{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T00:24:48Z","timestamp":1782951888738,"version":"3.54.5"},"reference-count":36,"publisher":"Wiley","issue":"22","license":[{"start":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T00:00:00Z","timestamp":1764115200000},"content-version":"vor","delay-in-days":25,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100017006","name":"Abramson Cancer Center","doi-asserted-by":"publisher","award":["2T32CA009615"],"award-info":[{"award-number":["2T32CA009615"]}],"id":[{"id":"10.13039\/100017006","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Tumor histology at diagnosis is used in conjunction with other prognostic features to risk stratify patients with neuroblastoma and to assign therapy regimens. In patients with high\u2010risk disease, adjustment of therapy is tailored to treatment response, largely based on disease imaging following induction chemotherapy and resection of the primary tumor. The goals of this study were to (i) quantify changes in histologic features in the primary tumor between diagnosis and resection, and (ii) assess the prognostic capability of such alterations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Tumor histology from paired samples at diagnosis and resection was evaluated from 94 patients with high\u2010risk neuroblastoma enrolled in Children's Oncology Group (COG) trials from 2001 to 2013. Presence of Schwannian stroma, neuropil, degree of differentiation, mitosis karyorrhexis index (MKI), necrosis, and percentage of neuroblastic cells were annotated. Changes in tumor histology between diagnosis and resection were analyzed for association with overall survival (OS) and progression\u2010free survival (PFS).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Significant changes between diagnosis and resection were observed in all histologic parameters (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.01), suggesting a more phenotypically differentiated tumor following induction therapy. A higher percentage of intermediate\u2010high MKI in tumor cells at diagnosis was associated with a lower PFS and OS (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05). No other histologic factor was associated with survival at diagnosis or resection. The tumor percentage of intermediate\u2010high MKI decreased by a mean of 75% from diagnosis to resection (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.0001). The shift from intermediate\/high MKI at diagnosis to low MKI at resection had a PFS hazard ratio (HR) of 2.1 (95% CI: 0.9, 4.9;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.0908) and OS HR\u2009=\u20092.3 (95% CI: 0.9, 5.9;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.0773).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our findings suggest that primary neuroblastoma tumors undergo a significant morphologic shift following induction chemotherapy to a differentiated, less mitotically active phenotype. However, the alterations are not prognostic of patient outcome either at resection alone, or when the change from diagnosis to resection is considered.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cam4.71332","type":"journal-article","created":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T12:58:57Z","timestamp":1764161937000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Histologic Response to Induction Chemotherapy in High\u2010Risk Neuroblastoma"],"prefix":"10.1002","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-0498-5544","authenticated-orcid":false,"given":"Monica","family":"Pomaville","sequence":"first","affiliation":[{"name":"Department of Pediatric Oncology Children's Hospital of Philadelphia  Philadelphia Pennsylvania 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USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rani E.","family":"George","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Harvard Medical School  Boston Massachusetts USA"},{"name":"Boston Children's Cancer and Blood Disorders Center  Boston Massachusetts USA"},{"name":"Department of Pediatric Oncology Dana\u2010Farber Cancer Institute  Boston Massachusetts 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