Pseudoprogression In Patients Research Articles

Differentiating tumour progression from pseudoprogression in patients with glioblastoma using multiparametric MRI imaging: Data from Barts Health NHS trust London

Differentiating tumour progression from pseudoprogression in patients with glioblastoma using multiparametric MRI imaging: Data from Barts Health NHS trust London

Inter-interpreter reliability of neuropathological assessment of disease status after early repeat resection for suspected recurrent glioblastoma.

2050Background: Distinction of true progression from pseudo-progression in patients with suspected recurrent glioblastoma (rGBM) is an important and common diagnostic challenge in neuro-oncology. T...

Differentiating Tumor Progression from Pseudoprogression in Patients with Glioblastomas Using Diffusion Tensor Imaging and Dynamic Susceptibility Contrast MRI.

Early assessment of treatment response is critical in patients with glioblastomas. A combination of DTI and DSC perfusion imaging parameters was evaluated to distinguish glioblastomas with true progression from mixed response and pseudoprogression. Forty-one patients with glioblastomas exhibiting enhancing lesions within 6 months after completion of chemoradiation therapy were retrospectively studied. All patients underwent surgery after MR imaging and were histologically classified as having true progression (>75% tumor), mixed response (25%-75% tumor), or pseudoprogression (<25% tumor). Mean diffusivity, fractional anisotropy, linear anisotropy coefficient, planar anisotropy coefficient, spheric anisotropy coefficient, and maximum relative cerebral blood volume values were measured from the enhancing tissue. A multivariate logistic regression analysis was used to determine the best model for classification of true progression from mixed response or pseudoprogression. Significantly elevated maximum relative cerebral blood volume, fractional anisotropy, linear anisotropy coefficient, and planar anisotropy coefficient and decreased spheric anisotropy coefficient were observed in true progression compared with pseudoprogression (P < .05). There were also significant differences in maximum relative cerebral blood volume, fractional anisotropy, planar anisotropy coefficient, and spheric anisotropy coefficient measurements between mixed response and true progression groups. The best model to distinguish true progression from non-true progression (pseudoprogression and mixed) consisted of fractional anisotropy, linear anisotropy coefficient, and maximum relative cerebral blood volume, resulting in an area under the curve of 0.905. This model also differentiated true progression from mixed response with an area under the curve of 0.901. A combination of fractional anisotropy and maximum relative cerebral blood volume differentiated pseudoprogression from nonpseudoprogression (true progression and mixed) with an area under the curve of 0.807. DTI and DSC perfusion imaging can improve accuracy in assessing treatment response and may aid in individualized treatment of patients with glioblastomas.

Independent Poor Prognostic Factors for True Progression after Radiation Therapy and Concomitant Temozolomide in Patients with Glioblastoma: Subependymal Enhancement and Low ADC Value.

Subependymal enhancement and DWI have been reported to be useful MR imaging markers for identifying true progression. Our aim was to determine whether the subependymal enhancement pattern and ADC can differentiate true progression from pseudoprogression in patients with glioblastoma multiforme treated with concurrent chemoradiotherapy by using temozolomide. Forty-two patients with glioblastoma multiforme with newly developed or enlarged enhancing lesions on the first follow-up MR images obtained within 2 months of concurrent chemoradiotherapy completion were included. Subependymal enhancement was analyzed for the presence, location, and pattern (local or distant relative to enhancing lesions). The mean ADC value and the fifth percentile of the cumulative ADC histogram were determined. A multiple logistic regression analysis was performed to identify independent factors associated with true progression. Distant subependymal enhancement (ie, extending >1 cm or isolated from the enhancing lesion) was significantly more common in true progression (n = 24) than in pseudoprogression (n = 18) (P = .042). The fifth percentile of the cumulative ADC histogram was significantly lower in true progression than in pseudoprogression (P = .014). Both the distant subependymal enhancement and the fifth percentile of the cumulative ADC histogram were independent factors associated with true progression (P = .041 and P = .033, respectively). Sensitivity and specificity for the diagnosis of true progression were 83% and 67%, respectively, by using both factors. Both the distant subependymal enhancement and the fifth percentile of the cumulative ADC histogram were significant independent factors predictive of true progression.

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

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.

Pseudoprogression in Patients with Glioblastoma: Assessment by Using Volume-weighted Voxel-based Multiparametric Clustering of MR Imaging Data in an Independent Test Set

To validate a volume-weighted voxel-based multiparametric clustering (VVMC) method for magnetic resonance imaging data that is designed to differentiate between pseudoprogression and early tumor progression (ETP) in patients with glioblastoma in an independent test set. This retrospective study was approved by the local institutional review board, with waiver of the need to obtain informed consent. The study patients were grouped chronologically into a training set (108 patients) and a test set (54 patients). The reference standard was pathologic findings or subsequent clinical-radiologic study results. By using the optimal cutoff determined in the training set, the diagnostic performance of VVMC was subsequently tested in the test set and was compared with that of single-parameter measurements (apparent diffusion coefficient [ADC], normalized cerebral blood volume [nCBV], and initial area under the time-signal intensity curve). Interreader agreement was highest for VVMC (intraclass correlation coefficient, 0.87-0.89). Receiver operating characteristic curve analysis revealed that VVMC performed the best as a classifier, although statistical significance was not demonstrated with respect to the nCBV in the training set. In the test set, the diagnostic accuracy of VVMC was higher than that of any single-parameter measurements, but this trend reached significance only for the ADC. When the entire population was considered, VVMC had significantly better diagnostic accuracy than did any single parameter (P = .003-.046 for reader 1; P = .002-.016 for reader 2). Results of fivefold cross validation confirmed the trends in both the training set and the test set. VVMC is a superior and more reproducible imaging biomarker than single-parameter measurements for differentiating between pseudoprogression and ETP in patients with glioblastoma. Online supplemental material is available for this article.

IT-26 * IDENTIFICATION OF PSEUDO-PROGRESSION IN NEW DIAGNOSED GLIOBLASTOMA (GBM) IN A RANDOMIZED PHASE 2 OF ICT-107: MRI AND PATHOLOGY CORRELATION

BACKGROUND: Previously reports of pseudo-progression in patients with brain tumor after therapeutic vaccines in pediatric and adult glioma (Pollack, JCO online on June 2, 2014 and Okada, JCO Jan 20, 2011; 29: 330-336) demonstrated that RANO criteria for tumor progression may not be adequate for immunotherapy trials. Similar observations were also seen in other checkpoint inhibitor in melanoma and NSLSC. METHODS: We identified 2 patients, who developed tumor progression by RANO criteria, underwent surgery following enrollment in a phase 2 randomized ICT-107 (an autologous vaccine consisting of patient dendritic cells pulsed with peptides from AIM-2, TRP-2, HER2/neu, IL-13Ra2, gp100, MAGE1) after radiation and Temozolomide (TMZ). RESULTS: The first case is a 69 years old Chinese male, who underwent 1st surgery of gross total resection right occipital GBM on 10/26/2011. Subsequently he received 19 cycles of TMZ and 9 vaccines/placebo. MRI from 7/2/2013 showed enhancement surrounding surgical cavity. After 2nd surgery, pathology showed only rare residual tumor cells with macrophages and positive CD 8 cells. He continued on this vaccine program and MRI showed more progression with finger-like extension into parietal lobe 4 months later. The 3rd surgery also showed extensive reactive changes with no active tumor cells. For 2nd case, a 62 years old male, who underwent first surgery on 7/11/2011 of right temporal lobe, developed 2 areas of enhancement after 6 cycles of TMZ and 7 vaccines/placebo on 4/18/2012. With 2nd surgery, pathology showed reactive gliosis without active tumor. The subject continued in this trial. CONCLUSION: Pseudo-progression was confirmed by pathology in these 2 patients at 20 and 9 months which were delayed comparing to pseudo-progression observed in patients treated with concurrent XRT/TMZ (3-6 months). Future iRANO criteria development is essential for immunotherapy trials. Accurately identifying and managing such patients is necessary to avoid premature termination of therapy.

Pseudoprogression in patients with glioblastoma: clinical relevance despite low incidence.

According to the Response Assessment in Neuro-Oncology criteria, new enhancement within the radiation field on contrast enhanced T1-weighted images within 12 weeks after completion of radiotherapy should not qualify for progressive disease, since up to 50% of these cases may be pseudoprogression (PsP). To validate this concept, we assessed incidence and overall survival (OS) of patients with suspected and confirmed PsP dependent on different time intervals and definitions of PsP. Patients with newly diagnosed glioblastoma and an enhancement increase of at least 25% after completion of standard radiochemotherapy at month 1, 4, 7, or 10 were eligible. Based on the development of the enhancement in follow-up examinations, patients were categorized as either PsP (subgrouped as complete resolution/decrease >50% and decrease <50%/stable) or true progression. Out of 548 patients, 79 fulfilled the inclusion criteria. Of these 79 patients, 9 (11.4%) showed PsP (6/45 patients at 1 month, 2/17 at 4 months, 1/9 at 7 months, and 0/8 at 10 months). Complete resolution of the enhancement was found in 1, decrease >50% in 3, decrease <50% in 2, and stable enhancement in 3 patients with PsP. Patients with PsP showed a significantly longer OS (P < .012). No difference in OS was found among PsP subgroups. This series challenges the current concept of PsP. Even though we could confirm a prolonged OS of patients with PsP, the incidence of PsP was lower than reported previously and extended beyond 12 weeks.

Prospective analysis of serial FLT-PET scanning to discriminate between true and pseudoprogression in glioblastoma.

2009 Background: Response evaluation in glioblastoma (GBM) patients after concomitant radiotherapy and temozolomide (TMZ) is hampered by the occurrence of progressive contrast enhancing lesions on MRI that do not reflect true tumor progression. 18F-fluorothymidine (FLT) is a Positron Emission Tomography (PET) tracer that is taken up by proliferating cells. The goal of this study was to prospectively assess the value of FLT-PET in discriminating between true progression and pseudoprogression in patients with primary GBM treated with radiotherapy and TMZ (NTR3680). Methods: FLT-PET scans were performed before start and 4 weeks after radiochemotherapy. MRI scans were performed at these time points and after 3 cycles of adjuvant TMZ. Macdonald criteria were used for response evaluation on MRI. Pseudoprogression was defined as progressive disease on MRI after radiochemotherapy, with stabilization or improvement of enhancing lesions after 3 cycles of adjuvant TMZ. Changes in SUVmax and tumor to normal brain tis...

The role of imaging in the management of progressive glioblastoma

Which imaging techniques most accurately differentiate true tumor progression from pseudo-progression or treatment related changes in patients with previously diagnosed glioblastoma? These recommendations apply to adults with previously diagnosed glioblastoma who are suspected of experiencing progression of the neoplastic process. Magnetic resonance imaging with and without gadolinium enhancement is recommended as the imaging surveillance method to detect the progression of previously diagnosed glioblastoma. Magnetic resonance spectroscopy is recommended as a diagnostic method to differentiate true tumor progression from treatment-related imaging changes or pseudo-progression in patients with suspected progressive glioblastoma. The routine use of positron emission tomography to identify progression of glioblastoma is not recommended. Single-photon emission computed tomography imaging is recommended as a diagnostic method to differentiate true tumor progression from treatment-related imaging changes or pseudo-progression in patients with suspected progressive glioblastoma.

Differentiation of Tumor Progression from Pseudoprogression in Patients with Posttreatment Glioblastoma Using Multiparametric Histogram Analysis

The multiparametric imaging can show us different aspects of tumor behavior and may help differentiation of tumor recurrence from treatment related change. Our aim was to differentiate tumor progression from pseudoprogression in patients with glioblastoma by using multiparametric histogram analysis of 2 consecutive MR imaging studies with relative cerebral blood volume and ADC values. Thirty-five consecutive patients with glioblastoma with new or increased size of enhancing lesions after concomitant chemoradiation therapy following surgical resection were included. Combined histograms were made by using the relative cerebral blood volume and ADC values of enhancing areas for initial and follow-up MR imaging, and subtracted histograms were also prepared. The histogram parameters between groups were compared. The diagnostic accuracy of tumor progression based on the histogram parameters of initial and follow-up MR imaging and subtracted histograms was compared and correlated with overall survival. Twenty-four pseudoprogressions and 11 tumor progressions were determined. Diagnosis based on the subtracted histogram mode with a multiparametric approach was more accurate than the diagnosis based on the uniparametric approach (area under the receiver operating characteristic curve of 0.877 versus 0.801), with 81.8% sensitivity and 100% specificity. A high mode of relative cerebral blood volume on the subtracted histogram by using a multiparametric approach (relative cerebral blood volume ×ADC) was the best predictor of true tumor progression (P < .001) and worse survival (P = .003). Multiparametric histogram analysis of posttreatment glioblastoma was useful to predict true tumor progression and worse survival.

Evaluation of pseudoprogression in patients with glioblastoma multiforme using dynamic magnetic resonance imaging with ferumoxytol calls RANO criteria into question

Diagnosis of pseudoprogression in patients with glioblastoma multiforme (GBM) is limited by Response Assessment in Neuro-Oncology (RANO) criteria to 3 months after chemoradiotherapy (CRT). Frequency of pseudoprogression occurring beyond this time limit was determined. Survival comparison was made between pseudoprogression and true progression patients as determined by using perfusion magnetic resonance imaging with ferumoxytol (p-MRI-Fe). Fifty-six patients with GBM who demonstrated conventional findings concerning for progression of disease post CRT were enrolled in institutional review board-approved MRI protocols. Dynamic susceptibility-weighted contrast-enhanced p-MRI-Fe was used to distinguish true progression from pseudoprogression using relative cerebral blood volume (rCBV) values. rCBV of 1.75 was assigned as the cutoff value. Participants were followed up using RANO criteria, and survival data were analyzed. Twenty-seven participants (48.2%) experienced pseudoprogression. Pseudoprogression occurred later than 3 months post CRT in 8 (29.6%) of these 27 participants (ie, 8 [14.3%] of the 56 patients meeting the inclusion criteria). Overall survival was significantly longer in participants with pseudoprogression (35.2 months) compared with those who never experienced pseudoprogression (14.3 months; P < .001). Pseudoprogression presented after 3 months post CRT in a considerable portion of patients with GBM, which raises doubts about the value of the 3-month time limit of the RANO criteria. Accurate rCBV measurement (eg, p-MRI-Fe) is suggested when there are radiographical concerns about progression of disease in GBM patients, regardless of any time limit. Pseudoprogression correlates with significantly better survival outcomes.

Prediction of Pseudoprogression in Patients with Glioblastomas Using the Initial and Final Area Under the Curves Ratio Derived from Dynamic Contrast-Enhanced T1-Weighted Perfusion MR Imaging

Dynamic contrast-enhanced T1-weighted perfusion MR imaging is much less susceptible to artifacts, and its high spatial resolution allows accurate characterization of the vascular microenvironment of the lesion. The purpose of this study was to test the predictive value of the initial and final area under the time signal-intensity curves ratio derived from dynamic contrast-enhanced perfusion MR imaging to differentiate pseudoprogression from early tumor progression in patients with glioblastomas. Seventy-nine consecutive patients who showed new or enlarged, contrast-enhancing lesions within the radiation field after concurrent chemoradiotherapy were assessed by use of conventional and dynamic contrast-enhanced perfusion MR imaging. The bimodal histogram parameters of the area under the time signal-intensity curves ratio, which included the mean area under the time signal-intensity curves ratio at a higher curve (mAUCRH), 3 cumulative histogram parameters (AUCR50, AUCR75, and AUCR90), and the area under the time signal-intensity curves ratio at mode (AUCRmode), were calculated and correlated with the final pathologic or clinical diagnosis. The best predictor for differentiation of pseudoprogression from early tumor progression was determined by receiver operating characteristic curve analyses. Seventy-nine study patients were subsequently classified as having pseudoprogression (n=37, 46.8%) or early tumor progression (n=42, 53.2%). There were statistically significant differences of mAUCRH, AUCR50, AUCR75, AUCR90, and AUCRmode between the 2 groups (P < .0001, each). Receiver operating characteristic curve analyses showed the mAUCRH to be the best single predictor of pseudoprogression, with a sensitivity of 90.1% and a specificity of 82.9%. AUCR50 was found to be the most specific predictor of pseudoprogression, with a sensitivity of 87.2% and a specificity of 83.1%. A bimodal histogram analysis of the area under the time signal-intensity curves ratio derived from dynamic contrast-enhanced perfusion MR imaging can be a potential, noninvasive imaging biomarker for monitoring early treatment response in patients with glioblastomas.

Pseudoprogression in patients with glioblastoma: added value of arterial spin labeling to dynamic susceptibility contrast perfusion MR imaging

Pseudoprogression is a treatment-related reaction with an increase in contrast-enhancing lesion size, followed by subsequent improvement. Differentiating tumor recurrence from pseudoprogression remains a problem in neuro-oncology. To validate the added value of arterial spin labeling (ASL), compared with dynamic susceptibility contrast (DSC) perfusion magnetic resonance imaging (MRI) alone, in distinguishing early tumor progression from pseudoprogression in patients with newly diagnosed glioblastoma multiforme (GBM). We retrospectively evaluated 117 consecutive patients with newly diagnosed GBM who underwent surgical resection and concurrent chemoradiotherapy (CCRT) as standard treatment modality. Sixty-two patients who developed contrast-enhancing lesions were assessed by both ASL and DSC perfusion MRI and classified into groups of early tumor recurrence (n = 34) or pseudoprogression (n = 28) based on pathologic analysis or clinical-radiologic follow-up. We used a qualitative analysis and semi-quantitative grade system on the basis of the tumor perfusion signal intensity into those equal to white matter (grade I), gray matter (grade II), and blood vessels (grade III) on ASL imaging. ASL grade was correlated with histogram parameters derived from DSC perfusion MRI. Pseudoprogression was observed in 15 (53.6%) patients with ASL grade I, 13 (46.4%) with grade II, and 0 (0%) with grade III, with early tumor progression observed in seven (20.6%) patients with ASL grade I, 11 (32.3%) with grade II, and 16 (47.1%) with grade III (P = 0.0022). DSC perfusion histogram parameters differed significantly among ASL grades. ASL grade was an independent predictor differentiating pseudoprogression from early tumor progression (odds ratio, 4.73; P = 0.0017). On qualitative review, adjunctive ASL produced eight (12.9%) more accurate results than DSC perfusion MRI alone. ASL improves the diagnostic accuracy of DSC perfusion MRI in differentiating pseudoprogression from early tumor progression.

Percent Change of Perfusion Skewness and Kurtosis: A Potential Imaging Biomarker for Early Treatment Response in Patients with Newly Diagnosed Glioblastomas

To test the predictive value of skewness and kurtosis changes of normalized cerebral blood volume (nCBV) during the early treatment period for differentiating early tumor progression from pseudoprogression in patients with newly diagnosed glioblastomas. The institutional review board approved this retrospective study. The authors assessed 135 patients with newly diagnosed glioblastomas who underwent concurrent chemotherapy and radiation therapy (CCRT) after surgical resection. Patients who developed new or enlarged contrast material-enhanced lesions after CCRT were assessed by means of conventional and perfusion magnetic resonance (MR) imaging. The percent change of skewness and kurtosis on nCBV histograms between the first and second post-CCRT follow-up were classified into four categories. Independent predictors of early tumor progression were determined by means of logistic regression analysis. Of 135 patients, 79 had new or enlarged contrast-enhanced lesions after CCRT, subsequently classified as early tumor progression (n = 42, 53.2%) and pseudoprogression (n = 37, 46.8%). Pseudoprogression was observed in 23 of 24 (95.8%) patients in category 1, 10 of 15 (66.7%) in category 2, four of 20 (20.0%) in category 3, and 0 of 20 (0%) in category 4 (χ(2) test, P < .0001). The histographic pattern of nCBV was the best independent predictor (odds ratio, 3.51; P = .0032) for early tumor progression, rather than each percent change of skewness or kurtosis; the histographic pattern of nCBV represented the largest area under the receiver operating characteristic curve (0.934; 95% confidence interval: 0.855, 0.977), with a sensitivity of 85.7% and a specificity of 89.2%. The percent change of skewness and kurtosis of nCBV may be a potential imaging biomarker for early treatment response in patients with newly diagnosed glioblastomas.

MRI perfusion in determining pseudoprogression in patients with glioblastoma

We examine the role of dynamic susceptibility contrast (DSC) magnetic resonance imaging (MRI) perfusion in differentiating pseudoprogression from progression in 20 consecutive patients with treated glioblastoma. MRI perfusion was performed, and relative cerebral blood volume (rCBV), relative peak height (rPH), and percent signal recovery (PSR) were measured. Pseudoprogression demonstrated lower median rCBV (P=.009) and rPH (P<.001), and higher PSR (P=.039) than progression. DSC MRI perfusion successfully identified pseudoprogression in patients who did not require a change in treatment despite radiographic worsening following chemoradiotherapy.

Impact of adjuvant anti-VEGF therapy on treatment-related pseudoprogression in patients with newly diagnosed glioblastoma receiving chemoradiation with or without anti-VEGF therapy.

2025 Background: Chemoradiation (CRT) can significantly modify the appearance of glioblastoma (GBM) on MRI, especially within the 3-month window after CRT. Pseudoprogression (PsP) is an increasingly recognized phenomenon in this scenario, and is thought to be secondary to increased permeability of the tumor vessels from irradiation, possibly enhanced by temozolomide (TMZ). We sought to determine if the addition of a VEGF signaling inhibitor (cediranib) during and after CRT had an impact on the frequency of PsP, by comparing two groups of patients with newly diagnosed GBMs. Methods: Two groups of patients enrolled in IRB-approved trials underwent serial MRIs at baseline, weekly during CRT and monthly thereafter. The control group received radiation plus TMZ, while the other group (CED) also received cediranib until progression (which was defined by RANO criteria) or toxicity. Patients that progressed up to 3 months after CRT were considered to have apparent progression (AP) and kept on treatment. Lesions that subsequently stabilized/regressed were classified as PsP, while those that maintained growth despite treatment were classified as true early progression (EP). Results: Forty patients were enrolled in CED and 11 as controls. Ten patients from CED and three controls were excluded due to treatment discontinuation before 3 months (drug-related toxicity and enrollment in post-CRT trials respectively). Three patients in CED (6%) had AP (all confirmed as EP) and no patients fulfilled criteria for PsP. Six patients from control (54%) had AP; 3 (27%) were eventually classified as EP and 3 (27%) as PsP. The frequency of PsP was significantly higher in the control group (p=0.0086). Conclusions: The addition of a VEGF inhibitor as part of adjuvant treatment in this cohort of glioblastoma patients prevented the development of early treatment-related effects (PsP). Suppressing the edema and mass effect that accompanies PsP may improve the tolerability of treatment. Additionally, this effect may be exploited as a strategy to make chemoradiation feasible in patients with large, unresectable tumors and/or poor baseline performance status.

Results of Early Reoperation for Suspected Pseudoprogression in Patients with Glioblastoma Multiforme

Results of Early Reoperation for Suspected Pseudoprogression in Patients with Glioblastoma Multiforme

Peri-ictal pseudoprogression in patients with brain tumor

Recent advances in the treatment of malignant gliomas have highlighted the fact that the appearance of new contrast-enhancing lesions on magnetic resonance imaging (MRI) is not always indicative of tumor recurrence. It has been suggested that transient seizure-related MRI changes could mimic disease progression (peri-ictal pseudoprogression [PIPG]). However, the clinical and MRI features associated with this situation have not been well described. Here, we consulted the databases of 6 institutions to identify patients with brain tumor who presented during the follow-up period transient MRI lesions wrongly suggesting tumor progression in a context of epileptic seizures. Ten patients were identified. All patients but 1 were long-term survivors who had initially been treated with radiotherapy. The PIPG episode occurred after a median interval of 11 years after radiotherapy. MRI features were highly similar across patients and consisted of transient focal cortical and/or leptomeningeal enhancing lesions that erroneously suggested tumor progression. All patients improved after adjustment of their antiepileptic drugs and transient oral corticosteroids, and MRI findings were normalized 3 months after the PIPG episode. Two patients demonstrated several seizure relapses with the same clinicoradiological pattern. After a median follow-up period of 3.5 years after the initial PIPG episode, only 1 patient presented with a tumor recurrence. In conclusion, in patients with brain tumor, especially in long-term survivors of radiotherapy, the appearance of new cortical and/or leptomeningeal contrast-enhancing lesions in a context of frequent seizures should raise the suspicion of PIPG. This phenomenon is important to recognize in order to avoid futile therapeutic escalation.

Potential utility of conventional MRI signs in diagnosing pseudoprogression in glioblastoma

To examine the potential utility of conventional MRI signs in differentiating pseudoprogression (PsP) from early progression (EP). This retrospective study reviewed initial postradiotherapy MRI scans of 321 patients with glioblastoma undergoing chemotherapy and radiotherapy. A total of 93 patients were found to have new or increased enhancing mass lesions, raising the possibility of PsP. Final diagnosis of PsP or EP was established upon review of surgical specimens from a second resection or by clinical and radiologic follow-up. A total of 11 MRI signs potentially helpful in the differentiation between PsP and EP were examined on the initial post-RT MRI and were correlated with the final diagnosis through χ(2) or Fisher exact test. Sixty-three (67.7%) of the 93 patients had EP, of which 22 (34.9%) were diagnosed by pathology. Thirty patients (32.3%) had PsP; 6 (16.7% of the 30) were diagnosed by pathology. Subependymal enhancement was predictive for EP (p = 0.001) with 38.1% sensitivity, 93.3% specificity, and 41.8% negative predictive value. The other 10 signs had no predictive value (p = 0.06-1.0). Conventional MRI signs have limited utility in diagnosing PsP in patients with recently treated glioblastomas and worsening enhancing lesions. We did not find a sign with a high negative predictive value for PsP that would have been the most useful for the clinical physician. When present, subependymal spread of the enhancing lesion is a useful MRI marker in identifying EP rather than PsP.