Cox proportional hazards deep neural network identifies peripheral blood complete remission to be at least equivalent to morphologic complete remission in predicting outcomes of patients treated with azacitidine-A prospective cohort study by the AGMT.
Autor: | Pleyer L; Austrian Group of Medical Tumor Therapy (AGMT) Study Group, Vienna, Austria.; Salzburg Cancer Research Institute (SCRI) Center for Clinical Cancer and Immunology Trials (CCCIT), Salzburg, Austria.; Cancer Cluster Salzburg (CCS), Salzburg, Austria.; 3rd Medical Department with Hematology, Medical Oncology, Hemostaseology, Rheumatology and Infectiology, Oncologic Center, Paracelsus Medical University, Salzburg, Austria., Vaisband M; Salzburg Cancer Research Institute (SCRI) Center for Clinical Cancer and Immunology Trials (CCCIT), Salzburg, Austria.; Cancer Cluster Salzburg (CCS), Salzburg, Austria.; 3rd Medical Department with Hematology, Medical Oncology, Hemostaseology, Rheumatology and Infectiology, Oncologic Center, Paracelsus Medical University, Salzburg, Austria.; Life & Medical Sciences Institute, University of Bonn, Bonn, Germany., Drost M; Assign Data Management and Biostatistics GmbH, Innsbruck, Austria., Pfeilstöcker M; Austrian Group of Medical Tumor Therapy (AGMT) Study Group, Vienna, Austria.; 3rd Medical Department for Hematology and Oncology, Hanusch Hospital, Vienna, Austria.; Ludwig Boltzmann Institute for Hematology and Oncology, Medical University Vienna, Vienna, Austria., Stauder R; Austrian Group of Medical Tumor Therapy (AGMT) Study Group, Vienna, Austria.; Department of Hematology and Oncology, Comprehensive Cancer Center Innsbruck (CCCI), Medical University of Innsbruck (MUI), Innsbruck, Austria., Heibl S; Austrian Group of Medical Tumor Therapy (AGMT) Study Group, Vienna, Austria.; 4th Medical Department of Internal Medicine, Hematology, Internistic Oncology and Palliative Medicine, Klinikum Wels-Grieskirchen GmbH, Wels, Austria., Sill H; Austrian Group of Medical Tumor Therapy (AGMT) Study Group, Vienna, Austria.; Division of Hematology, Medical University of Graz, Graz, Austria., Girschikofsky M; Austrian Group of Medical Tumor Therapy (AGMT) Study Group, Vienna, Austria.; 1st Medical Department, Hematology with Stem Cell Transplantation, Hemostaseology and Medical Oncology, Ordensklinikum Linz GmbH Elisabethinen, Linz, Austria., Stampfl-Mattersberger M; Austrian Group of Medical Tumor Therapy (AGMT) Study Group, Vienna, Austria.; Department of Internal Medicine 2, Wiener Gesundheitsverbund, Klinik Donaustadt, Vienna, Austria., Pichler A; Austrian Group of Medical Tumor Therapy (AGMT) Study Group, Vienna, Austria.; Department of Internal Medicine, Hematology and Internal Oncology, LKH Hochsteiermark, Leoben, Austria., Hartmann B; Austrian Group of Medical Tumor Therapy (AGMT) Study Group, Vienna, Austria.; Department of Internal Medicine 2, Landeskrankenhaus Feldkirch, Feldkirch, Austria., Petzer A; Austrian Group of Medical Tumor Therapy (AGMT) Study Group, Vienna, Austria.; Internal Medicine I: Medical Oncology and Hematology, Ordensklinikum Linz GmbH, Barmherzige Schwestern, Linz, Austria., Schreder M; Austrian Group of Medical Tumor Therapy (AGMT) Study Group, Vienna, Austria.; 1st Department of Internal Medicine, Center for Oncology and Hematology, Wiener Gesundheitsverbund, Klinik Ottakring, Vienna, Austria., Schmitt CA; Austrian Group of Medical Tumor Therapy (AGMT) Study Group, Vienna, Austria.; Department of Hematology and Internal Oncology, Kepler University Hospital, Johannes Kepler University, Linz, Austria.; Charité-University Medical Center, Molecular Cancer Research Center, Berlin, Germany., Vallet S; Austrian Group of Medical Tumor Therapy (AGMT) Study Group, Vienna, Austria.; University Hospital Krems, Department of Internal Medicine 2, Karl Landsteiner Private University of Health Sciences, Krems, Austria., Melchardt T; Austrian Group of Medical Tumor Therapy (AGMT) Study Group, Vienna, Austria.; Salzburg Cancer Research Institute (SCRI) Center for Clinical Cancer and Immunology Trials (CCCIT), Salzburg, Austria.; Cancer Cluster Salzburg (CCS), Salzburg, Austria.; 3rd Medical Department with Hematology, Medical Oncology, Hemostaseology, Rheumatology and Infectiology, Oncologic Center, Paracelsus Medical University, Salzburg, Austria., Zebisch A; Austrian Group of Medical Tumor Therapy (AGMT) Study Group, Vienna, Austria.; Division of Hematology, Medical University of Graz, Graz, Austria.; Otto Loewi Research Center for Vascular Biology, Immunology and Inflammation, Division of Pharmacology, Medical University of Graz, Graz, Austria., Pichler P; Austrian Group of Medical Tumor Therapy (AGMT) Study Group, Vienna, Austria.; Clinical Department for Internal Medicine, University Hospital St Poelten, Karl Landsteiner University of Health Sciences, St Poelten, Austria., Zaborsky N; Salzburg Cancer Research Institute (SCRI) Center for Clinical Cancer and Immunology Trials (CCCIT), Salzburg, Austria.; Cancer Cluster Salzburg (CCS), Salzburg, Austria.; 3rd Medical Department with Hematology, Medical Oncology, Hemostaseology, Rheumatology and Infectiology, Oncologic Center, Paracelsus Medical University, Salzburg, Austria.; Laboratory of Immunological and Molecular Cancer Research (LIMCR), Salzburg, Austria., Machherndl-Spandl S; Austrian Group of Medical Tumor Therapy (AGMT) Study Group, Vienna, Austria.; 1st Medical Department, Hematology with Stem Cell Transplantation, Hemostaseology and Medical Oncology, Ordensklinikum Linz GmbH Elisabethinen, Linz, Austria., Wolf D; Austrian Group of Medical Tumor Therapy (AGMT) Study Group, Vienna, Austria.; Department of Hematology and Oncology, Comprehensive Cancer Center Innsbruck (CCCI), Medical University of Innsbruck (MUI), Innsbruck, Austria., Keil F; Austrian Group of Medical Tumor Therapy (AGMT) Study Group, Vienna, Austria.; 3rd Medical Department for Hematology and Oncology, Hanusch Hospital, Vienna, Austria.; Ludwig Boltzmann Institute for Hematology and Oncology, Medical University Vienna, Vienna, Austria., Hasenauer J; Life & Medical Sciences Institute, University of Bonn, Bonn, Germany., Larcher-Senn J; Assign Data Management and Biostatistics GmbH, Innsbruck, Austria., Greil R; Austrian Group of Medical Tumor Therapy (AGMT) Study Group, Vienna, Austria.; Salzburg Cancer Research Institute (SCRI) Center for Clinical Cancer and Immunology Trials (CCCIT), Salzburg, Austria.; Cancer Cluster Salzburg (CCS), Salzburg, Austria.; 3rd Medical Department with Hematology, Medical Oncology, Hemostaseology, Rheumatology and Infectiology, Oncologic Center, Paracelsus Medical University, Salzburg, Austria. |
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Jazyk: | angličtina |
Zdroj: | American journal of hematology [Am J Hematol] 2023 Nov; Vol. 98 (11), pp. 1685-1698. Date of Electronic Publication: 2023 Aug 07. |
DOI: | 10.1002/ajh.27046 |
Abstrakt: | The current gold standard of response assessment in patients with myelodysplastic syndromes (MDS), chronic myelomonocytic leukemia (CMML), and acute myeloid leukemia (AML) is morphologic complete remission (CR) and CR with incomplete count recovery (CRi), both of which require an invasive BM evaluation. Outside of clinical trials, BM evaluations are only performed in ~50% of patients during follow-up, pinpointing a clinical need for response endpoints that do not necessitate BM assessments. We define and validate a new response type termed "peripheral blood complete remission" (PB-CR) that can be determined from the differential blood count and clinical parameters without necessitating a BM assessment. We compared the predictive value of PB-CR with morphologic CR/CRi in 1441 non-selected, consecutive patients diagnosed with MDS (n = 522; 36.2%), CMML (n = 132; 9.2%), or AML (n = 787; 54.6%), included within the Austrian Myeloid Registry (aMYELOIDr; NCT04438889). Time-to-event analyses were adjusted for 17 covariates remaining in the final Cox proportional hazards (CPH) model. DeepSurv, a CPH neural network model, and permutation-based feature importance were used to validate results. 1441 patients were included. Adjusted median overall survival for patients achieving PB-CR was 22.8 months (95%CI 18.9-26.2) versus 10.4 months (95%CI 9.7-11.2) for those who did not; HR = 0.366 (95%CI 0.303-0.441; p < .0001). Among patients achieving CR, those additionally achieving PB-CR had a median adjusted OS of 32.6 months (95%CI 26.2-49.2) versus 21.7 months (95%CI 16.9-27.7; HR = 0.400 [95%CI 0.190-0.844; p = .0161]) for those who did not. Our deep neural network analysis-based findings from a large, prospective cohort study indicate that BM evaluations solely for the purpose of identifying CR/CRi can be omitted. (© 2023 The Authors. American Journal of Hematology published by Wiley Periodicals LLC.) |
Databáze: | MEDLINE |
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