To the best of our knowledge, this study is the first one to assess HRQOL data using QLQ-C30 and BN20 questionnaires for exclusively meningioma patients who received radiotherapy. Our database search found only few publications evaluating HRQOL using QLQ-C30 and BN20 questionnaires in meningioma patients, mostly as unplanned subgroup analyses [17–19, 23]. Our HRQOL data shows that meningioma patients have lower QLQ-C30 and BN20 scores after radiotherapy than the general population (Supplementary Fig. S1) [20–22]. Moreover, our data shows slightly lower HRQOL results in comparison to already published data for meningioma patients, although comparability might be limited due to different data acquisition methods and patient group compositions [26]. For instance, Erharter et al. performed a preselection of patients excluding patients with severe cognitive impairment, which resulted in higher HRQOL scores [23]. No additional information about meningioma patient group composition is provided by Shin et al. [19]. Budrukkar et al. assessed HRQOL in a subgroup of patients with benign brain tumors, which was not limited to meningioma patients only [18]. Konglund et al. reported higher QLQ-C30 scores which is probably attributable to group differences as their cohort consisted to 94% of benign, resected meningiomas without radiotherapy [17]. Primary radiotherapy is often chosen for advanced, inoperable tumors and benign meningiomas should not be irradiated after complete resection according to the EANO guidelines for the diagnosis and treatment of meningioma [27, 28]. Our cohort predominantly consisted of patients with unfavorable tumor location or with incompletely resected meningiomas, prone to worse outcome with more clinically significant side effects and consequently lower HRQOL [13]. Furthermore, the rate of WHO grade II and III meningiomas was significantly higher with 31.9% in our study and 21 patients (17.6%) reported another malignant tumor before HRQOL assessment.
Another selection bias might result from the limited response rate of questionnaires (59.8%) in our study. Since only long-term HRQOL was assessed in our study, beneficial effects directly after radiotherapy or surgery resulting in functional gains and better HRQOL were not measured in contrast to the studies of Budrukkar et al., Konglund et al. and Bitterlich et al. [17, 18, 29]. HRQOL was determined with a median time of 4.8 years after treatment in our study providing the possibility of other diseases negatively influencing HRQOL, such as stroke or cognitive deterioration due to aging.
Physician-assessed severe acute toxicities appeared in only 5.9% of cases, confirming that radiotherapy has mild side effects when applied in meningioma patients. The one case of acute amaurosis could be attracted to tumor growth as the patient had severe visibility impairment prior to radiotherapy and received a palliative radiation with a lower dose. Albeit 36.2% of patients reported chronic toxicities, only 4.2% suffered from a chronic side effect CTCAE grade ≥3. Our findings are in line with previously published data in terms of acute and late toxicities (0-49.9%) [7, 10, 12, 14, 30, 31].
Our median applied dose of radiation was comparable with existing literature. Based on already published data, a dose of 54 – 60 Gy is indicated and well tolerated for WHO grade I meningiomas. In our WHO grade I meningioma cohort, a dose up to 66.0 Gy was accepted if histopathology specimens had angiomatous or fibrous components. For high-grade meningiomas (WHO grade II and III), a median total dose of 60.0 Gy was prescribed in our cohort. A minimum dose of 60 Gy is usually prescribed for WHO grade III meningiomas to ensure long-term local control [32, 33]. The dose prescription for WHO grade II meningiomas, however, is inconsistent throughout literature. Depending on the resection status, high dose radiation with 60 Gy or 70 Gy was prescribed for all WHO grade II meningioma patients in the EORTC 22042 study while newly diagnosed WHO grade II meningioma patients with gross total resection were treated with a lower radiation dose of 54 Gy in the RTOG 0539 study [34, 35]. Three-year progression-free survival (PFS) and OS were comparable in both studies. Long-term results for both studies have not been published yet. In retrospective analyses, dose escalation, however, is associated with improved clinical outcome and may be prescribed for WHO grade II meningiomas [32, 33, 36, 37].
Existing reports on factors influencing OS and LC for meningioma are inconsistent except for WHO grade [11, 15, 30, 38–41]. In line with these results, our data confirmed that the WHO grade had a significant impact on OS in univariate and multivariate analysis and affected local control as well. Due to the lack of studies with large patient numbers, statistics for OS and LC in WHO grade II and III meningiomas show a broad variance (0.0-89.0%) (Table 3) [30, 32, 33, 38, 40, 42, 43]. Our estimated 5-year LC for WHO grade II (66.7%) and WHO grade III (53.1%) meningiomas is compatible with the majority of published data (Table 3) [11, 13, 15, 30, 32, 33, 38, 40, 42, 44–47]. Our 5-year and 10-year OS rates for each WHO grade, however, seem to be more favorable in comparison to published ones. This might be due to our low number of high-risk meningioma patients limiting statistical information. In addition, histological grading in older samples was not updated to the revised WHO grading system from 2016 influencing the indication for radiotherapy, the target volume, applied dose and probably the outcome [48]. Although concordance for histopathological grading of meningioma is relatively high, there is still some interobserver and interinstitutional discrepancy, which might lead to a bias in outcome [49].
The lack of longitudinal assessment of HRQOL is a limiting factor of our analysis as HRQOL data was only assessed at a specific time point during follow-up. Hence, a pre-treatment survey is missing to compare if treatment had a beneficial or deteriorating effect on HRQOL.
Nevertheless, our data confirms that radiotherapy shows an excellent prognosis with regard to OS and LC in meningioma patients. In a cohort of mostly advanced or relapsed meningioma patients, radiotherapy lead to acceptable HRQOL and low toxicity. HRQOL deterioration should be considered and may guide decision making when opting for radiotherapy in meningioma patients. The considerable risk of recurrence in patients with high-grade meningiomas has to be taken in account. Prospective studies should aim for improvement of HRQOL without worsening outcome.