Atypical meningiomas carry a 7 to 8 fold increase in the risk of recurrence at five years compared to WHO grade I meningioma (11). In our series, when all patients were taken into consideration, as shown in Table 2, four prognostic factors were found to be statistically significant in the postoperative recurrence rate: Extent of resection, adjuvant RT, tumor localization, and progesterone expression.
Surgical resection is the first step in the treatment algorithm for the treatment of meningiomas. The impact of GTR on prognosis is well-grounded, given established literature revealing a complete tumor resection under relatively safe conditions remains an effective treatment technique and remains the mainstay of the approach to minimize the risk of recurrence and increase survival compared to STR in AMs (12–18). In our study, GTR was found to be one of the most important factors in the recurrence of AMs; 100% of tumors with STR only recurred as opposed to 34.8% of tumors with GTR only in similar follow-up times (Table 2).
Some studies present the active monitoring after GTR of AMs as a safe alternative to RT given the existing knowledge of no statistically significant impact on overall survival, but a possible role on progression-free survival (PFS) (15, 19) Although the role of surgical resection, particularly GTR is unequivocal in the management of AMs and late-term complications pertained to radiation-induced toxicity are known; recurrence remains a confrontational fact for AMs even after GTR. In our series, no patients had recurrence after RT (Table 2). However, the most important question still resides about the timing of RT. Early adjuvant radiation has been shown to improve long-term control (20, 21). Given the elevated risk of tumor recurrence with residual disease after surgery, adjuvant RT is a commonly accepted practice for AMs with STR (6). Park et al. recommend adjuvant therapy for AMs after STR (22). A clinical trial, The RTOG 0539 study, classified meningiomas into three risk groups: The low-risk group with new WHO grade 1 meningiomas after GTR or STR, the intermediate-risk group with recurrent WHO grade 1 meningiomas after GTR or STR, and WHO grade 2 meningiomas after GTR, and the high-risk group with WHO grade 3 meningioma and any recurrent WHO grade 2 meningioma, or a new WHO grade 2 meningioma after STR resection. The primary endpoint of the study, which is 3-year PFS was compared with historical controls (3-year PFS: 70% following GTR alone and 90% with GTR + RT). The 3-year overall survival rate for the intermediate-risk group was 96%. Still, the results represented rates obtained from treatment of newly diagnosed AMs with GTR and recurrent WHO Grade I meningioma irrespective of resection extent (23, 24). Unsurprisingly, in our series, STR of AMs without postop RT resulted in recurrence as correlated well with the findings of the high-risk group for the RTOG 0539 trial. Our intermediate-risk group, AMs with GTR revealed 38.4% recurrence in 52.73±33.302 months, which was longer than the 3-year follow-up time of the RTOG 0539 study (Table 2).
Two other factors were found to be significantly associated with recurrence of AMs besides the extent of resection and RT: Tumor localization and progesterone expression. AMs localized in skullbase-tentorium had a higher recurrence rate compared to tumors localized in convexity or parasagittal regions. Moreover, progesterone-negative tumors were correlated with recurrence. (Table 2).
Adjuvant therapy for high-risk group AMs with STR is commonly accepted; nevertheless, the role of adjuvant therapy in patients who have had GTR for AM is still debated in the intermediate group, and several studies reflected conflicting reports in the literature (20–22, 25–27). Early postoperative radiotherapy after resection of AM is increasingly being promoted, based on a single institutional series (24, 28–30). These previous retrospective studies of early adjuvant RT after surgical resection of WHO grade II meningioma have arrived at conflicting conclusions on whether adjuvant radiotherapy reduces recurrence and leads to overall survival benefit. Even if RTOG 0539 proposed the use of postoperative RT for newly diagnosed WHO Grade II regardless of the extent of resection (23, 24), surgical series do not necessarily agree with this conclusion (22, 31–34). Some studies compared the patients who received early postop adjuvant RT with those with salvage RT at their recurrences after GTR. Momin et al. found 26.4% of recurrence that required salvage RT after GTR. Although PFS was worse for the observation group compared to the early adjuvant RT group (PFS at 3 and 5 years after observation was 75.1%, 65.6%, and after adjuvant RT was 86.1% and 5,9.2%, respectively), patients who underwent observation with salvage radiation treatment had significantly longer radiation failure-free free survival (3-, 5-, and 10-year radiation failure-free survival rates were 97.7%, 90.3%, and 87.9%, respectively). The crucial question that remains to be answered is to reveal bad prognostic factors necessitating early postoperative adjuvant RT without waiting for the recurrence after GTR of AMs. In a series of 108 patients, Aghi et al. (20) found a 28% recurrence rate of AMs after GTR; and most recurrences occurred within five years after resection. In their study, factors predicting worse prognosis were older age, sheeting, and prominent nucleoli (20). In Komotar's series, 41% of patients who did not undergo postoperative radiotherapy after GTR showed recurrence. Residual tumor, parafalcine/parasagittal location, peritumoral edema, and a MI > 7 were all independently associated with early recurrence (35). Patients with early recurrence had worse neurological outcomes (36). If waited enough, a recurrence is unavoidable for all AMs as most recurrences occur in 5 years after GTR of AMs. However, we sought to determine factors to create a propensity towards early recurrence after GTR. In our series, preoperative tumor volume was the only statistically significant factor that affected the recurrence after GTR. The ROC analysis revealed a cut-off point for the volume, and any tumor greater than 27.5 cm3 had a higher recurrence rate (66.7%), and the risk of recurrence was 7.2 times higher in that group. On the contrary, 12 patients in the GTR group who had tumors smaller than 27.5 cm3 revealed no recurrence during their follow-up (9-108 months, median 40.75 months) (Table 3). Even if a statistical significance was not reached, probably due to small sample size; skullbase-tentorium localization, seizure at presentation, and lack of progesterone receptor expression could be predisposing factors for early recurrence (Table 3).