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DeMonte, Franco

Kamiya-Matsuoka, Carlos

McGovern, Susan L

Raza, Shaan M

Rubino, Franco

Schur, Solon

English

OpenWorks @ MD Anderson

Introduction and objective:Long-term follow up of meningiomas has demonstrated recurrence rates ofup to 60% after 15 years. There is limited data available to guide themanagement of recurrent and previously radiated skull base meningiomasand challenges related to salvage surgery, re-irradiation and lack of clearsystemic therapy strategies remain. In this study, we analyzed data fromour experience with recurrent and previously radiated meningiomas toassess the impact of salvage surgery and re-irradiation on PFS.References:1) Abry E, Thomassen IØ, Salvesen ØO, Torp SH: The significance of Ki-67/MIB-1 labeling index in human meningiomas: a literature study. Pathology-Research and Practice 206:810-815, 20102) Aras S, Ozkanli S, Erdem E, Gokalp S, Meral G, Erdogan CE: Investigation of Low and High DoseRate X-Ray Effects on Histopathological Changes and Prognostic Importance of Ki-67 In LaryngealCancer Radiotherapy. Available at SSRN 40372883) Porta et al. Pain Digest Pain Pain 1998;8:346-3523) Momin AA, Shao J, Soni P, Almeida JP, Suh JH, Murphy ES, et al: Outcomes of salvage radiation forrecurrent world health organization grade II meningiomas: a retrospective cohort study. Journal ofNeuro-Oncology 152:373-382, 20214) Clark VE, Erson-Omay Ez Fau - Serin A, Serin A Fau - Yin J, Yin J Fau - Cotney J, Cotney J Fau -Ozduman K, Ozduman K Fau - Avşar T, et al: Genomic analysis of non-NF2 meningiomas revealsmutations in TRAF7, KLF4, AKT1, and SMO.5) Goldbrunner R, Minniti G, Preusser M, Jenkinson MD, Sallabanda K, Houdart E, et al: EANOguidelines for the diagnosis and treatment of meningiomas, in, 2016, pp 383-3836) Durand A, Labrousse F, Jouvet A, Bauchet L, Kalamaridès M, Menei P, et al: WHO grade II and IIImeningiomas: a study of prognostic factors. Journal of neuro-oncology 95:367-375, 2009Methods:A retrospective cohort study of 48 patients with recurrent and previouslyradiated meningiomas who were treated between 1995 and 2021 wasconducted. Data were extracted from medical records and include clinical,radiologic, and pathologic reports. Patients were clustered according toWHO grades. We analyzed the complications related to re-irradiation andsalvage surgery and the impact of different treatment modalities on PFSusing Cox proportional hazard ratios.Title of the Poster Presentation Goes HereAuthors of the Poster Presentation Goes HereInstitutional and/or Graduate School of Biomedical Sciences Affiliation Goes Here Impact of Salvage Surgery and Re-irradiation for Radiation Failed Recurrent Skull Base MeningiomasFranco Rubino MD1; Solon Schur MD1; Susan L. McGovern MD2; Carlos Kamiya-Matsuoka MD3;  Franco DeMonte MD1; Shaan M. Raza MD11Department of Neurosurgery, Divisio  of Surgery, MD Anderson Cancer Center;  2 Department of Radiation On ology, Division of Radiatio  Onc logy, MD Anderson Cancer Center; 3 Department of Neuro-oncology, Division of Cancer Medicine, MD Anderson Cancer CenterFigure 1. Diagram outlining patient selectionFigure 2. A: Progression-free survival (PFS) according to WHO grades, asterisk indicates astatistically significant difference (p=<.0001). B: PFS according to age, asterisk indicates astatistically significant difference (p=.0025). C: PFS of WHO grade 1 radiated meningiomas bydifferent treatment modalities (p=.162), SX (surgery), reRT (re-irradiation). D: PFS of WHOgrade 1 radiated meningiomas by extent of resection (EOR) (p=.0087).Figure 3. A: Progression-free survival (PFS) of WHO grade 2 radiated meningiomas by differenttreatment modalities, asterisk indicates a statistically significant difference (reRT alone vs SXalone; p=.0238 and reRT+SX vs SX alone; p=.0008). B: PFS of WHO grade 2 radiatedmeningiomas by extent of resection (EOR) (p=.139). C: PFS of WHO grade 3 radiatedmeningiomas by different treatment modalities, asterisk indicates a statistically significantdifference (p=.0028). D: PFS of WHO grade 3 radiated meningiomas by EOR (p=.299).Results:• Patient Demographics and number of recurrencesForty-eight patients (33 WHO grade 1; 11 WHO grade 2; and 4 WHO grade3) were treated for 143 recurrences after their first radiation treatment.Although patients with higher grade meningiomas seem to have lower KPSat recurrence, there was no significant association between KPS andrecurrence rate (X2 [1, N = 143] =3.52, p=.06). The overall survival rate was56.2% after a mean follow-up period of 12.4±7.6 years, with 21 patientswith stable disease and 6 patients in hospice. Twenty patients from ourcohort (41.6%) had histologic progression (Figure 1 and Table 1).• Treatment offered to recurrencesSurgery alone (SX) was the most frequent treatment offered for recurrencesin WHO grade 1 and WHO grade 2 patients (37% and 19.8%, respectively).Patients with GTR had a median time to recurrence of 123, 15 and 6months for WHO grade 1, WHO grade 2 and WHO grade 3, respectively.Surgical procedures had a complication rate of 23.8% (20/84), and this rateincreased over time: 10% (1/10), 18.4% (7/38), 100% (1/1), 39.3% (11/28)and 100% (1/1) for first, second, third, fourth and fifth surgeries,respectively.Re-irradiation therapy was administered for seventy-three recurrences. Re-irradiation was used along the course of the disease one, two and threetime in 32 (66.7%), 13 (27%) and 3 patients (6.3%). Among them, 38 (52%)patients received EBRT, and 35 (48%) patients received SRS, with differentdoses.• Analysis of Factors Associated with PFSUpon conducting univariate log-rank and Cox proportional hazards analysis,we identified those variables that correlated with higher recurrence rate.Among demographics variables, the 3-year PFS was 43.5%, 24.5% and0%, for WHO grade 1, WHO grade 2 and WHO grade 3, respectively(Figure 2, A).Furthermore, age ≥60 years-old was associated with increased progression(HR 1.68; 95% CI, 1.15-2.44; p=.0025) (Figure 2, B). As seen in Table 2,patients with WHO grade 1 meningiomas who underwent a STR had a 3.4-fold increase of disease progression compared to patients where GTR wasachieved (HR 3.38; 95% CI, 1.268-9.03; p=.0189) (Figure 2, D). For WHOgrade 2 and 3 patients however, EOR was not associated with differences inPFS (Figure 3, B and D).Furthermore, age ≥60 years-old was associated with increased progression(HR 1.68; 95% CI, 1.15-2.44; p=.0025) (Figure 2, B).Table 1. Treatment Outcomes When looking at the impact of re-irradiation, WHO grade 3 patients whowere re-irradiated were significantly less likely to progress over thecourse of the study (HR 0.27; 95% CI, 0.078-0.975; p=.0028) (Figure 3,C). Furthermore, adjuvant re-irradiation of subtotally or totally resectedWHO grade 2 meningioma patients decreased the likelihood of diseaseprogression over the course of the study (HR 0.316; 95% CI, 0.1304-0.7682; p=.0029 for STR+RT and HR 0.259; 95% CI, 0.099-0.6747;p=.0048 for GTR+RT). (Figure 3, A). Repeat radiation was not found tobe associated with improved PFS in WHO grade 1 meningioma patients(Table 2).UNIVARIATE ANALYSIS HR CI (95%)Median PFS (months)P-ValuePatient demographicsAge <60 years-old Ref Ref 30 -≥60 years-old 1.68 1.156-2.443 11 0.0025KPS KPS 90-100 Ref Ref 26 -KPS 60-80 2.61 1.510-4.50 7 ˂0.0001Gender Female Ref Ref 15 -Male 1.288 0.8564-1.938 20 0.971Tumor featuresLocation AF/MF/PF/Combined - - - 0.2535Form Globoid Ref Ref 12 -En-Plaque 1.001 0.7012-1.429 20 0.1968WHO grade WHO 1 Ref Ref 30 -WHO 2 1.972 1.269-3.067 12 0.0002WHO 3 3.563 1.628-7.798 6 ˂0.0001KI-67 KI-67 0-9% Ref Ref 51 -KI-67 10-19% 2.285 1.249-4.178 12 0.003KI-67 ≥20% 3.426 1.771-6.628 6 ˂0.0001Treatment Related VariablesType of reRT SRS Ref Ref 28 -EBRT 0.8507 0.5280-1.371 36 0.483Treatment Modality WHO I SX Ref Ref 230.162SX + reRT - - 28reRT - - 32Systemic Therapy - - 14.5Treatment Modality WHO II SX Ref Ref 9 -SX + reRT 0.365 0.175-0.757 41 0.0008reRT 0.457 0.218-0.959 22 0.0238Systemic Therapy1 - - 18 -Treatment Modality WHO III SX Ref Ref 5.5 -SX + reRT 0.653 0.184-2.32 7 0.468reRT 0.276 0.078-0.975 14 0.0028EOR in WHO I GTR Ref Ref 123 -STR +/- reRT 0.2760 0.1272-0.5987 15 0.0087EOR in WHO II GTR +/- reRT2 Ref Ref 15 -STR +/- reRT3 0.8919 0.4321-1.841 9 0.139EOR in WHO III GTR +/- reRT Ref Ref 5.5 -STR +/- reRT 1.649 0.5297-5.132 7 0.2991Only 3 patients, unpowered for statistical purposes2 GTR + reRT = RR 0.259, 95% CI 0.099-0.6747, p=.0048, Median PFS=27 months3 STR + reRT= RR 0.316, 95% CI 0.1304-0.7682, p=.0029, Median PFS=52 monthsBold letters indicate statistical significanceTable 2. Univariate Analysis of prognostic factors affecting PFS Discussion:To our knowledge, this is the largest reported cohort of post-radiationrecurrent skull base meningiomas summarizing the impact of salvagesurgery and repeat radiation on tumor control rates. The management ofpost-radiation recurrence is not clear, but the decision should consider theWHO grading, along with the multidisciplinary treatments available.For WHO 1 meningiomas, despite the challenges associated withprevious radiation, we found a clear benefit of GTR over STR alone orcombined with RT. The impact of EOR on outcomes for WHO grade 2meningiomas remains unclear and is even less effective in malignantmeningiomas. One hypothesis to explain the lack of correlation betweenEOR and PFS could be the more aggressive behavior and a higherproliferative index labeling in tumors that recur versus tumors that don’trecur1. Furthermore, previous radiation might be a risk factor to increasethe aggressiveness of the tumor2.As seen in Table 2, patients with WHO grade 1 meningiomas whounderwent a STR had a 3.4-fold increase of disease progressioncompared to patients where GTR was achieved (HR 3.38; 95% CI,1.268-9.03; p=.0189) (Figure 2, D). For WHO grade 2 and 3 patientshowever, EOR was not associated with differences in PFS (Figure 3, Band D).This study also helps elucidate the potential role of re-irradiation withrecurrent skull base meningiomas. In our cohort, there were noassociated improvements in PFS with re-irradiation of grade 1meningiomas. Conversely, the role of radiation seems to be moreimportant for WHO 2 and WHO 3 meningiomas. Indeed, we found animprovement in PFS for re-irradiated WHO grade 2 meningiomas, but thisfinding is opposed to other authors3. Nevertheless, it is important tohighlight that our patient cohort consisted exclusively of skull basemeningiomas, which have a different genomic signature than convexitymeningiomas and have different biological and clinical behavior4. Althoughsurvival and tumor control are poor in WHO grade 3 meningiomas, thereis a consensus on the beneficial effect of radiation, irrespective of theEOR5, and in our cohort of anaplastic meningiomas, re-irradiationprovided a PFS benefit when compared with surgery alone,demonstrating that salvage RT still has a survival impact in alreadyradiated recurrences. Among demographic variables, age over 60 andKPS ≤ 70 were predictors of unfavorable results that have been seen inother studies6. To resume, we propose the following treatment algorithmaccording to our results and the literature reported (Figure 4).Figure 4. Diagram outlining proposed treatment algorithm for recurrent and radiated skull base meningiomasConflict of Interest:The authors declare that the research was conducted in the absence of any commercial or financialrelationships that could be construed as a potential conflict of interest.Conclusion:We presented a retrospective analysis with the largest cohort of radiated andrecurrent skull base meningiomas. According to our results, achieving GTR isthe best option for recurrent WHO grade 1 meningiomas, radiation is the bestoption for WHO grade 3 meningiomas, and radiation appears to provide abenefit in subtotally resected WHO grade 2 meningiomas. Reoperation forrecurrent skull base meningiomas is associated with a higher complicationrate. Further prospective studies are needed to validate our results.Abbreviations:HR, Hazard ratio; PFS, progression free survival; EOR, extent of resection; GTR, gross total resection; STR, subtotal resection. 

Impact of Salvage Surgery and Re-irradiation for Radiation Failed Recurrent Skull Base Meningiomas

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Impact of Salvage Surgery and Re-irradiation for Radiation Failed Recurrent Skull Base Meningiomas

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