Pathology concordance levels for meningioma classification and grading in NRG Oncology RTOG Trial 0539.
BACKGROUND
With advances in the understanding of histopathology on outcome, accurate meningioma grading becomes critical and drives treatment selection. The 2000 and 2007 WHO schema greatly increased the proportion of grade II meningiomas. Although associations with progression-free survival (PFS) and overall survival (OS) have been independently validated, interobserver concordance has not been formally assessed.


METHODS
Once mature, NRG Oncology RTOG-0539 will report PFS and OS in variably treated low-, intermediate-, and high-risk cohorts. We address concordance of histopathologic assessment between enrolling institutions and central review, performed by a single pathologist (AP), who is also involved in developing current WHO criteria.


RESULTS
The trial included 170 evaluable patients, 2 of whom had 2 eligible pathology reviews from different surgeries, resulting in 172 cases for analysis. Upon central review, 76 cases were categorized as WHO grade I, 71 as grade II, and 25 as grade III. Concordance for tumor grade was 87.2%. Among patients with WHO grades I, II, and III meningioma, respective concordance rates were 93.0%, 87.8%, and 93.6% (P values < .0001). Moderate to substantial agreement was encountered for individual grading criteria and were highest for brain invasion, ≥20 mitoses/10 high-powered field [HPF], and spontaneous necrosis, and lowest for small cells, sheeting, and ≥4 mitoses/10 HPF. In comparison, published concordance for gliomas in clinical trials have ranged from 8%-74%.


CONCLUSIONS
Our data suggest that current meningioma classification and grading are at least as objective and reproducible as for gliomas. Nevertheless, reproducibility remains suboptimal. Further improvements may be anticipated with education and clarification of subjective criteria, although development of biomarkers may be the most promising strategy.
Virginia Commonwealth University, Richmond, Virginia (C.L.R., M.S.A.); University of California, San Francisco, California (A.P., I.B.); NRG Oncology Statistics and Data Management Center, Philadelphia, Pennsylvnia (S.P.); Cleveland Clinic Foundation, Cleveland, Ohio (M.A.V., S.T.C.); Arizona Oncology Services Foundation, Phoenix, Arizona (D.B.); McMaster University, Hamilton, Ontario, Canada (W.M.); Medical University of South Carolina, Charleston, South Carolina (J.J.); University of Utah Health Science Center, Salt Lake City, Utah (D.S.); University Hospitals, Cleveland, Ohio (A.S.); Medical College of Wisconsin, Milwaukee, Wisconsin (J.B.); University of Maryland Medical System, Baltimore, Maryland (Y.K., M.M.); Carolinas Medical Center/Levine Cancer Institute, Charlotte, North Carolina (S.H.B.); Norton Cancer Institute, Louisville, Kentucky (A.C.S.); North Shore University Hospital CCOP, Manhasset, New York (B.B.).
C Leland
CL
Rogers
Virginia Commonwealth University, Richmond, Virginia (C.L.R., M.S.A.); University of California, San Francisco, California (A.P., I.B.); NRG Oncology Statistics and Data Management Center, Philadelphia, Pennsylvnia (S.P.); Cleveland Clinic Foundation, Cleveland, Ohio (M.A.V., S.T.C.); Arizona Oncology Services Foundation, Phoenix, Arizona (D.B.); McMaster University, Hamilton, Ontario, Canada (W.M.); Medical University of South Carolina, Charleston, South Carolina (J.J.); University of Utah Health Science Center, Salt Lake City, Utah (D.S.); University Hospitals, Cleveland, Ohio (A.S.); Medical College of Wisconsin, Milwaukee, Wisconsin (J.B.); University of Maryland Medical System, Baltimore, Maryland (Y.K., M.M.); Carolinas Medical Center/Levine Cancer Institute, Charlotte, North Carolina (S.H.B.); Norton Cancer Institute, Louisville, Kentucky (A.C.S.); North Shore University Hospital CCOP, Manhasset, New York (B.B.).
Arie
A
Perry
Virginia Commonwealth University, Richmond, Virginia (C.L.R., M.S.A.); University of California, San Francisco, California (A.P., I.B.); NRG Oncology Statistics and Data Management Center, Philadelphia, Pennsylvnia (S.P.); Cleveland Clinic Foundation, Cleveland, Ohio (M.A.V., S.T.C.); Arizona Oncology Services Foundation, Phoenix, Arizona (D.B.); McMaster University, Hamilton, Ontario, Canada (W.M.); Medical University of South Carolina, Charleston, South Carolina (J.J.); University of Utah Health Science Center, Salt Lake City, Utah (D.S.); University Hospitals, Cleveland, Ohio (A.S.); Medical College of Wisconsin, Milwaukee, Wisconsin (J.B.); University of Maryland Medical System, Baltimore, Maryland (Y.K., M.M.); Carolinas Medical Center/Levine Cancer Institute, Charlotte, North Carolina (S.H.B.); Norton Cancer Institute, Louisville, Kentucky (A.C.S.); North Shore University Hospital CCOP, Manhasset, New York (B.B.).
Stephanie
S
Pugh
Virginia Commonwealth University, Richmond, Virginia (C.L.R., M.S.A.); University of California, San Francisco, California (A.P., I.B.); NRG Oncology Statistics and Data Management Center, Philadelphia, Pennsylvnia (S.P.); Cleveland Clinic Foundation, Cleveland, Ohio (M.A.V., S.T.C.); Arizona Oncology Services Foundation, Phoenix, Arizona (D.B.); McMaster University, Hamilton, Ontario, Canada (W.M.); Medical University of South Carolina, Charleston, South Carolina (J.J.); University of Utah Health Science Center, Salt Lake City, Utah (D.S.); University Hospitals, Cleveland, Ohio (A.S.); Medical College of Wisconsin, Milwaukee, Wisconsin (J.B.); University of Maryland Medical System, Baltimore, Maryland (Y.K., M.M.); Carolinas Medical Center/Levine Cancer Institute, Charlotte, North Carolina (S.H.B.); Norton Cancer Institute, Louisville, Kentucky (A.C.S.); North Shore University Hospital CCOP, Manhasset, New York (B.B.).
Michael A
MA
Vogelbaum
Virginia Commonwealth University, Richmond, Virginia (C.L.R., M.S.A.); University of California, San Francisco, California (A.P., I.B.); NRG Oncology Statistics and Data Management Center, Philadelphia, Pennsylvnia (S.P.); Cleveland Clinic Foundation, Cleveland, Ohio (M.A.V., S.T.C.); Arizona Oncology Services Foundation, Phoenix, Arizona (D.B.); McMaster University, Hamilton, Ontario, Canada (W.M.); Medical University of South Carolina, Charleston, South Carolina (J.J.); University of Utah Health Science Center, Salt Lake City, Utah (D.S.); University Hospitals, Cleveland, Ohio (A.S.); Medical College of Wisconsin, Milwaukee, Wisconsin (J.B.); University of Maryland Medical System, Baltimore, Maryland (Y.K., M.M.); Carolinas Medical Center/Levine Cancer Institute, Charlotte, North Carolina (S.H.B.); Norton Cancer Institute, Louisville, Kentucky (A.C.S.); North Shore University Hospital CCOP, Manhasset, New York (B.B.).
David
D
Brachman
Virginia Commonwealth University, Richmond, Virginia (C.L.R., M.S.A.); University of California, San Francisco, California (A.P., I.B.); NRG Oncology Statistics and Data Management Center, Philadelphia, Pennsylvnia (S.P.); Cleveland Clinic Foundation, Cleveland, Ohio (M.A.V., S.T.C.); Arizona Oncology Services Foundation, Phoenix, Arizona (D.B.); McMaster University, Hamilton, Ontario, Canada (W.M.); Medical University of South Carolina, Charleston, South Carolina (J.J.); University of Utah Health Science Center, Salt Lake City, Utah (D.S.); University Hospitals, Cleveland, Ohio (A.S.); Medical College of Wisconsin, Milwaukee, Wisconsin (J.B.); University of Maryland Medical System, Baltimore, Maryland (Y.K., M.M.); Carolinas Medical Center/Levine Cancer Institute, Charlotte, North Carolina (S.H.B.); Norton Cancer Institute, Louisville, Kentucky (A.C.S.); North Shore University Hospital CCOP, Manhasset, New York (B.B.).
William
W
McMillan
Virginia Commonwealth University, Richmond, Virginia (C.L.R., M.S.A.); University of California, San Francisco, California (A.P., I.B.); NRG Oncology Statistics and Data Management Center, Philadelphia, Pennsylvnia (S.P.); Cleveland Clinic Foundation, Cleveland, Ohio (M.A.V., S.T.C.); Arizona Oncology Services Foundation, Phoenix, Arizona (D.B.); McMaster University, Hamilton, Ontario, Canada (W.M.); Medical University of South Carolina, Charleston, South Carolina (J.J.); University of Utah Health Science Center, Salt Lake City, Utah (D.S.); University Hospitals, Cleveland, Ohio (A.S.); Medical College of Wisconsin, Milwaukee, Wisconsin (J.B.); University of Maryland Medical System, Baltimore, Maryland (Y.K., M.M.); Carolinas Medical Center/Levine Cancer Institute, Charlotte, North Carolina (S.H.B.); Norton Cancer Institute, Louisville, Kentucky (A.C.S.); North Shore University Hospital CCOP, Manhasset, New York (B.B.).
Joseph
J
Jenrette
Virginia Commonwealth University, Richmond, Virginia (C.L.R., M.S.A.); University of California, San Francisco, California (A.P., I.B.); NRG Oncology Statistics and Data Management Center, Philadelphia, Pennsylvnia (S.P.); Cleveland Clinic Foundation, Cleveland, Ohio (M.A.V., S.T.C.); Arizona Oncology Services Foundation, Phoenix, Arizona (D.B.); McMaster University, Hamilton, Ontario, Canada (W.M.); Medical University of South Carolina, Charleston, South Carolina (J.J.); University of Utah Health Science Center, Salt Lake City, Utah (D.S.); University Hospitals, Cleveland, Ohio (A.S.); Medical College of Wisconsin, Milwaukee, Wisconsin (J.B.); University of Maryland Medical System, Baltimore, Maryland (Y.K., M.M.); Carolinas Medical Center/Levine Cancer Institute, Charlotte, North Carolina (S.H.B.); Norton Cancer Institute, Louisville, Kentucky (A.C.S.); North Shore University Hospital CCOP, Manhasset, New York (B.B.).
Igor
I
Barani
Virginia Commonwealth University, Richmond, Virginia (C.L.R., M.S.A.); University of California, San Francisco, California (A.P., I.B.); NRG Oncology Statistics and Data Management Center, Philadelphia, Pennsylvnia (S.P.); Cleveland Clinic Foundation, Cleveland, Ohio (M.A.V., S.T.C.); Arizona Oncology Services Foundation, Phoenix, Arizona (D.B.); McMaster University, Hamilton, Ontario, Canada (W.M.); Medical University of South Carolina, Charleston, South Carolina (J.J.); University of Utah Health Science Center, Salt Lake City, Utah (D.S.); University Hospitals, Cleveland, Ohio (A.S.); Medical College of Wisconsin, Milwaukee, Wisconsin (J.B.); University of Maryland Medical System, Baltimore, Maryland (Y.K., M.M.); Carolinas Medical Center/Levine Cancer Institute, Charlotte, North Carolina (S.H.B.); Norton Cancer Institute, Louisville, Kentucky (A.C.S.); North Shore University Hospital CCOP, Manhasset, New York (B.B.).
Dennis
D
Shrieve
Virginia Commonwealth University, Richmond, Virginia (C.L.R., M.S.A.); University of California, San Francisco, California (A.P., I.B.); NRG Oncology Statistics and Data Management Center, Philadelphia, Pennsylvnia (S.P.); Cleveland Clinic Foundation, Cleveland, Ohio (M.A.V., S.T.C.); Arizona Oncology Services Foundation, Phoenix, Arizona (D.B.); McMaster University, Hamilton, Ontario, Canada (W.M.); Medical University of South Carolina, Charleston, South Carolina (J.J.); University of Utah Health Science Center, Salt Lake City, Utah (D.S.); University Hospitals, Cleveland, Ohio (A.S.); Medical College of Wisconsin, Milwaukee, Wisconsin (J.B.); University of Maryland Medical System, Baltimore, Maryland (Y.K., M.M.); Carolinas Medical Center/Levine Cancer Institute, Charlotte, North Carolina (S.H.B.); Norton Cancer Institute, Louisville, Kentucky (A.C.S.); North Shore University Hospital CCOP, Manhasset, New York (B.B.).
Andy
A
Sloan
Virginia Commonwealth University, Richmond, Virginia (C.L.R., M.S.A.); University of California, San Francisco, California (A.P., I.B.); NRG Oncology Statistics and Data Management Center, Philadelphia, Pennsylvnia (S.P.); Cleveland Clinic Foundation, Cleveland, Ohio (M.A.V., S.T.C.); Arizona Oncology Services Foundation, Phoenix, Arizona (D.B.); McMaster University, Hamilton, Ontario, Canada (W.M.); Medical University of South Carolina, Charleston, South Carolina (J.J.); University of Utah Health Science Center, Salt Lake City, Utah (D.S.); University Hospitals, Cleveland, Ohio (A.S.); Medical College of Wisconsin, Milwaukee, Wisconsin (J.B.); University of Maryland Medical System, Baltimore, Maryland (Y.K., M.M.); Carolinas Medical Center/Levine Cancer Institute, Charlotte, North Carolina (S.H.B.); Norton Cancer Institute, Louisville, Kentucky (A.C.S.); North Shore University Hospital CCOP, Manhasset, New York (B.B.).
Joseph
J
Bovi
Virginia Commonwealth University, Richmond, Virginia (C.L.R., M.S.A.); University of California, San Francisco, California (A.P., I.B.); NRG Oncology Statistics and Data Management Center, Philadelphia, Pennsylvnia (S.P.); Cleveland Clinic Foundation, Cleveland, Ohio (M.A.V., S.T.C.); Arizona Oncology Services Foundation, Phoenix, Arizona (D.B.); McMaster University, Hamilton, Ontario, Canada (W.M.); Medical University of South Carolina, Charleston, South Carolina (J.J.); University of Utah Health Science Center, Salt Lake City, Utah (D.S.); University Hospitals, Cleveland, Ohio (A.S.); Medical College of Wisconsin, Milwaukee, Wisconsin (J.B.); University of Maryland Medical System, Baltimore, Maryland (Y.K., M.M.); Carolinas Medical Center/Levine Cancer Institute, Charlotte, North Carolina (S.H.B.); Norton Cancer Institute, Louisville, Kentucky (A.C.S.); North Shore University Hospital CCOP, Manhasset, New York (B.B.).
Young
Y
Kwok
Virginia Commonwealth University, Richmond, Virginia (C.L.R., M.S.A.); University of California, San Francisco, California (A.P., I.B.); NRG Oncology Statistics and Data Management Center, Philadelphia, Pennsylvnia (S.P.); Cleveland Clinic Foundation, Cleveland, Ohio (M.A.V., S.T.C.); Arizona Oncology Services Foundation, Phoenix, Arizona (D.B.); McMaster University, Hamilton, Ontario, Canada (W.M.); Medical University of South Carolina, Charleston, South Carolina (J.J.); University of Utah Health Science Center, Salt Lake City, Utah (D.S.); University Hospitals, Cleveland, Ohio (A.S.); Medical College of Wisconsin, Milwaukee, Wisconsin (J.B.); University of Maryland Medical System, Baltimore, Maryland (Y.K., M.M.); Carolinas Medical Center/Levine Cancer Institute, Charlotte, North Carolina (S.H.B.); Norton Cancer Institute, Louisville, Kentucky (A.C.S.); North Shore University Hospital CCOP, Manhasset, New York (B.B.).
Stuart H
SH
Burri
Virginia Commonwealth University, Richmond, Virginia (C.L.R., M.S.A.); University of California, San Francisco, California (A.P., I.B.); NRG Oncology Statistics and Data Management Center, Philadelphia, Pennsylvnia (S.P.); Cleveland Clinic Foundation, Cleveland, Ohio (M.A.V., S.T.C.); Arizona Oncology Services Foundation, Phoenix, Arizona (D.B.); McMaster University, Hamilton, Ontario, Canada (W.M.); Medical University of South Carolina, Charleston, South Carolina (J.J.); University of Utah Health Science Center, Salt Lake City, Utah (D.S.); University Hospitals, Cleveland, Ohio (A.S.); Medical College of Wisconsin, Milwaukee, Wisconsin (J.B.); University of Maryland Medical System, Baltimore, Maryland (Y.K., M.M.); Carolinas Medical Center/Levine Cancer Institute, Charlotte, North Carolina (S.H.B.); Norton Cancer Institute, Louisville, Kentucky (A.C.S.); North Shore University Hospital CCOP, Manhasset, New York (B.B.).
Samuel T
ST
Chao
Virginia Commonwealth University, Richmond, Virginia (C.L.R., M.S.A.); University of California, San Francisco, California (A.P., I.B.); NRG Oncology Statistics and Data Management Center, Philadelphia, Pennsylvnia (S.P.); Cleveland Clinic Foundation, Cleveland, Ohio (M.A.V., S.T.C.); Arizona Oncology Services Foundation, Phoenix, Arizona (D.B.); McMaster University, Hamilton, Ontario, Canada (W.M.); Medical University of South Carolina, Charleston, South Carolina (J.J.); University of Utah Health Science Center, Salt Lake City, Utah (D.S.); University Hospitals, Cleveland, Ohio (A.S.); Medical College of Wisconsin, Milwaukee, Wisconsin (J.B.); University of Maryland Medical System, Baltimore, Maryland (Y.K., M.M.); Carolinas Medical Center/Levine Cancer Institute, Charlotte, North Carolina (S.H.B.); Norton Cancer Institute, Louisville, Kentucky (A.C.S.); North Shore University Hospital CCOP, Manhasset, New York (B.B.).
Aaron C
AC
Spalding
Virginia Commonwealth University, Richmond, Virginia (C.L.R., M.S.A.); University of California, San Francisco, California (A.P., I.B.); NRG Oncology Statistics and Data Management Center, Philadelphia, Pennsylvnia (S.P.); Cleveland Clinic Foundation, Cleveland, Ohio (M.A.V., S.T.C.); Arizona Oncology Services Foundation, Phoenix, Arizona (D.B.); McMaster University, Hamilton, Ontario, Canada (W.M.); Medical University of South Carolina, Charleston, South Carolina (J.J.); University of Utah Health Science Center, Salt Lake City, Utah (D.S.); University Hospitals, Cleveland, Ohio (A.S.); Medical College of Wisconsin, Milwaukee, Wisconsin (J.B.); University of Maryland Medical System, Baltimore, Maryland (Y.K., M.M.); Carolinas Medical Center/Levine Cancer Institute, Charlotte, North Carolina (S.H.B.); Norton Cancer Institute, Louisville, Kentucky (A.C.S.); North Shore University Hospital CCOP, Manhasset, New York (B.B.).
Mitchell S
MS
Anscher
Virginia Commonwealth University, Richmond, Virginia (C.L.R., M.S.A.); University of California, San Francisco, California (A.P., I.B.); NRG Oncology Statistics and Data Management Center, Philadelphia, Pennsylvnia (S.P.); Cleveland Clinic Foundation, Cleveland, Ohio (M.A.V., S.T.C.); Arizona Oncology Services Foundation, Phoenix, Arizona (D.B.); McMaster University, Hamilton, Ontario, Canada (W.M.); Medical University of South Carolina, Charleston, South Carolina (J.J.); University of Utah Health Science Center, Salt Lake City, Utah (D.S.); University Hospitals, Cleveland, Ohio (A.S.); Medical College of Wisconsin, Milwaukee, Wisconsin (J.B.); University of Maryland Medical System, Baltimore, Maryland (Y.K., M.M.); Carolinas Medical Center/Levine Cancer Institute, Charlotte, North Carolina (S.H.B.); Norton Cancer Institute, Louisville, Kentucky (A.C.S.); North Shore University Hospital CCOP, Manhasset, New York (B.B.).
Beatrice
B
Bloom
Virginia Commonwealth University, Richmond, Virginia (C.L.R., M.S.A.); University of California, San Francisco, California (A.P., I.B.); NRG Oncology Statistics and Data Management Center, Philadelphia, Pennsylvnia (S.P.); Cleveland Clinic Foundation, Cleveland, Ohio (M.A.V., S.T.C.); Arizona Oncology Services Foundation, Phoenix, Arizona (D.B.); McMaster University, Hamilton, Ontario, Canada (W.M.); Medical University of South Carolina, Charleston, South Carolina (J.J.); University of Utah Health Science Center, Salt Lake City, Utah (D.S.); University Hospitals, Cleveland, Ohio (A.S.); Medical College of Wisconsin, Milwaukee, Wisconsin (J.B.); University of Maryland Medical System, Baltimore, Maryland (Y.K., M.M.); Carolinas Medical Center/Levine Cancer Institute, Charlotte, North Carolina (S.H.B.); Norton Cancer Institute, Louisville, Kentucky (A.C.S.); North Shore University Hospital CCOP, Manhasset, New York (B.B.).
Minesh
M
Mehta
D015331:Cohort Studies; D006801:Humans; D008577:Meningeal Neoplasms / Q000145:classification* / Q000473:pathology* / Q000601:surgery; D008579:Meningioma / Q000145:classification* / Q000473:pathology* / Q000601:surgery; D060787:Neoplasm Grading; D015588:Observer Variation; D011379:Prognosis
concordance; cooperative group trial; meningioma; pathology; tumor grade