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Objective: The objective of this study was to assess outcomes after Gamma Knife radiosurgery (GKRS) re-irradiation for palliation of patients with trigeminal pain secondary to recurrent malignant skull base tumors., Methods: From 2009 to 2016, 26 patients who had previously undergone radiation treatment to the head and neck received GKRS for palliation of trigeminal neuropathic pain secondary to recurrence of malignant skull base tumors. Twenty-two patients received single-fraction GKRS to a median dose of 17 Gy (range 15-20 Gy) prescribed to the 50% isodose line (range 43%-55%). Four patients received fractionated Gamma Knife Extend therapy to a median dose of 24 Gy in 3 fractions (range 21-27 Gy) prescribed to the 50% isodose line (range 45%-50%). Those with at least a 3-month follow-up were assessed for symptom palliation. Self-reported pain was evaluated by the numeric rating scale (NRS) and MD Anderson Symptom Inventory-Head and Neck (MDASI-HN) pain score. Frequency of as-needed (PRN) analgesic use and opioid requirement were also assessed. Baseline opioid dose was reported as a fentanyl-equivalent dose (FED) and PRN for breakthrough pain use as oral morphine-equivalent dose (OMED). The chi-square and Student t-tests were used to determine differences before and after GKRS., Results: Seven patients (29%) were excluded due to local disease progression. Two experienced progression at the first follow-up, and 5 had local recurrence from disease outside the GKRS volume. Nineteen patients were assessed for symptom palliation with a median follow-up duration of 10.4 months (range 3.0-34.4 months). At 3 months after GKRS, the NRS scores (n = 19) decreased from 4.65 ± 3.45 to 1.47 ± 2.11 (p < 0.001); MDASI-HN pain scores (n = 13) decreased from 5.02 ± 1.68 to 2.02 ± 1.54 (p < 0.01); scheduled FED (n = 19) decreased from 62.4 ± 102.1 to 27.9 ± 45.5 mcg/hr (p < 0.01); PRN OMED (n = 19) decreased from 43.9 ± 77.5 to 10.9 ± 20.8 mg/day (p = 0.02); and frequency of any PRN analgesic use (n = 19) decreased from 0.49 ± 0.55 to 1.33 ± 0.90 per day (p = 0.08). At 6 months after GKRS, 9 (56%) of 16 patients reported being pain free (NRS score 0), with 6 (67%) of the 9 being both pain free and not requiring analgesic medications. One patient treated early in our experience developed a temporary increase in trigeminal pain 3-4 days after GKRS requiring hospitalization. All subsequently treated patients were given a single dose of intravenous steroids immediately after GKRS followed by a 2-3-week oral steroid taper. No further cases of increased or new pain after treatment were observed after this intervention., Conclusions: GKRS for palliation of trigeminal pain secondary to recurrent malignant skull base tumors demonstrated a significant decrease in patient-reported pain and opioid requirement. Additional patients and a longer follow-up duration are needed to assess durability of symptom relief and local control.

Spine stereotactic radiosurgery (SSRS) is a noninvasive treatment for metastatic spine lesions. MD Anderson Cancer Center reports a quality assurance (QA) failure rate approaching 15% for SSRS cases, which we hypothesized is due to difficulties in accurately calculating dose resulting from a large number of small-area segments. Clinical plans typically use 9 beams with an average of 10 segments per beam and minimum segment area of 2-3 cm 2 . The purpose of this study was to identify a set of intensity-modulated radiation therapy (IMRT) planning parameters that attempts to optimize the balance among QA passing rate, plan quality, dose calculation accuracy, and delivery time for SSRS plans. Using Pinnacle version 9.10, we evaluated the effects of 2 IMRT parameters: maximum number of segments and minimum segment area. Initial evaluation of the data revealed that 5 segments per beam along with minimum segment area of 4 cm 2 and 4 monitor units (MU) per segment (5-4-4 plans) was the most promising. IMRT QA was performed using a PTW OCTAVIUS 4D phantom with a 2D detector array. Our data showed no significant plan quality change with decreased number of segments and increased minimum segment area. The average coverage of GTV and CTV was 82.5 ± 13% (clinical) vs 82.5 ± 13% (5-4-4) and 92.3 ± 8% (clinical) vs 91.5 ± 8% (5-4-4). Maximum point dose to cord was 11.4 ± 3.5 Gy (clinical) vs 11.0 ± 4.0 Gy (5-4-4). Total plan delivery time was decreased by an average of 11.3% for the 5-4-4 plans. For IMRT QA, the gamma index passing rate (distance to agreement: 2.5 mm, local dose difference: 4%) for the original plans vs the 5-4-4 plans averaged 90.3% and 91.9%, respectively. In conclusion, IMRT parameters of 5 segments per beam and 4 cm 2 minimum segment areas provided a better balance of plan quality, delivery efficiency, and plan dose calculation accuracy for SSRS., (Copyright © 2018 American Association of Medical Dosimetrists. All rights reserved.)

Purpose: We seek to establish the feasibility of using spine stereotactic radiosurgery (SSRS), allowing for spinal cord dose constraint relaxation, as the primary management of metastatic epidural spinal cord compression (MESCC) in inoperable patients., Methods and Materials: Inoperable patients with thoracic MESCC and no history of radiation were enrolled on this prospective phase 1 single-institution protocol. SSRS was delivered to a histology-dependent prescription dose of 18 or 24 Gy. Incremental spinal cord constraint relaxation was performed from a Dmax cohort of 10 Gy up to 16 Gy only if tumor progression occurred and the risk of radiation-induced myelopathy (RM) remained lower than the risk of tumor progression., Results: Thirty-two patients enrolled on the trial; 4, 12, 9, and 7 patients were in the 10 Gy, 12 Gy, 14 Gy, and 16 Gy cord Dmax cohorts, respectively. At baseline, there were 2 sites with MESCC grade 1A, 10 sites with grade 1B, 10 sites with grade 1C, 9 sites with grade 2, and 1 site with grade 3 disease. Among the 28 evaluable patients, the median overall survival was 28.6 months (95% confidence interval [CI], 9.2-48.0 months), and the 1-year local control was 89% (95% CI, 74%- 97%). With a median follow-up of 17 months, there were no cases of RM (upper 95% CI, 12%). In the cohort receiving a cord Dmax of 16 Gy, there were no cases of RM (upper 95% CI, 39%) with a median follow-up of 17 months (range, 12.7-21.0 months)., Conclusions: SSRS is a safe and effective tool in patients with MESCC. In high-risk inoperable patients with MESCC receiving SSRS, dose constraint relaxation of the cord constraint dmax to 16 Gy may be considered to optimize local control, with the acknowledgment that this is based on 6 evaluable patients who received this dose in this trial., (Copyright © 2018. Published by Elsevier Inc.)

Fractionated radiotherapy (FRT) plays a critical role in the management of gliomas. For glioblastoma, the irradiation dose of 60 Gy in 30 fractions with concomitant and adjuvant temozolomide is currently considered as a standard of treatment, and further dose escalation has failed to be of benefit in clinical trials. Hypofractionated radiation schedules may be applied in elderly patients or those with poor performance status. For anaplastic gliomas, the high-risk region is typically irradiated to a total dose of approximately 60 Gy in 1.8-2 Gy per fraction. For patients with 1p/19q co-deleted WHO grade III tumors (i.e., anaplastic oligodendrogliomas), FRT alone is currently not considered as an acceptable therapeutic approach. The use of adjuvant irradiation for low-grade gliomas is controversial; in high-risk patients, treatment with a dose of 45-54 Gy in 1.8 Gy per fraction is usually used. Long-term risks of FRT include radiation necrosis, neurocognitive decline, and neuroendocrine dysfunction. Modern techniques, such as intensity-modulated radiation therapy (IMRT) and proton therapy allow for modifications in radiation dosing and delivery while improving conformality and limiting irradiation of normal tissue., (© 2018 S. Karger AG, Basel.)

Purpose: To characterize outcomes of metastatic colorectal and non-small cell lung cancer (NSCLC) histologies, compared with other radiosensitive histologies, treated with spine stereotactic radiosurgery with regard to local control, overall survival, and predictors of response., Methods and Materials: A total of 127 patients with 148 spine stereotactic radiosurgery-treated metastatic lesions at our institution between 2003 and 2013 were reviewed. We assessed clinical endpoints in relation to histologic type, including local control (LC) and overall survival (OS), using univariate and multivariate analyses., Results: For all patients, the 1- and 2-year actuarial rates for LC were 82.6% and 75.8%, and rates for OS were 72.9% and 51.5% respectively. Among tumor histologies, 1-year cumulative incidence rates of local failure for thyroid, breast, lung, and colon cancer were 8.7%, 7.0%, 26.6%, and 39.6%, respectively. When analyzed together, NSCLC and colorectal cancers had significantly greater cumulative incidence rates at 1 and 2 years (30.4% and 38.7%, respectively) than other histologies (8.0% and 14.1% respectively, P=.0008). Non-small cell lung cancer/colorectal tumor status was a significant predictor of local failure in a competing risk univariate model (hazard ratio 2.12, 95% confidence interval 1.07-4.17, P=.03) and multivariate model (hazard ratio 2.35, 95% confidence interval 1.12-4.92, P=.024)., Conclusions: Spine stereotactic radiosurgery is an effective strategy in achieving local control of spine metastases, particularly among radiosensitive histologies. However, a subset of these classically defined histologies (NSCLC and colorectal) has a propensity toward local failure. In addition to resulting in poorer OS outcomes, the poor LC rates seen in NSCLC and colorectal cancers in this study are more consistent with a radioresistant phenotype, suggesting the need for optimized dosing regimens in this subgroup., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Spinal laser interstitial thermal therapy (LITT) appears to be a promising novel modality for treatment of epidural metastatic spine disease in patients who are poor candidates for larger-scale oncologic spinal surgery and can act synergetically with spinal stereotactic radiosurgery to maximize local control and palliate pain. This technique is ideally suited for the intraoperative MRI suite to monitor the extent of the ablation in the epidural space. As percutaneous navigation, imaging, and LITT technology improve, broader applicability of this minimally invasive technique in spinal oncology is foreseen., (Copyright © 2017 Elsevier Inc. All rights reserved.)

OBJECTIVE Given the relatively lower radiosensitivity of sarcomas and the locally infiltrative patterns of spread, the authors sought to investigate spine stereotactic radiosurgery (SSRS) outcomes for metastatic sarcomas and to analyze patterns of failure. METHODS The records of 48 patients with 66 sarcoma spinal metastases consecutively treated with SSRS between 2002 and 2013 were reviewed. The Kaplan-Meier method was used to estimate rates of overall survival (OS) and local control (LC). Local recurrences were categorized as occurring infield (within the 95% isodose line [IDL]), marginally (between the 20% and 95% IDLs), or out of field. RESULTS Median follow-up time was 19 months (range 1-121 months), and median age was 53 years (range 17-85 years). The most commonly treated histology was leiomyosarcoma (42%). Approximately two-thirds of the patients were treated with definitive SSRS (44 [67%]) versus postoperatively (22 [33%]). The actuarial 1-year OS and LC rates were 67% and 81%, respectively. Eighteen patients had a local relapse, which was more significantly associated with postoperative SSRS (p = 0.04). On multivariate modeling, receipt of postoperative SSRS neared significance for poorer LC (p = 0.06, subhazard ratio [SHR] 2.33), while only 2 covariates emerged as significantly correlated with LC: 1) biological equivalent dose (BED) > 48 Gy (vs BED ≤ 48 Gy, p = 0.006, SHR 0.21) and 2) single vertebral body involvement (vs multiple bodies, p = 0.03, SHR 0.27). Of the 18 local recurrences, 14 (78%) occurred at the margin, and while the majority of these cases relapsed within the epidural space, 4 relapsed within the paraspinal soft tissue. In addition, 1 relapse occurred out of field. Finally, the most common acute toxicity was fatigue (15 cases), with few late toxicities (4 insufficiency fractures, 3 neuropathies). CONCLUSIONS For metastatic sarcomas, SSRS provides durable tumor control with minimal toxicity. High-dose single-fraction regimens offer optimal LC, and given the infiltrative nature of sarcomas, when paraspinal soft tissues are involved, larger treatment volumes may be warranted.

The purpose of this study is to identify regions of spinal column in which more than three contiguous vertebrae can be reliably and quickly aligned within 1 mm using a 6-degree (6D) couch and full body immobilization device. We analyzed 45 cases treated over a 3-month period. Each case was aligned using ExacTrac x-ray positioning system with integrated 6D couch to be within 1° and 1 mm in all six dimensions. Cone-Beam computed tomography (CBCT) with at least 17.5 cm field of view (FOV) in the superior-inferior direction was taken immediately after ExacTrac positioning. It was used to examine the residual error of five to nine contiguous vertebrae visible in the FOV. The residual error of each vertebra was determined by expanding/contracting the vertebrae contour with a margin in millimeter integrals on the planning CT such that the new contours would enclose the corresponding vertebrae contour on CBCT. Submillimeter initial setup accuracy was consistently achieved in 98% (40/41) cases for a span of five or more vertebrae starting from T2 vertebra and extending caudally to S5. The curvature of spinal column along the cervical region and cervicothoracic junction was not easily reproducible between treatment and simulation. Fifty-seven percent (8/14) of cases in this region had residual setup error of more than 1 mm in nearby vertebrae after alignment using 6D couch with image guidance. In conclusion, 6D couch integrated with image guidance is convenient and accurately corrects small rotational shifts. Consequently, more than three contiguous vertebrae can be aligned within 1 mm with immobilization that reliably reproduces the curvature of the thoracic and lumbar spinal column. Ability of accurate setup is becoming less a concern in limiting the use of stereotactic radiosurgery or stereotactic body radiation therapy to treat multilevel spinal target., (© 2017 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.)

OBJECTIVE Image guidance for spinal procedures is based on 3D-fluoroscopy or CT, which provide poor visualization of soft tissues, including the spinal cord. To overcome this limitation, the authors developed a method to register intraoperative MRI (iMRI) of the spine into a neuronavigation system, allowing excellent visualization of the spinal cord. This novel technique improved the accuracy in the deployment of laser interstitial thermal therapy probes for the treatment of metastatic spinal cord compression. METHODS Patients were positioned prone on the MRI table under general anesthesia. Fiducial markers were applied on the skin of the back, and a plastic cradle was used to support the MRI coil. T2-weighted MRI sequences of the region of interest were exported to a standard navigation system. A reference array was sutured to the skin, and surface matching of the fiducial markers was performed. A navigated Jamshidi needle was advanced until contact was made with the dorsal elements; its position was confirmed with intraoperative fluoroscopy prior to advancement into a target in the epidural space. A screenshot of its final position was saved, and then the Jamshidi needle was exchanged for an MRI-compatible access cannula. MRI of the exact axial plane of each access cannula was obtained and compared with the corresponding screenshot saved during positioning. The discrepancy in millimeters between the trajectories was measured to evaluate accuracy of the image guidance RESULTS Thirteen individuals underwent implantation of 47 laser probes. The median absolute value of the discrepancy between the location predicted by the navigation system and the actual position of the access cannulas was 0.7 mm (range 0-3.2 mm). No injury or adverse event occurred during the procedures. CONCLUSIONS This study demonstrates the feasibility of image guidance based on MRI to perform laser interstitial thermotherapy of spinal metastasis. The authors' method permits excellent visualization of the spinal cord, improving safety and workflow during laser ablations in the epidural space. The results can be extrapolated to other indications, including biopsies or drainage of fluid collections near the spinal cord.

Purpose: We sought to validate the Prognostic Index for Spinal Metastases (PRISM), a scoring system that stratifies patients into subgroups by overall survival.Methods and materials: The PRISM was previously created from multivariate Cox regression with patients enrolled in prospective single institution trials of stereotactic spine radiosurgery (SSRS) for spinal metastasis. We assess model calibration and discrimination within a validation cohort of patients treated off-trial with SSRS for metastatic disease at the same institution., Results: The training and validation cohorts consisted of 205 and 249 patients respectively. Similar survival trends were shown in the 4 PRISM. Survival was significantly different between PRISM subgroups (P<0.0001). C-index for the validation cohort was 0.68 after stratification into subgroups., Conclusions: We internally validated the PRISM with patients treated off-protocol, demonstrating that it can distinguish subgroups by survival, which will be useful for individualizing treatment of spinal metastases and stratifying patients for clinical trials.

Background: Although surgery followed by radiation effectively treats metastatic epidural compression, the ideal surgical approach should enable fast recovery and rapid institution of radiation and systemic therapy directed at the primary tumor., Objective: To assess spinal laser interstitial thermotherapy (SLITT) as an alternative to surgery monitored in real time by thermal magnetic resonance (MR) images., Methods: Patients referred for spinal metastasis without motor deficits underwent MR-guided SLITT, followed by stereotactic radiosurgery. Clinical and radiological data were gathered prospectively, according to routine practice., Results: MR imaging-guided SLITT was performed on 19 patients with metastatic epidural compression. No procedures were discontinued because of technical difficulties, and no permanent neurological injuries occurred. The median follow-up duration was 28 weeks (range 10-64 weeks). Systemic therapy was not interrupted to perform the procedures. The mean preoperative visual analog scale scores of 4.72 (SD ± 0.67) decreased to 2.56 (SD ± 0.71, P = .043) at 1 month and remained improved from baseline at 3.25 (SD ± 0.75, P = .021) 3 months after the procedure. The preoperative mean EQ-5D index for quality of life was 0.67 (SD ± 0.07) and remained without significant change at 1 month 0.79 (SD ± 0.06, P = .317) and improved at 3 months 0.83 (SD ± 0.06, P = .04) after SLITT. Follow-up MR imaging after 2 months revealed significant decompression of the neural component in 16 patients. However, 3 patients showed progression at follow-up, 1 was treated with surgical decompression and stabilization and 2 were treated with repeated SLITT., Conclusion: MR-guided SLITT can be both a feasible and safe alternative to separation surgery in carefully selected cases of spinal metastatic tumor epidural compression., Abbreviations: cEBRT, conventional external beam radiation therapyESCC, epidural spinal cord compressionSLITT, spinal laser interstitial thermotherapySSRS, stereotactic spinal radiosurgeryVAS, visual analog scale.

OBJECTIVE An emerging paradigm for treating patients with epidural spinal cord compression (ESCC) caused by metastatic tumors is surgical decompression and stabilization, followed by stereotactic radiosurgery. In the setting of rapid progressive disease, interruption or delay in return to systemic treatment can lead to a negative impact in overall survival. To overcome this limitation, the authors introduce the use of spinal laser interstitial thermotherapy (sLITT) in association with percutaneous spinal stabilization to facilitate a rapid return to oncological treatment. METHODS The authors retrospectively reviewed a consecutive series of patients with ESCC and spinal instability who were considered to be poor surgical candidates and instead were treated with sLITT and percutaneous spinal stabilization. Demographic data, Spine Instability Neoplastic Scale score, degree of epidural compression before and after the procedure, length of hospital stay, and time to return to oncological treatment were analyzed. RESULTS Eight patients were treated with thermal ablation and percutaneous spinal stabilization. The primary tumors included melanoma (n = 3), lung (n = 3), thyroid (n = 1), and renal cell carcinoma (n = 1). The median Karnofsky Performance Scale score before and after the procedure was 60, and the median hospital stay was 5 days (range 3-18 days). The median Spine Instability Neoplastic Scale score was 13 (range 12-16). The mean modified postoperative ESCC score (2.75 ± 0.37) was significantly lower than the preoperative score (4.5 ± 0.27) (Mann-Whitney test, p = 0.0044). The median time to return to oncological treatment was 5 days (range 3-10 days). CONCLUSIONS The authors present the first cohort of sLITT associated with a percutaneous spinal stabilization for the treatment of ESCC and spinal instability. This minimally invasive technique can allow a faster recovery without prejudice of adjuvant systemic treatment, with adequate local control and spinal stabilization.

Background: Metastatic deposits to the spine in thyroid cancer patients represent the most common site of bone involvement and can contribute to pain, neurologic deficits, and death. This study sought to determine the efficacy and safety of spine stereotactic radiosurgery (SSRS) for thyroid cancer patients., Methods: Thyroid cancer patients with spine metastases were selected and analyzed from a cohort of patients who were prospectively enrolled in two single-institution Phase I/II studies. SSRS was delivered in single or multi-fraction schedules. Dose regimens ranged from 16-18 Gy in one fraction to 27-30 Gy in three to five fractions. Toxicity was graded according to the NCI-CTC toxicity scale. Local control was determined by serial post-treatment magnetic resonance imaging scans showing no evidence of progressive disease. Patients were followed until date of death or date of last known visit for survival analyses. Local control and overall survival rates were carried out using Kaplan-Meier estimates. The log-rank test was used to assess the equality of the survivor function across groups. A p-value of ≤0.05 was considered to be statistically significant., Results: A total of 27 spine lesions were treated in 23 patients over a six-year period. Median follow-up was 28.9 months (range 5-93 months). Local control was 88% at two years and 79% at three years. In patients with progressive disease following conventional radiation therapy, local control for salvage SSRS remained at 88% at three years. Patients requiring upfront surgical intervention and treated with adjuvant SSRS achieved sustained control rates of 86% at three years. Overall survival rates were 85% and 67% at one and two years, respectively. In patients classified with oligoprogression and controlled extra-spinal disease, overall survival was significantly higher than those with evidence of systemic progression (81% vs. 45% at two years; p = 0.01). Univariate analysis did not show significant correlations between local control and age, systemic disease status, prior (131)I therapy, SSRS fraction regimen, spine location, histological subtype, or time from initial diagnosis to evidence of spinal metastasis. No patient experienced any grade 3-5 toxicity. Pain flare was reported in 30% of patients, with only three patients (13%) requiring narcotics or short-course steroids. There was no evidence of vertebral body fracture in any patient that achieved local control in the treated area., Conclusions: SSRS for thyroid metastases as a primary or adjuvant/salvage therapy is well tolerated and yields high rates of local control.

OBJECTIVE The authors investigated the outcomes following spine stereotactic radiosurgery (SSRS) for patients with oligometastatic disease of the spine. METHODS The study was a secondary analysis of 38 of 209 patients enrolled in 2 separate institutional Phase I/II prospective protocols and treated with SSRS between 2002 and 2011. Of these 38 patients, 33 (87%) were treated for a solitary spine metastasis, with no other history of metastatic disease. SSRS was prescribed to 24 Gy in 1 fraction (8%), 18 Gy in 1 fraction (18%), 16 Gy in 1 fraction (11%), 27 Gy in 3 fractions (53%), 30 Gy in 5 fractions (8%), or 20 Gy in 5 fractions (3%). Seventeen patients (45%) received prior conventional external beam radiation therapy. RESULTS The median overall survival (OS) was 75.7 months, and the 2- and 5-year OS rates were 84% and 60%, respectively. In multivariate analysis, patients who had prior spine surgery and a better Karnofsky Performance Scale score had an improved OS (HR 0.16, 95% CI 0.05-0.52, p < 0.01, and HR 0.33, 95% CI 0.13%-0.84%, p = 0.02, respectively), and those who had undergone prior radiation therapy had a worse OS (HR 3.6, 95% CI 1.2%-10%, p = 0.02). The 1-, 2-, and 5-year local progression-free survival rates were 85%, 82%, and 78%, respectively. The median time to systemic therapy modification was 41 months. Two patients (5%) experienced late Grade 3-4 toxicity. CONCLUSIONS Patients with oligometastatic disease of the spine treated with SSRS can experience long-term survival and a long time before needing a modification in systemic therapy. In addition, SSRS leads to excellent local control and minimal late toxicity.

Purpose: To evaluate the outcomes in patients treated on prospective phase 1-2 protocols with postoperative stereotactic body radiation therapy (SBRT) and identify the associated prognostic variables., Methods and Materials: Sixty-six patients with 69 tumors were treated with SBRT on prospective phase 1-2 studies for spinal metastases between 2002 and 2010. All patients underwent SBRT after spine surgery, which included laminectomy, vertebrectomy, or a combination of these techniques. Renal cell carcinoma was the most common histology represented (n=35, 53%) followed by sarcomas (n=13, 20%). Thirty-one patients (47%) were treated with prior conventional radiation to the spine (median dose 30 Gy). Patients were followed up with spinal magnetic resonance imaging (MRI) studies to determine the treated tumor control (TC). Pain and other symptom data were collected prospectively to determine treatment response and toxicity., Results: The median follow-up time was 30 months (range, 1-145 months) for all patients and 75 months for living patients (range, 6-145 months). The actuarial 1-year rate of TC was 85%, adjacent vertebral body control was 85%, and overall survival (OS) was 74% (median 29 months). On multivariate competing-risks analysis, sarcoma histology (subhazard ratio [SHR] = 2.38, 95% confidence interval [CI] 1.05-5.6, P=.04) and larger preoperative tumor volumes (SHR=1.01, 95% CI 1.0-1.01, P=.006) were significantly associated with worse TC. Karnofsky performance status was the only significant predictor for OS on multivariate analysis. There were no differences in TC between patients treated with different surgical techniques or different preoperative or postoperative Bilsky grades. There were no grade 3 or higher neurologic toxicities., Conclusion: This study represents a large series of prospective data available on patients treated with SBRT in the postoperative setting. The combination of surgery with SBRT can offer patients with metastatic disease to the spine the chance of durable tumor control with minimal toxicity., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Removal of a pin during Gamma Knife stereotactic radiosurgery (GK-SRS) may be necessary to prevent collision and allow treatment., Objective: To investigate outcomes after GK-SRS for treatment of brain metastases using a head frame immobilized to the skull with only 3 pins., Methods: Between 2009 and 2014, we retrospectively reviewed the records of 1971 patients and identified 20 patients with multiple brain metastases treated with GK-SRS in which 1 anterior pin was removed immediately before treatment of a single posterior lesion. GK-SRS was also delivered to 116 other lesions in these 20 patients using the standard 4 pins during the same session, serving as an internal control for comparison. Endpoints included local control, dosimetric parameters, toxicity, and overall survival., Results: The median number of lesions treated per session was 6 (range, 2-14). The lesions treated using 3 pins were located in the occipital lobe (n = 14) or the cerebellum (n = 6). Median follow-up was 12.3 months. There was 1 local failure involving a control lesion. Lesions treated using 3 pins had a lower prescription isodose line. GK-SRS of a lesion using 3 pins did not cause any clinical toxicities or increase in radiographic edema or hemorrhage., Conclusion: Treating posteriorly located brain metastases with GK-SRS using only 3 pins provided excellent local control and no difference in treatment toxicity, which may make it a safe and reasonable option for lesions that may otherwise be difficult to treat.

OBJECTIVE The objective of this study was to compare fractionation schemes and outcomes of patients with renal cell carcinoma (RCC) treated in institutional prospective spinal stereotactic radiosurgery (SSRS) trials who did not previously undergo radiation treatment at the site of the SSRS. METHODS Patients enrolled in 2 separate institutional prospective protocols and treated with SSRS between 2002 and 2011 were included. A secondary analysis was performed on patients with previously nonirradiated RCC spinal metastases treated with either single-fraction (SF) or multifraction (MF) SSRS. RESULTS SSRS was performed in 47 spinal sites on 43 patients. The median age of the patients was 62 years (range 38-75 years). The most common histological subtype was clear cell (n = 30). Fifteen sites underwent surgery prior to the SSRS, with laminectomy the most common procedure performed (n = 10). All SF SSRS was delivered to a dose of 24 Gy (n = 21) while MF regiments were either 27 Gy in 3 fractions (n = 20) or 30 Gy in 5 fractions (n = 6). The median overall survival duration for the entire cohort was 22.8 months. The median local control (LC) for the entire cohort was 80.6 months with 1-year and 2-year actuarial LC rates of 82% and 68%, respectively. Single-fraction SSRS correlated with improved 1- and 2-year actuarial LC relative to MF SSRS (95% vs 71% and 86% vs 55%, respectively; p = 0.009). On competing risk analysis, SF SSRS showed superior LC to MF SSRS (subhazard ratio [SHR] 6.57, p = 0.014). On multivariate analysis for LC with tumor volume (p = 0.272), number of treated levels (p = 0.819), gross tumor volume (GTV) coverage (p = 0.225), and GTV minimum point dose (p = 0.97) as covariates, MF SSRS remained inferior to SF SSRS (SHR 5.26, p = 0.033) CONCLUSIONS SSRS offers durable LC for spinal metastases from RCC. Single-fraction SSRS is associated with improved LC over MF SSRS for previously nonirradiated RCC spinal metastases.

The aim of this study was to determine the predictability of vertebral compression fracture (VCF) development applying the spinal instability neoplastic score (SINS) prior to delivery of stereotactic spinal radiosurgery (SSRS) for spinal metastases. From two prospective cohorts of SSRS for spinal metastases, we selected patients with a low degree of cord compression or cauda equine from C3 to S1 and analyzed 79 patients enrolled according to binary SINS criteria. The primary endpoint was the development of a de novo VCF or progression of an existing fracture after SSRS. We identified 32 fractures (40.5%): 19 de novo and 13 progressive. The mean time to fracture after SSRT was 3.3 months (range, 0.4-34.1 months). In 41 patients with low SINS (0-6), 7 patients (17.1%) developed a fracture after SSRS. In 38 patients with high SINS (7-12), 25 (65.8%) developed a fracture. Among the 32 fractures, 15 were symptomatic. Patients with high SINS were more likely to experience symptomatic fractures (31.6%) than were patients with lower SINS (7.4%). On univariate and multivariate analysis, 24-month fracture-free rates were 78.7 and 33.7% in low and high SINS group, respectively and high SINS was found to be a significant risk factor for VCFs and symptomatic fractures (respectively, HR 5.6, p = 0.04; HR 5.3, p = 0.01). SINS is a useful tool for predicting the development of VCF after SSRS for spinal metastases. Prophylactic cement augmentation should not be considered for patients with lower SINS, since the risk of fracture is low.

Background and Purpose: Osseous pseudoprogression on MR imaging can mimic true progression in lesions treated with spine stereotactic radiosurgery. Our aim was to describe the prevalence and time course of osseous pseudoprogression to assist radiologists in the assessment of patients after spine stereotactic radiosurgery., Materials and Methods: A secondary analysis of 2 prospective trials was performed. MRIs before and after spine stereotactic radiosurgery were assessed for response. "Osseous pseudoprogression" was defined as transient growth in signal abnormality centered at the lesion with a sustained decline on follow-up MR imaging that was not attributable to chemotherapy., Results: From the initial set of 223 patients, 37 lesions in 36 patients met the inclusion criteria and were selected for secondary analysis. Five of the 37 lesions (14%) demonstrated osseous pseudoprogression, and 9 demonstrated progressive disease. There was a significant association between single-fraction therapy and the development of osseous pseudoprogression (P = .01), and there was a significant difference in osseous pseudoprogression-free survival between single- and multifraction regimens (P = .005). In lesions demonstrating osseous pseudoprogression, time-to-peak size occurred between 9.7 and 24.4 weeks after spine stereotactic radiosurgery (mean, 13.9 weeks; 95% CI, 8.6-19.1 weeks). The peak lesion size was between 4 and 10 mm larger than baseline. Most lesions returned to baseline size between 23 and 52.4 weeks following spine stereotactic radiosurgery., Conclusions: Progression on MR imaging performed between 3 and 6 months following spine stereotactic radiosurgery should be treated with caution because osseous pseudoprogression may be seen in more than one-third of these lesions. Single-fraction spine stereotactic radiosurgery may be associated with osseous pseudoprogression. The possibility of osseous pseudoprogression should be incorporated into the prospective criteria for assessment of local control following spine stereotactic radiosurgery., (© 2016 by American Journal of Neuroradiology.)

In order to accurately assess positioning errors in spinal SBRT, many institutions employ bony-fusion based imaging techniques, such as the ExacTrac™ (Brain Lab) system, in conjunction with 3D verification (performed via CT-on-rails in our practice). We hypothesized that the use of implanted gold fiducial markers could improve the accuracy of patient positioning over bony fusion alone. We addressed this question prospectively, enrolling patients on an IRB-approved protocol. Gold seeds were implanted in the vertebral pedicles flanking the target level. At treatment, setup error was calculated using two methods-standard kV image fusion, and geometric fiducial-based projection, with independent CT-on-rails verification. Analyses of residual set-up error showed that fiducial-based setup agreed with fusion-based determination, but did not significantly reduce error. Offline 6D fusion of the treatment and planning CT illustrated residual rotational error using standard or fiducial based setup. We conclude that the ExacTrac and CT-on-rails platform yields highly accurate results for spinal SBRT setup, with reduced residual error than previously reported. While the addition of fiducials did not further reduce error, the bony fusion approach is now prospectively validated in comparison to implanted fiducials. Both bony fusion and fiducial marker methods are associated with residual rotational error, thus 3D verification remains an important component of spinal SBRT treatment., Competing Interests: Authors’ disclosure of potential conflicts of interest The authors reported no conflict of interest.

Purpose: To assess the dosimetric effects of respiratory motion on the target and spinal cord in spinal stereotactic body radiation therapy (SBRT)., Methods and Materials: Thirty patients with 33 lesions were enrolled on a prospective clinical protocol and simulated with both free-breathing and four-dimensional (4-D) computed tomography (CT). We studied the target motion using 4-D data (10 phases) by registering a secondary image dataset (phase 1 to 9) to a primary image dataset (phase 0) and analyzing the displacement in both translational and rotational directions. The study of dosimetric impacts from respiration includes both the effect of potential target and spinal cord motion and anatomic changes in the beam path. A clinical step-and-shoot IMRT plan generated on the free-breathing CT was copied to the 4-D datasets to evaluate the difference in the dose-volume histogram of target and normal tissues in each phase of a breathing cycle., Results: Twenty three lesions had no motion in a breathing cycle; four lesions had anterior-posterior motion ≤ 0.2 mm; two lesions had lateral motion ≤ 0.2 mm; and eight lesions had superior-inferior motion, most ≤ 0.2 mm with the worst at 0.6 mm. The difference of maximum dose to 0.01 cm 3 of spinal cord in different phases of a breathing cycle was within 20 cGy in worst case. Target volumes that received the prescription dose (V100) varied little, with deviations of V100 of each phase from the average CT < 1% in most cases. Only when lesions were close to the diaphragm (e.g., at T11) did the V100 deviate by about 7% in the worst case scenario. However, this was caused by a small dose difference of 20 cGy to part of the target volume., Conclusions: Breathing induced target and spinal cord motion is negligible compared with other setup uncertainties. Dose calculation using averaged or free-breathing CT is reliable when posterior beams are used., Competing Interests: Authors’ disclosure of potential conflicts of interest The authors reported no conflict of interest.

Object: High-grade malignant spinal cord compression is commonly managed with a combination of surgery aimed at removing the epidural tumor, followed by spinal stereotactic radiosurgery (SSRS) aimed at local tumor control. The authors here introduce the use of spinal laser interstitial thermotherapy (SLITT) as an alternative to surgery prior to SSRS., Methods: Patients with a high degree of epidural malignant compression due to radioresistant tumors were selected for study. Visual analog scale (VAS) scores for pain and quality of life were obtained before and within 30 and 60 days after treatment. A laser probe was percutaneously placed in the epidural space. Real-time thermal MRI was used to monitor tissue damage in the region of interest. All patients received postoperative SSRS. The maximum thickness of the epidural tumor was measured, and the degree of epidural spinal cord compression (ESCC) was scored in pre- and postprocedure MRI., Results: In the 11 patients eligible for study, the mean VAS score for pain decreased from 6.18 in the preoperative period to 4.27 within 30 days and 2.8 within 60 days after the procedure. A similar VAS interrogating the percentage of quality of life demonstrated improvement from 60% preoperatively to 70% within both 30 and 60 days after treatment. Imaging follow-up 2 months after the procedure demonstrated a significant reduction in the mean thickness of the epidural tumor from 8.82 mm (95% CI 7.38-10.25) before treatment to 6.36 mm (95% CI 4.65-8.07) after SLITT and SSRS (p = 0.0001). The median preoperative ESCC Grade 2 was scored as 4, which was significantly higher than the score of 2 for Grade 1b (p = 0.04) on imaging follow-up 2 months after the procedure., Conclutions: The authors present the first report on an innovative minimally invasive alternative to surgery in the management of spinal metastasis. In their early experience, SLITT has provided local control with low morbidity and improvement in both pain and the quality of life of patients.

Purpose: To investigate local control, survival outcomes, and predictors of local relapse for patients treated with spine stereotactic body radiation therapy., Methods and Materials: We reviewed the records of 332 spinal metastases consecutively treated with stereotactic body radiation therapy between 2002 and 2012. The median follow-up for all living patients was 33 months (range, 0-111 months). Endpoints were overall survival and local control (LC); recurrences were classified as either in-field or marginal., Results: The 1-year actuarial LC and overall survival rates were 88% and 64%, respectively. Patients with local relapses had poorer dosimetric coverage of the gross tumor volume (GTV) compared with patients without recurrence (minimum dose [Dmin] biologically equivalent dose [BED] 23.9 vs 35.1 Gy, P<.001; D98 BED 41.8 vs 48.1 Gy, P=.001; D95 BED 47.2 vs 50.5 Gy, P=.004). Furthermore, patients with marginal recurrences had poorer prescription coverage of the GTV (86% vs 93%, P=.01) compared with those with in-field recurrences, potentially because of more upfront spinal canal disease (78% vs 24%, P=.001). Using a Cox regression univariate analysis, patients with a GTV BED Dmin ≥33.4 Gy (median dose) (equivalent to 14 Gy in 1 fraction) had a significantly higher 1-year LC rate (94% vs 80%, P=.001) compared with patients with a lower GTV BED Dmin; this factor was the only significant variable on multivariate Cox analysis associated with LC (P=.001, hazard ratio 0.29, 95% confidence interval 0.14-0.60) and also was the only variable significant in a separate competing risk multivariate model (P=.001, hazard ratio 0.30, 95% confidence interval 0.15-0.62)., Conclusions: Stereotactic body radiation therapy offers durable control for spinal metastases, but there is a subset of patients that recur locally. Patients with local relapse had significantly poorer tumor coverage, which was likely attributable to treatment planning directives that prioritized the spinal cord constraints over tumor coverage. When possible, we recommend maintaining a GTV Dmin above 14 Gy in 1 fraction and 21 Gy in 3 fractions., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Papillary tumor of the pineal region (PTPR) is a rare neuroectodermal tumor that was first described in 2003 and formally codified by the World Health Organization in 2007. Limited reports suggest surgical resection is the mainstay of treatment; however, the role of multimodality therapy is not well defined. We evaluated our institutional experience in the treatment of PTPR., Methods: A retrospective review of 8 patients with pathologically confirmed PTPR diagnosed between 1999 and 2013 was performed., Results: The median age at diagnosis was 37 years (range, 25-56 years). After a median follow-up period of 60 months (range, 10-170 months), 7 of 8 patients were still living. All patients underwent maximum safe surgical resection; 5 received adjuvant radiation (63%). Overall and progression-free survival 5 years after diagnosis were 100% and 51%, respectively. Progression-free survival 5 years after completion of adjuvant radiotherapy was 64%. Crude recurrence rates for patients receiving adjuvant radiotherapy (n = 5) and patients not receiving adjuvant radiotherapy (n = 3) were 20% and 67%, respectively. Crude recurrence rate after gross total resection (GTR) and no adjuvant radiotherapy (n = 2) was 100% versus 0% when adjuvant radiotherapy was administered after GTR (n = 2). After subtotal resection, 3 patients received adjuvant radiotherapy; 1 of these patients had out-of-field recurrence at 46 months (crude recurrence rate 33%). In all cases, salvage with radiation at the time of recurrence was effective., Conclusions: Our institutional experience confirms a recent multicenter retrospective series showing excellent survival but high risk of local recurrence for PTPR. Our findings suggest that radiotherapy provides durable local control, particularly when administered in the adjuvant setting after GTR., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Brainstem metastases (BSMs) represent a significant treatment challenge. Stereotactic radiosurgery (SRS) is often used to treat BSM. We report our experience in the treatment of BSM with Gamma Knife SRS (GK&#95;SRS)., Methods: The records of 1962 patients with brain metastases treated with GK&#95;SRS between 2009 and 2013 were retrospectively reviewed. Seventy-four patients with 77 BSMs and follow-up brain imaging were identified. Local control (LC), overall survival (OS), progression-free survival (PFS), and toxicity were assessed., Results: Median follow-up was 5.5 months (range, 0.2-48.5 months). Median tumor volume was 0.13 cm 3 (range, 0.003-5.58 cm 3 ). Median treatment dose was 16 Gy (range, 10-20 Gy) prescribed to 50% isodose line (range, 40%-86%). Crude LC was 94% (72/77). Kaplan-Meier estimate of median OS was 8.5 months (95% CI, 5.6-9.4 months). Symptomatic lesions and larger lesions, especially size ≥2 cm 3 , were associated with worse LC (HR = 8.70, P = .05; HR = 14.55, P = .02; HR = 62.81, P < .001) and worse OS (HR = 2.00, P = .02; HR = 2.14, P = .03; HR = 2.81, P = .008). Thirty-six percent of BSMs were symptomatic, of which 36% (10/28) resolved after SRS and 50% (14/28) had stable or improved symptoms. Actuarial median PFS was 3.9 months (95% CI, 2.7-4.9 months). Midbrain location was significant for worse PFS (HR = 2.29, P = .03). Toxicity was low (8%, 6/74), with size and midbrain location associated with increased toxicity (HR 1.57, P = .05; HR = 5.25, P = .045)., Conclusions: GK&#95;SRS is associated with high LC (94%) and low toxicity (8%) for BSMs. Presence of symptoms or lesion size ≥ 2 cm 3 was predictive of worse LC and OS.

Objective: To update outcomes and assess prognostic factors in the modern, multimodality treatment of patients with pineoblastoma., Methods: The medical records of patients with pineoblastoma evaluated at the M.D. Anderson Cancer Center between 1982 and 2012 were reviewed retrospectively., Results: Thirty-one patients with medical records suitable for review were identified. The majority of patients were female (67.7%) with a median age at diagnosis of 18.2 years (range, 0.3-52.8 years). Twenty-one patients underwent surgical resection, recorded as gross total (n = 9) or subtotal (n = 12) resections. Thirty patients received radiation with photon-based therapy (n = 16), proton-based therapy (n = 13), or radiosurgery (n = 1) to a median craniospinal irradiation dose of 36 Gy (range, 23.4-40 Gy) and a median focal dose of 54 Gy (range, 40-58.4 Gy). Twenty-eight patients received chemotherapy before (n = 10), during (n = 10), and after (n = 22) radiation. Median overall survival was 8.7 years for the entire cohort, with 2-, 5-, and 10- year actuarial rates of 89.5%, 69.4%, and 48.6%, respectively. Median disease-free survival was 10 years with 2-, 5-, and 10- year actuarial rates of 84.3%, 62.6%, and 55.7%, respectively. Univariate analysis failed to correlate age, sex, or extent of surgical resection with disease-free or overall survival., Conclusions: Modern, multimodality treatment of pineoblastoma yields a high rate of overall survival, with acceptable short- and long-term toxicity. A greater M-stage at presentation and development of disease recurrence correlate with worse overall survival. Patients who received focal radiation initially experienced a greater rate of disease recurrence compared with those treated to the craniospinal axis., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Purpose/objective(s): To perform a secondary analysis of institutional prospective spine stereotactic body radiation therapy (SBRT) trials to investigate posttreatment acute pain flare., Methods and Materials: Medical records for enrolled patients were reviewed. Study protocol included baseline and follow-up surveys with pain assessment by Brief Pain Inventory and documentation of pain medications. Patients were considered evaluable for pain flare if clinical note or follow-up survey was completed within 2 weeks of SBRT. Pain flare was defined as a clinical note indicating increased pain at the treated site or survey showing a 2-point increase in worst pain score, a 25% increase in analgesic intake, or the initiation of steroids. Binary logistic regression was used to determine predictive factors for pain flare occurrence., Results: Of the 210 enrolled patients, 195 (93%) were evaluable for pain flare, including 172 (88%) clinically, 135 (69%) by survey, and 112 (57%) by both methods. Of evaluable patients, 61 (31%) had undergone prior surgery, 57 (29%) had received prior radiation, and 34 (17%) took steroids during treatment, mostly for prior conditions. Pain flare was observed in 44 patients (23%). Median time to pain flare was 5 days (range, 0-20 days) after the start of treatment. On multivariate analysis, the only independent factor associated with pain flare was the number of treatment fractions (odds ratio = 0.66, P=.004). Age, sex, performance status, spine location, number of treated vertebrae, prior radiation, prior surgery, primary tumor histology, baseline pain score, and steroid use were not significant., Conclusions: Acute pain flare after spine SBRT is a relatively common event, for which patients should be counseled. Additional study is needed to determine whether prophylactic or symptomatic intervention is preferred., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Objective: This study sought to report patient characteristics, risk factors, and trends in management for astroblastoma patients., Methods: A retrospective analysis was conducted utilizing the Surveillance, Epidemiology and End Results Program of the National Cancer Institute., Results: Two hundred and thirty-nine patients were identified, with 206 patients receiving treatment. The median age at diagnosis was 35 years (range 0 to 84 years). Tumor location was available for 177 patients, and the majority were supratentorial (n = 144, 81.3%). The median overall survival and cause-specific survival for the cohort receiving treatment was 55 and 65 months, respectively. On univariate analysis, patients receiving surgery alone compared to only radiotherapy displayed improved overall survival (OS) and cause-specific survival (CSS) with a 5-year OS of 62.2% vs. 27.3%, P < .001, and CSS of 67.3% vs. 31.9%, P = .003. Supratentorial tumor location was associated with worse survival, with an estimated 5-year OS of 44.9% for supratentorial tumors compared to 75% for infratentorial tumors (hazard ratio 3.41 [95% CI, 1.76 to 6.62]; P < .001) and CSS of 47.5% (supratentorial) to 82% (infratentorial) (hazard ratio 3.95 [95% CI, 1.81 to 8.62]; P = .001). Age >60 years at diagnosis and treatment before 1990 were correlated with decreased survival on both the univariate and the multivariate analyses., Conclusions: To our knowledge, this is the largest report of astroblastoma patients described in the literature. Supratentorial tumor location, older age, and treatment prior to 1990 were poor prognostic factors., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Object: Stereotactic radiosurgery (SRS) is well established in the treatment of brain metastases, however it's exact role remains unclear. A single metastasis at presentation raises additional challenges, however there is minimal outcome data within this subgroup. We sought to evaluate the outcomes of treatment in patients with a single brain metastasis, as well as factors impacting local control., Methods: All patients treated with SRS for a single brain metastasis were evaluated. Data was collected regarding patient demographics, treatment characteristics, and treatment outcomes. Univariate analyses were performed to evaluate the impact of treatment and patient variables on these outcomes. Emphasis was placed on analyses of factors impacting LC., Results: Between 1998 and 2011, a total of 141 patients underwent SRS for a single brain metastasis; in addition 31 had surgical resection, 15 received whole brain radiotherapy (WBRT), and 2 underwent both. There was no statistical impact on local control (LC) or distant intracranial control (DIC) with the addition of WBRT or surgery (LC 74%, 100%, and 58%, and DIC 37%, 67%, and 49% for SRS alone, SRS + WBRT, and SRS + surgery, respectively, smallest p = 0.17). Local control was decreased with larger tumors, doses <20Gy, and tight overtreatment ratios (i.e. conformity) (largest p = 0.02), although the independence of these factors could not be established. Long term freedom from requiring future whole brain radiotherapy was 73%., Conclusions: SRS alone for patients with single brain metastases demonstrates acceptable intracranial outcomes. Further evaluation into factors impacting LC are warranted.

Objective: To investigate the influence of stereotactic radiosurgery on the risk of hemorrhage from brain metastases from malignant melanoma., Methods: A cohort of 110 patients treated with stereotactic radiosurgery (SRS) for 358 melanoma brain metastases was identified. The incidence of hemorrhage before and after SRS was determined by review of serial MRI scans. Statistical analysis was performed to determine the influence of SRS on rate of hemorrhage. Overall survival (OS) and local control (LC) were assessed and prognostic factors, including hemorrhage pre- or post-SRS were analyzed., Results: At presentation 83 of 358 (23.2%) melanoma metastases had hemorrhaged in 44 patients. Following SRS, 73 hemorrhages occurred in 358 treated tumors (20.4%). These rates were not significantly different; p=0.362, HR=0.846 (95% CI 0.591-1.211). The risk of post-SRS hemorrhage in patients was statistically significantly linked to previous hemorrhage. Fourteen of 65 patients (21.5%) who presented without hemorrhage prior to SRS subsequently demonstrated hemorrhage. Twenty-four of 44 patients (54.5%) who presented with hemorrhage went on to demonstrate further hemorrhage following SRS; p=0.005, HR 2.47 (95% CI 1.24-11.3). Mixed effects logistic regression modeling showed no influence of SRS on the risk of hemorrhage of a given lesion (p=0.99).OS at 1 year was better for patients presenting with a single metastasis (41.2%) compared to multiple metastases (20.3%, p=0.009). LC was 60.4% at 1 year following SRS. LC was significantly lower for metastases demonstrating hemorrhage either pre-SRS (51.7% vs 64.9%, p=0.03) or post-SRS (32.7% vs. 67.8%, p<0.001)., Conclusions: The current data show that SRS does not alter the risk of subsequent hemorrhage of treated metastases. However, hemorrhage may complicate follow-up assessment of response and LC following SRS. Careful assessment of imaging following SRS should include awareness that hemorrhage may mimic treatment failure in these patients.

Observation following gross-total resection (GTR) for non-anaplastic supratentorial ependymomas is often advocated based on small, retrospective series. The purpose of this study is to perform a population-based analysis to examine outcomes for this rare cohort of low-risk patients. A retrospective analysis was conducted utilizing the Surveillance, Epidemiology and End Results Program of the United States National Cancer Institute. We identified patients with supratentorial non-anaplastic ependymoma who underwent GTR alone or GTR followed by radiation. We identified 92 patients who met these criteria. The median age was 17.5 years (range 1-83) with the majority female (58 %) and white (75 %). Radiotherapy (RT) was delivered in half of patients. The 5-/10-year Kaplan-Meier estimated overall survival (OS) and cause-specific survival (CSS) for the overall cohort was 83.2/71.4 and 84.1/78.0 %, respectively. There was no evidence of decreased CSS (HR 0.52 [0.18-1.51]; p = 0.23) or OS (HR 0.63 [0.25-1.59]; p = 0.33) with the omission of RT on univariate analysis. Age ≥18 years correlated with worse OS (HR 4.01 [1.45-11.11]; p = 0.008) and CSS (HR 2.86 [0.99-8.31]; p = 0.05). RT did not impact outcome for this low-risk cohort of patients. Older age correlates with poor prognosis.

Background: Meningeal hemangiopericytoma (M-HPC) is a rare entity., Objective: To characterize our institutional experience in treating M-HPC., Methods: We reviewed the medical records of patients with M-HPC evaluated at The University of Texas M.D. Anderson Cancer Center between 1979 and 2009., Results: We identified 63 patients diagnosed between 1979 and 2009 with M-HPC treated with surgery alone or with postoperative radiotherapy (PORT). The majority were male (59%) and with a median age of 40.9 years (range, 0-71). Gross total resection (GTR) predominated (n = 31, 49%) followed by subtotal resection (n = 23, 37%) and unknown status (n = 9, 14.3%). PORT was delivered to 39 of the 63 patients (62%). The 5-, 10-, and 15-year overall survival were 90%, 68%, and 28%, respectively. The 5-, 10-, and 15-year local control (LC) were 70%, 37%, and 20%, respectively. The 5-, 10-, and 15-year metastasis-free survival were 85%, 39%, and 7%. PORT resulted in improved LC (hazard ratio [HR] 0.38, P = .008). Radiotherapy (RT) dose ≥60 Gy correlated with improved LC relative to <60 Gy (HR 0.12, P = .045). GTR correlated with improved LC (HR 0.40, P = .03). On multivariate analysis, PORT (HR 0.33, P = .003), GTR (HR = 0.33, P = .008), and RT dose ≥60 Gy (HR 0.33, P = .003) correlated with improved LC. Among those with GTR, PORT resulted in improved LC (HR 0.18, P = .027). Extent of resection and PORT did not correlate with improved overall survival., Conclusion: In M-HPC, both PORT and GTR independently correlate with improved LC. PORT improves LC following GTR. We recommend RT dose ≥60 Gy to optimize LC.

Objective: A change has recently been made to the Federation of Gynecology and Obstetrics (FIGO) staging system for cervical cancer to account for size within stage IIA cancers. This study was designed to investigate the impact of size within stage I-IIIB cervical carcinoma, and to validate these changes., Methods: The Surveillance, Epidemiology, and End Results Program database was used to extract data on patients from 1988 to 2008. Patients were included who had information recorded regarding stage, size, and type of treatment received. They were then stratified by stage and size, and analyzed for cause-specific survival (CSS) using Kaplan Meier estimates, as well as hazard ratios using Cox proportional hazards regression modeling., Results: A total of 18,649 cases were evaluated. All stages evaluated demonstrated improved CSS on Kaplan Meier estimates for smaller tumor sizes (largest p=0.0003). Hazard ratios were significantly worse for larger tumor sizes on both univariate and multivariate modeling. Specifically, stage IIA cancers demonstrated a hazard ratio of 2.0 on univariate, and 1.69 on multivariate analysis (C.I. 1.46-2.75, p<0.0001 and C.I. 1.20-2.38, p=0.0025, respectively). Further size subdivisions of 2 and 4cm for stage I, 4cm for stage IIB, and 4 and 6cm for stage IIIB also maintained prognostic significance. On multivariate analysis within each stage, size was the only variable to maintain independent significance in all stages evaluated., Conclusions: Size is independently prognostic within each stage in cervical cancer, validating the recent changes to the FIGO staging system., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: Intracranial hemangiopericytoma (HPC) is a rare malignancy for which treatment recommendations vary., Objective: We sought to characterize outcomes of HPC patients treated with postoperative external beam radiotherapy (PORT)., Methods: A retrospective analysis was conducted using the Surveillance, Epidemiology and End Results (SEER) Program of the US National Cancer Institute. We identified patients with intracranial hemangiopericytoma who underwent surgery alone or PORT., Results: We identified 88 patients with a diagnosis of HPC between 1982 and 2009 treated with surgery alone or PORT. The majority of patients were female (53%) and white (84%) with a median age of 50.5 years (range, 0-92 years). Gross total resection (GTR) was achieved in 55%, and PORT was delivered to 48% of the entire cohort. The median overall survival (OS) and cause-specific survival (CSS) were 111 months and 161 months, respectively. On univariate analysis, age older than 50 years correlated with poor OS (hazard ratio [HR]: 3.43; 95% confidence interval [CI]: 1.70-6.95; P = .001) and CSS (HR: 2.77; 95% CI: 1.18-6.48; P = .019). On multivariate analysis (MVA), age >50 years correlated with poor OS (HR: 3.69; 95% CI: 1.72-7.93; P = .001) and CSS (HR: 2.67; 95% CI: 1.08-6.59; P = .034). On MVA, GTR correlated with improved OS (HR: 0.28; 95% CI: 0.11-0.71; P = .007) and CSS (HR: 0.23; 95% CI: 0.07-0.76; P = .016). In addition, PORT correlated with improved OS (MVA HR: 0.02; 95% CI: 0.00-0.31; P = .005) and CSS (MVA HR: 0.02; 95% CI: 0.00-0.45; P = .015). Patients undergoing STR with PORT compared favorably with those undergoing GTR alone with respect to OS (HR: 0.43; 95% CI: 0.15-1.26; P = .13) and CSS (HR: 0.51; 95% CI: 0.15-1.78; P = .29)., Conclusion: In intracranial HPC, both PORT and GTR independently correlate with improved OS and CSS.

Introduction: No prospective randomized trials exist to delineate the role of combined chemoradiotherapy (CRT) in the treatment of vaginal cancer (VC). We sought to describe the utilization rate of CRT and evaluate the potential survival benefit of CRT over radiotherapy alone in VC., Methods: A retrospective analysis of the SEER-Medicare-linked database was performed analyzing women with VC treated with external beam radiation and/or brachytherapy and diagnosed between 1991 and 2005., Results: Of the 1709 primary VC patients in the SEER-Medicare database, 326 met inclusion criteria. Most were white (80.1%) and in the 70- to 74-year age group (42.1%). Squamous cell carcinoma was the most predominant histologic diagnosis (80.4%). Brachytherapy was used in 34% of patients, whereas cisplatin was the chemotherapy of choice in 59% of CRT patients. Median follow-up was 21.5 months. Kaplan-Meier estimated that 5-year cause-specific survival (CSS) and overall survival (OS) was 67.6% and 27.1%, respectively. Before 1999, CRT was used in 7.5% of patients compared with 36.1% of patients thereafter (P < 0.001). Chemoradiotherapy was less likely to be used in patients older than 80 years (P < 0.001) but was otherwise balanced in race, stage, grade, histologic diagnosis, comorbidities, and brachytherapy use. Chemoradiotherapy did not correlate with CSS (hazard ratio [HR], 0.91; P = 0.84) or OS (HR, 1.34; P = 0.21) by multivariate analysis. Factors associated with worse CSS include stage IVA disease (HR, 4.2; P = 0.003) and 2 or more comorbidities (HR, 2.89; P = 0.03). Factors associated with worse OS include age older than 80 years (HR, 1.78; P = 0.04), stage IVA disease (HR, 3.35; P < 0.0001), and 2 or more comorbidities (HR, 2.58; P = 0.001)., Conclusions: Chemoradiotherapy utilization for VC has increased since 1999. We failed to delineate a CSS or OS benefit for CRT in this cohort.

Objective: The objective of this study is to perform a patterns of care analysis for post-hysterectomy patients with node positive (LN+) or parametria positive cervical cancer., Methods: A retrospective analysis was conducted utilizing the Surveillance, Epidemiology and End Results (SEER) Program from 1973 to 2006. We identified 2247 women with cervical carcinoma who had undergone hysterectomy and were found to have LN+ and/or positive parametria., Results: Of the 2247 identified, 80.1% (1800) received postoperative radiotherapy (RT) while 19.9% (447) did not. Of those receiving RT, a significantly greater proportion had worse risk factors including higher clinical stage, and nodal bulk yet cause-specific survival (CSS) was equivalent between the two groups. RT utilization has increased over time from 67.2% in the cohort analyzed from 1973 to 1982 to 81.8% in the cohort analyzed from 2004 to 2006 (p = 0.0003). Blacks had worse CSS than whites (HR 1.35, 95% CI [1.05, 1.75]; p = 0.02). The proportion of those receiving RT was lower in blacks than whites (74.7% vs. 80.5%; p = 0.0358). From 1973 to 1982, 87.5% of blacks received RT while 62% of whites received RT (p = 0.0463). From 2004 to 2006, 64.4% of blacks received RT while 83.0% of whites received RT (p = 0.0024)., Conclusions: Despite randomized data supporting the use of postoperative concurrent chemoradiotherapy for LN+ or parametria positive cervical cancer, the proportion of blacks not receiving RT is increasing over time. This is the largest patterns of care analysis to date of RT in patients with LN+ and/or parametria positive cervical cancer., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Objectives: To perform a patterns of care analysis for patients with prostate cancer and high-risk pathologic factors following radical prostatectomy with regards to adjuvant radiation., Methods: A retrospective analysis was conducted using the Surveillance, Epidemiology and End Results (SEER) Program. We identified men from 2004 to 2005 with prostate adenocarcinoma (PA) who had undergone radical prostatectomy (RP) and were found to have extracapsular extension (ECE) with positive margins., Results: We identified 1427 PA patients with ECE and positive margins after an RP. Most were clinically staged as T1 or T2 before surgery (95.8%). Using the D'Amico Risk Stratification, 52.0% were high-risk, 39.7% were intermediate-risk, and 8.3% were low-risk. Of these, 18.2% (260) received ART, whereas 81.8% (1167) did not. Those who received ART had worse prognostic factors, such as Gleason scores > 7 (38.5% vs 24.8%; P < .0001), prostate-specific antigen level > 10 (44.6% vs 35.2%; P = .0045), pathologically positive lymph nodes (11.5% vs 6.4%; P = .006), and D'Amico high-risk disease (66.8% vs 48.7%; P < .0001). The use of ART based on geographic region ranged from 8.3%-34.2%., Conclusions: Less than 20% of patients with pT3 disease and positive margins received ART in the study period just before the publication of randomized data demonstrating an improvement in biochemical failure with ART in this SEER retrospective analysis. This is the largest patterns of care analysis to date of ART in patients with margin-positive pT3 prostate adenocarcinoma., (Published by Elsevier Inc.)

Epidermal growth factor receptor (EGFR) is a ubiquitously expressed receptor tyrosine kinase involved in the etiology of several human cancers. Cetuximab is an EGFR-blocking antibody that has been approved for the treatment of patients with head and neck squamous cell carcinoma and metastatic colorectal cancer. Previous reports have shown that EGFR translocation to the nucleus is associated with cell proliferation. Here we investigated mechanisms of acquired resistance to cetuximab using a model derived from the non-small cell lung cancer line H226. We demonstrated that cetuximab-resistant cells overexpress HER family ligands including epidermal growth factor (EGF), amphiregulin, heparin-binding EGF and beta-cellulin. Overexpression of these ligands is associated with the nuclear translocation of the EGFR and this process was mediated by the Src family kinases (SFK). Treatment of cetuximab-resistant cells with the SFK inhibitor, dasatinib, resulted in loss of nuclear EGFR, increased membrane expression of the EGFR and resensitization to cetuximab. In addition, expression of a nuclear localization sequence-tagged EGFR in cetuximab-sensitive cells increased resistance to cetuximab both in vitro and in mouse xenografts. Collectively, these data suggest that nuclear expression of EGFR may be an important molecular determinant of resistance to cetuximab therapy and provides a rationale for investigating nuclear EGFR as a biomarker for cetuximab response. Further, these data suggest a rationale for the design of clinical trials that examine the value of treating patients with cetuximab-resistant tumors with inhibitors of SFKs in combination with cetuximab.

Purpose: To examine the interaction between panitumumab, a fully human anti-epidermal growth factor receptor monoclonal antibody, and radiation in head-and-neck squamous cell carcinoma and non-small-cell lung cancer cell lines and xenografts., Methods and Materials: The head-and-neck squamous cell carcinoma lines UM-SCC1 and SCC-1483, as well as the non-small-cell lung cancer line H226, were studied. Tumor xenografts in athymic nude mice were used to assess the in vivo activity of panitumumab alone and combined with radiation. In vitro assays were performed to assess the effect of panitumumab on radiation-induced cell signaling, apoptosis, and DNA damage., Results: Panitumumab increased the radiosensitivity as measured by the clonogenic survival assay. Radiation-induced epidermal growth factor receptor phosphorylation and downstream signaling through mitogen-activated protein kinase (MAPK) and signal transducer and activator of transcription 3 (STAT3) was inhibited by panitumumab. Panitumumab augmented radiation-induced DNA damage by 1.2-1.6-fold in each of the cell lines studied as assessed by residual gamma-H(2)AX foci after radiation. Radiation-induced apoptosis was increased 1.4-1.9-fold by panitumumab, as evidenced by Annexin V-fluorescein isothiocyanate staining and flow cytometry. In vivo, the combination therapy of panitumumab and radiation was superior to panitumumab or radiation alone in the H226 xenografts (p = 0.01) and showed a similar trend in the SCC-1483 xenografts (p = 0.08). In vivo, immunohistochemistry demonstrated the ability of panitumumab to augment the antiproliferative and antiangiogenic effects of radiation., Conclusion: These studies have identified a favorable interaction in the combination of radiation and panitumumab in upper aerodigestive tract tumor models, both in vitro and in vivo. These data suggest that clinical investigations examining the combination of radiation and panitumumab in the treatment of epithelial tumors warrant additional pursuit.

Background: Recent evidence indicates that adolescent animals are more sensitive than adults to the disruptive effects of acute ethanol exposure on spatial learning. It is not yet known whether adolescent animals are also more sensitive than adults to the enduring neurobehavioral effects of repeated ethanol exposure. In this study, animals were exposed to ethanol in a binge-pattern during either adolescence or adulthood. At a time when all subjects were adults, spatial working memory was examined in the absence and presence of an acute ethanol challenge., Methods: Rats were exposed to ethanol (5.0 g/kg intraperitoneally) or isovolumetric saline at 48 hr intervals over 20 days. Exposure began on either postnatal day 30 (adolescent group) or 70 (adult group). Twenty days after the final injection, a time at which all animals were adults, the subjects were tested on an elevated plus maze and then were trained to perform a spatial working memory task on an eight-arm radial maze. At the beginning of each session of training on the working memory task, subjects retrieved food rewards on four of the eight arms. After a delay, subjects were placed on the maze and allowed to retrieve food from the remaining four arms., Results: Prior exposure to ethanol did not influence behavior on the plus maze. Performance of the groups did not differ during acquisition of the spatial working memory task with a 5 min delay or during subsequent testing with a 1 hr delay. However, animals treated with ethanol during adolescence exhibited larger working memory impairments during an ethanol challenge (1.5 g/kg intraperitoneally) than subjects in the other three groups., Conclusions: The findings indicate that binge pattern exposure to ethanol during adolescence enhances responsiveness to the memory-impairing effects of ethanol in adulthood.