Glioblastoma radiomics: can genomic and molecular characteristics correlate with imaging response patterns?
For glioblastoma (GBM), imaging response (IR) or pseudoprogression (PSP) is frequently observed after chemoradiation and may connote a favorable prognosis. With tumors categorized by the Cancer Genome Atlas Project (mesenchymal, classical, neural, and proneural) and by methylguanine-methyltransferase (MGMT) methylation status, we attempted to determine if certain genomic or molecular subtypes of GBM were specifically associated with IR or PSP.
Patients with GBM treated at two institutions were reviewed. Kaplan-Meier method was used to estimate overall survival (OS) and progression-free survival (PFS). Mantel-cox test determined effect of IR and PSP on OS and PFS. Fisher’s exact test was utilized to correlate IR and PSP with genomic subtypes and MGMT status.
Eighty-two patients with GBM were reviewed. The median OS and PFS were 17.9 months and 8.9 months. IR was observed in 28 (40%) and was associated with improved OS (median 29.4 vs 14.5 months p < 0.01) and PFS (median 17.7 vs 5.5 months, p < 0.01). PSP was observed in 14 (19.2%) and trended towards improved PFS (15.0 vs 7.7 months p = 0.08). Tumors with a proneural component had a higher rate of IR compared to those without a proneural component (IR 60% vs 28%; p = 0.03). MGMT methylation was associated with IR (58% vs 24%, p = 0.032), but not PSP (34%, p = 0.10).
IR is associated with improved OS and PFS. The proneural subtype and MGMT methylated tumors had higher rates of IR.
KeywordsImaging response Pseudoprogression TCGA subtype Glioblastoma Radiomics
Compliance with ethical standards
This study was funded in part by the Ben and Catherine Ivy Foundation (RP, GF: patient data collected from the Swedish Neuroscience Institute). The content is solely the responsibility of the respective authors and does not necessarily represent the official views of the Ben and Catherine Ivy Foundation.
Conflict of interest
The authors declare that they have no conflict of interest.
All procedures performed in the 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. For this type of study formal consent is not required.
For this type of retrospective study formal consent is not required.
- 2.Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJB, 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 (2005) Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 352:987–996CrossRefPubMedGoogle Scholar
- 3.Stupp R, Taillibert S, Kanner AA, Kesari S, Steinberg DM, Toms SA, Taylor LP, Lieberman F, Silvani A, Fink KL, Barnett GH, Zhu JJ, Henson JW, Engelhard HH, Chen TC, Tran DD, Sroubek J, Tran ND, Hottinger AF, Landolfi J, Desai R, Caroli M, Kew Y, Honnorat J, Idbaih A, Kirson ED, Weinberg U, Palti Y, Hegi ME, Ram Z (2015) Maintenance therapy with tumor-treating fields plus temozolomide vs temozolomide alone for glioblastoma: a randomized clinical trial. JAMA 314:2535–2543CrossRefPubMedGoogle Scholar
- 5.Hegi ME, Diserens A-C, Gorlia T, Hamou MF, de Tribolet N, Weller M, Kros JM, Hainfellner JA, Mason W, Mariani L, Bromberg JEC, Hau P, Mirimanoff RO, Cairncross JG, Janzer RC, Stupp R (2005) MGMT gene silencing and benefit from temozolomide in glioblastoma. N Engl J Med 352:997–1003CrossRefPubMedGoogle Scholar
- 6.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 360:765–773CrossRefPubMedPubMedCentralGoogle Scholar
- 8.Gutman DA, Cooper LAD, Hwang SN, Holder CA, Gao JJ, Aurora TD, Dunn WD Jr, Scarpace L, Mikkelsen T, Jain R, Wintermark M, Jilwan M, Raghavan P, Huang E, Clifford RJ, Mongkolwat P, Kleper V, Freymann J, Kirby J, Zinn PO, Moreno CS, Jaffe C, Colen R, Rubin DL, Saltz J, Flanders A, Brat DJ (2013) MR imaging predictors of molecular profile and survival: multi-institutional study of the TCGA glioblastoma data set. Radiology 267:560–569CrossRefPubMedPubMedCentralGoogle Scholar
- 11.Shah N, Feng X, Lankerovich M, et al (2016) Data from Ivy GAP. https://doi.org/10.7937/K9/TCIA.2016.XLWAN6NL
- 13.Wen PY, Macdonald DR, Reardon DA, Cloughesy TF, Sorensen AG, Galanis E, DeGroot J, Wick W, Gilbert MR, Lassman AB, Tsien C, Mikkelsen T, Wong ET, Chamberlain MC, Stupp R, Lamborn KR, Vogelbaum MA, van den Bent MJ, Chang SM (2010) Updated response assessment criteria for high-grade gliomas: response assessment in neuro-oncology working group. J Clin Oncol 28:1963–1972CrossRefPubMedGoogle Scholar
- 14.Holmes JA, Paulsson A, Peiffer AM et al (2014) Genomic predictors of infield and marginal failure for glioblastoma treated with concurrent radiation therapy and temozolomide: a step towards personalized radiation fields? Radiat Oncol 90:S291–S292Google Scholar
- 16.Verhaak RGW, Hoadley KA, Purdom E, Wang V, Qi Y, Wilkerson MD, Miller CR, Ding L, Golub T, Mesirov JP, Alexe G, Lawrence M, O'Kelly M, Tamayo P, Weir BA, Gabriel S, Winckler W, Gupta S, Jakkula L, Feiler HS, Hodgson JG, James CD, Sarkaria JN, Brennan C, Kahn A, Spellman PT, Wilson RK, Speed TP, Gray JW, Meyerson M, Getz G, Perou CM, Hayes DN (2010) Integrated genomic analysis identifies clinically relevant subtypes of glioblastoma characterized by abnormalities in PDGFRA, IDH1, EGFR, and NF1. Cancer Cell 17:98–110CrossRefPubMedPubMedCentralGoogle Scholar
- 17.The Allen Brain Institute Ivy Glioblastoma Atlas Project. http://help.brain-map.org/display/glioblastoma/Documentation
- 18.Bady P, Sciuscio D, Diserens A-C, Bloch J, van den Bent MJ, Marosi C, Dietrich PY, Weller M, Mariani L, Heppner FL, Mcdonald DR, Lacombe D, Stupp R, Delorenzi M, Hegi ME (2012) MGMT methylation analysis of glioblastoma on the Infinium methylation BeadChip identifies two distinct CpG regions associated with gene silencing and outcome, yielding a prediction model for comparisons across datasets, tumor grades, and CIMP-status. Acta Neuropathol 124:547–560CrossRefPubMedPubMedCentralGoogle Scholar
- 22.Geer CP, Simonds J, Anvery A, Chen MY, Burdette JH, Zapadka ME, Ellis TL, Tatter SB, Lesser GJ, Chan MD, McMullen KP, Johnson AJ (2012) Does MR perfusion imaging impact management decisions for patients with brain tumors? A prospective study. AJNR Am J Neuroradiol 33:556–562CrossRefPubMedGoogle Scholar
- 23.Tsuyuguchi N, Takami T, Sunada I, Iwai Y, Yamanaka K, Tanaka K, Nishikawa M, Ohata K, Torii K, Morino M, Nishio A, Hara M (2004) Methionine positron emission tomography for differentiation of recurrent brain tumor and radiation necrosis after stereotactic radiosurgery —in malignant glioma—. Ann Nucl Med 18:291–296CrossRefPubMedGoogle Scholar
- 24.Qian X, Tan H, Zhang J, et al (2016) Identification of biomarkers for pseudo and true progression of GBM based on radiogenomics study. Oncotarget 7(34):55377–55394. https://doi.org/10.18632/oncotarget.10553
- 25.Proposed Decision Memo for Next Generation Sequencing (NGS) for Medicare Beneficiaries with Advanced Cancer (CAG-00450N). https://www.cms.gov/medicare-coverage-database/details/nca-proposed-decision-memo.aspx?NCAId=290&bc=AAAAAAAAAAQAAA%3D%3D