Impact on survival of early tumor growth between surgery and radiotherapy in patients with de novo glioblastoma



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.

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  1. 1.

    Larjavaara S, Mäntylä R, Salminen T, Haapasalo H, Raitanen J, Jääskeläinen J et al (2007) Incidence of gliomas by anatomic location. Neuro Oncol 9(3):319–325.

    Article  PubMed  PubMed Central  Google Scholar 

  2. 2.

    Baldi I, Gruber A, Alioum A, Berteaud E, Lebailly P, Huchet A et al (2011) Descriptive epidemiology of CNS tumors in France: results from the Gironde Registry for the period 2000–2007. Neuro Oncol 13(12):1370–1378.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  3. 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.

    Article  PubMed  PubMed Central  Google Scholar 

  4. 4.

    Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJB et al (2005) Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 352(10):987–996.

    CAS  Article  Google Scholar 

  5. 5.

    Lacroix M, Abi-Said D, Fourney DR, Gokaslan ZL, Shi W, DeMonte F et al (2001) A multivariate analysis of 416 patients with glioblastoma multiforme: prognosis, extent of resection, and survival. J Neurosurg 95(2):190–198.

    CAS  Article  PubMed  Google Scholar 

  6. 6.

    Sanai N, Polley M-Y, McDermott MW, Parsa AT, Berger MS (2011) An extent of resection threshold for newly diagnosed glioblastomas. J Neurosurg 115(1):3–8.

    Article  PubMed  Google Scholar 

  7. 7.

    Oppenlander ME, Wolf AB, Snyder LA, Bina R, Wilson JR, Coons SW et al (2014) An extent of resection threshold for recurrent glioblastoma and its risk for neurological morbidity. J Neurosurg 120(4):846–853.

    Article  PubMed  Google Scholar 

  8. 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.

    Article  PubMed  PubMed Central  Google Scholar 

  9. 9.

    Hervey-Jumper SL, Berger MS (2016) Maximizing safe resection of low- and high-grade glioma. J Neurooncol 130(2):269–282.

    Article  PubMed  Google Scholar 

  10. 10.

    Wen PY, Macdonald DR, Reardon DA, Cloughesy TF, Sorensen AG, Galanis E et al (2010) Updated response assessment criteria for high-grade gliomas: response assessment in neuro-oncology working group. J Clin Oncol 28(11):1963–1972.

    Article  PubMed  Google Scholar 

  11. 11.

    Ellingson BM, Wen PY, Cloughesy TF (2017) Modified criteria for radiographic response assessment in glioblastoma clinical trials. Neurotherapeutics 14(2):307–320.

    Article  PubMed  PubMed Central  Google Scholar 

  12. 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. Accessed 5 Mar 2018

  13. 13.

    Pirzkall A, McGue C, Saraswathy S, Cha S, Liu R, Vandenberg S et al (2009) Tumor regrowth between surgery and initiation of adjuvant therapy in patients with newly diagnosed glioblastoma. Neuro Oncol 11(6):842–852.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  14. 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.

    Article  PubMed  Google Scholar 

  15. 15.

    Villanueva-Meyer JE, Han SJ, Cha S, Butowski NA (2017) Early tumor growth between initial resection and radiotherapy of glioblastoma: incidence and impact on clinical outcomes. J Neurooncol 134(1):213–219.

    Article  PubMed  PubMed Central  Google Scholar 

  16. 16.

    Farace P, Amelio D, Ricciardi GK, Zoccatelli G, Magon S, Pizzini F et al (2013) Early MRI changes in glioblastoma in the period between surgery and adjuvant therapy. J Neurooncol 111(2):177–185.

    CAS  Article  PubMed  Google Scholar 

  17. 17.

    Pennington C, Kilbride L, Grant R, Wardlaw JM (2006) A pilot study of brain tumour growth between radiotherapy planning and delivery. Clin Oncol (R Coll Radiol) 18(2):104–108.

    CAS  Article  Google Scholar 

  18. 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.

    Article  PubMed  Google Scholar 

  19. 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.

    Article  PubMed  Google Scholar 

  20. 20.

    Ekinci G, Akpinar IN, Baltacioğlu F, Erzen C, Kiliç T, Elmaci I et al (2003) Early-postoperative magnetic resonance imaging in glial tumors: prediction of tumor regrowth and recurrence. Eur J Radiol 45(2):99–107.

    Article  PubMed  Google Scholar 

  21. 21.

    Barani IJ, Cuttino LW, Benedict SH, Todor D, Bump EA, Wu Y et al (2007) Neural stem cell-preserving external-beam radiotherapy of central nervous system malignancies. Int J Radiat Oncol Biol Phys 68(4):978–985.

    Article  PubMed  Google Scholar 

  22. 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. Accessed 13 Nov 2017

  23. 23.

    Jafri NF, Clarke JL, Weinberg V, Barani IJ, Cha S (2013) Relationship of glioblastoma multiforme to the subventricular zone is associated with survival. Neuro Oncol 15(1):91–96.

    CAS  Article  PubMed  Google Scholar 

  24. 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.

    CAS  Article  PubMed  Google Scholar 

  25. 25.

    ElBanan MG, Amer AM, Zinn PO, Colen RR (2015) Imaging genomics of glioblastoma: state of the art bridge between genomics and neuroradiology. Neuroimaging Clin N Am 25(1):141–153.

    Article  PubMed  Google Scholar 

  26. 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.

    Article  PubMed  Google Scholar 

  27. 27.

    Grabowski MM, Recinos PF, Nowacki AS, Schroeder JL, Angelov L, Barnett GH et al (2014) Residual tumor volume versus extent of resection: predictors of survival after surgery for glioblastoma. J Neurosurg 121(5):1115–1123.

    Article  PubMed  Google Scholar 

  28. 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.

    Article  PubMed  Google Scholar 

  29. 29.

    Orringer D, Lau D, Khatri S, Zamora-Berridi GJ, Zhang K, Wu C et al (2012) Extent of resection in patients with glioblastoma: limiting factors, perception of resectability, and effect on survival. J Neurosurg 117(5):851–859.

    Article  PubMed  Google Scholar 

  30. 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.

    Article  PubMed  PubMed Central  Google Scholar 

  31. 31.

    Li YM, Suki D, Hess K, Sawaya R (2016) The influence of maximum safe resection of glioblastoma on survival in 1229 patients: can we do better than gross-total resection? J Neurosurg 124(4):977–988.

    Article  PubMed  Google Scholar 

  32. 32.

    Yordanova YN, Duffau H (2017) Supratotal resection of diffuse gliomas—an overview of its multifaceted implications. Neurochirurgie 63(3):243–249.

    CAS  Article  PubMed  Google Scholar 

  33. 33.

    Esquenazi Y, Friedman E, Liu Z, Zhu J-J, Hsu S, Tandon N (2017) The survival advantage of « Supratotal » resection of glioblastoma using selective cortical mapping and the subpial technique. Neurosurgery 81(2):275–288.

    Article  PubMed  Google Scholar 

  34. 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.

    Article  PubMed  Google Scholar 

  35. 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.

    Article  PubMed  Google Scholar 

  36. 36.

    Hsu CC-T, Watkins TW, Kwan GNC, Haacke EM (2016) Susceptibility-weighted imaging of glioma: update on current imaging status and future directions. J Neuroimaging 26(4):383–390.

    Article  PubMed  Google Scholar 

  37. 37.

    Fahrendorf D, Schwindt W, Wölfer J, Jeibmann A, Kooijman H, Kugel H et al (2013) Benefits of contrast-enhanced SWI in patients with glioblastoma multiforme. Eur Radiol 23(10):2868–2879.

    Article  PubMed  Google Scholar 

  38. 38.

    Salama GR, Heier LA, Patel P, Ramakrishna R, Magge R, Tsiouris AJ (2017) Diffusion weighted/tensor imaging, functional mri and perfusion weighted imaging in glioblastoma-foundations and future. Front Neurol 8:660.

    Article  PubMed  Google Scholar 

  39. 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.

    Article  PubMed  Google Scholar 

  40. 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.

    Article  PubMed  Google Scholar 

  41. 41.

    Khalifa J, Tensaouti F, Lotterie J-A, Catalaa I, Chaltiel L, Benouaich-Amiel A et al (2016) Do perfusion and diffusion MRI predict glioblastoma relapse sites following chemoradiation? J Neurooncol 130(1):181–192.

    CAS  Article  PubMed  Google Scholar 

  42. 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.

    CAS  Article  PubMed  Google Scholar 

  43. 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.

    Article  PubMed  Google Scholar 

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The authors acknowledge Saloua Charni (Biostatistician and clinical trials coordinator) for her help with the statistics and revision of this article.


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Correspondence to Amaury De Barros.

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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.

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De Barros, A., Attal, J., Roques, M. et al. Impact on survival of early tumor growth between surgery and radiotherapy in patients with de novo glioblastoma. J Neurooncol 142, 489–497 (2019).

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  • Glioblastoma
  • Radiotherapy
  • Extent of resection
  • Tumor regrowth