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      Is Open Access

      Radiation Necrosis, Pseudoprogression, Pseudoresponse, and Tumor Recurrence: Imaging Challenges for the Evaluation of Treated Gliomas

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          Abstract

          Glioblastoma (GBM) is the most common primary malignant type of brain neoplasm in adults and carries a dismal prognosis. The current standard of care for GBM is surgical excision followed by radiation therapy (RT) with concurrent and adjuvant temozolomide-based chemotherapy (TMZ) by six additional cycles. In addition, antiangiogenic therapy with an antivascular endothelial growth factor (VEGF) agent has been used for recurrent glioblastoma. Over the last years, new posttreatment entities such as pseudoprogression and pseudoresponse have been recognized, apart from radiation necrosis. This review article focuses on the role of different imaging techniques such as conventional magnetic resonance imaging (MRI), diffusion-weighted imaging (DWI), diffusion tensor imaging (DTI), dynamic contrast enhancement (DCE-MRI) and dynamic susceptibility contrast (DSE-MRI) perfusion, magnetic resonance spectroscopy (MRS), and PET/SPECT in differentiation of such treatment-related changes from tumor recurrence.

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          Response criteria for phase II studies of supratentorial malignant glioma.

          D R Macdonald, T L Cascino, S C Schold … (1990)
          We suggest "new" response criteria for phase II studies of supratentorial malignant glioma and favor rigorous criteria similar to those in medical oncology, with important modifications. Four response categories are proposed: complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD). Response in this scheme is based on major changes in tumor size on the enhanced computed tomographic (CT) or magnetic resonance imaging (MRI) scan. Scan changes are interpreted in light of steroid use and neurologic findings. We advocate careful patient selection, emphasize pitfalls in the assessment of response, and suggest guidelines to minimize misinterpretations of response.
          Article 0 comments Cited 269 times – based on 0 reviews     Review now
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            Incidence of early pseudo-progression in a cohort of malignant glioma patients treated with chemoirradiation with temozolomide.

            Jacoline E. Bromberg, J. de Visscher, T Swaak … (2008)
            Radiotherapy (RT) plus concomitant and adjuvant temozolomide (TMZ) is now the standard of care for patients with newly diagnosed glioblastoma. The occurrence of pseudo-progression directly after RT is a recognized phenomenon, but to the authors' knowledge its incidence after combined RT/TMZ is unknown. The occurrence of early pseudo-progression was retrospectively assessed in a cohort of malignant glioma patients treated with RT/TMZ. The pre-RT and post-RT brain scans from patients treated with RT/TMZ for a malignant glioma were reviewed. Scans were made before the start of RT, 4 weeks after the end of RT, and every 3 months thereafter. In addition, information was collected regarding clinical signs and symptoms, dexamethasone dose, histology, and survival. Eighty-five patients were identified. In 36 patients (42%) the first follow-up scan 4 weeks after the end of RT indicated disease progression. Of these 36 patients, 18 (50%) were diagnosed with pseudo-progression. None of the patients received additional treatment other than TMZ. Six of 18 patients with pseudo-progression and 12 of the 18 patients with real tumor progression developed new clinical signs and symptoms during RT or in the first 4 weeks thereafter. Up to 50% of malignant glioma patients treated with RT/TMZ and progression immediately after RT develop pseudo-progression. The current study data support the idea to continue TMZ in the case of progressive lesions immediately after RT/TMZ. Surgery should be considered in symptomatic cases. The inclusion of patients with progressive lesions developing directly after chemoradiation in studies regarding recurrent gliomas will lead to an overestimation of the results. (c) 2008 American Cancer Society.
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              MR perfusion-weighted imaging in the evaluation of high-grade gliomas after treatment: a systematic review and meta-analysis

              Praneil Patel, Hediyeh Baradaran, Diana Delgado … (2017)
              Background. Distinction between tumor and treatment related changes is crucial for clinical management of patients with high-grade gliomas. Our purpose was to evaluate whether dynamic susceptibility contrast-enhanced (DSC) and dynamic contrast enhanced (DCE) perfusion-weighted imaging (PWI) metrics can effectively differentiate between recurrent tumor and posttreatment changes within the enhancing signal abnormality on conventional MRI. Methods. A comprehensive literature search was performed for studies evaluating PWI-based differentiation of recurrent tumor and posttreatment changes in patients with high-grade gliomas (World Health Organization grades III and IV). Only studies published in the “temozolomide era” beginning in 2005 were included. Summary estimates of diagnostic accuracy were obtained by using a random-effects model. Results. Of 1581 abstracts screened, 28 articles were included. The pooled sensitivities and specificities of each study's best performing parameter were 90% and 88% (95% CI: 0.85–0.94; 0.83–0.92) and 89% and 85% (95% CI: 0.78–0.96; 0.77–0.91) for DSC and DCE, respectively. The pooled sensitivities and specificities for detecting tumor recurrence using the 2 most commonly evaluated parameters, mean relative cerebral blood volume (rCBV) (threshold range, 0.9–2.15) and maximum rCBV (threshold range, 1.49–3.1), were 88% and 88% (95% CI: 0.81–0.94; 0.78–0.95) and 93% and 76% (95% CI: 0.86–0.98; 0.66–0.85), respectively. Conclusions. PWI-derived thresholds separating viable tumor from treatment changes demonstrate relatively good accuracy in individual studies. However, because of significant variability in optimal reported thresholds and other limitations in the existing body of literature, further investigation and standardization is needed before implementing any particular quantitative PWI strategy across institutions.
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                Author and article information

                Contributors
                Chrissa Sioka:
                ORCID: http://orcid.org/0000-0002-2184-4945
                Journal
                Journal ID (nlm-ta): Contrast Media Mol Imaging
                Journal ID (iso-abbrev): Contrast Media Mol Imaging
                Journal ID (publisher-id): CMMI
                Title: Contrast Media & Molecular Imaging
                Publisher: Hindawi
                ISSN (Print): 1555-4309
                ISSN (Electronic): 1555-4317
                Publication date Collection: 2018
                Publication date (Electronic): 2 December 2018
                Volume: 2018
                Electronic Location Identifier: 6828396
                Affiliations
                1Department of Radiology, University Hospital of Ioannina, Ioannina, Greece
                2Department of Nuclear Medicine, University Hospital of Ioannina, Ioannina, Greece
                3Department of Neurosurgery, University Hospital of Ioannina, Ioannina, Greece
                Author notes

                Academic Editor: André L. B. de Barros

                Author information
                http://orcid.org/0000-0002-2184-4945
                Article
                DOI: 10.1155/2018/6828396
                PMC ID: 6305027
                PubMed ID: 30627060
                SO-VID: 644f9fc6-67be-4684-ab1f-f796a8cc8be8
                Copyright © Copyright © 2018 Anastasia Zikou et al.
                License:

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 9 July 2018
                Date accepted : 15 October 2018
                Categories
                Subject: Review Article

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