دورية أكاديمية
Interpretable artificial intelligence to optimise use of imatinib after resection in patients with localised gastrointestinal stromal tumours: an observational cohort study.
| العنوان: | Interpretable artificial intelligence to optimise use of imatinib after resection in patients with localised gastrointestinal stromal tumours: an observational cohort study. |
|---|---|
| المؤلفون: | Bertsimas D; Operations Research Center, Massachusetts Institute of Technology, Cambridge, MA, USA., Margonis GA; Operations Research Center, Massachusetts Institute of Technology, Cambridge, MA, USA; Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Sujichantararat S; Operations Research Center, Massachusetts Institute of Technology, Cambridge, MA, USA., Koulouras A; Operations Research Center, Massachusetts Institute of Technology, Cambridge, MA, USA., Ma Y; Operations Research Center, Massachusetts Institute of Technology, Cambridge, MA, USA., Antonescu CR; Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Brennan MF; Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Martín-Broto J; Medical Oncology Department, Fundación Jimenez Diaz University Hospital, Madrid, Spain; Medical Oncology Department, Hospital General de Villalba, Madrid, Spain; Instituto de Investigacion Sanitaria Fundacion Jimenez Diaz, Madrid, Spain., Tang S; Operations Research Center, Massachusetts Institute of Technology, Cambridge, MA, USA., Rutkowski P; Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland., Kreis ME; Department of General and Visceral Surgery, Charité-Universitätsmedizin Berlin, Berlin, Germany., Beyer K; Department of General and Visceral Surgery, Charité-Universitätsmedizin Berlin, Berlin, Germany., Wang J; Department of Surgery, University of California San Francisco, San Francisco, CA, USA., Bylina E; Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland., Sobczuk P; Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland., Gutierrez A; Medical Oncology Department, Fundación Jimenez Diaz University Hospital, Madrid, Spain; Medical Oncology Department, Hospital General de Villalba, Madrid, Spain; Instituto de Investigacion Sanitaria Fundacion Jimenez Diaz, Madrid, Spain., Jadeja B; Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Tap WD; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Chi P; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Department of Medicine, Weill Cornell Medical College, New York, NY, USA., Singer S; Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA. Electronic address: singers@mskcc.org. |
| المصدر: | The Lancet. Oncology [Lancet Oncol] 2024 Aug; Vol. 25 (8), pp. 1025-1037. Date of Electronic Publication: 2024 Jul 05. |
| نوع المنشور: | Journal Article; Observational Study |
| اللغة: | English |
| بيانات الدورية: | Publisher: Lancet Pub. Group Country of Publication: England NLM ID: 100957246 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1474-5488 (Electronic) Linking ISSN: 14702045 NLM ISO Abbreviation: Lancet Oncol Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: London : Lancet Pub. Group, c2000- |
| مواضيع طبية MeSH: | Gastrointestinal Stromal Tumors*/surgery , Gastrointestinal Stromal Tumors*/drug therapy , Gastrointestinal Stromal Tumors*/pathology , Imatinib Mesylate*/therapeutic use , Artificial Intelligence*, Humans ; Female ; Male ; Middle Aged ; Aged ; Antineoplastic Agents/therapeutic use ; Chemotherapy, Adjuvant ; Neoplasm Recurrence, Local/pathology ; Neoplasm Recurrence, Local/drug therapy ; Gastrointestinal Neoplasms/surgery ; Gastrointestinal Neoplasms/drug therapy ; Gastrointestinal Neoplasms/pathology ; Adult ; Cohort Studies ; Treatment Outcome |
| مستخلص: | Background: Current guidelines recommend use of adjuvant imatinib therapy for many patients with gastrointestinal stromal tumours (GISTs); however, its optimal treatment duration is unknown and some patient groups do not benefit from the therapy. We aimed to apply state-of-the-art, interpretable artificial intelligence (ie, predictions or prescription logic that can be easily understood) methods on real-world data to establish which groups of patients with GISTs should receive adjuvant imatinib, its optimal treatment duration, and the benefits conferred by this therapy. Methods: In this observational cohort study, we considered for inclusion all patients who underwent resection of primary, non-metastatic GISTs at the Memorial Sloan Kettering Cancer Center (MSKCC; New York, NY, USA) between Oct 1, 1982, and Dec 31, 2017, and who were classified as intermediate or high risk according to the Armed Forces Institute of Pathology Miettinen criteria and had complete follow-up data with no missing entries. A counterfactual random forest model, which used predictors of recurrence (mitotic count, tumour size, and tumour site) and imatinib duration to infer the probability of recurrence at 7 years for a given patient under each duration of imatinib treatment, was trained in the MSKCC cohort. Optimal policy trees (OPTs), a state-of-the-art interpretable AI-based method, were used to read the counterfactual random forest model by training a decision tree with the counterfactual predictions. The OPT recommendations were externally validated in two cohorts of patients from Poland (the Polish Clinical GIST Registry), who underwent GIST resection between Dec 1, 1981, and Dec 31, 2011, and from Spain (the Spanish Group for Research in Sarcomas), who underwent resection between Oct 1, 1987, and Jan 30, 2011. Findings: Among 1007 patients who underwent GIST surgery in MSKCC, 117 were included in the internal cohort; for the external cohorts, the Polish cohort comprised 363 patients and the Spanish cohort comprised 239 patients. The OPT did not recommend imatinib for patients with GISTs of gastric origin measuring less than 15·9 cm with a mitotic count of less than 11·5 mitoses per 5 mm 2 or for those with small GISTs (<5·4 cm) of any site with a count of less than 11·5 mitoses per 5 mm 2 . In this cohort, the OPT cutoffs had a sensitivity of 92·7% (95% CI 82·4-98·0) and a specificity of 33·9% (22·3-47·0). The application of these cutoffs in the two external cohorts would have spared 38 (29%) of 131 patients in the Spanish cohort and 44 (35%) of 126 patients in the Polish cohort from unnecessary treatment with imatinib. Meanwhile, the risk of undertreating patients in these cohorts was minimal (sensitivity 95·4% [95% CI 89·5-98·5] in the Spanish cohort and 92·4% [88·3-95·4] in the Polish cohort). The OPT tested 33 different durations of imatinib treatment (<5 years) and found that 5 years of treatment conferred the most benefit. Interpretation: If the identified patient subgroups were applied in clinical practice, as many as a third of the current cohort of candidates who do not benefit from adjuvant imatinib would be encouraged to not receive imatinib, subsequently avoiding unnecessary toxicity on patients and financial strain on health-care systems. Our finding that 5 years is the optimal duration of imatinib treatment could be the best source of evidence to inform clinical practice until 2028, when a randomised controlled trial with the same aims is expected to report its findings. Funding: National Cancer Institute. Competing Interests: Declaration of interests DB is a cofounding partner of Interpretable AI. JMB reports personal medical consulting fees from PharmaMar, Eli Lilly and Company, Bayer, GSK, Novartis, Roche, Asofarma, Tecnofarma, Amgen, and Boehringer Ingelheim; grants provided to his institution from Adaptimmune, Amgen, Ayala Pharmaceuticals, Bayer, Blueprint, BMS, Cebiotex, Celgene, Daiichi Sankyo, Deciphera, Eisai, GSK, IMMIX Biopharma, SpringWorks Therapeutics, Inhibrx, Karyiopharm, Lilly, Lixte, Novartis, Pfizer, PharmaMar, Philogen, PTC Therapeutics, and Ran Therapeutics; personal payment or honoraria for lectures and presentations from PharmaMar and for expert testimony from PharmaMar, Eli Lilly and Company, Bayer, Roche, Amgen, Boehringer Ingelheim, and Eisai; and personal support for attending meetings from FarmaMar and Novartis. JMB is also a member of the boards or committees for Asofarma, Tecnofarma, and Sarcoma Research Solutions, outside the submitted work. PC reports grants provided to her institution from Pfizer–Array, Deciphera, and Ningbo NewBay; and consulting fees from Deciphera and Ningbo NewBay. PC also serves on the advisory board and steering committee for Ningbo NewBay, and on the steering committee for Deciphera (unpaid), outside the submitted work. PR reports personal consulting fees from Bristol-Myers Squibb, MSD, Novartis, Pierre Fabre, Philogen, Pfizer, Genesis, and Madison Pharma; payment or honoraria for participating in lectures, presentations, speakers bureaus, manuscript writing, or educational events from Bristol-Myers Squibb, MSD, Novartis, Pfizer, Pierre Fabre, Sanofi, Merck, and AstraZeneca; personal support for attending meetings from Orphan Europe and Pierre Fabre; and other financial or non-financial interests provided to his institution from Novartis, Pfizer, Roche, and Bristol-Myers Squibb, outside the submitted work. AK reports a personal grant from the Onassis Foundation and ownership of Pfizer stocks. PS reports personal payment or honoraria for participation in lectures, presentations, speakers bureaus, manuscript writing, or educational events from Bristol-Myers Squibb, Gilead, and Sandoz; and personal support for attending meetings from Bristol-Myers Squibb, Novartis, and Pierre-Fabre. PS also serves as a board or committee member of Sandoz, the Polish Society of Clinical Oncology (unpaid), the European Society of Medical Oncology (unpaid), and the Connective Tissue Oncology Society (unpaid). PS also holds personal stocks at Celon Pharma. PS receives institutional funding for a drug clinical trial from Immutep; and reports other institutional research funding from Novartis, Pfizer, Roche, and Bristol-Myers Squibb, outside the submitted work. WDT reports personal fees from Eli Lilly, C4 Therapeutics, Daiichi Sankyo, Deciphera, Servier, Bayer Pharmaceuticals, Cogent, Foghorn Therapeutics, Amgen, AmMax Bio, Boehringer Ingelheim, BioAtla, Inhibrx, PharmaEssentia, Avacta, Ipsen, Sonata, Abbisko, and Aadi. WDT also holds a patent titled ‘Companion Diagnostic for CDK4 inhibitors - 14/854,329’ pending to the MSKCC–Sloan Kettering Institute, and another patent titled ‘Enigma and CDH18 as Companion Diagnostics for CDK4 inhibition – SKI2016-021-03’ issued to MSKCC–Sloan Kettering Institute. WDT also serves on the scientific advisory board for Certis Oncology Solutions; holds stock ownership and co-founder positions at Atropos Therapeutics; holds stock ownership and serves on the scientific advisory board for Innova Therapeutics; and is a member of the Strategic Advisory Board for The Osteosarcoma Institute, all outside the submitted work. JW reports grants provided to her institution from the University of California San Francisco Noyce Initiative Computational Innovator Postdoctoral Fellowship Award. All other authors declare no competing interests. (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.) |
| المشرفين على المادة: | 8A1O1M485B (Imatinib Mesylate) 0 (Antineoplastic Agents) |
| تواريخ الأحداث: | Date Created: 20240708 Date Completed: 20240801 Latest Revision: 20240801 |
| رمز التحديث: | 20240802 |
| DOI: | 10.1016/S1470-2045(24)00259-6 |
| PMID: | 38976997 |
| قاعدة البيانات: | MEDLINE |
Full Text via ClinicalKey 
Full Text Finder | تدمد: | 1474-5488 |
|---|---|
| DOI: | 10.1016/S1470-2045(24)00259-6 |