{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T12:21:25Z","timestamp":1788265285064,"version":"build-2803163510"},"reference-count":21,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T00:00:00Z","timestamp":1780963200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T00:00:00Z","timestamp":1780963200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2026,10,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Antiangiogenic treatment with ramucirumab (RAM) is a standard second\u2010line option in advanced gastric and gastroesophageal junction (GEJ) adenocarcinoma. However, reliable biomarkers are lacking. The phase II RAMIRIS trial compared RAM plus paclitaxel with RAM plus FOLFIRI (5\u2010fluororuracil, leucovorin and irinotecan) in this setting. We present the exploratory biomarker analysis evaluating placental growth factor (PlGF), carbonic anhydrase IX (CAIX), and tryptase. Plasma samples from 99 patients enrolled in RAMIRIS were collected at predefined timepoints (baseline, Cycle 2 Day 1, and Cycle 4 Day 1). PlGF, CAIX, and tryptase were quantified by ELISA. Associations with progression\u2010free survival (PFS) and overall survival (OS) were analyzed using dichotomized biomarker levels and Cox regression models. PlGF levels increased substantially under treatment, whereas CAIX showed a transient rise, followed by a slight decline, and tryptase remained stable. Elevated PlGF levels at baseline and early\u2010treatment (c2d1) were associated with shorter OS in univariate analysis (baseline HR\n                    <jats:sub>u<\/jats:sub>\n                    \u2009=\u20091.75;\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.020; c2d1 HR\n                    <jats:sub>u<\/jats:sub>\n                    \u2009=\u20091.69;\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.054). After multivariate adjustment, the association remained directionally consistent; although statistical support was retained only for c2d1 (baseline HR\n                    <jats:sub>m<\/jats:sub>\n                    \u2009=\u20091.41,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.198; c2d1 HR\n                    <jats:sub>m<\/jats:sub>\n                    \u2009=\u20091.85,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.030). CAIX and tryptase showed no consistent associations with survival. Elevated PlGF\u2014particularly its early increase during RAM\u2010based therapy\u2014was associated with shortened survival and may represent a dynamic marker of unfavorable prognosis in advanced gastric\/GEJ adenocarcinoma. Given the exploratory nature of this analysis, these findings should be considered hypothesis\u2010generating and require validation in independent biomarker\u2010driven studies.\n                  <\/jats:p>","DOI":"10.1002\/ijc.70567","type":"journal-article","created":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T06:16:38Z","timestamp":1781072198000},"page":"1817-1828","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Plasma\n                    <scp>PlGF<\/scp>\n                    as a Potential Biomarker in Ramucirumab\u2010Based Second\u2010Line Therapy for Advanced Gastroesophageal Adenocarcinoma: Exploratory Biomarker Analysis from the Phase\n                    <scp>II<\/scp>\n                    Part of the\n                    <scp>RAMIRIS<\/scp>\n                    Trial"],"prefix":"10.1002","volume":"159","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-9069-2587","authenticated-orcid":false,"given":"Jurek","family":"Hille","sequence":"first","affiliation":[{"name":"Department of Oncology, Hematology and Bone Marrow Transplantation With Section Pneumology University Medical Center Hamburg\u2010Eppendorf  Hamburg Germany"},{"name":"University Cancer Center Hamburg (UCCH), University Medical Center Hamburg\u2010Eppendorf  Hamburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvie","family":"Lorenzen","sequence":"additional","affiliation":[{"name":"Department of Medicine III TUM University Hospital, Technical University of Munich  Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Pauligk","sequence":"additional","affiliation":[{"name":"The Frankfurt Institute for Clinical Cancer Research IKF GmbH  Frankfurt\/Main Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria","family":"Gensch","sequence":"additional","affiliation":[{"name":"DKFZ\u2010Hector Cancer Institute at the University Medical Center Mannheim  Mannheim Germany"},{"name":"Division of Personalized Medical Oncology (A420) German Cancer Research Center (DKFZ), &amp; Deutsches Zentrum f\u00fcr Lungenforschung (DZL)  Heidelberg Germany"},{"name":"Department of Personalized Oncology University Hospital Mannheim, Medical Faculty Mannheim University of Heidelberg  Mannheim Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Thuss\u2010Patience","sequence":"additional","affiliation":[{"name":"Department of Hematology, Oncology and Cancer Immunology Charit\u00e9\u2010University Medicine Berlin  Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eray","family":"Goekkurt","sequence":"additional","affiliation":[{"name":"University Cancer Center Hamburg (UCCH), University Medical Center Hamburg\u2010Eppendorf  Hamburg Germany"},{"name":"Hematology\u2010Oncology Practice Eppendorf (HOPE)  Hamburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7654-2442","authenticated-orcid":false,"given":"Thomas","family":"Ettrich","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine I Ulm University Medical Center  Ulm Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florian","family":"Lordick","sequence":"additional","affiliation":[{"name":"Department of Oncology, Gastroenterology, Hepatology, and Pulmonology University Cancer Center Leipzig (UCCL), Leipzig University Medical Center  Leipzig Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carsten","family":"Bokemeyer","sequence":"additional","affiliation":[{"name":"Department of Oncology, Hematology and Bone Marrow Transplantation With Section Pneumology University Medical Center Hamburg\u2010Eppendorf  Hamburg Germany"},{"name":"University Cancer Center Hamburg (UCCH), University Medical Center Hamburg\u2010Eppendorf  Hamburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"M\u00fcller","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology Evang. Kliniken Essen\u2010Mitte  Essen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Reichardt","sequence":"additional","affiliation":[{"name":"Sarcoma Center Berlin\u2010Brandenburg Helios Klinikum Berlin\u2010Buch  Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"S\u00f6kler","sequence":"additional","affiliation":[{"name":"Oncology Spital Thun  Thun Switzerland"},{"name":"Second Department of Internal Medicine University Hospital T\u00fcbingen  T\u00fcbingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Pink","sequence":"additional","affiliation":[{"name":"Department of Oncology and Palliative Care Helios Klinikum Bad Saarow  Bad Saarow Germany"},{"name":"Department of Internal Medicine C University Hospital Greifswald  Greifswald Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Probst","sequence":"additional","affiliation":[{"name":"Department of Hematology, Oncology and Palliative Medicine Community Hospital Bielefeld  Bielefeld Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thorsten O.","family":"Goetze","sequence":"additional","affiliation":[{"name":"The Frankfurt Institute for Clinical Cancer Research IKF GmbH  Frankfurt\/Main Germany"},{"name":"Krankenhaus Nordwest, University Cancer Center Frankfurt  Frankfurt Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salah E.","family":"Al\u2010Batran","sequence":"additional","affiliation":[{"name":"The Frankfurt Institute for Clinical Cancer Research IKF GmbH  Frankfurt\/Main Germany"},{"name":"Krankenhaus Nordwest, University Cancer Center Frankfurt  Frankfurt Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonja","family":"Loges","sequence":"additional","affiliation":[{"name":"DKFZ\u2010Hector Cancer Institute at the University Medical Center Mannheim  Mannheim Germany"},{"name":"Division of Personalized Medical Oncology (A420) German Cancer Research Center (DKFZ), &amp; Deutsches Zentrum f\u00fcr Lungenforschung (DZL)  Heidelberg Germany"},{"name":"Department of Personalized Oncology University Hospital Mannheim, Medical Faculty Mannheim University of Heidelberg  Mannheim Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melanie","family":"Janning","sequence":"additional","affiliation":[{"name":"Department of Oncology, Hematology and Bone Marrow Transplantation With Section Pneumology University Medical Center Hamburg\u2010Eppendorf  Hamburg Germany"},{"name":"DKFZ\u2010Hector Cancer Institute at the University Medical Center Mannheim  Mannheim Germany"},{"name":"Department of Personalized Oncology University Hospital Mannheim, Medical Faculty Mannheim University of Heidelberg  Mannheim Germany"},{"name":"Liquid Biopsy and Single Cell Analysis Group, Division of Personalized Medical Oncology (A420) German Cancer Research Center (DKFZ) &amp; Deutsches Zentrum f\u00fcr Lungenforschung (DZL)  Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,6,9]]},"reference":[{"key":"e_1_2_13_2_1","unstructured":"J.Ferlay M.Ervik F.Lam et\u00a0al. \u201cGlobal Cancer Observatory: Cancer Today: yon France: International Agency for Research on Cancer \u201daccessed March 31 2025 https:\/\/gco.iarc.who.int\/today."},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/cac2.70017"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v8.i6.994"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470\u20102045(14)70420\u20106"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2022.07.004"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2022.01.015"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10456\u2010014\u20109420\u2010y"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008\u20105472.CAN\u201017\u20103415"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.3437"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.32163"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2010.02.039"},{"key":"e_1_2_13_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010017\u201000327\u20108"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2011.05.007"},{"key":"e_1_2_13_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clcc.2024.01.003"},{"key":"e_1_2_13_16_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078\u20100432.ccr\u201019\u20101985"},{"key":"e_1_2_13_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2019.10.026"},{"key":"e_1_2_13_18_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1700737"},{"key":"e_1_2_13_19_1","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.0307164"},{"key":"e_1_2_13_20_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdx767"},{"key":"e_1_2_13_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.2016.293"},{"key":"e_1_2_13_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00280\u2010019\u201003817\u20102"}],"container-title":["International Journal of Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ijc.70567","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ijc.70567","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ijc.70567","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T11:56:45Z","timestamp":1788263805000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ijc.70567"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,9]]},"references-count":21,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2026,10,1]]}},"alternative-id":["10.1002\/ijc.70567"],"URL":"https:\/\/doi.org\/10.1002\/ijc.70567","archive":["Portico"],"relation":{},"ISSN":["0020-7136","1097-0215"],"issn-type":[{"value":"0020-7136","type":"print"},{"value":"1097-0215","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,9]]},"assertion":[{"value":"2025-09-04","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-19","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-06-09","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}