The Radiologic Evaluation of Glioblastoma (GBM) and Differentiation from Pseudoprogression

Transcription

1 The Radiologic Evaluation of Glioblastoma (GBM) and Differentiation from Pseudoprogression Alexis Roy, Harvard Medical School, Year III

2 Our Patient AB: Clinical Presentation 53 year old female with a past medical history of breast cancer, brought to the ED by her husband due to worsening short term memory loss and confusion over the last couple of days A few months prior, she developed new-onset depression, insomnia, and frontal headaches Neurological exam Alert and oriented X 2 (she did not know the date) Speech, motor strength, coordination, and sensation were intact 2

3 Our Patient AB: Initial CT Scan Axial, CT head without contrast A mass is centered at the corpus callosum and crosses the midline. The mass splays the lateral ventricles with dilation of the lateral ventricle occipital horn. The mass contains cystic areas without hemorrhage or infarction. 3

4 Our Patient AB: Differential Diagnosis Differential diagnosis Malignancy Breast cancer metastasis Glial tumor Lymphoma Non-glial cell tumors (e.g., meningioma) Neurodegenerative disease: multiple sclerosis The crossing of the midline and the heterogeneous appearance of the mass put GBM at the top of the differential 4

5 Learning Objectives To understand the clinical presentation, radiologic findings on CT and MRI, and histologic features of glioblastoma To become familiar with the menu of tests available to image brain tumors To understand how the menu of tests can be applied to different patients using the index patient AB and companion patient XY To learn how PET-CT can be used to help differentiate true tumor progression from pseudoprogression 5

6 GBM: WHO Astrocytoma Classification Brain Tumors Metastasis Glial Origin Non-glial origin Choroid Plexus Ependymal cells Astrocytes Oliglodendrocytes Astrocytoma WHO Classification Pilocytic (Grade1) Diffuse astrocytoma (Grade2) Anaplastic astrocytoma (Grade 3) Glioblastoma (Grade 4) Grade is determined based on histologic features (e.g., nuclear atypia, mitosis, necrosis) and molecular/dna alterations (e.g., EGFR, PTEN, and MDM2). Louis et al. (2007) 6

7 GBM: Clinical Presentation Symptoms are progressive and typically evolve over the course of days to weeks Signs and symptoms depend on the size and location of the tumor The most common initial presenting symptom is headache (57%). Additional symptoms include: Memory loss and cognitive changes (39%) Language deficits (36%) Personality changes (27%) Seizures (23%) Chang et al. (2005) 7

8 GBM: Epidemiology Incidence: 2-4/100,000 adults per year 52% of all primary brain tumors Most commonly in adults years of age National Cancer Institute 8

9 GBM: Menu of Tests Non Contrast Head CT: Initial screening in emergency situations Detects bone involvement and calcifications Option for patients in whom MRI is contraindicated. MRI with gadolinium contrast: Largely replaced CT for diagnostic purposes Preferred imaging to characterize the mass due to its good tissue contrast resolution Better evaluation of meninges, subarachnoid space, and posterior fossa than CT PET-CT: Tumor has increased radiotracer uptake, which can help differentiate tumor from normal brain parenchyma 9

10 Part I: Interim Summary Thus far we have reviewed WHO astrocytoma classification Presentation and epidemiology of GBM Menu of tests for imaging brain tumors We have also introduced our patient AB, and provided you with her head CT without contrast and brief differential diagnosis Next, we will review some basic neuroanatomy and then proceed to examine the MRI images from our patient AB with the goal of becoming familiar with the MRI appearance of GBM on T1 pre- and post-contrast, T2, and FLAIR sequences. 10

11 Normal Neuroanatomy FRONTAL LOBE Genu CC Lateral ventricle Frontal Lobe Genu CC Rostrum CC Body CC Thalamus Splenium CC Occipital Lobe TEMPORAL LOBE Thalamus Cerebellum Splenium CC Lateral ventricle OCCIPITAL LOBE 11

12 Our patient AB: MRI T1 Weighted Axial slices, MRI TI, C- grey matter white matter In TI weighted images, white matter is hyperintense relative to grey matter. CSF within the ventricles has no signal (black). The mass crosses the midline by infiltrating the corpus callosum, and is hypointense to the white matter in which it sits. The center of the mass has a heterogeneous signal due to cystic spaces and/or necrosis. There is mass effect on the lateral ventricles, leading to impairment of CSF drainage with enlargement of the occipital horn of the lateral ventricle. 12

13 Our patient AB: MRI T1 pre- and postcontrast Axial slice, MRI TI, C- Provided for comparison Axial slice, MRI TI, C+ Since the brain is protected by the blood brain barrier (BBB), contrast is usually unable to enter the brain parenchyma. The irregular boarder of GBM is enhancing with contrast, indicating break down of the BBB. This suggests a higher degree of malignancy. It is important to note that contrast enhanced images cannot visualize the extent of GBM, because tumor can invade into surrounding parenchyma, where the BBB is still intact. 13 The central cystic component is non-enhancing.

14 Our patient AB: MRI T1, C+ Coronal, MRI TI, C+ Sagittal, MRI TI, C+ Example of Butterfly Glioma The left image shows a coronal view of the mass crossing the corpus callosum. This classic finding gives GBM its nickname of butterfly glioma. The mass also shows ring enhancement around a cystic core, which is typical for GBM. The right image shows a sagittal view of the mass localized to the splenium of the corpus callosum. 14

15 Our patient AB: MRI, T2 Weighted Axial, MRI T2 grey matter white matter In T2 weighted images, white matter is hypointense to grey matter. CSF is bright. Shown here are two sequential axial slices through the GBM. On T2, the mass is hyperintense to the surrounding white matter, due to its high water content. 15

16 Our Patient AB: MRI FLAIR Axial, MRI FLAIR Fluid-attenuation inversion recovery (FLAIR) is a MRI sequence that suppresses CSF signal to increase visualization of surrounding tumor edema. There is significant edema around the solid mass. 16

17 GBM: Microscopic Appearance 4 core samples were obtained from our patient AB, all of which were classified as Glioblastoma, WHO Astrocytoma Grade IV Histologic features of GBM: hypercellular, nuclear pleomorphism with increased mitotic figures, necrosis with palisading nuclei and vascular proliferation. Image from UpToDate 17

18 GBM: Treatment Standard treatment includes maximal surgical resection, and adjuvant focal beam radiation to the remaining tissue and systemic chemotherapy (temozolamide - oral alkylating agent) for 6 weeks PT AB was not amenable to surgery and received radiation therapy and temozolamide 18

19 GBM: Prognosis Median overall survival of 15 mo 5-year survival 5% Improved prognosis is associated with Younger age Better performance status More extensive surgical resection Our patient AB expired several months later Stupp et al. (2005), Gorlia et al. (2008) 19

20 Part II: Interim Summary We have now reviewed: MRI features of GBM on T1 pre- and postcontrast, T2, and FLAIR sequences Treatment and prognosis of GBM We will now introduce our companion patient XY to illuminate the utility of PET-CT in differentiating true tumor progression from pseudoprogression 20

21 Companion Patient XY: Medical Course XY is a 41 year old male, who presented to the ED with new-onset seizures. MRI showed a right temporal mass Biopsy confirmed GBM, Grade IV Astrocytoma The mass was resected followed by adjuvant radiation therapy and temozolomide. Several months later he had worsening of symptoms and underwent MRI and PET-CT to look for recurrence, which showed interval progression. 21

22 GBM: Pseudoprogression Although companion patient XY s MRI showed interval progression, it was difficult with MRI alone to differentiate true progression of his GBM from pseudoprogression Pseudoprogression: post-treatment, the tumor can appear more extentensive than baseline imaging, which can be accompanied by worsening symptoms. However, these changes are transient and the tumor eventually will reduce in size PET can help differentiate tumor progression vs. pseudoprogression, as true tumor progression will show more avid 18F-fluorodeoxyglucose (FDG) uptake 22

23 Companion patient XY: PET & MRI Axial, PET Axial T1, C+ Axial, T2 grey matter white matter On PET, grey matter contains metabolically active neurons, which accumulate radiotracer (FDG). White matter contains axons with myelin, which are less metabolically active. Tumor recurrence in the temporal lobe is not obvious on T1 post contrast (middle) or T2 (right), but the tumor shows clear FDG uptake on PET imaging (left), indicating recurrence and not pseudoprogression. 23

24 GBM: PET Limitations and Future Directions Both normal brain and gliomas have high metabolic activity and FDG uptake This limits the utility of FDG due to poor contrast differences between normal brain and tumor Currently in study are new PET tracers that have increased uptake in gliomas vs. normal brain, and increased uptake in high-grade gliomas vs. lowgrade. New tracers include: 11C-methionine (MET) 18F-flouroethyltyrosine (FET) Singhal et al. (2012), Mabary et al. (2015) 24

25 Summary We have reviewed the clinical presentation, epidemiology, radiologic and histologic appearance, treatment, and prognosis of glioblastoma. More specifically, we reviewed imaging from our patient AB to highlight the different radiologic findings of glioblastoma on non-contrast head CT and contrast enhanced MRI. We then look at imaging from companion patient XY to highlight the utility of PET imaging to differentiate disease recurrence from pseudoprogression. 25

26 References Bulakbasi, N., Guvenc, I., Onguru, O., Erdogan, E., Tayfun, C., & Ucoz, T. (2004). The added value of the apparent diffusion coefficient calculation to magnetic resonance imaging in the differentiation and grading of malignant brain tumors. J Comput Assist Tomogr, 28(6), Chang, S. M., Parney, I. F., Huang, W., Anderson, F. A., Jr., Asher, A. L., Bernstein, M.,... Laws, E. R. (2005). Patterns of care for adults with newly diagnosed malignant glioma. Jama, 293(5), doi: /jama Gorlia, T., van den Bent, M. J., Hegi, M. E., Mirimanoff, R. O., Weller, M., Cairncross, J. G.,... Stupp, R. (2008). Nomograms for predicting survival of patients with newly diagnosed glioblastoma: prognostic factor analysis of EORTC and NCIC trial /CE.3. Lancet Oncol, 9(1), doi: /s (07) Louis, David N., Ohgaki, Hiroko, Wiestler, Otmar D., Cavenee, Webster K., Burger, Peter C., Jouvet, Anne,... Kleihues, Paul. (2007). The 2007 WHO ClassiWcation of Tumours of the Central Nervous System. Acta Neuropathol, 114, Mabray, M. C., Barajas, R. F., Jr., & Cha, S. (2015). Modern brain tumor imaging. Brain Tumor Res Treat, 3(1), doi: /btrt Singhal, T., Narayanan, T. K., Jacobs, M. P., Bal, C., & Mantil, J. C. (2012). 11C-methionine PET for grading and prognostication in gliomas: a comparison study with 18F-FDG PET and contrast enhancement on MRI. J Nucl Med, 53(11), doi: /jnumed Stupp, R., Mason, W. P., van den Bent, M. J., Weller, M., Fisher, B., Taphoorn, M. J.,... Mirimanoff, R. O. (2005). Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med, 352(10), doi: /nekjoa Surveillance, Epidemiology, and End Results (SEER) Program ( SEER*Stat Database: Incidence - SEER 9 Regs Research Data, Nov 2014 Sub ( ) <Katrina/Rita Population Adjustment> - Linked To County Attributes - Total U.S., Counties, National Cancer Institute, DCCPS, Surveillance Research Program, Surveillance Systems Branch, released April 2015, based on the November 2014 submission. Louis, D., Schiff, D., Batchelor, T. (2014). Classification of Gliomas. Uptodate. Retrieved from &utdpopup=true 26

27 Acknowledgements Special thanks to Yuri Shif, MD, Elisa Franquet, MD, and Lauren Ferrara, MD, and Gillian Lieberman, MD for help with preparation of this presentation. 27