BACKGROUND: Pineoblastoma is a rare pineal region brain tumor. Treatment strategies have reflected those for other malignant embryonal brain tumors. PATIENTS AND METHODS: Original prospective treatment and outcome data from international trial groups were pooled. Cox regression models were developed considering treatment elements as time-dependent covariates. RESULTS: Data on 135 patients with pineoblastoma aged 0.01-20.7 (median 4.9) years were analyzed. Median observation time was 7.3 years. Favorable prognostic factors were age ≥4 years (hazard ratio [HR] for progression-free survival [PFS] 0.270, P < .001) and administration of radiotherapy (HR for PFS 0.282, P < .001). Metastatic disease (HR for PFS 2.015, P = .006), but not postoperative residual tumor, was associated with unfavorable prognosis. In 57 patients <4 years old, 5-year PFS/overall survival (OS) were 11 ± 4%/12 ± 4%. Two patients survived after chemotherapy only, while 3 of 16 treated with craniospinal irradiation (CSI) with boost, and 3 of 5 treated with high-dose chemotherapy (HDCT) and local radiotherapy survived. In 78 patients aged ≥4 years, PFS/OS were 72 ± 7%/73 ± 7% for patients without metastases, and 50 ± 10%/55 ± 10% with metastases. Seventy-three patients received radiotherapy (48 conventionally fractionated CSI, median dose 35.0 [18.0-45.0] Gy, 19 hyperfractionated CSI, 6 local radiotherapy), with (n = 68) or without (n = 6) chemotherapy. The treatment sequence had no impact; application of HDCT had weak impact on survival in older patients. CONCLUSION: Survival is poor in young children treated without radiotherapy. In these patients, combination of HDCT and local radiotherapy may warrant further evaluation in the absence of more specific or targeted treatments. CSI combined with chemotherapy is effective for older non-metastatic patients.

2nd Department of Pediatrics School of Medicine Semmelweis University Budapest Hungary

Brain Tumor Programme Department of Pediatric and Adolescent Oncology Institut Gustave Roussy Villejuif France

Department of Hematology Oncology and Stem Cell Transplant Ann and Robert H Lurie Children's Hospital of Chicago Chicago Illinois USA

Department of Neuropathology University of Bonn Bonn Germany

Department of Oncology University Children's Hospital Zurich Zurich Switzerland

Department of Pathology Children's Hospital Los Angeles and the University of Southern California Los Angeles California USA

Department of Pathology Radboud University Medical Center Nijmegen Netherlands

Department of Pathology St Jude Children's Research Hospital Memphis Tennessee USA

Department of Pathology VU University Medical Center Amsterdam Netherlands

Department of Pediatric Hematology and Oncology University Medical Center Hamburg Eppendorf Hamburg Germany

Department of Pediatric Hematoncology University Hospital de São João Porto Portugal

Department of Pediatric Oncology Hematology VU University Medical Center Amsterdam Netherlands

Department of Pediatrics and Adolescent Medicine Division of Pediatric Hematology and Oncology Medical University of Graz Graz Austria

Department of Pediatrics Division of Hematology Oncology and BMT Nationwide Children's Hospital and The Ohio State University Columbus Ohio USA

Department of Pediatrics Fondazione IRCCS Istituto Nazionale dei Tumori Milano Italy

Department of Pediatrics University of California Los Angeles Los Angeles California USA

Department of Radiological Oncological and Anatomo Pathological Sciences Sapienza University of Rome Rome Italy

Division of Pediatric Neurooncology German Cancer Research Center Heidelberg Germany

Institute of Biostatistics and Clinical Research University of Muenster Muenster Germany

IRCCS Neuromed Pozzilli Italy

Northern Institute for Cancer Research Newcastle University Newcastle upon Tyne UK

Oncology Unit Alder Hey Children's Hospital Liverpool UK

Pediatric Oncology Department University Hospital Brno Brno Czech Republic

Telethon Kids Institute Subiaco Western Australia

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Louis DN, Ohgaki H, Wiestler OD, et al. WHO Classification of Tumours of the Central Nervous System.4th ed Lyon: International Agency for Research on Cancer; 2007.

Gerber NU, von Hoff K, Resch A, et al. Treatment of children with central nervous system primitive neuroectodermal tumors/pinealoblastomas in the prospective multicentric trial HIT 2000 using hyperfractionated radiation therapy followed by maintenance chemotherapy. Int J Radiat Oncol Biol Phys. 2014;89(4):863–871. PubMed

Friedrich C, von Bueren AO, von Hoff K, et al. Treatment of young children with CNS-primitive neuroectodermal tumors/pineoblastomas in the prospective multicenter trial HIT 2000 using different chemotherapy regimens and radiotherapy. Neuro Oncol. 2013;15(2):224–234. PubMed PMC

Kaatsch P, Spix C. German Childhood Cancer Registry—Report 2013/2014 (1980–2013).Mainz, Germany: Institute of Medical Biostatistircs, Epidemiology and Informatics (IMBEI) at the University Medical Center of the Johannes Gutenberg University Mainz; 2014.

Rorke LB, Trojanowski JQ, Lee VM, et al. Primitive neuroectodermal tumors of the central nervous system. Brain Pathol. 1997;7(2):765–784. PubMed PMC

Miller S, Rogers HA, Lyon P, et al. Genome-wide molecular characterization of central nervous system primitive neuroectodermal tumor and pineoblastoma. Neuro Oncol. 2011;13(8):866–879. PubMed PMC

Sturm D, Orr BA, Toprak UH. New brain tumor entities emerge from molecular classification of CNS-PNETs. Cell. 2016;164:1060–1072. PubMed PMC

de Kock L, Sabbaghian N, Druker H, et al. Germ-line and somatic DICER1 mutations in pineoblastoma. Acta Neuropathol. 2014;128(4):583–595. PubMed PMC

Antoneli CB, Ribeiro Kde C, Sakamoto LH, et al. Trilateral retinoblastoma. Pediatr Blood Cancer. 2007;48(3):306–310. PubMed

Plowman PN, Pizer B, Kingston JE. Pineal parenchymal tumours: II. On the aggressive behaviour of pineoblastoma in patients with an inherited mutation of the RB1 gene. Clin Oncol (R Coll Radiol). 2004;16(4):244–247. PubMed

Hinkes BG, von Hoff K, Deinlein F, et al. Childhood pineoblastoma: experiences from the prospective multicenter trials HIT-SKK87, HIT-SKK92 and HIT91. J Neurooncol. 2007;81(2):217–223. PubMed

Villà S, Miller RC, Krengli M, et al. Primary pineal tumors: outcome and prognostic factors—a study from the Rare Cancer Network (RCN). Clin Transl Oncol. 2012;14(11):827–834. PubMed

Farnia B, Allen PK, Brown PD, et al. Clinical outcomes and patterns of failure in pineoblastoma: a 30-year, single-institution retrospective review. World Neurosurg. 2014;82(6):1232–1241. PubMed

Jakacki RI, Burger PC, Kocak M, et al. Outcome and prognostic factors for children with supratentorial primitive neuroectodermal tumors treated with carboplatin during radiotherapy: a report from the Children’s Oncology Group. Pediatr Blood Cancer. 2015;62(5):776–783. PubMed PMC

Jakacki RI, Zeltzer PM, Boyett JM, et al. Survival and prognostic factors following radiation and/or chemotherapy for primitive neuroectodermal tumors of the pineal region in infants and children: a report of the Childrens Cancer Group. J Clin Oncol. 1995;13(6):1377–1383. PubMed

Gilheeney SW, Saad A, Chi S, et al. Outcome of pediatric pineoblastoma after surgery, radiation and chemotherapy. J Neurooncol. 2008;89(1):89–95. PubMed

Pizer BL, Weston CL, Robinson KJ, et al. Analysis of patients with supratentorial primitive neuro-ectodermal tumours entered into the SIOP/UKCCSG PNET 3 study. Eur J Cancer. 2006;42(8):1120–1128. PubMed

Selvanathan SK, Hammouche S, Smethurst W, et al. Outcome and prognostic features in adult pineoblastomas: analysis of cases from the SEER database. Acta Neurochir (Wien). 2012;154(5):863–869. PubMed

Tate M, Sughrue ME, Rutkowski MJ, et al. The long-term postsurgical prognosis of patients with pineoblastoma. Cancer. 2012;118(1):173–179. PubMed

Duffner PK, Cohen ME, Sanford RA, et al. Lack of efficacy of postoperative chemotherapy and delayed radiation in very young children with pineoblastoma. Pediatric oncology group. Med Pediatr Oncol. 1995;25(1):38–44. PubMed

Fangusaro J, Finlay J, Sposto R, et al. Intensive chemotherapy followed by consolidative myeloablative chemotherapy with autologous hematopoietic cell rescue (AuHCR) in young children with newly diagnosed supratentorial primitive neuroectodermal tumors (sPNETs): report of the Head Start I and II experience. Pediatr Blood Cancer. 2008;50(2):312–318. PubMed

Gururangan S, McLaughlin C, Quinn J, et al. High-dose chemotherapy with autologous stem-cell rescue in children and adults with newly diagnosed pineoblastomas. J Clin Oncol. 2003;21(11):2187–2191. PubMed

Massimino M, Gandola L, Spreafico F, et al. Supratentorial primitive neuroectodermal tumors (S-PNET) in children: a prospective experience with adjuvant intensive chemotherapy and hyperfractionated accelerated radiotherapy. Int J Radiat Oncol Biol Phys. 2006;64(4):1031–1037. PubMed

Davidson TB, Ji L, Haley K, et al. Outcome of Head Start III multinational protocol for newly diagnosed central nervous system (CNS) primitive neuroectodermal tumors (pnet) of young children [abstract]. J.Clin.Oncol. 2011;29(15, suppl); abstr 9519.

Dufour C, Couanet D, Figarella-Branger D, et al. Sequential high-dose chemotherapy and reduced craniospinal iirradiation in young children with metastatic medulloblastoma [abstract]. Neuro Oncol. 2008;10(6):1083–1083.

Dufour C, Delisle MB, Geoffray A, et al. Tandem high-dose chemotherapy with stem cell rescue followed by risk-adapted radiation in children with high-risk cerebral primitive neuroectodermal tumor: results of the SFCE-Trial PNET HR+5 [abstract]. Pediatr Blood Cancer. 2014;61:S111–S111.

Rutkowski S, Gerber NU, von Hoff K, et al. ; German Pediatric Brain Tumor Study Group. Treatment of early childhood medulloblastoma by postoperative chemotherapy and deferred radiotherapy. Neuro Oncol. 2009;11(2):201–210. PubMed PMC

Rutkowski S, Bode U, Deinlein F, et al. Treatment of early childhood medulloblastoma by postoperative chemotherapy alone. N Engl J Med. 2005;352(10):978–986. PubMed

Grill J, Sainte-Rose C, Jouvet A, et al. ; French Society of Paediatric Oncology. Treatment of medulloblastoma with postoperative chemotherapy alone: an SFOP prospective trial in young children. Lancet Oncol. 2005;6(8):573–580. PubMed

Taylor RE, Bailey CC, Robinson K, et al. ; International Society of Paediatric Oncology; United Kingdom Children’s Cancer Study Group. Results of a randomized study of preradiation chemotherapy versus radiotherapy alone for nonmetastatic medulloblastoma: the International Society of Paediatric Oncology/United Kingdom Children’s Cancer Study Group PNET-3 Study. J Clin Oncol. 2003;21(8):1581–1591. PubMed

Grundy RG, Wilne SH, Robinson KJ, et al. ; Children’s Cancer and Leukaemia Group (formerly UKCCSG) Brain Tumour Committee. Primary postoperative chemotherapy without radiotherapy for treatment of brain tumours other than ependymoma in children under 3 years: results of the first UKCCSG/SIOP CNS 9204 trial. Eur J Cancer. 2010;46(1):120–133. PubMed

Akaike H. A new look at the statistical model identification. IEEE Trans Autom Control. 1974;19(6):716–723.

R Core Team. R: A language and environment for statistical computing. Vienna, Austria: R Foundation for Statistical Computing; 2016. https://www.R-project.org/ .

Therneau T. A Package for Survival Analysis in S. version 2.38; 2015. https://CRAN.R-project.org/package=survival.

Grabow D, Spix C, Blettner M, Kaatsch P. Strategy for long-term surveillance at the German Childhood Cancer Registry—an update. Klin Padiatr. 2011;223(3):159–164. PubMed

Reddy AT, Janss AJ, Phillips PC, et al. Outcome for children with supratentorial primitive neuroectodermal tumors treated with surgery, radiation, and chemotherapy. Cancer. 2000;88(9):2189–2193. PubMed

Duffner PK, Horowitz ME, Krischer JP, et al. The treatment of malignant brain tumors in infants and very young children: an update of the Pediatric Oncology Group experience. Neuro Oncol. 1999;1(2):152–161. PubMed PMC

Johnston DL, Keene DL, Lafay-Cousin L, et al. Supratentorial primitive neuroectodermal tumors: a Canadian pediatric brain tumor consortium report. J Neurooncol. 2008;86(1):101–108. PubMed

Timmermann B, Kortmann RD, Kühl J, et al. Role of radiotherapy in the treatment of supratentorial primitive neuroectodermal tumors in childhood: results of the prospective German brain tumor trials HIT 88/89 and 91. J Clin Oncol. 2002;20(3):842–849. PubMed

Timmermann B, Kortmann RD, Kühl J, et al. Role of radiotherapy in supratentorial primitive neuroectodermal tumor in young children: results of the German HIT-SKK87 and HIT-SKK92 trials. J Clin Oncol. 2006;24(10):1554–1560. PubMed

Broniscer A, Nicolaides TP, Dunkel IJ, et al. High-dose chemotherapy with autologous stem-cell rescue in the treatment of patients with recurrent non-cerebellar primitive neuroectodermal tumors. Pediatr Blood Cancer. 2004;42(3):261–267. PubMed

Klein JP, Rizzo JD, Zhang MJ, et al. Statistical methods for the analysis and presentation of the results of bone marrow transplants. Part 2: Regression modeling. Bone Marrow Transplant. 2001;28(11):1001–1011. PubMed