title: A pilot study of risk-adapted radiotherapy and chemotherapy in patients with supratentorial PNET.
abstract: We undertook this study to estimate the event-free survival (EFS) of patients with newly diagnosed supratentorial primitive neuroectodermal tumor (SPNET) treated with risk-adapted craniospinal irradiation (CSI) with additional radiation to the primary tumor site and subsequent high-dose chemotherapy supported by stem cell rescue. Between 1996 and 2003, 16 patients with SPNET were enrolled. High-risk (HR) disease was differentiated from average-risk (AR) disease by the presence of residual tumor (M(0) and tumor size > 1.5 cm(2)) or disseminated disease in the neuraxis (M(1)-M(3)). Patients received risk-adapted CSI: those with AR disease received 23.4 Gy; those with HR disease, 36-39.6 Gy. The tumor bed received a total of 55.8 Gy. Subsequently, all patients received four cycles of high-dose cyclophosphamide, cisplatin, and vincristine with stem cell support. The median age at diagnosis was 7.9 years; eight patients were female. Seven patients had pineal PNET. Twelve patients are alive at a median follow-up of 5.4 years. The 5-year EFS and overall survival (OS) estimates for all patients were 68% +/- 14% and 73% +/- 13%. The 5-year EFS and OS estimates were 75% +/- 17% and 88% +/- 13%, respectively, for the eight patients with AR disease and 60% +/- 19% and 58% +/- 19%, respectively, for the eight with HR disease. No deaths were due to toxicity. High-dose cyclophosphamide-based chemotherapy with stem cell support after risk-adapted CSI results in excellent EFS estimates for patients with newly diagnosed AR SPNET. Further, this chemotherapy allows for a reduction in the dose of CSI used to treat AR SPNET without compromising EFS.
authors.affiliation: Texas Children's Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA. mxchinta@txccc.org
authors.forename: Murali
authors.initials: M
authors.lastname: Chintagumpala
authors.forename: Tim
authors.initials: T
authors.lastname: Hassall
authors.forename: Shawna
authors.initials: S
authors.lastname: Palmer
authors.forename: David
authors.initials: D
authors.lastname: Ashley
authors.forename: Dana
authors.initials: D
authors.lastname: Wallace
authors.forename: Kimberly
authors.initials: K
authors.lastname: Kasow
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Merchant
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Krasin
authors.forename: Robert
authors.initials: R
authors.lastname: Dauser
authors.forename: Frederick
authors.initials: F
authors.lastname: Boop
authors.forename: Robert
authors.initials: R
authors.lastname: Krance
authors.forename: Shiao
authors.initials: S
authors.lastname: Woo
authors.forename: Robyn
authors.initials: R
authors.lastname: Cheuk
authors.forename: Ching
authors.initials: C
authors.lastname: Lau
authors.forename: Richard
authors.initials: R
authors.lastname: Gilbertson
authors.forename: Amar
authors.initials: A
authors.lastname: Gajjar
mesh_terms: D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy / Q000628:therapy*; D002648:Child; D002675:Child, Preschool; D002945:Cisplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy; D016371:Cranial Irradiation; D003520:Cyclophosphamide / Q000008:administration & dosage; D018572:Disease-Free Survival; D004307:Dose-Response Relationship, Radiation; D005260:Female; D005720:Gamma Rays; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008297:Male; D018242:Neuroectodermal Tumors, Primitive / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy / Q000628:therapy*; D010865:Pilot Projects; D012307:Risk Factors; D015173:Supratentorial Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy / Q000628:therapy*; D015996:Survival Rate; D016896:Treatment Outcome; D014750:Vincristine / Q000008:administration & dosage
chemical_list: D014750:Vincristine; D003520:Cyclophosphamide; D002945:Cisplatin
references.citation: J Clin Oncol. 1998 Jul;16(7):2486-93
references.pmid: 9667268
references.citation: Pediatr Blood Cancer. 2004 Mar;42(3):261-7
references.pmid: 14752864
references.citation: Br J Cancer. 1977 Jan;35(1):1-39
references.pmid: 831755
references.citation: J Clin Oncol. 1999 Jul;17(7):2127-36
references.pmid: 10561268
references.citation: Cancer. 1999 Jul 15;86(2):331-9
references.pmid: 10421270
references.citation: Cancer. 2000 May 1;88(9):2189-93
references.pmid: 10813733
references.citation: Int J Radiat Oncol Biol Phys. 1996 Mar 1;34(4):899-904
references.pmid: 8598368
references.citation: J Clin Oncol. 2004 Aug 15;22(16):3357-65
references.pmid: 15310781
references.citation: Mol Pathol. 2000 Dec;53(6):313-9
references.pmid: 11193050
references.citation: J Clin Oncol. 2003 Jun 1;21(11):2187-91
references.pmid: 12775745
references.citation: Int J Radiat Oncol Biol Phys. 2006 Mar 15;64(4):1031-7
references.pmid: 16343801
references.citation: J Clin Oncol. 2002 Feb 1;20(3):842-9
references.pmid: 11821469
references.citation: J Pediatr Psychol. 2005 Jan-Feb;30(1):65-78
references.pmid: 15610986
references.citation: J Clin Oncol. 2001 May 15;19(10):2696-704
references.pmid: 11352962
references.citation: J Clin Oncol. 2006 Sep 1;24(25):4202-8
references.pmid: 16943538
references.citation: J Clin Oncol. 1997 May;15(5):1814-23
references.pmid: 9164190
references.citation: Br J Cancer. 1976 Dec;34(6):585-612
references.pmid: 795448
references.citation: Cancer. 2003 Feb 15;97(4):1115-26
references.pmid: 12569614
references.citation: Eur J Cancer. 2006 May;42(8):1120-8
references.pmid: 16632346
references.citation: Lancet Oncol. 2006 Oct;7(10):813-20
references.pmid: 17012043
references.citation: J Clin Oncol. 1998 Jan;16(1):210-21
references.pmid: 9440745
references.citation: Klin Padiatr. 1998 Jul-Aug;210(4):227-33
references.pmid: 9743957
references.citation: J Clin Oncol. 1995 Jul;13(7):1687-96
references.pmid: 7602359
references.citation: Nature. 2002 Jan 24;415(6870):436-42
references.pmid: 11807556
references.citation: J Clin Oncol. 1995 Jun;13(6):1377-83
references.pmid: 7751882
references.citation: Cancer Genet Cytogenet. 1997 Aug;97(1):25-31
references.pmid: 9242214
references.citation: J Neuropathol Exp Neurol. 1983 Jan;42(1):1-15
references.pmid: 6296325
references.citation: Pediatr Neurosurg. 1995;22(1):1-7
references.pmid: 7888387
references.citation: J Neurooncol. 1985;3(1):23-33
references.pmid: 2987425