Browsing by Author "Stark, Daniel"

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    Outcomes of adolescent males with extracranial metastatic germ cell tumors: A report from the Malignant Germ Cell Tumor International Consortium
    (Wiley, 2021) Shaikh, Furqan; Stark, Daniel; Fonseca, Adriana; Dang, Ha; Xia, Caihong; Krailo, Mark; Pashankar, Farzana; Rodriguez-Galindo, Carlos; Olson, Thomas A.; Nicholson, James C.; Murray, Matthew J.; Amatruda, James F.; Billmire, Deborah; Stoneham, Sara; Frazier, A. Lindsay; Pediatrics, School of Medicine
    Background: Adolescents with extracranial metastatic germ cell tumors (GCTs) are often treated with regimens developed for children, but their clinical characteristics more closely resemble those of young adult patients. This study was designed to determine event-free survival (EFS) for adolescents with GCTs and compared them with children and young adults. Methods: An individual patient database of 11 GCT trials was assembled: 8 conducted by pediatric cooperative groups and 3 conducted by an adult group. Male patients aged 0 to 30 years with metastatic, nonseminomatous, malignant GCTs of the testis, retroperitoneum, or mediastinum who were treated with platinum-based chemotherapy were included. The age groups were categorized as children (0 to <11 years), adolescents (11 to <18 years), and young adults (18 to ≤30 years). The study compared EFS and adjusted for risk group by using Cox proportional hazards analysis. Results: From a total of 2024 individual records, 593 patients met the inclusion criteria: 90 were children, 109 were adolescents, and 394 were young adults. The 5-year EFS rate was lower for adolescents (72%; 95% confidence interval [CI], 62%-79%) than children (90%; 95% CI, 81%-95%; P = .003) or young adults (88%; 95% CI, 84%-91%; P = .0002). The International Germ Cell Cancer Collaborative Group risk group was associated with EFS in the adolescent age group (P = .0020). After adjustments for risk group, the difference in EFS between adolescents and children remained significant (hazard ratio, 0.30; P = .001). Conclusions: EFS for adolescent patients with metastatic GCTs was similar to that for young adults but significantly worse than for that children. This finding highlights the importance of coordinating initiatives across clinical trial organizations to improve outcomes for adolescents and young adults. Lay summary: Adolescent males with metastatic germ cell tumors (GCTs) are frequently treated with regimens developed for children. In this study, a large data set of male patients with metastatic GCTs across different age groups has been built to understand the outcomes of adolescent patients in comparison with children and young adults. The results suggest that adolescent males with metastatic GCTs have worse results than children and are more similar to young adults with GCTs. Therefore, the treatment of adolescents with GCTs should resemble therapeutic approaches for young adults.
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    Survival and New Prognosticators in Metastatic Seminoma: Results From the IGCCCG-Update Consortium
    (American Society of Clinical Oncology, 2021) Beyer, Jörg; Collette, Laurence; Sauvé, Nicolas; Daugaard, Gedske; Feldman, Darren R.; Tandstad, Torgrim; Tryakin, Alexey; Stahl, Olof; Gonzalez-Billalabeitia, Enrique; De Giorgi, Ugo; Culine, Stéphane; de Wit, Ronald; Hansen, Aaron R.; Bebek, Marko; Terbuch, Angelika; Albany, Costantine; Hentrich, Marcus; Gietema, Jourik A.; Negaard, Helene; Huddart, Robert A.; Lorch, Anja; Cafferty, Fay H.; Heng, Daniel Y. C.; Sweeney, Christopher J.; Winquist, Eric; Chovanec, Michal; Fankhauser, Christian; Stark, Daniel; Grimison, Peter; Necchi, Andrea; Tran, Ben; Heidenreich, Axel; Shamash, Jonathan; Sternberg, Cora N.; Vaughn, David J.; Duran, Ignacio; Bokemeyer, Carsten; Patrikidou, Anna; Cathomas, Richard; Assele, Samson; Gillessen, Silke; International Germ Cell Cancer Classification Update Consortium; Medicine, School of Medicine
    Purpose: The classification of the International Germ-Cell Cancer Collaborative Group (IGCCCG) has been a major advance in the management of germ-cell tumors, but relies on data of only 660 patients with seminoma treated between 1975 and 1990. We re-evaluated this classification in a database from a large international consortium. Materials and methods: Data on 2,451 men with metastatic seminoma treated with cisplatin- and etoposide-based first-line chemotherapy between 1990 and 2013 were collected from 30 institutions or collaborative groups in Australia, Europe, and North America. Clinical trial and registry data were included. Primary end points were progression-free survival (PFS) and overall survival (OS) calculated from day 1 of treatment. Variables at initial presentation were evaluated for their prognostic impact. Results were validated in an independent validation set of 764 additional patients. Results: Compared with the initial IGCCCG classification, in our modern series, 5-year PFS improved from 82% to 89% (95% CI, 87 to 90) and 5-year OS from 86% to 95% (95% CI, 94 to 96) in good prognosis, and from 67% to 79% (95% CI, 70 to 85) and 72% to 88% (95% CI, 80 to 93) in intermediate prognosis patients. Lactate dehydrogenase (LDH) proved to be an additional adverse prognostic factor. Good prognosis patients with LDH above 2.5× upper limit of normal had a 3-year PFS of 80% (95% CI, 75 to 84) and a 3-year OS of 92% (95% CI, 88 to 95) versus 92% (95% CI, 90 to 94) and 97% (95% CI, 96 to 98) in the group with lower LDH. Conclusion: PFS and OS in metastatic seminoma significantly improved in our modern series compared with the original data. The original IGCCCG classification retains its relevance, but can be further refined by adding LDH at a cutoff of 2.5× upper limit of normal as an additional adverse prognostic factor.