Childhood Extracranial Germ Cell Tumors Treatment (PDQ®)–Health Professional Version
- General Information About Childhood Extracranial Germ Cell Tumors (GCTs)
- Stage Information for Childhood Extracranial GCTs
- Treatment Option Overview for Childhood Extracranial GCTs
- Treatment of Mature and Immature Teratomas in Children
- Treatment of Malignant Gonadal GCTs in Children
- Treatment of Malignant Extragonadal Extracranial GCTs in Children
- Treatment of Recurrent Malignant GCTs in Children
- Changes to This Summary (08/11/2016)
- About This PDQ Summary
- View All Sections
General Information About Childhood Extracranial Germ Cell Tumors (GCTs)
Cancer in children and adolescents is rare, although the overall incidence of childhood cancer has slowly increased since 1975. Children and adolescents with cancer should be referred to medical centers that have a multidisciplinary team of cancer specialists with experience treating the cancers that occur during childhood and adolescence. This multidisciplinary team approach incorporates the skills of the following health care professionals and others to ensure that children receive treatment, supportive care, and rehabilitation that will achieve optimal survival and quality of life:
- Primary care physicians.
- Pediatric surgeons.
- Radiation oncologists.
- Pediatric medical oncologists and hematologists.
- Rehabilitation specialists.
- Pediatric nurse specialists.
- Social workers.
- Child life professionals.
Guidelines for pediatric cancer centers and their role in the treatment of pediatric patients with cancer have been outlined by the American Academy of Pediatrics. At these pediatric cancer centers, clinical trials are available for most of the cancer types that occur in children and adolescents, and the opportunity to participate in these trials is offered to most patients and families. Clinical trials for children and adolescents with cancer are generally designed to compare potentially better therapy with therapy that is currently accepted as standard. Most of the progress made in identifying curative therapies for childhood cancers has been achieved through clinical trials. Information about ongoing clinical trials is available from the NCI website.
Dramatic improvements in survival have been achieved for children and adolescents with cancer. Between 1975 and 2010, childhood cancer mortality decreased by more than 50%. During the period from 2002 to 2010, cancer mortality continued to decrease by 2.4% per year for children and adolescents with acute lymphoblastic leukemia, acute myeloid leukemia, Hodgkin and non-Hodgkin lymphoma, neuroblastoma, central nervous system tumors, and gonadal tumors, as compared with the period from 1975 to 1998 (plateauing from 1998 to 2001). Childhood and adolescent cancer survivors require close monitoring because late effects of cancer therapy may persist or develop months or years after treatment. (Refer to the PDQ summary on Late Effects of Treatment for Childhood Cancer for specific information about the incidence, type, and monitoring of late effects in childhood and adolescent cancer survivors.)
GCTs arise from primordial germ cells, which migrate during embryogenesis from the yolk sac through the mesentery to the gonads.[4,5] Childhood extracranial GCTs can be divided into the following two types:
Most childhood extragonadal GCTs arise in midline sites (i.e., sacrococcygeal, mediastinal, and retroperitoneal); the midline location may represent aberrant embryonic migration of the primordial germ cells.
Childhood extracranial GCTs are broadly classified as the following:
- Mature teratomas.
- Immature teratomas.
- Malignant GCTs.
GCTs comprise a variety of histologic diagnoses and can also be divided into the following histologic types:
- Dysgerminoma (ovary).
- Seminoma (testis).
- Teratoma (mature and immature).
- Yolk sac tumor (endodermal sinus tumor).
- Embryonal carcinoma.
- Mixed GCT (contains more than one of the histologies above).
(Refer to the PDQ summary on Childhood Central Nervous System Germ Cell Tumors Treatment for information about the treatment of intracranial germ cell tumors.)
Childhood GCTs are rare in children younger than 15 years, accounting for approximately 3% of cancers in this age group.[6-9] In the fetal/neonatal age group, most extracranial GCTs are benign teratomas occurring at midline locations, including sacrococcygeal, retroperitoneal, mediastinal, and cervical regions. Despite the small percentage of malignant teratomas that occur in this age group, perinatal tumors have a high morbidity rate caused by hydrops fetalis and premature delivery.[10,11]
Extracranial GCTs (particularly testicular GCTs) are much more common among adolescents aged 15 to 19 years, representing approximately 14% of cancers in this age group.
The incidence of extracranial GCTs by 5-year age group and gender is shown in Table 1.
Histologic Classification of Childhood Extracranial GCTs
Childhood extracranial GCTs comprise a variety of histologic diagnoses and can be broadly classified as the following:
The histologic properties of these tumors are heterogeneous and vary by primary tumor site and the gender and age of the patient.[12,13] Histologically identical GCTs that arise in younger children have different biological characteristics from those that arise in adolescents and young adults.
Mature teratomas usually occur in the ovary or at extragonadal locations. They are the most common histological subtype of childhood GCT.[15-17] Mature teratomas usually contain well-differentiated tissues from the ectodermal, mesodermal, and endodermal germ cell layers, and any tissue type may be found within the tumor.
Immature teratomas contain tissues from the ectodermal, mesodermal, and endodermal germ cell layers, but immature tissues, primarily neuroepithelial, are also present. Immature teratomas are graded from 0 to 3 on the basis of the amount of immature neural tissue found in the tumor specimen. Tumors of higher grade are more likely to have foci of yolk sac tumor. Immature teratomas may be classified as malignant tumors.
GCTs contain frankly malignant tissues of germ cell origin and, rarely, tissues of somatic origin. Isolated malignant elements may constitute a small fraction of a predominantly mature or immature teratoma.[22,24]
Malignant germ cell elements of children, adolescents, and young adults can be grouped broadly by location (refer to Tables 2 and 3).
Adolescent and young adult males present with more germinomas (testicular and mediastinal seminomas), and females present with more ovarian dysgerminomas.
Pediatric GCT Biology
The following biologically distinct subtypes of GCTs are found in children and adolescents:
It should be emphasized that very few pediatric GCT specimens have been analyzed to date. Biologic distinctions between GCTs in children and GCTs in adults may not be absolute, and biologic factors have not been shown to predict risk.[26-28]
- Children: During early childhood, both testicular teratomas and malignant testicular GCTs are identified. The malignant tumors are commonly composed of pure yolk sac tumor (also known as endodermal sinus tumor), are generally diploid or tetraploid, and often lack the isochromosome of the short arm of chromosome 12 that characterizes testicular cancer in young adults.[26,29-33] Deletions of chromosomes 1p, 4q, and 6q and gains of chromosomes 1q, 3, and 20q are reported as recurring chromosomal abnormalities for this group of tumors.[31-34]
- Adolescents and young adults: Testicular GCTs typically possess an isochromosome of the short arm of chromosome 12 [35-38] and are aneuploid.[29,38] Although adolescent testicular germ cell patients may be best treated at pediatric oncology centers, the treatment for adolescents older than 14 years follows the regimens used in adults. (Refer to the PDQ summary on Testicular Cancer Treatment for more information.)
Ovarian GCTs occur primarily in adolescent and young adult females. While most ovarian GCTs are benign mature teratomas, a heterogeneous group of malignant GCTs, including immature teratomas, dysgerminomas, yolk sac tumors, and mixed GCTs, do occur in females. The malignant ovarian GCT commonly shows increased copies of the short arm of chromosome 12.
Patients with pediatric ovarian GCTs have an excellent prognosis. One series of 66 patients monitored for more than 44 years reported recurrence rates of 4.5% and mortality rates of 3%.
(Refer to the PDQ summary on Ovarian Germ Cell Tumors Treatment for more information.)
Extragonadal extracranial GCTs
Extragonadal extracranial GCTs occur outside of the brain and gonads.
- Children: These tumors typically present at birth or during early childhood. Most of these tumors are benign teratomas occurring in the sacrococcygeal region, and thus are not included in Surveillance, Epidemiology, and End Results (SEER) data.[41,42] Malignant yolk sac tumor histology occurs in a minority of these tumors; however, they may have cytogenetic abnormalities similar to those observed for tumors occurring in the testes of young males.[30-32,34]
- Older children, adolescents, and young adults: The mediastinum is the most common primary site for extragonadal GCTs in older children and adolescents. Mediastinal GCTs in children younger than 8 years share the same genetic gains and losses as sacrococcygeal and testicular tumors in young children.[43-45] The gain in chromosome 12p has been reported in mediastinal tumors in children aged 8 years and older.[45,46]
There are few data about the potential genetic or environmental factors associated with childhood extragonadal extracranial GCTs. Patients with the following syndromes are at an increased risk of extragonadal extracranial GCTs:
Childhood extracranial GCTs develop at diffuse sites that include the testicles, ovaries, mediastinum, retroperitoneum, sacrum, and coccyx. The clinical features at presentation are specific for each site.
Diagnostic and Staging Evaluation
Diagnostic evaluation of GCTs includes imaging studies and measurement of tumor markers. In suspected cases, tumor markers can suggest the diagnosis before surgery and/or biopsy. This information can be used by the multidisciplinary team to make appropriate treatment choices.
Yolk sac tumors produce alpha-fetoprotein (AFP), while germinomas (seminomas and dysgerminomas), and especially choriocarcinomas, produce beta-human chorionic gonadotropin (beta-hCG), resulting in elevated serum levels of these substances. Most children with malignant GCTs will have a component of yolk sac tumor and have elevations of AFP levels,[54,55] which are serially monitored during treatment to help assess response to therapy.[22,24,54] Benign teratomas and immature teratomas may produce small elevations of AFP and beta-hCG.
During the first year of life, infants have a wide range of serum AFP levels, which are not associated with the presence of a GCT. Normal ranges have been described but are based on limited data.[56,57] The serum half-life of AFP is 5 to 7 days, and the serum half-life of beta-hCG is 1 to 2 days. Even though the data are limited, tumor markers are measured with each cycle of chemotherapy for all pediatric patients with malignant GCTs. It should be recognized that after initial chemotherapy, tumor markers may show a transient elevation.
Although few pediatric data exist, adult studies have shown that an unsatisfactory decline of elevated tumor markers is a poor prognostic finding.
Imaging tests may include the following:
- Computed tomography (CT) scan of the primary site and chest.
- Magnetic resonance imaging (MRI) of the primary site.
- Radionuclide bone scan or positron emission tomography scan (for postpubertal males).
Prognosis and Prognostic Factors
Prognosis and prognostic factors for extracranial GCTs depend on many circumstances, including the following:
- Histology (e.g., seminomatous vs. nonseminomatous).
- Age (e.g., young children vs. adolescents).
- Stage of disease.
- Primary site of disease.
- Tumor marker decline (AFP and beta-hCG) in response to therapy.
To better identify prognostic factors, data from five U.S. trials and two U.K. trials for malignant extracranial GCTs in children and adolescents were merged by the Malignant Germ Cell Tumor International Collaborative (MaGIC). The goal was to ascertain the important prognostic factors in 519 young patients, incorporating age at diagnosis, stage, and site of primary tumor, along with pretreatment AFP level and histology. Of these, patients aged 11 years and older with stage III or stage IV extragonadal disease or ovarian stage IV disease had a less than 70% likelihood of long-term disease-free survival, ranging from 40% (extragonadal stage IV) to 67% (ovarian stage IV). AFP levels and histologies other than pure yolk sac were also negative factors, but did not achieve statistical significance at the 0.05 level.[Level of evidence: 3iiiDii] This is the first age-focused investigation of these factors in young children and adolescents.
(Refer to the Treatment of Mature and Immature Teratomas in Children, Treatment of Malignant Gonadal GCTs in Children, and Treatment of Malignant Extragonadal Extracranial GCTs in Children sections of this summary for more information about prognosis and prognostic factors for childhood extragonadal extracranial GCTs.)
Follow-up After Treatment
There is little evidence to provide guidance on the follow-up care of children with extracranial GCTs.
The following tests and procedures may be performed at the physician's discretion when tumor markers are elevated at diagnosis:
- AFP and beta-hCG. Monitor AFP and beta-hCG levels monthly for 6 months (period of highest risk) and then every 3 months, for a total of 2 years (3 years for sacrococcygeal teratoma).
- Imaging tests. MRI/CT may be performed at the completion of therapy. Further imaging intervals have not been defined.
The following tests and procedures may be performed at the physician's discretion when tumor markers are normal at diagnosis:
- Imaging tests. Ultrasound or CT/MRI may be performed every 3 months for 2 years and then annually for 5 years for germinomas.
- Smith MA, Seibel NL, Altekruse SF, et al.: Outcomes for children and adolescents with cancer: challenges for the twenty-first century. J Clin Oncol 28 (15): 2625-34, 2010. [PUBMED Abstract]
- Corrigan JJ, Feig SA; American Academy of Pediatrics: Guidelines for pediatric cancer centers. Pediatrics 113 (6): 1833-5, 2004. [PUBMED Abstract]
- Smith MA, Altekruse SF, Adamson PC, et al.: Declining childhood and adolescent cancer mortality. Cancer 120 (16): 2497-506, 2014. [PUBMED Abstract]
- Dehner LP: Gonadal and extragonadal germ cell neoplasia of childhood. Hum Pathol 14 (6): 493-511, 1983. [PUBMED Abstract]
- McIntyre A, Gilbert D, Goddard N, et al.: Genes, chromosomes and the development of testicular germ cell tumors of adolescents and adults. Genes Chromosomes Cancer 47 (7): 547-57, 2008. [PUBMED Abstract]
- Miller RW, Young JL Jr, Novakovic B: Childhood cancer. Cancer 75 (1 Suppl): 395-405, 1995. [PUBMED Abstract]
- Ries LA, Smith MA, Gurney JG, et al., eds.: Cancer incidence and survival among children and adolescents: United States SEER Program 1975-1995. Bethesda, Md: National Cancer Institute, SEER Program, 1999. NIH Pub.No. 99-4649. Also available online. Last accessed March 07, 2016.
- Poynter JN, Amatruda JF, Ross JA: Trends in incidence and survival of pediatric and adolescent patients with germ cell tumors in the United States, 1975 to 2006. Cancer 116 (20): 4882-91, 2010. [PUBMED Abstract]
- Kaatsch P, Häfner C, Calaminus G, et al.: Pediatric germ cell tumors from 1987 to 2011: incidence rates, time trends, and survival. Pediatrics 135 (1): e136-43, 2015. [PUBMED Abstract]
- Isaacs H Jr: Perinatal (fetal and neonatal) germ cell tumors. J Pediatr Surg 39 (7): 1003-13, 2004. [PUBMED Abstract]
- Heerema-McKenney A, Harrison MR, Bratton B, et al.: Congenital teratoma: a clinicopathologic study of 22 fetal and neonatal tumors. Am J Surg Pathol 29 (1): 29-38, 2005. [PUBMED Abstract]
- Hawkins EP: Germ cell tumors. Am J Clin Pathol 109 (4 Suppl 1): S82-8, 1998. [PUBMED Abstract]
- Schneider DT, Calaminus G, Koch S, et al.: Epidemiologic analysis of 1,442 children and adolescents registered in the German germ cell tumor protocols. Pediatr Blood Cancer 42 (2): 169-75, 2004. [PUBMED Abstract]
- Horton Z, Schlatter M, Schultz S: Pediatric germ cell tumors. Surg Oncol 16 (3): 205-13, 2007. [PUBMED Abstract]
- Göbel U, Calaminus G, Engert J, et al.: Teratomas in infancy and childhood. Med Pediatr Oncol 31 (1): 8-15, 1998. [PUBMED Abstract]
- Rescorla FJ: Pediatric germ cell tumors. Semin Surg Oncol 16 (2): 144-58, 1999. [PUBMED Abstract]
- Harms D, Zahn S, Göbel U, et al.: Pathology and molecular biology of teratomas in childhood and adolescence. Klin Padiatr 218 (6): 296-302, 2006 Nov-Dec. [PUBMED Abstract]
- Tomlinson MW, Alaverdian AA, Alaverdian V: Testosterone-producing benign cystic teratoma with virilism. A case report. J Reprod Med 41 (12): 924-6, 1996. [PUBMED Abstract]
- Kallis P, Treasure T, Holmes SJ, et al.: Exocrine pancreatic function in mediastinal teratomata: an aid to preoperative diagnosis? Ann Thorac Surg 54 (4): 741-3, 1992. [PUBMED Abstract]
- Norris HJ, Zirkin HJ, Benson WL: Immature (malignant) teratoma of the ovary: a clinical and pathologic study of 58 cases. Cancer 37 (5): 2359-72, 1976. [PUBMED Abstract]
- Heifetz SA, Cushing B, Giller R, et al.: Immature teratomas in children: pathologic considerations: a report from the combined Pediatric Oncology Group/Children's Cancer Group. Am J Surg Pathol 22 (9): 1115-24, 1998. [PUBMED Abstract]
- Marina NM, Cushing B, Giller R, et al.: Complete surgical excision is effective treatment for children with immature teratomas with or without malignant elements: A Pediatric Oncology Group/Children's Cancer Group Intergroup Study. J Clin Oncol 17 (7): 2137-43, 1999. [PUBMED Abstract]
- Lam SK, Cheung LP: Inappropriate ADH secretion due to immature ovarian teratoma. Aust N Z J Obstet Gynaecol 36 (1): 104-5, 1996. [PUBMED Abstract]
- Göbel U, Calaminus G, Schneider DT, et al.: The malignant potential of teratomas in infancy and childhood: the MAKEI experiences in non-testicular teratoma and implications for a new protocol. Klin Padiatr 218 (6): 309-14, 2006 Nov-Dec. [PUBMED Abstract]
- Perlman EJ, Hawkins EP: Pediatric germ cell tumors: protocol update for pathologists. Pediatr Dev Pathol 1 (4): 328-35, 1998 Jul-Aug. [PUBMED Abstract]
- Palmer RD, Foster NA, Vowler SL, et al.: Malignant germ cell tumours of childhood: new associations of genomic imbalance. Br J Cancer 96 (4): 667-76, 2007. [PUBMED Abstract]
- Palmer RD, Barbosa-Morais NL, Gooding EL, et al.: Pediatric malignant germ cell tumors show characteristic transcriptome profiles. Cancer Res 68 (11): 4239-47, 2008. [PUBMED Abstract]
- Poynter JN, Hooten AJ, Frazier AL, et al.: Associations between variants in KITLG, SPRY4, BAK1, and DMRT1 and pediatric germ cell tumors. Genes Chromosomes Cancer 51 (3): 266-71, 2012. [PUBMED Abstract]
- Oosterhuis JW, Castedo SM, de Jong B, et al.: Ploidy of primary germ cell tumors of the testis. Pathogenetic and clinical relevance. Lab Invest 60 (1): 14-21, 1989. [PUBMED Abstract]
- Silver SA, Wiley JM, Perlman EJ: DNA ploidy analysis of pediatric germ cell tumors. Mod Pathol 7 (9): 951-6, 1994. [PUBMED Abstract]
- Perlman EJ, Cushing B, Hawkins E, et al.: Cytogenetic analysis of childhood endodermal sinus tumors: a Pediatric Oncology Group study. Pediatr Pathol 14 (4): 695-708, 1994 Jul-Aug. [PUBMED Abstract]
- Schneider DT, Schuster AE, Fritsch MK, et al.: Genetic analysis of childhood germ cell tumors with comparative genomic hybridization. Klin Padiatr 213 (4): 204-11, 2001 Jul-Aug. [PUBMED Abstract]
- Bussey KJ, Lawce HJ, Olson SB, 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 25 (2): 134-46, 1999. [PUBMED Abstract]
- Perlman EJ, Valentine MB, Griffin CA, et al.: Deletion of 1p36 in childhood endodermal sinus tumors by two-color fluorescence in situ hybridization: a pediatric oncology group study. Genes Chromosomes Cancer 16 (1): 15-20, 1996. [PUBMED Abstract]
- Rodriguez E, Houldsworth J, Reuter VE, et al.: Molecular cytogenetic analysis of i(12p)-negative human male germ cell tumors. Genes Chromosomes Cancer 8 (4): 230-6, 1993. [PUBMED Abstract]
- Bosl GJ, Ilson DH, Rodriguez E, et al.: Clinical relevance of the i(12p) marker chromosome in germ cell tumors. J Natl Cancer Inst 86 (5): 349-55, 1994. [PUBMED Abstract]
- Mostert MC, Verkerk AJ, van de Pol M, et al.: Identification of the critical region of 12p over-representation in testicular germ cell tumors of adolescents and adults. Oncogene 16 (20): 2617-27, 1998. [PUBMED Abstract]
- van Echten J, Oosterhuis JW, Looijenga LH, et al.: No recurrent structural abnormalities apart from i(12p) in primary germ cell tumors of the adult testis. Genes Chromosomes Cancer 14 (2): 133-44, 1995. [PUBMED Abstract]
- Riopel MA, Spellerberg A, Griffin CA, et al.: Genetic analysis of ovarian germ cell tumors by comparative genomic hybridization. Cancer Res 58 (14): 3105-10, 1998. [PUBMED Abstract]
- De Backer A, Madern GC, Oosterhuis JW, et al.: Ovarian germ cell tumors in children: a clinical study of 66 patients. Pediatr Blood Cancer 46 (4): 459-64, 2006. [PUBMED Abstract]
- Malogolowkin MH, Mahour GH, Krailo M, et al.: Germ cell tumors in infancy and childhood: a 45-year experience. Pediatr Pathol 10 (1-2): 231-41, 1990. [PUBMED Abstract]
- Marsden HB, Birch JM, Swindell R: Germ cell tumours of childhood: a review of 137 cases. J Clin Pathol 34 (8): 879-83, 1981. [PUBMED Abstract]
- Dal Cin P, Drochmans A, Moerman P, et al.: Isochromosome 12p in mediastinal germ cell tumor. Cancer Genet Cytogenet 42 (2): 243-51, 1989. [PUBMED Abstract]
- Aly MS, Dal Cin P, Jiskoot P, et al.: Competitive in situ hybridization in a mediastinal germ cell tumor. Cancer Genet Cytogenet 73 (1): 53-6, 1994. [PUBMED Abstract]
- Schneider DT, Schuster AE, Fritsch MK, et al.: Genetic analysis of mediastinal nonseminomatous germ cell tumors in children and adolescents. Genes Chromosomes Cancer 34 (1): 115-25, 2002. [PUBMED Abstract]
- McKenney JK, Heerema-McKenney A, Rouse RV: Extragonadal germ cell tumors: a review with emphasis on pathologic features, clinical prognostic variables, and differential diagnostic considerations. Adv Anat Pathol 14 (2): 69-92, 2007. [PUBMED Abstract]
- Dexeus FH, Logothetis CJ, Chong C, et al.: Genetic abnormalities in men with germ cell tumors. J Urol 140 (1): 80-4, 1988. [PUBMED Abstract]
- Nichols CR, Heerema NA, Palmer C, et al.: Klinefelter's syndrome associated with mediastinal germ cell neoplasms. J Clin Oncol 5 (8): 1290-4, 1987. [PUBMED Abstract]
- Lachman MF, Kim K, Koo BC: Mediastinal teratoma associated with Klinefelter's syndrome. Arch Pathol Lab Med 110 (11): 1067-71, 1986. [PUBMED Abstract]
- Coutin AS, Hamy A, Fondevilla M, et al.: [Pure 46XY gonadal dysgenesis] J Gynecol Obstet Biol Reprod (Paris) 25 (8): 792-6, 1996. [PUBMED Abstract]
- Amice V, Amice J, Bercovici JP, et al.: Gonadal tumor and H-Y antigen in 46,XY pure gonadal dysgenesis. Cancer 57 (7): 1313-7, 1986. [PUBMED Abstract]
- Tanaka Y, Sasaki Y, Tachibana K, et al.: Gonadal mixed germ cell tumor combined with a large hemangiomatous lesion in a patient with Turner's syndrome and 45,X/46,X, +mar karyotype. Arch Pathol Lab Med 118 (11): 1135-8, 1994. [PUBMED Abstract]
- Kota SK, Gayatri K, Pani JP, et al.: Dysgerminoma in a female with turner syndrome and Y chromosome material: A case-based review of literature. Indian J Endocrinol Metab 16 (3): 436-40, 2012. [PUBMED Abstract]
- 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]
- Marina N, Fontanesi J, Kun L, et al.: Treatment of childhood germ cell tumors. Review of the St. Jude experience from 1979 to 1988. Cancer 70 (10): 2568-75, 1992. [PUBMED Abstract]
- Wu JT, Book L, Sudar K: Serum alpha fetoprotein (AFP) levels in normal infants. Pediatr Res 15 (1): 50-2, 1981. [PUBMED Abstract]
- Blohm ME, Vesterling-Hörner D, Calaminus G, et al.: Alpha 1-fetoprotein (AFP) reference values in infants up to 2 years of age. Pediatr Hematol Oncol 15 (2): 135-42, 1998 Mar-Apr. [PUBMED Abstract]
- Vogelzang NJ, Lange PH, Goldman A, et al.: Acute changes of alpha-fetoprotein and human chorionic gonadotropin during induction chemotherapy of germ cell tumors. Cancer Res 42 (11): 4855-61, 1982. [PUBMED Abstract]
- Motzer RJ, Nichols CJ, Margolin KA, 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 25 (3): 247-56, 2007. [PUBMED Abstract]
- Frazier AL, Hale JP, Rodriguez-Galindo C, et al.: Revised risk classification for pediatric extracranial germ cell tumors based on 25 years of clinical trial data from the United Kingdom and United States. J Clin Oncol 33 (2): 195-201, 2015. [PUBMED Abstract]
No hay comentarios:
Publicar un comentario