{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T03:40:41Z","timestamp":1791430841638,"version":"4.3.3"},"reference-count":28,"publisher":"Oxford University Press (OUP)","issue":"9","funder":[{"name":"Intramural Research Program"},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Previous studies of hereditary retinoblastoma survivors have reported elevated mortality, particularly for sarcomas, compared with the general population. However, cause-specific mortality patterns for long-term hereditary and nonhereditary retinoblastoma survivors are poorly understood.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Among 2053 retinoblastoma patients diagnosed during 1914\u20132006 at two major US treatment centers and followed to 2016, we estimated cumulative mortality, standardized mortality ratios (SMRs), and absolute excess risks (AERs) compared with the US general population.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Most deaths occurred in 1129 hereditary retinoblastoma patients (n\u2009=\u2009518 deaths, cumulative mortality 70\u2009years after retinoblastoma\u2009=\u200975.8%, 95% CI = 69.0% to 82.6%; SMR\u2009=\u20098.5, 95% CI = 7.7 to 9.2). Of these, 267 were due to subsequent cancers (SMR\u2009=\u200927.4, 95% CI = 24.2 to 30.9; AER\u2009=\u200972.3 deaths\/10 000 person-years), for which SMRs were highest 15\u201329\u2009years after diagnosis (n\u2009=\u200969, SMR\u2009=\u200989.9, 95% CI = 70.0 to 113.8) but remained statistically significantly elevated at 60 and more years (n\u2009=\u200914, SMR\u2009=\u20096.7, 95% CI\u2009=\u20093.6 to 11.2), whereas AERs increased with time (AER&lt;15years = 38.0; AER60+years = 327.5). Increased risk of death due to cancers of pancreas, large intestines, and kidney were noted for the first time. Overall risk of subsequent cancers was greater for those treated with radiotherapy and chemotherapy compared to radiotherapy alone, although patterns varied by organ site. For 924 patients with nonhereditary retinoblastoma, we noted a modestly increased risk of death for subsequent cancers (n\u2009=\u200927, SMR\u2009=\u20091.8, 95% CI = 1.2 to 2.6) possibly due to treatment or misclassification of hereditary status. Risks of noncancer causes of death were not elevated for hereditary or nonhereditary patients.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Hereditary retinoblastoma survivors died mainly from an excess risk of subsequent cancers up to six decades later, highlighting the need to develop long-term clinical management guidelines for hereditary retinoblastoma survivors treated in the past.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/jnci\/djy227","type":"journal-article","created":{"date-parts":[[2018,12,5]],"date-time":"2018-12-05T23:15:34Z","timestamp":1544051734000},"page":"961-969","source":"Crossref","is-referenced-by-count":36,"title":["Patterns of Cause-Specific Mortality Among 2053 Survivors of Retinoblastoma, 1914\u20132016"],"prefix":"10.1093","volume":"111","author":[{"given":"Ruth A","family":"Kleinerman","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaret A","family":"Tucker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Byron S","family":"Sigel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David H","family":"Abramson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johanna M","family":"Seddon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lindsay M","family":"Morton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2019,1,30]]},"reference":[{"key":"2019091715525103400_djy227-B1","author":"Noone"},{"issue":"29","key":"2019091715525103400_djy227-B2","doi-asserted-by":"crossref","first-page":"3284","DOI":"10.1200\/JCO.2013.54.7844","article-title":"Risk of subsequent malignant neoplasms in long-term hereditary retinoblastoma survivors after chemotherapy and radiotherapy","volume":"32","author":"Wong","year":"2014","journal-title":"J Clin Oncol"},{"issue":"24","key":"2019091715525103400_djy227-B3","doi-asserted-by":"crossref","first-page":"1771","DOI":"10.1093\/jnci\/djn394","article-title":"Risk of second malignancies in survivors of retinoblastoma: more than 40 years of follow-up","volume":"100","author":"Marees","year":"2008","journal-title":"J Natl Cancer Inst"},{"issue":"12","key":"2019091715525103400_djy227-B4","doi-asserted-by":"crossref","first-page":"2455","DOI":"10.1038\/bjc.2013.228","article-title":"Second and subsequent tumours among 1927 retinoblastoma patients diagnosed in Britain 1951-2004","volume":"108","author":"MacCarthy","year":"2013","journal-title":"Br J Cancer"},{"issue":"1","key":"2019091715525103400_djy227-B5","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1002\/pbc.26193","article-title":"Incidence of second cancers after radiotherapy and systemic chemotherapy in heritable retinoblastoma survivors: a report from the German reference center","volume":"64","author":"Temming","year":"2017","journal-title":"Pediatr Blood Cancer"},{"issue":"18","key":"2019091715525103400_djy227-B6","doi-asserted-by":"crossref","first-page":"3245","DOI":"10.1016\/j.ejca.2009.05.011","article-title":"Cancer mortality in long-term survivors of retinoblastoma","volume":"45","author":"Marees","year":"2009","journal-title":"Eur J Cancer"},{"key":"2019091715525103400_djy227-B7","doi-asserted-by":"crossref","first-page":"i4351.","DOI":"10.1136\/bmj.i4351","article-title":"Long term cause specific mortality among 34 489 five year survivors of childhood cancer in Great Britain: population based cohort study","volume":"354","author":"Fidler","year":"2016","journal-title":"BMJ"},{"issue":"38","key":"2019091715525103400_djy227-B8","doi-asserted-by":"crossref","first-page":"5350","DOI":"10.1038\/sj.onc.1209786","article-title":"Mortality from second tumour among long-term survivors of retinoblastoma: a retrospective analysis of the Italian retinoblastoma registry","volume":"25","author":"Acquaviva","year":"2006","journal-title":"Oncogene"},{"issue":"26","key":"2019091715525103400_djy227-B9","doi-asserted-by":"crossref","first-page":"3183","DOI":"10.1200\/JCO.2015.65.4012","article-title":"How eye-preserving therapy affects long-term overall survival in heritable retinoblastoma survivors","volume":"34","author":"Temming","year":"2016","journal-title":"J Clin Oncol"},{"issue":"8","key":"2019091715525103400_djy227-B10","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1093\/jnci\/djp046","article-title":"Cause-specific mortality in long-term survivors of retinoblastoma","volume":"101","author":"Yu","year":"2009","journal-title":"J Natl Cancer Inst"},{"issue":"11","key":"2019091715525103400_djy227-B11","doi-asserted-by":"crossref","first-page":"1341","DOI":"10.1001\/jamaophthalmol.2015.3108","article-title":"Treatment of retinoblastoma in 2015: agreement and disagreement","volume":"133","author":"Abramson","year":"2015","journal-title":"JAMA Ophthalmol"},{"issue":"10","key":"2019091715525103400_djy227-B12","doi-asserted-by":"crossref","first-page":"2272","DOI":"10.1200\/JCO.2005.05.054","article-title":"Risk of new cancers after radiotherapy in long-term survivors of retinoblastoma: an extended follow-up","volume":"23","author":"Kleinerman","year":"2005","journal-title":"J Clin Oncol"},{"issue":"6","key":"2019091715525103400_djy227-B13","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1002\/(SICI)1097-0258(19990330)18:6<695::AID-SIM60>3.0.CO;2-O","article-title":"Estimation of failure probabilities in the presence of competing risks: new representations of old estimators","volume":"18","author":"Gooley","year":"1999","journal-title":"Stat Med"},{"issue":"3","key":"2019091715525103400_djy227-B14","article-title":"United States life tables 2000","volume":"51","author":"Arias","year":"2002","journal-title":"Natl Vital Stat Rep"},{"issue":"22","key":"2019091715525103400_djy227-B15","doi-asserted-by":"crossref","first-page":"2311","DOI":"10.1001\/jama.2011.747","article-title":"Long-term risks of subsequent primary neoplasms among survivors of childhood cancer","volume":"305","author":"Reulen","year":"2011","journal-title":"JAMA"},{"issue":"10","key":"2019091715525103400_djy227-B16","doi-asserted-by":"crossref","first-page":"2623","DOI":"10.1038\/bjc.2014.193","article-title":"Breast cancer risk after radiotherapy for heritable and non-heritable retinoblastoma: a US-UK study","volume":"110","author":"Little","year":"2014","journal-title":"Br J Cancer"},{"issue":"1","key":"2019091715525103400_djy227-B17","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1002\/pbc.24714","article-title":"Subsequent malignancies and their effect on survival in patients with retinoblastoma","volume":"61","author":"Shinohara","year":"2014","journal-title":"Pediatr Blood Cancer"},{"issue":"2","key":"2019091715525103400_djy227-B18","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1136\/bjophthalmol-2017-310328","article-title":"Second primary malignancies in retinoblastoma patients treated with intra-arterial chemotherapy: the first 10 years","volume":"102","author":"Habib","year":"2018","journal-title":"Br J Ophthalmol"},{"issue":"1","key":"2019091715525103400_djy227-B19","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1093\/jnci\/djk002","article-title":"Risk of soft tissue sarcomas by individual subtype in survivors of hereditary retinoblastoma","volume":"99","author":"Kleinerman","year":"2007","journal-title":"J Natl Cancer Inst"},{"issue":"2","key":"2019091715525103400_djy227-B20","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1016\/j.ygyno.2011.10.019","article-title":"Increased risk of secondary uterine leiomyosarcoma in hereditary retinoblastoma","volume":"124","author":"Francis","year":"2012","journal-title":"Gynecol Oncol"},{"issue":"15","key":"2019091715525103400_djy227-B21","doi-asserted-by":"crossref","first-page":"1262","DOI":"10.1001\/jama.1997.03550150066037","article-title":"Cancer incidence after retinoblastoma. Radiation dose and sarcoma risk","volume":"278","author":"Wong","year":"1997","journal-title":". JAMA"},{"issue":"9","key":"2019091715525103400_djy227-B22","doi-asserted-by":"crossref","first-page":"950","DOI":"10.1200\/JCO.2011.37.0239","article-title":"Variation of second cancer risk by family history of retinoblastoma among long-term survivors","volume":"30","author":"Kleinerman","year":"2012","journal-title":"J Clin Oncol"},{"key":"2019091715525103400_djy227-B23","doi-asserted-by":"crossref","first-page":"6744","DOI":"10.1038\/ncomms7744","article-title":"Whole-exome sequencing of pancreatic cancer defines genetic diversity and therapeutic targets","volume":"6","author":"Witkiewicz","year":"2015","journal-title":"Nat Commun"},{"key":"2019091715525103400_djy227-B24","doi-asserted-by":"crossref","DOI":"10.1016\/j.jid.2018.01.021","article-title":"Risks of melanoma and other cancers in melanoma-prone families over 4 decades","author":"Tucker","year":"2018","journal-title":"J Invest Dermatol"},{"issue":"7484","key":"2019091715525103400_djy227-B25","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1038\/nature12912","article-title":"Discovery and saturation analysis of cancer genes across 21 tumour types","volume":"505","author":"Lawrence","year":"2014","journal-title":"Nature"},{"issue":"21","key":"2019091715525103400_djy227-B26","doi-asserted-by":"crossref","first-page":"1528","DOI":"10.1093\/jnci\/djj411","article-title":"New primary neoplasms of the central nervous system in survivors of childhood cancer: a report from the Childhood Cancer Survivor Study","volume":"98","author":"Neglia","year":"2006","journal-title":"J Natl Cancer Inst"},{"issue":"8","key":"2019091715525103400_djy227-B27","doi-asserted-by":"crossref","first-page":"1464","DOI":"10.1158\/1055-9965.EPI-05-0783","article-title":"Tobacco use in adult long-term survivors of retinoblastoma","volume":"15","author":"Foster","year":"2006","journal-title":"Cancer Epidemiol Biomarkers Prev"},{"issue":"24","key":"2019091715525103400_djy227-B28","doi-asserted-by":"crossref","first-page":"2037","DOI":"10.1093\/jnci\/92.24.2037","article-title":"Hereditary retinoblastoma and risk of lung cancer","volume":"92","author":"Kleinerman","year":"2000","journal-title":"J Natl Cancer Inst"}],"container-title":["JNCI: Journal of the National Cancer Institute"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/jnci\/article-pdf\/111\/9\/961\/30011714\/djy227.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,9,17]],"date-time":"2019-09-17T15:59:47Z","timestamp":1568735987000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jnci\/article\/111\/9\/961\/5304459"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,1,30]]},"references-count":28,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2019,1,30]]},"published-print":{"date-parts":[[2019,9,1]]}},"URL":"https:\/\/doi.org\/10.1093\/jnci\/djy227","relation":{},"ISSN":["0027-8874","1460-2105"],"issn-type":[{"value":"0027-8874","type":"print"},{"value":"1460-2105","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2019,9]]},"published":{"date-parts":[[2019,1,30]]}}}