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Therapeutic impact of cytoreductive surgery and irradiation of posterior fossa ependymoma in the molecular era: a retrospective multicohort analysis

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

van Landeghem, Frank K H

Santi, Mariarita

van Veelen, Marie-Lise C

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 Nageswara

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

von Hoff, Katja

Alonso, Marta M

Tuñon, Teresa

SchĂĽller, Ulrich

Zitterbart, Karel

Sterba, 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

American Society of Clinical Oncology

2016-07-20

RB Pathology / patolĂłgia, kĂłrtan

RC0254 Neoplasms. Tumors. Oncology (including Cancer) / daganatok, tumorok, onkolĂłgia

RS Pharmacy and materia medica / gyógyszerészet, gyógyászati eszközök

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. METHODS: Four 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.

magyar

Article

PeerReviewed

info:eu-repo/semantics/article

text

http://real.mtak.hu/40458/7/2_vegl_Therapeutic%20Impact%20o...

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 van Landeghem, Frank K H and Santi, Mariarita and van Veelen, Marie-Lise C and Van Meir, Erwin G and Osuka, Satoru and Fan, Xing and Muraszko, Karin M and Tirapelli, Daniela P C and Oba-Shinjo, Sueli M and Marie, Suely K N and Carlotti, Carlos G and Lee, Ji Yeoun and Rao, Amulya A Nageswara 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 von Hoff, Katja and Alonso, Marta M and Tuñon, Teresa and Schüller, Ulrich and Zitterbart, Karel and Sterba, 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 Vera-Bolanos, 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 (2016) Therapeutic impact of cytoreductive surgery and irradiation of posterior fossa ependymoma in the molecular era: a retrospective multicohort analysis. Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 34 (21). pp. 2468-77. ISSN 1527-7755

http://real.mtak.hu/40458/

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

10.1200/jco.2015.65.7825