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Genetic analysis in patients with newly diagnosed glioblastomas treated with interferon-beta plus temozolomide in comparison with temozolomide alone

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Abstract

Purpose

This study aimed to explore the genetic alterations and to identify good responders in the experimental arm in the tumor samples from newly diagnosed glioblastoma (GBM) patients enrolled in JCOG0911; a randomized phase II trial was conducted to compare the efficacy of interferonβ (IFNβ) plus temozolomide (TMZ) with that of TMZ alone.

Experimental

design

Of 122 tumors, we performed deep targeted sequencing to determine the somatic mutations, copy number variations, and tumor mutation burden; pyrosequencing for O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation; Sanger sequencing for the telomerase reverse transcriptase (TERT) promoter; and microsatellite instability (MSI) testing in 95, 91, 91 and 72 tumors, respectively. We performed a multivariable Cox regression analysis using backward stepwise selection of variables including clinical factors (sex, age, performance status, residual tumor after resection, tumor location) and genetic alterations.

Results

Deep sequencing detected an IDH1 mutation in 13 tumors (14%). The MGMT promoter methylation by quantitative pyrosequencing was observed in 41% of the tumors. A mutation in the TERT promoter was observed in 69% of the tumors. While high tumor mutation burden (> 10 mutations per megabase) was seen in four tumors, none of the tumors displayed MSI-high. The clinical and genetic factors considered as independent favorable prognostic factors were gross total resection (hazard ratio [HR]: 0.49, 95% confidence interval, 0.30–0.81, P = 0.0049) and MGMT promoter methylation (HR: 0.43, 0.21–0.88, P = 0.023). However, tumor location at the temporal lobe (HR: 1.90, 1.22–2.95, P = 0.0046) was an independent unfavorable prognostic factor. No predictive factors specific to the TMZ + IFNβ + Radiotherapy (RT) group were found.

Conclusion

This additional sub-analytical study of JCOG0911 among patients with newly diagnosed GBM showed that tumor location at the temporal lobe, gross total resection, and MGMT promoter methylation were significant prognostic factors, although no factors specific to IFNβ addition were identified.

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References

  1. Ostrom QT, Gittleman H, Farah P, Ondracek A, Chen Y, Wolinsky Y, Stroup NE, Kruchko C, Barnholtz-Sloan JS (2013) CBTRUS statistical report: primary brain and central nervous system tumors diagnosed in the United States in 2006–2010. Neuro Oncol 15(2):1–56. https://doi.org/10.1093/neuonc/not151

    Article  Google Scholar 

  2. 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, Organisation E, for R, Treatment of Cancer Brain T, Radiotherapy G, National Cancer Institute of Canada Clinical Trials G, (2005) Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 352:987–996. https://doi.org/10.1056/NEJMoa043330

    Article  CAS  PubMed  Google Scholar 

  3. 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, E, Treatment of Cancer Brain T, Radiation Oncology G, National Cancer Institute of Canada Clinical Trials G (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 10:459–466. https://doi.org/10.1016/S1470-2045(09)70025-7

    Article  CAS  PubMed  Google Scholar 

  4. Weller M, Tabatabai G, Kastner B, Felsberg J, Steinbach JP, Wick A, Schnell O, Hau P, Herrlinger U, Sabel MC, Wirsching HG, Ketter R, Bahr O, Platten M, Tonn JC, Schlegel U, Marosi C, Goldbrunner R, Stupp R, Homicsko K, Pichler J, Nikkhah G, Meixensberger J, Vajkoczy P, Kollias S, Husing J, Reifenberger G, Wick W, Group DS (2015) MGMT promoter methylation is a strong prognostic biomarker for benefit from dose-intensified temozolomide rechallenge in progressive glioblastoma: the director trial. Clin Cancer Res 21:2057–2064. https://doi.org/10.1158/1078-0432.CCR-14-2737

    Article  CAS  PubMed  Google Scholar 

  5. Hegi ME, Diserens AC, Godard S, Dietrich PY, Regli L, Ostermann S, Otten P, Van Melle G, de Tribolet N, Stupp R (2004) Clinical trial substantiates the predictive value of O-6-methylguanine-DNA methyltransferase promoter methylation in glioblastoma patients treated with temozolomide. Clin Cancer Res 10:1871–1874. https://doi.org/10.1158/1078-0432.ccr-03-0384

    Article  CAS  PubMed  Google Scholar 

  6. 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 37:139–146. https://doi.org/10.1089/jir.2016.0094

    Article  CAS  PubMed  Google Scholar 

  7. GuhaSarkar D, Su Q, Gao G, Sena-Esteves M (2016) Systemic AAV9-IFNbeta gene delivery treats highly invasive glioblastoma. Neuro Oncol 18:1508–1518. https://doi.org/10.1093/neuonc/now097

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. 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 3:909–913. https://doi.org/10.3892/mco.2015.542

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. 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 65:7573–7579. https://doi.org/10.1158/0008-5472.CAN-05-0036

    Article  CAS  PubMed  Google Scholar 

  10. 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 61:653–659. https://doi.org/10.1007/s00280-007-0520-x

    Article  CAS  PubMed  Google Scholar 

  11. Wakabayashi T, Natsume A, Mizusawa J, Katayama H, Fukuda H, Sumi M, Nishikawa R, Narita Y, Muragaki Y, Maruyama T, Itosan T, Beppu T, Nakamura H, Kayama T, Sato S, Nagane M, Mishima K, Nakasu Y, Kurisu K, Yamasaki F, Sugiyama K, Onishi T, Iwadate Y, Terasaki M, Kobayashi H, Matsumura A, Ishikawa E, Sasaki H, Mukasa A, Matsuo T, Hirano H, Kumabe T, Shinoura N, Hashimoto N, Aoki T, Asai A, Abe T, Yoshino A, Arakawa Y, Asano K, Yoshimoto K, Shibui S, Members of Japan Clinical Oncology Group Brain Tumor Study G (2018) JCOG0911 INTEGRA study: a randomized screening phase II trial of interferonbeta plus temozolomide in comparison with temozolomide alone for newly diagnosed glioblastoma. J Neurooncol 138:627–636. https://doi.org/10.1007/s11060-018-2831-7

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Louis DN, Perry A, Reifenberger G, von Deimling A, Figarella-Branger D, Cavenee WK, Ohgaki H, Wiestler OD, Kleihues P, Ellison DW (2016) The 2016 World Health Organization Classification of Tumors of the Central Nervous System: a summary. Acta Neuropathol 131:803–820. https://doi.org/10.1007/s00401-016-1545-1

    Article  PubMed  Google Scholar 

  13. Li H, Durbin R (2009) Fast and accurate short read alignment with Burrows-Wheeler transform. Bioinformatics 25:1754–1760. https://doi.org/10.1093/bioinformatics/btp324

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Koboldt DC, Zhang Q, Larson DE, Shen D, McLellan MD, Lin L, Miller CA, Mardis ER, Ding L, Wilson RK (2012) VarScan 2: somatic mutation and copy number alteration discovery in cancer by exome sequencing. Genome Res 22:568–576. https://doi.org/10.1101/gr.129684.111

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Bamford S, Dawson E, Forbes S, Clements J, Pettett R, Dogan A, Flanagan A, Teague J, Futreal PA, Stratton MR, Wooster R (2004) The COSMIC (Catalogue of Somatic Mutations in Cancer) database and website. Br J Cancer 91:355–358. https://doi.org/10.1038/sj.bjc.6601894

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Davis JL, Grenert JP, Horvai AE (2014) Loss of heterozygosity and ` are rare in sporadic dedifferentiated liposarcoma: a study of 43 well-characterized cases. Arch Pathol Lab Med 138:823–827. https://doi.org/10.5858/arpa.2013-0236-OA

    Article  PubMed  Google Scholar 

  17. An B, Kondo Y, Okamoto Y, Shinjo K, Kanemitsu Y, Komori K, Hirai T, Sawaki A, Tajika M, Nakamura T, Yamao K, Yatabe Y, Fujii M, Murakami H, Osada H, Tani T, Matsuo K, Shen L, Issa JP, Sekido Y (2010) Characteristic methylation profile in CpG island methylator phenotype-negative distal colorectal cancers. Int J Cancer 127:2095–2105. https://doi.org/10.1002/ijc.25225

    Article  CAS  PubMed  Google Scholar 

  18. Shinjo K, Okamoto Y, An B, Yokoyama T, Takeuchi I, Fujii M, Osada H, Usami N, Hasegawa Y, Ito H, Hida T, Fujimoto N, Kishimoto T, Sekido Y, Kondo Y (2012) Integrated analysis of genetic and epigenetic alterations reveals CpG island methylator phenotype associated with distinct clinical characters of lung adenocarcinoma. Carcinogenesis 33:1277–1285. https://doi.org/10.1093/carcin/bgs154

    Article  CAS  PubMed  Google Scholar 

  19. Benjamini Y, Hochberg Y (1995) Controlling the false discovery rate: a practical and powerful approach to multiple testing. J Roy Stat Soc B 57:289–300

    Google Scholar 

  20. Aoki K, Nakamura H, Suzuki H, Matsuo K, Kataoka K, Shimamura T, Motomura K, Ohka F, Shiina S, Yamamoto T, Nagata Y, Yoshizato T, Mizoguchi M, Abe T, Momii Y, Muragaki Y, Watanabe R, Ito I, Sanada M, Yajima H, Morita N, Takeuchi I, Miyano S, Wakabayashi T, Ogawa S, Natsume A (2018) Prognostic relevance of genetic alterations in diffuse lower-grade gliomas. Neuro Oncol 20:66–77. https://doi.org/10.1093/neuonc/nox132

    Article  CAS  PubMed  Google Scholar 

  21. Rubin DB (2004) Multiple imputation for nonresponse in surveys. Wiley-Interscience, Hoboken, N.J.

    Google Scholar 

  22. Natsume A, Wakabayashi T, Ishii D, Maruta H, Fujii M, Shimato S, Ito M, Yoshida J (2008) A combination of IFN-beta and temozolomide in human glioma xenograft models: implication of p53-mediated MGMT downregulation. Cancer Chemother Pharmacol 61:653–659. https://doi.org/10.1007/s00280-007-0520-x

    Article  CAS  PubMed  Google Scholar 

  23. Lim SM, Kim HR, Lee JS, Lee KH, Lee YG, Min YJ, Cho EK, Lee SS, Kim BS, Choi MY, Shim HS, Chung JH, La Choi Y, Lee MJ, Kim M, Kim JH, Ali SM, Ahn MJ, Cho BC (2017) Open-Label, Multicenter, Phase II Study of Ceritinib in Patients With Non-Small-Cell Lung Cancer Harboring ROS1 Rearrangement. J Clin Oncol 35:2613–2618. https://doi.org/10.1200/JCO.2016.71.3701

    Article  CAS  PubMed  Google Scholar 

  24. Wu K, Liao X, Gong Y, He J, Zhou JK, Tan S, Pu W, Huang C, Wei YQ, Peng Y (2019) Circular RNA F-circSR derived from SLC34A2-ROS1 fusion gene promotes cell migration in non-small cell lung cancer. Mol Cancer 18:98. https://doi.org/10.1186/s12943-019-1028-9

    Article  PubMed  PubMed Central  Google Scholar 

  25. Chen J, Wang P, Cai R, Peng H, Zhang C, Zhang M (2019) SLC34A2 promotes neuroblastoma cell stemness via enhancement of miR-25/Gsk3beta-mediated activation of Wnt/beta-catenin signaling. FEBS Open Bio 9:527–537. https://doi.org/10.1002/2211-5463.12594

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Wang Y, Yang W, Pu Q, Yang Y, Ye S, Ma Q, Ren J, Cao Z, Zhong G, Zhang X, Liu L, Zhu W (2019) Correction to: The effects and mechanisms of SLC34A2 in tumorigenesis and progression of human non-small cell lung cancer. J Biomed Sci 26:18. https://doi.org/10.1186/s12929-019-0508-y

    Article  PubMed  PubMed Central  Google Scholar 

  27. Bhagwat AS, Roe JS, Mok BYL, Hohmann AF, Shi J, Vakoc CR (2016) BET Bromodomain Inhibition Releases the Mediator Complex from Select cis-Regulatory Elements. Cell Rep 15:519–530. https://doi.org/10.1016/j.celrep.2016.03.054

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Calpena E, Hervieu A, Kaserer T, Swagemakers SMA, Goos JAC, Popoola O, Ortiz-Ruiz MJ, Barbaro-Dieber T, Bownass L, Brilstra EH, Brimble E, Foulds N, Grebe TA, Harder AVE, Lees MM, Monaghan KG, Newbury-Ecob RA, Ong KR, Osio D, Reynoso Santos FJ, Ruzhnikov MRZ, Telegrafi A, van Binsbergen E, van Dooren MF, Deciphering Developmental Disorders S, van der Spek PJ, Blagg J, Twigg SRF, Mathijssen IMJ, Clarke PA, Wilkie AOM (2019) De Novo Missense Substitutions in the Gene Encoding CDK8, a Regulator of the Mediator Complex, Cause a Syndromic Developmental Disorder. Am J Hum Genet 104:709–720. https://doi.org/10.1016/j.ajhg.2019.02.006

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Lacroix M, Abi-Said D, Fourney DR, Gokaslan ZL, Shi W, DeMonte F, Lang FF, McCutcheon IE, Hassenbusch SJ, Holland E, Hess K, Michael C, Miller D, Sawaya R (2001) A multivariate analysis of 416 patients with glioblastoma multiforme: prognosis, extent of resection, and survival. J Neurosurg 95:190–198. https://doi.org/10.3171/jns.2001.95.2.0190

    Article  CAS  PubMed  Google Scholar 

  30. Lamborn KR, Chang SM, Prados MD (2004) Prognostic factors for survival of patients with glioblastoma: recursive partitioning analysis. Neuro Oncol 6:227–235. https://doi.org/10.1215/S1152851703000620

    Article  PubMed  PubMed Central  Google Scholar 

  31. Simpson JR, Horton J, Scott C, Curran WJ, Rubin P, Fischbach J, Isaacson S, Rotman M, Asbell SO, Nelson JS et al (1993) Influence of location and extent of surgical resection on survival of patients with glioblastoma multiforme: results of three consecutive Radiation Therapy Oncology Group (RTOG) clinical trials. Int J Radiat Oncol Biol Phys 26:239–244. https://doi.org/10.1016/0360-3016(93)90203-8

    Article  CAS  PubMed  Google Scholar 

  32. Jeremic B, Grujicic D, Antunovic V, Djuric L, Stojanovic M, Shibamoto Y (1994) Influence of extent of surgery and tumor location on treatment outcome of patients with glioblastoma multiforme treated with combined modality approach. J Neurooncol 21:177–185. https://doi.org/10.1007/bf01052902

    Article  CAS  PubMed  Google Scholar 

  33. 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 352:997–1003. https://doi.org/10.1056/NEJMoa043331

    Article  CAS  PubMed  Google Scholar 

  34. Olson RA, Brastianos PK, Palma DA (2011) Prognostic and predictive value of epigenetic silencing of MGMT in patients with high grade gliomas: a systematic review and meta-analysis. J Neurooncol 105:325–335. https://doi.org/10.1007/s11060-011-0594-5

    Article  PubMed  Google Scholar 

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Acknowledgements

The authors thank the FALCO biosystems (Kyoto, Japan) for their technical support and the members of JCOG Data Center/Operations Office (Mr. Junki Mizusawa, Dr. Keita Sasaki, and Dr. Hiroshi Katayama) for preparing this manuscript. This work was supported by a Grant-in-Aid for Scientific Research on Innovative Areas “Chemistry for Multimolecular Crowding Biosystems” (to A.N.; JSPS KAKEN grant no. 17928985).

Author information

Authors and Affiliations

  1. Department of Neurosurgery, Nagoya University Graduate School of Medicine, Nagoya, Japan

    Atsushi Natsume, Kosuke Aoki, Fumiharu Ohka, Sachi Maeda, Masaki Hirano, Alimu Adilijiang, Kazuya Motomura & Toshihiko Wakabayashi

  2. Radiation Oncology Department, Cancer Institute Hospital, Tokyo, Japan

    Minako Sumi

  3. Department of Neuro-Oncology/Neurosurgery, Saitama Medical University International Medical Center, Saitama, Japan

    Ryo Nishikawa & Kazuhiko Mishima

  4. Department of Neurosurgery and Neuro-Oncology, National Cancer Center Hospital, Tokyo, Japan

    Yoshitaka Narita & Soichiro Shibui

  5. Department of Neurosurgery, Tokyo Women’s Medical University, Tokyo, Japan

    Yoshihiro Muragaki & Takashi Maruyama

  6. Department of Neurosurgery, Nakamura Memorial Hospital, Sapporo, Japan

    Tamio Ito

  7. Department of Neurosurgery, Iwate Medical University, Iwate, Japan

    Takaaki Beppu

  8. Department of Neurosurgery, Kumamoto University Graduate School of Medicine, Kumamoto, Japan

    Hideo Nakamura

  9. Department of Neurosurgery, Yamagata University Graduate School of Medicine, Yamagata, Japan

    Takamasa Kayama & Shinya Sato

  10. Department of Neurosurgery, Faculty of Medicine, Kyorin University, Tokyo, Japan

    Motoo Nagane

  11. Department of Neurosurgery, Shizuoka Cancer Center, Shizuoka, Japan

    Yoko Nakasu

  12. Department of Neurosurgery, Hiroshima University Hospital, Hiroshima, Japan

    Kaoru Kurisu & Fumiyuki Yamasaki

  13. Department of Clinical Oncology & Neuro-Oncology Program, Hiroshima University Hospital, Hiroshima, Japan

    Kazuhiko Sugiyama

  14. Department of Neurosurgery, Ehime University Graduate School of Medicine, Ehime, Japan

    Takanori Onishi

  15. Department of Neurological Surgery, Chiba University Graduate School of Medicine, Chiba, Japan

    Yasuo Iwadate

  16. Department of Neurosurgery, Kurume University Graduate School of Medicine, Kurume, Japan

    Mizuhiko Terasaki

  17. Department of Neurosurgery, Hokkaido University Graduate School of Medicine, Sapporo, Japan

    Hiroyuki Kobayashi

  18. Department of Neurosurgery, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan

    Akira Matsumura & Eiichi Ishikawa

  19. Department of Neurosurgery, Keio University School of Medicine, Tokyo, Japan

    Hikaru Sasaki

  20. Department of Neurosurgery, The University of Tokyo Hospital, Tokyo, Japan

    Akitake Mukasa

  21. Department of Neurosurgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan

    Takayuki Matsuo

  22. Department of Neurosurgery, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan

    Hirofumi Hirano

  23. Department of Neurosurgery, Tohoku University Graduate School of Medicine, Sendai, Japan

    Toshihiro Kumabe

  24. Department of Neurosurgery, Tokyo Metropolitan Cancer and Infectious Disease Center Komagome Hospital, Tokyo, Japan

    Nobusada Shinoura

  25. Department of Neurosurgery, Osaka University Graduate School of Medicine, Osaka, Japan

    Naoya Hashimoto

  26. Department of Neurosurgery, Kitano Hospital, Osaka, Japan

    Tomokazu Aoki

  27. Department of Neurosurgery, Kansai Medical University, Osaka, Japan

    Akio Asai

  28. Department of Neurosurgery, Faculty of Medicine, Oita University, Oita, Japan

    Tatsuya Abe

  29. Department of Neurological Surgery, Nihon University Graduate School of Medicine, Tokyo, Japan

    Atsuo Yoshino

  30. Department of Neurosurgery, Kyoto University Graduate School of Medicine, Kyoto, Japan

    Yoshiki Arakawa

  31. Department of Neurosurgery, Hirosaki University Graduate School of Medicine, Hirosaki, Japan

    Kenichiro Asano

  32. Department of Neurosurgery, Graduate School of Medical Sciences, Kyusyu University, Fukuoka, Japan

    Koji Yoshimoto

  33. Center for Advanced Medicine and Clinical Research, Nagoya University Hospital, Nagoya, Japan

    Yusuke Okuno

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and Members of Japan Clinical Oncology Group Brain Tumor Study Group (JCOG-BTSG)

Corresponding author

Correspondence to Atsushi Natsume.

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Conflict of interest

TW has received research funding from Toray Co, Ltd, and MSD Co. Ltd. KS received honorarium from MSD. YN received honorarium from MSD, Chugai and Eisai, and research funding from Daiichi-Sankyo. M.N. received honorarium from MSD, Nippon-Kayaku, Chugai, Daiichi-Sankyo, AbbVie, Ono and Eisai, and research funding from Toray. RN received honorarium from MSD, Chugai, and Eisai. YA received honorarium from Nippon-Kayaku, Merck, and research funding from Merck. 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.

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Natsume, A., Aoki, K., Ohka, F. et al. Genetic analysis in patients with newly diagnosed glioblastomas treated with interferon-beta plus temozolomide in comparison with temozolomide alone. J Neurooncol 148, 17–27 (2020). https://doi.org/10.1007/s11060-020-03505-9

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  • Issue Date:

  • DOI: https://doi.org/10.1007/s11060-020-03505-9

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