Characterization of pseudoprogression in patients with glioblastoma: is histology the gold standard?

Abstract Pseudoprogression (psPD) refers to an increase in size or appearance of new areas of MRI contrast enhancement soon after completing chemoradiation, timely diagnosis of which has been a challenge. Given that tissue sampling of the MRI changes would be expected to accurately distinguish psPD from true progression when MRI changes are first seen, we examined the utility of surgery in diagnosing psPD and influencing patient outcome. We retrospectively reviewed data from adults with GBM who had MRI changes suggestive of progression within 3 months of chemoRT; of these, 34 underwent surgical resection. Three subsets–tumor, psPD or mixed-were identified based on histology and immunohistochemistry in the surgical group and by imaging characteristics in the nonsurgical group. A cohort of patients with stable disease post-chemoRT served as control. PFS and OS were determined using the Kaplan–Meier method and log rank analysis. Concordance for psPD between radiological interpretation and subsequent histological diagnosis was seen in only 32 % of cases (11/34) 95 %CI 19–49 %. A large proportion of patients had a histologically “mixed” pattern with tumor and treatment effect. No significant differences in PFS or OS were seen among the three subtypes. Surgical sampling and histologic review of MRI changes after chemoRT may not serve as a gold standard to distinguish psPD from true progression in GBM patients. Refinement of the histological criteria, careful intraoperative selection of regions of interest and advanced imaging modalities are needed for early differentiation of PsPD from progression to guide clinical management.

[1]  G. Schackert,et al.  Is there pseudoprogression in secondary glioblastomas? , 2013, International journal of radiation oncology, biology, physics.

[2]  R. Schmidt,et al.  Cancer therapy-associated CNS neuropathology: an update and review of the literature , 2006, Acta Neuropathologica.

[3]  Stephen T. C. Wong,et al.  Support vector machine multiparametric MRI identification of pseudoprogression from tumor recurrence in patients with resected glioblastoma , 2011, Journal of magnetic resonance imaging : JMRI.

[4]  Mark E Mullins,et al.  Radiation necrosis versus glioma recurrence: conventional MR imaging clues to diagnosis. , 2005, AJNR. American journal of neuroradiology.

[5]  R. Prayson,et al.  Role of MIB1 in Predicting Survival in Patients with Glioblastomas , 2005, Journal of Neuro-Oncology.

[6]  W. Shi,et al.  Potential utility of conventional MRI signs in diagnosing pseudoprogression in glioblastoma , 2011, Neurology.

[7]  P. Box.  Immediate post-radiotherapy changes in malignant glioma can mimic tumor progression , 2005 .

[8]  Andrew E. Sloan,et al.  Early necrosis following concurrent Temodar and radiotherapy in patients with glioblastoma , 2007, Journal of Neuro-Oncology.

[9]  Leland S. Hu,et al.  Reevaluating the imaging definition of tumor progression: perfusion MRI quantifies recurrent glioblastoma tumor fraction, pseudoprogression, and radiation necrosis to predict survival , 2012, Neuro-oncology.

[10]  Dieta Brandsma,et al.  Incidence of early pseudo‐progression in a cohort of malignant glioma patients treated with chemoirradiation with temozolomide , 2008, Cancer.

[11]  O. De Witte,et al.  High levels of cellular proliferation predict pseudoprogression in glioblastoma patients , 2011, International journal of oncology.

[12]  P. Wen,et al.  Effect of adding temozolomide to radiation therapy on the incidence of pseudo-progression , 2009, Journal of Neuro-Oncology.

[13]  Hong Liu,et al.  Multivoxel 3D proton MR spectroscopy in the distinction of recurrent glioma from radiation injury , 2007, Journal of Neuro-Oncology.

[14]  Susan Chang,et al.  Pseudoprogression and pseudoresponse: Challenges in brain tumor imaging , 2009, Current neurology and neuroscience reports.

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

[16]  Martin J. van den Bent,et al.  Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. , 2005, The New England journal of medicine.

[17]  A. Brandes,et al.  MGMT promoter methylation status can predict the incidence and outcome of pseudoprogression after concomitant radiochemotherapy in newly diagnosed glioblastoma patients. , 2008, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[18]  Timothy A. Chan,et al.  MRI perfusion in determining pseudoprogression in patients with glioblastoma. , 2013, Clinical imaging.

[19]  J. Uhm.  Updated Response Assessment Criteria for High-Grade Gliomas: Response Assessment in Neuro-Oncology Working Group , 2010 .

[20]  V. Levin,et al.  Evaluation of malignant glioma patients during the postirradiation period. , 1979, Journal of neurosurgery.

[21]  Maria I. Argyropoulou,et al.  Glioma recurrence versus radiation necrosis: accuracy of current imaging modalities , 2009, Journal of Neuro-Oncology.

[22]  William D Rooney,et al.  Potential for differentiation of pseudoprogression from true tumor progression with dynamic susceptibility-weighted contrast-enhanced magnetic resonance imaging using ferumoxytol vs. gadoteridol: a pilot study. , 2011, International journal of radiation oncology, biology, physics.

[23]  P. Kleihues,et al.  IDH1 Mutations as Molecular Signature and Predictive Factor of Secondary Glioblastomas , 2009, Clinical Cancer Research.

[24]  Kiyohiro Houkin,et al.  IDH1 mutation as a potential novel biomarker for distinguishing pseudoprogression from true progression in patients with glioblastoma treated with temozolomide and radiotherapy , 2013, Brain Tumor Pathology.

[25]  Bo Young Kim,et al.  Pathologic Diagnosis of Recurrent Glioblastoma: Morphologic, Immunohistochemical, and Molecular Analysis of 20 Paired Cases , 2012, The American journal of surgical pathology.

[26]  W. Rooney,et al.  Pseudoprogression of glioblastoma after chemo- and radiation therapy: diagnosis by using dynamic susceptibility-weighted contrast-enhanced perfusion MR imaging with ferumoxytol versus gadoteridol and correlation with survival. , 2013, Radiology.

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

[28]  A. von Deimling,et al.  Application of Mutant IDH1 Antibody to Differentiate Diffuse Glioma From Nonneoplastic Central Nervous System Lesions and Therapy-induced Changes , 2010, The American journal of surgical pathology.

[29]  Hong Liu,et al.  Distinction between recurrent glioma and radiation injury using magnetic resonance spectroscopy in combination with diffusion-weighted imaging. , 2007, International journal of radiation oncology, biology, physics.

[30]  J E Heiserman,et al.  Relative Cerebral Blood Volume Values to Differentiate High-Grade Glioma Recurrence from Posttreatment Radiation Effect: Direct Correlation between Image-Guided Tissue Histopathology and Localized Dynamic Susceptibility-Weighted Contrast-Enhanced Perfusion MR Imaging Measurements , 2009, American Journal of Neuroradiology.