Survival Benefit of Postoperative Radiation in Papillary Meningioma: Analysis of the National Cancer Data Base

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Medical College of Georgia/Augusta University Department of Radiation Oncology, Augusta, GA, 2Department of Neurosurgery, Georgia Regents University, Augusta, GA, 3Georgia Regents Health System, Augusta, GA, United States, 4Medical College of Georgia/Georgia Regents University Health System, Augusta, GA, 5Augusta University, Augusta, GA Purpose/Objective(s): Stereotactic radiosurgery (SRS) is a treatment modality for classic trigeminal neuralgia (cTN). The success of SRS in facilitating long term pain control (LTPC) and minimizing facial numbness (FN) is dependent on maximizing prescribed dose (PD) to the trigeminal nerve and minimizing PD to the brain stem (BS). We analyzed several internationally standardized SRS treatment parameters and assessed as a primary endpoint whether either of them would predict LTPC. Our secondary endpoint assessed the role of BS pertinent treatment parameters in FN risk. We hypothesized that higher energy and homogeneity indexes independently decrease the risk of treatment failure. Materials/Methods: Between 2007 and 2015, 178 cTN patients underwent Stereotactic Radiosurgery (SRS), with a 4 millimeter collimator. Pain outcomes were obtained in 100 of these patients. Pain before and after SRS was scored as level I-V per the Barrow Neurological Institute (BNI) pain intensity scoring criteria. Pain relief was graded as an improvement to BNI levels I, II, or III from pre-SRS BNI levels IV or V. Treatment failure (TF) was graded as a return to BNI levels IV or V or need for additional SRS or operative intervention. Time to TF (TTF) and FN (TFN) were measured. The energy index, conformity index, homogeneity index (HI) [(D2% minus D98%)/ D50%], and gradient index were calculated. BS D1CC, V10, and VB20 (volume receiving 20% of PD) were also assessed for purposes of secondary endpoint analysis. A statistical model using Cox regression evaluating our primary endpoint was designed comparing all TF and non-TF patients to determine TF risk. A similar model evaluating our secondary endpoint was designed comparing patients with and without FN to determine FN risk. Results: Median PD was 80 Gy [range (r): 70-80]. The median follow-up was 15 months (r: 1.5-82). The median time to initial response was 1 month (r: 0.05-5) and the median TTF was 20 months (r: 0-82). Ninety percent reported initial pain relief, and actuarial rates of freedom from TF at 12, 24, 36, and 48 months were 55, 40, 33, and 28%, respectively. Statistical modeling showed that HI was the only treatment parameter that independently predicted time to TF (P Z 0.0273). Each unit increase in HI had an 88.3% decrease in TF risk (HR Z 0.117; 95% CI Z 0.017-0.788). BS D1CC, V10, or VB20 did not predict FN. Conclusion: This is the first cTN series to suggest that optimization of the HI may enhance freedom from treatment failure and LTPC. Although this is a preliminary analysis, incorporation of the HI in treatment planning may be used to guide future SRS dosimetry in the treatment of cTN. Author Disclosure: E.M. Marchan: None. J. Vender: Vice Chair Neurosurgery; Medical College of Georgia Department of Neurosurgery. R.R. Cantrell: None. C. Alleyne: Chair Neurosurgery; Medical College of Georgia Department of Neurosurgery. C. Norris: None. N. Madden: None. J.A. Marascio: None. B.M. Rabatic: None. D. Zaenger: None. A. Al-Basheer: None. M. Aletan: None. A. Amoush: None. M. Pishgou: None. C.L. Ferguson: None. K. Huang: None. S. Shaaban: None. A. Green: None. F. Mott: None. R.E. Figueroa: None. W.F. Mourad: Interim Chair; Medical College of Georgia Department of Radiation Oncology.

1030 Optic Nerve Drifting and Dose Deformations on Optic Chiasma Due to Eyeball Movements During Frameless Pituitary Radiosurgery V. Shankar, V.R. Thakorbhai, C. Haritha, V. Kumar, and A.R. Gupta; Geetanjali Cancer Center, Udaipur, Rajasthan, India Purpose/Objective(s): Pituitary radiosurgery planning is complex because a highly conformal dose plan is needed to spare the optic apparatus (optic nerves, chiasm, and tracts) as well as any remaining normal pituitary gland. Dose selection is based on the tolerance of the adjacent structures. Present study we attempted to analyze the accumulated doses delivered to Optic apparatus when patients undergoing pituitary radiosurgery drift their eyeballs.

International Journal of Radiation Oncology  Biology  Physics Materials/Methods: Fifteen functional pituitary adenomas (8 women and 7 men) treated in 2015 underwent a double reinforced thermoplastic immobilization and thin slice cranial CT scan (0.625mm) and contrast enhanced stereotactic 3-D volume MRI scan (gradient recalled). Following CT-MR fusion, target volume and critical organ delineation all patients underwent volumetric radiosurgery (VMRS) planning using FFF technology using 5 mm MLC. Prescribed total dose was 18 Gy in single fraction. Constraints used: D-max Optic Chiasma <8 Gy, Vol 10Gy temporal lobe <10 mL. All patients simultaneously underwent 4-D CT simulation with voluntarily induced lateral eyeball motion (External voice command was used to induce motion during image acquisition). The contours of the original MR-CT scan were deformably mapped and accumulated doses (predicted doses) calculated on dose warped 4-D dataset using free form intensity based cubic B splines deformable registration algorithm. The registration accuracy was Quality assured using Reg-refine and Reg-reveal tools using alignment locks. The contribution of the varying geometric errors to optic apparatus between deformable accumulated predicted dose and original static CT Scan were quantified for tumor and OAR. Changes greater than 0.5 Gy, reported as percent change (normalized to prescription dose), were considered potentially significant. Results: Mean optic apparatus gaze shift was 2.5 mm for optic nerve (2-5 mm) and 1.7mm for optic chiasma (1.2 e 3 mm), respectively. All evaluable patients had accumulated dose deviations relative to the planned static prescription dose >5% on optic apparatus ranging from 1.5-6% and 3-6% for tumors. Conclusion: This is the first study reported in literature evaluating the accumulated dose differences in simulated optic drift scenario. Impeding the eyeball motion for frameless technology is not available from any of the commercial vendors, using FFF technology will offset the errors due to gaze shifts which happen during the treatment as the effective beam on time is 1.5 mts. Author Disclosure: V. Shankar: None. V.R. Thakorbhai: None. C. Haritha: None. V. Kumar: None. A.R. Gupta: None.

1031 Survival Benefit of Postoperative Radiation in Papillary Meningioma: Analysis of the National Cancer Data Base W. Sumner,1 A. Amini,1 T.C. Hankinson,2 N.K. Foreman,2 L.E. Gaspar,1 B.D. Kavanagh,1 S. Karam,3 C.G. Rusthoven,1 and A.K. Liu1; 1 Department of Radiation Oncology, University of Colorado Denver, Aurora, CO, 2Department of Pediatrics, Division of Hematology and Oncology, University of Colorado, Aurora, CO, 3University of Colorado Denver, Anschutz Medical Campus, Aurora, CO Purpose/Objective(s): Papillary meningioma represents a rare subset of World Health Organization (WHO) Grade III meningioma that portends an overall poor prognosis. There is relatively limited data regarding the benefit of postoperative radiation therapy (PORT). We used the National Cancer Data Base (NCDB) to compare overall survival (OS) outcomes of surgically resected papillary meningioma cases undergoing PORT compared to observation. Materials/Methods: The NCDB was queried for patients with papillary meningioma, diagnosed between 2004 and 2013, who underwent upfront surgery with or without PORT. Extent of surgery was not coded in the NCDB. Overall survival (OS) was determined using the Kaplan-Meier method. Univariate (UVA) and multivariate (MVA) analyses were performed using Cox proportional hazards regression models. Results: In total, 197 patients were identified; 94 patients underwent PORT, 103 patients were observed. Eleven patients received chemotherapy (6 with PORT, 5 without). Unadjusted 2-year OS was significantly better with PORT vs. observation (93.0% vs. 74.8%), as was 5-year OS (79.3% vs. 63.2%) (hazard ratio [HR] Z 0.47; 95% confidence interval [CI] Z 0.27-0.83; P Z 0.009). After accounting for age, gender, race, insurance status, comorbidity score, year of diagnosis, and receipt of chemotherapy, patients receiving PORT had improved OS compared to those who were observed (HR Z 0.45; 95% CI Z 0.25-0.83; P Z 0.011). On subset analysis by age group, the benefit of PORT vs. observation was significant

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in patients 18 years (n Z 13), with 2-year OS of 85.7% vs. 50.0% (HR Z 0.08; 95% CI Z 0.01-0.80; P Z 0.032) and for patients >18 years (n Z 184), with 2-year OS of 95.0% vs. 76.5% (HR Z 0.54; 95% CI Z 0.30-0.97; P Z 0.039), respectively. At 30 months, all patients 18 years who had not received RT had died. Conclusion: PORT appears to improve OS in both pediatric and adult patients with papillary meningioma in this population-based analysis and should therefore be considered in those who present with this rare, aggressive tumor. Author Disclosure: W. Sumner: None. A. Amini: None. T.C. Hankinson: None. N.K. Foreman: None. L.E. Gaspar: None. B.D. Kavanagh: None. S. Karam: None. C.G. Rusthoven: None. A.K. Liu: None.

Conclusion: Regions of cerebral cortex involved in higher-order cognitive functions such as attention and memory showed significant dose-dependent atrophy after radiotherapy, whereas primary sensory and motor areas did not. Author Disclosure: T.M. Seibert: None. R. Karunamuni: None. S. Kaifi: None. J. Burkeen: Employee; Louisiana State University. A. Krishnan: None. C. McDonald: None. N. White: None. N. Farid: None. H. Bartsch: None. T. Nguyen: None. V. Moiseenko: Honoraria; Varian Medical Systems. J. Brewer: Stock Options; CorTechs Labs, Inc., Human Longevity Institute, Inc. Advisory Board Member; Elan, Bristol-Myers Squibb, Avanir, Novartis, Genentech, Eli Lilly. A. Dale: Research Grant; GE Healthcare. Stock; CorTechs Labs, Inc. Stock Options; Human Longevity, Inc. Advisory Board Member; Human Longevity, Inc. J.A. Hattangadi: None.

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Selective Vulnerability of Cerebral Cortex Regions to Radiation DoseeDependent Atrophy T.M. Seibert, R. Karunamuni, S. Kaifi, J. Burkeen, A. Krishnan, C. McDonald, N. White, N. Farid, H. Bartsch, T. Nguyen, V. Moiseenko, J. Brewer, A. Dale, and J.A. Hattangadi; University of California, San Diego, La Jolla, CA

Funding Source, Self-Reported Conflicts of Interest, and the Interpretation of Conclusions of Phase 1, 2, and 3 Trials in NeuroOncology F.Y. Moraes,1 L.C. Mendez,2 J.H. Suh,3 N.K. Taunk,4 L. Souhami,5 B.J. Slotman,6 E. Weltman,7 and G.N. Marta, Sr8; 1Sı´rio Libaneˆs Hospital, Sa˜o Paulo, Brazil, 2Universidade de Sa˜o Paulo, Sa˜o Paulo, Brazil, 3Department of Radiation Oncology, Cleveland Clinic, Cleveland, OH, 4Memorial Sloan Kettering Cancer Center, New York, NY, 5McGill, Montreal, QC, Canada, 6VU University Medical Center, Amsterdam, Netherlands, 7Hospital Israelita Albert Einstein, Sao Paulo 04614-001, Brazil, 8 Department of Radiation Oncology Hospital Sı´rio-Libaneˆs and Instituto do Caˆncer do Estado de Sa˜o Paulo - Faculdade de Medicina da Universidade de Sa˜o Paulo, Sao Paulo, Brazil

Purpose/Objective(s): Brain radiation therapy (RT) is associated with cognitive impairment, which may be mediated in part by damage to cerebral cortex. Neurological deficits observed after RT typically involve decreased higher cognitive functions (i.e., attention and memory) rather than somatosensory defects or paralysis. We sought to find out whether higher-order association cortex is selectively vulnerable to radiationinduced atrophy using quantitative volumetric MRI. We hypothesized that radiation dose-dependent cortical thinning would be more likely in the entorhinal cortex (subserving memory) and inferior parietal cortex (active in memory retrieval and attention tasks) than in primary visual, sensory, or motor cortex. Materials/Methods: We measured change in cortical thickness among 23 glioma patients who received fractionated partial brain RT. Study patients had high-resolution 3-D volumetric MRI (T1-weighted IR-SPGR and T2 FLAIR) prior to and one year after radiotherapy. MRI data were corrected for distortion and registered to RT dose data. Automated software and visual verification were used to segment cerebral cortex and identify anatomic regions of interest. Tumor and surgical changes were censored. Two anatomic regions were selected (bilaterally) to represent high-order association cortex: entorhinal and inferior parietal. Two additional regions represented primary cortex: primary visual and paracentral lobule (primary sensory/motor for lower extremities). Cortical thickness was measured at pre-radiation baseline and at one year after RT for each region. Average change in cortical thickness in each region was tested for correlation with the radiation dose received. Student’s t-test was applied to assess whether greater cortical thinning (i.e., percent change in thickness) was observed after a larger radiation dose. Statistical significance was set at a Z 0.05. Results: Among 23 patients, median dose was 60 Gy and all received temozolamide. The most common tumor location was temporal lobe (48%). At one year post-RT, we found that cortical thinning was significantly correlated with radiation dose in the inferior parietal cortex (P < 0.01) and was borderline significant in the entorhinal cortex (P Z 0.05). In contrast, areas of primary cortex did not show dosedependent cortical thinning: paracentral cortex (P Z 0.90), primary visual (P Z 0.44). Mean change in cortical thickness for all entorhinal and inferior parietal regions receiving >40 Gy was -0.295 mm (P < 0.05) vs 0.014 mm (P Z 0.86) for primary cortex regions.

Purpose/Objective(s): To determine whether there is an association between industry sponsorship, article specific self-related conflict of interest (COI) with central nervous system (CNS) clinical trials (CT) positive conclusions. Materials/Methods: A systematic review was performed for original CT (Phase 1, Phase 2, Phase 3 CT and Randomized CT) on “Central Nervous System Neoplasms”[Mesh]. Two investigators analyzed each article according to demographics, relationships between funding source (industry, academia or cooperative, none or not described); article self-reported COI (present, none, or not reported) and conclusions (positive, neutral or negative). Logistic regression multivariable models were used to assess predictors of favorable conclusions and CT characteristics. Results: From February 2010 to February 2015, 1,258 articles were retrieved: 319 were considered eligible trials and 263 (82.4%), 39 (12.2%), 11 (3.4%), 4 (1.3%), and 2 (0.6%) evaluated drugs, radiotherapy, procedures, drugs and radiotherapy, and drugs and procedures, respectively. Funding source, COI statement and conclusion assessment are reported in Table 1. Positive conclusions were reported in 56.8%, 55.6%, and 60% of trials with industry, academia or cooperative and any COI, respectively, as compared with 77.8%, 76.4%, and 60.4% of those with no funding, not described funding source (OR Z 2.28, 95% CI Z 1.04-5.17, P Z 0.011) and no COI (P Z 0.997). Factors that were significantly associated with the presence of positive conclusion included trials in which design was phase 1 (OR Z 11.64, 95% CI Z 4.66-29.09, P < 0.001), geographic location (studies conducted outside North America or Europe) (OR Z 1.96, 95% CI Z 1.05-3.79, P Z 0.025), primary outcome (studies without overall survival or progression-free survival as primary endpoint) (OR Z 3.74, 95% CI Z 2.27-6.18, P < 0.001) and failure to disclose funding

Abstract 1033; Table 1. Absolute numbers and proportion of publication by year and associate Sponsorship, Conflict of interest and positive conclusion Year 2010 2011 2012 2013 2014

Total Trials by Year - n (%) 62 75 79 69 34

(19.4) (23.5) (24.8) (21.6) (10.6)

Related Sponsorship per Year* - n (%) 48 57 56 58 27

(19.5) (23.2) (22.7) (23.6) (11)

Presented COI per Year - n (%) 19 24 30 33 14

(15.8) (20) (25) (27.5) (11.7)

Positive Conclusion per Year - n (%) 33 42 51 43 23

(17.2) (21.9) (26.5) (22.4) (12.0)