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Bruce E. Pollock, Deborah A. Gorman and Paul D. Brown

Object

Although stereotactic radiosurgery is frequently performed for arteriovenous malformations (AVMs) in deep locations, outcomes after radiosurgery for these patients have not been well studied. The goal of this paper was to study these outcomes.

Methods

Between 1990 and 2000, 56 patients underwent radiosurgery for AVMs located in the basal ganglia (10 patients), thalamus (30 patients), or brainstem (16 patients). The median age of these patients was 34.2 years. Thirty-five patients (62%) had experienced previous bleeding. The AVMs were classified Grade IIIB in 62% of patients and Grade IV in 38% according to the modified Spetzler—Martin Scale; the median radiosurgery-based AVM score was 1.83. The median volume of the lesion was 3.8 cm3 and the median radiation dose delivered to its margin was 18 Gy. The median duration of follow-up review after radiosurgery was 45 months (range 3–121 months).

In seven patients (12%) hemorrhage occurred at a median of 12 months after radiosurgery; five patients (9%) died and two recovered without any deficit. Permanent radiation-related complications occurred in six (12%) of 51 patients (excluding the five patients who died of hemorrhage) after one procedure and in three (18%) of 17 patients after repeated radiosurgery. Obliteration of the AVM was noted in 24 patients (43%; obliteration was confirmed by angiography in 18 patients and by magnetic resonance [MR] imaging in six patients) after a single procedure and in 32 patients (57%; confirmed by angiography in 25 patients and by MR imaging in seven patients) after one or more procedures. Excellent outcomes (obliteration of the lesion without any new deficit) were obtained in 39% of patients after one radiosurgical procedure and in 48% after one or more procedures. Twelve (67%) of 18 patients with AVM scores lower than 1.5 had excellent outcomes compared with 15 (39%) of 38 patients with AVM scores greater than 1.5 (p = 0.053).

Conclusions

Less than half of the patients with deeply located AVMs were cured of the future risk of hemorrhage without new neurological deficits. This experience emphasizes the difficulty in treating patients with deeply located AVMs; the majority of whom are also poor candidates for resection or embolization.

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Mark P. Piedra, Paul D. Brown, Paul C. Carpenter and Michael J. Link

✓ The authors present the case of a 58-year-old woman who presented with symptoms of diabetes insipidus (DI) 1 year after she was found to have a Stage 3 (of 4) estrogen receptor—positive infiltrating ductal adenocarcinoma of the left breast with pulmonary and bone metastases. Magnetic resonance images demonstrated a solitary site of metastasis in the patient's pituitary stalk, and gamma knife surgery (GKS) was performed to treat the lesion. Three months after GKS the patient was able to reduce the medication she required for the DI. There was no evidence of pituitary failure and no negative effect on her vision.

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Bruce E. Pollock, Jeffrey T. Jacob, Paul D. Brown and Todd B. Nippoldt

Object

The authors reviewed outcomes after stereotactic radiosurgery for patients with acromegaly and analyzed factors associated with biochemical remission.

Methods

Retrospective analysis was performed for 46 consecutive cases of growth hormone (GH)–producing pituitary adenomas treated by radiosurgery between 1991 and 2004. Biochemical remission was defined as a fasting GH less than 2 ng/ml and a normal age- and sex-adjusted insulin-like growth factor–I (IGF-I) level while patients were not receiving any pituitary suppressive medications. The median follow up after radiosurgery was 63 months (range 22–168 months).

Twenty-three patients (50%) had biochemical remission documented at a median of 36 months (range 6–63 months) after one radiosurgical procedure. The actuarial rates of biochemical remission at 2 and 5 years after radiosurgery were 11 and 60%, respectively. Multivariate analysis showed that IGF-I levels less than 2.25 times the upper limit of normal (hazard ratio [HR] 2.9, 95% confidence interval [CI] 1.2–6.9, p = 0.02) and the absence of pituitary suppressive medications at the time of radiosurgery (HR 4.2, 95% CI 1.4–13.2, p = 0.01) correlated with biochemical remission. The incidence of new anterior pituitary deficits was 10% at 2 years and 33% at 5 years.

Conclusions

Discontinuation of pituitary suppressive medications at least 1 month before radiosurgery significantly improved endocrine outcomes for patients with acromegaly. Patients with GH–producing pituitary adenomas should not undergo further radiation therapy or surgery for at least 5 years after radiosurgery because GH and IGF-I levels continue to normalize over that interval.

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Atom Sarkar, Bruce E. Pollock, Paul D. Brown and Deborah A. Gorman

Object. Radiosurgery is commonly used for the treatment of patients with glioma. The goal of this study was to evaluate the safety and efficacy of radiosurgery in the management of patients with oligodendrogliomas (ODGs) or mixed oligoastrocytomas (OGAs).

Methods. A retrospective chart review of patients treated between May 1990 and January 2000 identified 18 patients (21 tumors) with either an ODG (10) or a mixed OGA (11) who had undergone radiosurgery. The median patient age was 43 years (range 23–67 years). Sixteen patients had undergone one or more tumor resections before radiosurgery; in two patients biopsy sampling alone had been performed. Tumor grades at the most recent operation were Grade 1 (one), Grade 2 (one), Grade 3 (12), and Grade 4 (seven patients). Seventeen patients had undergone prior radiotherapy; 11 were treated with chemotherapy before radiosurgery, and one had undergone a prior linear accelerator—based radiosurgery treatment. The median tumor volume was 8.2 cm3 (range 1.9–47.7 cm3); the median margin dose was 15 Gy (range 12–20 Gy); and the median maximum dose was 32 Gy (range 24–50 Gy).

In this heterogeneous group, 12 patients died whereas six remain alive. Survival after radiosurgery was 78%, 61%, and 44% at 12, 24, and 48 months, respectively. Factors associated with an improved survival rate included younger age and smaller tumors.

Conclusions. For patients with oligoastroglial tumors that have failed to respond to conventional therapies, radiosurgery may provide some survival benefit. Further study is needed to determine which subpopulation of these patients will have the best chances of enhanced survival from this treatment.

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Edward D. Wirth III, Daniel P. Theele, Thomas H. Mareci, Douglas K. Anderson, Stacey A. Brown and Paul J. Reier

✓ Magnetic resonance (MR) imaging was evaluated for its possible diagnostic application in determining the survival of fetal central nervous system tissue grafts in the injured spinal cord. Hemisection cavities were made at the T11—L1 level of eight adult female cats. Immediately thereafter, several pieces of tissue, either obtained from the fetal cat brain stem on embryonic Day 37 (E-37), from the fetal neocortex on E-37, or from the fetal spinal cord on E-23, were implanted into the cavities made in seven cats. The eighth cat served as a control for the effect of the lesion only. In another group of four animals, a static-load compression injury was made at the L-2 level. Seven weeks later, the lesion was resected in three cases and fragments of either fetal brainstem or spinal cord tissue were introduced. A small cyst was observed in a fourth cat in the compression injury group and a suspension of dissociated E-23 brain-stem cells was injected into this region of cavitation without disturbing the surrounding leptomeninges. Five months to 2 years posttransplantation, MR imaging was performed with a 2.0-tesla VIS imaging spectrometer by acquiring multislice spin-echo images (TR 1000 msec, TE 30 msec) in both the transverse and sagittal planes.

Collectively, these intermediate-weighted images revealed homogeneous, slightly hyperintense signals at the graft site relative to the neighboring host tissue in seven of the 11 graft recipients. Two of the remaining four cats exhibited signals from the graft site that were approximately isointense with the adjacent host spinal cord, and the final two cats and the lesion-only control presented with very hypointense transplant/resection regions. The hyperintense and isointense images were tentatively interpreted as representing viable graft tissue, whereas the hypointense transplant/resection sites were considered to be indicative of a lack of transplant survival or the absence of tissue in the lesion-only control animal.

Postmortem gross inspection of fixed specimens and light microscopy verified the MR findings in the control animal in 10 of the 11 graft recipients by showing either transplants and/or cysts corresponding to the MR images obtained. In one cat in the hemisection group, histological analysis revealed a very small piece of graft tissue that was not detected on the MR images. Therefore, it is suggested that within certain spatial- and contrast-resolution limits, MR imaging can reliably detect the presence of transplanted neural tissue in both the hemisected and compression-injured spinal cord of living animals. Thus, MR imaging can serve as an important adjunct to histological, electrophysiological, and long-term behavioral analyses of graft-mediated anatomical and functional repair of the injured spinal cord. It is further suggested that this noninvasive diagnostic approach offers many advantages in terms of the judicious and optimum use of valuable animal models, and that these findings address an important prerequisite (in situ verification of transplant survival) for any future clinical trials involving these or equivalent neural tissue grafting approaches, when such are warranted.

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Claudio E. Tatsui, Telmo A. B. Belsuzarri, Marilou Oro, Laurence D. Rhines, Jing Li, Amol J. Ghia, Behrang Amini, Heron Espinoza, Paul D. Brown and Ganesh Rao

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.

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Benjamin Farnia, K. Ranh Voong, Paul D. Brown, Pamela K. Allen, Nandita Guha-Thakurta, Sujit S. Prabhu, Ganesh Rao, Qianghu Wang, Zhongxiang Zhao and Anita Mahajan

Object

The authors' institution previously reported a 69% rate of crude local control for surgical management of lateral ventricle metastases at the University of Texas MD Anderson Cancer Center. For comparison, the authors here report their institutional experience with use of stereotactic radiosurgery (SRS) to treat intraventricular metastases.

Methods

To identify patients with intraventricular metastases for this retrospective review, the authors queried an institutional SRS database containing the medical records of 1962 patients with 5800 brain metastases who consecutively underwent SRS from June 2009 through October 2013. End points assessed were local control (crude and locoregional), distant failure–free survival, progression-free survival, and overall survival.

Results

Of the 1962 records examined, those for 25 (1.3%) patients with 30 (0.52%) intraventricular metastases were identified. Median patient age at SRS was 55.8 years. The most common primary malignancy was renal cell carcinoma (n = 13), followed by melanoma (n = 7) and breast adenocarcinoma (n = 5). Median tumor volume was 0.75 cm3 (range 0.01–5.6 cm3). Most lesions were located in the lateral ventricles (n = 25, 83.3%) and were treated to a median dose of 20 Gy (range 14–20 Gy). A total of 12 (48%) patients received whole-brain radiation therapy, most (n = 10) before SRS. With a median follow-up of 11.4 months (range 1.6–39.2 months), the rate of crude local control was 93.3%, and the rates of 6-month and 1-year actuarial locoregional control were 85.2% and 56.2%, respectively. The median overall survival time after SRS was 11.6 months (range 1.3–38.9 months), and the 6-month and 1-year actuarial rates were 87.1% and 46.7%, respectively. Disease dissemination developed in 7 (28%) patients as a second intraventricular metastatic lesion (n = 3, 12%), leptomeningeal disease (n = 3, 12%), or both (n = 1, 4%). Radiographic changes developed in 5 (20%) patients and included necrosis (n = 2, 8%) and hemorrhage (n = 3, 12%). A primary diagnosis of renal cell carcinoma was associated with an improved rate of distant failure–free survival (p = 0.05) and progression-free survival (p = 0.08).

Conclusions

SRS provides excellent local control for intraventricular metastases, with acceptable treatment-related toxicity, thereby supporting nonsurgical treatment for these lesions. The propensity for intraventricular dissemination among intraventricular metastases seems to be histologically dependent.

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Andrew J. Bishop, Randa Tao, B. Ashleigh Guadagnolo, Pamela K. Allen, Neal C. Rebueno, Xin A. Wang, Behrang Amini, Claudio E. Tatsui, Laurence D. Rhines, Jing Li, Eric L. Chang, Paul D. Brown and Amol J. Ghia

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.

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Amol J. Ghia, Eric L. Chang, Andrew J. Bishop, Hubert Y. Pan, Nicholas S. Boehling, Behrang Amini, Pamela K. Allen, Jing Li, Laurence D. Rhines, Nizar M. Tannir, Claudio E. Tatsui, Paul D. Brown and James N. Yang

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.

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Jonathan N. Sellin, William Reichardt, Andrew J. Bishop, Dima Suki, Laurence D. Rhines, Stephen H. Settle, Paul D. Brown, Jing Li, Ganesh Rao, Eric L. Chang and Claudio E. Tatsui

OBJECT

Palliative resection of renal cell carcinoma (RCC) spinal metastasis is indicated in cases of neurological compromise or mechanical instability, whereas conventional external beam radiotherapy (EBRT) is commonly used for pain control. Recently, spinal stereotactic radiosurgery (SRS) has emerged as a safe alternative, delivering higher therapeutic doses of radiation to spinal metastases. To better understand factors affecting survival in patients undergoing spinal SRS for metastatic RCC, the authors performed a retrospective analysis of a consecutive series of cases at a tertiary cancer center.

METHODS

Patients harboring contiguous sites of vertebral body involvement from metastatic RCC who received upfront spinal SRS treatment at The University of Texas MD Anderson Cancer Center between 2005 and 2012 were identified. Demographic data, pain scores, radiographic data, overall survival, complications, status of systemic disease, neurological and functional status, and time between primary diagnosis and diagnosis of metastasis (systemic and spinal) were analyzed to determine their influence on survival.

RESULTS

Thirty-seven patients receiving treatment for 40 distinct, contiguous sites of disease were included. The median overall survival after spinal SRS was 16.3 months (range 7.4–25.3 months). Univariate analysis revealed several factors significantly associated with improved overall survival. Local progression after spinal SRS was associated with worse overall survival compared with sustained local control (HR 3.4, 95% CI 1.6–7.4, p = 0.002). Median survival in patients with a Karnofsky Performance Scale (KPS) score ≥ 70 was longer than in patients with a KPS score < 70 (HR 4.7, 95% CI 2.1–10.7, p < 0.001). Patients with neurological deficits at the time of spinal SRS had a shorter median survival than those without (HR 4.2, 95% CI 1.4–12.0, p = 0.008). Individuals with nonprogressive systemic disease at the time of spinal SRS had a longer median survival than those with systemic progression at the time of treatment (HR 8.3, 95% CI 3.3–20.7, p < 0.001). Median survival in patients experiencing any metastasis < 12 months after primary RCC diagnosis was shorter than in patients experiencing any metastasis > 12 months after primary diagnosis, a difference that approached but did not attain significance (HR 1.9, 95% CI 0.90–4.1, p = 0.09). On multivariate analysis, local progression of disease after spinal SRS, metastasis < 12 months after primary, KPS score ≤ 70, and progression of systemic disease at time of spinal SRS all remained significant factors influencing survival (respectively, HR 3.7, p = 0.002; HR 2.6, p = 0.026; HR 4.0, p = 0.002; and HR 13.2, p < 0.001).

CONCLUSIONS

We identified several factors associated with survival after spinal SRS for RCC metastases, including local progression, time between first metastasis and primary RCC diagnosis, KPS score, presence of neurological deficits, and progressive metastatic disease. These factors should be taken into consideration when considering a patient for spinal SRS for RCC metastases.