    Witiw, Christopher D

    Radiology. Artificial intelligence

    2024  Volume 6, Issue 2, Page(s) e230088

    Abstract: Purpose To develop an automated triage tool to predict neurosurgical intervention for patients with traumatic brain injury (TBI). Materials and Methods A provincial trauma registry was reviewed to retrospectively identify patients with TBI from 2005 to ... ...

    Abstract Purpose To develop an automated triage tool to predict neurosurgical intervention for patients with traumatic brain injury (TBI). Materials and Methods A provincial trauma registry was reviewed to retrospectively identify patients with TBI from 2005 to 2022 treated at a specialized Canadian trauma center. Model training, validation, and testing were performed using head CT scans with binary reference standard patient-level labels corresponding to whether the patient received neurosurgical intervention. Performance and accuracy of the model, the Automated Surgical Intervention Support Tool for TBI (ASIST-TBI), were also assessed using a held-out consecutive test set of all patients with TBI presenting to the center between March 2021 and September 2022. Results Head CT scans from 2806 patients with TBI (mean age, 57 years ± 22 [SD]; 1955 [70%] men) were acquired between 2005 and 2021 and used for training, validation, and testing. Consecutive scans from an additional 612 patients (mean age, 61 years ± 22; 443 [72%] men) were used to assess the performance of ASIST-TBI. There was accurate prediction of neurosurgical intervention with an area under the receiver operating characteristic curve (AUC) of 0.92 (95% CI: 0.88, 0.94), accuracy of 87% (491 of 562), sensitivity of 87% (196 of 225), and specificity of 88% (295 of 337) on the test dataset. Performance on the held-out test dataset remained robust with an AUC of 0.89 (95% CI: 0.85, 0.91), accuracy of 84% (517 of 612), sensitivity of 85% (199 of 235), and specificity of 84% (318 of 377). Conclusion A novel deep learning model was developed that could accurately predict the requirement for neurosurgical intervention using acute TBI CT scans.
    MeSH term(s) Male ; Humans ; Middle Aged ; Female ; Retrospective Studies ; Canada ; Brain Injuries ; Brain Injuries, Traumatic/diagnostic imaging ; Neurosurgical Procedures
    Language English
    Publishing date 2024-01-10
    Publishing country United States
    Document type Journal Article
    ISSN 2638-6100
    ISSN (online) 2638-6100
    DOI 10.1148/ryai.230088
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  10. Article ; Online: Poziotinib in Treatment-Naive NSCLC Harboring HER2 Exon 20 Mutations: ZENITH20-4, A Multicenter, Multicohort, Open-Label, Phase 2 Trial (Cohort 4).

    Cornelissen, Robin / Prelaj, Arsela / Sun, Sophie / Baik, Christina / Wollner, Mirjana / Haura, Eric B / Mamdani, Hirva / Riess, Jonathan W / Cappuzzo, Federico / Garassino, Marina C / Heymach, John V / Socinski, Mark A / Leu, Szu-Yun / Bhat, Gajanan / Lebel, Francois / Le, Xiuning

    Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer

    2023  Volume 18, Issue 8, Page(s) 1031–1041

    Abstract: Introduction: ERBB2 or HER2 alterations are found in approximately 2% to 5% of NSCLCs; most are exon 20 insertion mutations. The efficacy and safety of poziotinib, an oral tyrosine kinase inhibitor, were assessed in patients with treatment-naive NSCLC ... ...

    Abstract Introduction: ERBB2 or HER2 alterations are found in approximately 2% to 5% of NSCLCs; most are exon 20 insertion mutations. The efficacy and safety of poziotinib, an oral tyrosine kinase inhibitor, were assessed in patients with treatment-naive NSCLC whose tumors harbor HER2 exon 20 insertions.
    Methods: ZENITH20 is an open-label, multicohort, multicenter, global, phase 2 trial. ZENITH20-C4 enrolled treatment-naive patients with NSCLC with tumors harboring HER2 exon 20 insertions. Poziotinib was administered 16 mg once daily (QD) or 8 mg twice daily (BID). The primary end point was objective response rate (ORR) by independent central review. Secondary and exploratory end points included disease control rate, duration of response, progression-free survival, and safety.
    Results: A total of 80 patients (16 mg QD, n = 47; 8 mg BID, n = 33) were treated in ZENITH20-C4. ORR was 39% (95% confidence interval [CI]: 28%-50%; 31 of 80), with a disease control rate of 73% (95% CI: 61%-82%; 58 of 80); 80% of the patients experienced tumor reduction. Median duration of response was 5.7 (95% CI: 4.6-11.9) months, and median progression-free survival was 5.6 (95% CI: 5.4-7.3) months. The most common grade 3 treatment-related adverse events were rash (QD, 45%; BID, 39%), stomatitis (QD, 21%; BID, 15%), and diarrhea (QD, 15%; BID, 21%). Among all subtypes of HER2 exon 20 insertions, seven patients (9%) harboring tumors with G778_P780dupGSP had the best clinical outcomes (ORR, 71%).
    Conclusions: Poziotinib was found to have clinically meaningful efficacy with a manageable toxicity profile for patients with treatment-naive NSCLC harboring HER2 exon 20 mutations.
    MeSH term(s) Humans ; Lung Neoplasms/drug therapy ; Lung Neoplasms/genetics ; Lung Neoplasms/pathology ; Mutation ; Carcinoma, Non-Small-Cell Lung/drug therapy ; Carcinoma, Non-Small-Cell Lung/genetics ; Carcinoma, Non-Small-Cell Lung/pathology ; Protein Kinase Inhibitors/pharmacology ; Exons
    Chemical Substances HM781-36B ; Protein Kinase Inhibitors
    Language English
    Publishing date 2023-03-21
    Publishing country United States
    Document type Multicenter Study ; Clinical Trial, Phase II ; Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2432037-7
    ISSN 1556-1380 ; 1556-0864
    ISSN (online) 1556-1380
    ISSN 1556-0864
    DOI 10.1016/j.jtho.2023.03.016
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