Analysis of the Factors Contributing to Vertebral Compression Fractures (VCF) After Spine Stereotactic Radiosurgery (SRS)

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International Journal of Radiation Oncology  Biology  Physics

light perception/no light perception. Thirty-seven percent (15/41) of patients had no change or improvement in their visual acuity categorization following treatment, 32% (13/41) had one level of decline, and 32% (13/41) had two or more levels of decline (Table). Conclusion: Image guided I-125 notched plaque brachytherapy for papillary choroidal melanoma resulted in high local control rates with meaningful short-term vision preservation at our institution. Notched plaque brachytherapy may be considered as a globe-preserving option rather than enucleation for tumors of the optic nerve head. Author Disclosure: J.V. Hegde: None. T.A. McCannel: None. J.M. Lamb: None. J. Wang: None. D. Demanes: None. M. Kamrava: None.

Conclusion: To guide safe practice in an increasingly applied, but understudied field, we present consensus contouring guidelines for common clinical scenarios in postoperative spine SBRT for malignant vertebral metastases. Author Disclosure: K.J. Redmond: Research Grant; Elekta AB. S.P. Robertson: None. S.S. Lo: Research Grant; Elekta AB. Honoraria; Varian Medical Systems. Leading effort to develop appropriateness criteria; ACR. developing refresher course; RSNA. S.G. Soltys: None. S. Ryu: None. T.R. McNutt: None. S.T. Chao: None. I.J. Barani: None. Y. Yamada: None. A.J. Ghia: None. E.L. Chang: Honoraria; Elekta AB. J.P. Sheehan: None. A. Sahgal: Research Grant; Elekta AB. Honoraria; Elekta AB.

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International Consensus Contouring Guidelines for Postoperative Spine Stereotactic Body Radiation Therapy (SBRT) K.J. Redmond,1 S.P. Robertson,1 S.S. Lo,2 S.G. Soltys,3 S. Ryu,4 T.R. McNutt,1 S.T. Chao,5 I.J. Barani,6 Y. Yamada,7 A.J. Ghia,8 E.L. Chang,9 J.P. Sheehan,10 and A. Sahgal11; 1Johns Hopkins University, Baltimore, MD, 2University Hospitals Case Medical Center, Cleveland, OH, 3Stanford University, Stanford, CA, 4Stony Brook University, Stony Brook, NY, 5Cleveland Clinic, Cleveland, OH, 6University of California, San Francisco, San Francisco, CA, 7Memorial Sloan Kettering Cancer Center, New York, NY, 8MD Anderson Cancer Center, Houston, TX, 9 University of Southern California, Keck School of Medicine, Los Angeles, CA, 10University of Virginia, Charlottesville, VA, 11Sunnybrook Health Science Centre, Odette Cancer Centre, Toronto, ON, Canada

Analysis of the Factors Contributing to Vertebral Compression Fractures (VCF) After Spine Stereotactic Radiosurgery (SRS) D. Boyce-Fappiano,1 E. Elibe,1 L. Schultz,1 S. Ryu,2 M.S.U. Siddiqui,1 I.J. Chetty,1 J. Kim,1 I. Lee,1 J. Rock,1 B. Movsas,1 and F. Siddiqui1; 1 Henry Ford Health System, Detroit, MI, 2Stony Brook University, Stony Brook, NY

Purpose/Objective(s): Although postoperative SBRT for malignant spinal tumors is increasingly performed in clinical practice, few guidelines exist. The purpose of this study was to develop consensus contouring guidelines to promote safe and effective treatment. Materials/Methods: Eleven spine specialists, representing 11 international centers, independently contoured the GTV, CTV, spinal cord, and spinal cord planning risk volume (PRV) for 10 common and representative clinical scenarios in postoperative spine SBRT for metastatic solid tumor malignancies. Cases include: preoperative circumferential disease with variable residual epidural involvement (none, focal, circumferential); C2 and odontoid disease with lateralized epidural extension s/p biopsy and stabilization; anterior epidural disease s/p decompression and stabilization; anterolateral epidural disease s/p decompression and stabilization; posterior epidural disease s/p decompression; lateralized epidural disease s/p decompression and stabilization; vertebral body fracture s/p vertebroplasty; extensive paraspinal extension s/p laminectomy. Contours were imported into Computational Environment for Radiotherapy Research. Agreement between physicians was calculated quantitatively with an expectation minimization algorithm using Simultaneous Truth and Performance Level Estimation (STAPLE) with kappa statistics. Target volume definition guidelines were established by finding the optimized confidence level consensus contours using histogram agreement analyses. Results: Eleven radiation oncologists and 1 neurosurgeon submitted contours. The mean sensitivity and specificity were 0.875 (range: 0.745 e 0.970) and 0.921 (range: 0.894 e 0.985) for CTV and 0.875 (range: 0.717 e 0.957) and 0.914 (range: 0.875 e 0.961) for spinal cord, respectively. Mean kappa agreement was 0.661 (range: 0.539 e 0.813) for CTVand 0.636 (range: 0.279 e 0.826) for spinal cord (P < .001 for all cases). Optimized consensus contours were established for all patients with an 80% confidence interval. Consensus contouring recommendations for the CTV include treatment of the entire preoperative extent of bony and epidural disease, plus the immediately adjacent bony anatomic compartment minus the cord PRV. Cases of preoperative circumferential epidural extension treated using donut distribution, regardless of the extent of residual epidural extension. Spinal instrumentation was excluded except in regions otherwise at risk for disease involvement. True spinal cord was delineated using a CT myelogram or T2 variant MRI. Planning target volume expansion ranged from 0e1.5 mm and cord PRV expansion ranged from 0e2 mm.

Purpose/Objective(s): Vertebral compression fractures (VCF) are one of the potential complications after spine SRS; VCFs can cause severe disabling pain or neurologic deficits. Limited data is available on the rate of developing an SRS induced VCF and the factors that may contribute. Our study aimed to determine this rate and to elucidate some of the factors that might increase the risk. Materials/Methods: Nineteen hundred five vertebral bodies from 791 patients were treated with SRS for the management of primary or metastatic spinal lesions at our institution from 2001 to 2013; EMRs of these patients were retrospectively reviewed after IRB approval. CT and MRI were used to evaluate the primary endpoints of this study: development of a new VCF, progression of an existing VCF, and requirement of stabilization surgery after SRS. In order to be considered an SRS induced VCF, the VCF development/progression must have occurred within vertebral bodies treated with SRS; VCFs that developed or progressed concurrently with tumor progression, and VCFs that received stabilization surgery prior to SRS or within one week following SRS, were not included as SRS induced VCFs. Kaplan-Meier estimates and Cox regression methods adjusting for multiple levels and treatments within a patient were used to assess the relationship of specific factors with developing a VCF using time between SRS and VCF diagnosis as the outcome. Results: Five hundred twenty-six patients (66%) were deceased. Median survival time post-SRS was 10.2 mo. Follow-up was available for 1093 spinal levels in 455 patients. Majority of lesions received 18 Gy/ 1 fr (53%) or 16 Gy/1 fr (29%). Dose was not associated with developing a VCF (P Z .12). Median tumor volume was 55.5 cm3 ranging from 0.12 e 813.7 cm3 and was not associated with developing a VCF (P Z .12). One hundred twenty-nine VCFs (11.8%) in 99 patients were potentially SRS induced: 47 (36%) de novo, 45 (35%) VCFs progressed, and 37 (29%) required stabilization surgery after SRS. Median time to an event was 2.7 mo (range, 5 d to 54.9 m) with 66% occurring within the first 6 mo. Patients with a prior VCF had higher rates of “new” VCF (17% vs 8%). Patients with hematological (P Z .007) and lung cancers (P < .001) had increased risks of VCF, while patients with prostate cancer had decreased risk (P Z .005). Stereotactic radiosurgery in thoracic levels had increased risk of VCF (P Z .031). Lytic lesions had significantly higher rates of VCF compared to mixed and blastic lesions (19% vs 14% vs 7%, P Z .004). Patients with any prior RT also had a decreased risk of VCF (8% vs 16%, P < .001). Use of bisphosphonates was not protective (P Z .7). Vertebral compression fracture rate with exclusion of multiple myeloma patients was 8.3%. Conclusion: Our VCF rate was 11.8%. Previous VCF, lytic lesions, a hematological or lung malignancy, and thoracic levels, may increase the likelihood of developing SRS-induced VCF. To the best of our knowledge, this is the largest reported experience analyzing SRS induced VCFs, with one of the lowest event rates.

Volume 93  Number 3S  Supplement 2015 Author Disclosure: D. Boyce-Fappiano: None. E. Elibe: None. L. Schultz: None. S. Ryu: Research Grant; Varian Medical Systems, Palo Alto, CA. directs clinical affairs; Stony Brook Medicine. Overseas Department; Stony Brook Medicine. M.U. Siddiqui: Research Grant; Varian Medical Systems, Palo Alto, CA. I.J. Chetty: Research Grant; Varian Medical Systems, Palo Alto, CA, Philips HealthCare, Best, Netherlands. chair; ASTRO Scientific Program Committee Annual Conference. Director; Henry Ford Hospital. J. Kim: Research Grant; Varian Medical Systems, Palo Alto, CA. I. Lee: None. J. Rock: None. B. Movsas: Research Grant; Varian Medical Systems, Palo Alto, CA. Chair; Henry Ford Hospital, ASTRO. F. Siddiqui: Research Grant; Varian Medical Systems, Palo Alto, CA. ASTRO annual meeting scientific committee; ASTRO. ASTRO Liaison; Medical Dosimetry Certification Board. overseas department; Henry Ford Hospital.

126 Clinical Outcomes of Melanoma Brain Metastases Treated With Stereotactic Radiation and Anti-PD-1 Therapy K.A. Ahmed, D.G. Stallworth, P.A.S. Johnstone, L.B. Harrison, A.B. Etame, J.S. Weber, and G.T. Gibney; H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL Purpose/Objective(s): The anti-PD-1 therapy nivolumab has demonstrated significant clinical activity in patients with metastatic melanoma; however, little is known about the safety and outcomes in patients receiving anti-PD-1 therapy and stereotactic radiation for the treatment of brain metastases (BMs). Materials/Methods: Data were analyzed retrospectively from two nivolumab protocols enrolling 181 mostly metastatic melanoma patients at our institution. Patients were included if BMs were diagnosed and treated with stereotactic radiation within 6 months of receiving nivolumab. The primary endpoint of this study was neurotoxicity during or after radiation assessed by history/clinical examination, steroid requirement and semi-quantification of edema (scale of 0e3) and hemorrhage of BMs demonstrating >20% volume increase on follow-up MRI; secondary endpoints were BM control and survival. Results: Twenty-six patients with a total of 73 BMs treated over 30 sessions were identified. Median age was 54 (range: 33e79 years), 9 (35%) female. The median number of treated lesions per patient was 2 (range, 1e10). Nivolumab was received in the adjuvant setting in 7 (27%) patients. Radiation was delivered concurrently, before, or after nivolumab in 17 (23%), 33 (45%), and 23 (32%) lesions, respectively. Median time between radiation and nivolumab dosing was 3 months (range, 0.4e6 months) in 56 BMs treated before and after nivolumab. Median planning target volume (PTV) was 0.51 cm3 (range: 0.04e54.6 cm3), and lesions were treated to a median dose of 21 Gy (range: 16e30 Gy). All BMs were treated with stereotactic radiosurgery (SRS) in a single session except 12 BMs treated with fractionated stereotactic radiation therapy, (FSRT) of which 9 were in the postoperative setting. Three patients were placed on prophylactic steroids during radiation. An additional patient experienced grade 2 headaches following SRS with symptomatic relief after steroid treatment. No other treatment-related neurologic toxicities (nausea, vision changes, or focal weakness) or scalp reactions were reported during or after radiation. Eight (11%) local failures with a >20% increase in volume were noted. Hemorrhage was noted in 4 of these lesions and edema in 7 lesions with one grade 1 event, four grade 2, and two grade 3 events. For patients receiving SRS, median follow-up to date is 9.4 months. KaplanMeier (KM) local BM control at 6 and 12 months were 93.1% and 85.2%, respectively. Median overall survival (OS) was 19.6 and 16.5 months from the date of brain metastases diagnosis and radiation treatment, respectively. Conclusion: In our retrospective series, stereotactic radiation to melanoma brain metastases is well tolerated in patients who received anti-PD-1 therapy. Compared to historical data, BM control rates are similar, whereas, survival appears prolonged. Prospective evaluation is warranted. Author Disclosure: K.A. Ahmed: None. D.G. Stallworth: None. P.A. Johnstone: None. L.B. Harrison: None. A.B. Etame: None. J.S. Weber: None. G.T. Gibney: None.

Oral Scientific Sessions

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127 Temporally-Dependent Intracranial Control of Melanoma Brain Metastasis by Stereotactic Radiation Therapy in Patients Treated With Immune Checkpoint Blockade W. Jiang,1 Y. Rodriguez,1 B.Y.S. Kim,2 C. Tang,1 L. Haydu,1 A. Mahajan,1 M.A. Davies,1 P. Hwu,1 E.P. Sulman,1 P.D. Brown,1 and J. Li1; 1MD Anderson Cancer Center, Houston, TX, 2Mayo Clinic, Jacksonville, FL Purpose/Objective(s): Immune checkpoint blockade with CTLA-4 inhibitors, such as Ipilimumab, enhances antitumor immunity through the activation and proliferation of peripheral T lymphocytes. Multiple studies have also proposed that radiation therapy can boost antitumor immune response via the stimulation of tumor specific antigen release; however, whether a synergistic benefit exists between radiation therapy and immune checkpoint blockade is unclear; in particular, the exact timing between these two treatment modalities to achieve optimal therapeutic benefits remains unknown. Materials/Methods: From 2007 to 2014, patients diagnosed with metastatic melanoma who received Ipilimumab and SRS to the brain for new metastases after the initiation of immunotherapy were identified. Intracranial recurrence after SRS was defined as new enhancing lesions or interval progression of existing lesions on neuroimaging that required additional therapy. ALC was measured at baseline for each patient prior to SRS treatment (median Z 5 days). Cox proportional hazards models were used to estimate and test association between ALC measurements and clinical endpoints. Results: A total of 71 metastatic melanoma patients were included in our final analysis. All patients were treated with 3 mg/kg of Ipilimumab, and all received at least 2 doses prior to SRS. Majority of the patients (87.1%) continued with systemic therapies after radiation treatment. The median age at the time of SRS treatment was 61.6 years (range: 16.3 to 89.3). The median number of metastatic lesions treated was 2 (range: 1e22), with a median treatment dose of 20.0 Gy (range: 17.0e22.0). The mean time of SRS treatment from the last administered dose of Ipilimumab was 4.96 months. Patients who received SRS treatment within 5.5 months (n Z 51) of their last dose of Ipilimumab had significantly improved intracranial control as compared to patients who received SRS treatments after 5.5 month (n Z 20) (Median ICC: 8.09 vs 3.63 month, HR Z 0.474, 95% CI Z 0.253e0.887, P Z .019). Circulating ALC was predictive of treatment responses, as patients with a baseline ALC 1000/mL (n Z 43) had reduced risk of intracranial recurrence compared to those with ALC <1000/mL (n Z 28), (HR Z 0.378, 95% CI Z 0.212e0.675, P Z .001). This difference remained significant on multivariate analysis incorporating intracranial tumor burden and radiation doses delivered (ALC  1000/mL, HR Z 0.412, 95% CI Z 0.225e0.753, P Z .004). Conclusion: We have identified a temporal association between SRS delivery and CTLA-4 inhibitor treatment that correlates with improved control of melanoma brain metastases. Among patients who received SRS after Ipilimumab treatment there was improved intracranial control when SRS was given within 5.5 months of the last Ipilimumab treatment. Furthermore, for patients who received SRS treatments, circulating ALC predicted intracranial disease control. Author Disclosure: W. Jiang: None. Y. Rodriguez: None. B.Y. Kim: None. C. Tang: None. L. Haydu: None. A. Mahajan: None. M.A. Davies: None. P. Hwu: None. E.P. Sulman: None. P.D. Brown: None. J. Li: None.

128 BRAF-V600 Mutational Status is a Significant Associate of Brain Metastases Recurrence in Patients With Melanoma: A Retrospective Study R. Maxwell,1 X. Ye,1 C. Bettegowda,1 W. Sharfman,1 K.J. Redmond,2 L.R. Kleinberg,2 and M. Lim2; 1Johns Hopkins University School of Medicine, Baltimore, MD, 2Johns Hopkins University, Baltimore, MD Purpose/Objective(s): Brain metastases (BM) are common in melanoma patients and carry a poor prognosis. Melanoma patients frequently harbor