| Objective: This study aimed to describe the incidence and trends of atypical meningiomas,explore risk factors on prognosis,especially the extent of tumor resection and the postoperative radiotherapy(PORT),and analyze the relationship between molecular grade and prognosis of atypical meningioma.Methods:(1)The data of atypical meningiomas patients was extracted from the Surveillance,Epidemiology and End Results(SEER)database from 2004 to 2018.The characteristics of incidence and trends were collected through the National Cancer Institute’s joint regression analysis by calculating annual percentage change(APC).(2)The information on atypical meningiomas patients were extracted from the SEER database and Tongji hospital,Tongji Medical College,Huazhong University of Science and Technology from 2010 to 2021,respectively.The Cox regression model was used to explore the influencing factors of prognosis.(3)Molecular parameters including chromosomal states of 1p,6q,and 10 q,telomerase reverse transcriptase(TERT)promoter mutations,and homozygous deletion of the cyclin-dependent kinase inhibitor 2A/B(CDKN2A/B)in atypical meninges between 2010 and 2020 were collected,then the molecular grade was carried out(high/intermediate/low-risk grade).The ability of molecular grade to predict prognosis was further analyzed.(4)Literature on the prognosis of atypical meningioma with GTR was retrieved and systematically analyzed from Web of Science,PubMed,Embase,and other databases between the date of establishment of the database to December 2022.The effect of PORT on recurrence rates,5-progression-free survival(PFS),and 5-overall survival(OS)after gross-total resection(GTR)of atypical meningioma were analyzed.Results:(1)A total of 4 476 atypical meningiomas were enrolled in the SEER database between 2004 to 2018.The annual incidence of atypical meningiomas was 3.298 per million people.The APC was 6.3%(P = 0.001),1.4%(P = 0.760),and 7.1%(P < 0.001)in the range of 2004-2009,2009-2012,and 2012-2018,respectively.(2)A total of 3 854 atypical meningiomas of the SEER database and 105 atypical meningiomas in our center were enrolled in the prognostic analysis.Multivariate Cox regression analysis showed that GTR significantly improved OS(P all <0.05).PORT did not prolong OS.Multivariate Cox regression analysis showed PORT was an independent predictor of recurrence-free survival(RFS)(P = 0.015).(3)The molecular parameters of 98 atypical meningioma patients were assessed for a molecular grade.Among them,13(13.3%)were in the low-risk group,63(64.3%)in the intermediate-risk group,and 22(22.4%)in the high-risk group.The molecular grade was an independent risk factor for RFS(P < 0.001)and OS(P = 0.003)in patients with atypical meningioma by multivariate Cox analyses.Atypical meningioma patients with higher risk grades harbored shorted RFS and OS.(4)Meta-analysis indicated that PORT could significantly reduce the recurrence rate(P < 0.001),and improve 5-PFS(P = 0.018),but could not improve 5-OS(P = 0.640)in patients with atypical meningiomas who underwent GTR.Conclusion:(1)The incidence of atypical meningiomas increased between 2004 to 2108.(2)PORT prolonged RFS and did not prolong OS in atypical meningioma patients.(3)PORT can significantly reduce the recurrence rate and improve 5-PFS,but it could not prolong the 5-OS in atypical meningioma patients with GTR.(4)Molecular grade can accurately identify patients at high risk of recurrence and death,and accurately predict prognosis in atypical meningiomas patients.Part Ⅰ: The prognostic factors of atypical meningiomas: a SEER-based studyObjective: The detection of brain invasion was integrated as a stand-alone criterion for atypical meningioma in the 2016 WHO classification.And this change may result in an increased incidence of atypical meningiomas.Given the raised incidence,progressive behavior,and higher risk of recurrence,it is important to establish an effective management strategy.This retrospective study collected data from the SEER database to analyze the incidence,its trend,and prognostic factors,especially the extent of tumor resection and PORT.Methods: The information on atypical meningiomas patients was extracted from the SEER database from 2004 to 2018.Characteristics of patients and tumors,treatments,and patient survival data were collected by inclusion and exclusion criteria.The incidence and its trends were collected through the National Cancer Institute’s joint regression analysis by calculating its APC.The multivariate Cox regression analysis was performed to explore independent prognostic factors.Results:(1)A total of 4 476 atypical meningiomas in the SEER database between 2004 and 2018 were included.The annual incidence of atypical meningiomas was 3.298 per million people.The APC was 6.3%(P = 0.001),1.4%(P = 0.760),and 7.1%(P < 0.001)in the range of 2004-2009,2009-2012,and 2012-2018,respectively.(2)Multivariate Cox regression analysis found that age at diagnosis(P < 0.001),gender(P = 0.015),ethnicity(P < 0.001),tumor size(P < 0.001),and extent of tumor resection(P < 0.001)were independent predictors of survival.PORT was not associated with OS in atypical meningioma patients.(3)Multivariate Cox regression analysis of OS involved 2 217 atypical meningioma patients who received GTR showed that age(P < 0.001)and tumor size(P = 0.001)were independent influencing factors.There was no significant difference in OS between patients with PORT and without PORT(P = 0.364).Conclusion: The incidence of atypical meningiomas increased between 2004 to 2018.Age ≥ 65 years,tumor with a diameter ≥ 53 mm,and non-GTR were associated with worse OS.Meanwhile,PORT of atypical meningiomas patients could not prolong OS,and PORT of the GTR subgroup also could not improve OS.Part Ⅱ: Prognostic factors of atypical meningioma: a single-center retrospective studyObjective: Tumor grade and extent of resection influence the prognosis of atypical meningioma.However,the WHO grade does not inconsistency with the biological behavior of meningiomas sometimes.With the development of molecular biology techniques,some studies have found molecular markers related to histological subtypes,grades,and prognosis of atypical meningioma recently.In 2021,WHO CNS5 proposed the integration of molecular and histological parameters for the diagnosis and management of meningiomas.Therefore,this study focused on molecular grade and verified the correlations between this classification and prognosis.Methods: The data was extracted from Tongji hospital,Tongji Medical College,Huazhong University of Science and Technology between 2010 and 2021.The risk factors affecting the prognosis were tested by Cox regression analysis.Molecular parameters including chromosomal states of 1p,6q,and 10 q,TERT promoter mutations,and homozygous deletion of CDKN2A/B in atypical meninges between 2010 and 2020 were collected,and then the molecular grade was carried out(high-risk /intermediate-risk /low-risk grade).The ability of molecular grade to predict prognosis was further analyzed.Results:(1)A total of 105 atypical meningioma patients between 2010 and 2021 were finally enrolled by inclusion and exclusion criteria.Multivariate Cox regression analysis showed that the intratumoral necrosis(P = 0.022),the extent of tumor resection(P < 0.001),and PORT(P = 0.015)were independent predictors of RFS of atypical meningioma.Meanwhile,multivariate Cox regression analysis showed that age at diagnosis(P = 0.003),tumor size(P = 0.013),and extent of tumor resection(P = 0.004)were independent predictors of OS.PORT had no significant effect on OS(P = 0.753).(2)Multivariate Cox regression analysis of prognosis in 87 GTR patients showed that PORT tended to prolong RFS(P = 0.065).Ki-67 index ≥ 10%(P = 0.040)was an independent prognostic factor influencing survival.PORT had no significant effect on the OS of atypical meningioma patients who underwent GTR(P = 0.889).(3)The molecular parameters of 98 atypical meningioma patients were assessed for molecular grade.Among them,13(13.3%)were in the low-risk group,63(64.3%)in the intermediate-risk group,and 22(22.4%)in the highrisk group.The molecular grade was an independent factor for RFS(P < 0.001)and OS(P = 0.003).Atypical meningioma patients with higher risk grades harbored shorted RFS and OS.Conclusion: There are many factors affecting RFS and OS in atypical meningioma patients.PORT significantly prolonged RFS in patients with atypical meningioma,and there was a tendency to prolong RFS in patients who underwent GTR.Meanwhile,PORT was not an independent prognostic factor affecting OS in atypical meningioma patients and patients who underwent GTR.Molecular risk grade can accurately identify patients at high risk of recurrence and death,and accurately predict the prognosis of atypical meningiomas patients.Part Ⅲ: Meta-analysis of the effectiveness of postoperative adjuvant radiotherapy in atypical meningioma patients after gross total resectionObjective: The primary treatment of atypical meningioma is surgery.PORT is an important adjuvant treatment of atypical meningioma.The 2021 National Comprehensive Cancer Network and European Association for Neuro-Oncology guidelines do not identify the application of PORT after GTR in patients with atypical meningiomas.This study aims to explore the effectiveness of PORT after GTR in patients with atypical meningiomas through a meta-analysis and hopes to provide a reference.Methods: Literature on the prognosis of atypical meningioma with GTR was retrieved and systematically analyzed from Web of Science,PubMed,Embase,and other databases between the date of establishment of the database to December 2022.The literature was enrolled according to inclusion and exclusion criteria and was evaluated for study quality.The effects of PORT on recurrence rates,5-PFS,and 5-OS after GTR of atypical meningioma were systematically analyzed.Results: Finally,28 literature with a total of 4 275 patients were included in the metaanalysis.And 3 227 patients received GTR and 840 patients received PORT after GTR.PORT could significantly reduce the recurrence rate(OR = 0.50,95% CI: 0.38-0.68,P < 0.001),improve 5-PFS(OR = 0.51,95% CI: 0.30-0.89,P = 0.018),but could not improve 5-OS(OR = 0.89,95% CI: 0.54-1.46,P = 0.640)in patients with atypical meningiomas who underwent GTR.Conclusion: PORT can significantly reduce the recurrence rate and prolong 5-PFS,but it could not prolong the 5-OS in atypical meningioma patients who underwent GTR. |
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