Influence of Cranial Radiotherapy on Outcome in Children With Acute Lymphoblastic Leukemia Treated With Contemporary Therapy

Ajay Vora, Anita Andreano, Ching Hon Pui, Stephen P. Hunger, Martin Schrappe, Anja Moericke, Andrea Biondi, Gabriele Escherich, Lewis B. Silverman, Nicholas Goulden, Mervi Taskinen, Rob Pieters, Keizo Horibe, Meenakshi Devidas, Franco Locatelli, Maria Grazia Valsecchi

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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 metaanalysis 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.

Original languageEnglish
Pages (from-to)919-926
Number of pages8
JournalJournal of Clinical Oncology
Volume34
Issue number9
DOIs
Publication statusPublished - Mar 20 2016

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Precursor Cell Lymphoblastic Leukemia-Lymphoma
Radiotherapy
Recurrence
Therapeutics
Central Nervous System Diseases
Stem Cell Transplantation
Disease-Free Survival
Bone Marrow
Survival
Incidence

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Vora, A., Andreano, A., Pui, C. H., Hunger, S. P., Schrappe, M., Moericke, A., ... Valsecchi, M. G. (2016). Influence of Cranial Radiotherapy on Outcome in Children With Acute Lymphoblastic Leukemia Treated With Contemporary Therapy. Journal of Clinical Oncology, 34(9), 919-926. https://doi.org/10.1200/JCO.2015.64.2850

Influence of Cranial Radiotherapy on Outcome in Children With Acute Lymphoblastic Leukemia Treated With Contemporary Therapy. / Vora, Ajay; Andreano, Anita; Pui, Ching Hon; Hunger, Stephen P.; Schrappe, Martin; Moericke, Anja; Biondi, Andrea; Escherich, Gabriele; Silverman, Lewis B.; Goulden, Nicholas; Taskinen, Mervi; Pieters, Rob; Horibe, Keizo; Devidas, Meenakshi; Locatelli, Franco; Valsecchi, Maria Grazia.

In: Journal of Clinical Oncology, Vol. 34, No. 9, 20.03.2016, p. 919-926.

Research output: Contribution to journalArticle

Vora, A, Andreano, A, Pui, CH, Hunger, SP, Schrappe, M, Moericke, A, Biondi, A, Escherich, G, Silverman, LB, Goulden, N, Taskinen, M, Pieters, R, Horibe, K, Devidas, M, Locatelli, F & Valsecchi, MG 2016, 'Influence of Cranial Radiotherapy on Outcome in Children With Acute Lymphoblastic Leukemia Treated With Contemporary Therapy', Journal of Clinical Oncology, vol. 34, no. 9, pp. 919-926. https://doi.org/10.1200/JCO.2015.64.2850
Vora, Ajay ; Andreano, Anita ; Pui, Ching Hon ; Hunger, Stephen P. ; Schrappe, Martin ; Moericke, Anja ; Biondi, Andrea ; Escherich, Gabriele ; Silverman, Lewis B. ; Goulden, Nicholas ; Taskinen, Mervi ; Pieters, Rob ; Horibe, Keizo ; Devidas, Meenakshi ; Locatelli, Franco ; Valsecchi, Maria Grazia. / Influence of Cranial Radiotherapy on Outcome in Children With Acute Lymphoblastic Leukemia Treated With Contemporary Therapy. In: Journal of Clinical Oncology. 2016 ; Vol. 34, No. 9. pp. 919-926.
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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 metaanalysis 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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AU - Vora, Ajay

AU - Andreano, Anita

AU - Pui, Ching Hon

AU - Hunger, Stephen P.

AU - Schrappe, Martin

AU - Moericke, Anja

AU - Biondi, Andrea

AU - Escherich, Gabriele

AU - Silverman, Lewis B.

AU - Goulden, Nicholas

AU - Taskinen, Mervi

AU - Pieters, Rob

AU - Horibe, Keizo

AU - Devidas, Meenakshi

AU - Locatelli, Franco

AU - Valsecchi, Maria Grazia

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N2 - 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 metaanalysis 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.

AB - 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 metaanalysis 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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