Ajay Vora1, Anita Andreano2, Ching-Hon Pui2, Stephen P Hunger2, Martin Schrappe2, Anja Moericke2, Andrea Biondi2, Gabriele Escherich2, Lewis B Silverman2, Nicholas Goulden2, Mervi Taskinen2, Rob Pieters2, Keizo Horibe2, Meenakshi Devidas2, Franco Locatelli2, Maria Grazia Valsecchi2. 1. Ajay Vora, Sheffield Children's Hospital and University of Sheffield, Sheffield; Nicholas Goulden, Great Ormond Street Hospital, London, United Kingdom; Anita Andreano and Maria Grazia Valsecchi, School of Medicine and Surgery, University of Milano-Bicocca, Milan; Andrea Biondi, University of Milano-Bicocca, Monza; Franco Locatelli, Bambino Gesù Children's Hospital, Rome, and University of Pavia, Pavia, Italy; Ching-Hon Pui, St Jude Children's Research Hospital and University of Tennessee Health Science Center, Memphis, TN; Stephen P. Hunger, Children's Hospital of Philadelphia and University of Pennsylvania Perelman School of Medicine, Philadelphia, PA; Lewis B. Silverman, Dana-Faber Cancer Institute and Boston Children's Hospital, Boston, MA; Meenakshi Devidas, Children's Oncology Group Statistics and Data Center and University of Florida, Gainesville, FL; Martin Schrappe and Anja Moericke, University Medical Centre and Christian-Albrechts-University, Kiel; Gabriele Escherich, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany; Mervi Taskinen, Helsinki University Hospital, Helsinki, Finland; Rob Pieters, Princess Máxima Center for Pediatric Oncology, Utrecht, and Dutch Childhood Oncology Group, the Hague, the Netherlands; and Keizo Horibe, National Hospital Organization Nagoya Medical Center, Nagoya, Japan. ajay.vora@sch.nhs.uk. 2. Ajay Vora, Sheffield Children's Hospital and University of Sheffield, Sheffield; Nicholas Goulden, Great Ormond Street Hospital, London, United Kingdom; Anita Andreano and Maria Grazia Valsecchi, School of Medicine and Surgery, University of Milano-Bicocca, Milan; Andrea Biondi, University of Milano-Bicocca, Monza; Franco Locatelli, Bambino Gesù Children's Hospital, Rome, and University of Pavia, Pavia, Italy; Ching-Hon Pui, St Jude Children's Research Hospital and University of Tennessee Health Science Center, Memphis, TN; Stephen P. Hunger, Children's Hospital of Philadelphia and University of Pennsylvania Perelman School of Medicine, Philadelphia, PA; Lewis B. Silverman, Dana-Faber Cancer Institute and Boston Children's Hospital, Boston, MA; Meenakshi Devidas, Children's Oncology Group Statistics and Data Center and University of Florida, Gainesville, FL; Martin Schrappe and Anja Moericke, University Medical Centre and Christian-Albrechts-University, Kiel; Gabriele Escherich, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany; Mervi Taskinen, Helsinki University Hospital, Helsinki, Finland; Rob Pieters, Princess Máxima Center for Pediatric Oncology, Utrecht, and Dutch Childhood Oncology Group, the Hague, the Netherlands; and Keizo Horibe, National Hospital Organization Nagoya Medical Center, Nagoya, Japan.
Abstract
PURPOSE: We sought to determine whether cranial radiotherapy (CRT) is necessary to prevent relapse in any subgroup of children with acute lymphoblastic leukemia (ALL). PATIENTS AND METHODS: We obtained aggregate data on relapse and survival outcomes for 16,623 patients age 1 to 18 years old with newly diagnosed ALL treated between 1996 and 2007 by 10 cooperative study groups from around the world. The proportion of patients eligible for prophylactic CRT varied from 0% to 33% by trial and was not related to the proportion eligible for allogeneic stem-cell transplantation in first complete remission. Using a random effects model, with CRT as a dichotomous covariate, we performed a single-arm meta-analysis to compare event-free survival and cumulative incidence of isolated or any CNS relapse and isolated bone marrow relapse in high-risk subgroups of patients who either did or did not receive CRT. RESULTS: Although there was significant heterogeneity in all outcome end points according to trial, CRT was associated with a reduced risk of relapse only in the small subgroup of patients with overt CNS disease at diagnosis, who had a significantly lower risk of isolated CNS relapse (4% with CRT v 17% without CRT; P = .02) and a trend toward lower risk of any CNS relapse (7% with CRT v 17% without CRT; P = .09). However, this group had a relatively high rate of events regardless of whether or not they received CRT (32% [95% CI, 26% to 39%] v 34% [95% CI, 19% to 54%]; P = .8). CONCLUSION: CRT does not have an impact on the risk of relapse in children with ALL treated on contemporary protocols.
PURPOSE: We sought to determine whether cranial radiotherapy (CRT) is necessary to prevent relapse in any subgroup of children with acute lymphoblastic leukemia (ALL). PATIENTS AND METHODS: We obtained aggregate data on relapse and survival outcomes for 16,623 patients age 1 to 18 years old with newly diagnosed ALL treated between 1996 and 2007 by 10 cooperative study groups from around the world. The proportion of patients eligible for prophylactic CRT varied from 0% to 33% by trial and was not related to the proportion eligible for allogeneic stem-cell transplantation in first complete remission. Using a random effects model, with CRT as a dichotomous covariate, we performed a single-arm meta-analysis to compare event-free survival and cumulative incidence of isolated or any CNS relapse and isolated bone marrow relapse in high-risk subgroups of patients who either did or did not receive CRT. RESULTS: Although there was significant heterogeneity in all outcome end points according to trial, CRT was associated with a reduced risk of relapse only in the small subgroup of patients with overt CNS disease at diagnosis, who had a significantly lower risk of isolated CNS relapse (4% with CRT v 17% without CRT; P = .02) and a trend toward lower risk of any CNS relapse (7% with CRT v 17% without CRT; P = .09). However, this group had a relatively high rate of events regardless of whether or not they received CRT (32% [95% CI, 26% to 39%] v 34% [95% CI, 19% to 54%]; P = .8). CONCLUSION: CRT does not have an impact on the risk of relapse in children with ALL treated on contemporary protocols.
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