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Relative Monocytopenia, a Proposed Correlate of Decreased Vasculogenesis, Is Associated With Improved Survival in Patients With Glioblastoma Multiforme
Volume 90 Number 1S Supplement 2014
2194 MR Enhancement as a Predictor for Malignant Degeneration in Progressive Low-Grade Gliomas: An Update With Survival Analysis A. Narang,1 K.L. Chaichana,1 J.D. Weingart,1 K.J. Redmond,1 M. Lim,1 A. Olivi,1 A. Quinones-Hinojosa,1 and L.R. Kleinberg2; 1Johns Hopkins University, Baltimore, MD, 2Johns Hopkins University, Baltimore, MD Purpose/Objective(s): In patients with low-grade gliomas, pathologic grade at time of progression has important therapeutic and prognostic implications. While new MR enhancement at time of progression is frequently used as a surrogate for high-grade transformation, we previously found that radiographic enhancement and pathologic grade can often be discordant. We have since substantially expanded our patient cohort to further explore the significance of these radiologic and pathologic findings at time of progression. Materials/Methods: Patients with a pathologic diagnosis of WHO grade II glioma who underwent biopsy or resection at time of progression from 1995-2010 were retrospectively reviewed (n Z 92), with 17 patients undergoing multiple repeat resections, allowing for 109 evaluable records. MRIs were examined for new contrast enhancement, which was analyzed as a predictor of high-grade transformation. The log-rank test was performed to compare Kaplan-Meier survival curves between patient subsets. Results: Median age at diagnosis was 40.0 years. Distribution of pathology consisted of astrocytoma (48%), oligodendroglioma (44%), and oligoastrocytoma (8%). Malignant degeneration was present in 74 specimens (68%). Sensitivity (sens) and specificity (spec) of MR contrast enhancement for high-grade transformation were 89% and 57% respectively, while positive (PPV) and negative predictive values (NPV) were 81% and 71%. Rate of prior radiation amongst patients with falsely positive MR enhancement (33%) was not significant higher than among true positives (40%). Values were similar when excluding patients who only underwent biopsy at time of progression (sens 89%, spec 60%, PPV 83%, NPV 71%). New contrast enhancement predicted worse survival (p Z 0.0005) in both patients maintaining low grade histology (mOS: 92.5 mos vs not reached) and those with high-grade transformation (mOS: 29.5 vs 76.7 mos), despite a similar distribution of grade 4 histology amongst false negatives and true positives. While patients who maintained low-grade histology did not experience worse survival with biopsy alone compared with resection, patients with high grade transformation fared poorly after biopsy alone (mOS: 2.9 mos vs 44.9 mos, p < 0.0001). Conclusions: New MRI enhancement and pathologic grade continued to be discordant in greater than 20% of cases, largely due to a lack of specificity of enhancement for predicting malignant degeneration. As such, pathologic confirmation should be attempted when safe, with maximally safe resection being the surgery of choice if high suspicion for malignant degeneration exists. Beyond functioning as a surrogate for pathologic grade, new MRI enhancement may independently predict for worse outcomes, a concept which merits further investigation. Author Disclosure: A. Narang: None. K.L. Chaichana: None. J.D. Weingart: None. K.J. Redmond: None. M. Lim: None. A. Olivi: None. A. Quinones-Hinojosa: None. L.R. Kleinberg: None.
2195 Does Delay of Start of Radiation Affect Clinical Outcomes of Glioblastoma D.M. Randolph,1 A.M. Peiffer,1 A.K. Paulsson,2 W. Hinson,3 A.W. Laxton,3 S.B. Tatter,3 W. Debinski,3 and M.D. Chan4; 1Wake Forest University Baptist Medical Center, Winston-Salem, NC, 2Wake Forest University School of Medicine, Winston-Salem, NC, 3Wake Forest University Baptist Medical Center, Winston-Salem, NC, 4Wake Forest University Medical Center, Winston-Salem, NC Purpose/Objective(s): Historical convention has dictated that radiation therapy (RT) start within 1 month of surgery. We reviewed our institutional experience for glioblastoma (GBM) to determine if time from
Poster Viewing Abstracts S295 surgery to start of RT affected clinical outcomes, and if any effect was affected by extent of resection or initial tumor volume. Occasionally, clinical trial enrollment causes a delay in start of RT and this effect was also assessed. Materials/Methods: From 5/11/1999 to 5/27/2010, a total of 161 patients underwent surgery followed by RT for GBM. Our retrospective review assessed overall survival (OS), time to progression (PFS), and incidence of clinically relevant early progression of disease prior to starting RT. Covariates analyzed included tumor volume and extent of resection. Electronic medical records and imaging review were used to retrospectively determine date of initial failure using the Response Assessment in Neuro-Oncology (RANO) criteria. Patients were stratified based on whether their surgery was a gross total resection (GTR), subtotal (STR) resection or biopsy. Treatment planning data were used to determine the volume of the tumor using a treatment planning system. Repeated Measures ANOVA was used to evaluate differences in surgical intervention. Kaplan-Meier analysis was used to estimate survival. Results: The median time from surgery to start of RT was 21 days for biopsy alone, 28 days for STR, and 28 days for GTR. For the entire population, there was no worsening in OS (11.7 vs 12.3 months, respectively, p < 0.6) or PFS (6.8 vs 6.6 months, p < 0.6) if there was a delay of greater than 4 weeks (vs no delay) from time of surgery to start of RT. For patients with biopsy alone or STR, there was no worsening of OS (p < 0.4) or PFS (p < 0.6) with a delay of greater than 28 days. With patients who underwent a gross total resection, there was a non-significant worsening in progression-free survival (7.1 vs 8 months, respectively, p Z 0.1) and a significant worsening of OS (12 vs 16.7 months, p < 0.01) if there was a delay to start RT greater than 28 days. In these patients with GTR, PFS was most impacted in those tumors that were larger (4.1 vs 6.8 months, p < 0.02) compared to smaller tumors (4 vs 6.6 months, p < 0.3). Delay in RT to allow for enrollment in a clinical trial did not worsen either PFS (7.3 vs 7, p Z 0.9) or OS (13.5 vs 16.3 months, p Z 0.9). 2 of 161 patients experienced clinically relevant progression of GBM prior to start of RT at a mean time of 33.5 days. Conclusions: We were unable to detect a statistically significant difference in OS or PFS in patients with greater than a 28 day delay in start of RT for the entire cohort. However, subgroup analysis suggests a benefit in PFS in patients with GTR and larger tumors. Author Disclosure: D.M. Randolph: None. A.M. Peiffer: None. A.K. Paulsson: None. W. Hinson: None. A.W. Laxton: None. S.B. Tatter: None. W. Debinski: None. M.D. Chan: None.
2196 Relative Monocytopenia, a Proposed Correlate of Decreased Vasculogenesis, Is Associated With Improved Survival in Patients With Glioblastoma Multiforme E. Osmundson, R. von Eyben, S. Nagpal, L. Recht, M. Brown, and S.G. Soltys; Stanford University, Stanford, CA Purpose/Objective(s): Lymphocytopenia is a known risk factor for poor survival in patients with glioblastoma multiforme (GBM). Conversely, preclinical models of GBM have demonstrated that the influx of bone marrow derived myelomonocytic cells to the tumor bed promotes vasculogenesis required for tumor recurrence after chemoradiation therapy (CRT). We evaluated the association of circulating monocyte and lymphocyte levels with overall survival in patients with GBM. We hypothesized that a low monocyte count, as a potential correlate for decreased vasculogenesis, is associated with improved survival. Materials/Methods: We retrospectively reviewed 125 patients with GBM, with available MGMT promoter methylation status, treated from 2005 - 2012. The mean, minimum and maximum absolute monocyte counts (AMC) and absolute lymphocyte counts (ALC) were obtained prior to CRT and at 7, 15, 45, 90, and 180 days after the start of CRT. Patients who did not undergo either chemotherapy or RT (n Z 18) or for whom a CRT start date was unavailable (n Z 3), had time 0 defined at 4 weeks after either biopsy or resection (if craniotomy performed). Cox
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proportional hazards analyzed factors predictive (p < 0.05) of overall survival (OS). Results: Of 125 tumors, 57 (46%) and 68 (54%) were positive (MGMT+) and negative (MGMT-) for promoter hypermethylation of MGMT. Median follow-up for MGMT+ and MGMT- patients was 21.3 and 10.0 months, respectively. Of the 107 of 125 patients who received first line CT, 106 (85%) received Temozolomide, and 100 (80%) received concurrent radiation therapy. Median OS of MGMT+ and MGMT- patients were 25.5 and 10.5 months, respectively (p < 0.001). Among MGMTpatients, higher mean and maximum AMC values at days (d) 7, 15, 45, 90 and 180 were significantly associated with poorer OS with greatest hazard ratios (HR) observed at later time points (HR for maximum AMC: d7 4.3, d15 4.2, d45 5.8, d90 7.7, d180 6.9; all p < 0.04). In contrast, higher mean ALC was associated with improved overall survival in MGMT- patients at day 7 (HR Z 0.4, p Z 0.03), day 15 (HR Z 0.3, p Z 0.02) and were nearly significant at days 45 (HR Z 0.4, p Z 0.06) and 90 (HR Z 0.4, p Z 0.05). Although not statistically significant, HR trended similarly for both mean AMC and ALC in MGMT+ patients at these time points (e.g., day 15 HR Z 3.8 (p Z 0.2) and HR Z 0.5 (p Z 0.3) respectively). Age at diagnosis, extent of surgical resection, and treatment with CRT were significantly associated with survival (all p < 0.02). In multivariate analyses incorporating all significant variables, neither AMC nor ALC remained significant. Conclusions: Higher AMC and lower ALC during therapy are significantly associated with poorer overall survival in patients with MGMTGBM. While larger sample sizes and further investigation are needed, these data suggest AMC during therapy is a potentially modifiable risk factor for poor survival, which may be positively affected by myelosuppressive therapy. Author Disclosure: E. Osmundson: None. R. von Eyben: None. S. Nagpal: None. L. Recht: None. M. Brown: None. S.G. Soltys: None.
surgical intervention prior to SFRT, and presence of brainstem compression were associated with events. Conclusions: SFRT is generally safe and effective for large acoustic neuromas. Larger tumors were associated with the need for further surgical intervention and a history of previous surgery was associated with the risk of neuropathies. Our series did not show improved rates of hearing preservation with conventionally fractionated radiation. In the era of advanced radiation capabilities, SFRT is an optimal treatment for large acoustic neuromas. However, the idea of hearing preservation with conventional fractionation requires further study. Author Disclosure: R. Wong: None.
2197 Outcome of Patients With Acoustic Neuroma Treated With Conventionally Fractionated Stereotactic Therapy: An Institution Experience R. Wong; National Cancer Centre, Singapore, Singapore Purpose/Objective(s): To Evaluate the efficacy of conventionally fractionated stereotactic radiation therapy in acoustic neuroma, toxicity of treatment and factors predictive of adverse events. Materials/Methods: Between 2007 and 2011, 75 patients with acoustic neuromas were treated in our stereotactic radiation therapy unit under protocol. Of these, 57 patients who had large tumors (>2.5 cm diameter), Koos IV (Brainstem compression) and who desired hearing preservation underwent SFRT. Treatment was delivered stereotactically. A standard dose of 50.4 Gy in 28 fractions was delivered to the 95% isodose line. Patients were followed up at 6 monthly intervals for clinical examination and had yearly MRI assessments. Results: The median age was 52 and gender was balanced. 75% were treated because of size or brainstem compression and 25% for hearing preservation. 15% had prior surgery. PTV volume ranged from 0.7 to 41.2 cc, with median volume being 14.09cc. At median follow-up of 41 months (range 16-78 months), the control rate was 92%. Of the 6 patients who had increment of size on MRI, 4 required excision and 2 remained asymptomatic. 2 patients (2.67%) developed symptomatic edema post-treatment (giddiness and/or cranial nerve deficits), which resolved subsequently with steroids. 8/19 (42%) patients treated for hearing preservation reported subjective worsening of hearing but only 4 (21%) were documented on audiogram. 5 patients (6.7%) had increased/new trigeminal neuropathy and 5 patients (6.7%) had new or worsening ear ache which eventually resolved. Rare complications included 1 patient with enlarging hydrocephalus requiring VP shunt, 1 patient with intratumoral bleed requiring surgical evacuation. The 3 year actuarial rate for progressive disease requiring surgery is 7% and the 3 year actuarial rate for freedom from any surgical intervention is 85.9%. On multivariate analysis, size of tumor,
2198 Predictors of Symptomatic Edema After Treatment of Intracranial Meningiomas With Single-Fraction Stereotactic Radiosurgery K. Meyer, A. Maitz, H. Ye, M. Manders, and I.S. Grills; Beaumont Health System, Royal Oak, MI Purpose/Objective(s): Stereotactic radiosurgery (SRS) provides a 10 year local control (LC) rate of up to 99% for intracranial meningiomas, but may be associated with higher post-treatment symptomatic edema rates. Prior reports have combined single and multi-fraction SRS when analyzing edema rates. The objective was to determine factors predictive of posttreatment edema after single fraction SRS alone to identify patients who may require either surgery or fractionated RT. Materials/Methods: Seventy-five patients with radiographic evidence of intracranial meningioma underwent gamma knife (GK) SRS alone at a single institution between 10/2007-7/2013. Those with prior surgical resection, radiation, multiple meningiomas or malignancy were excluded. All patients had pre- and post-GK MRIs, typically 6 mo, and 12 mo postGK then annually thereafter; all pre- and post-GK MRIs were reviewed for analysis. Tumor volume (TV) was contoured on the GK treatment T1 Gdenhanced MRI; treatment volume (TxV), defined as the volume receiving the prescribed dose, was calculated. Peri-tumoral edema was defined as the T2 FLAIR or equivalent volume less both TV and any pre-GK edema. TV, TxV, max linear dimension, age, sex, location of tumor, and marginal dose were evaluated for association with edema and symptomatic edema using chi-square and t-test. Results: Median age was 65 years (41 - 90); 7 male and 68 female. Median follow-up was 22 mo (3 e 60 mo). Median TV was 3.2 cc (0.25 e 23.8 cc); median TxV was 5.2 cc (0.47 e 37.9 cc). The median marginal dose was 13 Gy (10 e 17 Gy) prescribed to a median isodose line of 50% (3060%). 33 patients (44%) had pre-GK symptoms attributed to tumor; 9 (12%) had pre-GK edema on MRI. Symptoms improved or resolved after GK in 45% of these patients. 25 patients (33%) developed post-GK edema. 9 (12%) were symptomatic; 5 (6.6%) were treated with steroids. One had resection for steroid-refractory symptoms. LC was 100%. On univariate analysis, increasing TV (OR Z 1.2, p < 0.001), TxV (OR Z 1.2, p Z 0.001), and max linear dimension (OR Z 1.8, p Z 0.01) were associated with increased edema. There was no association for edema with or without symptoms for sex, location, or marginal dose. ROC analysis of tumor volume and edema found a cut point of 3.1 cc with sensitivity of 85% and specificity of 61%. Symptomatic edema was predicted by both TV (p Z 0.01) and edema volume (p < 0.001), with an edema volume of 2.1 cc predicting for symptoms (sensitivity 89% and specificity 100%) and TV of 5.2 cc predicting for symptoms (sensitivity 73% and specificity 70%). Conclusions: Larger tumor and treatment volumes were associated with higher rates of edema after SRS. Tumor volume greater than 5.2 cc was associated with an increased risk of symptomatic edema and edema volumes of at least 2.1 cc were more likely to be symptomatic. Patients with tumors larger than this size should be advised of this risk with a consideration for alternative therapies. Author Disclosure: K. Meyer: None. A. Maitz: None. H. Ye: None. M. Manders: None. I.S. Grills: None.
2194 MR Enhancement as a Predictor for Malignant Degeneration in Progressive Low-Grade Gliomas: An Update With Survival Analysis A. Narang,1 K.L. Chaichana,1 J.D. Weingart,1 K.J. Redmond,1 M. Lim,1 A. Olivi,1 A. Quinones-Hinojosa,1 and L.R. Kleinberg2; 1Johns Hopkins University, Baltimore, MD, 2Johns Hopkins University, Baltimore, MD Purpose/Objective(s): In patients with low-grade gliomas, pathologic grade at time of progression has important therapeutic and prognostic implications. While new MR enhancement at time of progression is frequently used as a surrogate for high-grade transformation, we previously found that radiographic enhancement and pathologic grade can often be discordant. We have since substantially expanded our patient cohort to further explore the significance of these radiologic and pathologic findings at time of progression. Materials/Methods: Patients with a pathologic diagnosis of WHO grade II glioma who underwent biopsy or resection at time of progression from 1995-2010 were retrospectively reviewed (n Z 92), with 17 patients undergoing multiple repeat resections, allowing for 109 evaluable records. MRIs were examined for new contrast enhancement, which was analyzed as a predictor of high-grade transformation. The log-rank test was performed to compare Kaplan-Meier survival curves between patient subsets. Results: Median age at diagnosis was 40.0 years. Distribution of pathology consisted of astrocytoma (48%), oligodendroglioma (44%), and oligoastrocytoma (8%). Malignant degeneration was present in 74 specimens (68%). Sensitivity (sens) and specificity (spec) of MR contrast enhancement for high-grade transformation were 89% and 57% respectively, while positive (PPV) and negative predictive values (NPV) were 81% and 71%. Rate of prior radiation amongst patients with falsely positive MR enhancement (33%) was not significant higher than among true positives (40%). Values were similar when excluding patients who only underwent biopsy at time of progression (sens 89%, spec 60%, PPV 83%, NPV 71%). New contrast enhancement predicted worse survival (p Z 0.0005) in both patients maintaining low grade histology (mOS: 92.5 mos vs not reached) and those with high-grade transformation (mOS: 29.5 vs 76.7 mos), despite a similar distribution of grade 4 histology amongst false negatives and true positives. While patients who maintained low-grade histology did not experience worse survival with biopsy alone compared with resection, patients with high grade transformation fared poorly after biopsy alone (mOS: 2.9 mos vs 44.9 mos, p < 0.0001). Conclusions: New MRI enhancement and pathologic grade continued to be discordant in greater than 20% of cases, largely due to a lack of specificity of enhancement for predicting malignant degeneration. As such, pathologic confirmation should be attempted when safe, with maximally safe resection being the surgery of choice if high suspicion for malignant degeneration exists. Beyond functioning as a surrogate for pathologic grade, new MRI enhancement may independently predict for worse outcomes, a concept which merits further investigation. Author Disclosure: A. Narang: None. K.L. Chaichana: None. J.D. Weingart: None. K.J. Redmond: None. M. Lim: None. A. Olivi: None. A. Quinones-Hinojosa: None. L.R. Kleinberg: None.
2195 Does Delay of Start of Radiation Affect Clinical Outcomes of Glioblastoma D.M. Randolph,1 A.M. Peiffer,1 A.K. Paulsson,2 W. Hinson,3 A.W. Laxton,3 S.B. Tatter,3 W. Debinski,3 and M.D. Chan4; 1Wake Forest University Baptist Medical Center, Winston-Salem, NC, 2Wake Forest University School of Medicine, Winston-Salem, NC, 3Wake Forest University Baptist Medical Center, Winston-Salem, NC, 4Wake Forest University Medical Center, Winston-Salem, NC Purpose/Objective(s): Historical convention has dictated that radiation therapy (RT) start within 1 month of surgery. We reviewed our institutional experience for glioblastoma (GBM) to determine if time from
Poster Viewing Abstracts S295 surgery to start of RT affected clinical outcomes, and if any effect was affected by extent of resection or initial tumor volume. Occasionally, clinical trial enrollment causes a delay in start of RT and this effect was also assessed. Materials/Methods: From 5/11/1999 to 5/27/2010, a total of 161 patients underwent surgery followed by RT for GBM. Our retrospective review assessed overall survival (OS), time to progression (PFS), and incidence of clinically relevant early progression of disease prior to starting RT. Covariates analyzed included tumor volume and extent of resection. Electronic medical records and imaging review were used to retrospectively determine date of initial failure using the Response Assessment in Neuro-Oncology (RANO) criteria. Patients were stratified based on whether their surgery was a gross total resection (GTR), subtotal (STR) resection or biopsy. Treatment planning data were used to determine the volume of the tumor using a treatment planning system. Repeated Measures ANOVA was used to evaluate differences in surgical intervention. Kaplan-Meier analysis was used to estimate survival. Results: The median time from surgery to start of RT was 21 days for biopsy alone, 28 days for STR, and 28 days for GTR. For the entire population, there was no worsening in OS (11.7 vs 12.3 months, respectively, p < 0.6) or PFS (6.8 vs 6.6 months, p < 0.6) if there was a delay of greater than 4 weeks (vs no delay) from time of surgery to start of RT. For patients with biopsy alone or STR, there was no worsening of OS (p < 0.4) or PFS (p < 0.6) with a delay of greater than 28 days. With patients who underwent a gross total resection, there was a non-significant worsening in progression-free survival (7.1 vs 8 months, respectively, p Z 0.1) and a significant worsening of OS (12 vs 16.7 months, p < 0.01) if there was a delay to start RT greater than 28 days. In these patients with GTR, PFS was most impacted in those tumors that were larger (4.1 vs 6.8 months, p < 0.02) compared to smaller tumors (4 vs 6.6 months, p < 0.3). Delay in RT to allow for enrollment in a clinical trial did not worsen either PFS (7.3 vs 7, p Z 0.9) or OS (13.5 vs 16.3 months, p Z 0.9). 2 of 161 patients experienced clinically relevant progression of GBM prior to start of RT at a mean time of 33.5 days. Conclusions: We were unable to detect a statistically significant difference in OS or PFS in patients with greater than a 28 day delay in start of RT for the entire cohort. However, subgroup analysis suggests a benefit in PFS in patients with GTR and larger tumors. Author Disclosure: D.M. Randolph: None. A.M. Peiffer: None. A.K. Paulsson: None. W. Hinson: None. A.W. Laxton: None. S.B. Tatter: None. W. Debinski: None. M.D. Chan: None.
2196 Relative Monocytopenia, a Proposed Correlate of Decreased Vasculogenesis, Is Associated With Improved Survival in Patients With Glioblastoma Multiforme E. Osmundson, R. von Eyben, S. Nagpal, L. Recht, M. Brown, and S.G. Soltys; Stanford University, Stanford, CA Purpose/Objective(s): Lymphocytopenia is a known risk factor for poor survival in patients with glioblastoma multiforme (GBM). Conversely, preclinical models of GBM have demonstrated that the influx of bone marrow derived myelomonocytic cells to the tumor bed promotes vasculogenesis required for tumor recurrence after chemoradiation therapy (CRT). We evaluated the association of circulating monocyte and lymphocyte levels with overall survival in patients with GBM. We hypothesized that a low monocyte count, as a potential correlate for decreased vasculogenesis, is associated with improved survival. Materials/Methods: We retrospectively reviewed 125 patients with GBM, with available MGMT promoter methylation status, treated from 2005 - 2012. The mean, minimum and maximum absolute monocyte counts (AMC) and absolute lymphocyte counts (ALC) were obtained prior to CRT and at 7, 15, 45, 90, and 180 days after the start of CRT. Patients who did not undergo either chemotherapy or RT (n Z 18) or for whom a CRT start date was unavailable (n Z 3), had time 0 defined at 4 weeks after either biopsy or resection (if craniotomy performed). Cox
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proportional hazards analyzed factors predictive (p < 0.05) of overall survival (OS). Results: Of 125 tumors, 57 (46%) and 68 (54%) were positive (MGMT+) and negative (MGMT-) for promoter hypermethylation of MGMT. Median follow-up for MGMT+ and MGMT- patients was 21.3 and 10.0 months, respectively. Of the 107 of 125 patients who received first line CT, 106 (85%) received Temozolomide, and 100 (80%) received concurrent radiation therapy. Median OS of MGMT+ and MGMT- patients were 25.5 and 10.5 months, respectively (p < 0.001). Among MGMTpatients, higher mean and maximum AMC values at days (d) 7, 15, 45, 90 and 180 were significantly associated with poorer OS with greatest hazard ratios (HR) observed at later time points (HR for maximum AMC: d7 4.3, d15 4.2, d45 5.8, d90 7.7, d180 6.9; all p < 0.04). In contrast, higher mean ALC was associated with improved overall survival in MGMT- patients at day 7 (HR Z 0.4, p Z 0.03), day 15 (HR Z 0.3, p Z 0.02) and were nearly significant at days 45 (HR Z 0.4, p Z 0.06) and 90 (HR Z 0.4, p Z 0.05). Although not statistically significant, HR trended similarly for both mean AMC and ALC in MGMT+ patients at these time points (e.g., day 15 HR Z 3.8 (p Z 0.2) and HR Z 0.5 (p Z 0.3) respectively). Age at diagnosis, extent of surgical resection, and treatment with CRT were significantly associated with survival (all p < 0.02). In multivariate analyses incorporating all significant variables, neither AMC nor ALC remained significant. Conclusions: Higher AMC and lower ALC during therapy are significantly associated with poorer overall survival in patients with MGMTGBM. While larger sample sizes and further investigation are needed, these data suggest AMC during therapy is a potentially modifiable risk factor for poor survival, which may be positively affected by myelosuppressive therapy. Author Disclosure: E. Osmundson: None. R. von Eyben: None. S. Nagpal: None. L. Recht: None. M. Brown: None. S.G. Soltys: None.
surgical intervention prior to SFRT, and presence of brainstem compression were associated with events. Conclusions: SFRT is generally safe and effective for large acoustic neuromas. Larger tumors were associated with the need for further surgical intervention and a history of previous surgery was associated with the risk of neuropathies. Our series did not show improved rates of hearing preservation with conventionally fractionated radiation. In the era of advanced radiation capabilities, SFRT is an optimal treatment for large acoustic neuromas. However, the idea of hearing preservation with conventional fractionation requires further study. Author Disclosure: R. Wong: None.
2197 Outcome of Patients With Acoustic Neuroma Treated With Conventionally Fractionated Stereotactic Therapy: An Institution Experience R. Wong; National Cancer Centre, Singapore, Singapore Purpose/Objective(s): To Evaluate the efficacy of conventionally fractionated stereotactic radiation therapy in acoustic neuroma, toxicity of treatment and factors predictive of adverse events. Materials/Methods: Between 2007 and 2011, 75 patients with acoustic neuromas were treated in our stereotactic radiation therapy unit under protocol. Of these, 57 patients who had large tumors (>2.5 cm diameter), Koos IV (Brainstem compression) and who desired hearing preservation underwent SFRT. Treatment was delivered stereotactically. A standard dose of 50.4 Gy in 28 fractions was delivered to the 95% isodose line. Patients were followed up at 6 monthly intervals for clinical examination and had yearly MRI assessments. Results: The median age was 52 and gender was balanced. 75% were treated because of size or brainstem compression and 25% for hearing preservation. 15% had prior surgery. PTV volume ranged from 0.7 to 41.2 cc, with median volume being 14.09cc. At median follow-up of 41 months (range 16-78 months), the control rate was 92%. Of the 6 patients who had increment of size on MRI, 4 required excision and 2 remained asymptomatic. 2 patients (2.67%) developed symptomatic edema post-treatment (giddiness and/or cranial nerve deficits), which resolved subsequently with steroids. 8/19 (42%) patients treated for hearing preservation reported subjective worsening of hearing but only 4 (21%) were documented on audiogram. 5 patients (6.7%) had increased/new trigeminal neuropathy and 5 patients (6.7%) had new or worsening ear ache which eventually resolved. Rare complications included 1 patient with enlarging hydrocephalus requiring VP shunt, 1 patient with intratumoral bleed requiring surgical evacuation. The 3 year actuarial rate for progressive disease requiring surgery is 7% and the 3 year actuarial rate for freedom from any surgical intervention is 85.9%. On multivariate analysis, size of tumor,
2198 Predictors of Symptomatic Edema After Treatment of Intracranial Meningiomas With Single-Fraction Stereotactic Radiosurgery K. Meyer, A. Maitz, H. Ye, M. Manders, and I.S. Grills; Beaumont Health System, Royal Oak, MI Purpose/Objective(s): Stereotactic radiosurgery (SRS) provides a 10 year local control (LC) rate of up to 99% for intracranial meningiomas, but may be associated with higher post-treatment symptomatic edema rates. Prior reports have combined single and multi-fraction SRS when analyzing edema rates. The objective was to determine factors predictive of posttreatment edema after single fraction SRS alone to identify patients who may require either surgery or fractionated RT. Materials/Methods: Seventy-five patients with radiographic evidence of intracranial meningioma underwent gamma knife (GK) SRS alone at a single institution between 10/2007-7/2013. Those with prior surgical resection, radiation, multiple meningiomas or malignancy were excluded. All patients had pre- and post-GK MRIs, typically 6 mo, and 12 mo postGK then annually thereafter; all pre- and post-GK MRIs were reviewed for analysis. Tumor volume (TV) was contoured on the GK treatment T1 Gdenhanced MRI; treatment volume (TxV), defined as the volume receiving the prescribed dose, was calculated. Peri-tumoral edema was defined as the T2 FLAIR or equivalent volume less both TV and any pre-GK edema. TV, TxV, max linear dimension, age, sex, location of tumor, and marginal dose were evaluated for association with edema and symptomatic edema using chi-square and t-test. Results: Median age was 65 years (41 - 90); 7 male and 68 female. Median follow-up was 22 mo (3 e 60 mo). Median TV was 3.2 cc (0.25 e 23.8 cc); median TxV was 5.2 cc (0.47 e 37.9 cc). The median marginal dose was 13 Gy (10 e 17 Gy) prescribed to a median isodose line of 50% (3060%). 33 patients (44%) had pre-GK symptoms attributed to tumor; 9 (12%) had pre-GK edema on MRI. Symptoms improved or resolved after GK in 45% of these patients. 25 patients (33%) developed post-GK edema. 9 (12%) were symptomatic; 5 (6.6%) were treated with steroids. One had resection for steroid-refractory symptoms. LC was 100%. On univariate analysis, increasing TV (OR Z 1.2, p < 0.001), TxV (OR Z 1.2, p Z 0.001), and max linear dimension (OR Z 1.8, p Z 0.01) were associated with increased edema. There was no association for edema with or without symptoms for sex, location, or marginal dose. ROC analysis of tumor volume and edema found a cut point of 3.1 cc with sensitivity of 85% and specificity of 61%. Symptomatic edema was predicted by both TV (p Z 0.01) and edema volume (p < 0.001), with an edema volume of 2.1 cc predicting for symptoms (sensitivity 89% and specificity 100%) and TV of 5.2 cc predicting for symptoms (sensitivity 73% and specificity 70%). Conclusions: Larger tumor and treatment volumes were associated with higher rates of edema after SRS. Tumor volume greater than 5.2 cc was associated with an increased risk of symptomatic edema and edema volumes of at least 2.1 cc were more likely to be symptomatic. Patients with tumors larger than this size should be advised of this risk with a consideration for alternative therapies. Author Disclosure: K. Meyer: None. A. Maitz: None. H. Ye: None. M. Manders: None. I.S. Grills: None.