A prognostic cytogenetic scoring system to guide the adjuvant management of patients with atypical meningioma.
BACKGROUND
The appropriate use of adjuvant therapy in patients with gross totally resected atypical meningioma requires an accurate assessment of recurrence risk. We sought to determine whether cytogenetic/genetic characterization may facilitate better estimation of the probability of recurrence.


METHODS
We first analyzed our clinical database, including high-resolution DNA copy number data, to identify 11 common copy number aberrations in a pilot cohort of meningiomas of all grades. We summed these aberrations to devise a cytogenetic abnormality score (CAS) and determined the CAS from archived tissue of a separate cohort of 32 patients with gross totally resected atypical meningioma managed with surgery alone. Propensity score adjusted Cox regression was used to determine whether the CAS was predictive of recurrence.


RESULTS
An association between higher CAS and higher grade was noted in our pilot cohort with heterogeneity among atypical tumors. Among the 32 patients who underwent gross total resection of an atypical meningioma, the CAS was not significantly associated with age, gender, performance status, or tumor size/location but was associated with the risk of recurrence on univariable analysis (hazard ratio per aberration = 1.52; 95% CI = 1.08-2.14; P = .02). After adjustment, the impact of the dichotomized number of copy aberrations remained significantly associated with recurrence risk (hazard ratio = 4.47; 95% CI = 1.01-19.87; P = .05).


CONCLUSIONS
The number of copy number aberrations is strongly associated with recurrence risk in patients with atypical meningioma following gross total resection and may inform the appropriate use of adjuvant radiation therapy in these patients or be useful for stratification in clinical trials.
Department of Radiation Oncology, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts (A.A.A., M.C.H., N.D.A., B.M.A.); Department of Pathology, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts (M.A., K.L.L., A.H.L., S.S.); Department of Neurosurgery, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts (W.L.B., O.A-M., I.F.D.); Center for Neuro-Oncology, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts (E.Q.L., L.N., M.L.R., A.D.N., D.A.R., P.Y.W., R.B.).
Ayal A
AA
Aizer
Department of Radiation Oncology, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts (A.A.A., M.C.H., N.D.A., B.M.A.); Department of Pathology, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts (M.A., K.L.L., A.H.L., S.S.); Department of Neurosurgery, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts (W.L.B., O.A-M., I.F.D.); Center for Neuro-Oncology, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts (E.Q.L., L.N., M.L.R., A.D.N., D.A.R., P.Y.W., R.B.).
Malak
M
Abedalthagafi
Department of Radiation Oncology, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts (A.A.A., M.C.H., N.D.A., B.M.A.); Department of Pathology, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts (M.A., K.L.L., A.H.L., S.S.); Department of Neurosurgery, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts (W.L.B., O.A-M., I.F.D.); Center for Neuro-Oncology, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts (E.Q.L., L.N., M.L.R., A.D.N., D.A.R., P.Y.W., R.B.).
Wenya Linda
WL
Bi
Department of Radiation Oncology, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts (A.A.A., M.C.H., N.D.A., B.M.A.); Department of Pathology, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts (M.A., K.L.L., A.H.L., S.S.); Department of Neurosurgery, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts (W.L.B., O.A-M., I.F.D.); Center for Neuro-Oncology, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts (E.Q.L., L.N., M.L.R., A.D.N., D.A.R., P.Y.W., R.B.).
Margaret C
MC
Horvath
Department of Radiation Oncology, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts (A.A.A., M.C.H., N.D.A., B.M.A.); Department of Pathology, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts (M.A., K.L.L., A.H.L., S.S.); Department of Neurosurgery, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts (W.L.B., O.A-M., I.F.D.); Center for Neuro-Oncology, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts (E.Q.L., L.N., M.L.R., A.D.N., D.A.R., P.Y.W., R.B.).
Nils D
ND
Arvold
Department of Radiation Oncology, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts (A.A.A., M.C.H., N.D.A., B.M.A.); Department of Pathology, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts (M.A., K.L.L., A.H.L., S.S.); Department of Neurosurgery, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts (W.L.B., O.A-M., I.F.D.); Center for Neuro-Oncology, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts (E.Q.L., L.N., M.L.R., A.D.N., D.A.R., P.Y.W., R.B.).
Ossama
O
Al-Mefty
Department of Radiation Oncology, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts (A.A.A., M.C.H., N.D.A., B.M.A.); Department of Pathology, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts (M.A., K.L.L., A.H.L., S.S.); Department of Neurosurgery, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts (W.L.B., O.A-M., I.F.D.); Center for Neuro-Oncology, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts (E.Q.L., L.N., M.L.R., A.D.N., D.A.R., P.Y.W., R.B.).
Eudocia Q
EQ
Lee
Department of Radiation Oncology, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts (A.A.A., M.C.H., N.D.A., B.M.A.); Department of Pathology, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts (M.A., K.L.L., A.H.L., S.S.); Department of Neurosurgery, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts (W.L.B., O.A-M., I.F.D.); Center for Neuro-Oncology, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts (E.Q.L., L.N., M.L.R., A.D.N., D.A.R., P.Y.W., R.B.).
Lakshmi
L
Nayak
Department of Radiation Oncology, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts (A.A.A., M.C.H., N.D.A., B.M.A.); Department of Pathology, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts (M.A., K.L.L., A.H.L., S.S.); Department of Neurosurgery, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts (W.L.B., O.A-M., I.F.D.); Center for Neuro-Oncology, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts (E.Q.L., L.N., M.L.R., A.D.N., D.A.R., P.Y.W., R.B.).
Mikael L
ML
Rinne
Department of Radiation Oncology, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts (A.A.A., M.C.H., N.D.A., B.M.A.); Department of Pathology, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts (M.A., K.L.L., A.H.L., S.S.); Department of Neurosurgery, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts (W.L.B., O.A-M., I.F.D.); Center for Neuro-Oncology, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts (E.Q.L., L.N., M.L.R., A.D.N., D.A.R., P.Y.W., R.B.).
Andrew D
AD
Norden
Department of Radiation Oncology, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts (A.A.A., M.C.H., N.D.A., B.M.A.); Department of Pathology, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts (M.A., K.L.L., A.H.L., S.S.); Department of Neurosurgery, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts (W.L.B., O.A-M., I.F.D.); Center for Neuro-Oncology, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts (E.Q.L., L.N., M.L.R., A.D.N., D.A.R., P.Y.W., R.B.).
David A
DA
Reardon
Department of Radiation Oncology, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts (A.A.A., M.C.H., N.D.A., B.M.A.); Department of Pathology, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts (M.A., K.L.L., A.H.L., S.S.); Department of Neurosurgery, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts (W.L.B., O.A-M., I.F.D.); Center for Neuro-Oncology, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts (E.Q.L., L.N., M.L.R., A.D.N., D.A.R., P.Y.W., R.B.).
Patrick Y
PY
Wen
Department of Radiation Oncology, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts (A.A.A., M.C.H., N.D.A., B.M.A.); Department of Pathology, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts (M.A., K.L.L., A.H.L., S.S.); Department of Neurosurgery, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts (W.L.B., O.A-M., I.F.D.); Center for Neuro-Oncology, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts (E.Q.L., L.N., M.L.R., A.D.N., D.A.R., P.Y.W., R.B.).
Keith L
KL
Ligon
Department of Radiation Oncology, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts (A.A.A., M.C.H., N.D.A., B.M.A.); Department of Pathology, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts (M.A., K.L.L., A.H.L., S.S.); Department of Neurosurgery, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts (W.L.B., O.A-M., I.F.D.); Center for Neuro-Oncology, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts (E.Q.L., L.N., M.L.R., A.D.N., D.A.R., P.Y.W., R.B.).
Azra H
AH
Ligon
Department of Radiation Oncology, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts (A.A.A., M.C.H., N.D.A., B.M.A.); Department of Pathology, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts (M.A., K.L.L., A.H.L., S.S.); Department of Neurosurgery, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts (W.L.B., O.A-M., I.F.D.); Center for Neuro-Oncology, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts (E.Q.L., L.N., M.L.R., A.D.N., D.A.R., P.Y.W., R.B.).
Rameen
R
Beroukhim
Department of Radiation Oncology, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts (A.A.A., M.C.H., N.D.A., B.M.A.); Department of Pathology, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts (M.A., K.L.L., A.H.L., S.S.); Department of Neurosurgery, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts (W.L.B., O.A-M., I.F.D.); Center for Neuro-Oncology, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts (E.Q.L., L.N., M.L.R., A.D.N., D.A.R., P.Y.W., R.B.).
Ian F
IF
Dunn
Department of Radiation Oncology, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts (A.A.A., M.C.H., N.D.A., B.M.A.); Department of Pathology, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts (M.A., K.L.L., A.H.L., S.S.); Department of Neurosurgery, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts (W.L.B., O.A-M., I.F.D.); Center for Neuro-Oncology, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts (E.Q.L., L.N., M.L.R., A.D.N., D.A.R., P.Y.W., R.B.).
Sandro
S
Santagata
Department of Radiation Oncology, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts (A.A.A., M.C.H., N.D.A., B.M.A.); Department of Pathology, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts (M.A., K.L.L., A.H.L., S.S.); Department of Neurosurgery, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts (W.L.B., O.A-M., I.F.D.); Center for Neuro-Oncology, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts (E.Q.L., L.N., M.L.R., A.D.N., D.A.R., P.Y.W., R.B.).
Brian M
BM
Alexander
D000465:Algorithms; D059186:Chemoradiotherapy, Adjuvant; D015331:Cohort Studies; D055028:Comparative Genomic Hybridization; D056915:DNA Copy Number Variations; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008577:Meningeal Neoplasms / Q000235:genetics / Q000473:pathology* / Q000628:therapy; D008579:Meningioma / Q000235:genetics / Q000473:pathology* / Q000628:therapy; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000235:genetics / Q000473:pathology* / Q000628:therapy; D009367:Neoplasm Staging; D010865:Pilot Projects; D011379:Prognosis; D015996:Survival Rate
atypical; copy number; meningioma; recurrence; resected