{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T00:42:15Z","timestamp":1767832935170,"version":"3.49.0"},"reference-count":20,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2023,1,16]],"date-time":"2023-01-16T00:00:00Z","timestamp":1673827200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pediatric Blood &amp; Cancer"],"published-print":{"date-parts":[[2023,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background and aims<\/jats:title><jats:p>Data on the outcome and prognostic indicators in extracranial relapsed\/refractory germ cell tumors (rel\/ref\u2010GCTs) in children are limited to a few studies. This study looks at remission rates and outcomes of rel\/ref\u2010GCTs treated with conventional salvage chemotherapy (SC) regimens without stem cell rescue at a single center in the developing world.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Patients treated at our center from January 2009 to December 2018 were included. Risk at primary presentation was stratified as all completely excised teratomas and stage I gonadal tumors being low risk (LR); stage IV ovarian, stage III\u2013IV extragonadal GCTs as high risk (HR), and the remaining as intermediate risk (IR). SC regimens were: vinblastine\u2013ifosfamide\u2013cisplatin\/carboplatin <jats:italic>or<\/jats:italic> paclitaxel\u2013ifosfamide\u2013cisplatin\/carboplatin, <jats:italic>or<\/jats:italic> cisplatin\/carboplatin\u2013etoposide\u2013bleomycin. Local therapy was either surgery and\/or radiotherapy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The analyzable cohort comprised 50 patients (44 = rel\u2010GCTs; 6 = ref\u2010GCTs) with a median age of 3.8\u00a0years and male:female ratio of 1.27:1. Primary location was ovary in 16 (32%), testicular in 10 (20%), and extragonadal in the rest (48%). Local, metastatic, and combined progression was noted in 28 (56%), 14 (28%), and eight (16%) patients, respectively, at a median time of 8.5\u00a0months. At a median follow\u2010up of 60\u00a0months, the 5\u2010year event\u2010free survival (EFS) and overall survival (OS) of the entire cohort (<jats:italic>n<\/jats:italic>\u00a0=\u00a050) were 42.4% and 50.0%, respectively. In patients previously exposed to platinum analogs (<jats:italic>n<\/jats:italic>\u00a0=\u00a038), 5\u2010year\u2010EFS and OS were 27.7% and 31.7%, respectively. Local relapses did better when compared to metastatic and combined relapses (5\u2010year EFS: 64% vs. 23% vs. 0%; <jats:italic>p<\/jats:italic>\u00a0=\u00a0.009). LR and IR tumors did better compared to HR (5\u2010year EFS: 81.5% vs. 49.3% vs. 6.5%; <jats:italic>p<\/jats:italic>\u00a0=\u00a0.002). Patients with normalization of tumor markers after two cycles had a superior EFS (57.6% vs. 0%; <jats:italic>p<\/jats:italic>\u00a0&lt;\u00a0.001). Relapsed tumors fared better than primary refractory GCTs (5\u2010year EFS: 48.6% vs. 0%; <jats:italic>p<\/jats:italic>\u00a0&lt;\u00a0.001).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Primary refractory GCTs, extragonadal rel\u2010GCTs, and rel\/ref\u2010GCTs with a poor biochemical response did poorly with conventional SC and need alternative treatment strategies. The rel\/ref\u2010testicular GCTs had the best chance of salvage despite a second recurrence (5\u2010year EFS and OS: 28.60% and 42.90%, respectively).<\/jats:p><\/jats:sec>","DOI":"10.1002\/pbc.30179","type":"journal-article","created":{"date-parts":[[2023,1,16]],"date-time":"2023-01-16T11:49:38Z","timestamp":1673869778000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Outcomes of relapsed\/refractory extracranial germ cell tumors treated on conventional salvage chemotherapy without stem cell rescue: Experience from a tertiary cancer center"],"prefix":"10.1002","volume":"70","author":[{"given":"Subramaniam","family":"Ramanathan","sequence":"first","affiliation":[{"name":"Department of Paediatric Oncology, Great North Children's Hospital Royal Victoria Infirmary  Newcastle upon Tyne Tyne and Wear UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0127-7987","authenticated-orcid":false,"given":"Maya","family":"Prasad","sequence":"additional","affiliation":[{"name":"Department of Paediatric Oncology Tata Memorial hospital  Mumbai Maharashtra India"},{"name":"Homi Bhabha National Institute  Mumbai Maharashtra India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tushar","family":"Vora","sequence":"additional","affiliation":[{"name":"Department of Paediatric Oncology SickKids Hospital  Toronto Ontario Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6459-2058","authenticated-orcid":false,"given":"Cheriyalinkal Parambil","family":"Badira","sequence":"additional","affiliation":[{"name":"Department of Paediatric Oncology Tata Memorial hospital  Mumbai Maharashtra India"},{"name":"Homi Bhabha National Institute  Mumbai Maharashtra India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seema","family":"Kembhavi","sequence":"additional","affiliation":[{"name":"Department of Radiology Mackay Hospital and Health Services  Mackay Queensland Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mukta","family":"Ramadwar","sequence":"additional","affiliation":[{"name":"Homi Bhabha National Institute  Mumbai Maharashtra India"},{"name":"Department of Pathology Tata Memorial Hospital  Mumbai Maharashtra India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nehal","family":"Khanna","sequence":"additional","affiliation":[{"name":"Homi Bhabha National Institute  Mumbai Maharashtra India"},{"name":"Department of Radiation Oncology Tata Memorial Hospital  Mumbai Maharashtra India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8558-4225","authenticated-orcid":false,"given":"Siddhartha","family":"Laskar","sequence":"additional","affiliation":[{"name":"Homi Bhabha National Institute  Mumbai Maharashtra India"},{"name":"Department of Radiation Oncology Tata Memorial Hospital  Mumbai Maharashtra India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mary Ann","family":"Muckaden","sequence":"additional","affiliation":[{"name":"Homi Bhabha National Institute  Mumbai Maharashtra India"},{"name":"Department of Palliative Medicine Tata Memorial Hospital  Mumbai Maharashtra India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6770-5887","authenticated-orcid":false,"given":"Sajid","family":"Qureshi","sequence":"additional","affiliation":[{"name":"Homi Bhabha National Institute  Mumbai Maharashtra India"},{"name":"Department of Paediatric Surgery Tata Memorial Hospital  Mumbai Maharashtra India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shripad","family":"Banavali","sequence":"additional","affiliation":[{"name":"Department of Paediatric Oncology Tata Memorial hospital  Mumbai Maharashtra India"},{"name":"Homi Bhabha National Institute  Mumbai Maharashtra India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Girish","family":"Chinnaswamy","sequence":"additional","affiliation":[{"name":"Department of Paediatric Oncology Tata Memorial hospital  Mumbai Maharashtra India"},{"name":"Homi Bhabha National Institute  Mumbai Maharashtra India"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2023,1,16]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.28125"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.24730"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.27111"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjc.6602724"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(13)70271-7"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.29765"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2000.18.12.2413"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2005.19.638"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.7326\/0003\u20104819\u2010109\u20107\u2010540"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2000.18.22.3809"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2001.19.7.1951"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa067749"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2009.25.1561"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2006.09.2148"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1097\/CAD.0000000000000100"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.7150\/jca.2.374"},{"key":"e_1_2_10_18_1","unstructured":"Standard\u2010dose combination chemotherapy or high\u2010dose combination chemotherapy and stem cell transplant in treating patients with relapsed or refractory germ cell tumors.NIH US;2016. Accessed October 12 2020.https:\/\/www.cancer.gov\/about\u2010cancer\/treatment\/clinical\u2010trials\/search\/v?id=NCT02375204"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2016.69.5395"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2009.26.8128"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2014.60.5337"}],"container-title":["Pediatric Blood &amp; Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/pbc.30179","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/pbc.30179","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/pbc.30179","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,21]],"date-time":"2023-08-21T17:00:26Z","timestamp":1692637226000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/pbc.30179"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1,16]]},"references-count":20,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2023,4]]}},"alternative-id":["10.1002\/pbc.30179"],"URL":"https:\/\/doi.org\/10.1002\/pbc.30179","archive":["Portico"],"relation":{},"ISSN":["1545-5009","1545-5017"],"issn-type":[{"value":"1545-5009","type":"print"},{"value":"1545-5017","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,1,16]]},"assertion":[{"value":"2022-10-07","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-12-06","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-01-16","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e30179"}}