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@article{1366206,
author = {Thompson, Eric M. and Hielscher, Thomas and Bouffet, Eric and Remke, Marc and Luu, Betty and Gururangan, Sridharan and McLendon, Roger E. and Bigner, Darell D. and Lipp, Eric S. and Perreault, Sebastien and Cho, YoonandJae and Grant, Gerald and Kim, SeungandKi and Lee, Ji Yeoun and Rao, Amulya A Nageswara and Giannini, Caterina and Li, Kay Ka Wai and Ng, HoandKeung and Yao, Yu and Kumabe, Toshihiro and Tominaga, Teiji and Grajkowska, Wieslawa A. and PerekandPolnik, Marta and Low, David C. Y. and Seow, Wan Tew and Chang, Kenneth T. E. and Mora, Jaume and Pollack, Ian F. and Hamilton, Ronald L. and Leary, Sarah and Moore, Andrew S. and Ingram, Wendy J. and Hallahan, Andrew R. and Jouvet, Anne and FèvreandMontange, Michelle and Vasiljevic, Alexandre and FaureandConter, Cecile and Shofuda, Tomoko and Kagawa, Naoki and Hashimoto, Naoya and Jabado, Nada and Weil, Alexander G. and Gayden, Tenzin and Wataya, Takafumi and Shalaby, Tarek and Grotzer, Michael and Zitterbart, Karel and Štěrba, Jaroslav and Křen, Leoš and Hortobágyi, Tibor and Klekner, Almos and László, Bognár and Pócza, Tímea and Hauser, Peter and Schüller, Ulrich and Jung, Shin and Jang, WooandYoul and French, Pim J. and Kros, Johan M. and Veelen, MarieandLise C. van and Massimi, Luca and Leonard, Jeffrey R. and Rubin, Joshua B. and Vibhakar, Rajeev and Chambless, Lola B. and Cooper, Michael K. and Thompson, Reid C. and Faria, Claudia C. and Carvalho, Alice and Nunes, Sofia and Pimentel, José and Fan, Xing and Muraszko, Karin M. and LópezandAguilar, Enrique and Lyden, David and Garzia, Livia and Shih, David J. H. and Kijima, Noriyuki and Schneider, Christian and Adamski, Jennifer and Northcott, Paul A. and Kool, Marcel and Jones, David T.W. and Chan, Jennifer A. and Nikolic, Ana and Garre, Maria Luisa and Meir, Erwin G. Van and Osuka, Satoru and Olson, Jeffrey J. and Jahangiri, Arman and Castro, Brandyn A. and Gupta, Nalin and Weiss, William A. and MoxonandEmre, Iska and Mabbott, Donald J. and Lassaletta, Alvaro and Hawkins, Cynthia E. and Tabori, Uri and Drake, James and Kulkarni, Abhaya and Dirks, Peter and Rutka, James T. and Korshunov, Andrey and Pfister, Stefan M. and Packer, Roger J. and Ramaswamy, Vijay and Taylor, Michael D.},
article_location = {New York},
article_number = {4},
doi = {http://dx.doi.org/10.1016/S1470-2045(15)00581-1},
keywords = {POSTERIOR-FOSSA TUMORS; CHILDRENS CANCER GROUP; RISK MEDULLOBLASTOMA; RADIATION-THERAPY; ADJUVANT CHEMOTHERAPY; RANDOMIZED-TRIAL; PHASE-III; ONCOLOGY; CHILDHOOD; PATTERNS},
language = {eng},
issn = {1470-2045},
journal = {Lancet Oncology},
title = {Prognostic value of medulloblastoma extent of resection after accounting for molecular subgroup: a retrospective integrated clinical and molecular analysis},
volume = {17},
year = {2016}
}
TY - JOUR
ID - 1366206
AU - Thompson, Eric M. - Hielscher, Thomas - Bouffet, Eric - Remke, Marc - Luu, Betty - Gururangan, Sridharan - McLendon, Roger E. - Bigner, Darell D. - Lipp, Eric S. - Perreault, Sebastien - Cho, Yoon-Jae - Grant, Gerald - Kim, Seung-Ki - Lee, Ji Yeoun - Rao, Amulya A Nageswara - Giannini, Caterina - Li, Kay Ka Wai - Ng, Ho-Keung - Yao, Yu - Kumabe, Toshihiro - Tominaga, Teiji - Grajkowska, Wieslawa A. - Perek-Polnik, Marta - Low, David C. Y. - Seow, Wan Tew - Chang, Kenneth T. E. - Mora, Jaume - Pollack, Ian F. - Hamilton, Ronald L. - Leary, Sarah - Moore, Andrew S. - Ingram, Wendy J. - Hallahan, Andrew R. - Jouvet, Anne - Fèvre-Montange, Michelle - Vasiljevic, Alexandre - Faure-Conter, Cecile - Shofuda, Tomoko - Kagawa, Naoki - Hashimoto, Naoya - Jabado, Nada - Weil, Alexander G. - Gayden, Tenzin - Wataya, Takafumi - Shalaby, Tarek - Grotzer, Michael - Zitterbart, Karel - Štěrba, Jaroslav - Křen, Leoš - Hortobágyi, Tibor - Klekner, Almos - László, Bognár - Pócza, Tímea - Hauser, Peter - Schüller, Ulrich - Jung, Shin - Jang, Woo-Youl - French, Pim J. - Kros, Johan M. - Veelen, Marie-Lise C. van - Massimi, Luca - Leonard, Jeffrey R. - Rubin, Joshua B. - Vibhakar, Rajeev - Chambless, Lola B. - Cooper, Michael K. - Thompson, Reid C. - Faria, Claudia C. - Carvalho, Alice - Nunes, Sofia - Pimentel, José - Fan, Xing - Muraszko, Karin M. - López-Aguilar, Enrique - Lyden, David - Garzia, Livia - Shih, David J. H. - Kijima, Noriyuki - Schneider, Christian - Adamski, Jennifer - Northcott, Paul A. - Kool, Marcel - Jones, David T.W. - Chan, Jennifer A. - Nikolic, Ana - Garre, Maria Luisa - Meir, Erwin G. Van - Osuka, Satoru - Olson, Jeffrey J. - Jahangiri, Arman - Castro, Brandyn A. - Gupta, Nalin - Weiss, William A. - Moxon-Emre, Iska - Mabbott, Donald J. - Lassaletta, Alvaro - Hawkins, Cynthia E. - Tabori, Uri - Drake, James - Kulkarni, Abhaya - Dirks, Peter - Rutka, James T. - Korshunov, Andrey - Pfister, Stefan M. - Packer, Roger J. - Ramaswamy, Vijay - Taylor, Michael D.
PY - 2016
TI - Prognostic value of medulloblastoma extent of resection after accounting for molecular subgroup: a retrospective integrated clinical and molecular analysis
JF - Lancet Oncology
VL - 17
IS - 4
SP - 484-495
EP - 484-495
PB - Elsevier Science INC
SN - 14702045
KW - POSTERIOR-FOSSA TUMORS
KW - CHILDRENS CANCER GROUP
KW - RISK MEDULLOBLASTOMA
KW - RADIATION-THERAPY
KW - ADJUVANT CHEMOTHERAPY
KW - RANDOMIZED-TRIAL
KW - PHASE-III
KW - ONCOLOGY
KW - CHILDHOOD
KW - PATTERNS
N2 - Background Patients with incomplete surgical resection of medulloblastoma are controversially regarded as having a marker of high-risk disease, which leads to patients undergoing aggressive surgical resections, so-called second-look surgeries, and intensified chemoradiotherapy. All previous studies assessing the clinical importance of extent of resection have not accounted for molecular subgroup. We analysed the prognostic value of extent of resection in a subgroup-specific manner. Methods We retrospectively identified patients who had a histological diagnosis of medulloblastoma and complete data about extent of resection and survival from centres participating in the Medulloblastoma Advanced Genomics International Consortium. We collected from resections done between April, 1997, and February, 2013, at 35 international institutions. We established medulloblastoma subgroup affiliation by gene expression profiling on frozen or formalin-fixed paraffin-embedded tissues. We classified extent of resection on the basis of postoperative imaging as gross total resection (no residual tumour), near-total resection (< 1.5 cm(2) tumour remaining), or sub-total resection (>= 1.5 cm(2) tumour remaining). We did multivariable analyses of overall survival and progression-free survival using the variables molecular subgroup (WNT, SHH, group 4, and group 3), age (< 3 vs >= 3 years old), metastatic status (metastases vs no metastases), geographical location of therapy (North America/Australia vs rest of the world), receipt of chemotherapy (yes vs no) and receipt of craniospinal irradiation (< 30 Gy or > 30 Gy vs no craniospinal irradiation). The primary analysis outcome was the effect of extent of resection by molecular subgroup and the effects of other clinical variables on overall and progression-free survival. Findings We included 787 patients with medulloblastoma (86 with WNT tumours, 242 with SHH tumours, 163 with group 3 tumours, and 296 with group 4 tumours) in our multivariable Cox models of progression-free and overall survival. We found that the prognostic benefit of increased extent of resection for patients with medulloblastoma is attenuated after molecular subgroup affiliation is taken into account. We identified a progression-free survival benefit for gross total resection over sub-total resection (hazard ratio [HR] 1.45, 95% CI 1.07-1.96, p=0.16) but no overall survival benefit (HR 1.23, 0.87-1.72, p=0.24). We saw no progression-free survival or overall survival benefit for gross total resection compared with near-total resection (HR 1.05, 0.71-1.53, p=0.8158 for progression-free survival and HR 1.14, 0.75-1.72, p=0.55 for overall survival). No significant survival benefit existed for greater extent of resection for patients with WNT, SHH, or group 3 tumours (HR 1.03, 0.67-1.58, p=0.89 for sub-total resection vs gross total resection). For patients with group 4 tumours, gross total resection conferred a benefit to progression-free survival compared with sub-total resection (HR 1.97, 1.22-3.17, p= 0.0056), especially for those with metastatic disease (HR 2.22, 1.00-4.93, p= 0.050). However, gross total resection had no effect on overall survival compared with sub-total resection in patients with group 4 tumours (HR 1.67, 0.93-2.99, p= 0.084). Interpretation The prognostic benefit of increased extent of resection for patients with medulloblastoma is attenuated after molecular subgroup affiliation is taken into account. Although maximum safe surgical resection should remain the standard of care, surgical removal of small residual portions of medulloblastoma is not recommended when the likelihood of neurological morbidity is high because there is no definitive benefit to gross total resection compared with near-total resection.
ER -
THOMPSON, Eric M., Thomas HIELSCHER, Eric BOUFFET, Marc REMKE, Betty LUU, Sridharan GURURANGAN, Roger E. MCLENDON, Darell D. BIGNER, Eric S. LIPP, Sebastien PERREAULT, Yoon-Jae CHO, Gerald GRANT, Seung-Ki KIM, Ji Yeoun LEE, Amulya A Nageswara RAO, Caterina GIANNINI, Kay Ka Wai LI, Ho-Keung NG, Yu YAO, Toshihiro KUMABE, Teiji TOMINAGA, Wieslawa A. GRAJKOWSKA, Marta PEREK-POLNIK, David C. Y. LOW, Wan Tew SEOW, Kenneth T. E. CHANG, Jaume MORA, Ian F. POLLACK, Ronald L. HAMILTON, Sarah LEARY, Andrew S. MOORE, Wendy J. INGRAM, Andrew R. HALLAHAN, Anne JOUVET, Michelle FÈVRE-MONTANGE, Alexandre VASILJEVIC, Cecile FAURE-CONTER, Tomoko SHOFUDA, Naoki KAGAWA, Naoya HASHIMOTO, Nada JABADO, Alexander G. WEIL, Tenzin GAYDEN, Takafumi WATAYA, Tarek SHALABY, Michael GROTZER, Karel ZITTERBART, Jaroslav ŠTĚRBA, Leoš KŘEN, Tibor HORTOBÁGYI, Almos KLEKNER, Bognár LÁSZLÓ, Tímea PÓCZA, Peter HAUSER, Ulrich SCHÜLLER, Shin JUNG, Woo-Youl JANG, Pim J. FRENCH, Johan M. KROS, Marie-Lise C. van VEELEN, Luca MASSIMI, Jeffrey R. LEONARD, Joshua B. RUBIN, Rajeev VIBHAKAR, Lola B. CHAMBLESS, Michael K. COOPER, Reid C. THOMPSON, Claudia C. FARIA, Alice CARVALHO, Sofia NUNES, José PIMENTEL, Xing FAN, Karin M. MURASZKO, Enrique LÓPEZ-AGUILAR, David LYDEN, Livia GARZIA, David J. H. SHIH, Noriyuki KIJIMA, Christian SCHNEIDER, Jennifer ADAMSKI, Paul A. NORTHCOTT, Marcel KOOL, David T.W. JONES, Jennifer A. CHAN, Ana NIKOLIC, Maria Luisa GARRE, Erwin G. Van MEIR, Satoru OSUKA, Jeffrey J. OLSON, Arman JAHANGIRI, Brandyn A. CASTRO, Nalin GUPTA, William A. WEISS, Iska MOXON-EMRE, Donald J. MABBOTT, Alvaro LASSALETTA, Cynthia E. HAWKINS, Uri TABORI, James DRAKE, Abhaya KULKARNI, Peter DIRKS, James T. RUTKA, Andrey KORSHUNOV, Stefan M. PFISTER, Roger J. PACKER, Vijay RAMASWAMY and Michael D. TAYLOR. Prognostic value of medulloblastoma extent of resection after accounting for molecular subgroup: a retrospective integrated clinical and molecular analysis. \textit{Lancet Oncology}. New York: Elsevier Science INC, 2016, vol.~17, No~4, p.~484-495. ISSN~1470-2045. Available from: https://dx.doi.org/10.1016/S1470-2045(15)00581-1.
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