{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,23]],"date-time":"2026-05-23T13:06:11Z","timestamp":1779541571889,"version":"3.53.1"},"reference-count":21,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T00:00:00Z","timestamp":1773360000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T00:00:00Z","timestamp":1773360000000},"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":["Pediatric Blood &amp;amp; Cancer"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>Chemoimmunotherapy with irinotecan, temozolomide, and dinutuximab (I\/T\/DIN) has emerged as first\u2010line therapy for relapsed\/refractory (r\/r) high\u2010risk neuroblastoma (HRNB) in North America. Topotecan and cyclophosphamide (T\/C) are often used in combination with dinutuximab in the setting of lack of response, progression, or incomplete response following I\/T\/DIN, but efficacy and tolerability are unknown.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Eligible patients received one or more cycles of T\/C\/DIN for r\/r HRNB. Response was assessed using the 2017 International Neuroblastoma Response Criteria.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Fifty\u2010four patients with r\/r HRNB were included. Patients received a median of four cycles of T\/C\/DIN (range = 1\u201316); 48 (89%) had previously received I\/T\/DIN. Twenty\u2010three patients (42.6%) had an objective response (complete\/partial\/minor; OR) to T\/C\/DIN, 21 (38.9%) had stable disease, and 10 (18.5%) had progressive disease as best response. Among patients who previously received I\/T\/DIN, objective response rate (ORR) to T\/C\/DIN was 54% in those with prior OR to I\/T\/DIN and 23% in those without prior OR (adjusted odds ratio 4.40, 95% confidence interval [CI]: 1.09\u201317.75). Patients who had experienced on\u2010therapy progression with I\/T\/DIN had a similar ORR to T\/C\/DIN compared to those who never progressed (38% vs. 41%,\n                      <jats:italic>p<\/jats:italic>\n                      = 1.0). Twenty\u2010one patients (39%) required T\/C\/DIN dose modification\u201411 (52%) due to hematologic toxicity. Seven patients (13%) discontinued T\/C\/DIN due to toxicity.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>T\/C\/DIN is an effective regimen for patients with r\/r HRNB, producing ORRs similar to prior reports in chemoimmunotherapy\u2010na\u00efve patients treated with I\/T\/DIN. Prior chemoimmunotherapy response may predict response to T\/C\/DIN, but even patients who progress while receiving I\/T\/DIN may benefit from the T\/C\/DIN combination.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/1545-5017.70195","type":"journal-article","created":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T10:50:30Z","timestamp":1773399030000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Efficacy and Tolerability of Topotecan\/Cyclophosphamide\/Dinutuximab in Relapsed and Refractory High\u2010Risk Neuroblastoma: A Multi\u2010Institutional Retrospective Study"],"prefix":"10.1002","volume":"73","author":[{"given":"Benjamin J.","family":"Lerman","sequence":"first","affiliation":[{"name":"Department of Pediatrics University of California San Francisco and Benioff Children's Hospitals  San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madeleine","family":"King","sequence":"additional","affiliation":[{"name":"Pediatric Hematology Oncology C.S. Mott Children's Hospital  Ann Arbor Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajen","family":"Mody","sequence":"additional","affiliation":[{"name":"Pediatric Hematology Oncology C.S. Mott Children's Hospital  Ann Arbor Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara\u2010Jane","family":"Onyeama","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Children's Hospital Los Angeles, Keck School of Medicine University of Southern California  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Araz","family":"Marachelian","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Children's Hospital Los Angeles, Keck School of Medicine University of Southern California  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Cash","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Aflac Cancer and Blood Disorders Center, Children's Healthcare of Atlanta Emory University School of Medicine  Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara M.","family":"Federico","sequence":"additional","affiliation":[{"name":"Department of Pediatrics St. Jude Children's Research Hospital  Memphis Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meaghan","family":"Granger","sequence":"additional","affiliation":[{"name":"Department of Pediatrics St. Jude Children's Research Hospital  Memphis Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ami V.","family":"Desai","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of Chicago  Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suzanne","family":"Shusterman","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Dana\u2010Farber\/Boston Children's Cancer and Blood Disorders Centers Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer H.","family":"Foster","sequence":"additional","affiliation":[{"name":"Pediatric Hematology\/Oncology Texas Children's Hospital  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Sokol","sequence":"additional","affiliation":[{"name":"Division of Pediatric Hematology, Oncology, Neuro\u2010oncology, and Stem Cell Transplant, Ann &amp; Robert H. Lurie Children's Hospital of Chicago Northwestern Feinberg School of Medicine  Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chelsee","family":"Greer","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Cook Children's Medical Center  Fort Worth Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keri","family":"Streby","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Nationwide Children's Hospital and the Ohio State University College of Medicine  Columbus Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Holly J.","family":"Meany","sequence":"additional","affiliation":[{"name":"Center for Cancer and Blood Disorders Children's National Hospital  Washington, Columbia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kieuhoa T.","family":"Vo","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of California San Francisco and Benioff Children's Hospitals  San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaret E.","family":"Macy","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of Colorado Anschutz Medical Campus and Children's Hospital Colorado  Aurora Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rochelle","family":"Bagatell","sequence":"additional","affiliation":[{"name":"Division of Oncology, Department of Pediatrics Perelman School of Medicine, Children's Hospital of Philadelphia, University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,3,13]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pcl.2007.10.014"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2007.13.8925"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2008.16.6785"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.22693"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.30934"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.20.00203"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470\u20102045(17)30355\u20108"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.22.01273"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2024.114001"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.21.00278"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.34445"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2016.72.0177"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097\u20100142(19990715)86:2<349::AID\u2010CNCR20>3.0.CO;2\u2010Y"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.30873"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2009.27.5016"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1101\/2021.06.09.447746"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/s43018\u2010022\u201000405\u2010x"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1382931"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3899"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010023\u201038239\u20105"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers13122904"}],"container-title":["Pediatric Blood &amp; 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