Survival benefit for patients with diffuse intrinsic pontine glioma (DIPG) undergoing re-irradiation at first progression: A matched-cohort analysis on behalf of the SIOP-E-HGG/DIPG working group.
Overall survival (OS) of patients with diffuse intrinsic pontine glioma (DIPG) is poor. The purpose of this study is to analyse benefit and toxicity of re-irradiation at first progression.



At first progression, 31 children with DIPG, aged 2-16 years, underwent re-irradiation (dose 19.8-30.0 Gy) alone (n = 16) or combined with systemic therapy (n = 15). At initial presentation, all patients had typical symptoms and characteristic MRI features of DIPG, or biopsy-proven high-grade glioma. An interval of ≥3 months after upfront radiotherapy was required before re-irradiation. Thirty-nine patients fulfilling the same criteria receiving radiotherapy at diagnosis, followed by best supportive care (n = 20) or systemic therapy (n = 19) at progression but no re-irradiation, were eligible for a matched-cohort analysis.



Median OS for patients undergoing re-irradiation was 13.7 months. For a similar median progression-free survival after upfront radiotherapy (8.2 versus 7.7 months; P = .58), a significant benefit in median OS (13.7 versus 10.3 months; P = .04) was observed in favour of patients undergoing re-irradiation. Survival benefit of re-irradiation increased with a longer interval between end-of-radiotherapy and first progression (3-6 months: 4.0 versus 2.7; P < .01; 6-12 months: 6.4 versus 3.3; P = .04). Clinical improvement with re-irradiation was observed in 24/31 (77%) patients. No grade 4-5 toxicity was recorded. On multivariable analysis, interval to progression (corrected hazard ratio = .27-.54; P < .01) and re-irradiation (corrected hazard ratio = .18-.22; P < .01) remained prognostic for survival. A risk score (RS), comprising 5 categories, was developed to predict survival from first progression (ROC: .79). Median survival ranges from 1.0 month (RS-1) to 6.7 months (RS-5).



The majority of patients with DIPG, responding to upfront radiotherapy, do benefit of re-irradiation with acceptable tolerability.
Department of Radiation Oncology, University Medical Center Utrecht and Princess Maxima Center for Pediatric Oncology, Utrecht, The Netherlands. Electronic address: g.o.r.janssens@umcutrecht.nl.
Geert O
GO
Janssens
Pediatric Radiotherapy Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy.
Lorenza
L
Gandola
Department of Radiotherapy, Gustave Roussy Cancer Campus, Villejuif Cedex, France.
Stephanie
S
Bolle
Department of Clinical Oncology, The Royal Marsden NHS Foundation Trust, Sutton, UK.
Henry
H
Mandeville
Department of Radiation Oncology, Hospital Vall d'Hebron, Barcelona, Spain.
Monica
M
Ramos-Albiac
Department of Radiation Oncology, Leuven Cancer Institute, University Hospitals Leuven, Leuven, Belgium.
Karen
K
van Beek
Department of Clinical Oncology, University Hospital Birmingham, Birmingham, UK.
Helen
H
Benghiat
Department of Radiation Oncology, Radboud University Medical Centre, Nijmegen, The Netherlands.
Bianca
B
Hoeben
Department of Pediatric Hematology and Oncology, Hospital Sant Joan de Deu, Barcelona, Spain.
Andres
A
Morales La Madrid
Department of Radiation Therapy, University Hospital Leipzig, Leipzig, Germany.
Rolf-Dieter
RD
Kortmann
Pediatric Oncology Unit, Great Ormond Street Hospital, London, UK.
Darren
D
Hargrave
Department of Radiation Oncology, Leuven Cancer Institute, University Hospitals Leuven, Leuven, Belgium.
Johan
J
Menten
Pediatric Radiotherapy Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy.
Emilia
E
Pecori
Pediatrics Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy.
Veronica
V
Biassoni
Department of Hematology & Oncology, University of Geneva, Geneva, Switzerland; Department of Pediatric Hematology & Oncology, University Hospital Goettingen, Goettingen, Germany.
Andre O
AO
von Bueren
Department of Pediatric Oncology & Hematology, VU University Medical Center, Amsterdam, The Netherlands.
Dannis G
DG
van Vuurden
Pediatrics Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy.
Maura
M
Massimino
Division of Pediatric Neuro-oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Dominik
D
Sturm
Department of Radiation Oncology, University Medical Center Utrecht and Princess Maxima Center for Pediatric Oncology, Utrecht, The Netherlands.
Max
M
Peters
Department of Pediatric Hematology & Oncology, University Hospital Goettingen, Goettingen, Germany.
Christof M
CM
Kramm
D000293:Adolescent; D020295:Brain Stem Neoplasms / Q000401:mortality / Q000532:radiotherapy*; D002648:Child; D002675:Child, Preschool; D018450:Disease Progression; D005260:Female; D005910:Glioma / Q000401:mortality / Q000532:radiotherapy*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D015999:Multivariate Analysis; D011379:Prognosis; D000069475:Re-Irradiation / Q000706:statistics & numerical data*; D012189:Retrospective Studies; D016019:Survival Analysis
Diffuse intrinsic pontine glioma (DIPG); Matched-cohort analysis; Radiotherapy; Re-irradiation; Survival prediction model