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A pilot study of risk-adapted radiotherapy and chemotherapy in patients with supratentorial PNET

Texas Children's Cancer Center, Baylor College of Medicine, Houston, TX, USA (M.C.); Royal Children's Hospital, Department of Haematology/Oncology, Herston, Brisbane, Australia (T.H., R.C.); Division of Behavioral Medicine (S.P.) and Division of Radiation Oncology (T.E.M., M.J.K.), Department of Radiological Sciences; Division of Neurosurgery (F.B.), Department of Biostatistics (D.W.); Divisions of Bone Marrow Transplantation (K.K.) and Neuro-Oncology (A.G.), Department of Oncology; and Department of Developmental Neurobiology (R.G.), St. Jude Children's Research Hospital, Memphis, TN, USA; Royal Children's Hospital, Department of Clinical Haematology and Oncology, Parkville, Australia (D.A.); Department of Pediatric Neurosurgery, Texas Children's Hospital, Houston, TX, USA (R.D.); Texas Children's Cancer Center, Houston, TX, USA (R.K., C.L.); Department of Radiation Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA (S.W.)

Address correspondence to Murali Chintagumpala, Texas Children's Cancer Center, 6621 Fannin St., Houston, TX 77030, USA (mxchinta{at}txccc.org).

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 (M₀ and tumor size > 1.5 cm²) or disseminated disease in the neuraxis (M₁–M₃). 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.

Key Words: autologous stem cell rescue • craniospinal radiotherapy • dose-intensive chemotherapy • event-free survival • risk-adapted therapy • supratentorial PNET

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