Standard Treatment Options
Treatment Options Under Clinical Evaluation
Current Clinical Trials

Note: Some citations in the text of this section are followed by a level of evidence. The PDQ Pediatric and Adult Treatment Editorial Boards use a formal ranking system to help the reader judge the strength of evidence linked to the reported results of a therapeutic strategy. (Refer to the PDQ summary on Levels of Evidence for more information.)

Extragonadal germ cell tumors (GCT) (i.e., sacrococcygeal, mediastinal, and retroperitoneal) account for greater than 60% of pediatric GCT, whereas in adults they account for more 5% to 10% of such tumors.[1] Children with extragonadal malignant GCT, particularly those with advanced stage, have the highest risk of treatment failure for any GCT presentation.[2,3] In a study of prognostic factors in pediatric extragonadal malignant GCT, age older than 12 years was the most important prognostic factor. In a multivariate analysis, children aged 12 years or older with thoracic tumors had six times the risk of death compared with children younger than 12 years with primary tumors other than thoracic.[4] Outcome has improved remarkably, however, since the advent of platinum-based chemotherapy and the use of a multidisciplinary treatment approach.[2,5] Complete resection prior to chemotherapy may be possible in some patients without major morbidity, but for patients with locally advanced sacrococcygeal tumors, mediastinal tumors, or large pelvic tumors, tumor biopsy followed by preoperative chemotherapy can facilitate subsequent complete tumor resection and improve ultimate patient outcome.[5-8]

Sacrococcygeal GCT are the most common extragonadal tumors and represent 40% of all childhood germ cell tumors.[9] They are usually diagnosed at birth, when large external lesions predominate (usually benign or immature teratomas), or later in the first years of life, when presacral lesions with higher malignancy rates predominate.[9] Malignant sacrococcygeal tumors are usually very advanced at diagnosis; two-thirds of patients have locoregional disease and metastases are present in 50% of the patients.[7,10,11] Because of advanced presentation, the management of sacrococcygeal tumors requires a multimodal approach with chemotherapy followed by delayed tumor resection. Platinum-based therapies, with either cisplatin or carboplatin, are the cornerstone of treatment. The cisplatin, etoposide, and bleomycin (PEB) regimen or the carboplatin, etoposide, and bleomycin (JEB) regimen produces event-free survival (EFS) rates of 75% to 85%; overall survival rates of 80% to 90% can be achieved.[7,8] Surgery is usually facilitated by preoperative chemotherapy, and completeness of surgical resection is a very important prognostic factor. Patients with resected tumors with negative microscopic margins have EFS rates greater than 90%. Patients with microscopic margins have EFS rates of 75% to 85%; patients with macroscopic residual disease after surgery have EFS rates less than 40%. In any patient with a sacrococcygeal GCT, resection of the coccyx is mandatory.[7,8]

Mediastinal GCT account for 15% to 20% of malignant nongonadal, extracranial GCT in children.[5] The histology of mediastinal GCT is dependent on age, with teratomas predominating among infants and with yolk sac tumor histology predominating among children aged 1 to 4 years.[6] Children with mediastinal teratomas are treated with tumor resection, which is curative in almost all patients.[6] Children with malignant, nonmetastatic mediastinal GCT who receive cisplatin-based chemotherapy have 5-year EFS and overall survival (OS) rates of 90%, but an EFS closer to 70% occurs with metastatic mediastinal tumors.[5,6] As occurs with sacrococcygeal tumors, primary chemotherapy is usually necessary to facilitate surgical resection of mediastinal GCT, and the completeness of resection is a very important prognostic indicator.[6,12] Survival rates for the older adolescent and young adult population with mediastinal tumors are generally less than 50%.[4,13-16] Level of evidence: 3iiA (Refer to the PDQ summary on Extragonadal Germ Cell Tumor Treatment for more information.)

Malignant GCT located in the retroperitoneum or abdomen usually present in children before age 5 years; most tumors are of advanced stage and locally unresectable at diagnosis.[17] A limited biopsy followed by platinum-based chemotherapy to shrink tumor bulk can lead to complete tumor resection in most patients. Despite advanced-stage disease in most patients, the 6-year EFS using PEB was 83% in the Pediatric Oncology Group /Children's Cancer Group intergroup study.[17]

Surgery: The role for surgery at diagnosis for extragonadal tumors is age- and site-dependent and must be individualized. Depending on the clinical setting, the appropriate surgical approach may range from no surgery (e.g., mediastinal primary tumor in a patient with a compromised airway and elevated tumor markers), to biopsy, to primary resection. In some cases, an appropriate strategy is biopsy at diagnosis followed by subsequent surgery in selected patients who have residual masses following chemotherapy.

Stages I and II

• Surgery and treatment with four to six courses of standard PEB. These patients have an OS outcome greater than 90% with this regimen, suggesting that a reduction in therapy could be considered.[2,18]



• Surgery and treatment with six courses of JEB.[5]

Stages III and IV

• Surgery and treatment with four to six courses of standard PEB. These patients have an OS outcome approaching 80% with this regimen.[2]



• • Surgery and treatment with six courses of JEB yield similar OS.[5]

The following are examples of national and/or institutional clinical trials that are currently being conducted. Information about ongoing clinical trials is available from the NCI Web site.

• The Children’s Oncology Group (COG) trial, AGCT0132, is currently studying the effect of decreased chemotherapy for stages I-II extragonadal GCT (three courses of PEB over 3 days) with the goal of decreasing the duration and cumulative doses of chemotherapy (25% dose reduction) and lessening the cost of treatment. Strict guidelines for the evaluation and follow-up of the "observation" patients are mandated to ensure that disease recurrence or regrowth is detected early.



• A completed COG trial investigated the addition of cyclophosphamide to standard-dose PEB. The results of this study are pending.



• Several international pediatric trials are studying surgery and observation for stage I extragonadal GCT.

Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with childhood extragonadal germ cell tumor. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

References

1. Pantoja E, Llobet R, Gonzalez-Flores B: Retroperitoneal teratoma: historical review. J Urol 115 (5): 520-3, 1976.  [PUBMED Abstract]
   
   
2. Cushing B, Giller R, Cullen JW, et al.: Randomized comparison of combination chemotherapy with etoposide, bleomycin, and either high-dose or standard-dose cisplatin in children and adolescents with high-risk malignant germ cell tumors: a pediatric intergroup study--Pediatric Oncology Group 9049 and Children's Cancer Group 8882. J Clin Oncol 22 (13): 2691-700, 2004.  [PUBMED Abstract]
   
   
3. Baranzelli MC, Kramar A, Bouffet E, et al.: Prognostic factors in children with localized malignant nonseminomatous germ cell tumors. J Clin Oncol 17 (4): 1212, 1999.  [PUBMED Abstract]
   
   
4. Marina N, London WB, Frazier AL, et al.: Prognostic factors in children with extragonadal malignant germ cell tumors: a pediatric intergroup study. J Clin Oncol 24 (16): 2544-8, 2006.  [PUBMED Abstract]
   
   
5. Mann JR, Raafat F, Robinson K, et al.: The United Kingdom Children's Cancer Study Group's second germ cell tumor study: carboplatin, etoposide, and bleomycin are effective treatment for children with malignant extracranial germ cell tumors, with acceptable toxicity. J Clin Oncol 18 (22): 3809-18, 2000.  [PUBMED Abstract]
   
   
6. Schneider DT, Calaminus G, Reinhard H, 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 18 (4): 832-9, 2000.  [PUBMED Abstract]
   
   
7. Göbel U, Schneider DT, Calaminus G, et al.: Multimodal treatment of malignant sacrococcygeal germ cell tumors: a prospective analysis of 66 patients of the German cooperative protocols MAKEI 83/86 and 89. J Clin Oncol 19 (7): 1943-50, 2001.  [PUBMED Abstract]
   
   
8. Rescorla F, Billmire D, Stolar C, et al.: The effect of cisplatin dose and surgical resection in children with malignant germ cell tumors at the sacrococcygeal region: a pediatric intergroup trial (POG 9049/CCG 8882). J Pediatr Surg 36 (1): 12-7, 2001.  [PUBMED Abstract]
   
   
9. Altman RP, Randolph JG, Lilly JR: Sacrococcygeal teratoma: American Academy of Pediatrics Surgical Section Survey-1973. J Pediatr Surg 9 (3): 389-98, 1974.  [PUBMED Abstract]
   
   
10. Rescorla FJ, Sawin RS, Coran AG, et al.: Long-term outcome for infants and children with sacrococcygeal teratoma: a report from the Childrens Cancer Group. J Pediatr Surg 33 (2): 171-6, 1998.  [PUBMED Abstract]
    
    
11. Calaminus G, Schneider DT, Bökkerink JP, 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 21 (5): 781-6, 2003.  [PUBMED Abstract]
    
    
12. Billmire D, Vinocur C, Rescorla F, et al.: Malignant mediastinal germ cell tumors: an intergroup study. J Pediatr Surg 36 (1): 18-24, 2001.  [PUBMED Abstract]
    
    
13. Vuky J, Bains M, Bacik J, et al.: Role of postchemotherapy adjunctive surgery in the management of patients with nonseminoma arising from the mediastinum. J Clin Oncol 19 (3): 682-8, 2001.  [PUBMED Abstract]
    
    
14. Ganjoo KN, Rieger KM, Kesler KA, et al.: Results of modern therapy for patients with mediastinal nonseminomatous germ cell tumors. Cancer 88 (5): 1051-6, 2000.  [PUBMED Abstract]
    
    
15. Bokemeyer C, Nichols CR, Droz JP, et al.: Extragonadal germ cell tumors of the mediastinum and retroperitoneum: results from an international analysis. J Clin Oncol 20 (7): 1864-73, 2002.  [PUBMED Abstract]
    
    
16. Kang CH, Kim YT, Jheon SH, et al.: Surgical treatment of malignant mediastinal nonseminomatous germ cell tumor. Ann Thorac Surg 85 (2): 379-84, 2008.  [PUBMED Abstract]
    
    
17. Billmire D, Vinocur C, Rescorla F, et al.: Malignant retroperitoneal and abdominal germ cell tumors: an intergroup study. J Pediatr Surg 38 (3): 315-8; discussion 315-8, 2003.  [PUBMED Abstract]
    
    
18. Rogers PC, Olson TA, Cullen JW, et al.: Treatment of children and adolescents with stage II testicular and stages I and II ovarian malignant germ cell tumors: A Pediatric Intergroup Study--Pediatric Oncology Group 9048 and Children's Cancer Group 8891. J Clin Oncol 22 (17): 3563-9, 2004.  [PUBMED Abstract]
    
    

Back to Top

< Previous Section  |  Next Section >