{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T23:15:52Z","timestamp":1792451752937,"version":"4.5.0"},"reference-count":12,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"5","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["JCO Precis Oncol"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:sec>\n                    <jats:title>PURPOSE<\/jats:title>\n                    <jats:p>Trastuzumab deruxtecan (T-DXd) is an antibody-drug conjugate approved for human epidermal growth factor receptor 2 (HER2)\u2013positive gastric cancer (GC) and gastroesophageal junction adenocarcinoma (GEJA). Eligibility for T-DXd therapy currently relies on conventional HER2 immunohistochemistry (IHC) scoring per ASCO\/CAP guidelines. Computational pathology tools such as quantitative continuous scoring (QCS) offer precise quantification of HER2 expression, enabling improved scores reflective of T-DXd's mechanism of action.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>We used HER2-QCS scoring to identify biomarker signatures in the DESTINY-Gastric01 cohort, with external validation in DESTINY-Gastric02.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      QCS-derived continuous spatial proximity score (cSPS) and density of HER2-positive cells in tumor epithelium (DPC) displayed significant survival benefits for biomarker-positive versus biomarker-negative patients in the DESTINY-Gastric01 T-DXd arm (Cox regression:\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt; .0001). These signatures were validated in the DESTINY-Gastric02 cohort (log-rank\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt; .0001).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>Our findings indicate that cSPS and DPC are predictive of T-DXd clinical outcomes, supporting the potential future use of QCS as a quantitative approach to identify patients with GC who might benefit most from T-DXd therapy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1200\/po-25-00823","type":"journal-article","created":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T19:59:13Z","timestamp":1779998353000},"update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":1,"title":["Human Epidermal Growth Factor Receptor 2 Quantification Using Computational Pathology to Identify Novel Biomarkers for Trastuzumab Deruxtecan\u2013Treated Human Epidermal Growth Factor Receptor 2\u2013Positive Gastric Cancer"],"prefix":"10.1200","volume":"10","clinical-trial-number":[{"clinical-trial-number":"nct04014075","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct03329690","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5079-6997","authenticated-orcid":true,"given":"Ansh","family":"Kapil","sequence":"first","affiliation":[{"name":"AstraZeneca Computational Pathology GmbH, Oncology Research and Development, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4235-6120","authenticated-orcid":true,"given":"Henrik","family":"Failmezger","sequence":"additional","affiliation":[{"name":"AstraZeneca Computational Pathology GmbH, Oncology Research and Development, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Fu","sequence":"additional","affiliation":[{"name":"AstraZeneca Computational Pathology GmbH, Oncology Research and Development, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1217-7818","authenticated-orcid":true,"given":"Andreas","family":"Spitzm\u00fcller","sequence":"additional","affiliation":[{"name":"AstraZeneca Computational Pathology GmbH, Oncology Research and Development, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Chan","sequence":"additional","affiliation":[{"name":"AstraZeneca Computational Pathology GmbH, Oncology Research and Development, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanne","family":"Haneder","sequence":"additional","affiliation":[{"name":"AstraZeneca Computational Pathology GmbH, Oncology Research and Development, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6332-5844","authenticated-orcid":true,"given":"Anatoliy","family":"Shumilov","sequence":"additional","affiliation":[{"name":"AstraZeneca Computational Pathology GmbH, Oncology Research and Development, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alice","family":"Barkell","sequence":"additional","affiliation":[{"name":"AstraZeneca Translational Medicine, Early Oncology, Cambridge, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshihiro","family":"Oguma","sequence":"additional","affiliation":[{"name":"Daiichi Sankyo Inc, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koichiro","family":"Inaki","sequence":"additional","affiliation":[{"name":"Daiichi Sankyo Inc, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-5649-2650","authenticated-orcid":true,"given":"Fumitaka","family":"Suto","sequence":"additional","affiliation":[{"name":"Daiichi Sankyo Inc, Basking Ridge, NJ"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Allard","sequence":"additional","affiliation":[{"name":"Daiichi Sankyo Inc, Basking Ridge, NJ"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4911-6165","authenticated-orcid":true,"given":"Jeeyun","family":"Lee","sequence":"additional","affiliation":[{"name":"Samsung Medical Center, Sungkyunkwan University School of Medicine, Gangnam-gu, Seoul, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arthur W.","family":"Lambert","sequence":"additional","affiliation":[{"name":"AstraZeneca, Waltham, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"Schick","sequence":"additional","affiliation":[{"name":"AstraZeneca Computational Pathology GmbH, Oncology Research and Development, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. Carl","family":"Barrett","sequence":"additional","affiliation":[{"name":"AstraZeneca, Waltham, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0709-5295","authenticated-orcid":true,"given":"G\u00fcnter","family":"Schmidt","sequence":"additional","affiliation":[{"name":"AstraZeneca Computational Pathology GmbH, Oncology Research and Development, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hadassah","family":"Sade","sequence":"additional","affiliation":[{"name":"AstraZeneca Computational Pathology GmbH, Oncology Research and Development, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Gustavson","sequence":"additional","affiliation":[{"name":"AstraZeneca Computational Pathology GmbH, Oncology Research and Development, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danielle","family":"Carroll","sequence":"additional","affiliation":[{"name":"AstraZeneca Translational Medicine, Early Oncology, Cambridge, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabiola","family":"Cecchi","sequence":"additional","affiliation":[{"name":"AstraZeneca, Gaithersburg, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"233","reference":[{"key":"e_1_3_10_2_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2008.19.9844"},{"key":"e_1_3_10_3_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2004413"},{"key":"e_1_3_10_4_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-15-2822"},{"key":"e_1_3_10_5_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1914510"},{"key":"e_1_3_10_6_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.23.02005"},{"key":"e_1_3_10_7_2","doi-asserted-by":"publisher","DOI":"10.1111\/cas.12966"},{"key":"e_1_3_10_8_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2203690"},{"key":"e_1_3_10_9_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.22.02864"},{"key":"e_1_3_10_10_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2559.2008.03028.x"},{"key":"e_1_3_10_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-024-61957-9"},{"key":"e_1_3_10_12_2","volume-title":"A Phase 2, Open-Label, Single-Arm Trial of Trastuzumab Deruxtecan (DS 8201a) in HER2-Positive, Unresectable or Metastatic Gastric or Gastro-Esophageal Junction (GEJ) Adenocarcinoma Subjects Who Have Progressed on or After a Trastuzumab-Containing Regimen (DESTINY-Gastric02)","author":"Daiichi Sankyo, Inc","year":"2022","unstructured":"Daiichi Sankyo, Inc: A Phase 2, Open-Label, Single-Arm Trial of Trastuzumab Deruxtecan (DS 8201a) in HER2-Positive, Unresectable or Metastatic Gastric or Gastro-Esophageal Junction (GEJ) Adenocarcinoma Subjects Who Have Progressed on or After a Trastuzumab-Containing Regimen (DESTINY-Gastric02). 2022. https:\/\/clinicaltrials.gov\/ct2\/show\/NCT04014075"},{"key":"e_1_3_10_13_2","doi-asserted-by":"publisher","DOI":"10.1256\/qj.02.166"}],"container-title":["JCO Precision Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ascopubs.org\/doi\/pdfdirect\/10.1200\/PO-25-00823","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T19:59:23Z","timestamp":1780430363000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascopubs.org\/doi\/10.1200\/PO-25-00823"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5]]},"references-count":12,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2026,5]]}},"alternative-id":["10.1200\/PO-25-00823"],"URL":"https:\/\/doi.org\/10.1200\/po-25-00823","relation":{},"ISSN":["2473-4284"],"issn-type":[{"value":"2473-4284","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5]]},"assertion":[{"value":"2025-08-27","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-02-20","order":1,"name":"revised","label":"Revised","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-06","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-28","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e2500823"}}