Clinical, radiologic, pathologic, and molecular characteristics of long-term survivors of Diffuse Intrinsic Pontine Glioma (DIPG)

A collaborative report from the International and European Society for Pediatric Oncology DIPG registries

Lindsey M. Hoffman, Sophie E.M.Veldhuijzen Van Zanten, Niclas Colditz, Joshua Baugh, Brooklyn Chaney, Marion Hoffmann, Adam Lane, Christine Fuller, Lili Miles, Cynthia Hawkins, Ute Bartels, Eric Bouffet, Stewart Goldman, Sarah Leary, Nicholas K. Foreman, Roger Packer, Katherine E. Warren, Alberto Broniscer, Mark W. Kieran, Jane Minturn & 53 others Melanie Comito, Emmett Broxson, Chie-Schin Shih, Soumen Khatua, Murali Chintagumpala, Anne Sophie Carret, Nancy Yanez Escorza, Timothy Hassall, David S. Ziegler, Nicholas Gottardo, Hetal Dholaria, Renee Doughman, Martin Benesch, Rachid Drissi, Javad Nazarian, Nada Jabado, Nathalie Boddaert, Pascale Varlet, Géraldine Giraud, David Castel, Stephanie Puget, Chris Jones, Esther Hulleman, Piergiorgio Modena, Marzia Giagnacovo, Manila Antonelli, Torsten Pietsch, Gerrit H. Gielen, David T.W. Jones, Dominik Sturm, Stefan M. Pfister, Nicolas U. Gerber, Michael A. Grotzer, Elke Pfaff, André O. Von Bueren, Darren Hargrave, Guirish A. Solanki, Filip Jadrijevic Cvrlje, Gertjan J.L. Kaspers, William P. Vandertop, Jacques Grill, Simon Bailey, Veronica Biassoni, Maura Massimino, Raphaël Calmon, Esther Sanchez, Brigitte Bison, Monika Warmuth-Metz, James Leach, Blaise Jones, Dannis G. Van Vuurden, Christof M. Kramm, Maryam Fouladi

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Purpose Diffuse intrinsic pontine glioma (DIPG) is a brainstem malignancy with a median survival of , 1 year. The International and European Society for Pediatric Oncology DIPG Registries collaborated to compare clinical, radiologic, and histomolecular characteristics between short-term survivors (STSs) and long-term survivors (LTSs). Materials and Methods Data abstracted from registry databases included patients from North America, Australia, Germany, Austria, Switzerland, the Netherlands, Italy, France, the United Kingdom, and Croatia. Results Among 1,130 pediatric and young adults with radiographically confirmed DIPG, 122 (11%) were excluded. Of the 1,008 remaining patients, 101 (10%) were LTSs (survival $ 2 years). Median survival time was 11 months (interquartile range, 7.5 to 16 months), and 1-, 2-, 3-, 4-, and 5-year survival rates were 42.3%(95%CI, 38.1%to 44.1%), 9.6%(95% CI, 7.8% to 11.3%), 4.3% (95% CI, 3.2% to 5.8%), 3.2% (95% CI, 2.4%to 4.6%), and 2.2% (95%CI, 1.4%to 3.4%), respectively. LTSs, compared with STSs, more commonly presented at age < 3 or > 10 years (11%v 3% and 33% v 23%, respectively; P<001) and with longer symptom duration (P<001). STSs, compared with LTSs, more commonly presented with cranial nerve palsy (83%v 73%, respectively; P = .008), ring enhancement (38% v23%, respectively; P = .007), necrosis (42%v 26%, respectively; P = .009), and extrapontine extension (92%v 86%, respectively; P = .04). LTSs more commonly received systemic therapy at diagnosis (88% v 75% for STSs; P = .005). Biopsies and autopsies were performed in 299 patients (30%) and 77 patients (10%), respectively; 181 tumors (48%) were molecularly characterized. LTSs were more likely to harbor a HIST1H3B mutation (odds ratio, 1.28; 95% CI, 1.1 to 1.5; P = .002). Conclusion We report clinical, radiologic, and molecular factors that correlate with survival in children and young adults with DIPG, which are important for risk stratification in future clinical trials.

Original languageEnglish (US)
Pages (from-to)1963-1972
Number of pages10
JournalJournal of Clinical Oncology
Volume36
Issue number19
DOIs
StatePublished - Jul 1 2018

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Glioma
Survivors
Registries
Pediatrics
Survival
Young Adult
Cranial Nerve Diseases
Croatia
Austria
North America
Switzerland
Netherlands
Italy
Brain Stem
France
Germany
Autopsy
Neoplasms
Necrosis
Survival Rate

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Clinical, radiologic, pathologic, and molecular characteristics of long-term survivors of Diffuse Intrinsic Pontine Glioma (DIPG) : A collaborative report from the International and European Society for Pediatric Oncology DIPG registries. / Hoffman, Lindsey M.; Van Zanten, Sophie E.M.Veldhuijzen; Colditz, Niclas; Baugh, Joshua; Chaney, Brooklyn; Hoffmann, Marion; Lane, Adam; Fuller, Christine; Miles, Lili; Hawkins, Cynthia; Bartels, Ute; Bouffet, Eric; Goldman, Stewart; Leary, Sarah; Foreman, Nicholas K.; Packer, Roger; Warren, Katherine E.; Broniscer, Alberto; Kieran, Mark W.; Minturn, Jane; Comito, Melanie; Broxson, Emmett; Shih, Chie-Schin; Khatua, Soumen; Chintagumpala, Murali; Carret, Anne Sophie; Escorza, Nancy Yanez; Hassall, Timothy; Ziegler, David S.; Gottardo, Nicholas; Dholaria, Hetal; Doughman, Renee; Benesch, Martin; Drissi, Rachid; Nazarian, Javad; Jabado, Nada; Boddaert, Nathalie; Varlet, Pascale; Giraud, Géraldine; Castel, David; Puget, Stephanie; Jones, Chris; Hulleman, Esther; Modena, Piergiorgio; Giagnacovo, Marzia; Antonelli, Manila; Pietsch, Torsten; Gielen, Gerrit H.; Jones, David T.W.; Sturm, Dominik; Pfister, Stefan M.; Gerber, Nicolas U.; Grotzer, Michael A.; Pfaff, Elke; Von Bueren, André O.; Hargrave, Darren; Solanki, Guirish A.; Cvrlje, Filip Jadrijevic; Kaspers, Gertjan J.L.; Vandertop, William P.; Grill, Jacques; Bailey, Simon; Biassoni, Veronica; Massimino, Maura; Calmon, Raphaël; Sanchez, Esther; Bison, Brigitte; Warmuth-Metz, Monika; Leach, James; Jones, Blaise; Van Vuurden, Dannis G.; Kramm, Christof M.; Fouladi, Maryam.

In: Journal of Clinical Oncology, Vol. 36, No. 19, 01.07.2018, p. 1963-1972.

Research output: Contribution to journalArticle

Hoffman, LM, Van Zanten, SEMV, Colditz, N, Baugh, J, Chaney, B, Hoffmann, M, Lane, A, Fuller, C, Miles, L, Hawkins, C, Bartels, U, Bouffet, E, Goldman, S, Leary, S, Foreman, NK, Packer, R, Warren, KE, Broniscer, A, Kieran, MW, Minturn, J, Comito, M, Broxson, E, Shih, C-S, Khatua, S, Chintagumpala, M, Carret, AS, Escorza, NY, Hassall, T, Ziegler, DS, Gottardo, N, Dholaria, H, Doughman, R, Benesch, M, Drissi, R, Nazarian, J, Jabado, N, Boddaert, N, Varlet, P, Giraud, G, Castel, D, Puget, S, Jones, C, Hulleman, E, Modena, P, Giagnacovo, M, Antonelli, M, Pietsch, T, Gielen, GH, Jones, DTW, Sturm, D, Pfister, SM, Gerber, NU, Grotzer, MA, Pfaff, E, Von Bueren, AO, Hargrave, D, Solanki, GA, Cvrlje, FJ, Kaspers, GJL, Vandertop, WP, Grill, J, Bailey, S, Biassoni, V, Massimino, M, Calmon, R, Sanchez, E, Bison, B, Warmuth-Metz, M, Leach, J, Jones, B, Van Vuurden, DG, Kramm, CM & Fouladi, M 2018, 'Clinical, radiologic, pathologic, and molecular characteristics of long-term survivors of Diffuse Intrinsic Pontine Glioma (DIPG): A collaborative report from the International and European Society for Pediatric Oncology DIPG registries', Journal of Clinical Oncology, vol. 36, no. 19, pp. 1963-1972. https://doi.org/10.1200/JCO.2017.75.9308
Hoffman, Lindsey M. ; Van Zanten, Sophie E.M.Veldhuijzen ; Colditz, Niclas ; Baugh, Joshua ; Chaney, Brooklyn ; Hoffmann, Marion ; Lane, Adam ; Fuller, Christine ; Miles, Lili ; Hawkins, Cynthia ; Bartels, Ute ; Bouffet, Eric ; Goldman, Stewart ; Leary, Sarah ; Foreman, Nicholas K. ; Packer, Roger ; Warren, Katherine E. ; Broniscer, Alberto ; Kieran, Mark W. ; Minturn, Jane ; Comito, Melanie ; Broxson, Emmett ; Shih, Chie-Schin ; Khatua, Soumen ; Chintagumpala, Murali ; Carret, Anne Sophie ; Escorza, Nancy Yanez ; Hassall, Timothy ; Ziegler, David S. ; Gottardo, Nicholas ; Dholaria, Hetal ; Doughman, Renee ; Benesch, Martin ; Drissi, Rachid ; Nazarian, Javad ; Jabado, Nada ; Boddaert, Nathalie ; Varlet, Pascale ; Giraud, Géraldine ; Castel, David ; Puget, Stephanie ; Jones, Chris ; Hulleman, Esther ; Modena, Piergiorgio ; Giagnacovo, Marzia ; Antonelli, Manila ; Pietsch, Torsten ; Gielen, Gerrit H. ; Jones, David T.W. ; Sturm, Dominik ; Pfister, Stefan M. ; Gerber, Nicolas U. ; Grotzer, Michael A. ; Pfaff, Elke ; Von Bueren, André O. ; Hargrave, Darren ; Solanki, Guirish A. ; Cvrlje, Filip Jadrijevic ; Kaspers, Gertjan J.L. ; Vandertop, William P. ; Grill, Jacques ; Bailey, Simon ; Biassoni, Veronica ; Massimino, Maura ; Calmon, Raphaël ; Sanchez, Esther ; Bison, Brigitte ; Warmuth-Metz, Monika ; Leach, James ; Jones, Blaise ; Van Vuurden, Dannis G. ; Kramm, Christof M. ; Fouladi, Maryam. / Clinical, radiologic, pathologic, and molecular characteristics of long-term survivors of Diffuse Intrinsic Pontine Glioma (DIPG) : A collaborative report from the International and European Society for Pediatric Oncology DIPG registries. In: Journal of Clinical Oncology. 2018 ; Vol. 36, No. 19. pp. 1963-1972.
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title = "Clinical, radiologic, pathologic, and molecular characteristics of long-term survivors of Diffuse Intrinsic Pontine Glioma (DIPG): A collaborative report from the International and European Society for Pediatric Oncology DIPG registries",
abstract = "Purpose Diffuse intrinsic pontine glioma (DIPG) is a brainstem malignancy with a median survival of , 1 year. The International and European Society for Pediatric Oncology DIPG Registries collaborated to compare clinical, radiologic, and histomolecular characteristics between short-term survivors (STSs) and long-term survivors (LTSs). Materials and Methods Data abstracted from registry databases included patients from North America, Australia, Germany, Austria, Switzerland, the Netherlands, Italy, France, the United Kingdom, and Croatia. Results Among 1,130 pediatric and young adults with radiographically confirmed DIPG, 122 (11{\%}) were excluded. Of the 1,008 remaining patients, 101 (10{\%}) were LTSs (survival $ 2 years). Median survival time was 11 months (interquartile range, 7.5 to 16 months), and 1-, 2-, 3-, 4-, and 5-year survival rates were 42.3{\%}(95{\%}CI, 38.1{\%}to 44.1{\%}), 9.6{\%}(95{\%} CI, 7.8{\%} to 11.3{\%}), 4.3{\%} (95{\%} CI, 3.2{\%} to 5.8{\%}), 3.2{\%} (95{\%} CI, 2.4{\%}to 4.6{\%}), and 2.2{\%} (95{\%}CI, 1.4{\%}to 3.4{\%}), respectively. LTSs, compared with STSs, more commonly presented at age < 3 or > 10 years (11{\%}v 3{\%} and 33{\%} v 23{\%}, respectively; P<001) and with longer symptom duration (P<001). STSs, compared with LTSs, more commonly presented with cranial nerve palsy (83{\%}v 73{\%}, respectively; P = .008), ring enhancement (38{\%} v23{\%}, respectively; P = .007), necrosis (42{\%}v 26{\%}, respectively; P = .009), and extrapontine extension (92{\%}v 86{\%}, respectively; P = .04). LTSs more commonly received systemic therapy at diagnosis (88{\%} v 75{\%} for STSs; P = .005). Biopsies and autopsies were performed in 299 patients (30{\%}) and 77 patients (10{\%}), respectively; 181 tumors (48{\%}) were molecularly characterized. LTSs were more likely to harbor a HIST1H3B mutation (odds ratio, 1.28; 95{\%} CI, 1.1 to 1.5; P = .002). Conclusion We report clinical, radiologic, and molecular factors that correlate with survival in children and young adults with DIPG, which are important for risk stratification in future clinical trials.",
author = "Hoffman, {Lindsey M.} and {Van Zanten}, {Sophie E.M.Veldhuijzen} and Niclas Colditz and Joshua Baugh and Brooklyn Chaney and Marion Hoffmann and Adam Lane and Christine Fuller and Lili Miles and Cynthia Hawkins and Ute Bartels and Eric Bouffet and Stewart Goldman and Sarah Leary and Foreman, {Nicholas K.} and Roger Packer and Warren, {Katherine E.} and Alberto Broniscer and Kieran, {Mark W.} and Jane Minturn and Melanie Comito and Emmett Broxson and Chie-Schin Shih and Soumen Khatua and Murali Chintagumpala and Carret, {Anne Sophie} and Escorza, {Nancy Yanez} and Timothy Hassall and Ziegler, {David S.} and Nicholas Gottardo and Hetal Dholaria and Renee Doughman and Martin Benesch and Rachid Drissi and Javad Nazarian and Nada Jabado and Nathalie Boddaert and Pascale Varlet and G{\'e}raldine Giraud and David Castel and Stephanie Puget and Chris Jones and Esther Hulleman and Piergiorgio Modena and Marzia Giagnacovo and Manila Antonelli and Torsten Pietsch and Gielen, {Gerrit H.} and Jones, {David T.W.} and Dominik Sturm and Pfister, {Stefan M.} and Gerber, {Nicolas U.} and Grotzer, {Michael A.} and Elke Pfaff and {Von Bueren}, {Andr{\'e} O.} and Darren Hargrave and Solanki, {Guirish A.} and Cvrlje, {Filip Jadrijevic} and Kaspers, {Gertjan J.L.} and Vandertop, {William P.} and Jacques Grill and Simon Bailey and Veronica Biassoni and Maura Massimino and Rapha{\"e}l Calmon and Esther Sanchez and Brigitte Bison and Monika Warmuth-Metz and James Leach and Blaise Jones and {Van Vuurden}, {Dannis G.} and Kramm, {Christof M.} and Maryam Fouladi",
year = "2018",
month = "7",
day = "1",
doi = "10.1200/JCO.2017.75.9308",
language = "English (US)",
volume = "36",
pages = "1963--1972",
journal = "Journal of Clinical Oncology",
issn = "0732-183X",
publisher = "American Society of Clinical Oncology",
number = "19",

}

TY - JOUR

T1 - Clinical, radiologic, pathologic, and molecular characteristics of long-term survivors of Diffuse Intrinsic Pontine Glioma (DIPG)

T2 - A collaborative report from the International and European Society for Pediatric Oncology DIPG registries

AU - Hoffman, Lindsey M.

AU - Van Zanten, Sophie E.M.Veldhuijzen

AU - Colditz, Niclas

AU - Baugh, Joshua

AU - Chaney, Brooklyn

AU - Hoffmann, Marion

AU - Lane, Adam

AU - Fuller, Christine

AU - Miles, Lili

AU - Hawkins, Cynthia

AU - Bartels, Ute

AU - Bouffet, Eric

AU - Goldman, Stewart

AU - Leary, Sarah

AU - Foreman, Nicholas K.

AU - Packer, Roger

AU - Warren, Katherine E.

AU - Broniscer, Alberto

AU - Kieran, Mark W.

AU - Minturn, Jane

AU - Comito, Melanie

AU - Broxson, Emmett

AU - Shih, Chie-Schin

AU - Khatua, Soumen

AU - Chintagumpala, Murali

AU - Carret, Anne Sophie

AU - Escorza, Nancy Yanez

AU - Hassall, Timothy

AU - Ziegler, David S.

AU - Gottardo, Nicholas

AU - Dholaria, Hetal

AU - Doughman, Renee

AU - Benesch, Martin

AU - Drissi, Rachid

AU - Nazarian, Javad

AU - Jabado, Nada

AU - Boddaert, Nathalie

AU - Varlet, Pascale

AU - Giraud, Géraldine

AU - Castel, David

AU - Puget, Stephanie

AU - Jones, Chris

AU - Hulleman, Esther

AU - Modena, Piergiorgio

AU - Giagnacovo, Marzia

AU - Antonelli, Manila

AU - Pietsch, Torsten

AU - Gielen, Gerrit H.

AU - Jones, David T.W.

AU - Sturm, Dominik

AU - Pfister, Stefan M.

AU - Gerber, Nicolas U.

AU - Grotzer, Michael A.

AU - Pfaff, Elke

AU - Von Bueren, André O.

AU - Hargrave, Darren

AU - Solanki, Guirish A.

AU - Cvrlje, Filip Jadrijevic

AU - Kaspers, Gertjan J.L.

AU - Vandertop, William P.

AU - Grill, Jacques

AU - Bailey, Simon

AU - Biassoni, Veronica

AU - Massimino, Maura

AU - Calmon, Raphaël

AU - Sanchez, Esther

AU - Bison, Brigitte

AU - Warmuth-Metz, Monika

AU - Leach, James

AU - Jones, Blaise

AU - Van Vuurden, Dannis G.

AU - Kramm, Christof M.

AU - Fouladi, Maryam

PY - 2018/7/1

Y1 - 2018/7/1

N2 - Purpose Diffuse intrinsic pontine glioma (DIPG) is a brainstem malignancy with a median survival of , 1 year. The International and European Society for Pediatric Oncology DIPG Registries collaborated to compare clinical, radiologic, and histomolecular characteristics between short-term survivors (STSs) and long-term survivors (LTSs). Materials and Methods Data abstracted from registry databases included patients from North America, Australia, Germany, Austria, Switzerland, the Netherlands, Italy, France, the United Kingdom, and Croatia. Results Among 1,130 pediatric and young adults with radiographically confirmed DIPG, 122 (11%) were excluded. Of the 1,008 remaining patients, 101 (10%) were LTSs (survival $ 2 years). Median survival time was 11 months (interquartile range, 7.5 to 16 months), and 1-, 2-, 3-, 4-, and 5-year survival rates were 42.3%(95%CI, 38.1%to 44.1%), 9.6%(95% CI, 7.8% to 11.3%), 4.3% (95% CI, 3.2% to 5.8%), 3.2% (95% CI, 2.4%to 4.6%), and 2.2% (95%CI, 1.4%to 3.4%), respectively. LTSs, compared with STSs, more commonly presented at age < 3 or > 10 years (11%v 3% and 33% v 23%, respectively; P<001) and with longer symptom duration (P<001). STSs, compared with LTSs, more commonly presented with cranial nerve palsy (83%v 73%, respectively; P = .008), ring enhancement (38% v23%, respectively; P = .007), necrosis (42%v 26%, respectively; P = .009), and extrapontine extension (92%v 86%, respectively; P = .04). LTSs more commonly received systemic therapy at diagnosis (88% v 75% for STSs; P = .005). Biopsies and autopsies were performed in 299 patients (30%) and 77 patients (10%), respectively; 181 tumors (48%) were molecularly characterized. LTSs were more likely to harbor a HIST1H3B mutation (odds ratio, 1.28; 95% CI, 1.1 to 1.5; P = .002). Conclusion We report clinical, radiologic, and molecular factors that correlate with survival in children and young adults with DIPG, which are important for risk stratification in future clinical trials.

AB - Purpose Diffuse intrinsic pontine glioma (DIPG) is a brainstem malignancy with a median survival of , 1 year. The International and European Society for Pediatric Oncology DIPG Registries collaborated to compare clinical, radiologic, and histomolecular characteristics between short-term survivors (STSs) and long-term survivors (LTSs). Materials and Methods Data abstracted from registry databases included patients from North America, Australia, Germany, Austria, Switzerland, the Netherlands, Italy, France, the United Kingdom, and Croatia. Results Among 1,130 pediatric and young adults with radiographically confirmed DIPG, 122 (11%) were excluded. Of the 1,008 remaining patients, 101 (10%) were LTSs (survival $ 2 years). Median survival time was 11 months (interquartile range, 7.5 to 16 months), and 1-, 2-, 3-, 4-, and 5-year survival rates were 42.3%(95%CI, 38.1%to 44.1%), 9.6%(95% CI, 7.8% to 11.3%), 4.3% (95% CI, 3.2% to 5.8%), 3.2% (95% CI, 2.4%to 4.6%), and 2.2% (95%CI, 1.4%to 3.4%), respectively. LTSs, compared with STSs, more commonly presented at age < 3 or > 10 years (11%v 3% and 33% v 23%, respectively; P<001) and with longer symptom duration (P<001). STSs, compared with LTSs, more commonly presented with cranial nerve palsy (83%v 73%, respectively; P = .008), ring enhancement (38% v23%, respectively; P = .007), necrosis (42%v 26%, respectively; P = .009), and extrapontine extension (92%v 86%, respectively; P = .04). LTSs more commonly received systemic therapy at diagnosis (88% v 75% for STSs; P = .005). Biopsies and autopsies were performed in 299 patients (30%) and 77 patients (10%), respectively; 181 tumors (48%) were molecularly characterized. LTSs were more likely to harbor a HIST1H3B mutation (odds ratio, 1.28; 95% CI, 1.1 to 1.5; P = .002). Conclusion We report clinical, radiologic, and molecular factors that correlate with survival in children and young adults with DIPG, which are important for risk stratification in future clinical trials.

UR - http://www.scopus.com/inward/record.url?scp=85049646163&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85049646163&partnerID=8YFLogxK

U2 - 10.1200/JCO.2017.75.9308

DO - 10.1200/JCO.2017.75.9308

M3 - Article

VL - 36

SP - 1963

EP - 1972

JO - Journal of Clinical Oncology

JF - Journal of Clinical Oncology

SN - 0732-183X

IS - 19

ER -