Avani D Rao1, Arif S Rashid1, Qinyu Chen1, Rosangela C Villar2, Daria Kobyzeva3, Kristina Nilsson4, Karin Dieckmann5, Alexey Nechesnyuk3, Ralph Ermoian6, Sara Alcorn1, Shannon M MacDonald7, Matthew M Ladra1, Eric C Ford6, Brian A Winey7, Maria Luisa S Figueiredo8, Michael J Chen8, Stephanie A Terezakis9. 1. Department of Radiation and Molecular Radiation Sciences, Sidney Kimmel Comprehensive Cancer Center Johns Hopkins School of Medicine, Baltimore, Maryland. 2. Department of Radiation Oncology, Centro Infantil Boldrini, São Paulo, Brazil. 3. Department of Radiation Oncology, Federal Research and Clinical Centre of Pediatric Hematology, Oncology and Immunology, Moscow, Russia. 4. Department of Radiation Oncology, Uppsala University Hospital, Uppsala, Sweden. 5. Department of Radiation Oncology, Universitätklinik Für Strahlentherapie und Strahlenbiologie, Wien, Germany. 6. Department of Radiation Oncology, University of Washington, Seattle, Washington. 7. Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts. 8. Department of Radiation Oncology, Grupo de Apoio ao Adolescente e à Criança com Câncer, São Paulo, Brazil. 9. Department of Radiation and Molecular Radiation Sciences, Sidney Kimmel Comprehensive Cancer Center Johns Hopkins School of Medicine, Baltimore, Maryland. Electronic address: sterezak@jhmi.edu.
Abstract
PURPOSE: Reirradiation has been proposed as an effective modality for recurrent central nervous system (CNS) malignancies in adults. We evaluated the toxicity and outcomes of CNS reirradiation in pediatric patients. METHODS AND MATERIALS: The data from pediatric patients <21 years of age at the initial diagnosis who developed a recurrent CNS malignancy that received repeat radiation therapy (RT) across 5 facilities in an international pediatric research consortium were retrospectively reviewed. RESULTS: Sixty-seven pediatric patients underwent CNS reirradiation. The primary diagnoses included medulloblastoma/primitive neuroectodermal tumor (n=20; 30%), ependymoma (n=19; 28%), germ cell tumor (n=8; 12%), high-grade glioma (n=9; 13%), low-grade glioma (n=5; 7%), and other (n=6; 9%). The median age at the first course of RT was 8.5 years (range 0.5-19.5) and was 12.3 years (range 3.3-30.2) at reirradiation. The median interval between RT courses was 2.0 years (range 0.3-16.5). The median radiation dose and fractionation in equivalent 2-Gy fractions was 63.7 Gy (range 27.6-74.8) for initial RT and 53.1 Gy (range 18.6-70.1) for repeat RT. The relapse location was infield in 52 patients (78%) and surrounding the initial RT field in 15 patients (22%). Thirty-seven patients (58%) underwent gross or subtotal resection at recurrence. The techniques used for reirradiation were intensity modulated RT (n=46), 3-dimensional conformal RT (n=9), stereotactic radiosurgery (n=4; 12-13 Gy × 1 or 5 Gy × 5), protons (n=4), combined modality (n=3), 2-dimensional RT (n=1), and brachytherapy (n=1). Radiation necrosis was detected in 2 patients after the first RT course and 1 additional patient after reirradiation. Six patients (9%) developed secondary neoplasms after initial RT (1 hematologic, 5 intracranial). One patient developed a secondary neoplasm identified shortly after repeat RT. The median overall survival after completion of repeat RT was 12.8 months for the entire cohort and 20.5 and 8.4 months for patients with recurrent ependymoma and medulloblastoma after reirradiation, respectively. CONCLUSIONS: CNS reirradiation in pediatric patients could be a reasonable treatment option, with moderate survival noted after repeat RT. However, prospective data characterizing the rates of local control and toxicity are needed.
PURPOSE: Reirradiation has been proposed as an effective modality for recurrent central nervous system (CNS) malignancies in adults. We evaluated the toxicity and outcomes of CNS reirradiation in pediatric patients. METHODS AND MATERIALS: The data from pediatric patients <21 years of age at the initial diagnosis who developed a recurrent CNS malignancy that received repeat radiation therapy (RT) across 5 facilities in an international pediatric research consortium were retrospectively reviewed. RESULTS: Sixty-seven pediatric patients underwent CNS reirradiation. The primary diagnoses included medulloblastoma/primitive neuroectodermal tumor (n=20; 30%), ependymoma (n=19; 28%), germ cell tumor (n=8; 12%), high-grade glioma (n=9; 13%), low-grade glioma (n=5; 7%), and other (n=6; 9%). The median age at the first course of RT was 8.5 years (range 0.5-19.5) and was 12.3 years (range 3.3-30.2) at reirradiation. The median interval between RT courses was 2.0 years (range 0.3-16.5). The median radiation dose and fractionation in equivalent 2-Gy fractions was 63.7 Gy (range 27.6-74.8) for initial RT and 53.1 Gy (range 18.6-70.1) for repeat RT. The relapse location was infield in 52 patients (78%) and surrounding the initial RT field in 15 patients (22%). Thirty-seven patients (58%) underwent gross or subtotal resection at recurrence. The techniques used for reirradiation were intensity modulated RT (n=46), 3-dimensional conformal RT (n=9), stereotactic radiosurgery (n=4; 12-13 Gy × 1 or 5 Gy × 5), protons (n=4), combined modality (n=3), 2-dimensional RT (n=1), and brachytherapy (n=1). Radiation necrosis was detected in 2 patients after the first RT course and 1 additional patient after reirradiation. Six patients (9%) developed secondary neoplasms after initial RT (1 hematologic, 5 intracranial). One patient developed a secondary neoplasm identified shortly after repeat RT. The median overall survival after completion of repeat RT was 12.8 months for the entire cohort and 20.5 and 8.4 months for patients with recurrent ependymoma and medulloblastoma after reirradiation, respectively. CONCLUSIONS: CNS reirradiation in pediatric patients could be a reasonable treatment option, with moderate survival noted after repeat RT. However, prospective data characterizing the rates of local control and toxicity are needed.
Authors: Erin E Crotty; Sarah E S Leary; J Russell Geyer; James M Olson; Nathan E Millard; Aimee A Sato; Ralph P Ermoian; Bonnie L Cole; Christina M Lockwood; Vera A Paulson; Samuel R Browd; Richard G Ellenbogen; Jason S Hauptman; Amy Lee; Jeffrey G Ojemann; Nicholas A Vitanza Journal: J Neurooncol Date: 2020-06-16 Impact factor: 4.130
Authors: Francesco Cuccia; Gianluca Mortellaro; Lucia Ognibene; Giuseppe Craparo; Antonio Lo Casto; Giuseppe Ferrera Journal: In Vivo Date: 2020 May-Jun Impact factor: 2.155
Authors: Derek S Tsang; Nasim Sarhan; Vijay Ramaswamy; Liana Nobre; Ryan Yee; Michael D Taylor; Cynthia Hawkins; Ute Bartels; Annie Huang; Uri Tabori; David C Hodgson; Eric Bouffet; Normand Laperriere Journal: J Neurooncol Date: 2019-08-29 Impact factor: 4.130
Authors: Felix Ehret; Markus Kufeld; Christoph Fürweger; Alfred Haidenberger; Paul Windisch; Carolin Senger; Melina Kord; Malte Träger; David Kaul; Christian Schichor; Jörg-Christian Tonn; Alexander Muacevic Journal: Front Oncol Date: 2021-04-29 Impact factor: 6.244
Authors: Aleksandra Napieralska; Iwona Brąclik; Michał Radwan; Marek Mandera; Sławomir Blamek Journal: Childs Nerv Syst Date: 2018-12-04 Impact factor: 1.475
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