Defining Treatment‐Related Adverse Effects in Patients with Glioma: Distinctive Features of Pseudoprogression and Treatment‐Induced Necrosis. (18th June 2020)

• Record Type: Journal Article
• Authors: Winter, Sebastian F.; Vaios, Eugene J.; Muzikansky, Alona; Martinez‐Lage, Maria; Bussière, Marc R.; Shih, Helen A.; Loeffler, Jay; Karschnia, Philipp; Loebel, Franziska; Vajkoczy, Peter; Dietrich, Jorg
• Is Part Of: Oncologist. Volume 25:Number 8(2020)
• Page Start: e1221
• Page End: e1232
• Publication Date: 2020-06-18
• Subjects: Tissue necrosis -- Pseudoprogression -- Treatment‐related effects -- Malignant glioma -- Neurotoxicity; Oncology -- Periodicals; Tumors -- Periodicals; Cancérologie -- Périodiques; Tumeurs -- Périodiques; Oncology; Tumors; Neoplasms; Electronic journals; Periodicals; Periodicals; 616.994
• DOI: 10.1634/theoncologist.2020-0085
• Languages: English
• ISSNs: 1083-7159

Abstract

Abstract: Background: Pseudoprogression (PP) and treatment‐induced brain tissue necrosis (TN) are challenging cancer treatment–related effects. Both phenomena remain insufficiently defined; differentiation from recurrent disease frequently necessitates tissue biopsy. We here characterize distinctive features of PP and TN to facilitate noninvasive diagnosis and clinical management. Materials and Methods: Patients with glioma and confirmed PP (defined as appearance <5 months after radiotherapy [RT] completion) or TN (>5 months after RT) were retrospectively compared using clinical, radiographic, and histopathological data. Each imaging event/lesion (region of interest [ROI]) diagnosed as PP or TN was longitudinally evaluated by serial imaging. Results: We identified 64 cases of mostly (80%) biopsy‐confirmed PP ( n = 27) and TN ( n = 37), comprising 137 ROIs in total. Median time of onset for PP and TN was 1 and 11 months after RT, respectively. Clinically, PP occurred more frequently during active antineoplastic treatment, necessitated more steroid‐based interventions, and was associated with glioblastoma (81 vs. 40%), fewer IDH1 mutations, and shorter median overall survival. Radiographically, TN lesions often initially manifested periventricularly ( n = 22/37; 60%), were more numerous (median, 2 vs. 1 ROIs), and contained fewer malignant elements upon biopsy. By contrast, PP predominantly developed around the tumor resection cavity as a non‐nodular, ring‐like enhancing structure. Both PP and TN lesions almost exclusively developed in the main prior radiation field. Presence of either condition appeared to be associated with above‐average overall survival. Conclusion: PP and TN occur in clinically distinct patient populations and exhibit differences in spatial radiographic pattern. Increased familiarity with both conditions and their unique features will improve patient management and may avoid unnecessary surgical procedures. Implications for Practice: Pseudoprogression (PP) and treatment‐induced brain tissue necrosis (TN) are challenging treatment‐related effects mimicking tumor progression in patients with brain cancer. Affected patients frequently require surgery to guide management. PP and TN remain arbitrarily defined and insufficiently characterized. Lack of clear diagnostic criteria compromises treatment and may adversely affect outcome interpretation in clinical trials. The present findings in a cohort of patients with glioma with PP/TN suggest that both phenomena exhibit unique clinical and imaging characteristics, manifest in different patient populations, and should be classified as distinct clinical conditions. Increased familiarity with PP and TN key features may guide clinicians toward timely noninvasive diagnosis, circumvent potentially unnecessary surgical procedures, and improve response assessment in neuro‐oncology. Abstract : Cancer treatment–related adverse effects on the brain are a major diagnostic and therapeutic challenge in neuro‐oncology. This article describes the key clinical and imaging features of pseudoprogression and treatment‐induced brain tissue necrosis in patients with malignant glioma in an attempt to improve the current understanding of these conditions, facilitate the noninvasive diagnosis of treatment‐related adverse effects, and improve response assessment in neuro‐oncology.