title: Multimodal therapy in children and adolescents with newly diagnosed atypical teratoid rhabdoid tumor: individual pooled data analysis and review of the literature.
abstract: Atypical teratoid rhabdoid tumour (ATRT) is a malignant tumour of the central nervous system with a dismal prognosis. There is no consensus on optimal treatment and different multimodal strategies are currently being used in an attempt to improve outcomes. To evaluate the impact of high-dose chemotherapy followed by autologous stem-cell rescue (HD48 SCR), radiotherapy (RT) at first line, intrathecal chemotherapy (IT) and extent of surgical resection upon recurrence-free survival (RFS) and overall survival (OS). An online database search identified prospective and retrospective studies focused on the treatment of children and adolescents with newly diagnosed ATRT. Clinical, therapeutic and outcome data were extracted and an individual pooled data analysis was conducted. Out of 389 publications, 12 manuscripts were included in our review. Data from 332 patients were analysed. Median age at diagnosis was 37 months (range 1-231). HD-SCR, RT and IT had been administered to 28.6% (58/203), 49.6% (118/238) and 21% (65/310) of the patients, respectively. Gross total resection (GTR) had been achieved in 46.5% (152/327) of the cases. In the multivariate analysis, hazard ratios (95% Confidence Interval) for HD-SCR were: RFS-HR = 0.570 (0.357-0.910) p = 0.019, and OS-HR = 0.388 (0.214-0.704) p = 0.002; and for RT: RFS-HR = 0.551 (0.351-0.866) p = 0.01, and OS-HR = 0.393 (0.216-0.712) p = 0.002. IT and GTR were not significantly associated with improved RFS or OS in the multivariate analysis. In our pooled data review, HD-SCR and RT at first line were associated with improved outcomes in children and adolescents with newly diagnosed ATRT.
authors.affiliation: Children and Young People's Unit, The Royal Marsden NHS Foundation Trust, Downs Road, Sutton, Surrey, SM2 5PT, UK.
authors.forename: D
authors.initials: D
authors.lastname: Schrey
authors.affiliation: Children and Young People's Unit, The Royal Marsden NHS Foundation Trust, Downs Road, Sutton, Surrey, SM2 5PT, UK.|Divisions of Clinical Studies and Cancer Therapeutics, The Institute of Cancer Research, 15 Cotswold Road, Sutton, Surrey, SM2 5NG, UK.
authors.forename: F
authors.initials: F
authors.lastname: Carceller Lechón
authors.affiliation: Department of Surgery, St Mark's Hospital, Watford Road, Harrow, Middlesex, HA1 3UJ, UK.|Department of Surgery and Cancer, Imperial College, Paddington, London, W2 1NY, UK.
authors.forename: G
authors.initials: G
authors.lastname: Malietzis
authors.affiliation: Children and Young People's Unit, The Royal Marsden NHS Foundation Trust, Downs Road, Sutton, Surrey, SM2 5PT, UK.|Divisions of Clinical Studies and Cancer Therapeutics, The Institute of Cancer Research, 15 Cotswold Road, Sutton, Surrey, SM2 5NG, UK.|Clinical Research Programme, Spanish National Cancer Research Centre (CNIO), Calle de Melchor Fernandez Almagro, num. 3, 28029, Madrid, Spain.
authors.forename: L
authors.initials: L
authors.lastname: Moreno
authors.affiliation: Department of Pediatric and Adolescent Oncology, Institute Gustave Roussy, 114 rue Edouard Vaillant, 94805, Villejuif, France.
authors.forename: C
authors.initials: C
authors.lastname: Dufour
authors.affiliation: Pediatric Neuro-Oncology, Dana-Farber Cancer Institute, 450 Brookline Ave, Boston, MA, 02215, USA.
authors.forename: S
authors.initials: S
authors.lastname: Chi
authors.affiliation: Division of Pediatric Hematology Oncology and Bone Marrow Transplantation, Alberta Children's Hospital, Calgary, AB, T3B 6A8, Canada.
authors.forename: L
authors.initials: L
authors.lastname: Lafay-Cousin
authors.affiliation: Department for Pediatric Hematology and Oncology, University Hospital Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany.
authors.forename: K
authors.initials: K
authors.lastname: von Hoff
authors.affiliation: Department of Surgery and Cancer, Imperial College, Paddington, London, W2 1NY, UK.
authors.forename: T
authors.initials: T
authors.lastname: Athanasiou
authors.affiliation: Children and Young People's Unit, The Royal Marsden NHS Foundation Trust, Downs Road, Sutton, Surrey, SM2 5PT, UK.|Divisions of Clinical Studies and Cancer Therapeutics, The Institute of Cancer Research, 15 Cotswold Road, Sutton, Surrey, SM2 5NG, UK.
authors.forename: L V
authors.initials: LV
authors.lastname: Marshall
authors.affiliation: Children and Young People's Unit, The Royal Marsden NHS Foundation Trust, Downs Road, Sutton, Surrey, SM2 5PT, UK. Stergios.Zacharoulis@rmh.nhs.uk.|Divisions of Clinical Studies and Cancer Therapeutics, The Institute of Cancer Research, 15 Cotswold Road, Sutton, Surrey, SM2 5NG, UK. Stergios.Zacharoulis@rmh.nhs.uk.
authors.forename: S
authors.initials: S
authors.lastname: Zacharoulis
mesh_terms: D000293:Adolescent; D000970:Antineoplastic Agents / Q000627:therapeutic use; D016543:Central Nervous System Neoplasms / Q000628:therapy*; D002648:Child; D003131:Combined Modality Therapy; D016208:Databases, Factual / Q000706:statistics & numerical data; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D011878:Radiotherapy; D018335:Rhabdoid Tumor / Q000628:therapy*; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents
keywords: Atypical teratoid rhabdoid tumor; Autologous transplant; Childhood brain tumors; High dose chemotherapy; Meta-analysis; Stem cell rescue