We analyzed a large series of CKRT outcome on the CSMs. The median of PFS was 48 (IQR 23–73) months with 5-year local control rate over 80% (Table 3). A significant difference was observed in PFS between grade I and II CSMs (Fig. 1B). There was no difference in PFS depending on the history of previous surgery (Fig. 1C). No variables significantly predicted PD. Cranial neuropathies rarely occurred (0.9%), however we have to be careful of peritumoral edema (4.4%) especially CSMs’ main attachment is around the anterior clinoid process. Although CSMs are frequently formidable lesion to deal with, CKRT provided an effective local control rate (LCR) with low rate of AE (Table 2).
Radiological outcome of CKRT
To the best of our knowledge, no large case series exist that featured CKRT outcome on the CSMs. From a similar study where CKRT outcome was assessed on the skull base meningiomas, 1-, 3-, and 10-year LCR were 99.4, 96.8, and 80.3% respectively, which was comparable to our results.[1] Other study on intracranial meningiomas showed 2 year LCR of 81%, which was a bit lower than ours (93.8%).[8] On the other hand, gamma knife radiation surgery (GKS) on the sellar and parasellar meningiomas showed LCR of 98%, 88%, and 82% at 3-, 5-, and 10-year respectively. Compared to our results, GKS provided a little better LCR than CKRT.[15] Another study of GKS on CSMs showed LCR of 98.2%, 93.4%, 88.9%, and 76.2% at 2-, 4-, 6-, and 10-year respectively.[12] Comparing their study to ours, their result was a little better than ours as well. However, it must be noted that both studies[12, 15] on GKS included only benign (WHO grade I) meningiomas, and that grade II/ III meningiomas were excluded. Consequently it is understandable that LCR was better than ours. The comparisons of similar past studies to ours is summarized in the Table 3. Having said that, GKS may be better than CKRT in terms of LC.
Adverse outcome
The major AE we keep in mind is that on the vision. In our cohort, visual decline was seen in one patient (0.9%). This rate is lower than 3% in a study of GKS on the sellar and parasellar meningiomas[15]. The risk of damage to the other cranial nerves was 0%. As for the pituitary function, no patients experienced new or worsening hypopituitarism as opposed to the past studies on gamma knife (0.5–1.8%).[15, 12] The comparisons of AE is summarized in the Table 3. As shown in the table, CKRT seems to have lower AE than GKS. However, since the median follow-up of the CKRT is shorter than GKS, further observation of CKRT arm should be done to show that CKRT is better in terms of AE. In addition to the visual change, we need to keep in mind peritumoral edema as a potential side effect. Reviewing the past literature, cerebral edema after therapeutic radiation occurred in 4–19% depending on the studies.[10, 5, 9, 2, 17, 7, 16] The risk factors were tumor location, radiation dose, and tumor volume among others.[9] In our case, all the five edema (4.4%) occurred in CSMs near the anterior clinoid process and most patients (80%) had some degree of headache.
As for the other adverse outcomes, we found cases with cavernous carotid stenosis (CCS) and cases with NPH which underwent VPS. CCS may be due to chronic occlusion of the artery by the encasing tumor or the late-phase AE of radiation. NPH requiring VPS may be due to high protein contents in the cerebrospinal fluids as a result of the underlying CSMs, AE of surgical resection, AE of radiation, or idiopathic NPH. Consequently, these two adverse outcomes as well as death were not necessarily AE of radiation therapy alone (Table 2). CCS were asymptomatic in all three patients (2.7%). In a similar recent study on the radiosurgery’s effect on the internal carotid artery, nine patients (5.8%) out of 155 cavernous sinus meningioma patients treated with stereotactic radiosurgery resulted in CCS.[6] In their cohort, symptomatic CCS were rare, which is in line with our result. Regarding NPH, since all patients developed and underwent VPS within one year after the last CKRT, we need to monitor them for any signs of NPH in their first year especially if they had a previous history of surgical resection.
Treatment suggestion
Comparing our data and the past literature on GKS, CKRT has comparable treatment effect on PFS with low risk of AE. Since gross total resection of CSMs while preserving important structures sometimes pose a great challenge, for incidentally- found CSMs, in addition to observation and surgical resection, upfront CKRT may be a reasonable choice as well as GKS[13]. All asymptomatic patients who underwent upfront CKRT resulted in local control (100%). However, we need to keep in mind the possibility of transient new-onset or worsening of peritumoral edema (11%, two patients out of 17 in our cohort) especially if the tumor involves the anterior clinoid process. As for symptomatic CSMs, 1) maximal safe resection followed by CKRT, or 2) upfront CKRT are reasonable treatment options depending on the degree of neurologic worsening (Fig. 2). Since PFS was better in grade I than grade II CSMs (p = 0.02), all grade II CSMs should be followed by adjuvant CKRT to improve PFS. In our cohort, no variables (age, sex, previous operation, time to CKRT, target volume, and form of CKRT) except pathology grade were found to be statistically significant in affecting PFS. This result is in line with a similar past study.[15] Considering the effectiveness of CKRT on the CSMs regardless of previous status of operation, we do not have to stick to achieving Simpson grade I – III resection at the risk of irreversible surgical complications.[14] Finally, as stated in the result section, although not being significant, we found some trends in upfront CKRT (p = 0.11) having longer PFS than adjuvant CKRT. It may be possible that if pathology data had been available in more patients, the p- value would have been significant. If we were able to identify WHO grade I meningiomas by radiological findings, upfront CKRT would be suitable for asymptomatic patients.
Limitation
Several limitations exist in this study. First, since our facility is a referred center for CKRT, not all the detailed clinical information was available. We referred the patients’ information to their primary hospitals, however we were not able to obtain the reply from all. For this reason, we excluded those with no more than six months’ follow-up. Second, the histopathological subtypes (WHO grade) of meningioma was not available in some surgically treated patients. Consequently information on the WHO grade were missing in the 28 (37%) patients. Finally, since we have many censored data on PFS curves, and we have to interpret the data carefully.