Pathology concordance levels for meningioma classification and grading in NRG Oncology RTOG Trial 0539

Rogers, C. Leland; Perry, Arie; Pugh, Stephanie L.; Vogelbaum, Michael A.; Brachman, David; McMillan, W. G.; Jenrette, Joseph M.; Barani, Igor J.; Shrieve, Dennis C.; Sloan, Andy; Bovi, Joseph; Kwok, Young; Burri, Stuart H.; Chao, Samuel T.; Spalding, Aaron C.; Anscher, Mitchell S.; Bloom, Beatrice; Mehta, Minesh P.

doi:10.1093/neuonc/nov247

Cited by 100 publications

(97 citation statements)

References 31 publications

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“…8,9,17,31,39 A secondary analysis from NRG Oncology RTOG 0539, a comparison of histopathologic concordance between the enrolling institution and central review, was recently published. 42 We found a concordance rate of 87.8% for WHO grade II, statistically inferior to WHO grades I and III, for which the rates were, respectively 93.0% and 93.6% (p < .0001). Twenty-two cases were reclassified after central review.…”

Section: Discussionmentioning

confidence: 57%

“…For instance, there was only slight agreement on focal papillary and focal clear cell; fair agreement for focal rhabdoid, chordoid, and small cells; and moderate agreement on hypercellularity, macronucleoli, sheeting, diffuse papillary, anaplasia, and mitoses ≥4 per 10 high power fields (HPF). 42 The number of mitoses is a critical element, as it is the most common differentiating factor for meningioma grade. Improvements in concordance may require clarifications of criteria with lower rates of interobserver concordance, and the development of biomarkers predictive of clinical outcome.…”

Section: Discussionmentioning

confidence: 99%

“…Previous grading standards were not broadly accepted, but, based upon a recently published secondary endpoint analysis of pathology concordance from NRG Oncology RTOG 0539, the WHO 2000 and 2007 standards appear to have been broadly followed, at least among institutions enrolling patients on NRG Oncology RTOG cooperative group trials. 42 …”

Section: Introductionmentioning

confidence: 99%

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

Rogers

Zhang

Vogelbaum

et al. 2018

Journal of Neurosurgery

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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...

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Section: Discussionmentioning

confidence: 57%

Section: Discussionmentioning

confidence: 99%

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

Rogers

Zhang

Vogelbaum

et al. 2018

Journal of Neurosurgery

Self Cite

180

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“…Although oftenthis was based on small series, it prompted the allocation allotment of distinct WHO grades to specific meningioma subtypes. However, this approach has been increasingly questioned due to suboptimal inter-observer reproducibility 7,23 , most recently reported in a large Radiation Therapy Oncology Group …”

Section: Discussionmentioning

confidence: 99%

“…subtypes and three grades of malignancy 4 , but some of the diagnostic criteria are vaguely defined and subject to a high inter-observer bias, indicating thea need for more reliable biomarkers 5,7 .…”

Section: Introductionmentioning

confidence: 99%

DNA methylation-based classification and grading system for meningioma: a multicentre, retrospective analysis

Sahm¹,

Schrimpf²,

Stichel³

et al. 2017

The Lancet Oncology

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560

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Link to publication record in Explore Bristol Research PDF-document This is the author accepted manuscript (AAM). The final published version (version of record) is available online via Lancet at https://www.sciencedirect.com/science/article/pii/S1470204517301559?via%3Dihub . Please refer to any applicable terms of use of the publisher. University of Bristol -Explore Bristol Research General rightsThis document is made available in accordance with publisher policies. Please cite only the published version using the reference above. Full terms of use are available:

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