- Email: [email protected]
Benign Meningiomas With Atypical Features: Correlation of Histopathological Features With Clinical Outcomes
Digital Poster Discussion Abstracts S159
Volume 87 Number 2S Supplement 2013 Results: Between 1991 and 2000, 47 patients were enrolled with 25 (53%) randomized to the 55.8 Gy (RBE) arm. Median follow-up is 13.2 years among 32 surviving patients. PFS was similar between 55.8 Gy (RBE) versus 63 Gy (RBE) arms at 5 years (88% vs 95%) and 10 years (83% vs 86%), but there was a suggestion of improved PFS with higher dose at 15 years (39% vs 64%), although the overall difference was not significant (p Z 0.202). Similarly, with the limited patient numbers, the OS at 5 years (88% vs 95%), 10 years (83% vs 86%), and 15 years (51% vs 77%) did not represent a significant difference (p Z 0.189). All patients completed the prescribed radiation therapy without complication. Acute toxicity within the first 6 months from treatment completion was predominantly grade 1-2 and transient. One case of grade 3 weakness occurred in the 55.8 Gy (RBE) arm and one case of acute grade 3 fatigue occurred in the 63 Gy (RBE) arm. Late effects potentially attributable to radiation were also largely grade 1-2 but involved deficits in multiple domains including multiple cranial neuropathies, persistent headaches, ataxia, and persistent fatigue. One case of asymptomatic brain necrosis occurred in the 55.8 Gy (RBE) arm and two cases occurred in the 63 Gy (RBE) arm. There was no correlation of toxicities with treatment arm. There were no deaths secondary to radiation. Conclusions: Benign meningioma patients treated with 55.8 to 63 Gy (RBE) sustain a reasonably high PFS within the first decade post-irradiation but continue to experience late failures thereafter. Proton therapy may offer a means of safer dose escalation to achieve more durable long term control. Author Disclosure: H.A. Shih: E. Research Grant; NCI. F. Honoraria; International Journal of Radiation Oncology Biology Physics. N. Royalty; UpToDate. N.N. Niu: None. E. Pan: None. J. Daartz: None. B.Y. Yeap: None. J.E. Munzenrider: None. J.S. Loeffler: None.
1029 Benign Meningiomas With Atypical Features: Correlation of Histopathological Features With Clinical Outcomes A.E. Marciscano, A.O. Stemmer-Rachamimov, A. Niemierko, W.T. Curry, F.G. Barker, R.L. Martuza, K.S. Oh, J.S. Loeffler, and H.A. Shih; Massachusetts General Hospital, Boston, MA Purpose/Objective(s): Benign meningiomas with atypical features may behave more aggressively than similarly graded benign tumors without atypia. Our primary objective is to determine if there is prognostic significance of atypical features in benign meningiomas. Materials/Methods: We retrospectively reviewed patients treated at our institution from 2002-2012 who fulfilled the 2007 WHO criteria for grade I meningioma as well as having at least one but less than three features of atypia (increased cellularity, sheeting, high N/C ratio, necrosis, prominent nucleoli). Clinical, radiographic, and pathologic data were reviewed. Tumor progression and recurrence were defined by serial radiological imaging. Both univariate and multivariate Cox regression analysis were utilized for statistical analysis. Results: Sixty-eight patients met inclusion criteria. Median age at diagnosis was 56.5 years. Fifty-four (79%) patients were female. Median follow-up was 40.9 months. Median tumor size at diagnosis was 4.4 cm and proliferative index at diagnosis was 3.9%. Twenty-two of 68 (32.4%) patients had progressed/recurred. Median time from progression/recurrence after initial diagnosis was 24.4 months and time to progression/ recurrence after treatment was 17.2 months. On multivariate analysis, atypical features significantly associated with increased risk of progression/recurrence were sheeting (Hazard Ratio [HR] Z 3.2; 95% CI: 1.110.3; p Z 0.05), cellularity (HR Z 5.7; 95% CI: 1.6-20.6; p Z 0.008), and necrosis (HR Z 9.0; 95% CI: 2.4-33.4; p Z 0.001). Notably, on univariate analysis, tumor size, proliferative index, and number of atypical features present were not significant. No patient that underwent RT as definitive (n Z 1) or adjuvant therapy (n Z 6) as initial/primary therapeutic intervention experienced progression or recurrence of disease at time of last follow-up. On multivariate analysis, factors associated with increased risk
of tumor progression/recurrence included all non-Simpson grade I resection (HR Z 10; 95% CI: 1.4-75.2; p Z 0.02), prominent nucleoli (HR Z 7.8; 95% CI: 2.0-31.1; p Z 0.003), and necrosis (HR Z 7.3; 95% CI: 2.125.6; p Z 0.002). Conclusions: Grade I benign meningiomas possessing atypical features of necrosis, prominent nucleoli and sheeting are at significantly increased risk of tumor recurrence/progression. These patients may benefit from further consideration of additional surgery and/or radiation. Author Disclosure: A.E. Marciscano: None. A.O. Stemmer-Rachamimov: None. A. Niemierko: None. W.T. Curry: None. F.G. Barker: None. R.L. Martuza: None. K.S. Oh: None. J.S. Loeffler: None. H.A. Shih: E. Research Grant; NCI/NIH. F. Honoraria; IJROBP. N. Royalty; UpToDate.
1030 Combining Fractionated Stereotactic Radiation Therapy and Bevacizumab for Recurrent High-Grade Glioma: Outcomes Analysis J.J. Siglin,1 C.E. Champ,1 I. Zhang,2 T. Dan,1 J. Glass,1 J.J. Evans,1 D.W. Andrews,1 M. Werner-Wasik,1 and W. Shi1; 1Thomas Jefferson University Hospital, Philadelphia, PA, 2Jefferson Medical College, Philadelphia, PA Purpose/Objective(s): This study reports the outcomes of the largest cohort to date of patients receiving both bevacizumab (BEV) and fractionated stereotactic radiation therapy (FSRT) for progressive or recurrent high grade glioma (HGG). Furthermore, the sequence of these two treatment regimens was analyzed to determine an optimal treatment paradigm for recurrent HGG. Materials/Methods: Retrospective review was conducted of patients initially treated with external beam radiation therapy for pathologically confirmed WHO grade III (AA) or IV (GBM) glioma that subsequently recurred. Patients were identified who had received reirradiation with FSRT as well as BEV for their recurrence. FSRT was most commonly delivered in 3.5 Gy fractions to a total dose of 35 Gy. Survival from initial diagnosis, as well as from recurrence and re-irradiation, were utilized as study endpoints. Date of recurrence was defined as the date to radiographic evidence of progressive/recurrent disease. Kaplan-Meier curves were generated utilizing a log-rank test with a p value of 0.05 considered significant to compare treatment sequences in terms of survival outcomes. Results: A total of 68 patients with recurrent/progressive HGG (GBM Z 54, AA Z 14) had received both BEV and FSRT at our institution. Patient characteristics were as follows: median KPS at recurrence was 70 (range, 60-100); median age at recurrence was 57.6; median time to radiographic recurrence/progression was 7.5 months (mos) and 36.8% of patients had surgery for recurrence. The median time from the start of BEV to FSRT was 7.8 mos and from FSRT to the start of BEV was 5.5 mos. For the entire cohort, median survival time (MST) was 25.2 mos and MST from recurrence was 13.7 mos (25.2 mos and 13.5 mos for GBM only). In patients that received BEV prior to FSRT (n Z 38), MST and MST from recurrence were 25.9 and 13.6 mo respectively. In patients receiving FSRT first (n Z 30), MST and MST from recurrence were 21.9 mos and 13.7 mos, respectively. Sequencing of FSRT and BEV at recurrence had no statistically significant effect on MST (p Z 0.73) or survival from radiographic recurrence (p Z 0.91). The only significant difference between the sequences was in the metric of survival from re-irradiation. MST from reirradiation was 12.4 mos in the FSRT-first group compared to 5.7 mos in the BEV-first group (p Z 0.002). Conclusions: The combination of FSRT and BEV for recurrent/progressive HGG provide promising results in terms of overall survival and survival from recurrence. While combining these treatment modalities appear to improve upon the historic outcomes of either treatment alone, the sequence of administration of BEV and FSRT has no impact on survival. The outcomes data from this study support the ongoing RTOG trial exploring the combination of BEV and FSRT for recurrent HGG. Author Disclosure: J.J. Siglin: None. C.E. Champ: None. I. Zhang: None. T. Dan: None. J. Glass: None. J.J. Evans: None. D.W. Andrews: None. M. Werner-Wasik: None. W. Shi: None.
Volume 87 Number 2S Supplement 2013 Results: Between 1991 and 2000, 47 patients were enrolled with 25 (53%) randomized to the 55.8 Gy (RBE) arm. Median follow-up is 13.2 years among 32 surviving patients. PFS was similar between 55.8 Gy (RBE) versus 63 Gy (RBE) arms at 5 years (88% vs 95%) and 10 years (83% vs 86%), but there was a suggestion of improved PFS with higher dose at 15 years (39% vs 64%), although the overall difference was not significant (p Z 0.202). Similarly, with the limited patient numbers, the OS at 5 years (88% vs 95%), 10 years (83% vs 86%), and 15 years (51% vs 77%) did not represent a significant difference (p Z 0.189). All patients completed the prescribed radiation therapy without complication. Acute toxicity within the first 6 months from treatment completion was predominantly grade 1-2 and transient. One case of grade 3 weakness occurred in the 55.8 Gy (RBE) arm and one case of acute grade 3 fatigue occurred in the 63 Gy (RBE) arm. Late effects potentially attributable to radiation were also largely grade 1-2 but involved deficits in multiple domains including multiple cranial neuropathies, persistent headaches, ataxia, and persistent fatigue. One case of asymptomatic brain necrosis occurred in the 55.8 Gy (RBE) arm and two cases occurred in the 63 Gy (RBE) arm. There was no correlation of toxicities with treatment arm. There were no deaths secondary to radiation. Conclusions: Benign meningioma patients treated with 55.8 to 63 Gy (RBE) sustain a reasonably high PFS within the first decade post-irradiation but continue to experience late failures thereafter. Proton therapy may offer a means of safer dose escalation to achieve more durable long term control. Author Disclosure: H.A. Shih: E. Research Grant; NCI. F. Honoraria; International Journal of Radiation Oncology Biology Physics. N. Royalty; UpToDate. N.N. Niu: None. E. Pan: None. J. Daartz: None. B.Y. Yeap: None. J.E. Munzenrider: None. J.S. Loeffler: None.
1029 Benign Meningiomas With Atypical Features: Correlation of Histopathological Features With Clinical Outcomes A.E. Marciscano, A.O. Stemmer-Rachamimov, A. Niemierko, W.T. Curry, F.G. Barker, R.L. Martuza, K.S. Oh, J.S. Loeffler, and H.A. Shih; Massachusetts General Hospital, Boston, MA Purpose/Objective(s): Benign meningiomas with atypical features may behave more aggressively than similarly graded benign tumors without atypia. Our primary objective is to determine if there is prognostic significance of atypical features in benign meningiomas. Materials/Methods: We retrospectively reviewed patients treated at our institution from 2002-2012 who fulfilled the 2007 WHO criteria for grade I meningioma as well as having at least one but less than three features of atypia (increased cellularity, sheeting, high N/C ratio, necrosis, prominent nucleoli). Clinical, radiographic, and pathologic data were reviewed. Tumor progression and recurrence were defined by serial radiological imaging. Both univariate and multivariate Cox regression analysis were utilized for statistical analysis. Results: Sixty-eight patients met inclusion criteria. Median age at diagnosis was 56.5 years. Fifty-four (79%) patients were female. Median follow-up was 40.9 months. Median tumor size at diagnosis was 4.4 cm and proliferative index at diagnosis was 3.9%. Twenty-two of 68 (32.4%) patients had progressed/recurred. Median time from progression/recurrence after initial diagnosis was 24.4 months and time to progression/ recurrence after treatment was 17.2 months. On multivariate analysis, atypical features significantly associated with increased risk of progression/recurrence were sheeting (Hazard Ratio [HR] Z 3.2; 95% CI: 1.110.3; p Z 0.05), cellularity (HR Z 5.7; 95% CI: 1.6-20.6; p Z 0.008), and necrosis (HR Z 9.0; 95% CI: 2.4-33.4; p Z 0.001). Notably, on univariate analysis, tumor size, proliferative index, and number of atypical features present were not significant. No patient that underwent RT as definitive (n Z 1) or adjuvant therapy (n Z 6) as initial/primary therapeutic intervention experienced progression or recurrence of disease at time of last follow-up. On multivariate analysis, factors associated with increased risk
of tumor progression/recurrence included all non-Simpson grade I resection (HR Z 10; 95% CI: 1.4-75.2; p Z 0.02), prominent nucleoli (HR Z 7.8; 95% CI: 2.0-31.1; p Z 0.003), and necrosis (HR Z 7.3; 95% CI: 2.125.6; p Z 0.002). Conclusions: Grade I benign meningiomas possessing atypical features of necrosis, prominent nucleoli and sheeting are at significantly increased risk of tumor recurrence/progression. These patients may benefit from further consideration of additional surgery and/or radiation. Author Disclosure: A.E. Marciscano: None. A.O. Stemmer-Rachamimov: None. A. Niemierko: None. W.T. Curry: None. F.G. Barker: None. R.L. Martuza: None. K.S. Oh: None. J.S. Loeffler: None. H.A. Shih: E. Research Grant; NCI/NIH. F. Honoraria; IJROBP. N. Royalty; UpToDate.
1030 Combining Fractionated Stereotactic Radiation Therapy and Bevacizumab for Recurrent High-Grade Glioma: Outcomes Analysis J.J. Siglin,1 C.E. Champ,1 I. Zhang,2 T. Dan,1 J. Glass,1 J.J. Evans,1 D.W. Andrews,1 M. Werner-Wasik,1 and W. Shi1; 1Thomas Jefferson University Hospital, Philadelphia, PA, 2Jefferson Medical College, Philadelphia, PA Purpose/Objective(s): This study reports the outcomes of the largest cohort to date of patients receiving both bevacizumab (BEV) and fractionated stereotactic radiation therapy (FSRT) for progressive or recurrent high grade glioma (HGG). Furthermore, the sequence of these two treatment regimens was analyzed to determine an optimal treatment paradigm for recurrent HGG. Materials/Methods: Retrospective review was conducted of patients initially treated with external beam radiation therapy for pathologically confirmed WHO grade III (AA) or IV (GBM) glioma that subsequently recurred. Patients were identified who had received reirradiation with FSRT as well as BEV for their recurrence. FSRT was most commonly delivered in 3.5 Gy fractions to a total dose of 35 Gy. Survival from initial diagnosis, as well as from recurrence and re-irradiation, were utilized as study endpoints. Date of recurrence was defined as the date to radiographic evidence of progressive/recurrent disease. Kaplan-Meier curves were generated utilizing a log-rank test with a p value of 0.05 considered significant to compare treatment sequences in terms of survival outcomes. Results: A total of 68 patients with recurrent/progressive HGG (GBM Z 54, AA Z 14) had received both BEV and FSRT at our institution. Patient characteristics were as follows: median KPS at recurrence was 70 (range, 60-100); median age at recurrence was 57.6; median time to radiographic recurrence/progression was 7.5 months (mos) and 36.8% of patients had surgery for recurrence. The median time from the start of BEV to FSRT was 7.8 mos and from FSRT to the start of BEV was 5.5 mos. For the entire cohort, median survival time (MST) was 25.2 mos and MST from recurrence was 13.7 mos (25.2 mos and 13.5 mos for GBM only). In patients that received BEV prior to FSRT (n Z 38), MST and MST from recurrence were 25.9 and 13.6 mo respectively. In patients receiving FSRT first (n Z 30), MST and MST from recurrence were 21.9 mos and 13.7 mos, respectively. Sequencing of FSRT and BEV at recurrence had no statistically significant effect on MST (p Z 0.73) or survival from radiographic recurrence (p Z 0.91). The only significant difference between the sequences was in the metric of survival from re-irradiation. MST from reirradiation was 12.4 mos in the FSRT-first group compared to 5.7 mos in the BEV-first group (p Z 0.002). Conclusions: The combination of FSRT and BEV for recurrent/progressive HGG provide promising results in terms of overall survival and survival from recurrence. While combining these treatment modalities appear to improve upon the historic outcomes of either treatment alone, the sequence of administration of BEV and FSRT has no impact on survival. The outcomes data from this study support the ongoing RTOG trial exploring the combination of BEV and FSRT for recurrent HGG. Author Disclosure: J.J. Siglin: None. C.E. Champ: None. I. Zhang: None. T. Dan: None. J. Glass: None. J.J. Evans: None. D.W. Andrews: None. M. Werner-Wasik: None. W. Shi: None.