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Nicholas S. Boehling, David R. Grosshans, Pamela K. Allen, Mary F. McAleer, Allen W. Burton, Syed Azeem, Laurence D. Rhines and Eric L. Chang

Object

The aim of this study was to identify potential risk factors for and determine the rate of vertebral compression fracture (VCF) after intensity-modulated, near-simultaneous, CT image–guided stereotactic body radiotherapy (SBRT) for spinal metastases.

Methods

The study group consisted of 123 vertebral bodies (VBs) in 93 patients enrolled in prospective protocols for metastatic disease. Data from these patients were retrospectively analyzed. Stereotactic body radiotherapy consisted of 1, 3, or 5 fractions for overall median doses of 18, 27, and 30 Gy, respectively. Magnetic resonance imaging studies, obtained at baseline and at each follow-up, were evaluated for VCFs, tumor involvement, and radiographic progression. Self-reported average pain levels were scored based on the 11-point (0–10) Brief Pain Inventory both at baseline and at follow-up. Obesity was defined as a body mass index ≥ 30.

Results

The median imaging follow-up was 14.9 months (range 1–71 months). Twenty-five new or progressing fractures (20%) were identified, and the median time to progression was 3 months after SBRT. The most common histologies included renal cancer (36 VBs, 10 fractures, 10 tumor progressions), breast cancer (20 VBs, 0 fractures, 5 tumor progressions), thyroid cancer (14 VBs, 1 fracture, 2 tumor progressions), non–small cell lung cancer (13 VBs, 3 fractures, 3 tumor progressions), and sarcoma (9 VBs, 2 fractures, 2 tumor progressions). Fifteen VBs were treated with kyphoplasty or vertebroplasty after SBRT, with 5 procedures done for preexisting VCFs. Tumor progression was noted in 32 locations (26%) with 5 months' median time to progression. At the time of noted fracture progression there was a trend toward higher average pain scores but no significant change in the median value. Univariate logistic regression showed that an age > 55 years (HR 6.05, 95% CI 2.1–17.47), a preexisting fracture (HR 5.05, 95% CI 1.94–13.16), baseline pain and narcotic use before SBRT (pain: HR 1.31, 95% CI 1.06–1.62; narcotic: HR 2.98, 95% CI 1.17–7.56) and after SBRT (pain: HR 1.34, 95% CI 1.06–1.70; narcotic: HR 3.63, 95% CI 1.41–9.29) were statistically significant predictors of fracture progression. On multivariate analysis an age > 55 years (HR 10.66, 95% CI 2.81–40.36), a preexisting fracture (HR 9.17, 95% CI 2.31–36.43), and baseline pain (HR 1.41, 95% CI 1.05–1.9) were found to be significant risks, whereas obesity (HR 0.02, 95% CI 0–0.2) was protective.

Conclusions

Stereotactic body radiotherapy is associated with a significant risk (20%) of VCF. Risk factors for VCF include an age > 55 years, a preexisting fracture, and baseline pain. These risk factors may aid in the selection of which spinal SBRT patients should be considered for prophylactic vertebral stabilization or augmentation procedures. Clinical trial registration no.: NCT00508443.

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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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Jennifer C. Ho, Chad Tang, Brian J. Deegan, Pamela K. Allen, Eric Jonasch, Behrang Amini, Xin A. Wang, Jing Li, Claudio E. Tatsui, Laurence D. Rhines, Paul D. Brown and Amol J. Ghia

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.

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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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Anna Likhacheva, Chelsea C. Pinnix, Neil Parikh, Pamela K. Allen, Nandita Guha-Thakurta, Mary McAleer, Erik P. Sulman, Anita Mahajan, Almon Shiu, Dershan Luo, Max Chiu, Paul D. Brown, Sujit S. Prabhu and Eric L. Chang

Object

Brain metastases present a therapeutic challenge because patients with metastatic cancers live longer now than in the recent past due to systemic therapies that, while effective, may not penetrate the blood-brain barrier. In the present study the authors sought to validate the Diagnosis-Specific Graded Prognostic Assessment (DS-GPA), a new prognostic index that takes into account the histological characteristics of the primary tumor, and the Radiation Therapy Ontology Group Recursive Partitioning Analysis (RPA) system by using a single-institution database of patients who were treated initially with stereotactic radiosurgery (SRS) alone for brain metastases.

Methods

Investigators retrospectively identified adult patients who had undergone SRS at a single institution, MD Anderson Cancer Center, for initial treatment of brain metastases between 2003 and 2010 but excluded those who had undergone craniotomy and/or whole-brain radiation therapy at an earlier time; the final number was 251. The Leksell Gamma Knife was used to treat 223 patients, and a linear accelerator was used to treat 28 patients. The patient population was grouped according to DS-GPA scores as follows: 0–0.5 (7 patients), 1 (33 patients), 1.5 (25 patients), 2 (63 patients), 2.5 (14 patients), 3 (68 patients), and 3.5–4 (41 patients). The same patients were also grouped according to RPA classes: 1 (24 patients), 2 (216 patients), and 3 (11 patients). The most common histological diagnoses were non–small cell lung cancer (34%), melanoma (29%), and breast carcinoma (16%). The median number of lesions was 2 (range 1–9) and the median total tumor volume was 0.9 cm3 (range 0.3–22.9 cm3). The median radiation dose was 20 Gy (range 14–24 Gy). Stereotactic radiosurgery was performed as the sole treatment (62% of patients) or combined with a salvage treatment consisting of SRS (22%), whole-brain radiation therapy (12%), or resection (4%). The median duration of follow-up was 9.4 months.

Results

In this patient group the median overall survival was 11.1 months. The DS-GPA prognostic index divided patients into prognostically significant groups. Median survival times were 2.8 months for DS-GPA Scores 0–0.5, 3.9 months for Score 1, 6.6 months for Score 1.5, 12.9 months for Score 2, 11.9 months for Score 2.5, 12.2 months for Score 3, and 31.4 months for Scores 3.5–4 (p < 0.0001). In the RPA groups, the median overall survival times were 38.8 months for Class 1, 9.4 months for Class 2, and 2.8 months for Class 3 (p < 0.0001). Neither the RPA class nor the DS-GPA score was prognostic for local tumor control or new lesion–free survival. A multivariate analysis revealed that patient age > 60 years, Karnofsky Performance Scale score ≤ 80%, and total lesion volume > 2 cm3 were significant adverse prognostic factors for overall survival.

Conclusions

Application of the DS-GPA to a database of patients with brain metastases who were treated with SRS appears to be valid and offers additional prognostic refinement over that provided by the RPA. The DS-GPA may also allow for improved selection of patients to undergo initial SRS alone and should be studied further.

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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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Eric L. Chang, Almon S. Shiu, Ehud Mendel, Leni A. Mathews, Anita Mahajan, Pamela K. Allen, Jeffrey S. Weinberg, Barry W. Brown, Xin Shelly Wang, Shiao Y. Woo, Charles Cleeland, Moshe H. Maor and Laurence D. Rhines

Object.

The authors report data concerning the safety, effectiveness, and patterns of failure obtained in a Phase I/II study of stereotactic body radiotherapy (SBRT) for spinal metastatic tumors.

Methods.

Sixty-three cancer patients underwent near-simultaneous computed tomography–guided SBRT. Spinal magnetic resonance imaging was conducted at baseline and at each follow-up visit. The National Cancer Institute Common Toxicity Criteria 2.0 assessments were used to evaluate toxicity.

Results.

The median tumor volume of 74 spinal metastatic lesions was 37.4 cm3 (range 1.6–358 cm3). No neuropathy or myelopathy was observed during a median follow-up period of 21.3 months (range 0.9–49.6 months). The actuarial 1-year tumor progression–free incidence was 84% for all tumors. Pattern-of-failure analysis showed two primary mechanisms of failure: 1) recurrence in the bone adjacent to the site of previous treatment, and 2) recurrence in the epidural space adjacent to the spinal cord. Grade 3 or 4 toxicities were limited to acute Grade 3 nausea, vomiting, and diarrhea (one case); Grade 3 dysphagia and trismus (one case); and Grade 3 noncardiac chest pain (one case). There was no subacute or late Grade 3 or 4 toxicity.

Conclusions.

Analysis of the data obtained in the present study supports the safety and effectiveness of SBRT in cases of spinal metastatic cancer. The authors consider it prudent to routinely treat the pedicles and posterior elements using a wide bone margin posterior to the diseased vertebrae because of the possible direct extension into these structures. For patients without a history of radiotherapy, more liberal spinal cord dose constraints than those used in this study could be applied to help reduce failures in the epidural space.

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David Boyce-Fappiano, Olsi Gjyshi, Todd A. Pezzi, Pamela K. Allen, Moaaz Solimman, Nicolette Taku, Michael B. Bernstein, Maria E. Cabanillas, Behrang Amini, Claudio E. Tatsui, Laurence D. Rhines, Xin A. Wang, Tina M. Briere, Debra Nana Yeboa, Andrew J. Bishop, Jing Li and Amol J. Ghia

OBJECTIVE

Patients with metastatic thyroid cancer have prolonged survival compared to those with other primary tumors. The spine is the most common site of osseous involvement in cases of metastatic thyroid cancer. As a result, obtaining durable local control (LC) in the spine is crucial. This study aimed to evaluate the efficacy of spine stereotactic radiosurgery (SSRS) in patients with metastatic thyroid cancer.

METHODS

Information on patients with metastatic thyroid cancer treated with SSRS for spinal metastases was retrospectively evaluated. SSRS was delivered with a simultaneous integrated boost technique using single- or multiple-fraction treatments. LC, defined as stable or reduced disease volume, was evaluated by examining posttreatment MRI, CT, and PET studies.

RESULTS

A total of 133 lesions were treated in 67 patients. The median follow-up duration was 31 months. Dose regimens for SSRS included 18 Gy in 1 fraction, 27 Gy in 3 fractions, and 30 Gy in 5 fractions. The histology distribution was 36% follicular, 33% papillary, 15% medullary, 13% Hurthle cell, and 3% anaplastic. The 1-, 2-, and 5-year LC rates were 96%, 89%, and 82%, respectively. The median overall survival (OS) was 43 months, with 1-, 2-, and 5-year survival rates of 86%, 74%, and 44%, respectively. There was no correlation between the absolute biological equivalent dose (BED) and OS or LC. Patients with effective LC had a trend toward improved OS when compared to patients who had local failure: 68 versus 28 months (p = 0.07). In terms of toxicity, 5 vertebral compression fractures (2.8%) occurred, and only 1 case (0.6%) of greater than or equal to grade 3 toxicity (esophageal stenosis) was reported.

CONCLUSIONS

SSRS is a safe and effective treatment option with excellent LC and minimal toxicity for patients with metastatic thyroid cancer. No association with increased radiation dose or BED was found, suggesting that such patients can be effectively treated with reduced dose regimens.