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Title: Stereotactic Body Radiation Therapy for Spinal Metastases in the Postoperative Setting: A Secondary Analysis of Mature Phase 1-2 Trials

Abstract

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 withmore » 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.« less

Authors:
; ; ; ;  [1];  [2];  [1];  [3];  [4]; ;  [5];  [1];  [1]
  1. Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States)
  2. Department of Radiation Oncology, USC Norris Cancer Hospital, Keck School of Medicine of USC, Los Angeles, California (United States)
  3. Department of Neuroradiology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States)
  4. Department of Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States)
  5. Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States)
Publication Date:
OSTI Identifier:
22648759
Resource Type:
Journal Article
Resource Relation:
Journal Name: International Journal of Radiation Oncology, Biology and Physics; Journal Volume: 95; Journal Issue: 5; Other Information: Copyright (c) 2016 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; GY RANGE 10-100; MULTIVARIATE ANALYSIS; NMR IMAGING; PATIENTS; RADIATION HAZARDS; RADIOTHERAPY; SARCOMAS; SURGERY; TOXICITY; VERTEBRAE

Citation Formats

Tao, Randa, Bishop, Andrew J., Brownlee, Zachary, Allen, Pamela K., Settle, Stephen H., Chang, Eric L., Wang, Xin, Amini, Behrang, Tannir, Nizar M., Tatsui, Claudio, Rhines, Laurence D., Brown, Paul D., and Ghia, Amol J., E-mail: ajghia@mdanderson.org. Stereotactic Body Radiation Therapy for Spinal Metastases in the Postoperative Setting: A Secondary Analysis of Mature Phase 1-2 Trials. United States: N. p., 2016. Web. doi:10.1016/J.IJROBP.2016.03.022.
Tao, Randa, Bishop, Andrew J., Brownlee, Zachary, Allen, Pamela K., Settle, Stephen H., Chang, Eric L., Wang, Xin, Amini, Behrang, Tannir, Nizar M., Tatsui, Claudio, Rhines, Laurence D., Brown, Paul D., & Ghia, Amol J., E-mail: ajghia@mdanderson.org. Stereotactic Body Radiation Therapy for Spinal Metastases in the Postoperative Setting: A Secondary Analysis of Mature Phase 1-2 Trials. United States. doi:10.1016/J.IJROBP.2016.03.022.
Tao, Randa, Bishop, Andrew J., Brownlee, Zachary, Allen, Pamela K., Settle, Stephen H., Chang, Eric L., Wang, Xin, Amini, Behrang, Tannir, Nizar M., Tatsui, Claudio, Rhines, Laurence D., Brown, Paul D., and Ghia, Amol J., E-mail: ajghia@mdanderson.org. Mon . "Stereotactic Body Radiation Therapy for Spinal Metastases in the Postoperative Setting: A Secondary Analysis of Mature Phase 1-2 Trials". United States. doi:10.1016/J.IJROBP.2016.03.022.
@article{osti_22648759,
title = {Stereotactic Body Radiation Therapy for Spinal Metastases in the Postoperative Setting: A Secondary Analysis of Mature Phase 1-2 Trials},
author = {Tao, Randa and Bishop, Andrew J. and Brownlee, Zachary and Allen, Pamela K. and Settle, Stephen H. and Chang, Eric L. and Wang, Xin and Amini, Behrang and Tannir, Nizar M. and Tatsui, Claudio and Rhines, Laurence D. and Brown, Paul D. and Ghia, Amol J., E-mail: ajghia@mdanderson.org},
abstractNote = {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.},
doi = {10.1016/J.IJROBP.2016.03.022},
journal = {International Journal of Radiation Oncology, Biology and Physics},
number = 5,
volume = 95,
place = {United States},
year = {Mon Aug 01 00:00:00 EDT 2016},
month = {Mon Aug 01 00:00:00 EDT 2016}
}
  • 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 analgesicmore » 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.« less
  • Purpose: To perform an individual patient data (IPD) meta-analysis of randomized controlled trials evaluating stereotactic radiosurgery (SRS) with or without whole-brain radiation therapy (WBRT) for patients presenting with 1 to 4 brain metastases. Method and Materials: Three trials were identified through a literature search, and IPD were obtained. Outcomes of interest were survival, local failure, and distant brain failure. The treatment effect was estimated after adjustments for age, recursive partitioning analysis (RPA) score, number of brain metastases, and treatment arm. Results: A total of 364 of the pooled 389 patients met eligibility criteria, of whom 51% were treated with SRSmore » alone and 49% were treated with SRS plus WBRT. For survival, age was a significant effect modifier (P=.04) favoring SRS alone in patients ≤50 years of age, and no significant differences were observed in older patients. Hazard ratios (HRs) for patients 35, 40, 45, and 50 years of age were 0.46 (95% confidence interval [CI] = 0.24-0.90), 0.52 (95% CI = 0.29-0.92), 0.58 (95% CI = 0.35-0.95), and 0.64 (95% CI = 0.42-0.99), respectively. Patients with a single metastasis had significantly better survival than those who had 2 to 4 metastases. For distant brain failure, age was a significant effect modifier (P=.043), with similar rates in the 2 arms for patients ≤50 of age; otherwise, the risk was reduced with WBRT for patients >50 years of age. Patients with a single metastasis also had a significantly lower risk of distant brain failure than patients who had 2 to 4 metastases. Local control significantly favored additional WBRT in all age groups. Conclusions: For patients ≤50 years of age, SRS alone favored survival, in addition, the initial omission of WBRT did not impact distant brain relapse rates. SRS alone may be the preferred treatment for this age group.« less
  • Purpose: To generate a prognostic index using recursive partitioning analysis (RPA) for patients undergoing spine stereotactic body radiation therapy (sSBRT) for spinal metastases (sMet). Methods and Materials: From an institutional review board-approved database, 174 patients were treated for sMet with sSBRT between February 2006 and August 2009. Median dose was 14 Gy (range, 8-24 Gy), typically in a single fraction (range, 1-5). Kaplan-Meier analysis was performed to detect any correlation between survival and histology. Histologies were divided into favorable (breast and prostate), radioresistant (renal cell, melanoma and sarcoma), and other (all other histologies). RPA was performed to identify any associationmore » of the following variables with overall survival (OS) following sSBRT: histology, gender, age, Karnofsky performance status (KPS), control of primary, extraosseous metastases, time from primary diagnosis (TPD), dose of sSBRT ({<=}14 Gy vs. >14 Gy), extent of spine disease (epidural only, bone and epidural, bone only), upfront or salvage treatment, presence of paraspinal extension, and previous surgery. Results: Median follow-up was 8.9 months. Median OS time from sSBRT was 10.7 months. Median OS intervals for favorable histologies were 14 months, 11.2 months for radioresistant histologies, and 7.3 months for other histologies (p = 0.02). RPA analysis resulted in three classes (p < 0.0001). Class 1 was defined as TPD of >30 months and KPS of >70; Class 2 was TPD of >30 months and KPS of {<=}70 or a TPD of {<=}30 months and age <70 years old; Class 3 was TPD of {<=}30 months and age {>=}70 years old. Median OS was 21.1 months for Class 1 (n = 59), 8.7 months for Class 2 (n = 104), and 2.4 months for Class 3 (n = 11). Conclusion: sSBRT patients treated for sMet have a wide variability in OS. We developed an RPA classification system that is predictive of OS. While many patients are treated for palliation of pain or to avoid symptomatic progression, this index may be used to predict which patients may benefit most from sSBRT.« less
  • Purpose: Radiation Therapy Oncology Group (RTOG) 9508 showed a survival advantage for patients with 1 but not 2 or 3 brain metastasis (BM) treated with whole-brain radiation therapy (WBRT) and stereotactic radiosurgery (SRS) versus WBRT alone. An improved prognostic index, the graded prognostic assessment (GPA) has been developed. Our hypothesis was that if the data from RTOG 9508 were poststratified by the GPA, the conclusions may vary. Methods and Materials: In this analysis, 252 of the 331 patients were evaluable by GPA. Of those, 211 had lung cancer. Breast cancer patients were excluded because the components of the breast GPAmore » are not in the RTOG database. Multiple Cox regression was used to compare survival between treatment groups, adjusting for GPA. Treatment comparisons within subgroups were performed with the log-rank test. A free online tool ( (brainmetgpa.com)) simplified GPA use. Results: The fundamental conclusions of the primary analysis were confirmed in that there was no survival benefit overall for patients with 1 to 3 metastases; however, there was a benefit for the subset of patients with GPA 3.5 to 4.0 (median survival time [MST] for WBRT + SRS vs WBRT alone was 21.0 versus 10.3 months, P=.05) regardless of the number of metastases. Among patients with GPA 3.5 to 4.0 treated with WBRT and SRS, the MST for patients with 1 versus 2 to 3 metastases was 21 and 14.1 months, respectively. Conclusions: This secondary analysis of predominantly lung cancer patients, consistent with the original analysis, shows no survival advantage for the group overall when treated with WBRT and SRS; however, in patients with high GPA (3.5-4), there is a survival advantage regardless of whether they have 1, 2, or 3 BM. This benefit did not extend to patients with lower GPA. Prospective validation of this survival benefit for patients with multiple BM and high GPA when treated with WBRT and SRS is warranted.« less
  • Purpose: There exists uncertainty in the prognosis of patients following spinal metastasis treatment. We sought to create a scoring system that stratifies patients based on overall survival. Methods and Materials: Patients enrolled in 2 prospective trials investigating stereotactic spine radiation surgery (SSRS) for spinal metastasis with ≥3-year follow-up were analyzed. A multivariate Cox regression model was used to create a survival model. Pretreatment variables included were race, sex, age, performance status, tumor histology, extent of vertebrae involvement, previous therapy at the SSRS site, disease burden, and timing of diagnosis and metastasis. Four survival groups were generated based on the model-derivedmore » survival score. Results: Median follow-up in the 206 patients included in this analysis was 70 months (range: 37-133 months). Seven variables were selected: female sex (hazard ratio [HR] = 0.7, P=.02), Karnofsky performance score (HR = 0.8 per 10-point increase above 60, P=.007), previous surgery at the SSRS site (HR = 0.7, P=.02), previous radiation at the SSRS site (HR = 1.8, P=.001), the SSRS site as the only site of metastatic disease (HR = 0.5, P=.01), number of organ systems involved outside of bone (HR = 1.4 per involved system, P<.001), and >5 year interval from initial diagnosis to detection of spine metastasis (HR = 0.5, P<.001). The median survival among all patients was 25.5 months and was significantly different among survival groups (in group 1 [excellent prognosis], median survival was not reached; group 2 reached 32.4 months; group 3 reached 22.2 months; and group 4 [poor prognosis] reached 9.1 months; P<.001). Pretreatment symptom burden was significantly higher in the patient group with poor survival than in the group with excellent survival (all metrics, P<.05). Conclusions: We developed the prognostic index for spinal metastases (PRISM) model, a new model that identified patient subgroups with poor and excellent prognoses.« less