{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T09:08:38Z","timestamp":1790500118872,"version":"4.1.0"},"reference-count":20,"publisher":"Springer Science and Business Media LLC","issue":"3","license":[{"start":{"date-parts":[[2018,3,20]],"date-time":"2018-03-20T00:00:00Z","timestamp":1521504000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Neurooncol"],"published-print":{"date-parts":[[2018,7]]},"DOI":"10.1007\/s11060-018-2831-7","type":"journal-article","created":{"date-parts":[[2018,3,20]],"date-time":"2018-03-20T03:29:55Z","timestamp":1521516595000},"page":"627-636","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":62,"title":["JCOG0911 INTEGRA study: a randomized screening phase II trial of interferon\u03b2 plus temozolomide in comparison with temozolomide alone for newly diagnosed glioblastoma"],"prefix":"10.1007","volume":"138","author":[{"name":"Members of Japan Clinical Oncology Group Brain Tumor Study Group (JCOG-BTSG)","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshihiko","family":"Wakabayashi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9113-0470","authenticated-orcid":false,"given":"Atsushi","family":"Natsume","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junki","family":"Mizusawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Katayama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haruhiko","family":"Fukuda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minako","family":"Sumi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryo","family":"Nishikawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshitaka","family":"Narita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshihiro","family":"Muragaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Maruyama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tamio","family":"Ito","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takaaki","family":"Beppu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideo","family":"Nakamura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takamasa","family":"Kayama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinya","family":"Sato","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Motoo","family":"Nagane","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuhiko","family":"Mishima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoko","family":"Nakasu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaoru","family":"Kurisu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fumiyuki","family":"Yamasaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuhiko","family":"Sugiyama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takanori","family":"Onishi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuo","family":"Iwadate","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mizuhiko","family":"Terasaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroyuki","family":"Kobayashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akira","family":"Matsumura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eiichi","family":"Ishikawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hikaru","family":"Sasaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akitake","family":"Mukasa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takayuki","family":"Matsuo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hirofumi","family":"Hirano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshihiro","family":"Kumabe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nobusada","family":"Shinoura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoya","family":"Hashimoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomokazu","family":"Aoki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akio","family":"Asai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatsuya","family":"Abe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atsuo","family":"Yoshino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshiki","family":"Arakawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenichiro","family":"Asano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koji","family":"Yoshimoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soichiro","family":"Shibui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2018,3,20]]},"reference":[{"key":"2831_CR1","doi-asserted-by":"publisher","first-page":"v1","DOI":"10.1093\/neuonc\/nox158","volume":"19","author":"QT Ostrom","year":"2017","unstructured":"Ostrom QT, Gittleman H, Liao P, Vecchione-Koval T, Wolinsky Y, Kruchko C, Barnholtz-Sloan JS (2017) CBTRUS statistical report: primary brain and other central nervous system tumors diagnosed in the United States in 2010\u20132014. Neuro Oncol 19:v1\u2013v88. \n                    https:\/\/doi.org\/10.1093\/neuonc\/nox158","journal-title":"Neuro Oncol"},{"key":"2831_CR2","doi-asserted-by":"publisher","first-page":"459","DOI":"10.1016\/S1470-2045(09)70025-7","volume":"10","author":"R Stupp","year":"2009","unstructured":"Stupp R, Hegi ME, Mason WP, van den Bent MJ, Taphoorn MJ, Janzer RC, Ludwin SK, Allgeier A, Fisher B, Belanger K, Hau P, Brandes AA, Gijtenbeek J, Marosi C, Vecht CJ, Mokhtari K, Wesseling P, Villa S, Eisenhauer E, Gorlia T, Weller M, Lacombe D, Cairncross JG, Mirimanoff RO, European Organisation for Research and Treatment of Cancer Brain Tumour and Radiation Oncology Groups, National Cancer Institute of Canada Clinical Trials Group (2009) Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial. Lancet Oncol 10:459\u2013466 \n                    https:\/\/doi.org\/10.1016\/S1470-2045(09)70025-7","journal-title":"Lancet Oncol"},{"key":"2831_CR3","doi-asserted-by":"publisher","first-page":"987","DOI":"10.1056\/NEJMoa043330","volume":"352","author":"R Stupp","year":"2005","unstructured":"Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, Belanger K, Brandes AA, Marosi C, Bogdahn U, Curschmann J, Janzer RC, Ludwin SK, Gorlia T, Allgeier A, Lacombe D, Cairncross JG, Eisenhauer E, Mirimanoff RO, European Organisation for Research and Treatment of Cancer Brain Tumor and Radiotherapy Groups, National Cancer Institute of Canada Clinical Trials Group (2005) Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 352: 987\u2013996 \n                    https:\/\/doi.org\/10.1056\/NEJMoa043330","journal-title":"N Engl J Med"},{"key":"2831_CR4","doi-asserted-by":"publisher","first-page":"699","DOI":"10.1056\/NEJMoa1308573","volume":"370","author":"MR Gilbert","year":"2014","unstructured":"Gilbert MR, Dignam JJ, Armstrong TS, Wefel JS, Blumenthal DT, Vogelbaum MA, Colman H, Chakravarti A, Pugh S, Won M, Jeraj R, Brown PD, Jaeckle KA, Schiff D, Stieber VW, Brachman DG, Werner-Wasik M, Tremont-Lukats IW, Sulman EP, Aldape KD, Curran WJ Jr, Mehta MP (2014) A randomized trial of bevacizumab for newly diagnosed glioblastoma. N Engl J Med 370:699\u2013708. \n                    https:\/\/doi.org\/10.1056\/NEJMoa1308573","journal-title":"N Engl J Med"},{"key":"2831_CR5","doi-asserted-by":"publisher","first-page":"709","DOI":"10.1056\/NEJMoa1308345","volume":"370","author":"OL Chinot","year":"2014","unstructured":"Chinot OL, Wick W, Mason W, Henriksson R, Saran F, Nishikawa R, Carpentier AF, Hoang-Xuan K, Kavan P, Cernea D, Brandes AA, Hilton M, Abrey L, Cloughesy T (2014) Bevacizumab plus radiotherapy-temozolomide for newly diagnosed glioblastoma. N Engl J Med 370:709\u2013722. \n                    https:\/\/doi.org\/10.1056\/NEJMoa1308345","journal-title":"N Engl J Med"},{"key":"2831_CR6","doi-asserted-by":"publisher","first-page":"997","DOI":"10.1056\/NEJMoa043331","volume":"352","author":"ME Hegi","year":"2005","unstructured":"Hegi ME, Diserens AC, Gorlia T, Hamou MF, de Tribolet N, Weller M, Kros JM, Hainfellner JA, Mason W, Mariani L, Bromberg JE, Hau P, Mirimanoff RO, Cairncross JG, Janzer RC, Stupp R (2005) MGMT gene silencing and benefit from temozolomide in glioblastoma. N Engl J Med 352:997\u20131003","journal-title":"N Engl J Med"},{"key":"2831_CR7","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1089\/jir.2016.0094","volume":"37","author":"V Galani","year":"2017","unstructured":"Galani V, Papadatos SS, Alexiou G, Galani A, Kyritsis AP (2017) In vitro and in vivo preclinical effects of type I IFNs on gliomas. J Interferon Cytokine Res 37:139\u2013146. \n                    https:\/\/doi.org\/10.1089\/jir.2016.0094","journal-title":"J Interferon Cytokine Res"},{"key":"2831_CR8","doi-asserted-by":"publisher","first-page":"1508","DOI":"10.1093\/neuonc\/now097","volume":"18","author":"D GuhaSarkar","year":"2016","unstructured":"GuhaSarkar D, Su Q, Gao G, Sena-Esteves M (2016) Systemic AAV9-IFNbeta gene delivery treats highly invasive glioblastoma. Neuro Oncol 18:1508\u20131518. \n                    https:\/\/doi.org\/10.1093\/neuonc\/now097","journal-title":"Neuro Oncol"},{"key":"2831_CR9","doi-asserted-by":"publisher","first-page":"237","DOI":"10.1023\/A:1023668705040","volume":"8","author":"M Chawla-Sarkar","year":"2003","unstructured":"Chawla-Sarkar M, Lindner DJ, Liu YF, Williams BR, Sen GC, Silverman RH, Borden EC (2003) Apoptosis and interferons: role of interferon-stimulated genes as mediators of apoptosis. Apoptosis 8:237\u2013249","journal-title":"Apoptosis"},{"key":"2831_CR10","doi-asserted-by":"publisher","first-page":"909","DOI":"10.3892\/mco.2015.542","volume":"3","author":"H Kawaji","year":"2015","unstructured":"Kawaji H, Tokuyama T, Yamasaki T, Amano S, Sakai N, Namba H (2015) Interferon-beta and temozolomide combination therapy for temozolomide monotherapy-refractory malignant gliomas. Mol Clin Oncol 3:909\u2013913. \n                    https:\/\/doi.org\/10.3892\/mco.2015.542","journal-title":"Mol Clin Oncol"},{"key":"2831_CR11","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1023\/A:1006405512579","volume":"49","author":"T Wakabayashi","year":"2000","unstructured":"Wakabayashi T, Hatano N, Kajita Y, Yoshida T, Mizuno M, Taniguchi K, Ohno T, Nagasaka T, Yoshida J (2000) Initial and maintenance combination treatment with interferon-beta, MCNU (Ranimustine), and radiotherapy for patients with previously untreated malignant glioma. J Neurooncol 49:57\u201362","journal-title":"J Neurooncol"},{"key":"2831_CR12","doi-asserted-by":"publisher","first-page":"7573","DOI":"10.1158\/0008-5472.CAN-05-0036","volume":"65","author":"A Natsume","year":"2005","unstructured":"Natsume A, Ishii D, Wakabayashi T, Tsuno T, Hatano H, Mizuno M, Yoshida J (2005) IFN-beta down-regulates the expression of DNA repair gene MGMT and sensitizes resistant glioma cells to temozolomide. Cancer Res 65:7573\u20137579. \n                    https:\/\/doi.org\/10.1158\/0008-5472.CAN-05-0036","journal-title":"Cancer Res"},{"key":"2831_CR13","doi-asserted-by":"publisher","first-page":"653","DOI":"10.1007\/s00280-007-0520-x","volume":"61","author":"A Natsume","year":"2007","unstructured":"Natsume A, Wakabayashi T, Ishii D, Maruta H, Fujii M, Shimato S, Ito M, Yoshida J (2007) A combination of IFN-beta and temozolomide in human glioma xenograft models: implication of p53-mediated MGMT downregulation. Cancer Chemother Pharmacol 61:653\u2013659","journal-title":"Cancer Chemother Pharmacol"},{"key":"2831_CR14","doi-asserted-by":"publisher","first-page":"573","DOI":"10.1007\/s11060-011-0529-1","volume":"104","author":"T Wakabayashi","year":"2011","unstructured":"Wakabayashi T, Kayama T, Nishikawa R, Takahashi H, Hashimoto N, Takahashi J, Aoki T, Sugiyama K, Ogura M, Natsume A, Yoshida J (2011) A multicenter phase I trial of combination therapy with interferon-beta and temozolomide for high-grade gliomas (INTEGRA study): the final report. J Neurooncol 104:573\u2013577. \n                    https:\/\/doi.org\/10.1007\/s11060-011-0529-1","journal-title":"J Neurooncol"},{"key":"2831_CR15","doi-asserted-by":"publisher","first-page":"715","DOI":"10.1093\/jjco\/hyn095","volume":"38","author":"T Wakabayashi","year":"2008","unstructured":"Wakabayashi T, Kayama T, Nishikawa R, Takahashi H, Yoshimine T, Hashimoto N, Aoki T, Kurisu K, Natsume A, Ogura M, Yoshida J (2008) A multicenter phase I trial of interferon-beta and temozolomide combination therapy for high-grade gliomas (INTEGRA study). Jpn J Clin Oncol 38:715\u2013718. \n                    https:\/\/doi.org\/10.1093\/jjco\/hyn095","journal-title":"Jpn J Clin Oncol"},{"key":"2831_CR16","doi-asserted-by":"publisher","first-page":"1721","DOI":"10.1002\/cncr.25637","volume":"117","author":"K Motomura","year":"2011","unstructured":"Motomura K, Natsume A, Kishida Y, Higashi H, Kondo Y, Nakasu Y, Abe T, Namba H, Wakai K, Wakabayashi T (2011) Benefits of interferon-beta and temozolomide combination therapy for newly diagnosed primary glioblastoma with the unmethylated MGMT promoter: a multicenter study. Cancer 117:1721\u20131730. \n                    https:\/\/doi.org\/10.1002\/cncr.25637","journal-title":"Cancer"},{"key":"2831_CR17","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1007\/BF01808547","volume":"127","author":"J Yoshida","year":"1994","unstructured":"Yoshida J, Kajita Y, Wakabayashi T, Sugita K (1994) Long-term follow-up results of 175 patients with malignant glioma: importance of radical tumour resection and postoperative adjuvant therapy with interferon, ACNU and radiation. Acta Neurochir 127:55\u201359","journal-title":"Acta Neurochir"},{"key":"2831_CR18","doi-asserted-by":"publisher","first-page":"633","DOI":"10.1007\/s007010070106","volume":"142","author":"N Hatano","year":"2000","unstructured":"Hatano N, Wakabayashi T, Kajita Y, Mizuno M, Ohno T, Nakayashiki N, Takemura A, Yoshida J (2000) Efficacy of post operative adjuvant therapy with human interferon beta, MCNU and radiation (IMR) for malignant glioma: comparison among three protocols. Acta Neurochir 142:633\u2013638 (discussion 639)","journal-title":"Acta Neurochir"},{"key":"2831_CR19","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1007\/s11060-004-2160-x","volume":"72","author":"T Watanabe","year":"2005","unstructured":"Watanabe T, Katayama Y, Yoshino A, Fukaya C, Yamamoto T (2005) Human interferon beta, nimustine hydrochloride, and radiation therapy in the treatment of newly diagnosed malignant astrocytomas. J Neurooncol 72:57\u201362. \n                    https:\/\/doi.org\/10.1007\/s11060-004-2160-x","journal-title":"J Neurooncol"},{"key":"2831_CR20","doi-asserted-by":"publisher","first-page":"818","DOI":"10.1016\/j.ijrobp.2006.05.021","volume":"66","author":"H Colman","year":"2006","unstructured":"Colman H, Berkey BA, Maor MH, Groves MD, Schultz CJ, Vermeulen S, Nelson DF, Mehta MP, Yung WK, Radiation Therapy Oncology G (2006) Phase II Radiation Therapy Oncology Group trial of conventional radiation therapy followed by treatment with recombinant interferon-beta for supratentorial glioblastoma: results of RTOG 9710. Int J Radiat Oncol Biol Phys 66:818\u2013824. \n                    https:\/\/doi.org\/10.1016\/j.ijrobp.2006.05.021","journal-title":"Int J Radiat Oncol Biol Phys"}],"container-title":["Journal of Neuro-Oncology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/article\/10.1007\/s11060-018-2831-7\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s11060-018-2831-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s11060-018-2831-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,3,19]],"date-time":"2019-03-19T21:27:45Z","timestamp":1553030865000},"score":1,"resource":{"primary":{"URL":"http:\/\/link.springer.com\/10.1007\/s11060-018-2831-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,3,20]]},"references-count":20,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2018,7]]}},"alternative-id":["2831"],"URL":"https:\/\/doi.org\/10.1007\/s11060-018-2831-7","relation":{},"ISSN":["0167-594X","1573-7373"],"issn-type":[{"value":"0167-594X","type":"print"},{"value":"1573-7373","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,3,20]]},"assertion":[{"value":"13 November 2017","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 February 2018","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 March 2018","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Compliance with ethical standards"}},{"value":"T.W. has received research funding from Toray Co, Ltd, and MSD Co. Ltd. K.S. received honorarium fundings from MSD. M.N. received honorarium and research fundings from MSD, Chugai, and Eisai, and research funding from Daiichi-Sankyo. R.N. received honorarium and research fundings from MSD, Chugai, and Eisai. The other authors declare that they have no conflict of interest. All authors have registered online Self-reported COI Disclosure Statement Forms through the website for Japan Neurosurgical Society members.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}