Pseudoprogression and Treatment Effect

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Pseudoprogression: early transient enhancing lesions

Pseudoprogression is defined as enhancing changes seen on MRI within the first 3 months after treatment of glioblastoma with fractionated radiotherapy. Pseudoprogression represents treatment effects rather than treatment failure, which, with time, either successively recovers or stabilizes without being linked to subordinate outcomes.14 Since postoperative radiotherapy and concomitant temozolomide were established as the standard treatment of glioblastoma, there has been an increase in

Radiation necrosis: delayed enhancing lesions

Since the randomized clinical trials in the 1970s demonstrating an improvement in overall survival, postoperative whole-brain radiotherapy at a daily dose of 2 Gy per fraction given over a 6-week period for a total dose of 60 Gy has become part of the standard treatment of glioblastoma.3, 27 Patients treated with radiation therapy in this manner often exhibit enhancement in radiation within 3 to 12 months of completing radiation. This phenomenon is called radiation necrosis and is now a common

Antiangiogenic therapy for glioblastoma: radiologic and nonradiologic biomarkers of efficacy

Bevacizumab, a monoclonal anti-VEGF antibody, has been studied in phase II trials of patients with recurrent glioblastoma and demonstrated a 23-week medial progression-free survival when administered in combination with irinotecan.8, 9 A study of patients with glioblastoma treated with bevacizumab revealed decreased tumor hypoxia and increased tumoral VEGF expression, which were directly associated with radiographic response and prolonged survival following treatment.55

VEGF levels have been

Response assessment in neuro-oncology criteria for high-grade gliomas

Until recently, the MacDonald Criteria,13 first published in 1990, served as the standard for determining response assessment in high-grade gliomas. It provided an objective radiologic assessment of the tumor response based primarily on 2-dimensional enhancing tumor area deriving from contrast-enhanced computed tomography.70 The use of corticosteroids and fluctuations in patients’ neurologic status were also taken into consideration. The Macdonald criteria were also further applied to MRI,

Distinguishing treatment effect or pseudoprogression from true progression

Conventional MRI with gadolinium contrast enhancement fails to differentiate between true tumor recurrence, pseudoprogression, or radiation necrosis.14, 29, 37, 73 This form of imaging is also unable to distinguish true treatment response from the anti-VEGF treatment’s impact at palliating radiation necrosis, a distinction that is important because anti-VEGF is used more commonly with drugs, such as bevacizumab.69 Although new studies have suggested findings on conventional MRI, such as

Summary

The postoperative administration of adjuvant temozolomide and radiation is the new standard of care in patients with newly diagnosed glioblastoma. Pseudoprogression and radiation necrosis are common treatment effects that add much confusion in the detection of tumor recurrence using conventional MRI with gadolinium enhancement. These challenges are confounded with the recent increasing use of antiangiogenic therapy to treat newly diagnosed and recurrent glioblastoma. Until randomized trials

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