Derek S Tsang1,2, Nasim Sarhan3, Vijay Ramaswamy4, Liana Nobre4, Ryan Yee3, Michael D Taylor5, Cynthia Hawkins6, Ute Bartels4, Annie Huang4, Uri Tabori4, David C Hodgson3,4, Eric Bouffet4, Normand Laperriere3,4. 1. Radiation Medicine Program, Princess Margaret Cancer Centre, University Health Network, 610 University Avenue, Toronto, ON, M5G 2M9, Canada. derek.tsang@rmp.uhn.ca. 2. Division of Haematology/Oncology, Hospital for Sick Children, Toronto, ON, Canada. derek.tsang@rmp.uhn.ca. 3. Radiation Medicine Program, Princess Margaret Cancer Centre, University Health Network, 610 University Avenue, Toronto, ON, M5G 2M9, Canada. 4. Division of Haematology/Oncology, Hospital for Sick Children, Toronto, ON, Canada. 5. Division of Neurosurgery, Hospital for Sick Children, Toronto, ON, Canada. 6. Paediatric Laboratory Medicine, Hospital for Sick Children, Toronto, ON, Canada.
Abstract
PURPOSE: Children with recurrent medulloblastoma have a poor prognosis. Re-irradiation is an option for some patients, but has not been well-studied in the era of molecular characterization for pediatric medulloblastoma. METHODS: This was a retrospective cohort study of 14 children age 18 years and younger at initial diagnosis with recurrent medulloblastoma, who received two or more courses of radiation therapy (RT). Molecular subgrouping was performed using nanoString and was available for nine patients. The primary study endpoint was overall survival. RESULTS: Re-irradiation (RT2) was directed at the supratentorial brain in six patients, infratentorial brain in one patient, and spine in seven patients. In addition, six patients received stem cell transplant as part of salvage therapy. Median OS for all patients was 12.4 months. One patient with recurrent Wnt-activated medulloblastoma remains alive with 154 months' survival; median survival was not reached for four patients with Group 4 disease, while three with Shh-activated disease had median survival of 2.2 months. A single patient with Group 3 disease died 4.3 months after RT2. Patients treated with RT2 to the spine for diffuse disease had poorer OS (p = 0.02), as compared to focal RT2 for intracranial recurrence. Distant failure, outside RT2 volumes, was the predominant pattern of recurrence after RT2. CONCLUSIONS: Re-irradiation for recurrent pediatric medulloblastoma can offer some patients disease control, particularly those with focally recurrent disease in the brain. Prospective studies are needed to confirm subgroups of patients who may benefit most from RT2.
PURPOSE:Children with recurrent medulloblastoma have a poor prognosis. Re-irradiation is an option for some patients, but has not been well-studied in the era of molecular characterization for pediatric medulloblastoma. METHODS: This was a retrospective cohort study of 14 children age 18 years and younger at initial diagnosis with recurrent medulloblastoma, who received two or more courses of radiation therapy (RT). Molecular subgrouping was performed using nanoString and was available for nine patients. The primary study endpoint was overall survival. RESULTS: Re-irradiation (RT2) was directed at the supratentorial brain in six patients, infratentorial brain in one patient, and spine in seven patients. In addition, six patients received stem cell transplant as part of salvage therapy. Median OS for all patients was 12.4 months. One patient with recurrent Wnt-activated medulloblastoma remains alive with 154 months' survival; median survival was not reached for four patients with Group 4 disease, while three with Shh-activated disease had median survival of 2.2 months. A single patient with Group 3 disease died 4.3 months after RT2. Patients treated with RT2 to the spine for diffuse disease had poorer OS (p = 0.02), as compared to focal RT2 for intracranial recurrence. Distant failure, outside RT2 volumes, was the predominant pattern of recurrence after RT2. CONCLUSIONS: Re-irradiation for recurrent pediatric medulloblastoma can offer some patients disease control, particularly those with focally recurrent disease in the brain. Prospective studies are needed to confirm subgroups of patients who may benefit most from RT2.
Authors: Amar Gajjar; Murali Chintagumpala; David Ashley; Stewart Kellie; Larry E Kun; Thomas E Merchant; Shaio Woo; Greg Wheeler; Valerie Ahern; Matthew J Krasin; Maryam Fouladi; Alberto Broniscer; Robert Krance; Gregory A Hale; Clinton F Stewart; Robert Dauser; Robert A Sanford; Christine Fuller; Ching Lau; James M Boyett; Dana Wallace; Richard J Gilbertson Journal: Lancet Oncol Date: 2006-10 Impact factor: 41.316
Authors: Avani D Rao; Arif S Rashid; Qinyu Chen; Rosangela C Villar; Daria Kobyzeva; Kristina Nilsson; Karin Dieckmann; Alexey Nechesnyuk; Ralph Ermoian; Sara Alcorn; Shannon M MacDonald; Matthew M Ladra; Eric C Ford; Brian A Winey; Maria Luisa S Figueiredo; Michael J Chen; Stephanie A Terezakis Journal: Int J Radiat Oncol Biol Phys Date: 2017-07-29 Impact factor: 7.038
Authors: Elise Régnier; Anne Laprie; Anne Ducassou; Stéphanie Bolle; Stéphane Supiot; Xavier Muracciole; Line Claude; Sophie Chapet; Bernard Coche-Dequéant; Céline Vigneron; Julie Leseur; Pierre Y Bondiau; Jean L Habrand; Valérie Bernier Journal: Radiother Oncol Date: 2018-12-20 Impact factor: 6.280
Authors: Florence M G Cavalli; Marc Remke; Ladislav Rampasek; John Peacock; David J H Shih; Betty Luu; Livia Garzia; Jonathon Torchia; Carolina Nor; A Sorana Morrissy; Sameer Agnihotri; Yuan Yao Thompson; Claudia M Kuzan-Fischer; Hamza Farooq; Keren Isaev; Craig Daniels; Byung-Kyu Cho; Seung-Ki Kim; Kyu-Chang Wang; Ji Yeoun Lee; Wieslawa A Grajkowska; Marta Perek-Polnik; Alexandre Vasiljevic; Cecile Faure-Conter; Anne Jouvet; Caterina Giannini; Amulya A Nageswara Rao; Kay Ka Wai Li; Ho-Keung Ng; Charles G Eberhart; Ian F Pollack; Ronald L Hamilton; G Yancey Gillespie; James M Olson; Sarah Leary; William A Weiss; Boleslaw Lach; Lola B Chambless; Reid C Thompson; Michael K Cooper; Rajeev Vibhakar; Peter Hauser; Marie-Lise C van Veelen; Johan M Kros; Pim J French; Young Shin Ra; Toshihiro Kumabe; Enrique López-Aguilar; Karel Zitterbart; Jaroslav Sterba; Gaetano Finocchiaro; Maura Massimino; Erwin G Van Meir; Satoru Osuka; Tomoko Shofuda; Almos Klekner; Massimo Zollo; Jeffrey R Leonard; Joshua B Rubin; Nada Jabado; Steffen Albrecht; Jaume Mora; Timothy E Van Meter; Shin Jung; Andrew S Moore; Andrew R Hallahan; Jennifer A Chan; Daniela P C Tirapelli; Carlos G Carlotti; Maryam Fouladi; José Pimentel; Claudia C Faria; Ali G Saad; Luca Massimi; Linda M Liau; Helen Wheeler; Hideo Nakamura; Samer K Elbabaa; Mario Perezpeña-Diazconti; Fernando Chico Ponce de León; Shenandoah Robinson; Michal Zapotocky; Alvaro Lassaletta; Annie Huang; Cynthia E Hawkins; Uri Tabori; Eric Bouffet; Ute Bartels; Peter B Dirks; James T Rutka; Gary D Bader; Jüri Reimand; Anna Goldenberg; Vijay Ramaswamy; Michael D Taylor Journal: Cancer Cell Date: 2017-06-12 Impact factor: 31.743
Authors: Frank Saran; Brigitta G Baumert; Antonia L Creak; Alan P Warrington; Sue Ashley; Daphne Traish; Michael Brada Journal: Pediatr Blood Cancer Date: 2008-03 Impact factor: 3.167
Authors: Edward C Schwalbe; Janet C Lindsey; Sirintra Nakjang; Stephen Crosier; Amanda J Smith; Debbie Hicks; Gholamreza Rafiee; Rebecca M Hill; Alice Iliasova; Thomas Stone; Barry Pizer; Antony Michalski; Abhijit Joshi; Stephen B Wharton; Thomas S Jacques; Simon Bailey; Daniel Williamson; Steven C Clifford Journal: Lancet Oncol Date: 2017-05-22 Impact factor: 41.316
Authors: Rebecca M Hill; Sabine L A Plasschaert; Beate Timmermann; Christelle Dufour; Kristian Aquilina; Shivaram Avula; Laura Donovan; Maarten Lequin; Torsten Pietsch; Ulrich Thomale; Stephan Tippelt; Pieter Wesseling; Stefan Rutkowski; Steven C Clifford; Stefan M Pfister; Simon Bailey; Gudrun Fleischhack Journal: Cancers (Basel) Date: 2021-12-28 Impact factor: 6.575
Authors: Christine Gaab; Jonas E Adolph; Stephan Tippelt; Ruth Mikasch; Denise Obrecht; Martin Mynarek; Stefan Rutkowski; Stefan M Pfister; Till Milde; Olaf Witt; Brigitte Bison; Monika Warmuth-Metz; Rolf-Dieter Kortmann; Stefan Dietzsch; Torsten Pietsch; Beate Timmermann; Ronald Sträter; Udo Bode; Andreas Faldum; Robert Kwiecien; Gudrun Fleischhack Journal: Cancers (Basel) Date: 2022-01-18 Impact factor: 6.639
Authors: Simon Bailey; Nicolas André; Lorenza Gandola; Maura Massimino; Stefan Rutkowski; Steven C Clifford Journal: Cancers (Basel) Date: 2022-01-13 Impact factor: 6.575