{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T10:02:04Z","timestamp":1775469724104,"version":"3.50.1"},"reference-count":173,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T00:00:00Z","timestamp":1775433600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Department of Excellence-DIMET, Universit\u00e0 del Piemonte Orientale, Novara, Italy"},{"name":"AIL Novara VCO ODV, Italy"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>The integration of emerging technologies and real-world data is transforming the landscape of hematologic clinical trials. Artificial intelligence (AI) offers remarkable capabilities for predictive modeling, patient stratification, and adaptive trial design, while circulating tumor DNA (ctDNA) provides a minimally invasive biomarker for disease monitoring, the early detection of relapse, and treatment response assessment. Concurrently, real-world evidence (RWE) complements traditional clinical trial data by capturing treatment effectiveness, safety, and patient outcomes in broader, heterogeneous populations. This review examines the synergistic potential of AI, ctDNA, and RWE to optimize trial design and decision-making in hematologic malignancies. We discuss methodological innovations, including AI-driven patient selection, ctDNA-guided adaptive interventions, and the incorporation of RWE for external control arms and post-marketing surveillance. Key challenges, such as data standardization, regulatory considerations, and ethical implications, are also addressed. By integrating these advanced tools, clinical trials in hematology can achieve greater efficiency, precision, and translatability, ultimately accelerating the development of personalized therapies and improving patient outcomes.<\/jats:p>","DOI":"10.3390\/cancers18071173","type":"journal-article","created":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T08:58:48Z","timestamp":1775465928000},"page":"1173","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Integrating Artificial Intelligence, Circulating Tumor DNA, and Real-World Evidence to Optimize Hematologic Clinical Trials: Toward Adaptive and Learning Trial Designs"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3969-0112","authenticated-orcid":false,"given":"Abdurraouf Mokhtar","family":"Mahmoud","sequence":"first","affiliation":[{"name":"Division of Hematology, Department of Translational Medicine, University of Eastern Piedmont, 28100 Novara, Italy"},{"name":"Hematology Clinical Trial Unit, Azienda Ospedaliero-Universitaria Maggiore della Carit\u00e0, Via Solaroli 17, 28100 Novara, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-6246-9576","authenticated-orcid":false,"given":"Jasmitaben Prakashbhai","family":"Touti","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Translational Medicine, University of Eastern Piedmont, 28100 Novara, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Syed Rubina","family":"Zaidi","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Translational Medicine, University of Eastern Piedmont, 28100 Novara, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-6090-4872","authenticated-orcid":false,"given":"Ahad Ahmed","family":"Kodipad","sequence":"additional","affiliation":[{"name":"Department of Pediatric Abdominal Transplantation and Hepatopancratobilary Surgery, Nationwide Children\u2019s Hospital, Columbus, OH 43205, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Clara","family":"Deambrogi","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Translational Medicine, University of Eastern Piedmont, 28100 Novara, Italy"},{"name":"Hematology Clinical Trial Unit, Azienda Ospedaliero-Universitaria Maggiore della Carit\u00e0, Via Solaroli 17, 28100 Novara, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e7253","DOI":"10.1002\/cam4.7253","article-title":"Artificial intelligence to unlock real-world evidence in clinical oncology: A primer on recent advances","volume":"13","author":"Bryant","year":"2024","journal-title":"Cancer Med."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Alhamrani, S.Q., Ball, G.R., El-Sherif, A.A., Ahmed, S., Mousa, N.O., Alghorayed, S.A., Alatawi, N.A., Ali, A.M., Alqahtani, F.A., and Gabre, R.M. 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