Mature Local Control and Reirradiation Rates Comparing Spine Stereotactic Body Radiation Therapy With Conventional Palliative External Beam Radiation Therapy.

PURPOSE: Stereotactic body radiation therapy (SBRT) improves complete pain response for painful spinal metastases compared with conventional external beam radiation therapy (cEBRT). We report mature local control and reirradiation rates in a large cohort of patients treated with SBRT versus cEBRT enrolled previously in the Canadian Clinical Trials Group Symptom Control 24 phase 2/3 trial. METHODS AND MATERIALS: One hundred thirty-seven of 229 (60%) patients randomized to 24 Gy in 2 SBRT fractions or 20 Gy in 5 cEBRT fractions were retrospectively reviewed. By including all treated spinal segments, we report on 66 patients (119 spine segments) treated with SBRT and 71 patients (169 segments) treated with cEBRT. The primary outcomes were magnetic resonance-based local control and reirradiation rates for each treated spine segment. RESULTS: The median follow-up was 11.3 months (interquartile range, 5.3-27.7 months), and median overall survival in the SBRT and cEBRT cohorts were 21.6 (95% confidence interval [CI], 11.3, upper bound not reached) and 18.9 (95% CI, 12.2-29.1) months (P = .428), respectively. The cohorts were balanced with respect to radioresistant histology and presence of mass (paraspinal and/or epidural disease extension). Risk of local failure after SBRT versus cEBRT at 6, 12, and 24 months were 2.8% (95% CI, 0.8%-7.4%) versus 11.2% (95% CI, 6.9%-16.6%), 6.1% (95% CI, 2.5%-12.1%) versus 28.4% (95% CI, 21.3%-35.9%), and 14.8% (95% CI, 8.2-23.1%) versus 35.6% (95% CI, 27.8%-43.6%), respectively (P < .001). cEBRT (hazard ratio [HR], 3.48; 95% CI, 1.94-6.25; P < .001) and presence of mass (HR, 2.07; 95% CI, 1.29-3.31; P = .002) independently predicted local failure on multivariable analysis. The 1-year reirradiation rates and median times to reirradiation after SBRT versus cEBRT were 2.2% (95% CI, 0.4-7.0%) versus 15.8% (95% CI, 10.4%-22.3%) (P = .002) and 22.9 months versus 9.5 months, respectively. cEBRT (HR, 2.60; 95% CI, 1.27-5.30; P = .009) and radioresistant histology (HR, 2.00; 95% CI, 1.12-3.60; P = .020) independently predicted for reirradiation. Eight of 12 iatrogenic vertebral compression fractures were after SBRT and 4 of 12 after cEBRT; grade 3 adverse fracture effects were isolated to the SBRT cohort (5 of 12). CONCLUSIONS: Risk of local failure and reirradiation is lower with SBRT compared with cEBRT for spinal metastases. Although the iatrogenic vertebral compression fracture rates were within expectations, grade 3 vertebral compression fractures were isolated to the SBRT cohort.

Evaluation of predictive factors of vertebral compression fracture after conventional palliative radiotherapy for spinal metastasis from colorectal cancer.

OBJECTIVE Delayed consequences of spinal radiotherapy (RT), including vertebral compression fracture (VCF), are critical complications. However, the predisposing factors that contribute to VCF after conventional RT are unclear. The aim of this study was to assess the incidence of VCF and to determine the predictors of VCF following conventional spinal RT specific to colorectal cancer (CRC). METHODS The authors retrospectively reviewed 237 spinal segments (147 metastatic and 90 nonmetastatic) in 53 patients with CRC who underwent RT with a median total dose of 30 Gy in 10 fractions between January 2007 and December 2014. The primary end point was the development of a VCF following RT, either de novo VCF or the progression of a baseline VCF. VCFs were assessed using the spinal instability neoplastic score (SINS) criteria. RESULTS Among all 237 spinal segments, 22 VCFs (9.3%) were observed following RT, including 13 de novo and 9 progressive fractures, and the median time to VCF was 4 months. All VCFs developed in metastatic spines. Among 147 metastatic spinal segments, 22 fractures were observed, with a 12-month cumulative incidence of VCF of 14.8%. Results of multivariable analysis indicated sex (p = 0.023) and SINS class II/III (p < 0.001) as risk factors related to development of a VCF in metastatic spinal segments. Among the SINS criteria, a lytic tumor and the presence of a baseline VCF were identified as predictors of VCF in metastatic spinal segments. CONCLUSIONS In osteolytic or mixed lesions that were predominant in spinal metastases of CRC, the incidence of VCF was not negligible, even in patients treated with conventional spinal RT. This was especially evident in patients with spinal metastases with a SINS score ≥ 7. Presence of a baseline VCF after spinal RT is a predictor of VCF development and should be observed carefully.

Interaction of radiation therapy and radiofrequency kyphoplasty in the treatment of myeloma patients.

BACKGROUND: 30% of myeloma patients suffer from vertebral compression fractures (VCF). Consequently, augmentation often becomes inevitable to prevent further problems. This study evaluated the interaction of radiation therapy (RT) and radiofrequency kyphoplasty (RFK) in the treatment of myeloma associated VCF. METHODS: Eighty-six myeloma patients with VCF were treated with RFK followed by radiation therapy (RFK group) or vice versa (RT group). Visual analgoue scale (VAS), Oswestry-Disability-Index (ODI), vertebral height and kyphosis angle were assessed preoperatively, 3-4 days, 3 and 6 months postoperatively. Adverse events like cement leakage or additional fractures were documented. RESULTS: Both groups achieved comparable outcomes, but the course of VAS and kyphosis angle differed. Early postoperative kyphosis angles improved significantly in the RFK group, but significantly worsened afterwards. The RT group showed a trend towards significantly improvement postoperatively and minor worsening afterwards. VAS remained constant in the RT group and worsened in the RFK group after 6 months. More cement leakages and additional fractures were noted in the RT group. CONCLUSIONS: RFK is an effective method for treating VCF in myeloma patients independent of treatment order with regard to radiation therapy. However, RT should be conducted after RFK to minimize risks of cement extrusion and additional fractures.

The use of vertebral augmentation and external beam radiation therapy in the multimodal management of malignant vertebral compression fractures.

BACKGROUND: Vertebral augmentation (VA) techniques such as vertebroplasty and kyphoplasty are increasingly performed minimally invasive procedures for osteoporotic or malignant compression fractures (MCFs) and involve injection of polymethylmethacrylate (PMMA) cement directly into a compressed vertebral body. OBJECTIVE: This article will evaluate the efficacy of VA in relieving fracture-related pain. We also intend to identify procedural and clinical variables that could potentially influence outcomes in this population. In the subset of patients with cancer who received both external beam radiation therapy (EBRT) and VA, we will assess the impact of the treatment sequence on pain outcomes. STUDY DESIGN: We performed a retrospective analysis of 201 cases of patients with cancer and MCFs who underwent one or more vertebral augmentation procedures at our institution between 2003 and 2009. The majority of cancers represented were multiple myeloma, metastatic lung cancer, and metastatic breast cancer. The primary outcome measure was pain relief, as measured by the Visual Analog Scale and a 4-point pain scale. SETTING: We present an institutional experience at an academic medical center of 201 cases of MCFs. METHODS: We compiled an institutional database of vertebroplasty and kyphoplasty cases using paper and electronic medical records. Our data collection methodology has been previously reported and includes variables such as procedure dates, gender, age, type of malignancy, fracture etiology, history of cancer treatment, type of procedure performed, vertebral level treated, the number of levels treated per procedure, complications, and follow-up information on pain response. The updated dataset incorporates new variables including information on pain medications and standardized questionnaires such as the Visual Analog Scale (VAS) for pain and the Roland Morris Disability Questionnaire (RMDQ). RESULTS: In the 201 cases of MCFs, a total of 316 vertebral levels were treated with either vertebroplasty or kyphoplasty. Follow-up data on pain relief was available for 190 out of 201 cases (95%). Among this subgroup, 168 cases (88%) with MCFs responded. Thirty-nine percent (39%) of the time patients experienced complete pain resolution. In only 4% of cases did patients report worsening of their fracture-related pain post-procedure. There was no difference in pain outcomes with regard to sequencing of EBRT and VA. LIMITATIONS: One of the limitations of our analysis is that it did not evaluate the effect of pain improvement or resolution before and after EBRT alone and on activities of daily living in the majority of patients. However, one of the main goals of this analysis is to address previous limitations. We attempt to standardize outcome measures by using the Visual Analog Scale (VAS) for pain and the Roland Morris Disability Questionnaire (RMDQ). CONCLUSION: A multimodality approach for the management of MCFs includes VA procedures. The majority of patients with MCFs have excellent palliation with this approach. In patients who receive both EBRT and VA, the sequence in which they are given does not affect pain improvement outcomes.

Polymethylmethacrylate and radioisotopes in vertebral augmentation: an explanation of underlying principles.

We recently reported a novel concept for combining radioactive isotope technology with polymethylmethacrylate (PMMA) cement used for vertebral augmentation and have advocated that pain physicians become aware of this new concept when treating malignant compression fractures. The use of vertebral augmentation for malignant compression fractures is steadily increasing, and the goal of this novel approach would be to stabilize the fractured vertebral body while also controlling proliferation of the tumor cells in the vertebral body that caused the vertebral fracture. This approach would therefore provide mechanical stabilization of the fractured vertebral body at the same time as direct targeting of the cancer cells causing the fracture. For our analysis, we investigated six specific radioisotopes with regard to physical and biologic properties as they would interact with PMMA and local bone metastatic disease, taking into consideration anatomical, biological and physical characteristics. The radioisotopes investigated include beta emitting (plus and minus) sources, as well as low energy and mid-energy photon sources and are: P-32, Ho-166, Y-90, I-125, F-18, and Tc-99m. We review the advantages and disadvantages of each radioisotope. In addition, this paper serves to provide pain physicians with a basic background of the biologic principles (Biologically Effective Dose) and statistical modeling (Monte Carlo method) used in that analysis. We also review the potential complications when using radioactive sources in a clinical setting. Understanding the methodologies employed in determining isotope selection empowers the practitioner by fostering understanding of this presently theoretical treatment option. We believe that embedding radioisotopes in PMMA is merely a first step in the road of local treatment for symptomatic local lesions in the setting of systemic disease.