Intermediate-risk meningioma: initial outcomes from NRG Oncology RTOG 0539

Abstract

Objective(s) This is the first clinical outcomes report of NRG Oncology RTOG 0539, detailing the primary endpoint, 3-year progression-free survival (3yPFS), compared to a predefined historical control for intermediate-risk meningioma, and secondarily evaluating overall survival (OS), local failure, and prospectively scored adverse events (AEs). Methods NRG Oncology RTOG 0539 was a phase II clinical trial allocating meningioma patients to 1 of 3 prognostic groups and management strategies according to WHO grade, recurrence status, and resection extent. For the intermediate-risk group (Group 2), eligible patients had either newly diagnosed WHO grade II meningioma with gross total resection (GTR, Simpson I-III) or recurrent WHO grade I of any resection extent. Pathology and imaging were centrally reviewed. Patients were treated with radiation therapy (RT), either intensity modulated (IMRT) or 3D conformal (3DCRT), 54 Gy in 30 fractions. The RT target volume was defined as the tumor bed and any nodular enhancement (e.g. recurrent WHO grade I patients) with a minimum 8 mm and maximum 15 mm margin, depending upon tumor locale and set-up reproducibility of RT method. The primary endpoint was 3yPFS. Results were compared to historical controls (3yPFS 70% following GTR alone and 90% with GTR + RT). AEs were scored using NCI Common Toxicity Criteria. Results Fifty-six patients enrolled in the intermediate-risk group; 3 were ineligible. Additionally, 1 did not receive RT, and 4 withdrew without recurrence before 3 years. Thus 52 patients received protocol therapy, and 48 were evaluable for the primary endpoint, 3y PFS which was 93.8% (p=.0003). Within 3 years there were 3 PFS events: 1 WHO grade II patient died of disease, 1 WHO grade II patient progressed and remained alive, and 1 recurrent WHO grade I patient died from undetermined cause without progression. Three-year local failure was 4.1%, and 3-year OS 96%. After 3 years 2 additional patients progressed: 1 recurrent WHO grade I, and the other WHO grade II; both remain alive. Among 52 evaluable patients who received protocol treatment, 36 (69.2%) were WHO II with GTR, and 16 (30.8%) recurrent WHO I. There was no significant difference in PFS between these subgroups (p=.52, HR 0.56, 95% CI 0.09 to 3.35), validating their consolidation. Of the 52 evaluable patients, 44 (84.6%) received IMRT, and 50 (96.2%) were treated per protocol or with acceptable variation. AEs (definitely, probably or possibly related to protocol treatment) were limited to grade 1 or 2, with no reported grade 3 events. Conclusion This is the first clinical outcomes report from NRG Oncology RTOG 0539. Patients with intermediate-risk meningioma treated with RT experienced excellent 3yPFS with a low rate of local failure, and a low risk of adverse events. These results support the use of post-operative RT for newly diagnosed gross totally resected WHO grade II, or recurrent WHO grade I meningioma irrespective of resection extent. They also document minimal toxicity and high rates of tumor contr...

Preoperative and postoperative prediction of long-term meningioma outcomes

“…Our nomograms were trained on the full sample to produce a single model, and although 10-fold cross-validation was used for training and 100 bootstraps were used to test its stability, proper validation requires an external dataset. The aforementioned barriers to accurate meningioma diagnosis across different histopathologic eras have precluded our efforts to assemble larger data sets thus far, but we are hopeful that modern prospective meningioma trials will yield valuable and accurate data sets for future predictive model refinement [ 8 , 9 ].…”

“…Indeed, the majority of clinical data from meningioma patients, such as demographic and radiologic features, are largely ignored when prognosticating outcome. These data are omitted from clinical decisions because prospective, multi-institution trials have yet to identify clear features that influence meningioma outcomes [ 8 , 9 ], and no tractable algorithms or predictive models have been developed.…”

The role of Simpson grading in meningiomas after integration of the updated WHO classification and adjuvant radiotherapy

“…It may seem obvious that leaving tumor tissue or infiltrated dura behind results in a significant risk of tumor regrowth. However, it remains uncertain where the prognostic role of Simpson grading stands today, especially in light of the established importance of adjuvant radiotherapy for selected cases [2,3,6,13,14] and the recent reclassification of former grade I meningiomas with brain invasion as grade II atypical meningiomas [7]. The aim of this single-center retrospective study was to analyze the prognostic impact of the extent of resection according to the Simpson grading in light of the updated WHO classification together with established prognostic factors and adjuvant radiotherapy.…”

Evaluation of Radiosurgery Target Volume Determination for Meningiomas Based on Computed Tomography (CT) And Magnetic Resonance Imaging (MRI)

“…Higher grade meningiomas have a high tendency for recurrence even after comprehensive surgical resection, which renders adjuvant RT a viable adjuvant therapeutic option for these patients [5]. A recent study has supported the use of RT for management of newly diagnosed WHO grade II meningiomas after gross total resection and for management of recurrent WHO grade I meningiomas to achieve improved local control [6].…”