Impact on survival of early tumor growth between surgery and radiotherapy in patients with de novo glioblastoma
- 164 Downloads
Systematic pre-radiotherapy MRI in patients with newly resected glioblastoma (OMS 2016) sometimes reveals tumor growth in the period between surgery and radiotherapy. We evaluated the relation between early tumor growth and overall survival (OS) with the aim of finding predictors of regrowth.
Seventy-five patients from 25 to 84 years old (Median age 62 years) with preoperative, immediate postoperative, and preradiotherapy MRI were included. Volumetric measurements were made on each of the three MRI scans and clinical and molecular parameters were collected for each case.
Fifty-four patients (72%) had an early regrowth with a median contrast enhancement volume of 3.61 cm3—range 0.12–71.93 cm3. The median OS was 24 months in patients with no early tumor growth and 17.1 months in those with early tumor regrowth (p = 0.0024). In the population with initial complete resection (27 patients), the median OS was 25.3 months (19 patients) in those with no early tumor growth between surgery and radiotherapy compared to 16.3 months (8 patients) in those with tumor regrowth. In multivariate analysis, the initial extent of resection (p < 0.001) and the delay between postoperative MRI and preradiotherapy MRI (p < 0.001) were significant independent prognostic factors of regrowth and of poorer outcome.
We demonstrated that, in addition to the well known issue of incomplete resection, longer delays between surgery and adjuvant treatment is an independent factors of tumor regrowth and a risk factor of poorer outcomes for the patients. To overcome the delay factor, we suggest shortening the usual time between surgery and radiotherapy.
KeywordsGlioblastoma Radiotherapy Extent of resection Tumor regrowth
The authors acknowledge Saloua Charni (Biostatistician and clinical trials coordinator) for her help with the statistics and revision of this article.
No funding for this study.
Compliance with ethical standards
Conflict of interest
The authors declare they have no conflict of interest.
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. French law concerning retrospective studies stipulate that the CNIL (“Commission nationale informatique et libertés”) has to be informed in accordance with the French law text : Décret n°2005-1309 du 20 octobre 2005 pris pour l’application de la loi n° 78-17 du 6 janvier 1978 relative à l’informatique, aux fichiers et aux libertés.
- 3.Ostrom QT, Gittleman H, Liao P, Vecchione-Koval T, Wolinsky Y, Kruchko C et al (2017) CBTRUS statistical report: primary brain and other central nervous system tumors diagnosed in the United States in 2010–2014. Neuro-oncol 19(suppl_5):v1–v88. https://doi.org/10.1093/neuonc/nox158 CrossRefPubMedPubMedCentralGoogle Scholar
- 8.Ellingson BM, Abrey LE, Nelson SJ, Kaufmann TJ, Garcia J, Chinot O et al (2018) Validation of post-operative residual contrast enhancing tumor volume as an independent prognostic factor for overall survival in newly diagnosed glioblastoma. Neuro-oncol. https://doi.org/10.1093/neuonc/noy053 CrossRefPubMedPubMedCentralGoogle Scholar
- 12.Kanaly CW, Ding D, Mehta AI, Waller AF, Crocker I, Desjardins A et al (2011) A novel method for volumetric MRI response assessment of enhancing brain tumors. PLoS ONE. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3027624/. Accessed 5 Mar 2018
- 14.Majós C, Cos M, Castañer S, Pons A, Gil M, Fernández-Coello A et al (2016) Preradiotherapy MR imaging: a prospective pilot study of the usefulness of performing an MR examination shortly before radiation therapy in patients with glioblastoma. AJNR Am J Neuroradiol 37(12):2224–2230. https://doi.org/10.3174/ajnr.A4917 CrossRefPubMedGoogle Scholar
- 18.Smith JS, Cha S, Mayo MC, McDermott MW, Parsa AT, Chang SM et al (2005) Serial diffusion-weighted magnetic resonance imaging in cases of glioma: distinguishing tumor recurrence from postresection injury. J Neurosurg 103(3):428–438. https://doi.org/10.3171/jns.2005.103.3.0428 CrossRefPubMedGoogle Scholar
- 19.Louis DN, Perry A, Reifenberger G, Deimling A von, Figarella-Branger D, Cavenee WK et al (2016) The 2016 World Health Organization classification of tumors of the central nervous system: a summary. Acta Neuropathol 131(6):803–820. https://doi.org/10.1007/s00401-016-1545-1 CrossRefPubMedGoogle Scholar
- 22.Khalifa J, Tensaouti F, Lusque A, Plas B, Lotterie J-A, Benouaich-Amiel A et al (2017) Subventricular zones: new key targets for glioblastoma treatment. Radiat Oncol. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5397708/. Accessed 13 Nov 2017
- 24.Attal J, Chaltiel L, Lubrano V, Sol JC, Lanaspeze C, Vieillevigne L et al (2018) Subventricular zone involvement at recurrence is a strong predictive factor of outcome following high grade glioma reirradiation. J Neurooncol 136(2):413–419. https://doi.org/10.1007/s11060-017-2669-4 CrossRefPubMedGoogle Scholar
- 26.Kickingereder P, Bonekamp D, Nowosielski M, Kratz A, Sill M, Burth S et al (2016) Radiogenomics of glioblastoma: machine learning-based classification of molecular characteristics by using multiparametric and multiregional MR imaging features. Radiology 281(3):907–918. https://doi.org/10.1148/radiol.2016161382 CrossRefPubMedGoogle Scholar
- 28.Chaichana KL, Jusue-Torres I, Navarro-Ramirez R, Raza SM, Pascual-Gallego M, Ibrahim A et al (2014) Establishing percent resection and residual volume thresholds affecting survival and recurrence for patients with newly diagnosed intracranial glioblastoma. Neuro-oncol 16(1):113–122. https://doi.org/10.1093/neuonc/not137 CrossRefPubMedGoogle Scholar
- 30.Brown TJ, Brennan MC, Li M, Church EW, Brandmeir NJ, Rakszawski KL et al (2016) Association of the extent of resection with survival in glioblastoma: a systematic review and meta-analysis. JAMA Oncol 2(11):1460–1469. https://doi.org/10.1001/jamaoncol.2016.1373 CrossRefPubMedPubMedCentralGoogle Scholar
- 34.Pessina F, Navarria P, Cozzi L, Ascolese AM, Simonelli M, Santoro A et al (2017) Maximize surgical resection beyond contrast-enhancing boundaries in newly diagnosed glioblastoma multiforme: is it useful and safe? A single institution retrospective experience. J Neurooncol 135(1):129–139. https://doi.org/10.1007/s11060-017-2559-9 CrossRefPubMedGoogle Scholar
- 35.Yan J-L, van der Hoorn A, Larkin TJ, Boonzaier NR, Matys T, Price SJ (2017) Extent of resection of peritumoral diffusion tensor imaging-detected abnormality as a predictor of survival in adult glioblastoma patients. J Neurosurg 126(1):234–241. https://doi.org/10.3171/2016.1.JNS152153 CrossRefPubMedGoogle Scholar
- 39.Boonzaier NR, Larkin TJ, Matys T, van der Hoorn A, Yan J-L, Price SJ (2017) Multiparametric MR imaging of diffusion and perfusion in contrast-enhancing and nonenhancing components in patients with glioblastoma. Radiology 284(1):180–190. https://doi.org/10.1148/radiol.2017160150 CrossRefPubMedGoogle Scholar
- 40.Juan-Albarracín J, Fuster-Garcia E, Pérez-Girbés A, Aparici-Robles F, Alberich-Bayarri Á, Revert-Ventura A et al (2018) Glioblastoma: vascular habitats detected at preoperative dynamic susceptibility-weighted contrast-enhanced perfusion MR imaging predict survival. Radiology. https://doi.org/10.1148/radiol.2017170845 CrossRefPubMedGoogle Scholar
- 42.Khalifa J, Tensaouti F, Chaltiel L, Lotterie J-A, Catalaa I, Sunyach MP et al (2016) Identification of a candidate biomarker from perfusion MRI to anticipate glioblastoma progression after chemoradiation. Eur Radiol 26(11):4194–4203. https://doi.org/10.1007/s00330-016-4234-5 CrossRefPubMedGoogle Scholar
- 43.Laprie A, Catalaa I, Cassol E, McKnight TR, Berchery D, Marre D et al (2008) Proton magnetic resonance spectroscopic imaging in newly diagnosed glioblastoma: predictive value for the site of postradiotherapy relapse in a prospective longitudinal study. Int J Radiat Oncol Biol Phys 70(3):773–781. https://doi.org/10.1016/j.ijrobp.2007.10.039 CrossRefPubMedGoogle Scholar