Therapeutic Impact of Cytoreductive Surgery and Irradiation of
Posterior Fossa Ependymoma in the Molecular Era: A
Retrospective Multicohort Analysis

J 2016

Therapeutic Impact of Cytoreductive Surgery and Irradiation of Posterior Fossa Ependymoma in the Molecular Era: A Retrospective Multicohort Analysis

RAMASWAMY, Vijay, Thomas HIELSCHER, Stephen C. MACK, Alvaro LASSALETTA, Tong LIN et. al.

Basic information

Original name

Therapeutic Impact of Cytoreductive Surgery and Irradiation of Posterior Fossa Ependymoma in the Molecular Era: A Retrospective Multicohort Analysis

Authors

RAMASWAMY, Vijay (124 Canada), Thomas HIELSCHER (276 Germany), Stephen C. MACK (124 Canada), Alvaro LASSALETTA (124 Canada), Tong LIN (840 United States of America), Kristian W. PAJTLER (276 Germany), David T.W. JONES (276 Germany), Betty LUU (124 Canada), Florence M.G. CAVALLI (124 Canada), Kenneth ALDAPE (124 Canada), Marc REMKE (276 Germany), Martin MYNAREK (276 Germany), Stefan RUTKOWSKI (276 Germany), Sridharan GURURANGAN (840 United States of America), Roger E. MCLENDON (840 United States of America), Eric S. LIPP (840 United States of America), Christopher DUNHAM (124 Canada), Juliette HUKIN (124 Canada), David D. EISENSTAT (124 Canada), Dorcas FULTON (124 Canada), Frank K. H. van LANDEGHEM (124 Canada), Mariarita SANTI (840 United States of America), Marie-Lise C. van VEELEN (528 Netherlands), Erwin G. VAN MEIR (840 United States of America), Satoru OSUKA (840 United States of America), Xing FAN (840 United States of America), Karin M. MURASZKO (840 United States of America), Daniela P.C. TIRAPELLI (76 Brazil), Sueli M. OBA-SHINJO (76 Brazil), Suely K.N. MARIE (76 Brazil), Carlos G. CARLOTTI (76 Brazil), Ji Yeoun LEE (410 Republic of Korea), Amulya A. Nagesware RAO (840 United States of America), Caterina GIANNINI (840 United States of America), Claudia C. FARIA (620 Portugal), Sofia NUNES (620 Portugal), Jaume MORA (724 Spain), Ronald L. HAMILTON (840 United States of America), Peter HAUSER (348 Hungary), Nada JABADO (124 Canada), Kevin PETRECCA (124 Canada), Shin JUNG (410 Republic of Korea), Luca MASSIMI (380 Italy), Massimo ZOLLO (380 Italy), Giuseppe CINALLI (380 Italy), László BOGNÁR (348 Hungary), Almos KLEKNER (348 Hungary), Tibor HORTOBÁGYI (348 Hungary), Sarah LEARY (840 United States of America), Ralph P. ERMOIAN (840 United States of America), James M. OLSON (840 United States of America), Jeffrey R. LEONARD (840 United States of America), Corrine GARDNER (840 United States of America), Wieslawa A. GRAJKOWSKA (616 Poland), Lola B. CHAMBLESS (840 United States of America), Jason CAIN (36 Australia), Charles G. EBERHART (840 United States of America), Sama AHSAN (840 United States of America), Maura MASSIMINO (380 Italy), Felice GIANGASPERO (380 Italy), Francesca R. BUTTARELLI (380 Italy), Roger J. PACKER (840 United States of America), Lyndsey EMERY (840 United States of America), William H. YONG (840 United States of America), Horacio SOTO (840 United States of America), Linda M. LIAU (840 United States of America), Richard EVERSON (840 United States of America), Andrew GROSSBACH (840 United States of America), Tarek SHALABY (756 Switzerland), Michael GROTZER (756 Switzerland), Matthias A. KARAJANNIS (840 United States of America), David ZAGZAG (840 United States of America), Helen WHEELER (36 Australia), Katja von HOFF (276 Germany), Marta M. ALONSO (724 Spain), Teresa TUON (724 Spain), Ulrich SCHÜLLER (276 Germany), Karel ZITTERBART (203 Czech Republic, guarantor, belonging to the institution), Jaroslav ŠTĚRBA (203 Czech Republic, belonging to the institution), Jennifer A. CHAN (124 Canada), Miguel GUZMAN (840 United States of America), Samer K. ELBABAA (840 United States of America), Howard COLMAN (840 United States of America), Girish DHALL (840 United States of America), Paul G. FISHER (840 United States of America), Maryam FOULADI (840 United States of America), Amar GAJJAR (840 United States of America), Stewart GOLDMAN (840 United States of America), Eugene HWANG (840 United States of America), Marcel KOOL (276 Germany), Harshad LADHA (840 United States of America), Elizabeth VERA-BOLANOS (840 United States of America), Khalida WANI (840 United States of America), Frank LIEBERMAN (840 United States of America), Tom MIKKELSEN (840 United States of America), Antonio M. OMURO (840 United States of America), Ian F. POLLACK (840 United States of America), Michael PRADOS (840 United States of America), H. Ian ROBINS (840 United States of America), Riccardo SOFFIETTI (380 Italy), Jing WU (840 United States of America), Phillipe METELLUS (250 France), Uri TABORI (124 Canada), Ute BARTELS (124 Canada), Eric BOUFFET (124 Canada), Cynthia E. HAWKINS (124 Canada), James T. RUTKA (124 Canada), Peter DIRKS (124 Canada), Stefan M. PFISTER (276 Germany), Thomas E. MERCHANT (840 United States of America), Mark R. GILBERT (840 United States of America), Terri S. ARMSTRONG (840 United States of America), Andrey KORSHUNOV (276 Germany), David W. ELLISON (840 United States of America) and Michael D. TAYLOR (124 Canada)

Edition

Journal of Clinical Oncology, Alexandria, American Society of Clinical Oncology, 2016, 0732-183X

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30200 3.2 Clinical medicine

Country of publisher

United States of America

Confidentiality degree

není předmětem státního či obchodního tajemství

Impact factor

Impact factor: 24.008

RIV identification code

RIV/00216224:14110/16:00092056

Organization unit

Faculty of Medicine

DOI

http://dx.doi.org/10.1200/JCO.2015.65.7825

UT WoS

000381497000006

Keywords in English

CONFORMAL RADIATION-THERAPY; NEWLY-DIAGNOSED EPENDYMOMA; PHASE-II TRIAL; BRAIN-TUMORS; PEDIATRIC-PATIENTS; CRANIAL RADIATION; CHILDREN; CHILDHOOD; CHEMOTHERAPY; AGE

Abstract

V originále

Purpose Posterior fossa ependymoma comprises two distinct molecular variants termed EPN_PFA and EPN_PFB that have a distinct biology and natural history. The therapeutic value of cytoreductive surgery and radiation therapy for posterior fossa ependymoma after accounting for molecular subgroup is not known.MethodsFour independent nonoverlapping retrospective cohorts of posterior fossa ependymomas (n = 820) were profiled using genome-wide methylation arrays. Risk stratification models were designed based on known clinical and newly described molecular biomarkers identified by multivariable Cox proportional hazards analyses. Results Molecular subgroup is a powerful independent predictor of outcome even when accounting for age or treatment regimen. Incompletely resected EPN_PFA ependymomas have a dismal prognosis, with a 5-year progression-free survival ranging from 26.1% to 56.8% across all four cohorts. Although first-line (adjuvant) radiation is clearly beneficial for completely resected EPN_PFA, a substantial proportion of patients with EPN_PFB can be cured with surgery alone, and patients with relapsed EPN_PFB can often be treated successfully with delayed external-beam irradiation. Conclusion The most impactful biomarker for posterior fossa ependymoma is molecular subgroup affiliation, independent of other demographic or treatment variables. However, both EPN_PFA and EPN_PFB still benefit from increased extent of resection, with the survival rates being particularly poor for subtotally resected EPN_PFA, even with adjuvant radiation therapy. Patients with EPN_PFB who undergo gross total resection are at lower risk for relapse and should be considered for inclusion in a randomized clinical trial of observation alone with radiation reserved for those who experience recurrence.

Links

ROZV/20/LF/2015, interní kód MU

Name: LF - Příspěvek IP 2015

Investor: Ministry of Education, Youth and Sports of the CR

Citovat

RAMASWAMY, Vijay, Thomas HIELSCHER, Stephen C. MACK, Alvaro LASSALETTA, Tong LIN, Kristian W. PAJTLER, David T.W. JONES, Betty LUU, Florence M.G. CAVALLI, Kenneth ALDAPE, Marc REMKE, Martin MYNAREK, Stefan RUTKOWSKI, Sridharan GURURANGAN, Roger E. MCLENDON, Eric S. LIPP, Christopher DUNHAM, Juliette HUKIN, David D. EISENSTAT, Dorcas FULTON, Frank K. H. van LANDEGHEM, Mariarita SANTI, Marie-Lise C. van VEELEN, Erwin G. VAN MEIR, Satoru OSUKA, Xing FAN, Karin M. MURASZKO, Daniela P.C. TIRAPELLI, Sueli M. OBA-SHINJO, Suely K.N. MARIE, Carlos G. CARLOTTI, Ji Yeoun LEE, Amulya A. Nagesware RAO, Caterina GIANNINI, Claudia C. FARIA, Sofia NUNES, Jaume MORA, Ronald L. HAMILTON, Peter HAUSER, Nada JABADO, Kevin PETRECCA, Shin JUNG, Luca MASSIMI, Massimo ZOLLO, Giuseppe CINALLI, László BOGNÁR, Almos KLEKNER, Tibor HORTOBÁGYI, Sarah LEARY, Ralph P. ERMOIAN, James M. OLSON, Jeffrey R. LEONARD, Corrine GARDNER, Wieslawa A. GRAJKOWSKA, Lola B. CHAMBLESS, Jason CAIN, Charles G. EBERHART, Sama AHSAN, Maura MASSIMINO, Felice GIANGASPERO, Francesca R. BUTTARELLI, Roger J. PACKER, Lyndsey EMERY, William H. YONG, Horacio SOTO, Linda M. LIAU, Richard EVERSON, Andrew GROSSBACH, Tarek SHALABY, Michael GROTZER, Matthias A. KARAJANNIS, David ZAGZAG, Helen WHEELER, Katja von HOFF, Marta M. ALONSO, Teresa TUON, Ulrich SCHÜLLER, Karel ZITTERBART, Jaroslav ŠTĚRBA, Jennifer A. CHAN, Miguel GUZMAN, Samer K. ELBABAA, Howard COLMAN, Girish DHALL, Paul G. FISHER, Maryam FOULADI, Amar GAJJAR, Stewart GOLDMAN, Eugene HWANG, Marcel KOOL, Harshad LADHA, Elizabeth VERA-BOLANOS, Khalida WANI, Frank LIEBERMAN, Tom MIKKELSEN, Antonio M. OMURO, Ian F. POLLACK, Michael PRADOS, H. Ian ROBINS, Riccardo SOFFIETTI, Jing WU, Phillipe METELLUS, Uri TABORI, Ute BARTELS, Eric BOUFFET, Cynthia E. HAWKINS, James T. RUTKA, Peter DIRKS, Stefan M. PFISTER, Thomas E. MERCHANT, Mark R. GILBERT, Terri S. ARMSTRONG, Andrey KORSHUNOV, David W. ELLISON and Michael D. TAYLOR. Therapeutic Impact of Cytoreductive Surgery and Irradiation of Posterior Fossa Ependymoma in the Molecular Era: A Retrospective Multicohort Analysis. Journal of Clinical Oncology. Alexandria: American Society of Clinical Oncology, 2016, vol. 34, No 21, p. 2468-2490. ISSN 0732-183X. Available from: https://dx.doi.org/10.1200/JCO.2015.65.7825.

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   author = {Ramaswamy, Vijay and Hielscher, Thomas and Mack, Stephen C. and Lassaletta, Alvaro and Lin, Tong and Pajtler, Kristian W. and Jones, David T.W. and Luu, Betty and Cavalli, Florence M.G. and Aldape, Kenneth and Remke, Marc and Mynarek, Martin and Rutkowski, Stefan and Gururangan, Sridharan and McLendon, Roger E. and Lipp, Eric S. and Dunham, Christopher and Hukin, Juliette and Eisenstat, David D. and Fulton, Dorcas and Landeghem, Frank K. H. van and Santi, Mariarita and Veelen, MarieandLise C. van and Van Meir, Erwin G. and Osuka, Satoru and Fan, Xing and Muraszko, Karin M. and Tirapelli, Daniela P.C. and ObaandShinjo, Sueli M. and Marie, Suely K.N. and Carlotti, Carlos G. and Lee, Ji Yeoun and Rao, Amulya A. Nagesware and Giannini, Caterina and Faria, Claudia C. and Nunes, Sofia and Mora, Jaume and Hamilton, Ronald L. and Hauser, Peter and Jabado, Nada and Petrecca, Kevin and Jung, Shin and Massimi, Luca and Zollo, Massimo and Cinalli, Giuseppe and Bognár, László and Klekner, Almos and Hortobágyi, Tibor and Leary, Sarah and Ermoian, Ralph P. and Olson, James M. and Leonard, Jeffrey R. and Gardner, Corrine and Grajkowska, Wieslawa A. and Chambless, Lola B. and Cain, Jason and Eberhart, Charles G. and Ahsan, Sama and Massimino, Maura and Giangaspero, Felice and Buttarelli, Francesca R. and Packer, Roger J. and Emery, Lyndsey and Yong, William H. and Soto, Horacio and Liau, Linda M. and Everson, Richard and Grossbach, Andrew and Shalaby, Tarek and Grotzer, Michael and Karajannis, Matthias A. and Zagzag, David and Wheeler, Helen and Hoff, Katja von and Alonso, Marta M. and Tuon, Teresa and Schüller, Ulrich and Zitterbart, Karel and Štěrba, Jaroslav and Chan, Jennifer A. and Guzman, Miguel and Elbabaa, Samer K. and Colman, Howard and Dhall, Girish and Fisher, Paul G. and Fouladi, Maryam and Gajjar, Amar and Goldman, Stewart and Hwang, Eugene and Kool, Marcel and Ladha, Harshad and VeraandBolanos, Elizabeth and Wani, Khalida and Lieberman, Frank and Mikkelsen, Tom and Omuro, Antonio M. and Pollack, Ian F. and Prados, Michael and Robins, H. Ian and Soffietti, Riccardo and Wu, Jing and Metellus, Phillipe and Tabori, Uri and Bartels, Ute and Bouffet, Eric and Hawkins, Cynthia E. and Rutka, James T. and Dirks, Peter and Pfister, Stefan M. and Merchant, Thomas E. and Gilbert, Mark R. and Armstrong, Terri S. and Korshunov, Andrey and Ellison, David W. and Taylor, Michael D.},
   article_location = {Alexandria},
   article_number = {21},
   doi = {http://dx.doi.org/10.1200/JCO.2015.65.7825},
   keywords = {CONFORMAL RADIATION-THERAPY; NEWLY-DIAGNOSED EPENDYMOMA; PHASE-II TRIAL; BRAIN-TUMORS; PEDIATRIC-PATIENTS; CRANIAL RADIATION; CHILDREN; CHILDHOOD; CHEMOTHERAPY; AGE},
   language = {eng},
   issn = {0732-183X},
   journal = {Journal of Clinical Oncology},
   title = {Therapeutic Impact of Cytoreductive Surgery and Irradiation of Posterior Fossa Ependymoma in the Molecular Era: A Retrospective Multicohort Analysis},
   volume = {34},
   year = {2016}
}

TY  - JOUR
ID  - 1362990
AU  - Ramaswamy, Vijay - Hielscher, Thomas - Mack, Stephen C. - Lassaletta, Alvaro - Lin, Tong - Pajtler, Kristian W. - Jones, David T.W. - Luu, Betty - Cavalli, Florence M.G. - Aldape, Kenneth - Remke, Marc - Mynarek, Martin - Rutkowski, Stefan - Gururangan, Sridharan - McLendon, Roger E. - Lipp, Eric S. - Dunham, Christopher - Hukin, Juliette - Eisenstat, David D. - Fulton, Dorcas - Landeghem, Frank K. H. van - Santi, Mariarita - Veelen, Marie-Lise C. van - Van Meir, Erwin G. - Osuka, Satoru - Fan, Xing - Muraszko, Karin M. - Tirapelli, Daniela P.C. - Oba-Shinjo, Sueli M. - Marie, Suely K.N. - Carlotti, Carlos G. - Lee, Ji Yeoun - Rao, Amulya A. Nagesware - Giannini, Caterina - Faria, Claudia C. - Nunes, Sofia - Mora, Jaume - Hamilton, Ronald L. - Hauser, Peter - Jabado, Nada - Petrecca, Kevin - Jung, Shin - Massimi, Luca - Zollo, Massimo - Cinalli, Giuseppe - Bognár, László - Klekner, Almos - Hortobágyi, Tibor - Leary, Sarah - Ermoian, Ralph P. - Olson, James M. - Leonard, Jeffrey R. - Gardner, Corrine - Grajkowska, Wieslawa A. - Chambless, Lola B. - Cain, Jason - Eberhart, Charles G. - Ahsan, Sama - Massimino, Maura - Giangaspero, Felice - Buttarelli, Francesca R. - Packer, Roger J. - Emery, Lyndsey - Yong, William H. - Soto, Horacio - Liau, Linda M. - Everson, Richard - Grossbach, Andrew - Shalaby, Tarek - Grotzer, Michael - Karajannis, Matthias A. - Zagzag, David - Wheeler, Helen - Hoff, Katja von - Alonso, Marta M. - Tuon, Teresa - Schüller, Ulrich - Zitterbart, Karel - Štěrba, Jaroslav - Chan, Jennifer A. - Guzman, Miguel - Elbabaa, Samer K. - Colman, Howard - Dhall, Girish - Fisher, Paul G. - Fouladi, Maryam - Gajjar, Amar - Goldman, Stewart - Hwang, Eugene - Kool, Marcel - Ladha, Harshad - Vera-Bolanos, Elizabeth - Wani, Khalida - Lieberman, Frank - Mikkelsen, Tom - Omuro, Antonio M. - Pollack, Ian F. - Prados, Michael - Robins, H. Ian - Soffietti, Riccardo - Wu, Jing - Metellus, Phillipe - Tabori, Uri - Bartels, Ute - Bouffet, Eric - Hawkins, Cynthia E. - Rutka, James T. - Dirks, Peter - Pfister, Stefan M. - Merchant, Thomas E. - Gilbert, Mark R. - Armstrong, Terri S. - Korshunov, Andrey - Ellison, David W. - Taylor, Michael D.
PY  - 2016
TI  - Therapeutic Impact of Cytoreductive Surgery and Irradiation of Posterior Fossa Ependymoma in the Molecular Era: A Retrospective Multicohort Analysis
JF  - Journal of Clinical Oncology
VL  - 34
IS  - 21
SP  - 2468-2490
EP  - 2468-2490
PB  - American Society of Clinical Oncology
SN  - 0732183X
KW  - CONFORMAL RADIATION-THERAPY
KW  - NEWLY-DIAGNOSED EPENDYMOMA
KW  - PHASE-II TRIAL
KW  - BRAIN-TUMORS
KW  - PEDIATRIC-PATIENTS
KW  - CRANIAL RADIATION
KW  - CHILDREN
KW  - CHILDHOOD
KW  - CHEMOTHERAPY
KW  - AGE
N2  - Purpose Posterior fossa ependymoma comprises two distinct molecular variants termed EPN_PFA and EPN_PFB that have a distinct biology and natural history. The therapeutic value of cytoreductive surgery and radiation therapy for posterior fossa ependymoma after accounting for molecular subgroup is not known.MethodsFour independent nonoverlapping retrospective cohorts of posterior fossa ependymomas (n = 820) were profiled using genome-wide methylation arrays. Risk stratification models were designed based on known clinical and newly described molecular biomarkers identified by multivariable Cox proportional hazards analyses. Results Molecular subgroup is a powerful independent predictor of outcome even when accounting for age or treatment regimen. Incompletely resected EPN_PFA ependymomas have a dismal prognosis, with a 5-year progression-free survival ranging from 26.1% to 56.8% across all four cohorts. Although first-line (adjuvant) radiation is clearly beneficial for completely resected EPN_PFA, a substantial proportion of patients with EPN_PFB can be cured with surgery alone, and patients with relapsed EPN_PFB can often be treated successfully with delayed external-beam irradiation. Conclusion The most impactful biomarker for posterior fossa ependymoma is molecular subgroup affiliation, independent of other demographic or treatment variables. However, both EPN_PFA and EPN_PFB still benefit from increased extent of resection, with the survival rates being particularly poor for subtotally resected EPN_PFA, even with adjuvant radiation therapy. Patients with EPN_PFB who undergo gross total resection are at lower risk for relapse and should be considered for inclusion in a randomized clinical trial of observation alone with radiation reserved for those who experience recurrence.
ER  -

RAMASWAMY, Vijay, Thomas HIELSCHER, Stephen C. MACK, Alvaro LASSALETTA, Tong LIN, Kristian W. PAJTLER, David T.W. JONES, Betty LUU, Florence M.G. CAVALLI, Kenneth ALDAPE, Marc REMKE, Martin MYNAREK, Stefan RUTKOWSKI, Sridharan GURURANGAN, Roger E. MCLENDON, Eric S. LIPP, Christopher DUNHAM, Juliette HUKIN, David D. EISENSTAT, Dorcas FULTON, Frank K. H. van LANDEGHEM, Mariarita SANTI, Marie-Lise C. van VEELEN, Erwin G. VAN MEIR, Satoru OSUKA, Xing FAN, Karin M. MURASZKO, Daniela P.C. TIRAPELLI, Sueli M. OBA-SHINJO, Suely K.N. MARIE, Carlos G. CARLOTTI, Ji Yeoun LEE, Amulya A. Nagesware RAO, Caterina GIANNINI, Claudia C. FARIA, Sofia NUNES, Jaume MORA, Ronald L. HAMILTON, Peter HAUSER, Nada JABADO, Kevin PETRECCA, Shin JUNG, Luca MASSIMI, Massimo ZOLLO, Giuseppe CINALLI, László BOGNÁR, Almos KLEKNER, Tibor HORTOBÁGYI, Sarah LEARY, Ralph P. ERMOIAN, James M. OLSON, Jeffrey R. LEONARD, Corrine GARDNER, Wieslawa A. GRAJKOWSKA, Lola B. CHAMBLESS, Jason CAIN, Charles G. EBERHART, Sama AHSAN, Maura MASSIMINO, Felice GIANGASPERO, Francesca R. BUTTARELLI, Roger J. PACKER, Lyndsey EMERY, William H. YONG, Horacio SOTO, Linda M. LIAU, Richard EVERSON, Andrew GROSSBACH, Tarek SHALABY, Michael GROTZER, Matthias A. KARAJANNIS, David ZAGZAG, Helen WHEELER, Katja von HOFF, Marta M. ALONSO, Teresa TUON, Ulrich SCHÜLLER, Karel ZITTERBART, Jaroslav ŠTĚRBA, Jennifer A. CHAN, Miguel GUZMAN, Samer K. ELBABAA, Howard COLMAN, Girish DHALL, Paul G. FISHER, Maryam FOULADI, Amar GAJJAR, Stewart GOLDMAN, Eugene HWANG, Marcel KOOL, Harshad LADHA, Elizabeth VERA-BOLANOS, Khalida WANI, Frank LIEBERMAN, Tom MIKKELSEN, Antonio M. OMURO, Ian F. POLLACK, Michael PRADOS, H. Ian ROBINS, Riccardo SOFFIETTI, Jing WU, Phillipe METELLUS, Uri TABORI, Ute BARTELS, Eric BOUFFET, Cynthia E. HAWKINS, James T. RUTKA, Peter DIRKS, Stefan M. PFISTER, Thomas E. MERCHANT, Mark R. GILBERT, Terri S. ARMSTRONG, Andrey KORSHUNOV, David W. ELLISON and Michael D. TAYLOR. Therapeutic Impact of Cytoreductive Surgery and Irradiation of Posterior Fossa Ependymoma in the Molecular Era: A Retrospective Multicohort Analysis. \textit{Journal of Clinical Oncology}. Alexandria: American Society of Clinical Oncology, 2016, vol.~34, No~21, p.~2468-2490. ISSN~0732-183X. Available from: https://dx.doi.org/10.1200/JCO.2015.65.7825.

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