High-dose chemotherapy with autologous stem-cell rescue in the treatment of patients with recurrent non-cerebellar primitive neuroectodermal tumors

• Published in: Pediatric Blood & Cancer Vol. 42; no. 3; pp. 261 - 267
• Main Authors: Broniscer, Alberto, Nicolaides, Theodore P., Dunkel, Ira J., Gardner, Sharon L., Johnson Jr, James, Allen, Jeffrey C., Sposto, Richard, Finlay, Jonathan L.
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01-03-2004; Wiley
• Subjects: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Antineoplastic Combined Chemotherapy Protocols - toxicity; Biological and medical sciences; brain tumors; chemotherapy; Child; Child, Preschool; Clinical Trials as Topic; Combined Modality Therapy; Disease-Free Survival; Female; General aspects; Hematopoietic Stem Cell Transplantation - adverse effects; Humans; Infant; Male; Medical sciences; Multicenter Studies as Topic; myeloablative; Neuroectodermal Tumors - complications; Neuroectodermal Tumors - therapy; PNET; Recurrence; recurrent CNS tumors; Retrospective Studies; Salvage Therapy - methods; Transplantation Conditioning - adverse effects; Transplantation Conditioning - methods; Transplantation, Autologous; Treatment Outcome; Tumors; Antineoplastic agent; Cerebellum; Human; Pediatrics; Relapse; recurrent CNS tumors; Stem cell; myeloablative; Central nervous system; Hematopoietic cell; PNET; Encephalon; Neuroectodermal tumor; Chemotherapy; Primitive; Cancerology; Treatment; brain tumors; Myelosuppression; High dose
• ISSN: 1545-5009; 1545-5017; 1096-911X
• DOI: 10.1002/pbc.10369

Background
Recurrent non‐cerebellar primitive neuroectodermal tumors (PNETs) carry a dismal prognosis when treated with conventional chemotherapy alone. XSWe tested the efficacy of high‐dose chemotherapy (HDC) followed by autologous stem‐cell rescue (ASCR) in this setting.
Procedure
Eligibility mandated either minimal residual disease or evidence of chemosensitivity before HDC. Conditioning consisted of carboplatin (CBDCA) (500 mg/m2 or AUC = 7 mg/ml min using the Calvert formula) on days −8 to −6, thiotepa (300 mg/m2), and etoposide (250 mg/m2) on days −5 to −3. Irradiation was given post HDC selectively.
Results
Among 17 patients treated in this study, there were eight pineoblastoma(s) (pineo), seven cortical PNETs, and two arising elsewhere. Relapse was either local (nine) or metastatic to the brain (four) or spine (four). Two patients received HDC as the sole therapy for recurrence; additionally, eight underwent surgical debulking before HDC, and nine received irradiation, including six after HDC. Median age at ASCR was 3.9 years. Two patients died of toxicity (11%) and ten experienced tumor relapse (range: 23–361 days post ASCR). Five patients with cortical PNETs remain alive disease‐free (median follow‐up: 8.3 years); four of them received irradiation post HDC. The difference in 5‐year event‐free survival (EFS) between patients with pineo and other supratentorial PNETs was significant (0 vs. 62.5 ± 17%, P = 0.0065). Both surgery at relapse and irradiation post HDC were favorable prognostic factors (P = 0.006 and 0.01, respectively).
Conclusions
Patients with recurrent cortical PNETs can be cured with this strategy. Surgical debulking before, and irradiation after HDC play an important role in treatment success. © 2003 Wiley‐Liss, Inc.