Long-term natural history of neurofibromatosis Type 2–associated intracranial tumors

Abstract

Object Neurofibromatosis Type 2 (NF2) is a heritable tumor predisposition syndrome that leads to the development of multiple intracranial tumors, including meningiomas and schwannomas. Because the natural history of these tumors has not been determined, their optimal management has not been established. To define the natural history of NF2-associated intracranial tumors and to optimize management strategies, the authors evaluated long-term clinical and radiographic data in patients with NF2. Methods Consecutive NF2 patients with a minimum of 4 years of serial clinical and MRI follow-up were analyzed. Results Seventeen patients, 9 males and 8 females, were included in this analysis (mean follow-up 9.5 ± 4.8 years, range 4.0–20.7 years). The mean age at initial evaluation was 33.2 ± 15.5 years (range 12.3–57.6 years). Patients harbored 182 intracranial neoplasms, 164 of which were assessable for growth rate analysis (18 vestibular schwannomas [VSs], 11 nonvestibular cranial nerve [CN] schwannomas, and 135 meningiomas) and 152 of which were assessable for growth pattern analysis (15 VSs, 9 nonvestibular CN schwannomas, and 128 meningiomas). New tumors developed in patients over the course of the imaging follow-up: 66 meningiomas, 2 VSs, and 2 nonvestibular CN schwannomas. Overall, 45 tumors (29.6%) exhibited linear growth, 17 tumors (11.2%) exhibited exponential growth, and 90 tumors (59.2%) displayed a saltatory growth pattern characterized by alternating periods of growth and quiescence (mean quiescent period 2.3 ± 2.1 years, range 0.4–11.7 years). Further, the saltatory pattern was the most frequently identified growth pattern for each tumor type: meningiomas 60.9%, VSs 46.7%, and nonvestibular schwannoma 55.6%. A younger age at the onset of NF2-related symptoms (p = 0.01) and female sex (p = 0.05) were associated with an increased growth rate in meningiomas. The identification of saltatory growth in meningiomas increased with the duration of follow-up (p = 0.01). Conclusions Neurofibromatosis Type 2–associated intracranial tumors most frequently demonstrated a saltatory growth pattern. Because new tumors can develop in NF2 patients over their lifetime and because radiographic progression and symptom formation are unpredictable, resection may be best reserved for symptom-producing tumors. Moreover, establishing the efficacy of nonsurgical therapeutic interventions must be based on long-term follow-up (several years).

Reliability of the Size Evaluation Method for Meningiomas: Maximum Diameter, ABC/2 Formula, and Planimetry Method

“…According to the results of this study, the use of the ABC/2 formula should be limited to non-skull base meningiomas with regular and round or ellipsoid shapes. To obtain a more accurate tumor volume using the ABC/2 formula, Dirks et al have recommended using the ABC/2 formula by dividing the tumor into compartments for multilobulated tumors (2). Although the ABC/2 formula appears to be useful for calculating the growth rate of a tumor rather than quantification of tumor volume, this has been reported as an underestimation (1).…”

“…The ABC/2 formula is frequently used to calculate the volume of intracerebral hemorrhage (ICH) because of its simplicity and quickness; however, the accuracy of the ABC/2 formula has been previously debated (20)(21)(22)(23)(24). Although some studies have used the ABC/2 formula (2,25,26) or the original ellipsoid volume (10,19,27) to measure the volume of intracranial tumors, including meningiomas, few studies have evaluated the accuracy of ABC/2 formula for intracranial tumors. The planimetry method presents a more approximate volume for the real tumor and has been applied in many studies (3,4,(11)(12)(13)(14)(15); however, this method is more cumbersome than the ABC/2 method.…”

Phase II study of mTORC1 inhibition by everolimus in neurofibromatosis type 2 patients with growing vestibular schwannomas

“…Upon reintroduction of everolimus, VS stabilization was immediately resumed, indicating that inhibition of mTORC1 had a direct inhibitory effect on VS growth, which therefore cannot be ascribed to a ''saltatory'' VS progression pattern. A saltatory growth pattern was described in a single retrospective analysis of digitized MRI films and has never been reported in any other VS natural history series [29]. Based on our observation, we do not recommend stopping everolimus treatment when it led a stabilization of growing VS.…”

Clinical course of vestibular schwannoma in pediatric neurofibromatosis Type 2

“…1,5,10,18,21 Our study showed 0.33 cm 3 /year of actuarial growth rate, suggesting a slow natural course of VS in children. Our study suggests that the natural growth rate may be slow only in children.…”

“…Moreover, tumor growth on follow-up examination in the absence of symptoms or signs is not by itself an indication for surgery because the majority of NF2-associated tumors will enlarge for a certain period of time and then have prolonged silent periods of inactivity while the patient remains asymptomatic. 10 In general, neurological deterioration or cosmetic reasons are the indications for surgery in patients with NF2.…”