Imaging-Based Patterns of Failure following Re-Irradiation for Recurrent/Progressive High-Grade Glioma

Abstract

Background: Re-irradiation (ReRT) is an effective treatment modality in appropriately selected patients with recurrent/progressive high-grade glioma (HGG). The literature is limited regarding recurrence patterns following ReRT, which was investigated in the current study.

Methods: Patients with available radiation (RT) contours, dosimetry, and imaging-based evidence of recurrence were included in the retrospective study. All patients were treated with fractionated focal conformal RT. Recurrence was detected on imaging with magnetic resonance imaging (MRI) and/ or amino-acid positron emission tomography (PET), which was co-registered with the RT planning dataset. Failure patterns were classified as central, marginal, and distant if >80%, 20-80%, or <20% of the recurrence volumes were within 95% isodose lines, respectively.

Results: Thirty-seven patients were included in the current analysis. A total of 92% of patients had undergone surgery before ReRT, and 84% received chemotherapy. The median time to recurrence was 9 months. Central, marginal, and distant failures were seen in 27 (73%), 4 (11%), and 6 (16%) patients, respectively. None of the patient-, disease-, or treatment-related factors were significantly different across different recurrence patterns.

Conclusion: Failures are seen predominantly within the high-dose region following ReRT in recurrent/ progressive HGG.

Keywords: MRI; PET; high-grade glioma; patterns of failure; re-irradiation; recurrence.

Figure 1

Progression-free survival (a) and overall survival (b) following re-irradiation in high-grade glioma.

Figure 2

Progression in a 32-year male with IDH-mutant astrocytoma. (a) shows residual disease following treatment completion, with (b) showing an increase in disease extent (arrow) after 7 years, as appreciated on axial T2-FLAIR sequences when reirradiation was considered. Representative images showing an increase in disease extent over medial extent of the cavity on coronal T2w sequence (c,d). (e) shows T1w-post gadolinium images showing no uptake of contrast in the area of new disease, suggesting absence of transformation to grade 4. (f) shows PET avidity over the area of active disease.

Figure 3

Progression in a 47-year female with glioblastoma with MGMT gene promoter methylation. (a) shows T1w axial view following completion of adjuvant chemotherapy (after surgery and radiation), with (b) showing local recurrence after 2.5 years with enhancing component and cystic component (arrow). (c,d) represented the surgical cavity on T1w contrast and T2w FLAIR axial view when the patient was considered for reirradiation.

Figure 4

Disease evolution from first progression to subsequent recurrence following re-irradiation in a 25-year female with IDH-mutant grade 3 astrocytoma. (a) shows T1w contrast-enhanced MRI with resection cavity over the right frontal region, with contrast-enhancing recurrent disease seen over the posterior aspect of the cavity (arrow) in (b). Subsequent imaging shows MRI following resection of the disease in (c), which was confirmed as recurrent HGG. (d) shows an enhancing area with central necrosis over the resected and re-irradiated region (8 months following ReRT) over the right frontal-parietal, which was not showing any metabolic uptake on corresponding PET imaging in (e). However, the other area of enhancing nodule over the left periventricular region shows high avidity, considered a distant recurrence. (f) shows MRI performed after 2 months, which confirmed new areas of distant disease, while the re-irradiated region (non-avid on PET) continued to be stable, confirming RT-related changes.

Figure 5

Two patients with central recurrence, each in the upper and lower panel. (a) (37-year male with IDH-mutant astrocytoma) shows target volumes (GTV: red, CTV: blue; PTV: magenta) on T2-FLAIR MRI. The CTV was drawn to include all areas of T2w hyperintensity. (b,c) is T2-FLAIR and T1w contrast images showing recurrent disease (arrow) and its relation with the 95% isodose line (orange line). (d) (56-year male with recurrent glioblastoma) shows the target volumes for another patient volumes (GTV: red, CTV: blue; PTV: magenta) on T1w contrast MRI. The GTV was the enhancing disease, with CTV drawn as an expansion of 10 mm around the enhancing disease. (e,f) show the recurrence volumes with respect to target volumes and the 95% isodose line (orange), respectively. The major portion of recurrent disease can be seen lying within the 95% isodose line.

Figure 6

Demonstration of marginal recurrence following re-irradiation for a 43-year female with transformed high-grade glioma. (a) shows the target volumes (GTV: red, CTV: blue; PTV: magenta) on T1w contrast MRI. The GTV was the enhancing disease, with CTV drawn as an expansion of 10 mm around the enhancing disease. (b,c) demonstrates recurrent disease (arrows) with respect to target volumes and 95% isodose line (orange), 1. (d) is a representation from lower axial slices showing the growth of recurrent disease further beyond the 95% isodose line.

Figure 7

Distant relapse following re-irradiation in a 38-year male with IDH-mutant astrocytoma with transformation (radiological) to grade 4 during reirradiation. (a,b) show the target volumes (GTV: red, CTV: blue; PTV: magenta) on T1w contrast and T2w images. The GTV encompassed all the T2w altered signals, including the enhancing disease, while CTV was 10–15 mm expansion along the brain parenchyma. (c) represents the response in the primary re-irradiated region 6 months following ReRT, while the lower panel shows axial (d), coronal (e), and sagittal (f) T1w contrast MRI from the same time-point demonstrating distant areas of recurrent disease (arrow) beyond the 95% isodose line (orange).