International Journal of Radiation Oncology*Biology*Physics
Clinical InvestigationProbabilities of Radiation Myelopathy Specific to Stereotactic Body Radiation Therapy to Guide Safe Practice
Introduction
The Quantitative Analysis of Normal Tissue Effects in the Clinic (QUANTEC) report was published with the intent to summarize modern radiation therapy dose-volume histogram (DVH) outcome data, and provide evidence-based guidelines for normal tissue tolerance (1) One of the challenges for the spinal cord analysis was the lack of DVH-based data specific to radiation myelopathy (RM) cases (2). They were essentially unable to make evidence-based recommendations for spinal cord tolerance specific to hypofractionated modern radiation therapy, as per stereotactic body radiation therapy (SBRT) practice (2).
The major features that separates SBRT (>5 Gy/fraction) from conventional radiation (≤5 Gy/fraction) treatments are: (1) the delivery of very high dose per fraction radiation in a single, or a few fractions (typically up to 5), to yield a biologically equivalent dose (BED) that would otherwise be considered radical/curative (3); (2) the inherent sensitivity of the dose distribution secondary to the steep dose gradient beyond the target volume, such that millimeter positional variations may yield a delivered dose to an adjacent organ at risk (OAR) greater than what was expected (4); and (3) as both the tumor tissue and normal tissues are more sensitive to high dose per fraction radiation, there is greater potential for tumor response and normal tissue complications (5).
One of the most critical and dose-limiting organs at risk (OAR) for safe SBRT practice for any target—be it spine, liver, or lung—is the spinal cord. The lack of evidence-based spinal cord dose limits specific to SBRT practice is likely why we have been witnessing the re-emergence of the feared late toxicity of radiation-induced myelopathy (RM), which has been otherwise considered a rare toxicity of the past secondary to more crude radiation therapy. There are now 9 known cases of RM directly attributable to spine SBRT in patients with no prior history of radiation exposure. Through a multi-institutional collaboration, we analyzed the actual DVH data for each RM case, and compared them to a cohort of patients treated with spine SBRT who had not developed RM. The data were modeled using logistic regression to generate a probability profile for RM specific to SBRT to guide safe practice.
Section snippets
RM cases
The diagnosis of RM is a diagnosis of exclusion and defined as neurologic signs and symptoms consistent with radiation damage in the form of necrosis to the segment of the spinal cord irradiated, without MRI evidence of recurrent or progressive tumor affecting the spinal cord (6). Clinical and DVH data from 9 RM cases attributed to spine SBRT were identified based on a multi-institutional and international collaboration and included in this analysis. Data were acquired under local institutional
Results
Tumor and patient characteristics for the 66 controls are shown in Table 1. The median follow-up for the entire control group was 15 months (range, 4-29 months). No patient in the control group or RM group had been exposed to prior radiation. The clinical details for the first 5 RM patients have been described in our previous report and summarized in Table 2 (5). Patients 6, 7, 8, and 9 represent 4 new cases with a summary also in Table 2, and we provide a brief clinical description in the
Discussion
RM is a late toxicity secondary to overdosing the spinal cord, and has been virtually unheard of in the modern era of 3-dimensional conformal conventionally fractionated (1.8-3.0 Gy/fraction) radiation therapy. This devastating late effect has re-emerged as a direct result of SBRT practice, where high-dose radiation is delivered adjacent to the spinal cord to be spared. Reasons why we have observed 9 cases of RM to date are likely the following: (1) a lack of understanding of tolerance to the
Conclusion
We report logistic estimates for the probability of RM specific to 1- to 5-fraction SBRT based on the thecal sac contour and delivery using a dedicated SBRT unit. Dose within small volumes of spinal cord predicts the likelihood of RM post-SBRT, and we report doses that yield 1%-5% risks of RM. For a risk of RM of less than 5%, we recommend limiting the thecal sac Pmax volume dose to 12.4 Gy in a single fraction, 17.0 Gy in 2 fractions, 20.3 Gy in 3 fractions, 23.0 Gy in 4 fractions, and 25.3 Gy
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Conflict of interest: none.