Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
eEdE-91 Treatment-Related MR Imaging Findings in Patients with Glioma after Radiotherapy and Chemotherapy Xiao Li, MD ([email protected]) Fanny Morón, MD Baylor College of Medicine, Houston, Texas Disclosure • No potential conflicts of interest to disclose. Introduction • Purpose – To provide a broad review of the various treatmentrelated changes and characteristic MR imaging findings in patients with glioma after undergoing radiotherapy and chemotherapy. • General Categories – Treatment strategies and treatment response monitoring – Chemotherapy-related imaging changes – Radiotherapy-related imaging changes Menu – Click Links to Jump to Topic • Treatment and Monitoring – Treatment Strategies – RANO Criteria • Chemotherapeutic effects – Pseudoprogression • Anti-angiogenic agent effects – Pseudoresponse • Radiotherapy side effects – Leukoencephalopathy – Radiation necrosis – Radiation-induced • Meningioma • Cavernous malformation • Microbleeds Treatment Strategies • Glioblastoma is the most common malignant primary brain tumor • 30% of patients will have treatment-related changes on imaging. • Standard of Care – Surgical resection – First line: XRT with concomitant/adjuvant temozolomide (TMZ) chemotherapy. – Second line: Anti-angiogenic therapy, Bevacizumab (BEV) for recurrent glioblastoma. Response Assessment in Neuro-Oncology (RANO) Criteria Enhancing disease Complete Response Disappearance of all enhancing disease sustained for > 4 weeks Partial Response Stable Disease >50% decrease in measureable enhancing lesions sustained > 4 weeks Progression Does not qualify 25% of more for complete increase in response, partial enhancing lesions response or progression Non-enhancing disease T2/Flair lesions New lesions Stable/improved Stable Increase No new lesions Present Clinical Features Stable or reduced corticosteroids (compared to baseline) clinically stable or improved Clinical deterioration Chemotherapy Imaging-Related Changes • Traditional chemotherapy primarily induce DNA damage to dividing cells and/or interfere with DNA repair. • Chemotherapy treatments also create difficulty in post-treatment response interpretation. Pseudoprogression • Non-tumoral increased enhancement +/- size of lesion after treatment • Most cases result in spontaneous “remission” in first 3 months or stability for 6 months • Can occur in combination with XRT (30%) • More common in (+) methylated status • Sign of good response Mechanism of Pseudoprogression • Demyelination (hypoxia and endothelial damage, necrosis) • Necrosis • Activation VEGF: Increase permeability of blood-brain barrier (BBB) leading to enhancement and vasogenic edema Concordant Imaging (Treatment response) TRIF Temozolomide Related Imaging Findings Concordant Imaging (True tumor progression) Discordant Imaging (False tumor progression) Pseudoprogression • Reduction – Contrast enhancement – FLAIR hyperintensity – DWI hyperintensity – ADC hypointensity – rCBV • Worsen: All of the above features + high rCBV • Increase – Contrast enhancement • Decrease – rCBV • F/U – Resolution of enhancement Pseudoprogression / TRIF Initial Postoperative: No significant residue T1+C FLAIR rCBV DWI T1+C 3 Months later after XRT-TMZ: New enhancing lesion along the margins of the resection cavity without increased perfusion T1+C 9 Months Later: Spontaneous resolution of enhancing, non-hyperemic lesion rCBV Biological Imaging-related Changes • Biological therapy – Treatments that exploit the immune system to recognize and fight cancer cells – For example, Bevacizumab (BEV) inhibits angiogenesis by acting as an antibody that targets vascular endothelial growth factor (VEGF). Bevacizumab (Avastin) Facts • Antiangiogenic drug used for recurrent GBM – “Normalize”-stabilize tumor vasculature and BBB. – Has measurable radiographic response • Overall Benefit? – Improves symptoms from mass effect and quality of life, but does not improve overall survival – May not be beneficial in unselected populations – However, no validated biomarkers for patients stratification BEV Pseudoresponse • Post-treatment decrease in contrast enhancement usually not associated with true tumor reduction. • Fast reduction in tumor contrast enhancement (within days) • Decreased vascular permeability, improves edema BEV Related Imaging Findings (BRIF) Imaging role? – Biomarker to better select suitable patients – Early detection of treatment failure (avoid complications, minimize neurological damage, avoid unnecessary procedures and early therapy modification) – Currently, follow-up imaging is the most often used method for treatment monitoring. BEV Related Imaging Findings (BRIF) • • • • MRP: rCBV values tend to be lower in BRIF compared to tumor and normal WM DWI: Restricted diffusion is more prominent on BRIF than GBM and normal WM MRS: Cho/Cr and Cho/NAA ratios are elevated in recurrent tumor Combination of modalities increases accuracy. • Reduction – Contrast enhancement – FLAIR hyperintensity – DWI hyperintensity – ADC hypointensity – rCBV Concordant Imaging (Treatment response) BRIF Bevacizumab Related Imaging Findings Concordant Imaging (True tumor progression) • Worsen: All of the above features + high rCBV • Reduction Discordant Imaging (Failed treatment) Pseudoresponse – Contrast enhancement • Increase – DWI hyperintensity – ADC hypointensity Pseudoresponse with Worsening Restricted Diffusion Baseline recurrent GBM: Bifrontal enhancing tumor with extensive FLAIR hyperintensity, small focal areas of restricted diffusion (↑), and no significant increased perfusion. T1+C FLAIR DWI ADC CBV 2 months after Avastin: Resolution of enhancement with worsening areas of restricted diffusion (↑). T1+C FLAIR DWI ADC CBV Pseudoresponse with Local Improvement but New Metastasis and Gliomatosis T1+C T1+C T1+C T1+C FLAIR DWI rCBV Recurrent L frontal enhancing and hyperfused (↑) tumor FLAIR DWI rCBV 3 Months After Avastin: Improved L frontal local recurrent (↑) tumor FLAIR DWI rCBV However, new infiltrating gliomatosis (↑) and hyperperfused metastasis (↑) Pseudoresponse with Transient Restrictive Diffusion (Part 1) T1+C At presentation: Ring-enhancing GBM T1+C S/P Near Total Surgical resection 3 months after SX/XRT/TMZ: Recurrent enhancing tumor was started on BEV T1+C FLAIR DWI ADC Pseudoresponse with Transient Restrictive Diffusion, Possible Pseudoinfarct. (Part 2) T1+C FLAIR DWI ADC rCBV 3 months after BEV: Improved enhancement. New area of restricted diffusion without increased perfusion. (↑) T1+C FLAIR 12 m after BEV: Stable resolution of restricted diffusion DWI Explanations for BRIF Pseudoresponse • • • • • • Viable hypercellular tumor Pseudo-infarct/infarct Atypical necrosis Promotes metastasis and gliomatosis phenotype Mix of tumor and treatment effect Resistance to therapy (vessel co-option, mimicry, hypoxia-induced upregulation of other angiogenic factor, among other mechanisms) Treatment Effects Related to Radiation • Leukoencephalopathy • Radiation necrosis • Radiation-induced – Meningioma – Vascular malformation • Telangiectasia • Cavernous Malformation – Microbleeds Radiation Injury Mechanism • • • • Targeting dividing cells directly/indirectly Vascular damage Endocrine disturbance Neural structural fibrosis Phases of Irradiation Changes • Acute phase (during or shortly after radiation): Only focal damage with reversible glial glycogen depositions • Subacute phase (up to 12 weeks after radiation): Cell death of myelin-producing oligodendrocytes occurs followed remyelinization of the brain tissue. • Chronic phase (months to years after completing radiation): Diffuse changes due to wall thickening of the vascular structures, decreasing number of glialsupporting cells, and diffuse demyelinization. Leukoencephalopathy • Leukoencephalopathy develop months to years after treatment. • Often seen in post-XRT and exacerbate in combination with chemotherapy. • MRI Findings – Progression of white matter confluent FLAIR hyperintensity. – Progressive atrophy – May have transient areas of white matter enhancement. FLAIR T1+C rCBV CBV 2 years after whole brain radiation and boost to the L thalamus+TMZ FLAIR At presentation: Non-enhancing non-hyperemic infiltrating glioma FLAIR Atrophy & Leukoencephalopathy in 3 years interval FLAIR 3 years with progression of atrophy and confluent FLAIR hyperintensity FLAIR Radiation Necrosis • Incidence: 5-25% • Often occurs 3-12 months after treatment, but can occur up to years/decades later • Potentiates in combination with chemo Radiation Necrosis vs Reoccurrence • Similarities – Contrast enhancement – Mass effect – Vasogenic edema • Differences – Tumor, not radiation necrosis, has increased rCBV – Radiation necrosis tends to be stable or improved over time Radiation Necrosis Imaging Patterns of Enhancement • New enhancement on initially non-enhancing tumor • Distant enhancing foci • Periventricular and callosal enhancing foci • Soap bubble or Swiss cheese Evolution • Stable or improved (70%) • Variable (30%): - Re-appear - Progress (re-radiation) - New distant lesions Advanced Imaging • Low rCVB. • No restricted diffusion • MRS low choline peak FLAIR T1+C Preoperative MRI shows infiltrative glioma. Radiation-Induced Necrosis (Part 1) FLAIR T1+C T1+C 2 years after Sx and completion XRT/TMZ: No significant residue. ASL 3 years: New enhancing lesion without increased perfusion (radiation necrosis on pathology). Radiation-Induced Necrosis (Part 2) T1+C FLAIR 4.5 years: New enhancing “soap bubble” distant foci (↑) , not hyper-perfused on DSC (↑), still on surveillance thought to be new distant foci of radiation necrosis CBV Radiation-Induced Meningioma • Most common CNS neoplasm known to be caused by ionizing radiation • Risk increases with increased doses. Even low doses significantly increase risk • Often present with multiple meningiomas and higher proportion of atypical or anaplastic compared to spontaneous meningioma • Lower mean age of presentation in those exposed to radiation. 29 to 38 years for those exposed to high dose radiation versus 45-58 years in spontaneous Radiation-Induced Meningioma Recurrence 18 months after total resection/XRT (60Gy)/TMZ, (no extra-axial lesions/clean surgical flap), underwent redo GBM resection. T1+C T1+C T1+C CBV T1+C Follow up 11 months later, after GBM Resection x 2 + XRT boost (20 Gy) +TMZ, a collision meningioma in the resection-radiation site (at bone flap) is present. Vascular Malformation • Radiation can cause early vascular changes such as increased capillary permeability and vasodilation as well as delayed injury leading to occlusion/infarction and proliferative changes such as capillary telangiectasia and cavernous malformation. • Capillary telangiectasias are thin walled capillaries with intervening normal brain parenchyma and occurs 3-9 months after irradiation. Cavernous malformation do not contain the intervening brain parenchyma and tend to develop years later. • Cavernous malformation on imaging – Distinctive “popcorn “ appearance with minimal surrounding edema – CT show ring-like calcification with core reticulation of variable attenuation – MRI show core heterogeneous intensity with dark peripheral hemosiderin rim Radiation-Induced Cavernous Malformation Initial: Brainstem pilocytic astrocytoma at presentation. Received wide-field radiation. (↑): Popcorn appearance with surrounding hemosiderin rim (↑): minimal/no enhancement. 10 years later: New lesion in the left temporal lobe consistent with cavernous malformation CO: Jeremy Jones MD Cerebral Microbleeds • Radiation can cause cerebral hemorrhage that results in the formation of cerebral microbleeds (CMBs). Contain focal perivascular collections of hemosiderin and persists for years. • Imaging – Hemosiderin contains iron and has associated susceptibility effects. – Small, round, hypointense lesions on T2*-weighted images obtained using gradient echo sequences. – Increase in number over time since irradiation and correlate with dose and target volume – May be a useful measurement of radiation injury Radiation-Induced Vascular Lesions History: 15 yo s/p infratentorial medulloblastoma resection with radiation 6 years ago New tiny left temporal parietal hypointense foci in otherwise unremarkable supratentorial brain. (↑) CO: Jeremy Jones MD References • • • • • • • • • • • • Bian W, Hess CP, Chang SM, Nelson SJ, Lupo JM. Susceptibility-weighted MR imaging of radiation therapy-induced cerebral microbleeds in patients with glioma: a comparison between 3T and 7T. Neuroradiology. 2014;56(2):91-6. Ebi J, Sato H, Nakajima M, Shishido F. Incidence of leukoencephalopathy after whole-brain radiation therapy for brain metastases. Int J Radiat Oncol Biol Phys. 2013;85(5):1212-7. Hygino da cruz LC, Rodriguez I, Domingues RC, Gasparetto EL, Sorensen AG. Pseudoprogression and pseudoresponse: imaging challenges in the assessment of posttreatment glioma. AJNR Am J Neuroradiol. 2011;32(11):1978-85. Jain R, Robertson PL, Gandhi D, Gujar SK, Muraszko KM, Gebarski S. Radiation-induced cavernomas of the brain. AJNR Am J Neuroradiol. 2005;26(5):1158-62. Kumar AJ, Leeds NE, Fuller GN, et al. Malignant gliomas: MR imaging spectrum of radiation therapy- and chemotherapy-induced necrosis of the brain after treatment. Radiology. 2000;217(2):377-84. Pope WB, Young JR, Ellingson BM. Advances in MRI assessment of gliomas and response to anti-VEGF therapy. Curr Neurol Neurosci Rep. 2011;11(3):336-44. Stuplich M, Hadizadeh DR, Kuchelmeister K, et al. Late and prolonged pseudoprogression in glioblastoma after treatment with lomustine and temozolomide. J Clin Oncol. 2012;30(21):e180-3. Stone JB, Deangelis LM. Cancer-treatment-induced neurotoxicity-focus on newer treatments. Nat Rev Clin Oncol. 2016;13(2):92-105. Umansky F, Shoshan Y, Rosenthal G, Fraifeld S, Spektor S. Radiation-induced meningioma. Neurosurg Focus. 2008;24(5):E7. Walker AJ, Ruzevick J, Malayeri AA, et al. Postradiation imaging changes in the CNS: how can we differentiate between treatment effect and disease progression?. Future Oncol. 2014;10(7):1277-97. Welzel T, Niethammer A, Mende U, et al. Diffusion tensor imaging screening of radiation-induced changes in the white matter after prophylactic cranial irradiation of patients with small cell lung cancer: first results of a prospective study. AJNR Am J Neuroradiol. 2008;29(2):379-83. Wen PY, Macdonald DR, Reardon DA, et al. Updated response assessment criteria for high-grade gliomas: response assessment in neuro-oncology working group. J Clin Oncol. 2010;28(11):1963-72.