Postradiation imaging changes in the CNS: how can we differentiate between treatment effect and disease progression?

Abstract

A familiar challenge for neuroradiologists and neuro-oncologists is differentiating between radiation treatment effect and disease progression in the CNS. Both entities are characterized by an increase in contrast enhancement on MRI and present with similar clinical signs and symptoms that may occur either in close temporal proximity to the treatment or later in the disease course. When radiation-related imaging changes or clinical deterioration are mistaken for disease progression, patients may be subject to unnecessary surgery and/or a change from otherwise effective therapy. Similarly, when disease progression is mistaken for treatment effect, a potentially ineffective therapy may be continued in the face of progressive disease. Here we describe the three types of radiation injury to the brain based on the time to development of signs and symptoms--acute, subacute and late--and then review specific imaging changes after intensity-modulated radiation therapy, stereotactic radiosurgery and brachytherapy. We provide an overview of these phenomena in the treatment of a wide range of malignant and benign CNS illnesses. Finally, we review the published data regarding imaging techniques under investigation to address this well-known problem.

Keywords: pseudoprogression; radiation treatment effect; radionecrosis; radiosurgery.

Conflict of interest statement

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

Figures

Figure 1. Treatment effect after stereotactic radiosurgery

Four brain metastases were treated with stereotactic radiosurgery in a single fraction, 18 Gy × 1. (A) Radiation therapy treatment plan. (B) Pretreatment T1-weighted postcontrast MRI. (C) 6 months post-treatment, with increased T1 enhancement.

Figure 2. Restricted diffusion associated with tumor progression after resection of brain metastases followed by radiosurgery

(A) T1-weighted postcontrast MRI demonstrating right supratentorial peripherally enhancing mass with (B) associated T2 fluid attenuated inversion recovery (FLAIR) hyperintensity. Pathology revealed metastatic poorly differentiated adenocarcinoma consistent with a lung primary. (C) Postoperative T1-weighted postcontrast. (D) Postoperative T2 FLAIR. Five months after adjuvant stereotactic radiosurgery, MRI showed (E) new contrast enhancement on T1 weighted postcontrast imaging. (F) T2 FLAIR with associated hyperintensity and 5 months later (10 months postradiation), MRI showed (G) progression of contrast-enhancing lesion. (H) Diffusion weighted imaging showed restricted diffusion. MRI 1 month later showed (I) progression of enhancement and (J) worsening T2 FLAIR hyperintensity. At this point she developed symptoms and underwent re-do craniotomy. Pathology revealed metastatic adenocarcinoma. (K) T1-weighted postcontrast MRI 3 months following whole brain radiation therapy (RT). (L) T1-weighted postcontrast MRI 3 months following whole brain RT 6 months postwhole brain RT demonstrating no evidence of CNS progression.

Figure 3. Lack of restricted diffusion in radionecrosis after surgery and chemoradiation for glioblastoma multiforme

(A) Postoperative T1 postcontrast. (B) Postoperative T2 fluid attenuated inversion recovery (FLAIR). (C) Radiation therapy (RT) plan, initial volume to 46 Gy. (D) RT treatment plan, cone down to 60 Gy. First follow-up MRI 2 months after irradiation showed a new area of contrast enhancement just inferior to the tumor bed without evidence of restricted diffusion. (E) T1 postcontrast; (F) T2 FLAIR; (G) apparent diffusion coefficient map; (H) diffusion weighted imaging: b = 800. The man was asymptomatic and underwent resection. Final path: gliosis with focal necrosis. No evidence of tumor.