Prospective data regarding postoperative RT for meningiomas are limited. Most published studies are retrospective, small and heterogeneous, while other studies are ongoing.
The results of the current national decision-making analysis reflect consensus in several clinical scenarios but also reveal broad uncertainties in the decision to offer postoperative RT with different applications (conventional vs. hypofractionation vs. SRS) as well as a range of prescribed doses.
Consensus for postoperative management was only found for WHO grade III meningiomas for both the indication for irradiation after surgery and the regimens used. Furthermore, and not included in the analysis, three out of ten centres applied an additional boost of 6 to 10 Gy (3-5 × 2 Gy) on the residual tumour up to an overall dose of 66-70 Gy (33-35 × 2 Gy) for incompletely resected WHO grade III meningiomas.
Specific details of the RT devices, preferred techniques (e.g., distribution of beams) or dose prescription were not included in our analysis.
For treatment decisions, information about the surgical status is crucial. The historically evolved Simpson classification is a subjective evaluation by the surgeon quantifying the extent of resection. Depending on the location of the tumour (i.e., skull base meningiomas), its uniform application may be even more difficult. An alternative categorization has already been proposed (gross total vs. subtotal resection) to define more homogeneous study populations . One should be aware of this potential bias, as it has significant implications for postoperative management.
Two centres included proliferation indices using MIB-1 staining or the number of mitoses per high-power field. Both centres provided no specific cut-off value for dividing high and low proliferation. Proliferation status may lead to recommendations for or against postoperative irradiation. In addition to the vague quantitative specification, one must keep in mind that the indices themselves can vary from different samples in one tumour since the tumour tissue is not homogenous. Furthermore, the results can also differ subjectively based on the investigating pathologist or laboratory .
The majority of the centres used size for decision-making in therapy. Even though this was a common criterion, no specific cut-off value for small or large was agreed upon since centres used different diameters as well as volumes to make this distinction.
Even though the frequency of meningiomas is high and the procedures seem to be standardized, the level of evidence for postoperative treatment recommendations is low and often depends on local experience. For WHO grade I tumors, the current NCCN  and EANO  guidelines recommend observation in cases of complete resection and consider postoperative irradiation for incompletely resected tumours or symptomatic patients. Our results reflect the recommendations, as the vast majority (between 80 and 100%) of the centres omitted postoperative radiotherapy for completely resected WHO grade I tumours without risk factors but showed less consensus for incompletely resected tumours and/or tumours with risk factors. If fractionated RT was applied, centres used 50.4-54 Gy in 1.8-2.0 Gy single doses as mentioned in both guidelines. In the case of small tumours, the EANO guidelines recommend SRS of a 14-16 Gy single dose, and a few centres applied this strategy.
For completely resected WHO grade II tumours, RT can be considered according to the two abovementioned guidelines. As the recommendations for completely resected WHO grade II tumours remain vague, the applied options in our survey also show various RT approaches with a high variability of admitted doses, although almost all centres apply doses within the recommendations of 54-60 Gy, with only one centre applying SRS.
The NCCN guidelines  and the EANO guidelines  clearly recommend postoperative irradiation in cases of incompletely resected WHO grade II tumours and all WHO grade III tumours. Our findings significantly reflect the recommendations since all centres use postoperative radiotherapy. Nearly all centres are in the range of the dose recommendations of the NCCN for WHO grade III tumours of 59.4-60 Gy in 1.8-2.0 Gy fractions, and one centre uses the minimal recommended dose by the EANO of 54 Gy. Additionally, one centre used SRS for small tumours.
As within the current guidelines, recommendations of recurrent or progressive disease for postoperative RT vary, and RT can be considered as one of many options. Our results reflect a wide range of daily uses. The majority of experts recommended omitting adjuvant treatment for completely resected WHO grade I tumours without recurrence. Although no certain time period was defined to identify recurrence or tumour progression, most experts agreed on cranial MRI (cMRI) within 3-6 months after surgery for tumour evaluation. Several strategies and intervals to determine therapy success or monitor tumour growth were implemented, and no standardized timing to proceed with therapy for progressing or recurrent tumours was agreed upon. When no postoperative RT was performed, follow-up cMRI every 3-6 months was recommended. Follow-up strategies were beyond the scope of this study.
Furthermore, the experts unanimously agreed to offer RT for incompletely resected WHO grade II meningiomas, but the schedules offered differed widely. Of note, there was no consensus for any other scenario. Indeed, multiple treatment options or irradiation regimens for the same scenario were considered among the different experts, again pointing to surprising uncertainties in the management of this condition. Our findings match the results of RTOG 0539, which supports postoperative radiotherapy of WHO grade III, incomplete resected WHO grade II and recurrent WHO grade I and II tumours due to a high local failure rate [21, 22].
The new WHO classification of brain tumours  has newly added the criterion of brain invasion for atypical meningioma of WHO grade II. This criterion had a separate impact on the decision-making of only one centre, where it was used independently of the WHO classification for postoperative treatment. The presence of brain invasion leads to increased volumes of radiation and influences the choice of the fractionation scheme.
In WHO low-grade and slow-growing tumours, watchful waiting might be a valid option [20, 37]. Neither this scenario nor the primary RT of meningiomas were addressed in this study, but both options should be discussed and considered according to the clinical setting [38,39,40].
Neurosurgery and RT are the mainstays of meningioma treatment, and systemic treatment modalities have been widely studied, unfortunately, with limited success. Such treatments have been used as salvage therapy but are essentially less effective . However, a recent randomized phase II study provided evidence for the use of sunitinib as a targeted treatment for progressive or recurrent WHO grade II and III meningiomas with a median time to progression of 5.2 months in heavily pretreated meningiomas . Tumours with VEGFR2 expression demonstrated a better response rate and median time to progression than non-VEGFR2-expressing tumours (6.4 vs. 1.4 months; p = 0.005). In addition to bevacizumab, which also has clinical efficacy in these highly vascularized tumours , sunitinib can be a valuable option in meningioma patients failing local therapies. As systemic treatments have been explored only in heavily pretreated patients, their true potential is biased, and such therapies might be more effective and safer (i.e., wound healing) if used in the earlier stages of the disease. Beyond that, the combination of concurrent and sequential radioimmunotherapy has to be investigated further regarding its effects, benefits and risks. The use of systemic therapies was not investigated in this decision-making analysis since it was beyond the scope of this paper.
Shared decision-making plays an especially important role when various therapy options are available. Side-effect profiles and the convenience of each therapy have to be discussed extensively , especially considering that new treatments develop rapidly but are not yet abundantly available or not yet integrated in the standard of care. Physicians’ awareness of multiple treatment approaches may provide more room to engage patient preferences in a shared decision-making process. Unfortunately, only limited research is available on the interaction between new systemic treatments and established treatments, making counselling patients even more difficult. However, physicians can also be a source for bias, as they reflect side effects based on personal or centre experience; for example, they may overestimate the benefit and neglect the side effects of irradiation. Due to a lack of standard care, the patient is highly dependent on the experience and advice of the treating centre and MDT.
Recently, postoperative irradiation has been the topic of several studies, in which a benefit in WHO grade III meningiomas was demonstrated [27, 45]. Currently, the ROAM trial is investigating the role of adjuvant RT vs. observation for completely resected WHO grade II tumours, and the results are eagerly awaited. Further prospective research is needed to clarify the irradiation strategies in different settings.
Our study has some limitations. In clinical practice, multifocal occurrence either at initial diagnosis or at progression is a strong limiting factor for local therapies, including RT. The clinical term meningiomatosis is not mentioned in the current WHO classification and is not restricted to a WHO grade but perfectly describes the condition of continuous and multifocal intracranial spread of neoplastic meningioma cells .
This important clinical problem was not formally addressed in our analysis, as it was not explicitly reported by the centres. However, this condition might be addressed under the term “zugzwang” or “need to treat”. In clinical practice, these patients underwent several attempts of local tumour treatment with surgical resection and/or (repeated) RT. As a frequent side effect, these patients suffer from wound healing problems and have a substantially higher risk of wound infection. This also affects the possibility of systemic therapies (i.e., bevacizumab and sunitinib), which are also associated with wound healing problems, ultimately leading to a therapeutic dilemma.