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Imaging scoring systems for preoperative molecular diagnoses of lower-grade gliomas

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Abstract

Recent advance in molecular characterization of gliomas showed that patient prognosis and/or tumor chemosensitivity correlate with certain molecular signatures; however, this information is available only after tumor resection. If molecular information is available by routine radiological examinations, surgical strategy as well as overall treatment strategy could be designed preoperatively.With the aim to establish an imaging scoring system for preoperative diagnosis of molecular status in lower-grade gliomas (WHO grade 2 or 3, LrGGs), we investigated 8 imaging features available on routine CT and MRI in 45 LGGs (discovery cohort) and compared them with the status of 1p/19q codeletion, IDH mutations, and MGMT promoter methylation. The scoring systems were established based on the imaging features significantly associated with each molecular signature, and were tested in the another 52 LrGGs (validation cohort).For prediction of 1p/19q codeletion, the scoring system is composed of calcification, indistinct tumor border on T1, paramagnetic susceptibility effect on T1, and cystic component on FLAIR. For prediction of MGMT promoter methylation, the scoring system is composed of indistinct tumor border, surface localization (FLAIR), and cystic component. The scoring system for prediction of IDH status was not established. The 1p/19q score ≥ 3 showed PPV of 96.2% and specificity of 98.1%, and the MGMT methylation score ≥ 2 showed PPV of 77.4% and specificity of 67.6% in the entire cohort.These scoring systems based on widely available imaging information may help to preoperatively design personalized treatment in patients with LrGG.

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References

  1. Brown R, Zlatescu M, Sijben A, Roldan G, Easaw J, Forsyth P, Parney I, Sevick R, Yan E, Demetrick D, Schiff D, Cairncross G, Mitchell R (2008) The use of magnetic resonance imaging to noninvasively detect genetic signatures in oligodendroglioma. Clin Cancer Res: Off J Am Assoc Cancer Res 14:2357–2362. https://doi.org/10.1158/1078-0432.ccr-07-1964

    Article  CAS  Google Scholar 

  2. Cairncross JG, Ueki K, Zlatescu MC, Lisle DK, Finkelstein DM, Hammond RR, Silver JS, Stark PC, Macdonald DR, Ino Y, Ramsay DA, Louis DN (1998) Specific genetic predictors of chemotherapeutic response and survival in patients with anaplastic oligodendrogliomas. J Natl Cancer Inst 90:1473–1479

    Article  CAS  PubMed  Google Scholar 

  3. Choi C, Ganji SK, DeBerardinis RJ, Hatanpaa KJ, Rakheja D, Kovacs Z, Yang XL, Mashimo T, Raisanen JM, Marin-Valencia I, Pascual JM, Madden CJ, Mickey BE, Malloy CR, Bachoo RM, Maher EA (2012) 2-hydroxyglutarate detection by magnetic resonance spectroscopy in IDH-mutated patients with gliomas. Nat Med 18:624–629. https://doi.org/10.1038/nm.2682

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Drabycz S, Roldan G, de Robles P, Adler D, McIntyre JB, Magliocco AM, Cairncross JG, Mitchell JR (2010) An analysis of image texture, tumor location, and MGMT promoter methylation in glioblastoma using magnetic resonance imaging. NeuroImage 49:1398–1405. https://doi.org/10.1016/j.neuroimage.2009.09.049

    Article  CAS  PubMed  Google Scholar 

  5. Ellingson BM, Cloughesy TF, Pope WB, Zaw TM, Phillips H, Lalezari S, Nghiemphu PL, Ibrahim H, Naeini KM, Harris RJ, Lai A (2012) Anatomic localization of O6-methylguanine DNA methyltransferase (MGMT) promoter methylated and unmethylated tumors: a radiographic study in 358 de novo human glioblastomas. NeuroImage 59:908–916. https://doi.org/10.1016/j.neuroimage.2011.09.076

    Article  CAS  PubMed  Google Scholar 

  6. Eoli M, Menghi F, Bruzzone MG, De Simone T, Valletta L, Pollo B, Bissola L, Silvani A, Bianchessi D, D'Incerti L, Filippini G, Broggi G, Boiardi A, Finocchiaro G (2007) Methylation of O6-methylguanine DNA methyltransferase and loss of heterozygosity on 19q and/or 17p are overlapping features of secondary glioblastomas with prolonged survival. Clin Cancer Res: Off J Am Assoc Cancer Res 13:2606–2613. https://doi.org/10.1158/1078-0432.CCR-06-2184

    Article  CAS  Google Scholar 

  7. Ezaki T, Sasaki H, Hirose Y, Miwa T, Yoshida K, Kawase T (2011) Molecular characteristics of pediatric non-ependymal, nonpilocytic gliomas associated with resistance to temozolomide. Mol Med Rep 4:1101–1105. https://doi.org/10.3892/mmr.2011.573

    Article  CAS  PubMed  Google Scholar 

  8. Gupta A, Omuro AM, Shah AD, Graber JJ, Shi W, Zhang Z, Young RJ (2012) Continuing the search for MR imaging biomarkers for MGMT promoter methylation status: conventional and perfusion MRI revisited. Neuroradiology 54:641–643. https://doi.org/10.1007/s00234-011-0970-z

    Article  PubMed  Google Scholar 

  9. Hayashi S, Kitamura Y, Hirose Y, Yoshida K, Sasaki H (2017) Molecular-genetic and clinicopathological prognostic factors in patients with gliomas showing total 1p19q loss: gain of chromosome 19p and histological grade III negatively correlate with patient’s prognosis. J Neuro-Oncol 132:119–126. https://doi.org/10.1007/s11060-016-2344-1

    Article  CAS  Google Scholar 

  10. Hirose Y, Aldape K, Takahashi M, Berger MS, Feuerstein BG (2001) Tissue microdissection and degenerate oligonucleotide primed-polymerase chain reaction (DOP-PCR) is an effective method to analyze genetic aberrations in invasive tumors. J Mol Diagn: JMD 3:62–67. https://doi.org/10.1016/s1525-1578(10)60653-8

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Jenkinson MD, Smith TS, Joyce KA, Fildes D, Broome J, du Plessis DG, Haylock B, Husband DJ, Warnke PC, Walker C (2006) Cerebral blood volume, genotype and chemosensitivity in oligodendroglial tumours. Neuroradiology 48:703–713. https://doi.org/10.1007/s00234-006-0122-z

    Article  PubMed  PubMed Central  Google Scholar 

  12. Kalinina J, Carroll A, Wang L, Yu Q, Mancheno DE, Wu S, Liu F, Ahn J, He M, Mao H, Van Meir EG (2012) Detection of “oncometabolite” 2-hydroxyglutarate by magnetic resonance analysis as a biomarker of IDH1/2 mutations in glioma. J Mol Med 90:1161–1171. https://doi.org/10.1007/s00109-012-0888-x

    Article  CAS  PubMed  Google Scholar 

  13. Kleihues P, Burger PC, Scheithauer BW (1993) Histological typing of tumors of the central nervous system, 2nd edn. Springer, Berlin

    Book  Google Scholar 

  14. Kleihues P, Cavanee W (2000) Pathology and genetics of tumors of the nervous system. International Agency for Research on Cancer Press, Lyon

    Google Scholar 

  15. Korfiatis P, Kline TL, Coufalova L, Lachance DH, Parney IF, Carter RE, Buckner JC, Erickson BJ (2016) MRI texture features as biomarkers to predict MGMT methylation status in glioblastomas. Med Phys 43:2835–2844. https://doi.org/10.1118/1.4948668

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Louis DN, Ohgaki H, Wiestler OD, Cavenee WK (2007) WHO classification of tumours of the central nervous system, 4th edn. International agency for research on cancer, Lyon

    Google Scholar 

  17. Louis DN, Ohgaki H, Wiestler OD, Cavenee WK, Ellison DW, Figarella-Branger D, Perry A, Reifenberger G, von Deimling A (2016) WHO classification of tumours of the central nervous system. Revised 4th Edition edn. International agency for research on cancer, Lyon

    Google Scholar 

  18. Megyesi JF, Kachur E, Lee DH, Zlatescu MC, Betensky RA, Forsyth PA, Okada Y, Sasaki H, Mizoguchi M, Louis DN, Cairncross JG (2004) Imaging correlates of molecular signatures in oligodendrogliomas. Clin Cancer Res: Off J Am Assoc Cancer Res 10:4303–4306. https://doi.org/10.1158/1078-0432.ccr-04-0209

    Article  Google Scholar 

  19. Miwa T, Hirose Y, Sasaki H, Ezaki T, Yoshida K, Kawase T (2011) Single-copy gain of chromosome 1q is a negative prognostic marker in pediatric nonependymal, nonpilocytic gliomas. Neurosurgery 68:206–212. https://doi.org/10.1227/NEU.0b013e3181fd2c2e

    Article  PubMed  Google Scholar 

  20. Miwa T, Hirose Y, Sasaki H, Ikeda E, Yoshida K, Kawase T (2009) Genetic characterization of adult infratentorial gliomas. J Neuro-Oncol 91:251–255. https://doi.org/10.1007/s11060-008-9714-2

    Article  Google Scholar 

  21. Nishiyama Y, Sasaki H, Nagahisa S, Adachi K, Hayashi T, Yoshida K, Kawase T, Hattori N, Murayama K, Abe M, Hasegawa M, Hirose Y (2014) Radiological features of supratentorial gliomas are associated with their genetic aberrations. Neurosurg Rev 37:291–299; discussion 299-300. https://doi.org/10.1007/s10143-013-0515-5

    Article  PubMed  Google Scholar 

  22. Pope WB, Qiao XJ, Kim HJ, Lai A, Nghiemphu P, Xue X, Ellingson BM, Schiff D, Aregawi D, Cha S, Puduvalli VK, Wu J, Yung WK, Young GS, Vredenburgh J, Barboriak D, Abrey LE, Mikkelsen T, Jain R, Paleologos NA, Rn PL, Prados M, Goldin J, Wen PY, Cloughesy T (2012) Apparent diffusion coefficient histogram analysis stratifies progression-free and overall survival in patients with recurrent GBM treated with bevacizumab: a multi-center study. J Neuro-Oncol 108:491–498. https://doi.org/10.1007/s11060-012-0847-y

    Article  CAS  Google Scholar 

  23. Qi S, Yu L, Li H, Ou Y, Qiu X, Ding Y, Han H, Zhang X (2014) Isocitrate dehydrogenase mutation is associated with tumor location and magnetic resonance imaging characteristics in astrocytic neoplasms. Oncol Lett 7:1895–1902. https://doi.org/10.3892/ol.2014.2013

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Saito T, Maruyama T, Muragaki Y, Tanaka M, Nitta M, Shinoda J, Aki T, Iseki H, Kurisu K, Okada Y (2013) 11C-methionine uptake correlates with combined 1p and 19q loss of heterozygosity in oligodendroglial tumors. AJNR Am J Neuroradiol 34:85–91. https://doi.org/10.3174/ajnr.A3173

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Sanai N, Berger MS (2008) Glioma extent of resection and its impact on patient outcome. Neurosurgery 62:753–764 discussion 264-756

    Article  PubMed  Google Scholar 

  26. Sasaki H, Hirose Y, Yazaki T, Kitamura Y, Katayama M, Kimura T, Fujiwara H, Toda M, Ohira T, Yoshida K (2015) Upfront chemotherapy and subsequent resection for molecularly defined gliomas. J Neuro-Oncol 124:127–135. https://doi.org/10.1007/s11060-015-1817-y

    Article  CAS  Google Scholar 

  27. Sasaki H, Zlatescu MC, Betensky RA, Ino Y, Cairncross JG, Louis DN (2001) PTEN is a target of chromosome 10q loss in anaplastic oligodendrogliomas and PTEN alterations are associated with poor prognosis. Am J Pathol 159:359–367. https://doi.org/10.1016/s0002-9440(10)61702-6

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Smith JS, Chang EF, Lamborn KR, Chang SM, Prados MD, Cha S, Tihan T, Vandenberg S, McDermott MW, Berger MS (2008) Role of extent of resection in the long-term outcome of low-grade hemispheric gliomas. J Clin Oncol: Off J Am Soc Clin Oncol 26:1338–1345. https://doi.org/10.1200/JCO.2007.13.9337

    Article  Google Scholar 

  29. Sonoda Y, Shibahara I, Kawaguchi T, Saito R, Kanamori M, Watanabe M, Suzuki H, Kumabe T, Tominaga T (2015) Association between molecular alterations and tumor location and MRI characteristics in anaplastic gliomas. Brain Tumor Pathol 32:99–104. https://doi.org/10.1007/s10014-014-0211-3

    Article  CAS  PubMed  Google Scholar 

  30. van den Bent MJ, Baumert B, Erridge SC, Vogelbaum MA, Nowak AK, Sanson M, Brandes AA, Clement PM, Baurain JF, Mason WP, Wheeler H, Chinot OL, Gill S, Griffin M, Brachman DG, Taal W, Ruda R, Weller M, McBain C, Reijneveld J, Enting RH, Weber DC, Lesimple T, Clenton S, Gijtenbeek A, Pascoe S, Herrlinger U, Hau P, Dhermain F, van Heuvel I, Stupp R, Aldape K, Jenkins RB, Dubbink HJ, Dinjens WNM, Wesseling P, Nuyens S, Golfinopoulos V, Gorlia T, Wick W, Kros JM (2017) Interim results from the CATNON trial (EORTC study 26053-22054) of treatment with concurrent and adjuvant temozolomide for 1p/19q non-co-deleted anaplastic glioma: a phase 3, randomised, open-label intergroup study. Lancet (Lond, Engl) 390:1645–1653. https://doi.org/10.1016/s0140-6736(17)31442-3

    Article  CAS  Google Scholar 

  31. Walker C, du Plessis DG, Fildes D, Haylock B, Husband D, Jenkinson MD, Joyce KA, Broome J, Kopitski K, Prosser J, Smith T, Vinjamuri S, Warnke PC (2004) Correlation of molecular genetics with molecular and morphological imaging in gliomas with an oligodendroglial component. Clin Cancer Res: Off J Am Assoc Cancer Res 10:7182–7191. https://doi.org/10.1158/1078-0432.CCR-04-0681

    Article  CAS  Google Scholar 

  32. Xiong J, Tan W, Wen J, Pan J, Wang Y, Zhang J, Geng D (2016) Combination of diffusion tensor imaging and conventional MRI correlates with isocitrate dehydrogenase 1/2 mutations but not 1p/19q genotyping in oligodendroglial tumours. Eur Radiol 26:1705–1715. https://doi.org/10.1007/s00330-015-4025-4

    Article  PubMed  Google Scholar 

  33. Yan H, Parsons DW, Jin G, McLendon R, Rasheed BA, Yuan W, Kos I, Batinic-Haberle I, Jones S, Riggins GJ, Friedman H, Friedman A, Reardon D, Herndon J, Kinzler KW, Velculescu VE, Vogelstein B, Bigner DD (2009) IDH1 and IDH2 mutations in gliomas. N Engl J Med 360:765–773. https://doi.org/10.1056/NEJMoa0808710

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Zhang B, Chang K, Ramkissoon S, Tanguturi S, Bi WL, Reardon DA, Ligon KL, Alexander BM, Wen PY, Huang RY (2017) Multimodal MRI features predict isocitrate dehydrogenase genotype in high-grade gliomas. Neuro-Oncology 19:109–117. https://doi.org/10.1093/neuonc/now121

    Article  CAS  PubMed  Google Scholar 

  35. Zhou H, Vallieres M, Bai HX, Su C, Tang H, Oldridge D, Zhang Z, Xiao B, Liao W, Tao Y, Zhou J, Zhang P, Yang L (2017) MRI features predict survival and molecular markers in diffuse lower-grade gliomas. Neuro-Oncology 19:862–870. https://doi.org/10.1093/neuonc/now256

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Zlatescu MC, TehraniYazdi A, Sasaki H, Megyesi JF, Betensky RA, Louis DN, Cairncross JG (2001) Tumor location and growth pattern correlate with genetic signature in oligodendroglial neoplasms. Cancer Res 61:6713–6715

    CAS  PubMed  Google Scholar 

  37. Zulch KJ (1979) Histological typing of tumors of the central nervous system. World Health Organization, Genova

    Google Scholar 

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Acknowledgements

We greatly thank Ms. Naoko Tsuzaki at Department of Neurosurgery, Keio University School of Medicine for technical assistance of laboratory works. The authors also greatly thank Dr. Takayuki Abe at Center for Clinical Research, Department of Preventive Medicine and Public Health, Keio University School of Medicine, for statistical advice.

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Authors and Affiliations

  1. Department of Neurosurgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan

    Tokunori Kanazawa, Saeko Tanaka, Kazunari Yoshida & Hikaru Sasaki

  2. Department of Diagnostic Radiology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan

    Hirokazu Fujiwara & Hidenori Takahashi

  3. Department of Neurosurgery, Fujita Health University School of Medicine, 1-98 Dengakugakubo, Kutusukake-cho, Toyoake, Aichi, 470-1192, Japan

    Yuya Nishiyama & Yuichi Hirose

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  1. Tokunori Kanazawa
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Correspondence to Hikaru Sasaki.

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This study has been conducted as a part of the collaborative translational research approved by the Institutional Review Board at Keio University and Fujita Health University. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Kanazawa, T., Fujiwara, H., Takahashi, H. et al. Imaging scoring systems for preoperative molecular diagnoses of lower-grade gliomas. Neurosurg Rev 42, 433–441 (2019). https://doi.org/10.1007/s10143-018-0981-x

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