{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T00:47:12Z","timestamp":1778028432466,"version":"3.51.4"},"reference-count":44,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2020,5,7]],"date-time":"2020-05-07T00:00:00Z","timestamp":1588809600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>The majority of pediatric patients are cured of their primary cancer with current advanced developments in pediatric cancer therapy. However, survivors often experience long-term complications from therapies for primary cancer. The delayed mortality rate has been decreasing with the effort to reduce the therapeutic exposure of patients with pediatric cancers. Our study investigates the incidence of sarcoma as second cancer in pediatric cancer survivors. We present a 9-year-old male who survived embryonal hepatoblastoma diagnosed at 22 months of age. At 4.5 years of age, he presented with a non-metastatic primitive neuroectodermal tumor (PNET) of the left submandibular area. He has no evidence of recurrence of either cancer for 51 months after finishing all chemotherapy and radiotherapy. We used the Surveillance, Epidemiology, and End Results (SEER) database to identify the current rate of second sarcomas in pediatric cancer survivors. Our literature review and large population analysis emphasize the impact of sarcoma as a second malignancy and provide help to physicians caring for pediatric cancer survivors.<\/jats:p>","DOI":"10.3390\/medicina56050224","type":"journal-article","created":{"date-parts":[[2020,5,8]],"date-time":"2020-05-08T03:45:20Z","timestamp":1588909520000},"page":"224","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Sarcoma as Second Cancer in a Childhood Cancer Survivor: Case Report, Large Population Analysis and Literature Review"],"prefix":"10.3390","volume":"56","author":[{"given":"Thinh H.","family":"Nguyen","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Texas Tech University Health Sciences Center School of Medicine, Lubbock, TX 79430, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4068-7375","authenticated-orcid":false,"given":"Monish Ram","family":"Makena","sequence":"additional","affiliation":[{"name":"Department of Physiology, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4526-3026","authenticated-orcid":false,"given":"Siddhartha","family":"Yavvari","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, Usual"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maninder","family":"Kaur","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Texas Tech University Health Sciences Center School of Medicine, Lubbock, TX 79430, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Teresia","family":"Pham","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Texas Tech University Health Sciences Center School of Medicine, Lubbock, TX 79430, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eduardo","family":"Urias","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Texas Tech University Health Sciences Center School of Medicine, Lubbock, TX 79430, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Narendra","family":"Panapitiya","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Texas Tech University Health Sciences Center School of Medicine, Lubbock, TX 79430, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8116-0369","authenticated-orcid":false,"given":"Mohamad M.","family":"Al-Rahawan","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Texas Tech University Health Sciences Center School of Medicine, Lubbock, TX 79430, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,5,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2514","DOI":"10.1002\/cncr.28763","article-title":"Childhood Cancer Survivor Study Infections among long-term survivors of childhood and adolescent cancer: a report from the Childhood Cancer Survivor Study","volume":"120","author":"Perkins","year":"2014","journal-title":"Cancer"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1056\/NEJMoa1510795","article-title":"Reduction in Late Mortality among 5-Year Survivors of Childhood Cancer","volume":"374","author":"Armstrong","year":"2016","journal-title":"New Engl. J. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1254","DOI":"10.3346\/jkms.2016.31.8.1254","article-title":"Characteristics and Outcomes of Second Malignant Neoplasms after Childhood Cancer Treatment: Multi-Center Retrospective Survey","volume":"31","author":"Koh","year":"2016","journal-title":"J. Korean Med. Sci."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1007\/s10147-015-0927-z","article-title":"Secondary cancers after a childhood cancer diagnosis: a nationwide hospital-based retrospective cohort study in Japan","volume":"21","author":"Ishida","year":"2015","journal-title":"Int. J. Clin. Oncol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"e406","DOI":"10.1097\/MPH.0000000000000971","article-title":"Second Neoplasms in Children Following a Treatment for Acute Leukemia and\/or Lymphoma","volume":"39","author":"Felice","year":"2017","journal-title":"J. Pediatr. Hematol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1093\/jnci\/djx165","article-title":"Risk of Subsequent Bone Cancers Among 69 460 Five-Year Survivors of Childhood and Adolescent Cancer in Europe","volume":"110","author":"Fidler","year":"2017","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_7","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\u20132004","volume":"108","author":"MacCarthy","year":"2013","journal-title":"Br. J. Cancer."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"910","DOI":"10.1002\/ijc.25706","article-title":"Risk of second cancer after lymphohematopoietic neoplasm","volume":"129","author":"Royle","year":"2010","journal-title":"Int. J. Cancer"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1083","DOI":"10.1093\/jnci\/djq238","article-title":"Subsequent neoplasms in 5-year survivors of childhood cancer: the Childhood Cancer Survivor Study","volume":"102","author":"Friedman","year":"2010","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1093\/jnci\/djk052","article-title":"Secondary Sarcomas in Childhood Cancer Survivors: A Report From the Childhood Cancer Survivor Study","volume":"99","author":"Henderson","year":"2007","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2016\/5043640","article-title":"Ewing\u2019s Sarcoma as a Second Malignancy in Long-Term Survivors of Childhood Hematologic Malignancies","volume":"2016","author":"Wolpert","year":"2016","journal-title":"Sarcoma"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"618","DOI":"10.1093\/jnci\/93.8.618","article-title":"Second Malignant Neoplasms in Five-Year Survivors of Childhood Cancer: Childhood Cancer Survivor Study","volume":"93","author":"Neglia","year":"2001","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"3292","DOI":"10.1016\/j.ejca.2013.05.017","article-title":"Incidence and mortality of second sarcomas \u2013 A population-based study","volume":"49","author":"Bjerkehagen","year":"2013","journal-title":"Eur. J. Cancer"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1038\/bjc.2011.559","article-title":"Why do patients with radiation-induced sarcomas have a poor sarcoma-related survival?","volume":"106","author":"Bjerkehagen","year":"2011","journal-title":"Br. J. Cancer"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1169","DOI":"10.1016\/j.ijrobp.2005.04.008","article-title":"Radiation-induced osteosarcomas in the pediatric population","volume":"63","author":"Koshy","year":"2005","journal-title":"Int. J. Radiat. Oncol."},{"key":"ref_16","first-page":"381","article-title":"Risk of second bone sarcoma following childhood cancer: role of radiation therapy treatment","volume":"53","author":"Schwartz","year":"2014","journal-title":"Radiat. Environ. Biophys."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1016\/j.radonc.2008.12.016","article-title":"Can we reduce the incidence of second primary malignancies occurring after radiotherapy? A critical review","volume":"91","author":"Tubiana","year":"2009","journal-title":"Radiother. Oncol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1016\/j.ijrobp.2010.02.004","article-title":"Radiation Therapy and Late Mortality From Second Sarcoma, Carcinoma, and Hematological Malignancies After a Solid Cancer in Childhood","volume":"80","author":"Tukenova","year":"2011","journal-title":"Int. J. Radiat. Oncol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1026","DOI":"10.3892\/ol.2015.3257","article-title":"Secondary osteosarcoma arising from osteochondroma following autologous stem cell transplantation with total-body irradiation for neuroblastoma: A case report","volume":"10","author":"Kawashima","year":"2015","journal-title":"Oncol. Lett."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1002\/ijc.20002","article-title":"Radiation dose, chemotherapy and risk of soft tissue sarcoma after solid tumours during childhood","volume":"110","author":"Rubino","year":"2004","journal-title":"Int. J. Cancer"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1056\/NEJM198709033171002","article-title":"Bone Sarcomas Linked to Radiotherapy and Chemotherapy in Children","volume":"317","author":"Tucker","year":"1987","journal-title":"New Engl. J. Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1038\/bjc.2017.198","article-title":"Chemotherapy with radiotherapy influences time-to-development of radiation-induced sarcomas: a multicenter study","volume":"117","author":"Zhang","year":"2017","journal-title":"Br. J. Cancer"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2288","DOI":"10.1200\/JCO.2016.71.6902","article-title":"Long-Term Risk of Subsequent Malignant Neoplasms After Treatment of Childhood Cancer in the DCOG LATER Study Cohort: Role of Chemotherapy","volume":"35","author":"Teepen","year":"2017","journal-title":"J. Clin. Oncol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1139","DOI":"10.1158\/1078-0432.CCR-14-1882","article-title":"Activity of MM-398, nanoliposomal irinotecan (nal-IRI), in Ewing\u2019s family tumor xenografts is associated with high exposure of tumor to drug and high SLFN11 expression","volume":"21","author":"Kang","year":"2015","journal-title":"Clin. Cancer Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"4363","DOI":"10.1158\/0008-5472.CAN-08-3229","article-title":"Ewing sarcoma fusion protein EWSR1\/FLI1 interacts with EWSR1 leading to mitotic defects in zebrafish embryos and human cell lines","volume":"69","author":"Embree","year":"2009","journal-title":"Cancer Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"363","DOI":"10.4103\/0019-5413.69304","article-title":"Pathology of Ewing\u2019s sarcoma\/PNET: Current opinion and emerging concepts","volume":"44","author":"Desai","year":"2010","journal-title":"Indian J. Orthop."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1016\/j.acthis.2015.01.005","article-title":"Cyclin D1 is a useful marker for soft tissue Ewing\u2019s sarcoma\/peripheral Primitive Neuroectodermal Tumor in children and adolescents: A comparative immunohistochemical study with rhabdomyosarcoma","volume":"117","author":"Magro","year":"2015","journal-title":"Acta Histochem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1038\/sj.onc.1201559","article-title":"Mechanisms of p16INK4A inactivation in non small-cell lung cancers","volume":"16","author":"Gazzeri","year":"1998","journal-title":"Oncogene"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1182\/blood-2015-07-661835","article-title":"Whole-exome sequencing identifies novel MPL and JAK2 mutations in triple-negative myeloproliferative neoplasms","volume":"127","author":"Feenstra","year":"2016","journal-title":"Blood"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.eclinm.2019.10.002","article-title":"Risk of a second cancer in Canadians diagnosed with a first cancer in childhood or adolescence","volume":"16","author":"Zakaria","year":"2019","journal-title":"EClinicalMedicine"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"806","DOI":"10.1093\/jjco\/hyy102","article-title":"Secondary bone\/soft tissue sarcoma in childhood cancer survivors: a nationwide hospital-based case-series study in Japan","volume":"48","author":"Ishida","year":"2018","journal-title":"Jpn. J. Clin. Oncol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"258","DOI":"10.5694\/j.1326-5377.2010.tb03902.x","article-title":"Late mortality and second cancers in an Australian cohort of childhood cancer survivors","volume":"193","author":"Wilson","year":"2010","journal-title":"Med J. Aust."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"722","DOI":"10.1016\/j.wneu.2017.02.031","article-title":"Secondary Craniofacial Sarcomas Following Retinoblastoma: A Systematic Review","volume":"101","author":"Yamanaka","year":"2017","journal-title":"World Neurosurg."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"270","DOI":"10.3109\/08880018.2012.668748","article-title":"Osteosarcoma Following Growth Hormone Therapy in Recurrent Acute Lymphoblastic Leukemia and Rapadilino Syndrome","volume":"29","author":"Sandoval","year":"2012","journal-title":"Pediatr. Hematol. Oncol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2475","DOI":"10.1182\/blood-2016-08-735795","article-title":"Histiocytic sarcoma: secondary neoplasm or \u201ctransdifferentiation\u201d in the setting of B-acute lymphoblastic leukemia","volume":"128","author":"Thakral","year":"2016","journal-title":"Blood"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1664","DOI":"10.1002\/pbc.26067","article-title":"Osteosarcoma After Hematopoietic Stem Cell Transplantation in Children and Adolescents: Case Report and Review of the Literature","volume":"63","author":"Kebudi","year":"2016","journal-title":"Pediatr. Blood Cancer"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1016\/j.joms.2015.07.013","article-title":"Clinical Characteristics of Radiation-Induced Sarcoma of the Head and Neck: Review of 15 Cases and 323 Cases in the Literature","volume":"74","author":"Zhu","year":"2016","journal-title":"J. Oral Maxillofac. Surg."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1647","DOI":"10.1200\/JCO.18.01099","article-title":"Subsequent Breast Cancer in Female Childhood Cancer Survivors in the St Jude Lifetime Cohort Study (SJLIFE)","volume":"37","author":"Ehrhardt","year":"2019","journal-title":"J. Clin. Oncol."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Yavvari, S., Makena, Y., Sukhavasi, S., and Makena, M.R. (2019). Large Population Analysis of Secondary Cancers in Pediatric Leukemia Survivors. Children, 6.","DOI":"10.3390\/children6120130"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1002\/ajh.20012","article-title":"Second malignant neoplasms in childhood acute lymphoblastic leukemia: Primitive neuroectodermal tumor of the chest wall with germline p53 mutation as a second malignant neoplasm","volume":"76","author":"Suarez","year":"2004","journal-title":"Am. J. Hematol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1007\/BF02758571","article-title":"Primitive neuroectodermal tumor (PNET) as second malignancy after treatment of Hodgkin\u2019s disease","volume":"73","author":"Khadwal","year":"2006","journal-title":"Indian J. Pediatr."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1080\/028418602760169361","article-title":"Therapy-associated solid tumors","volume":"41","author":"Travis","year":"2002","journal-title":"Acta Oncol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1764","DOI":"10.1002\/ijc.28991","article-title":"Secondary malignancies in pediatric cancer survivors: Perspectives and review of the literature","volume":"135","author":"Choi","year":"2014","journal-title":"Int. J. Cancer"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.semradonc.2009.09.002","article-title":"Secondary malignancies across the age spectrum","volume":"20","author":"Ng","year":"2010","journal-title":"Semin. Radiat. Oncol."}],"container-title":["Medicina"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1648-9144\/56\/5\/224\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T09:26:29Z","timestamp":1760174789000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1648-9144\/56\/5\/224"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,5,7]]},"references-count":44,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2020,5]]}},"alternative-id":["medicina56050224"],"URL":"https:\/\/doi.org\/10.3390\/medicina56050224","relation":{},"ISSN":["1648-9144"],"issn-type":[{"value":"1648-9144","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,5,7]]}}}