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  • Author or Editor: Laurence Rhines x
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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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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.

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Arjun Sahgal, Mark Bilsky, Eric L. Chang, Lijun Ma, Yoshiya Yamada, Laurence D. Rhines, Daniel Létourneau, Matthew Foote, Eugene Yu, David A. Larson and Michael G. Fehlings

Stereotactic body radiotherapy (SBRT) for spinal metastases is an emerging therapeutic option aimed at delivering high biologically effective doses to metastases while sparing the adjacent normal tissues. This technique has emerged following advances in radiation delivery that include sophisticated radiation treatment planning software, body immobilization devices, and capabilities of detecting and correcting patient positional deviations with imageguided radiotherapy. There are limited clinical data specifically supporting the role of SBRT as a superior alternative to conventional radiation in the postoperative patient. The focus of this review was to examine the evidence pertaining to spine SBRT in the treatment of spinal metastases and to provide a comprehensive analysis of published patterns of failure, with emphasis on the postoperative patient.

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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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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.