Predictors of Durability of Response for Stereotactic Radiosurgery in the Treatment of Trigeminal Neuralgia

Volume 84  Number 3S  Supplement 2012 Author Disclosure: M. Shenouda: None. B.T. Sadek: None. R.F. Abi Raad: None. S.I. Goldberg: None. A.G. Taghian: None.

90 Five Decades of Adult Low-grade Gliomas: Patterns of Care Over Time R. Youland,1 P.D. Brown,2 J.C. Buckner,1 I.F. Parney,1 J.H. Uhm,1 and N.N. Laack1; 1Mayo Clinic, Rochester, MN, 2The University of Texas MD Anderson Cancer Center, Houston, TX Purpose/Objective(s): To identify changes in patient presentations, treatments and outcomes of low-grade gliomas (LGGs) over the past 50 years. Materials/Methods: Records of 852 adults diagnosed between 1960 and 2010 with WHO grade II LGGs were reviewed. Patients were grouped by those diagnosed before (group I: 1960-1989) and after (group II: 19902010) the widespread use of modern imaging. Survival curves were plotted using the Kaplan-Meier method and compared with the log-rank test. Statistical analysis of prognostic factors employed the Chi-squared test and Fisher’s exact test. Results: Median follow-up was 19.9 and 6.9 years for group I and group II, respectively. Overall, 296 (34.7%) patients received a surgical gross total resection (GTR) or radical subtotal resection (rSTR) and 556 (65.3%) received subtotal resection (STR) or biopsy alone (Bx). Post-operatively, 541 patients received radiation therapy (PORT), 118 received chemotherapy and 295 were observed. Patient gender and age at diagnosis were similar between the two groups (p > 0.05). Those diagnosed before 1990 more often presented with seizures (78% vs. 69%, p Z 0.01), headaches (46% vs. 23%, p < 0.0001) and sensory/motor impairment (40% vs. 28%, p Z 0.0002). In group II, significantly more oligodendrogliomas (44% vs. 10%, p < 0.0001) and fewer astrocytomas were identified histologically (22% vs. 59%, p < 0.0001). Over time, GTR was achieved more often (31% vs. 13%, p < 0.0001), fewer patients received PORT (58% vs. 74%, p < 0.0001) and more received chemotherapy (18% vs. 6%, p < 0.0001) in group II compared with group I. In both groups, PORT was preferentially delivered to patients with astrocytomas (p < 0.01) and those receiving STR/Bx (p < 0.0001). In group II, additional factors associated with the use of PORT included tumors 5 cm (p Z 0.002), those in deep locations (p < 0.0001), and patients over 40 years of age (p < 0.0001). Overall, 498 patients (59%) experienced progression, including 159 in group I and 339 in group II. Additionally, 419 (49%) deaths were recorded, which includes 233 from group I and 186 from group II. Median progression free survival (PFS) and overall survival (OS) were 4.4 and 8.9 years, respectively. While PFS was similar between the groups (p > 0.05), OS was better in group II (10-year OS, 54%) compared with group I (34%; p < 0.0001). Conclusions: OS for LGG appears to be improving over the last 50 years, despite similar rates of progression. In the modern cohort, more patients are being diagnosed with oligodendrogliomas and are undergoing extensive resections (GTR/rSTR), both of which are associated with improvements in OS. Due to risk factor stratification by clinicians, the use of PORT has declined and is primarily being used to treat high-risk tumors in modern patients. Author Disclosure: R. Youland: None. P.D. Brown: None. J.C. Buckner: None. I.F. Parney: None. J.H. Uhm: None. N.N. Laack: None.

91 Proton Therapy for Low-grade Gliomas: A Pilot Study H.A. Shih, J.C. Sherman, L.B. Nachtigall, B.K. Winrich, B.Y. Yeap, T.T. Batchelor, L.T. Thornton, K.S. Oh, W.T. Curry, and J.S. Loeffler; Massachusetts General Hospital, Boston, MA Purpose/Objective(s): To evaluate the role of proton therapy in the management of patients with low grade gliomas in regard to toxicity and progression free survival (PFS). Materials/Methods: WHO grade II glioma patients indicated for radiation therapy were enrolled in a prospective single arm trial of involved field proton therapy receiving a dose of 54 Gy(RBE) in 30 fractions. No prior

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cranial irradiation was permitted. Comprehensive baseline and regular post treatment evaluations of neuroendocrine function, neurocognitive functions, quality of life (QOL), and PFS were performed. Results: Of the 20 patients (median age 37.5) enrolled, 13 (65%) were men and 11 (55%) patients were treated at the time of progression. Primary tumor locations were frontal (11), temporal (8), and occipital (1) lobes. All patients tolerated the delivery of proton therapy without difficulty. Median follow-up after proton therapy was 2.7 years among 18 surviving patients with ongoing follow-up. New endocrine dysfunction was detected in 11 patients (55%, 95% CI 33-77%) including 13 new hormonal deficiencies. The axes affected were thyroid (20%), testosterone (23% of men), cortisol (15%), and growth hormone (15%). New neuroendocrine deficits were not associated with direct irradiation to the hypothalamic-pituitary complex (p Z 1.00). Baseline level of intellectual functioning on a standardized IQ measure was slightly above the normative mean for the group and remained stable at last follow-up. Executive function as measured on standardized tests of attention, working memory, behavior initiation and cognitive flexibility was also in the average range, though slightly below the normative mean at baseline (range of mean z-scores -0.38 to -0.12) but with improvement at 24 months (range of mean changes -0.03 to 0.82) and at last follow-up (range of mean changes 0.17 to 0.84). On baseline memory measures, learning and retention of verbal and visual information was within normal limits, though below the normative mean (range of mean z-scores -0.91 to -0.70); however, memory scores at last follow-up were improved (range of mean changes -0.03 to 0.66). QOL assessment by FACT-Brain show overall improvement at both 2 and 3 years follow-up with mean increase of 7.7 and 8.7 in total score, respectively. PFS at 2 and 3 years was 94% and 85%, respectively. Conclusions: Early results demonstrate that low grade glioma patients tolerate proton therapy well and a subset develops neuroendocrine deficiencies. There is no evidence for early decline in intelligence, executive function, memory, or QOL which may be partially attributable to limited integral dose to the brain by use of proton therapy. PFS is equivalent to that of photon based therapy. Author Disclosure: H.A. Shih: None. J.C. Sherman: None. L.B. Nachtigall: None. B.K. Winrich: None. B.Y. Yeap: None. T.T. Batchelor: None. L.T. Thornton: None. K.S. Oh: None. W.T. Curry: None. J.S. Loeffler: None.

92 Predictors of Durability of Response for Stereotactic Radiosurgery in the Treatment of Trigeminal Neuralgia J. Lucas, K. Marshall, D. Bourland, E. Shaw, T. Ellis, S. Tatter, and M.D. Chan; Wake Forest Baptist Medical Center, Winston-Salem, NC Purpose/Objective(s): A time-dependent failure pattern has emerged for the use of Radiosurgery) in the treatment of Trigeminal Neuralgia (TN) where pain relapse increases with increasing time after GRS. We aimed to determine factors associated with the durability of treatment response after GRS in the treatment of TN. Materials/Methods: Between 1999 and 2008, 777 GRS procedures for patients with TN were performed at our institution. Electronic medical records and telephone interviews were used to obtain follow-up data. Barrow Neurologic Institute (BNI) pain scale was used to determine preGRS and post-GRS pain scores. Evaluable fu data were obtained for 448 patients. Burchiel types I (n Z 353), type II (61) and atypical facial pain (32) were included in the analysis. Median follow-up time was 21.2 months (mos) (range, 3-86 mos). The mean maximum prescribed dose was 88 Gy (range, 80-97 Gy). Dosimetric variables recorded included dose to the dorsal root entry zone dose (DREZ), petrous dural ridge (PDR), pons maximum dose, and the cisternal nerve length. Other variables assessed included pain quality, prior surgical procedures, comorbidities, age, sex, post-GRS medication, and Burchiel subtype of TN. Cox proportional hazard regression was performed to identify covariates which affected time to treatment failure defined as time to BNI IV-V pain relapse (TTR). Predictors of GRS-associated complications were identified using a logistic regression analysis.

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Results: Freedom from BNI III-IV failure at 1, 2, and 5 years (yrs) was 73.3%, 64.5%, and 41.8%, respectively. Freedom from salvage surgery at 1, 2, and 5 yrs was 82%, 72%, and 50%, respectively. Freedom from BNI III-IV failure at 1, 2, and 5 yrs was 68%, 47%, and 25% for type II TN (log rank p < 0.001), and 46%, 41%, and 17% for atypical facial pain (log-rank p < 0.001). A total of 42% of patients developed post-GRS trigeminal dysfunction. Multivariate analysis revealed that development of postGKRS numbness (HR Z 0.47, p Z < 0.0001), and improved post-GRS BNI score at 6 mos (HR Z 0.009, p Z < 0.0001) were the dominant factors predictive of a durable response. For each increasing level of reported pain relief, we observed a corresponding decrease in the hazard for TTR. Non-Burchiel type I TN (HR Z 1.64, p Z 0.019) predicted for decreased durability of response. A logistic regression analysis was performed for the dominant factors predictive of GRS complications showed that increasing DREZ dose (OR 1.024, p Z 0.01) and the presence of paroxysmal sharp pain prior to treatment (OR 1.93, p Z 0.01) were associated with an increased risk of post-GRS trigeminal dysfunction. Conclusions: The durability of GRS for TN depends predominantly on the Burchiel pain type at presentation, post treatment BNI score, and the development of facial numbness after GRS. Author Disclosure: J. Lucas: None. K. Marshall: None. D. Bourland: None. E. Shaw: None. T. Ellis: None. S. Tatter: None. M.D. Chan: None.

Author Disclosure: J.A. Hattangadi: None. P. Chapman: None. D. Kim: None. M. Bussiere: None. A. Niemierko: None. A. Rowell: None. J. Daartz: None. C. Ogilvy: None. J. Loeffler: None. H. Shih: None.

93 Single Fraction Proton Beam Stereotactic Radiosurgery (PSRS) for Inoperable Cerebral Arteriovenous Malformations (AVMs) J.A. Hattangadi,1 P. Chapman,2 D. Kim,2 M. Bussiere,2 A. Niemierko,2 A. Rowell,2 J. Daartz,2 C. Ogilvy,2 J. Loeffler,2 and H. Shih2; 1Harvard Radiation Oncology Program, Boston, MA, 2Massachusetts General Hospital, Boston, MA Purpose/Objective(s): To evaluate AVM obliteration and post-treatment hemorrhage rates in a large single-institution experience of patients with inoperable cerebral AVMs who underwent PSRS. Materials/Methods: From 1991-2010, 242 consecutive patients with 254 cerebral AVMs received single fraction PSRS. Median age of the cohort was 39 years, 55% presented with neurologic deficits, and 22% had prior unsuccessful surgery or embolization. Twenty-three percent of AVMs were in high-risk areas (basal ganglia, thalamus, or brainstem). Median AVM target volume was 3.5 cc (range, 0.1-28.1) and the most common prescription dose was 15 Gray radiobiologic equivalent, prescribed to the 90% isodose. Univariable (UVA) and multivariable analyses (MVA) were performed to assess factors associated with obliteration and hemorrhage. Results: Median follow-up was 33 months (range, 12-195 months). Median time to total obliteration was 27 months (range, 2-174 months) and the 5- and 10-year cumulative incidence of total obliteration was 68% and 88%, respectively. On UVA, smaller target volume (hazard ratio [HR] 0.89, 95% confidence interval [CI] 0.85-0.93, p < 0.0001), smaller treatment volume (HR Z 0.93, 95% CI 0.90-0.96, p < 0.0001), and higher prescription dose (HR Z 1.16, 95% CI 1.07-1.26, p Z 0.001) were associated with total obliteration. On MVA, high risk location (adjusted HR Z [AHR] 0.46, 95% CI 0.29-0.75, p Z 0.002) and smaller target volume (AHR Z 0.86, 95% CI 0.81-0.92, p < 0.0001) were associated with total obliteration. There were 9 cases of post-treatment hemorrhage and cumulative incidence at 5 years was 7%. All hemorrhagic events occurred among patients with less than total obliteration, and three of these events were fatal. Larger target volume (HR Z 1.07, 95% CI 1.01-1.15, p Z 0.037) and larger treatment volume (HR Z 1.05, 95% CI 1.01-1.10, p Z 0.024) were associated with increased risk of hemorrhage. The most common complication was seizure, controlled with medications, both acutely (7%) and long-term (9.1%). Conclusions: The current series is the largest modern series of PSRS for cerebral AVMs. We show that cerebral AVMs can be safely treated with PSRS with a high rate of success and minimal morbidity. Post-treatment hemorrhage remains a small but potentially fatal risk among patients who have not responded to treatment.

94 Technique for Using Dynamic CT Angiography (dCTA) for Frameless Stereotactic Radiosurgical (SRS) Planning of Intracranial Arteriovenous Malformations (AVM) A. Haridass, S. Chakraborty, R. Chatelain, J. Szanto, C. Lum, S. Malone, and J. Sinclair; The Ottawa Hospital, Ottawa, ON, Canada Purpose/Objective(s): SRS is a safe and effective means of treating small, deep seated brain AVMs. Selective catheter angiograms continue to be the gold standard for localizing the AVM nidus but their 2D images makes integration into 3D radiation treatment planning(TP) difficult. Rotational 3D DSA has poor spatial resolution than CT angiogram. The new dynamic CTA(dCTA) is capable of imaging the whole brain with high spatial and temporal resolution. It makes it possible to choose a volume of brain with optimum level of contrast showing only the nidus without significant enhancement of the adjacent draining veins. The aim of our research is to define the utility of dCTA in determining the 3D contour of the nidus for accurate SRS targeting. We describe a technique for integration of dCTA into SRS TP for intracranial AVMs. Materials/Methods: The patients were scanned on a 320 slice CT scanner that has 16 cm of coverage to image the entire brain in a single rotation. For dCTA, following a timing bolus, the scan sequence and injection of the contrast (@ 5 mL/s, 35 mL) were started. At 7 seconds, a ‘mask’ noncontrast scan (300 mA 80 KV) was obtained to enable digital subtraction from the angiographic datasets. The angiographic acquisition was started 1s before the contrast arrival at the skull base as determined by the timing bolus. Dynamic continuous acquisition (100 mA 80 KV, 1/sec) of whole brain images were obtained for 16 seconds, allowing imaging to start with no contrast, continuing to peak arterial enhancement and end with the venous return phase. A complete data volume was reconstructed every 0.5 seconds (temporal resolution of 2 images/sec). The spatial resolution of each slice was 512 x 512 pixels with a 0.5 mm thickness. The data volumes are processed to create a digitally subtracted dCTA. The datasets were reviewed by the Neuroradiologist, Neurosurgeon and Radiation Oncologist to determine the temporal phase (T + 0s to T + 16s) of imaging best demonstrating the AVM nidus without contrast highlighting the draining veins of the AVM. This volume was then reformatted to the TP specifications (1 x 1 x 1 mm voxels) and the DICOM data was imported to the TP system for coregistration with the MRI to contour the nidus and treated to a dose of 12-20 Gy. This method adds more certainty in differentiating the nidus from the draining venous structures than using standard CTA that gives a snapshot view of the AVM. Results: Between October 2010 and November 2011, 9 patients were treated for inoperable small AVMs on a robotic radiosurgery system. Conclusions: We have described a technique for use of dynamic CT Angiograms in SRS treatment planning for AVMs. Further research regarding its utility in supplementing catheter angiograms in this setting is ongoing. Author Disclosure: A. Haridass: None. S. Chakraborty: None. R. Chatelain: None. J. Szanto: None. C. Lum: None. S. Malone: None. J. Sinclair: None.

95 Long-term Outcomes of Low-dose Fractionated Stereotactic Radiation Therapy of 46.8 Gy for Acoustic Schwannomas C.E. Champ, S. Mayekar, M.V. Mishra, D.W. Andrews, M. Werner-Wasik, K. Chapman, V. Gunn, H. Liu, J.J. Evans, and W. Shi; Thomas Jefferson University Hospital, Philadelphia, PA Purpose/Objective(s): Fractionated Stereotactic Radiation therapy (FSRT) is a noninvasive treatment for acoustic schwannomas (AS). An initial report from our institution has shown that a lower radiation treatment dose of 46.8 Gy results in improved hearing preservation when