Retrospective analysis of recurrence patterns and clinical outcome of grade II meningiomas following postoperative radiotherapy

Abstract

Background: Atypical meningiomas exhibit a high tendency for tumor recurrence even after multimodal therapy. Information regarding recurrence patterns after additive radiotherapy is scarce but could improve radiotherapy planning and therapy decision. We conducted an analysis of recurrence patterns with regard to target volumes and dose coverage assessing target volume definition and postulated areas of tumor re-growth origin. Prognostic factors contributing to relapse were evaluated.

Methods: The clinical outcome of patients who had completed additive, somatostatin receptor (SSTR)-PET/CT-based fractionated intensity-modulated radiotherapy for atypical meningioma between 2007 and 2017 was analyzed. In case of tumor recurrence/progression, treatment planning was evaluated for coverage of the initial target volumes and the recurrent tumor tissue. We proposed a model evaluating the dose distribution in postulated areas of tumor re-growth origin. The median of proliferation marker MIB-1 was assessed as a prognostic factor for local progression and new distant tumor lesions.

Results: Data from 31 patients who had received adjuvant (n = 11) or salvage radiotherapy (n = 20) were evaluated. Prescribed dose ranged from 54.0 to 60.0 Gy. Local control at five years was 67.9%. Analysis of treatment plans of the eight patients experiencing local failure proved sufficient extent of target volumes and coverage of the prescribed dose of at least 50.0 Gy as determined by mean dose, D98, D2, and equivalent uniform dose (EUD) of all initial target volumes, postulated growth-areas, and areas of recurrent tumor tissue. In all cases, local failure occurred in high-dose volumes. Tumors with a MIB-1 expression above the median (8%) showed a higher tendency for re-growth.

Conclusions: The model showed adequate target volume and relative dose distribution but absolute dose appears lower in recurrent tumors without reaching statistical significance. This might provide a rationale for dose escalation studies. Biological factors such as MIB-1 might aid patients' stratification for dose escalation.

Keywords: Additive radiotherapy; Atypical meningioma; MIB-1; Recurrence pattern analysis; SSTR-PET/CT; Treatment planning.

Fig. 1

Clinical example for a SSTR-PET-CT imaging with high tracer uptake exhibited by the meningioma (red); b dose distribution as delivered during treatment (GTV (dark red), PTV (red)); c delineation of GTVini (blue) and GTVrt (red), CTV (light blue) and PTV (grey)

Fig. 2

Schematic depiction of volumes. a Delineation of the initial GTV (GTVini), analysis volume GTV at recurrence/progression (GTVrt), and their intersection. b Schematic depiction of volumes. These volumes were postulated in order to identify regions within and adjacent to the initial GTV (GTVini, dark blue, dark blue outline) that might contribute to growth of recurrent tumor. GTV at recurrence (GTVrt, red margin) includes possible residual initial tumor tissue. Progression zone = new tissue without overlap with GTVini, green. Growth zone = 3 mm margin within the GTVini bordering on the progression zone (depicted in orange). Subclinical infiltration = GTVini + a 6 mm margin in all directions (depicted in turquoise). Initial CTV depicted in light blue, initial PTV in light grey. c Example of target volume and analysis volume evaluation in matched contrast enhanced T1 MR imaging showing recurrent tumor tissue, using colors corresponding to b. For clarity reasons, subclinical infiltration was omitted in this example

Fig. 3

Box plot diagrams comparing the median, interquartile range, and range of a D98 of the PTV, b D2 of the PTV, c Mean dose of the PTV, and d EUD of the PTV between groups. All doses are reported in Gy. Boxes are reporting the interquartile range. Whiskers are indicating the range. Circles are referring to data points exceeding the range within 1.5 times the interquartile range. Stars are referring to data points exceeding 2.5 times the interquartile range

Fig. 4

Kaplan-Meier curves regarding a local control and b distant control. Three patients experienced both local failure and new distant lesions. Time interval refers to time since start of radiotherapy. Number of patients at risk is detailed below the corresponding curves

Fig. 5

Kaplan-Meier curves regarding a local control with regard to the interval between last tumor resection and start of radiotherapy with a postoperative interval of 12 weeks; b local control with regard to the interval between last tumor resection and start of radiotherapy with a postoperative interval of 1 year; c local control with regard to macroscopic tumor before the start of radiotherapy. Time interval refers to time since start of radiotherapy. Log rank values refer to the whole observation period. Number of patients at risk detailed below the corresponding curves

Fig. 6

Kaplan-Meier curves depicting a local control with regard to MIB-1 proliferation index [median 8%]; b distant intracerebral control with regard to MIB-1 proliferation index, as determined in the histology of the tumor lesion that received postoperative radiotherapy. Time interval refers to time since start of radiotherapy. Log rank values refer to the whole observation period. Number of patients at risk is detailed below the corresponding curves