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Brainstem Dose in Stereotactic Radiosurgery for Trigeminal Neuralgia
Volume 93 Number 3S Supplement 2015 Purpose/Objective(s): Recurrent meningiomas present a therapeutic challenge, often progressing despite multimodality salvage therapy. While radiation therapy is frequently utilized in the upfront setting for high-risk lesions, there is limited information regarding toxicity and outcomes following re-irradiation (re-RT) after recurrence. Our aim was to determine the local control (LC), overall survival (OS), and treatment-related toxicity after salvage re-irradiation. Materials/Methods: From our institutional database, we identified 154 patients with meningioma treated with conventionally fractionated radiation (cfRT) or stereotactic radiosurgery (SRS) between 1994 e2013. From this cohort, 24 patients (inclusive of 25 lesions) underwent re-RT for recurrent disease. Recurrence was defined as tumor regrowth within the original treatment volume and was confirmed by multidisciplinary consensus. Using Kaplan-Meier analysis, we estimated rates of LC and OS after re-RT. We evaluated predictors of clinical outcomes using Cox-Regression. Toxicity was collected retrospectively and graded according to the NCI CTCAE v4.03. Results: Median follow-up after re-RTwas 28.1 months (range 1.4 e 174.2). Patient median age was 60 years (41 e 81). Meningioma grade at the time of re-RT was WHO I (benign) in 20%, WHO II (atypical) in 52%, and WHO III (anaplastic) in 28%. The initial course of RTwas cfRT (76%; median dose 54 Gy) or SRS (24%; median dose 14 Gy). Re-RT modalities included cfRT (12%), SRS (24%), hypofractionated RT (16%), protons (8%), and temporary (32P) or permanent (125I) brachytherapy (40%). At the time of recurrence, the majority of patients underwent surgery in addition to radiation (72%). Nineteen lesions (76%) recurred after re-RT. The 1-year actuarial LC after re-RT was 50%, with a median time to progression of 10 months. WHO grade I or III predicted for worse LC on multivariate analysis (p Z .026 and .008, respectively). Of those lesions that recurred after re-RT, 8 (42%) underwent a second course of re-irradiation. The median OS after re-RT was 31.7 months, with a 2-yr OS of 69.6%. There were no significant predictors of OS. After re-RT, 34.8% of patients experienced Grade 2 - 3 toxicity. There were no grade 34 events. The most common adverse events were lethargy, ataxia, paresthesia, and weakness. Radionecrosis developed in 6 patients (24%), 4 of whom required long-term corticosteroids. Conclusion: Multimodality re-irradiation for recurrent meningiomas provides a 1-year LC rate of 50% with a low rate of serious toxicity (13%). Although most tumors studied were high grade, the 2-year overall survival was nearly 70%. Given the propensity for these recurrent lesions to relapse locally, further investigation is needed into potential predictive and targetable molecular biomarkers to improve outcomes in this challenging cohort of patients. Author Disclosure: R.M. Lanning: Employee; Bristol-Myers Squibb. M.O. Chohan: None. C. Ryan: None. R. Singh: None. Z.A. Kohutek: None. S.Q. Ogilvie: None. L. Cambridge: None. Y. Yamada: None. V. Tabar: None. K. Beal: None. P.H. Gutin: None.
2221 Brainstem Dose in Stereotactic Radiosurgery for Trigeminal Neuralgia R.B. Maymani, A.N. Arain, S. Ahmad, and O. Algan; University of Oklahoma Health Sciences Center, Oklahoma City, OK Purpose/Objective(s): Stereotactic radiosurgery (SRS) is a highly effective treatment for trigeminal neuralgia (TN). Doses of 70 to 90 Gy are delivered in a single fraction to the dorsal root entry zone (DREZ) of the involved trigeminal nerve, which can result in delivery of high dose to the adjacent brainstem. We report our institutional experience with stereotactic radiosurgery for TN focusing on prescription dose and dose to organs at risk. Materials/Methods: An IRB-approved retrospective review was completed of all TN patients treated with stereotactic radiosurgery at a University Center from 1997 to 2015. Two hundred twenty-eight patients (88 men, 140 women) were identified with a median age of 65 (range 22 to 101). Twentyfour patients (10.5%) had been previously treated. Ninety-nine targets (43.4%) were left-sided and 129 (56.6%) right-sided. MRI-based planning was used in all cases. Maximum point doses to the brainstem, cerebellum, cochlea, and lens are reported. Volume-based parameters are available for the brainstem in some cases. A single 4mm shot was utilized in 223 cases (97.8%), placed at the DREZ in 169 cases (74.1%). Dose was prescribed to
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the 100% isodose line (IDL) in the majority of cases (92.5%) with a median dose of 75 Gy (range 60-90 Gy). Plugs were used to protect organs at risk in 138 cases (60.5%). Descriptive statistics were used for calculating median, maximum and minimum values. Results: The maximum dose to the brainstem ranged from 3.5 to 77.9 Gy (median 15.2 Gy). The maximum dose to the cerebellum ranged from 0.8 to 24.8 Gy (median 4.6 Gy). The maximum dose to the ipsilateral cochlea ranged from <0.01 to 2.9 Gy (median 1 Gy). Thirty-two patients had a brainstem dose volume histogram (DVH) available with 2, 5, and 10 Gy volumes reported. In this population the maximum brainstem dose ranged from 6.8 to 48 Gy (median 11.7 Gy). The 2 Gy IDL included a median of 16% of the brainstem with a maximum of 32% and a minimum of 2%. The 5 Gy IDL covered a median of 3% of the brainstem with a maximum of 11% and a minimum of 1%. The 10 Gy IDL encompassed a median of 1% of the brainstem with a maximum of 5% and a minimum of 0%. DVH parameters reported here likely overestimate dose as a limited portion of the brainstem was identified. This population also includes a patient with TN secondary to skull base trauma in which a portion of the pons was intentionally treated. Conclusion: Stereotactic radiosurgery for TN can result in dose to the brainstem that exceeds conventional dose constraints. High maximum doses are seen, but DVH analysis shows rapid dose falloff with a very small volume of brainstem receiving above 10 Gy. Complication rates reported in the literature are quite low, suggesting that these pinpoint doses do not result in measurable toxicity. Our data adds further to discussion regarding brainstem tolerance and mechanism of action in SRS for TN. Author Disclosure: R.B. Maymani: None. A.N. Arain: None. S. Ahmad: None. O. Algan: None.
2222 A Multi-institutional Analysis of Patients Treated With Stereotactic Radiosurgery for Brain Metastases From Radioresistant Histologies C.A. Smith,1 E. McTyre,2 S. Isom,3 V.E. Kennedy,4 G. Luo,5 M. MoralesPaliza,5 W. Hinson,2 A.J. Cmelak,5 S.B. Tatter,2 M.D. Chan,2 and A. Attia5; 1Department of Radiation Oncology, Vanderbilt University Medical Center, Nashville, TN, 2Wake Forest University Baptist Medical Center, Winston-Salem, NC, 3Wake Forest School of Medicine, WinstonSalem, NC, 4Vanderbilt University School of Medicine, Nashville, TN, 5 Vanderbilt University Medical Center, Nashville, TN Purpose/Objective(s): Melanoma (Mel) and Renal Cell Carcinoma (RCC) are radioresistant histologies with a propensity for metastasis to the brain. Stereotactic radiosurgery (SRS) has been implicated in improving clinical outcomes in these histologies. This is a multi-institution retrospective cohort of patients receiving SRS as their first CNS-directed radiation therapy for brain metastases. Materials/Methods: Between 2004 and 2014, 387 patients with newly diagnosed brain metastases from Mel (nZ264) or RCC (nZ123) were treated with SRS across 2 major academic radiosurgery centers. Overall survival (OS), local failure (LF), distant brain failure (DBF), and neurologic death were estimated using Kaplan-Meier method from time of SRS treatment. Factors including age, gender, minimal prescribed dose, number of brain metastases, systemic disease burden, status of systemic disease, and Diagnosis-Specific Graded Prognostic Assessment (DS-GPA) were evaluated. Multivariate Cox proportional hazard regression model was used to determine covariates that predicted for OS, LF, DBF, and neurologic death. Results: Median overall survival was significantly greater for patients with RCC (11.1 mos) than Mel (6.4 mos) (pZ0.0089). OS at 1 year was 45.4% for RCC and 30.9% for Mel. There was no difference between histologies in rates of local failure following SRS (absolute RCC 10.6% vs Mel 9.1%, pZ.459). Distant brain failure was significantly less for RCC (42.3% at 1 year, Median time to DBF 13.3 mos) than for Mel (68.1% at 1 year, Median time to DBF 5 mos) (p<0.0001). Documented neurologic death occurred less in patients with RCC (21.1%) than Mel (29.5%) (pZ0.0026). Only 4/387 patients (1%) developed symptomatic radionecrosis. On multivariate analysis, DS-GPA (RCC p <0.0001, Mel pZ0.016) predicted for improved OS, while progressive or unknown systemic disease status at time of SRS (RCC pZ0.0055, Mel p<0.0001) predicted for poor OS.
2221 Brainstem Dose in Stereotactic Radiosurgery for Trigeminal Neuralgia R.B. Maymani, A.N. Arain, S. Ahmad, and O. Algan; University of Oklahoma Health Sciences Center, Oklahoma City, OK Purpose/Objective(s): Stereotactic radiosurgery (SRS) is a highly effective treatment for trigeminal neuralgia (TN). Doses of 70 to 90 Gy are delivered in a single fraction to the dorsal root entry zone (DREZ) of the involved trigeminal nerve, which can result in delivery of high dose to the adjacent brainstem. We report our institutional experience with stereotactic radiosurgery for TN focusing on prescription dose and dose to organs at risk. Materials/Methods: An IRB-approved retrospective review was completed of all TN patients treated with stereotactic radiosurgery at a University Center from 1997 to 2015. Two hundred twenty-eight patients (88 men, 140 women) were identified with a median age of 65 (range 22 to 101). Twentyfour patients (10.5%) had been previously treated. Ninety-nine targets (43.4%) were left-sided and 129 (56.6%) right-sided. MRI-based planning was used in all cases. Maximum point doses to the brainstem, cerebellum, cochlea, and lens are reported. Volume-based parameters are available for the brainstem in some cases. A single 4mm shot was utilized in 223 cases (97.8%), placed at the DREZ in 169 cases (74.1%). Dose was prescribed to
Poster Viewing Session
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the 100% isodose line (IDL) in the majority of cases (92.5%) with a median dose of 75 Gy (range 60-90 Gy). Plugs were used to protect organs at risk in 138 cases (60.5%). Descriptive statistics were used for calculating median, maximum and minimum values. Results: The maximum dose to the brainstem ranged from 3.5 to 77.9 Gy (median 15.2 Gy). The maximum dose to the cerebellum ranged from 0.8 to 24.8 Gy (median 4.6 Gy). The maximum dose to the ipsilateral cochlea ranged from <0.01 to 2.9 Gy (median 1 Gy). Thirty-two patients had a brainstem dose volume histogram (DVH) available with 2, 5, and 10 Gy volumes reported. In this population the maximum brainstem dose ranged from 6.8 to 48 Gy (median 11.7 Gy). The 2 Gy IDL included a median of 16% of the brainstem with a maximum of 32% and a minimum of 2%. The 5 Gy IDL covered a median of 3% of the brainstem with a maximum of 11% and a minimum of 1%. The 10 Gy IDL encompassed a median of 1% of the brainstem with a maximum of 5% and a minimum of 0%. DVH parameters reported here likely overestimate dose as a limited portion of the brainstem was identified. This population also includes a patient with TN secondary to skull base trauma in which a portion of the pons was intentionally treated. Conclusion: Stereotactic radiosurgery for TN can result in dose to the brainstem that exceeds conventional dose constraints. High maximum doses are seen, but DVH analysis shows rapid dose falloff with a very small volume of brainstem receiving above 10 Gy. Complication rates reported in the literature are quite low, suggesting that these pinpoint doses do not result in measurable toxicity. Our data adds further to discussion regarding brainstem tolerance and mechanism of action in SRS for TN. Author Disclosure: R.B. Maymani: None. A.N. Arain: None. S. Ahmad: None. O. Algan: None.
2222 A Multi-institutional Analysis of Patients Treated With Stereotactic Radiosurgery for Brain Metastases From Radioresistant Histologies C.A. Smith,1 E. McTyre,2 S. Isom,3 V.E. Kennedy,4 G. Luo,5 M. MoralesPaliza,5 W. Hinson,2 A.J. Cmelak,5 S.B. Tatter,2 M.D. Chan,2 and A. Attia5; 1Department of Radiation Oncology, Vanderbilt University Medical Center, Nashville, TN, 2Wake Forest University Baptist Medical Center, Winston-Salem, NC, 3Wake Forest School of Medicine, WinstonSalem, NC, 4Vanderbilt University School of Medicine, Nashville, TN, 5 Vanderbilt University Medical Center, Nashville, TN Purpose/Objective(s): Melanoma (Mel) and Renal Cell Carcinoma (RCC) are radioresistant histologies with a propensity for metastasis to the brain. Stereotactic radiosurgery (SRS) has been implicated in improving clinical outcomes in these histologies. This is a multi-institution retrospective cohort of patients receiving SRS as their first CNS-directed radiation therapy for brain metastases. Materials/Methods: Between 2004 and 2014, 387 patients with newly diagnosed brain metastases from Mel (nZ264) or RCC (nZ123) were treated with SRS across 2 major academic radiosurgery centers. Overall survival (OS), local failure (LF), distant brain failure (DBF), and neurologic death were estimated using Kaplan-Meier method from time of SRS treatment. Factors including age, gender, minimal prescribed dose, number of brain metastases, systemic disease burden, status of systemic disease, and Diagnosis-Specific Graded Prognostic Assessment (DS-GPA) were evaluated. Multivariate Cox proportional hazard regression model was used to determine covariates that predicted for OS, LF, DBF, and neurologic death. Results: Median overall survival was significantly greater for patients with RCC (11.1 mos) than Mel (6.4 mos) (pZ0.0089). OS at 1 year was 45.4% for RCC and 30.9% for Mel. There was no difference between histologies in rates of local failure following SRS (absolute RCC 10.6% vs Mel 9.1%, pZ.459). Distant brain failure was significantly less for RCC (42.3% at 1 year, Median time to DBF 13.3 mos) than for Mel (68.1% at 1 year, Median time to DBF 5 mos) (p<0.0001). Documented neurologic death occurred less in patients with RCC (21.1%) than Mel (29.5%) (pZ0.0026). Only 4/387 patients (1%) developed symptomatic radionecrosis. On multivariate analysis, DS-GPA (RCC p <0.0001, Mel pZ0.016) predicted for improved OS, while progressive or unknown systemic disease status at time of SRS (RCC pZ0.0055, Mel p<0.0001) predicted for poor OS.