Pathmanaban, Omar Nathan

Abstract Background DNA methylation profiling can be used to robustly predict postsurgical outcomes and response to radiotherapy (RT) for meningioma patients. To allow for seamless integration of these complementary models into clinical practice, a practical framework is needed. Methods We leveraged a cohort of nearly 2000 surgically-treated meningiomas with DNA methylation profiling and clinical outcomes data. Existing methylation-based prediction models were dichotomized to yield four risk groups: low and high recurrent risk, each with RT sensitive and resistant subgroups. Risk groups were correlated with progression-free survival in the context of existing biomarkers including extent of resection and WHO grade. Results We first demonstrated that all risk groups benefit from gross total resection. All “high-risk, RT sensitive” tumors (n = 306, 15.7%) also benefited from adjuvant RT: after GTR, median PFS increased from 4.68 (4.13-9.48) years to not reached (P = .003); after subtotal resection (STR), from 2.12 (1.59-3.02) to 4.09 (3.41-not reached) years (P = .004). “Low-risk, RT sensitive cases” (n = 1207, 61.8%) also benefited from RT after STR (median PFS 7.39 (6.66-12.8) vs. 16.53 (10.35-not reached) years, P = .03), suggesting that RT be considered in these patients. Neither “low-risk RT resistant” (n = 84, 4.3%) nor “high-risk RT resistant” (n = 356, 18.2%) cases benefited from RT, and the latter group was associated with universally poor outcomes. Conclusions We identify methylation-defined risk groups of meningioma for which additional benefit is gained from adjuvant RT, leading to a clinical decision-making framework for straightforward integration of molecular models into clinical practice.

BACKGROUND AND OBJECTIVES: Surgery in NF2-related schwannomatosis (NF2-SWN) vestibular schwannoma (VS) carries a higher risk of facial nerve damage, hearing loss, and partial resection, than in sporadic cases. Radiosurgery is also associated with higher failure compared with sporadic schwannomas. Nowadays, bevacizumab (BEV) is frequently considered in the NF2-SWN population. However, some patients experience progression despite treatment. Among other surgical risks, in BEV-treated patients, hemorrhage and impaired healing are specific considerations. These concerns have led manufacturers to recommend stopping BEV 6 to 8 weeks preoperatively. The aim of our multicentric study was to assess the perioperative bleeding risk and postoperative outcomes in NF2-SWN patients undergoing VS surgery after preoperative BEV treatment. METHODS: Our retrospective analysis included medical and surgical records along with imaging reviews from 4 high-volume tertiary academic referral centers for NF2-SWN and VS. RESULTS: A total of 21 patients met the inclusion criteria. VS had a mean volume of 13.2 ±7.6 cm 3 corresponding to 1 KOOS III and 20 KOOS IV. BEV was stopped at a mean of 5.8 ± 4.0 months before surgery with a total mean treatment duration of 33.7 ± 20.7 months and a monthly dose of 10.2 ± 4.1 mg/kg. Intraoperatively, the tumor was assessed to be bloody by the operating surgeons in 7 patients. Late BEV discontinuation and high cumulative dose independently predicted perioperative bleeding and longer surgery duration. No other complication such as wound dehiscence was reported. CONCLUSION: Our findings suggest that a higher cumulative BEV dose (∼600 mg/kg) and a longer interval between BEV discontinuation and surgery (∼8 months) are associated with a modest but statistically significant increase in intraoperative bleeding risk. Based on these observations, a BEV-free window between 6 weeks and 6 months (depending on the clinical scenario) before tumor resection seems optimal, particularly for patients with high cumulative exposure.

OBJECTIVE Preoperative differentiation of facial nerve schwannoma (FNS) from vestibular schwannoma (VS) can be challenging, and failure to differentiate between these two pathologies can result in potentially avoidable facial nerve injury. This study presents the combined experience of two high-volume centers in the management of intraoperatively diagnosed FNSs. The authors highlight clinical and imaging features that can distinguish FNS from VS and provide an algorithm to help manage intraoperatively diagnosed FNS. METHODS Operative records of 1484 presumed sporadic VS resections between January 2012 and December 2021 were reviewed, and patients with intraoperatively diagnosed FNSs were identified. Clinical data and preoperative imaging were retrospectively reviewed for features suggestive of FNS, and factors associated with good postoperative facial nerve function (House-Brackmann [HB] grade ≤ 2) were identified. A preoperative imaging protocol for suspected VS and recommendations for surgical decision-making following an intraoperative FNS diagnosis were created. RESULTS Nineteen patients (1.3%) with FNSs were identified. All patients had normal facial motor function preoperatively. In 12 patients (63%), preoperative imaging demonstrated no features suggestive of FNS, with the remainder showing subtle enhancement of the geniculate/labyrinthine facial segment, widening/erosion of the fallopian canal, or multiple tumor nodules in retrospect. Eleven (57.9%) of the 19 patients underwent a retrosigmoid craniotomy, and in the remaining patients, a translabyrinthine (n = 6) or transotic (n = 2) approach was used. Following FNS diagnosis, 6 (32%) of the tumors underwent gross-total resection (GTR) and cable nerve grafting, 6 (32%) underwent subtotal resection (STR) and bony decompression of the meatal facial nerve segment, and 7 (36%) underwent bony decompression only. All patients undergoing subtotal debulking or bony decompression exhibited normal postoperative facial function (HB grade I). At the last clinical follow-up, patients who underwent GTR with a facial nerve graft had HB grade III (3 of 6 patients) or IV facial function. Tumor recurrence/regrowth occurred in 3 patients (16%), all of whom had been treated with either bony decompression or STR. CONCLUSIONS Intraoperative diagnosis of an FNS during a presumed VS resection is rare, but its incidence can be reduced further by maintaining a high index of suspicion and undertaking further imaging in patients with atypical clinical or imaging features. If an intraoperative diagnosis does occur, conservative surgical management with bony decompression of the facial nerve only is recommended, unless there is significant mass effect on surrounding structures.