In this single-institution study of 26 patients with 33 RIMs, we found an absolute growth rate of 0.19 cm³ per year and a relative growth rate of 34.5% per year. Unsurprisingly, surgically treated tumors demonstrated a higher growth rate in comparison to patients undergoing observation or radiosurgery. Symptomatic presentation was correlated to increased baseline volume. In addition, younger age at RIM diagnosis and shorter latency period were correlated with increased RGR although not AGR.
These findings are in sharp contrast to a recent study by Gillespie and Islim, where a mean growth rate of 0.62 cm³ per year and RGR of 72% per year were described for RIM [14]. Notably, the mean baseline volume of 4.9 cm³ found in their study was also significantly higher (almost 25 times) when compared to ours. There are several explanations for this discrepancy. First, we are potentially dealing with different cohorts. For their group, most patients treated were referrals from other centers and potential self-selection for more aggressive RIM is possible as noted by the authors. Such selection bias was minimized since the pediatric oncology department in our institution served the whole country until two decades ago, and patients are regularly followed into adulthood (median total follow-up time of 27 years). Therefore, the tumor was detected in most cases at a very early stage. Second, small tumors can considerably increase in size which may be only reflected in the RGR and not the AGR. A small tumor can double or triple in size and be indicated for surgery, without necessarily displaying a high AGR [17]. Despite, given that the RGR was more than twice higher compared to our study, it suggests that their cohort was indeed faster growing. Third, it is not well known what type of growth pattern RIMs follow. A more quiescent phase preceding a phase of exponential growth, as proposed for sporadic meningiomas [19–21], is possible. As the tumor volume is considerably higher in the study of Gillespie and Islim, it suggests that those tumors were growing for a significant period before being diagnosed. This is supported by their long latency period (34.4 years) contrary to ours (20.4 years), the number of symptomatic cases (52%) contrary to ours (23%), and the already mentioned greater baseline volume.
Currently, there is no consensus on what constitutes growth, fast/slow growth, or significant growth for meningiomas, much less for RIM. Therefore, even in recently published papers, different authors use different criteria to report on the same endpoints [14, 17, 19, 22]. Adopting the growth criteria used by Gillespie and Islim (≥ 2 cm³ AGR or ≥ 1 cm³ AGR + ≥ RGR 30%) only 3 out of 33 (9%) meningiomas fulfilled the criterion for fast growth in contrast to 39.7% in their study [14]. Given that 21/33 of RIM (63%) underwent intervention during the observed study period, this criterion seemed to underappreciate the potential for small tumors to become problematic. Taking an increase of RGR alone by more than 15% per year as suggested by others [19, 22], this number increases to 28 out of 33 (84.8%) meningiomas in comparison to 95.9% in their study, which on the other hand seemed to overestimate the risk. Given that there should be relevance associated with used criteria, particularly for clinicians to identify those patients at “risk” for early intervention, we found neither criterion above to be particularly useful for our cohort. Thus, we decided to use values for AGR and RGR that would naturally split our cohort into a fast and slow growing cohort and used an AGR of ≥ 0.2 cm³/year and a change in RGR by ≥ 30% as a cut-offs to define fast growth (see Fig. 3). Based on this, 54.5% of our cohort fulfilled the criteria and we have used these to further investigate prognostic factors for growth.
We confirm the findings of Gillespie and Islim, that show younger age at diagnosis and surgically treated tumors to be correlated with tumor growth rate [14]. While it is established that the latency period is correlated with the dose of radiotherapy dose [4, 23–25], we support previous findings [14] that the dose is not correlated to the tumor growth rate. Another correlation was found between the length of the latency period with the RGR (p = 0.005), a finding not highlighted before. This suggests that patients diagnosed earlier may profit from more frequent follow-up examinations in comparison to older patients. As illustrated in Table 2, the correlation of RGR with age and latency period did not reach statistical significance when doing the same analysis with the AGR. This lack of correlation can best be explained by the minimal tumor volume at the time of diagnosis as discussed above. Unlike Gillespie and Islim, we did not find a statistically significant correlation between the baseline volume and the subsequent RIM growth rate, which could be again due to the differences in baseline volumes in both of our studies and the likelihood of larger tumors to be diagnosed in a point in time, where they exhibit exponential growth [21, 26].
Our study poses new important questions regarding the growth pattern of these tumors and the correct criteria for growth measurement to identify RIM at risk for intervention. We also suggest that based on our data younger patients with short latency periods profit from “tighter” screening intervals after diagnosis. Ultimately, more studies that observe the natural history of RIMs over a longer period will be needed to fully elucidate their growth pattern and examine which growth criteria are most relevant.
Study strengths and limitations
Most patients were treated for their initial tumor at our hospital having the only pediatric oncology center in the whole Czech Republic until 1998, thus ensuring minimal selection bias and oncological treatment consistency. Additionally, MRI screening programs at our institution allowed us to evaluate MRI scans from the moment of diagnosis and before, giving us an insight into the early tumor dynamic, which is missing in most studies.
Our results were predominantly limited by the sample size and the retrospective nature of this study. Additionally, heterogeneous follow-up periods for some tumors, including some short time intervals after resection might underestimate the true recurrence rate that could be observed in a long-term perspective. Another factor is the small number of radiosurgically managed patients, consequently not allowing more in-depth comparison.