{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T13:18:58Z","timestamp":1787663938510,"version":"build-2736575974"},"reference-count":21,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T00:00:00Z","timestamp":1786320000000},"content-version":"vor","delay-in-days":9,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82473237"],"award-info":[{"award-number":["82473237"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Thrombocytopenia is a common toxicity of oxaliplatin\u2010based chemotherapy and may be linked to hepatic sinusoidal obstruction and splenic enlargement. In the TORCH trial, adding PD\u20101 blockade to an oxaliplatin\u2010containing total neoadjuvant therapy (TNT) regimen improved tumor response in patients with locally advanced rectal cancer (LARC), but thrombocytopenia appeared more frequent and more severe. Here, we evaluated whether adding PD\u20101 blockade to TNT increased thrombocytopenia risk and explored its association with hepatic injury and splenomegaly.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We retrospectively reviewed 181 LARC patients treated at Fudan University Shanghai Cancer Center. The cohort included 44 patients who received long\u2010course chemoradiotherapy (LCRT) followed by oxaliplatin\u2010containing chemotherapy (Ox\u2010TNT), 41 who received LCRT followed by irinotecan\u2010based chemotherapy (Iri\u2010TNT), and 96 who received short\u2010course radiotherapy plus six cycles of CAPOX and toripalimab (iTNT). We collected serial blood test results and measured liver and spleen volumes before and after treatment. Thrombocytopenia was graded according to CTCAE v5.0.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Among 181 patients, thrombocytopenia occurred in 118 (65.2%), and splenomegaly in 69 (38.1%). Both events were most frequent in iTNT group, with incidences of 83.3% and 61.5%, respectively. Rates were lower in Ox\u2010based TNT group (50.0% and 13.6%) and in Iri\u2010based TNT group (39.0% and 9.8%), respectively. Platelet count showed an inverse correlation with both increased AST level (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001) and splenic volume (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001). In multivariate analysis, iTNT (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.002), splenomegaly (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.003), and older age (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.004) were independently associated with G2\u20104 thrombocytopenia. Factors that independently predicted splenomegaly included iTNT (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001), direct bilirubin (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.031), hepatomegaly (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.032), and AST (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.032). In the iTNT group, splenomegaly (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.009) and older age (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.033) remained associated with G2\u20104 thrombocytopenia. Lower CD8\n                      <jats:sup>+<\/jats:sup>\n                      CD28\n                      <jats:sup>+<\/jats:sup>\n                      T cells and higher NK cells were associated with thrombocytopenia.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>PD\u20101 blockade added to TNT was associated with more severe thrombocytopenia than conventional TNT in LARC patients, possibly through greater hepatic injury and splenomegaly.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cam4.72183","type":"journal-article","created":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T06:07:13Z","timestamp":1786428433000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Comparison of Thrombocytopenia and Splenomegaly in Locally Advanced Rectal Cancer Patients Receiving Total Neoadjuvant Therapy With and Without Immunotherapy"],"prefix":"10.1002","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-9373-3767","authenticated-orcid":false,"given":"Shuwen","family":"Li","sequence":"first","affiliation":[{"name":"Department of Radiation Oncology Fudan University Shanghai Cancer Center  Shanghai China"},{"name":"Shanghai Clinical Research Center for Radiation Oncology  Shanghai China"},{"name":"Shanghai Key Laboratory of Radiation Oncology  Shanghai China"},{"name":"Department of Oncology, Shanghai Medical College Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-2275-8774","authenticated-orcid":false,"given":"Mingxu","family":"Yan","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology Fudan University Shanghai Cancer Center  Shanghai China"},{"name":"Shanghai Clinical Research Center for Radiation Oncology  Shanghai 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