Clinical and Experimental Pediatrics

대한소아청소년과학회 (The Korean Pediatric Society)
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Prognostic factors in children with extracranial germ cell tumors treated with cisplatin-based chemotherapy

  • Kim, Jinsup (Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Lee, Na Hee (Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Lee, Soo Hyun (Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Yoo, Keon Hee (Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Sung, Ki Woong (Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Koo, Hong Hoe (Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Seo, Jeong-Meen (Division of Pediatric Surgery, Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Lee, Suk-Koo (Division of Pediatric Surgery, Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine)
  • 투고 : 2014.09.14
  • 심사 : 2014.11.05
  • 발행 : 2015.10.15
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Purpose: To evaluate the outcomes and prognostic factors in children with extracranial germ cell tumors (GCTs) treated at a single institution. Methods: Sixty-six children diagnosed with extracranial GCTs between 1996 and 2012 were included in the study. Primary treatment was surgical excision, followed by six cycles of cisplatin-based chemotherapy. The survival rates were compared according to the International Germ Cell Cancer Cooperative Group classification used for GCTs in adults to validate the classification guidelines for GCTs in children. Results: The median patient age was 4.4 years. In 34 patients (51.5%), the primary tumor site was the gonad. Extragonadal GCTs were detected in 32 patients. The 5-year overall survival and event-free survival (EFS) were $92.0%{\pm}3.5%$ and $90.4%{\pm}3.7%$, respectively. In univariate analysis, tumor histology, metastasis, and elevated alpha-fetoprotein were not prognostic factors in children with extracranial GCTs. However, EFS was poorer in patients with mediastinal disease (n=12, $66.7%{\pm}13.6%$) than in those with nonmediastinal disease (n=54, $96.0%{\pm}2.8%$) (P=0.001). The 5-year EFS was lower in patients older than 10 years, (n=21, $80.0%{\pm}8.9%$) compared with those younger than 10 years (n=45, $95.2%{\pm}3.3%$) (P=0.04). Multivariate analysis identified the mediastinal tumor site as the only independent prognostic factor. Conclusion: The prognosis of children with extracranial GCTs was favorable. However, nongerminomatous mediastinal tumors were associated with poor survival in children. Further research is needed to improve the prognosis of children with malignant mediastinal GCTs.

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참고문헌

  1. Decatris MP, Wilkinson PM, Welch RS, Metzner M, Morgenstern GR, Dougall M. High-dose chemotherapy and autologous haematopoietic support in poor risk non-seminomatous germ-cell tumours: an effective first-line therapy with minimal toxicity. Ann Oncol 2000;11:427-34. https://doi.org/10.1023/A:1008393512723
  2. Simonelli M, Rosti G, Banna GL, Pedrazzoli P; Italian Germ cell cancer Group (IGG); Gruppo Italiano Trapianto Midollo Osseo, Cellule Staminali Emopoietiche e Terapia Cellulare (GITMO). Intensified chemotherapy with stem-cell rescue in germ-cell tumors. Ann Oncol 2012;23:815-22. https://doi.org/10.1093/annonc/mdr403
  3. Loehrer PJ Sr, Gonin R, Nichols CR, Weathers T, Einhorn LH. Vinblastine plus ifosfamide plus cisplatin as initial salvage therapy in recurrent germ cell tumor. J Clin Oncol 1998;16:2500-4. https://doi.org/10.1200/JCO.1998.16.7.2500
  4. McCaffrey JA, Mazumdar M, Bajorin DF, Bosl GJ, Vlamis V, Motzer RJ. Ifosfamide-and cisplatin-containing chemotherapy as first-line salvage therapy in germ cell tumors: response and survival. J Clin Oncol 1997;15:2559-63. https://doi.org/10.1200/JCO.1997.15.7.2559
  5. International Germ Cell Consensus Classification: a prognostic factor-based staging system for metastatic germ cell cancers. International Germ Cell Cancer Collaborative Group. J Clin Oncol 1997;15:594-603. https://doi.org/10.1200/JCO.1997.15.2.594
  6. Bokemeyer C, Kollmannsberger C, Meisner C, Harstrick A, Beyer J, Metzner B, et al. First-line high-dose chemotherapy compared with standard-dose PEB/VIP chemotherapy in patients with advanced germ cell tumors: A multivariate and matched-pair analysis. J Clin Oncol 1999;17:3450-6. https://doi.org/10.1200/JCO.1999.17.11.3450
  7. Hartmann JT, Gauler T, Metzner B, Gerl A, Casper J, Rick O, et al. Phase I/II study of sequential dose-intensified ifosfamide, cisplatin, and etoposide plus paclitaxel as induction chemotherapy for poor prognosis germ cell tumors by the German Testicular Cancer Study Group. J Clin Oncol 2007;25:5742-7. https://doi.org/10.1200/JCO.2007.11.9099
  8. Motzer RJ, Nichols CJ, Margolin KA, Bacik J, Richardson PG, Vogelzang NJ, et al. Phase III randomized trial of conventional-dose chemotherapy with or without high-dose chemotherapy and autologous hematopoietic stem-cell rescue as first-line treatment for patients with poor-prognosis metastatic germ cell tumors. J Clin Oncol 2007;25:247-56. https://doi.org/10.1200/JCO.2005.05.4528
  9. Calaminus G, Schneider DT, Bokkerink JP, Gadner H, Harms D, Willers R, et al. Prognostic value of tumor size, metastases, extension into bone, and increased tumor marker in children with malignant sacrococcygeal germ cell tumors: a prospective evaluation of 71 patients treated in the German cooperative protocols Maligne Keimzelltumoren (MAKEI) 83/86 and MAKEI 89. J Clin Oncol 2003; 21:781-6. https://doi.org/10.1200/JCO.2003.03.125
  10. Schneider DT, Calaminus G, Reinhard H, Gutjahr P, Kremens B, Harms D, et al. Primary mediastinal germ cell tumors in children and adolescents: results of the German cooperative protocols MAKEI 83/86, 89, and 96. J Clin Oncol 2000;18:832-9. https://doi.org/10.1200/JCO.2000.18.4.832
  11. Baranzelli MC, Kramar A, Bouffet E, Quintana E, Rubie H, Edan C, et al. Prognostic factors in children with localized malignant nonseminomatous germ cell tumors. J Clin Oncol 1999;17:1212. https://doi.org/10.1200/JCO.1999.17.4.1212
  12. De Backer A, Madern GC, Pieters R, Haentjens P, Hakvoort-Cammel FG, Oosterhuis JW, et al. Influence of tumor site and histology on long-term survival in 193 children with extracranial germ cell tumors. Eur J Pediatr Surg 2008;18:1-6. https://doi.org/10.1055/s-2007-989399
  13. Marina N, London WB, Frazier AL, Lauer S, Rescorla F, Cushing B, et al. Prognostic factors in children with extragonadal malignant germ cell tumors: a pediatric intergroup study. J Clin Oncol 2006; 24:2544-8. https://doi.org/10.1200/JCO.2005.04.1251
  14. Frazier AL, Rumcheva P, Olson T, Giller R, Cushing B, Cullen J, et al. Application of the adult international germ cell classification system to pediatric malignant non-seminomatous germ cell tumors: a report from the Children's Oncology Group. Pediatr Blood Cancer 2008;50:746-51. https://doi.org/10.1002/pbc.21304
  15. Aass N, Klepp O, Cavallin-Stahl E, Dahl O, Wicklund H, Unsgaard B, et al. Prognostic factors in unselected patients with nonseminomatous metastatic testicular cancer: a multicenter experience. J Clin Oncol 1991;9:818-26. https://doi.org/10.1200/JCO.1991.9.5.818
  16. Kaye SB, Mead GM, Fossa S, Cullen M, deWit R, Bodrogi I, et al. Intensive induction-sequential chemotherapy with BOP/VIP-B compared with treatment with BEP/EP for poor-prognosis metastatic nonseminomatous germ cell tumor: a Randomized Medical Research Council/European Organization for Research and Treatment of Cancer study. J Clin Oncol 1998;16:692-701. https://doi.org/10.1200/JCO.1998.16.2.692
  17. Bajorin DF, Mazumdar M, Meyers M, Motzer RJ, Vlamis V, Lin P, et al. Metastatic germ cell tumors: modeling for response to chemotherapy. J Clin Oncol 1998;16:707-15. https://doi.org/10.1200/JCO.1998.16.2.707
  18. Lo Curto M, Lumia F, Alaggio R, Cecchetto G, Almasio P, Indolfi P, et al. Malignant germ cell tumors in childhood: results of the first Italian cooperative study "TCG 91". Med Pediatr Oncol 2003;41: 417-25. https://doi.org/10.1002/mpo.10324
  19. Bussey KJ, Lawce HJ, Olson SB, Arthur DC, Kalousek DK, Krailo M, et al. Chromosome abnormalities of eighty-one pediatric germ cell tumors: sex-, age-, site-, and histopathology-related differences: a Children's Cancer Group study. Genes Chromosomes Cancer 1999; 25:134-46. https://doi.org/10.1002/(SICI)1098-2264(199906)25:2<134::AID-GCC9>3.0.CO;2-Y
  20. Perlman EJ, Cushing B, Hawkins E, Griffin CA. Cytogenetic analysis of childhood endodermal sinus tumors: a Pediatric Oncology Group study. Pediatr Pathol 1994;14:695-708. https://doi.org/10.3109/15513819409023342
  21. Schneider DT, Schuster AE, Fritsch MK, Calaminus G, Gobel U, Harms D, et al. Genetic analysis of mediastinal nonseminomatous germ cell tumors in children and adolescents. Genes Chromosomes Cancer 2002;34:115-25. https://doi.org/10.1002/gcc.10053
  22. Zahn S, Sievers S, Alemazkour K, Orb S, Harms D, Schulz WA, et al. Imbalances of chromosome arm 1p in pediatric and adult germ cell tumors are caused by true allelic loss: a combined comparative genomic hybridization and microsatellite analysis. Genes Chromosomes Cancer 2006;45:995-1006. https://doi.org/10.1002/gcc.20363
  23. Ablin AR, Krailo MD, Ramsay NK, Malogolowkin MH, Isaacs H, Raney RB, et al. Results of treatment of malignant germ cell tumors in 93 children: a report from the Childrens Cancer Study Group. J Clin Oncol 1991;9:1782-92. https://doi.org/10.1200/JCO.1991.9.10.1782
  24. Bokemeyer C, Schleucher N, Metzner B, Thomas M, Rick O, Schmoll HJ, et al. First-line sequential high-dose VIP chemotherapy with autologous transplantation for patients with primary mediastinal nonseminomatous germ cell tumours: a prospective trial. Br J Cancer 2003;89:29-35. https://doi.org/10.1038/sj.bjc.6600999
  25. Daugaard G, Skoneczna I, Aass N, De Wit R, De Santis M, Dumez H, et al. A randomized phase III study comparing standard dose BEP with sequential high-dose cisplatin, etoposide, and ifosfamide (VIP) plus stem-cell support in males with poor-prognosis germ-cell cancer. An intergroup study of EORTC, GTCSG, and Grupo Germinal (EORTC 30974). Ann Oncol 2011;22:1054-61. https://doi.org/10.1093/annonc/mdq575

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  1. Malignant sacrococcygeal germ cell tumors in children in Taiwan : A retrospective single-center case series vol.100, pp.4, 2021, https://doi.org/10.1097/md.0000000000024323
  2. Assessment of Resectability of Mediastinal Germ Cell Tumor Using Preoperative Computed Tomography vol.272, pp.None, 2015, https://doi.org/10.1016/j.jss.2021.11.002