By Lisa Braverman, Red Journal Managing Editor
Chia-Lin (Eric) Tseng, MD, with the department of radiation oncology at Sunnybrook Health Sciences Centre at the University of Toronto in Canada, answered a few questions from the Red Journal editorial team about his recent co-authored article
, “Imaging-Based Outcomes for 24 Gy in 2 Daily Fractions for Patients with De Novo Spinal Metastases Treated with Spine Stereotactic Body Radiation Therapy (SBRT).” SA-CME is available for this article through ASTRO Academy
Tell us about your study.
Spine stereotactic body radiation therapy (SBRT) has been made possible in recent years due to advances in patient immobilization, target visualization and delivery techniques. Consequently, it has emerged as a potential treatment option for selected patients with spinal metastases. However, as there is currently no level I evidence, ongoing randomized studies (NCT00922974, NCT02512965) are expected to provide higher quality outcome data with respect to spine SBRT versus conventional radiation. In this study, we report mature outcomes for a large cohort of patients with no prior radiation (de novo) to the spine treated with 24 Gray (Gy) in two daily fractions for metastases, which represents the same SBRT regimen under evaluation in the Symptom Control-24, phase-3 randomized trial (NCT02512965). Our study provides evidence supporting the safety and high efficacy of this fractionation scheme in achieving tumor control for de novo spinal metastases. The outcomes presented in this study will serve as benchmark data for ongoing trials of this regimen.
Why is there such a wide variety of fractionation schemas for the spine, even when treating the same cancer type?
The optimal dose fractionation for spine SBRT in the setting of metastases is uncertain at present. Several dose-fractionation schemes for spine SBRT are currently in use, most commonly 16 to 24 Gy in one fraction, 24 Gy in two fractions, 24 to 27 Gy in three fractions and 30 to 35 Gy in five fractions. However, no level I evidence exists to support the use of one fractionation over another. Although some published reports have suggested improved local control with single fraction SBRT compared with a multi-fraction approach, single fraction treatment has also been associated with a much higher risk of vertebral compression fracture
(VCF), according to recent studies
. A recent systematic review
of post-SBRT VCF based on 11 studies using a variety of fractionation schemes reported an overall crude VCF rate of 13.9 percent and a salvage intervention rate of 37 percent (range 11 percent-60 percent). The challenge with purported higher local control rates of one fractionation scheme over another is the retrospective nature of the reported data, which are subject to various biases and heterogeneity of the treated population, including histology. A randomized clinical trial (NCT01223248), although not specific to spine, is currently open to address this question, comparing 24 Gy in one fraction to 27 Gy in three fractions delivered to sites of cancer metastasis.
What do you think are the advantages of SBRT compared with regular external beam radiation therapy for spine metastases?
Spine SBRT may be employed as an alternative to conventional palliative radiation in the treatment of de novo metastases, in re-irradiation and in the postoperative setting, although currently without the support of level I evidence. We are awaiting the results of randomized studies comparing SBRT with conventional radiation (NCT00922974, NCT02512965). The use of higher doses per fraction in SBRT, particularly 8 Gy or more, may increase tumor cell kill compared with conventional external beam radiation via a number of mechanisms, including radiation-induced tumor-antigen specific immune response, endothelial/vascular injury or simply increased cell death due to a higher delivered biologically effective dose. To date, most published institutional series have reported high local control rates, ranging from 80 percent to 96 percent at one year, for spine SBRT of de novo metastases. Furthermore, spine SBRT is particularly suitable in the context of re-irradiation as it allows dose escalation to the tumor while achieving rapid dose falloff to minimize spinal cord dose exposure.
Should all metastatic cancer patients with spine disease have SBRT? Which ones should not?
The optimal management of spinal metastases is complex and requires a multidisciplinary approach with input from radiation oncology, spine surgery, medical oncology and radiology. Considerations should be given to patient factors, oncologic factors and treatment-specific factors. Patient factors may include neurological function, pain, age, comorbidities, performance status, estimated life expectancy and patient preferences. Oncologic factors may include tumor histology and molecular characteristics, overall disease burden, patient response to prior treatments and available systemic therapeutic options. Treatment-specific factors may include location of the metastatic disease within the spine, grade of epidural disease, radiographic appearance, prior surgical or radiation treatment and degree of spinal instability. In general, patients who have very poor performance status, high grade epidural spinal cord compression (Bilsky 3) or cauda equina compression, or who have frank spinal instability (SINS ≥ 13) are considered unsuitable for upfront spine SBRT. Ultimately, level I randomized evidence is needed to more definitively understand the indications, clinical outcomes and appropriate patient selection for spine SBRT.
Are there any special considerations with regard to the use of spine SBRT?
Yes, spine SBRT is complex not only in its planning and delivery, but in the multidisciplinary clinical decision-making process necessary for implementation. Therefore, it is critical not only for physicians to understand the technical know-how, but the rapidly evolving clinical concepts and appropriate application of spine SBRT in selected patients. Caution must be exercised when this treatment is used in the absence of sufficient experience and/or multidisciplinary support.