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

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

doi:10.1016/j.ejca.2016.12.007

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

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

Research output: Contribution to journal › Article › peer-review

123 Citations (Scopus)

Abstract

BACKGROUND: 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.

METHODS: 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.

RESULTS: 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).

CONCLUSIONS: The majority of patients with DIPG, responding to upfront radiotherapy, do benefit of re-irradiation with acceptable tolerability.

Original language	English
Pages (from-to)	38-47
Number of pages	10
Journal	European Journal of Cancer
Volume	73
DOIs	https://doi.org/10.1016/j.ejca.2016.12.007
Publication status	Published - Mar 2017
Externally published	Yes

Keywords

Adolescent
Brain Stem Neoplasms/mortality
Child
Child, Preschool
Disease Progression
Female
Glioma/mortality
Humans
Magnetic Resonance Imaging
Male
Multivariate Analysis
Prognosis
Re-Irradiation/statistics & numerical data
Retrospective Studies
Survival Analysis

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10.1016/j.ejca.2016.12.007

Cite this

Janssens, G. O., Gandola, L., Bolle, S., Mandeville, H., Ramos-Albiac, M., van Beek, K., Benghiat, H., Hoeben, B., Morales La Madrid, A., Kortmann, R.-D., Hargrave, D., Menten, J., Pecori, E., Biassoni, V., von Bueren, A. O., van Vuurden, D. G., Massimino, M., Sturm, D., Peters, M., & Kramm, C. M. (2017). 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. European Journal of Cancer, 73, 38-47. https://doi.org/10.1016/j.ejca.2016.12.007

@article{e115d1379bf54eb09d804779bec19be5,

title = "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",

abstract = "BACKGROUND: 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.METHODS: 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.RESULTS: 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).CONCLUSIONS: The majority of patients with DIPG, responding to upfront radiotherapy, do benefit of re-irradiation with acceptable tolerability.",

keywords = "Adolescent, Brain Stem Neoplasms/mortality, Child, Child, Preschool, Disease Progression, Female, Glioma/mortality, Humans, Magnetic Resonance Imaging, Male, Multivariate Analysis, Prognosis, Re-Irradiation/statistics \& numerical data, Retrospective Studies, Survival Analysis",

author = "Janssens, \{Geert O\} and Lorenza Gandola and Stephanie Bolle and Henry Mandeville and Monica Ramos-Albiac and \{van Beek\}, Karen and Helen Benghiat and Bianca Hoeben and \{Morales La Madrid\}, Andres and Rolf-Dieter Kortmann and Darren Hargrave and Johan Menten and Emilia Pecori and Veronica Biassoni and \{von Bueren\}, \{Andre O\} and \{van Vuurden\}, \{Dannis G\} and Maura Massimino and Dominik Sturm and Max Peters and Kramm, \{Christof M\}",

year = "2017",

month = mar,

doi = "10.1016/j.ejca.2016.12.007",

language = "English",

volume = "73",

pages = "38--47",

journal = "European Journal of Cancer",

issn = "1879-0852",

publisher = "Elsevier Ltd.",

}

Janssens, GO, Gandola, L, Bolle, S, Mandeville, H, Ramos-Albiac, M, van Beek, K, Benghiat, H, Hoeben, B, Morales La Madrid, A, Kortmann, R-D, Hargrave, D, Menten, J, Pecori, E, Biassoni, V, von Bueren, AO, van Vuurden, DG, Massimino, M, Sturm, D, Peters, M & Kramm, CM 2017, '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', European Journal of Cancer, vol. 73, pp. 38-47. https://doi.org/10.1016/j.ejca.2016.12.007

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. / Janssens, Geert O; Gandola, Lorenza; Bolle, Stephanie et al.
In: European Journal of Cancer, Vol. 73, 03.2017, p. 38-47.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Survival benefit for patients with diffuse intrinsic pontine glioma (DIPG) undergoing re-irradiation at first progression

T2 - A matched-cohort analysis on behalf of the SIOP-E-HGG/DIPG working group

AU - Janssens, Geert O

AU - Gandola, Lorenza

AU - Bolle, Stephanie

AU - Mandeville, Henry

AU - Ramos-Albiac, Monica

AU - van Beek, Karen

AU - Benghiat, Helen

AU - Hoeben, Bianca

AU - Morales La Madrid, Andres

AU - Kortmann, Rolf-Dieter

AU - Hargrave, Darren

AU - Menten, Johan

AU - Pecori, Emilia

AU - Biassoni, Veronica

AU - von Bueren, Andre O

AU - van Vuurden, Dannis G

AU - Massimino, Maura

AU - Sturm, Dominik

AU - Peters, Max

AU - Kramm, Christof M

PY - 2017/3

Y1 - 2017/3

N2 - BACKGROUND: 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.METHODS: 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.RESULTS: 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).CONCLUSIONS: The majority of patients with DIPG, responding to upfront radiotherapy, do benefit of re-irradiation with acceptable tolerability.

AB - BACKGROUND: 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.METHODS: 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.RESULTS: 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).CONCLUSIONS: The majority of patients with DIPG, responding to upfront radiotherapy, do benefit of re-irradiation with acceptable tolerability.

KW - Adolescent

KW - Brain Stem Neoplasms/mortality

KW - Child

KW - Child, Preschool

KW - Disease Progression

KW - Female

KW - Glioma/mortality

KW - Humans

KW - Magnetic Resonance Imaging

KW - Male

KW - Multivariate Analysis

KW - Prognosis

KW - Re-Irradiation/statistics & numerical data

KW - Retrospective Studies

KW - Survival Analysis

UR - https://www.scopus.com/pages/publications/85012281778

U2 - 10.1016/j.ejca.2016.12.007

DO - 10.1016/j.ejca.2016.12.007

M3 - Article

C2 - 28161497

SN - 1879-0852

VL - 73

SP - 38

EP - 47

JO - European Journal of Cancer

JF - European Journal of Cancer

ER -

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

Abstract

Keywords

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