Growth dynamics of untreated glioblastomas in vivo.

BACKGROUND Glioblastomas are primary malignant brain tumors with a dismal prognosis. Knowledge of growth rates and underlying growth dynamics is useful for understanding basic tumor biology, developing realistic tumor models, and planning treatment logistics. METHODS By using repeated pretreatment contrast-enhanced T1-weighted MRI scans from 106 patients (aged 26-83 years), we studied the growth dynamics of untreated glioblastomas in vivo. Growth rates were calculated as specific growth rates and equivalent volume doubling times. The fit of different possible growth models was assessed using maximum likelihood estimations. RESULTS There were large variations in growth rates between patients. The median specific growth rate of the tumors was 1.4% per day, and the equivalent volume doubling time was 49.6 days. Exploring 3 different tumor growth models showed similar statistical fit for a Gompertzian growth model and a linear radial growth model and worse fit for an exponential growth model. However, large tumors had significantly lower growth rates than smaller tumors, supporting the assumption that glioblastomas reach a plateau phase and thus exhibit Gompertzian growth. CONCLUSION Based on the fast growth rate of glioblastoma shown in this study, it is evident that poor treatment logistics will influence tumor size before surgery and can cause significant regrowth before adjuvant treatment. Since there is a known association between tumor volume, extent of surgical resection, and response to adjuvant therapy, it is likely that waiting times play a role in patient outcomes.

[1]  Susan M. Chang,et al.  Updated response assessment criteria for high-grade gliomas: response assessment in neuro-oncology working group. , 2010, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[2]  S. Bauer,et al.  A survey of MRI-based medical image analysis for brain tumor studies , 2013, Physics in medicine and biology.

[3]  R. Crevoisier,et al.  Waiting times before initiation of radiotherapy might not affect outcomes for patients with glioblastoma: a French retrospective analysis of patients treated in the era of concomitant temozolomide and radiotherapy , 2012, Journal of Neuro-Oncology.

[4]  B A Kall,et al.  Imaging-based stereotaxic serial biopsies in untreated intracranial glial neoplasms. , 1987, Journal of neurosurgery.

[5]  Roberto Chignola,et al.  Estimating the growth kinetics of experimental tumors from as few as two determinations of tumor size: implications for clinical oncology , 2005, IEEE Transactions on Biomedical Engineering.

[6]  P. Wen,et al.  Response Assessment in Neuro-Oncology , 2011, Current oncology reports.

[7]  R. Gonzalez,et al.  Clinical and radiographic features of peritumoral infarction following resection of glioblastoma , 2006, Neurology.

[8]  A. Kanner,et al.  Delayed initiation of radiotherapy for glioblastoma: how important is it to push to the front (or the back) of the line? , 2011, Journal of Neuro-Oncology.

[9]  Z L Gokaslan,et al.  A multivariate analysis of 416 patients with glioblastoma multiforme: prognosis, extent of resection, and survival. , 2001, Journal of neurosurgery.

[10]  T. Kuwabara,et al.  Estimation of rate of growth of malignant brain tumors by computed tomography scanning. , 1983, Surgical neurology.

[11]  Laird Ak DYNAMICS OF TUMOR GROWTH. , 1964 .

[12]  J. Jito,et al.  Growth curve analysis of asymptomatic and symptomatic meningiomas , 2011, Journal of Neuro-Oncology.

[13]  J. Cairncross,et al.  Corticosteroid-induced magnetic resonance imaging changes in patients with recurrent malignant glioma. , 1994, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[14]  F. Zanella,et al.  Fluorescence-guided surgery with 5-aminolevulinic acid for resection of malignant glioma: a randomised controlled multicentre phase III trial. , 2006, The Lancet. Oncology.

[15]  Anne G. Osborn,et al.  Osborn's brain : imaging, pathology, and anatomy , 2013 .

[16]  Peter Canoll,et al.  Glial progenitor cell recruitment drives aggressive glioma growth: mathematical and experimental modelling , 2012, Journal of The Royal Society Interface.

[17]  Robert J. Maciunas,et al.  Factors affecting perceived tumor volumes in magnetic resonance imaging , 2006, Annals of Biomedical Engineering.

[18]  O. J. Dunn Multiple Comparisons Using Rank Sums , 1964 .

[19]  Amy S Nowacki,et al.  Residual tumor volume versus extent of resection: predictors of survival after surgery for glioblastoma. , 2014, Journal of neurosurgery.

[20]  V. Nguyen,et al.  Glioblastoma Presenting with Steroid-Induced Pseudoregression of Contrast Enhancement on Magnetic Resonance Imaging , 2012, Case reports in neurological medicine.

[21]  Kristin R. Swanson,et al.  The Evolution of Mathematical Modeling of Glioma Proliferation and Invasion , 2007, Journal of neuropathology and experimental neurology.

[22]  J. Wardlaw,et al.  A pilot study of brain tumour growth between radiotherapy planning and delivery. , 2006, Clinical oncology (Royal College of Radiologists (Great Britain)).

[23]  P Van Tassel,et al.  Malignant gliomas: MR imaging spectrum of radiation therapy- and chemotherapy-induced necrosis of the brain after treatment. , 2000, Radiology.

[24]  J M Bland,et al.  Statistical methods for assessing agreement between two methods of clinical measurement , 1986 .

[25]  Albert Lai,et al.  Prognostic significance of growth kinetics in newly diagnosed glioblastomas revealed by combining serial imaging with a novel biomathematical model. , 2009, Cancer research.

[26]  Mordecai Schwartz A biomathematical approach to clinical tumor growth , 1961, Cancer.

[27]  Tormod Selbekk,et al.  Ultrasound-guided operations in unselected high-grade gliomas—overall results, impact of image quality and patient selection , 2010, Acta Neurochirurgica.

[28]  W Ellis,et al.  The influence of volumetric tumor doubling time, DNA ploidy, and histologic grade on the survival of patients with intracranial astrocytomas. , 1995, AJNR. American journal of neuroradiology.

[29]  Paul Thompson,et al.  Mapping tumor growth rates in patients with malignant gliomas: A test of two algorithms , 2000, NeuroImage.

[30]  Tom Børge Johannesen,et al.  [High-grade gliomas in adults]. , 2011, Tidsskrift for den Norske laegeforening : tidsskrift for praktisk medicin, ny raekke.

[31]  B. Gliński,et al.  Prognostic value of the interval from surgery to initiation of radiation therapy in correlation with some histo-clinical parameters in patients with malignant supratentorial gliomas , 2012, Contemporary oncology.

[32]  Volker Seifert,et al.  Intraoperative MRI guidance and extent of resection in glioma surgery: a randomised, controlled trial. , 2011, The Lancet. Oncology.

[33]  Eva Forssell-Aronsson,et al.  Specific growth rate versus doubling time for quantitative characterization of tumor growth rate. , 2007, Cancer research.

[34]  Dieta Brandsma,et al.  Clinical features, mechanisms, and management of pseudoprogression in malignant gliomas. , 2008, The Lancet. Oncology.

[35]  A. Jakola,et al.  Glioblastoma resection: in search of a threshold between worthwhile and futile. , 2014, Neuro-oncology.

[36]  Y. Yamada,et al.  Temporal relationship of post-operative radiotherapy with temozolomide and oncologic outcome for glioblastoma , 2013, Journal of Neuro-Oncology.

[37]  K. Tsuboi,et al.  Regrowth patterns of supratentorial gliomas: estimation from computed tomographic scans. , 1986, Neurosurgery.

[38]  Mitchel S Berger,et al.  An extent of resection threshold for newly diagnosed glioblastomas. , 2011, Journal of neurosurgery.

[39]  E. Helseth,et al.  A population-based study on the effect of temozolomide in the treatment of glioblastoma multiforme. , 2012, Neuro-oncology.