Classification of Progression Patterns in Glioblastoma: Analysis of Predictive Factors and Clinical Implications

Abstract

Background: This study was designed to explore the progression patterns of IDHwildtype glioblastoma (GBM) at first recurrence after chemoradiotherapy. Methods: Records from 247 patients who underwent progression after diagnosis of IDHwildtype GBM was retrospectively reviewed. Progression patterns were classified as either local, distant, subependymal or leptomeningeal dissemination based on the preoperative and serial postoperative radiographic images. The clinical and molecular characteristics of different progression patterns were analyzed. Results: A total of 186 (75.3%) patients had local progression, 15 (6.1%) patients had distant progression, 33 (13.3%) patients had subependymal dissemination, and 13 (5.3%) patients had leptomeningeal dissemination. The most favorable survival occurred in patients with local progression, while no significant difference of survival was found among patients with distant progression, subependymal or leptomeningeal dissemination who were thereby reclassified into non-local group. Multivariable analysis showed that chemotherapy was a protective factor for non-local progression, while gender of male, subventricular zone (SVZ) involvement and O 6-methylguanine-DNAmethyltransferase (MGMT) promoter methylation were confirmed as risk factors for non-local progression (P < 0.05). Based on the factors screened by multivariable analysis, a nomogram was constructed which conferred high accuracy in predicting non-local progression. Patients in non-local group could be divided into long-and shortterm survivors who differed in the rates of SVZ involvement, MGMT promoter methylation and reirradiation (P < 0.05), and a nomogram integrating these factors showed high accuracy in predicting long-term survivors. Conclusion: Patients harboring different progression patterns conferred distinct clinical and molecular characteristics. Our nomograms could provide theoretical references for physicians to make more personalized and precise treatment decisions.

Differential Predictors and Clinical Implications Associated With Long-Term Survivors in IDH Wildtype and Mutant Glioblastoma

“…When tumor progressed, re-operation and reirradiation were performed if possible. Rechallenge with chemotherapy which commonly consisted of a combination of bevacizumab and temozolomide (TMZ) could be also attempted if patients showed relatively normal laboratory tests and maintained a reasonable performance status (ECOG: 0-2) ( 13 ).…”

T2/FLAIR Abnormity Could Be the Early Sign of Glioblastoma Dissemination

“…Local recurrence dominates the patterns of GBM progression (ranging from 60-85%) 11 . The standard care of GBM demands radiotherapy to eliminate the residual tumor cells and postpone tumor recurrence.…”

“…All MRI studies were performed on subependymal spread (lesions disseminated along with the subependymal zone) and leptomeningeal dissemination (diffuse leptomeningeal enhancement around the contours of the gyri and sulci with/without multiple nodular deposited in the subarachnoid space) based on the initial MR images with progression 11 . We also employed the principles of RANO for low-grade glioma to evaluate the dynamic change of T2/FLAIR of this GBM cohort 19 .…”

“…Multifocal or multicentric lesions could not only be diagnosed for primary GBM but in tumor recurrence or progression. Though local recurrence dominates the patterns of progression, non-local progression, including distant intracranial metastasis, subependymal spread, and leptomeningeal dissemination, as well as extracranial visceral metastasis, occurs in 2-34.5% GBM patients 11 . The RANO and modi ed RANO criteria require new emerged or signi cantly enlarged CE lesions as the necessary evidence to consider tumor progression [12][13][14] , nevertheless, non-local recurrence could be similar to nCE multifocal or multicentric GBMs.…”

T2/FLAIR Abnormity Could be the Sign of Glioblastoma Dissemination

“…Multifocal or multicentric lesions could not only be diagnosed for primary GBM but for recurrent or progressed tumors. Though local recurrence dominates the patterns of progression, non-local progression, such as distant intracranial metastasis, subependymal spread, and leptomeningeal dissemination, and extracranial visceral metastasis, occurs in 2-34.5% patients with GBM (12,13). The Response Assessment in Neuro-Oncology (RANO) and modified RANO criteria warrant new emerged or significantly enlarged CE lesions as the necessary and essential evidence to consider tumor progression for Bevacizumab-naïve patients (14)(15)(16), nevertheless, non-local recurrence could be similar to nCE multifocal or multicentric GBMs.…”