Pre-radiation chemotherapy with response-based radiation therapy in children with central nervous system germ cell tumors: a report from the Children's Oncology Group.
BACKGROUND
This Phase II study was designed to determine response to chemotherapy and survival after response-based radiation (RT) in children with CNS germ cell tumors.


METHODS
Children with germinomas and normal markers received cisplatin 100 mg/m(2) + etoposide, alternating with vincristine + cyclophosphamide (CPM) 2 g/m(2)/d, for four cycles. Children with nongerminomatous tumors or with abnormal markers received doubled doses of cisplatin and CPM. For germinoma patients in complete response (CR), RT was decreased from 50.4 to 30.6 Gy. High-risk patients received neuraxis RT: 50.4 Gy local + 30.6 Gy neuraxis in CR; 54 Gy local + 36 Gy if less than CR.


RESULTS
Of 12 germinoma patients, 4 had cerebrospinal fluid (CSF) human chorionic gonadotropin (HCG) 6.9-21 mIU/ml. Of 14 nongerminomatous patients, HCG in serum or CSF was >50 mIU/ml in 9, alpha-fetoprotein (AFP) abnormal in 9. Four germinoma patients attained CR, six PR, one SD, one not evaluable after resection. Two nongerminomatous patients had CR, three PR, three SD, one PD, four not evaluable after resection; one inadequately treated patient had progressive disease (PD). Both PD patients died; one SD patient died during a seizure. Eleven germinoma patients are PF at median 66 months; one patient in CR refused RT, had PD at 10 months, received RT, and was PF at 56 months. Eleven of 14 nongerminomatous patients were PF at median 58 months.


CONCLUSIONS
Response (germinoma, 91%; nongerminomatous, 55%) and survival are encouraging after this regimen plus response-based RT.
Kretschmar
C
C
Boston Floating Hospital for Infants and Children, Boston, Massachusetts, USA. ckretschmar@Tufts-NEMC.org
Kleinberg
L
L
Greenberg
M
M
Burger
P
P
Holmes
Emi
E
Wharam
M
M
D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000097:blood / Q000134:cerebrospinal fluid; D001932:Brain Neoplasms / Q000097:blood / Q000134:cerebrospinal fluid / Q000188:drug therapy* / Q000532:radiotherapy / Q000601:surgery; D002648:Child; D002675:Child, Preschool; D006063:Chorionic Gonadotropin / Q000097:blood / Q000134:cerebrospinal fluid; D002945:Cisplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy; D016371:Cranial Irradiation; D003520:Cyclophosphamide / Q000008:administration & dosage; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005047:Etoposide / Q000008:administration & dosage; D018237:Germinoma / Q000097:blood / Q000134:cerebrospinal fluid / Q000188:drug therapy / Q000532:radiotherapy / Q000601:surgery; D006801:Humans; D007223:Infant; D020360:Neoadjuvant Therapy; D009373:Neoplasms, Germ Cell and Embryonal / Q000097:blood / Q000134:cerebrospinal fluid / Q000188:drug therapy* / Q000532:radiotherapy / Q000601:surgery; D010865:Pilot Projects; D010871:Pinealoma / Q000097:blood / Q000134:cerebrospinal fluid / Q000188:drug therapy / Q000532:radiotherapy / Q000601:surgery; D012306:Risk; D016896:Treatment Outcome; D014750:Vincristine / Q000008:administration & dosage; D000509:alpha-Fetoproteins / Q000032:analysis / Q000134:cerebrospinal fluid
D014408:Biomarkers, Tumor; D006063:Chorionic Gonadotropin; D000509:alpha-Fetoproteins; D014750:Vincristine; D005047:Etoposide; D003520:Cyclophosphamide; D002945:Cisplatin