Resection Cavity Dynamics Following Implantation of Cesium-131 (Cs-131) Brachytherapy for Resection Brain Metastases Based on CT-Planning

Volume 87  Number 2S  Supplement 2013 months). When analyzing the time to recurrence in 2 month intervals, the highest rates of local brain failure occurred between 6-12 months after SRS. The highest rates of distant brain failure occurred between 4-12 months after SRS. Salvage options include SRS and WBRT; 12 patients (16%) were eventually salvaged by WBRT. Median overall survival was 18 months. Conclusions: For patients with a resected single brain metastasis treated with post-op SRS, local and distant brain failures were highest 4-12 months after radiosurgery. Therefore, surveillance imaging should be most frequent, possibly every 2 months, during the first year post-treatment and the frequency could be decreased thereafter. Author Disclosure: K. Kalakota: None. S.S. Rakhra: None. O. Hideki: None. I. Helenowski: None. M.H. Marymont: None. J.A. Kalapurakal: None. J.P. Chandler: None. M.P. Mehta: G. Consultant; Abbott, BristolMeyers-Squibb, Elekta, Genentech, Merck, Novartis, Novocure, Viewray. L. Stock Options; Accuray, Pharmacyclics. Q. Leadership; Pharmacyclics.

1034 Brain Metastases and Resection Cavities From Colorectal Carcinoma Treated With Stereotactic Radiosurgery Have Poor Local Control Compared to Noncolorectal Histology J. Pai,1 Z. Wang,1 J.L. Shaffer,1 I.C. Gibbs,1 D.T. Chang,1 A.C. Koong,1 S.D. Chang,2 G.R. Harsh,2 G. Li,2 and S.G. Soltys1; 1Department of Radiation Oncology, Stanford University Medical Center, Stanford, CA, 2 Department of Neurosurgery, Stanford University Medical Center, Stanford, CA Purpose/Objective(s): Colorectal carcinoma (CRC) metastases to the liver and lung have been shown to have poor local control to stereotactic ablative body radiation therapy. We sought to determine if similar radioresistance is seen for CRC brain metastases treated with stereotactic radiosurgery (SRS). Materials/Methods: We retrospectively evaluated the outcomes of SRS targeting 36 intact brain metastases and 18 post-resection cavities from 30 patients with evaluable follow-up with CRC treated from 2002-2012. Results were compared to 157 resection cavities from non-CRC histology as well as our previously published results of SRS for 145 intact metastases from radioresistant histologies (renal cell carcinoma [RCC] and melanoma). The Kaplan-Meier product-limit method was used to estimate rates of Local Control (LC) and Overall Survival (OS). The dose from hypofractionated SRS (1-5 fractions) was converted to a single session equivalent dose (SSED) (a/b of 10). Variables associated with LC and OS were evaluated with the Cox proportional hazards and log rank methods. Variables analyzed included Planning Target Volume (PTV) size and SSED (as continuous variables), and histology (CRC vs non-CRC). Results: For patients with CRC, the median follow-up was 10.7 months (range, 3-55 months). The median OS for patients with CRC was 11 months (range, 3-55 months) versus 15 months (range, 1-156 months) for non-CRC. The median SSED for intact brain lesions and resection cavities was 20 Gy10 (range, 15 - 24 Gy10) and 16 Gy10 (range, 12 - 24 Gy10), respectively. For intact metastases, the 1 year LC was 48% for CRC vs 87% for RCC/melanoma. For resection cavities, the 1 year LC was 56% for CRC vs 85% for non-CRC (p < 0.001). On univariate analysis, factors predictive of LC for intact metastases were CRC histology (p < 0.001) and PTV size (HR 0.141, p Z 0.002). LC at 1 year was 22% and 76% for tumor volume greater than vs less than the median PTV of 1.7 cc, respectively (p Z 0.01). For resection cavities, both PTV size and SSED were predictive for LC (SSED: HR Z 0.807, p Z 0.025; PTV: HR Z 0.667, p Z 0.04). Conclusions: Patients with CRC brain metastases have poor rates of LC compared to non-CRC patients. Further investigation is warranted to identify methods of intensifying treatment for this radioresistant histology. Author Disclosure: J. Pai: None. Z. Wang: None. J.L. Shaffer: None. I.C. Gibbs: None. D.T. Chang: None. A.C. Koong: None. S.D. Chang: None. G.R. Harsh: None. G. Li: None. S.G. Soltys: None.

Digital Poster Discussion Abstracts S161

1035 Factors Influencing Local Control and Survival in Patients Treated With Radiosurgery Following Surgical Resection of CNS Metastases J.C. Rosenberg,1 P. Rava,1 T.A. Dipetrillo,1 I. Mihaylov,2 D. Cielo,2 R. Cosgrove,2 and J.T. Hepel2; 1Tufts University Affiliated Hospitals, Boston, MA, 2Rhode Island Hospital, Providence, RI Purpose/Objective(s): To evaluate outcomes in patients with brain metastases treated with stereotactic radiosurgery to the resection bed. Materials/Methods: In compliance with IRB approval, patients with CNS metastases who underwent surgery followed by SRS to the operative bed from 2002-2010 were identified. SRS was performed using a gadolinium-enhanced, high-resolution, T1-weighted MRI delivering a mean dose of 18Gy (range, 14-22 Gy) prescribed to encompass the entire resection cavity. Whole brain irradiation was reserved for salvage. Patients were followed every 3 months clinically and with MRI. To assess any effect of treatment margin, a planning margin was estimated by comparing resection cavity and prescription isodose volumes assuming equivalent spheres. Outcomes were evaluated using KaplanMeier and log-rank analyses. Results: Eighty-seven consecutive patients with a median follow-up of 14 months (range, 2-257 months) were included. Mean age was 59 years and all patients had a KPS 70. NSCLC represented 49% of patients, and 29% had extracranial metastases. A solitary lesion was treated in 59%, while others received SRS to a mean of 3.4 lesions. The 1 and 2-yr local control rate were both 75%. Local failure was significantly associated with larger tumor size (>3 cm) (p Z 0.02) and larger resection cavity volume (>14 cc) (p Z 0.04). Local failure at 1 year was 89% vs 65% for cavities 14 cc vs >14 cc, respectively. Extent of resection, time from surgery to SRS, radiation dose, and histology were not significant. The median estimated target margin was 2.5 mm. Local control was not dependent on planning margin using either 2 mm or 3 mm as a cutoff. Regional CNS control at 1and 2-yrs was 56% and 39%, respectively. Median overall survival was 14.3 months, with 1-, 2-, and 5-yr actuarial survival of 54%, 39%, and 20%, respectively. Univariate analysis showed that only the presence of extracranial metastases was associated with regional CNS failure (p Z 0.03) and with worse survival (p < 0.001). There were no treatment related deaths. Imaging changes consistent with necrosis occurred in 10% of patients. Conclusions: SRS to the resection cavity is well-tolerated as sole treatment following surgery. Excellent local control is achievable, however, for larger resection cavities, local control is not optimal. No influence between planning margin and local control was identified. A subset of patients can achieve extended survival with this approach, but appropriate patient selection is crucial. Further studies are necessary to establish the relative value of this approach and the most appropriate patient population. Author Disclosure: J.C. Rosenberg: None. P. Rava: None. T.A. Dipetrillo: None. I. Mihaylov: None. D. Cielo: None. R. Cosgrove: None. J.T. Hepel: None.

1036 Resection Cavity Dynamics Following Implantation of Cesium-131 (Cs-131) Brachytherapy for Resection Brain Metastases Based on CT-Planning M. Yondorf, L. Nedialkova, B. Parashar, D. Nori, K. Chao, J. Boockvar, S. Pannullo, P. Stieg, T. Schwartz, and A. Wernicke; Weill Cornell Medical College, New York, NY Purpose/Objective(s): Velocity of tumor shrinkage is one of the factors that correlate with incidence of radiation necrosis (RN), with rapid shrinkage causing significant irradiation of surrounding brain tissue that originally outside the target volume. Our institution has reported the effective use of intra-operative application of Cs-131 brachytherapy for patients with newly diagnosed brain metastases with 0% of clinical RN as compared to I-125 which causes RN 0-26%. In this study, we prospectively

International Journal of Radiation Oncology  Biology  Physics

S162 Digital Poster Abstract 1036; Table Median (range) volumes for isodose lines Isodose line (%) 100 80 50 30

CT1 (cm3) 4.54 6.14 11.50 22.55

(1.30-15.10) (1.77-20.10) (3.48-36.40) (7.14-68.00)

Median percent change in volumes

CT2 (cm3) 4.56 6.12 11.50 22.59

(1.34-15.23) (1.84-20.10) (3.56-36.50) (7.30-68.25)

CT3 (cm3) 4.54 6.16 11.49 22.65

assess the resection cavity dynamics with the goal of determining the dose distribution over time and its potential impact on RN. Materials/Methods: After IRB approval, 24 patients underwent neurosurgical resection and intra-operative Cs-131 brachytherapy for newly diagnosed brain metastases on a prospective trial. At the time of resection the seeds were secured with Surgicel to prevent seeds migration and Tisseel is also added to resist cavity shrinkage. Fourteen of 24 patients received 3 post-operative CT scans (CT1 Z 1-2 days post-operative, CT2 Z 14 days, CT3 Z 30 days) and were included in this analysis. This time frame was analyzed as Cs-131 delivers 90% of the intended dose at 33 days post-implant. For each scan, BrachyVision software was utilized and each implanted seed was identified. The volume of dose distribution was then calculated based on the properties of the individual seeds for the 100%, 80%, 50%, and 30% isodose lines. Results: The Table lists the median volumes for each of the isodose lines for each timepoint and the median percent change in volumes for each of the isodose lines at each timepoint. There was no significant change in volume between CT1 and CT2 for any of the isodose lines (p > 0.97), or between CT1 and CT3 (p > 0.98), implying that the tumor cavity remained intact. Conclusions: Resection cavity shrinkage demonstrated in this study over time is negligible, thus potentially explaining 0% incidence of clinical RN in this patient population. Our results are supported by the literature which indicates that no statistically significant volume change occurs up to 33 days after surgery for most patients (Atalar et al). This potentially explains why the short t1/2 of Cs-131 makes an ideal radioisotope as compared to I-125 where resection cavity shrinkage may be of consequence as it only delivers 90% of its intended dose in a 200 day period. Author Disclosure: M. Yondorf: None. L. Nedialkova: None. B. Parashar: None. D. Nori: None. K. Chao: None. J. Boockvar: None. S. Pannullo: None. P. Stieg: None. T. Schwartz: None. A. Wernicke: None.

1037 Quantification of the Effect of Arm Position on Normal Tissue Location and Dosimetry in Pediatric Hodgkin Lymphoma K.A. Denniston and C. Lin; University of Nebraska Medical Center, Omaha, NE Purpose/Objective(s): Modern combined modality therapy for Hodgkin Lymphoma (HL) is associated with excellent patient outcomes. For this reason, treatment related late normal tissue toxicity is of primary concern when radiation treatment plans are designed. This study aimed to quantify the effect treatment position has on normal tissue spatial and dosimetric relationships in mediastinal irradiation for pediatric HL. Materials/Methods: The records of HL patients who received radiation therapy (RT) between 2008 and 2013 were reviewed. All pediatric patients received RT supine with arms akimbo and underwent post-chemotherapy PET/CT, primarily with arms raised. The anterior midline T6-7 disc space was defined on both CT simulation and PET/CT image sets and used as a reference. The lungs and humeral heads were contoured for all patients. For females, the breasts were also contoured and the nipple positions identified. The volumetric centers of all contoured organs were defined and the distance from the T6-7 disc space computed. A theoretical radiation plan was constructed for the raised arm CT dataset, using the same

(1.37-15.10) (1.88-20.00) (3.58-36.00) (7.31-67.24)

Isodose line (%)

CT1 (cm3)

100 80 50 30

0.00% 0.00% 0.00% 0.00%

CT2 (cm3) 0.44% 0.33% 0.00% 0.16%

CT3 (cm3) 0.11% 0.24% 0.09% 0.44%

technique as the arms akimbo plan. Dosimetric parameters analyzed include V5 (volume [cc] receiving 5 Gy), V10, V15, V20, mean and maximum dose. Arm position related spatial and dosimetric differences were compared using the Mann-Whitney test. Results: The study population was comprised of 16 pediatric HL patients treated with mediastinal RT (7 female, 9 male). Median patient age was 15 years (range, 12-18 years). The median lateral distance from the breast center/nipple to midline with arms akimbo was significantly larger than with arms raised (8.62 vs 7.73 cm for left breast, p Z 0.04; 10.73 vs 9.23 cm for left nipple, p Z 0.04; 8.71 vs 7.02 cm for right breast, p Z 0.0041; and 9.88 vs 7.93 cm, p Z 0.007 for right nipple). Raised arm position was associated with a median 2.75/2.95 cm decrease in breast/nipple separation. Increasing breast volume was correlated with larger arm position related changes in breast/nipple separation (Pearsons r Z 0.74, p Z 0.06, and r Z 0.85, p Z 0.02). Raised arm position also yielded increased median left and right breast V5, V10, V15, V20, and mean dose. Treatment position had no effect on humeral head or lung position, total lung dosimetry or on craniocaudal breast or nipple position. Conclusions: When treating young female HL patients with mediastinal RT, a raised arm versus akimbo position is associated with a statistically significant shift in bilateral breast position toward the midline and a resultant increase in radiation dose to the breasts. However, arm position had no effect on lung spatial or dosimetric characteristics. These findings warrant consideration when determining the optimal treatment position for female HL patients. Author Disclosure: K.A. Denniston: None. C. Lin: None.

1038 Phase 2 Study of Consolidative Involved-Node Proton Therapy in Patients With Hodgkin Lymphoma: Early Outcomes B.S. Hoppe,1 S. Flampouri,1 N.H. Dang,2 J.W. Lynch,2 C.G. Morris,1 Z. Li,1 and N.P. Mendenhall1; 1University of Florida Proton Therapy Institute, Jacksonville, FL, 2Department of Medicine, College of Medicine, University of Florida, Gainesville, FL Purpose/Objective(s): To describe the early outcomes of patients with Hodgkin lymphoma (HL) involving the mediastinum treated with consolidative involved-node proton therapy (INPT) on a prospective study. Materials/Methods: Between September 2009 and March 2012, 16 patients with de novo HL consented to treatment with double-scatter INPT on an IRB-approved protocol after completing chemotherapy. The cohort included 4 males and 12 females; the median age was 22 years (range, 7-57 years). Stage distribution included favorable early-stage (IIA, n Z 2), unfavorable early-stage (B symptoms and/or bulky disease, n Z 12), and advanced-stage (IIIA bulky, n Z 2) disease. Six patients were treated per pediatric protocols with 4 cycles of ABVE-PC or VAMP chemotherapy and 15 to 25.5 CGE of INPT. Ten patients were treated with 3 to 6 cycles of ABVD followed by INPT to between 30.6 and 36 CGE after a complete response(CR) by positron emission tomography (PET) to ABVD (n Z 8) or 39.6 CGE after a partial response (PR) by PET (PR; n Z 2). Patients were evaluated for toxicity weekly via Common Terminology Criteria for Adverse Events, v3.0, during treatment, then every 3 months for the first 2 years, and then every 6 months for the subsequent 3 years. Basic blood work and computed tomography (CT) and/or PET scans were performed every 6 to 12 months after treatment. Progression-free (PFS) and