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

Publication date: March 2017
Source:European Journal of Cancer, Volume 73
Author(s): Geert O. Janssens, Lorenza Gandola, Stephanie Bolle, Henry Mandeville, Monica Ramos-Albiac, Karen van Beek, Helen Benghiat, Bianca Hoeben, Andres Morales La Madrid, Rolf-Dieter Kortmann, Darren Hargrave, Johan Menten, Emilia Pecori, Veronica Biassoni, Andre O. von Bueren, Dannis G. van Vuurden, Maura Massimino, Dominik Sturm, Max Peters, Christof M. Kramm
BackgroundOverall 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.MethodsAt 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.ResultsMedian 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).ConclusionsThe majority of patients with DIPG, responding to upfront radiotherapy, do benefit of re-irradiation with acceptable tolerability.



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