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 IDH-wildtype glioblastoma (GBM) at first recurrence after chemoradiotherapy.

Methods: Records from 247 patients who underwent progression after diagnosis of IDH-wildtype 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 O⁶-methylguanine-DNA-methyltransferase (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 short-term 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.

Keywords: glioblastoma; nomogram; prognosis; progression; subventricular zone.

Figure 1

(A) Axial T1 image showing tumor recurred at the resection cavity (yellow arrow). (B) Sagittal T1 image showing a new lesion far from the original resection cavity was found (yellow arrow). (C) Axial T1 image showing subependymal dissemination (yellow arrows); (D) Axial T1 image showing superficial leptomeningeal dissemination; (E) Sagittal T1 image of spine demonstrating enhanced lesions (yellow arrows). (F) Median time from diagnosis to development of progression was 8.5 months for local progression, 7.0 months for distant progression, 6.0 months for subependymal dissemination and 6.0 months for leptomeningeal dissemination (P = 0.422). (G) Median OS was 23.0 months for patients with local progression, 17.0 months for patients with distant progression, 13.0 months for subependymal dissemination and 14.0 months for leptomeningeal dissemination (P = 0.0001). (H) Median PPS was 11.0 months for patients with local progression, 8.5 months for patients with distant progression, 5.5 months for subependymal dissemination and 6.0 months for leptomeningeal dissemination (P = 0.0001).

Figure 2

Survival comparisons among different progression patterns (A, B) and patients with non-local progression could be divided into long-term and short-term survivors (C, D).

Figure 3

Nomogram model for predicting the risk of being non-local progression in patients with IDH-wildtype GBM (A) and calibration curve of the nomogram model (B).

Figure 4

Nomogram model for predicting the probability of being long-term survivors in patients with non-local progression (A) and calibration curve of the nomogram model (B).

Figure 5

Forest plot of multivariable Cox proportional hazard regression analysis. Variables with a hazard ratio larger than 1 were considered as risk factors, while those with a hazard ratio less than 1 were considered as protective factors.