Therapeutic Impact of Cytoreductive Surgery and Irradiation of Posterior Fossa Ependymoma in the Molecular Era: A Retrospective Multicohort Analysis
Autoři
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 a Michael D. TAYLOR
Vydání
Journal of Clinical Oncology, Alexandria, American Society of Clinical Oncology, 2016, 0732-183X
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.
Návaznosti
ROZV/20/LF/2015, interní kód MU
Název: LF - Příspěvek IP 2015
Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, LF - Příspěvek IP 2015
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 a 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, roč. 34, č. 21, s. 2468-2490. ISSN 0732-183X. Dostupné z: https://doi.org/10.1200/JCO.2015.65.7825.
@article{1362990, 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 = {https://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 a 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, roč.~34, č.~21, s.~2468-2490. ISSN~0732-183X. Dostupné z: https://doi.org/10.1200/JCO.2015.65.7825.