Incidental brain findings on MRI, including subclinical vascular pathologic changes, are common in the general population. The most frequent are brain infarcts, followed by cerebral aneurysms and benign primary tumors. Information on the natural course of these lesions is needed to inform clinical management 1).
Among patients older than age 70 years who underwent operation for asymptomatic meningioma, the neurological morbidity rate was 23.3%; it was 3.5% among younger patients. This indicates that the advisability of surgery in elderly patients with asymptomatic meningiomas must be considered very carefully 2).
GKS can control tumors clinically and radiologically with high probability. Although the risk of transient adverse events exists, proactive GKS may be a reasonable treatment option when there are no comorbidities limiting life expectancy 3).
In the series of Yano et al., approximately 63% of asymptomatic meningiomas did not exhibit tumor growth, and only 6% of all patients with these lesions experienced symptoms during the observation period. To avoid surgery-related incidences of morbidity in patients with asymptomatic meningiomas, conservative treatment with close follow-up review may be the best therapeutic strategy 4).
They analyzed the correlation of the growth pattern of meningioma with patient gender, tumor location, tumor calcification, T2 weighted image signal intensity in magnetic resonance imaging (MRI), and Meningioma peritumoral edema.
The growth rate of meningioma was negatively correlated with tumor calcification (odds ratio [OR]: 0.23; 95% confidence interval (CI), 0.11-0.46; p < 0.001) but positively associated with MRI T2 signal intensity (OR: 2.75; 95% CI, 1.75-4.33; p < 0.001). No correlations were found between tumor growth and other factors such as gender (OR: 1.29; 95% CI, 0.84-1.99; p = 0.24), skull base location (OR: 0.80; 95% CI, 0.25-2.58; p = 0.70), and peritumoral brain edema (OR: 1.24; 95% CI, 0.29-5.27; p = 0.77).
Two factors, tumor calcification and low MRI T2 signal intensity, indicate the possibility of a slow growth meningioma. In such cases of asymptomatic meningioma, a follow-up strategy can be preferentially considered 5).
Compared with published rates of symptom development in patients with untreated meningiomas, results in a study of Salvetti et al., indicated that patients with asymptomatic lesions may benefit from prophylactic radiosurgery prior to the appearance of symptoms. Additionally, GKS is a treatment option that offers low morbidity 6).
They retrospectively analyzed their prospectively kept database on patients treated with Gamma Knife surgery and found 42 consecutive patients who had been treated for asymptomatic meningiomas over a 14- year period. The diagnosis was suspected from an imaging study or was confirmed by a previous surgery. Over a mean imaging and clinical follow-up period of 59 and 76 months, respectively, only 1 tumor (2.4%) increased in size. Interestingly, 2 patients without tumor growth demonstrated clinical symptomatology related to the tumor. Only 1 patient showed possible signs of radiation-induced injury. The actuarial tumor control rates were 100%, 95.7%, and 95.7% at 2, 5, and 10 years, respectively. This paper, which is very well written and very well discussed, is timely because it addresses a very important clinical issue—whether asymptomatic meningiomas should or should not be treated. In addition, the study confirms that radiosurgery is an effective and safe treatment modality to achieve “control” of meningiomas. This finding, of course, is not new, and there is plenty of evidence in the literature to that effect. The study has some limitations, such as its retrospective nature, possible biases, and a follow-up that, although relatively complete, was somewhat short for a benign tumor and not ideal in that many of the patients, because of the widespread referral pattern, were not seen in follow-up at the authors’ institution. Perhaps the major limitation is the small number of patients, but we assume that at this very busy radiosurgical center, the small number of treated asymptomatic meningiomas is a reflection of this group’s very conservative attitude about treating asymptomatic patients with meningiomas. The authors discuss these limitations very well. We would also add that their definition of a “stable” tumor, which most would interpret as no growth at all, is a bit generous in that they allow growth up to 15% of the initial tumor volume. The authors’ indications for treating patients fell into 4 categories—residual tumor after surgery, recurrent tumor after surgery, documented tumor growth, or patient preference—which unfortunately creates a relatively heterogeneous cohort. There needs to be no discussion about treating tumors with documented recurrence or growth. The issue of whether to treat or to observe residual tumor after surgery can be discussed with the larger issue of whether or not to treat asymptomatic meningiomas. More controversial, in our minds, is the issue of treating in response to patient preference. This is an indication that lends itself to abuse in many settings given the relatively good safety profile of radiosurgery. However, knowing the well-earned, excellent reputation of this group, We suspect that they were very careful in this respect and treated patients under the rubric of patient preference only in those cases in which they truly did not know whether treatment or no treatment was the preferred option. We are sure, for example, that they would not offer radiosurgery to an elderly patient with an asymptomatic, 1-cm, calcified convexity meningioma even if such a patient would prefer to have that treatment. It is important to know that in this series of 42 patients, 11 (26.2%) were treated because of documented tumor growth and 5 (11.9%) because of recurrent tumor. We have every reason to expect that since these tumors had grown, they would have continued to grow if left untreated, and yet only 1 tumor (we are not told if this tumor fell in the category with proven tumor growth or not) grew significantly after treatment; this is fairly convincing evidence of the effectiveness of radiosurgery in controlling tumor growth. The fact that 23 tumors (54.7%) in this series showed a > 15% reduction in tumor volume serves as further evidence of the effectiveness of radiosurgery. Moreover, there was no growth or new symptom in any of the 7 cases of tumors in the cavernous sinus, a location where other studies have shown that at least half of the patients experience new symptomatology and/or tumor growth over the follow-up period if left untreated.
Elhammady and Heros would like to expand on the authors’ discussion of whether asymptomatic meningiomas should or should not be treated. Obviously, they all agree that not all asymptomatic meningiomas should be treated; therefore, it is important to analyze what characteristics of the patient and the tumor are predictive of tumor growth or symptom development in those who present with an asymptomatic meningioma 7).
The effect of tumor size on future lesion growth or symptom development has been addressed in several studies. Sughrue et al. systematically reviewed the natural history of untreated meningiomas.
They identified 22 studies comprising 675 patients who were followed up by serial MRI for a median period of 4.6 years. The authors found that approximately three-quarters of untreated meningiomas 2.5 cm or smaller demonstrated no growth (51%) or grew 10% or less per year (26%). Patients with initial tumor diameters smaller than 2 cm (approximately 2%) rarely demonstrated new or worsening symptoms. Patients with initial tumor diameters of 2–2.5 cm had a marked difference in the rate of symptom progression based on whether their tumors grew more than or less than 10% per year (42% vs 0%). Patients with initial tumor diameters of 2.5–3 cm had new or worsening symptoms 17% of the time. These findings suggest that the majority of tumors smaller than 2.5 cm in diameter will not cause symptoms over the 5-year period following their discovery and that close observation with serial imaging is reasonable in these patients. On the other hand, larger lesions may be considered for early intervention 8).
A study of Kim et al., aimed to verify the effect of proactive Gamma Knife surgery (GKS) in the treatment of asymptomatic meningioma compared with the natural course without any therapeutic intervention.
From January 2006 to May 2017, 354 patients newly diagnosed with asymptomatic meningioma were reviewed and categorized into GKS (n = 153) and observation (n = 201) groups. Clinical and radiological progression rates were examined, and changes in volume were analyzed.
Clinical progression (i.e., clinician-judged progression), combining symptomatic progression (n = 43) and clinician-judged increase in size using images routinely acquired (n = 34), occurred in 4 patients (2.6%) and 73 patients (36.3%) in the GKS and observation groups, respectively (p < 0.001). The clinical progression-free survival (PFS) rates in the GKS and observation groups were 98.7% and 64.6%, respectively, at 5 years (p < 0.001), and 92.9% and 42.7%, respectively, at 10 years (p < 0.001). The radiological tumor control rate was 94.1% in the GKS group, and radiological progression was noted in 141 patients (70.1%) in the observation group. The radiological PFS rates in the GKS and observation groups were 94.4% and 38.5%, respectively, at 5 years (p < 0.001), and 88.5% and 7.9%, respectively, at 10 years (p < 0.001). Young age, absence of calcification, peritumoral edema, and high T2 signal intensity were correlated with clinical progression in the observation group. Volumetric analysis showed that untreated tumors gradually increased in size. However, GKS-treated tumors shrank gradually, although transient volume expansion was observed in the first 6 months. Adverse events developed in 26 of the 195 GKS-treated patients (13.3%), including 1 (0.5%) major event requiring microsurgery due to severe edema after GKS. Peritumoral edema was related to the development of adverse events (p = 0.004).
Asymptomatic meningioma is a benign disease; however, nearly two-thirds of patients experience tumor growth and one-third of untreated patients eventually require neurosurgical interventions during watchful waiting. GKS can control tumors clinically and radiologically with high probability. Although the risk of transient adverse events exists, proactive GKS may be a reasonable treatment option when there are no comorbidities limiting life expectancy 9).