Rahul Krishnatry1,2,3, Nataliya Zhukova1,2,4,5, Ana S Guerreiro Stucklin1, Jason D Pole5, Matthew Mistry2,4,6, Iris Fried7, Vijay Ramaswamy1,8, Ute Bartels1,8, Annie Huang1,2,8, Normand Laperriere1,3, Peter Dirks2,9, Paul C Nathan1,8, Mark Greenberg1,5,8, David Malkin1,4,5,8, Cynthia Hawkins2,10, Pratiti Bandopadhayay11,12, Mark W Kieran11, Peter E Manley11, Eric Bouffet1,8, Uri Tabori1,2,6,8. 1. Division of Hematology/Oncology, University of Toronto, Toronto, Canada. 2. Labatt Brain Tumor Research Centre, University of Toronto, Toronto, Canada. 3. Radiation Medicine Program, Princess Margaret Hospital, University of Toronto, Toronto, Canada. 4. Program in Genetics and Genome Biology, University of Toronto, Toronto, Canada. 5. Pediatric Oncology Group of Ontario, Toronto, Canada. 6. Hospital for Sick Children and Institute of Medical Science, University of Toronto, Toronto, Canada. 7. Hadassah Medical Centre, Jerusalem, Israel. 8. Department of Pediatrics, University of Toronto, Toronto, Canada. 9. Division of Neurosurgery, University of Toronto, Toronto, Canada. 10. Division of Pathology, University of Toronto, Toronto, Canada. 11. Division of Pediatric Hematology/Oncology, Department of Pediatric Oncology, Dana-Farber Cancer Institute/Boston Children's Hospital, Boston, Massachusetts. 12. Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts.
Abstract
BACKGROUND: The determinants of outcomes for adult survivors of pediatric low-grade glioma (PLGG) are largely unknown. METHODS: This study collected population-based follow-up information for all PLGG patients diagnosed in Ontario, Canada from 1985 to 2012 (n = 1202) and determined factors affecting survival. The impact of upfront radiation treatment on overall survival (OS) was determined for a cohort of Ontario patients and an independent reference cohort from the Surveillance, Epidemiology, and End Results database. RESULTS: At a median follow-up of 12.73 years (range, 0.02-33 years), only 93 deaths (7.7%) were recorded, and the 20-year OS rate was 90.1% ± 1.1%. Children with neurofibromatosis type 1 had excellent survival and no tumor-related deaths during adulthood. Adverse risk factors included pleomorphic xanthoastrocytoma (P < .001) and a thalamic location (P < .001). For patients with unresectable tumors surviving more than 5 years after the diagnosis, upfront radiotherapy was associated with an approximately 3-fold increased risk of overall late deaths (hazard ratio [HR], 3.3; 95% confidence interval [CI], 1.6-6.6; P = .001) and an approximately 4-fold increased risk of tumor-related deaths (HR, 4.4; 95% CI, 1.3-14.6; P = .013). In a multivariate analysis, radiotherapy was the most significant factor associated with late all-cause deaths (HR, 3.0; 95% CI, 1.3-7.0; P = .012) and tumor-related deaths (HR, 4.4; 95% CI, 1.3-14.6; P = 0.014). A similar association between radiotherapy and late deaths was observed in the independent reference cohort (P < .001). In contrast to early deaths, late mortality was associated not with PLGG progression but rather with tumor transformation and non-oncological causes. CONCLUSIONS: The course of PLGG is associated with excellent long-term survival, but this is hampered by increased delayed mortality in patients receiving upfront radiotherapy. These observations should be considered when treatment options are being weighed for these patients.
BACKGROUND: The determinants of outcomes for adult survivors of pediatric low-grade glioma (PLGG) are largely unknown. METHODS: This study collected population-based follow-up information for all PLGG patients diagnosed in Ontario, Canada from 1985 to 2012 (n = 1202) and determined factors affecting survival. The impact of upfront radiation treatment on overall survival (OS) was determined for a cohort of Ontario patients and an independent reference cohort from the Surveillance, Epidemiology, and End Results database. RESULTS: At a median follow-up of 12.73 years (range, 0.02-33 years), only 93 deaths (7.7%) were recorded, and the 20-year OS rate was 90.1% ± 1.1%. Children with neurofibromatosis type 1 had excellent survival and no tumor-related deaths during adulthood. Adverse risk factors included pleomorphic xanthoastrocytoma (P < .001) and a thalamic location (P < .001). For patients with unresectable tumors surviving more than 5 years after the diagnosis, upfront radiotherapy was associated with an approximately 3-fold increased risk of overall late deaths (hazard ratio [HR], 3.3; 95% confidence interval [CI], 1.6-6.6; P = .001) and an approximately 4-fold increased risk of tumor-related deaths (HR, 4.4; 95% CI, 1.3-14.6; P = .013). In a multivariate analysis, radiotherapy was the most significant factor associated with late all-cause deaths (HR, 3.0; 95% CI, 1.3-7.0; P = .012) and tumor-related deaths (HR, 4.4; 95% CI, 1.3-14.6; P = 0.014). A similar association between radiotherapy and late deaths was observed in the independent reference cohort (P < .001). In contrast to early deaths, late mortality was associated not with PLGG progression but rather with tumor transformation and non-oncological causes. CONCLUSIONS: The course of PLGG is associated with excellent long-term survival, but this is hampered by increased delayed mortality in patients receiving upfront radiotherapy. These observations should be considered when treatment options are being weighed for these patients.
Authors: Joel M Cherlow; Dennis W W Shaw; Linda R Margraf; Daniel C Bowers; Jie Huang; Maryam Fouladi; Arzu Onar-Thomas; Tianni Zhou; Ian F Pollack; Amar Gajjar; Sandy K Kessel; Patricia L Cullen; Kevin McMullen; John C Wellons; Thomas E Merchant Journal: Int J Radiat Oncol Biol Phys Date: 2018-11-10 Impact factor: 7.038
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Authors: Liana Nobre; Michal Zapotocky; Vijay Ramaswamy; Scott Ryall; Julie Bennett; Daniel Alderete; Julia Balaguer Guill; Lorena Baroni; Ute Bartels; Abhishek Bavle; Miriam Bornhorst; Daniel R Boue; Adela Canete; Murali Chintagumpala; Scott L Coven; Ofelia Cruz; Sonika Dahiya; Peter Dirks; Ira J Dunkel; David Eisenstat; Cecile Faure Conter; Elizabeth Finch; Jonathan L Finlay; Didier Frappaz; Maria Luisa Garre; Karen Gauvain; Anne Grete Bechensteen; Jordan R Hansford; Inga Harting; Peter Hauser; Lili-Naz Hazrati; Annie Huang; Sarah G Injac; Valentina Iurilli; Matthias Karajannis; Gurcharanjeet Kaur; Martin Kyncl; Lenka Krskova; Normand Laperriere; Valerie Larouche; Alvaro Lassaletta; Sarah Leary; Frank Lin; Samantha Mascelli; Tara McKeown; Till Milde; Andres Morales La Madrid; Giovanni Morana; Helena Morse; Naureen Mushtaq; Diana S Osorio; Roger Packer; Zdenek Pavelka; Eduardo Quiroga-Cantero; James Rutka; Magnus Sabel; Duarte Salgado; Palma Solano; Jaroslav Sterba; Jack Su; David Sumerauer; Michael D Taylor; Helen Toledano; Derek S Tsang; Mariana Valente Fernandes; Frank van Landeghem; Cornelis M van Tilburg; Bev Wilson; Olaf Witt; Josef Zamecnik; Eric Bouffet; Cynthia Hawkins; Uri Tabori Journal: JCO Precis Oncol Date: 2020-05-20
Authors: Roger J Packer; Stephan Pfister; Eric Bouffet; Robert Avery; Pratiti Bandopadhayay; Miriam Bornhorst; Daniel C Bowers; David Ellison; Jason Fangusaro; Nicholas Foreman; Maryam Fouladi; Amar Gajjar; Daphne Haas-Kogan; Cynthia Hawkins; Cheng-Ying Ho; Eugene Hwang; Nada Jabado; Lindsay B Kilburn; Alvaro Lassaletta; Keith L Ligon; Maura Massimino; Schouten-van Meeteren; Sabine Mueller; Theo Nicolaides; Giorgio Perilongo; Uri Tabori; Gilbert Vezina; Katherine Warren; Olaf Witt; Yuan Zhu; David T Jones; Mark Kieran Journal: Neuro Oncol Date: 2017-06-01 Impact factor: 12.300