International Journal of Radiation Oncology*Biology*Physics
QUANTEC: Organ Specific PaperRadiation Dose–Volume Effects in the Spinal Cord
Section snippets
Clinical Significance
The spinal cord consists of bundles of motor and sensory tracts, surrounded by the thecal sac, which is, in turn, encased by the spinal canal (1). Although the cord proper extends from the base of skull through the top of the lumbar spine, individual nerves continue down the spinal canal to the level of the pelvis. Portions of the spinal cord are often included in radiotherapy (RT) fields for treatment of malignancies involving the neck, thorax, abdomen, and pelvis. In addition, metastatic
Endpoints
Herein, myelopathy is defined as a Grade 2 or higher myelitis, per Common Terminology Criteria for Adverse Events v3.0 (4). Asymptomatic changes in the cord detected radiographically or mild signs/symptoms such as Babinski's sign or L'Hermitte syndrome are not classified as myelopathy for purpose of this analysis. Thus, a diagnosis of myelopathy is based on the appearance of signs/symptoms of sensory or motor deficits, loss of function or pain, now frequently confirmed by magnetic resonance
Challenges Defining Volumes
In conventional external beam RT, the field generally encompasses the entire circumference of the cord, vertebral body, and spinal nerve roots at the treated levels. Thus, precise organ definition is not critical in conventional RT apart from appropriately identifying the level of the involved cord. Delineation of the cord in body radiosurgery is unsettled (6) with various studies contouring the critical organ in the axial plane as the spinal cord, the spinal cord +2–3 mm, the thecal sac and
Preclinical studies
A large number of small-animal studies have explored spinal cord tolerance to de novo radiation and reirradiation, including time-dependent repair of such damage. Several reports suggest regional differences in radiosensitivity across the spinal cord 8, 9. The clinical endpoint in most studies is paralysis, with the spinal cord showing nonspecific white matter necrosis. The pathogenesis of injury is generally believed to be primarily from vascular/endothelial damage, glial cell injury, or both 3
Factors Affecting Risk
Animal studies suggest that the immature spine is slightly more susceptible to radiation-induced complications and the latent period is shorter 13, 57, 58, 59. For example, Ruifrok (57) found that the 50% effect dose in 1-week-old rats was 19.5 Gy vs. 21.5 Gy in adult animals (p < 0.05). The latency to complications increased from about 2 weeks after irradiation in the 1-week-old rats to 6–8 months in the adults (59). Although the ultimate white matter changes were the same in animals
Conventionally fractionated, full-circumference irradiation
Using the data in Table 1, Table 2, Schultheiss 18, 69 estimated the risk of myelopathy as a function of dose using a probability distribution model. In this model, the probability of myelopathy was derived from the data in Table 1, Table 2 adjusted for estimated overall survival (18). A good fit to the combined cervical and thoracic cord data was not possible and separate analyses were performed. For the cervical cord data, values of D50 = 69.4 Gy and α/β = 0.87 Gy were obtained with a Pearson
Special Situations
As discussed in detail previously, hypofractionation via radiosurgery is increasingly employed in the treatment of spinal lesions. Though reports of toxicity are rare, the follow-up time is short and patient numbers small. Caution should be observed in specifying the dose, taking special care to limit the dose to the cord by precise immobilization and image guidance. Predictions based on conventional fractionation should not be applied to such treatments without further careful study. The
Recommended Dose–Volume Limits
With conventional fractionation of 2 Gy per day including the full cord cross-section, a total dose of 50 Gy, 60 Gy, and ∼69 Gy are associated with a 0.2, 6, and 50% rate of myelopathy. For reirradiation of the full cord cross-section at 2 Gy per day after prior conventionally fractionated treatment, cord tolerance appears to increase at least 25% 6 months after the initial course of RT based on animal and human studies. For partial cord irradiation as part of spine radiosurgery, a maximum cord
Future Toxicity Studies
In cases where it is appropriate to irradiate only a partial circumference of the cord (as in irradiation of vertebral body lesions) or spare the interior of the cord (epidural disease), dose tolerance may be increased. SBRT, particularly using intensity-modulated RT techniques, appears well suited for that purpose, as it can be used to deliver concave-shaped RT dose distributions around organs at risk (56). Studies to better understand the importance of the spatial distribution of dose (and,
Toxicity Scoring
We recommend that the Common Terminology Criteria for Adverse Events (version 3) be used to score both acute and late spinal cord injury.
Acknowledgment
Dr. Kirkpatrick has a research grant from Varian Medical Systems, Palo Alto, Ca.
References (70)
- et al.
Radiation response of the central nervous system
Int J Radiat Oncol Biol Phys
(1995) - et al.
Radiation myelopathy of the cervical spinal cord. Time, dose, and volume factors
Int J Radiat Oncol Biol Phys
(1978) - et al.
Dose-volume effects in rat thoracolumbar spinal cord: The effects of nonuniform dose distribution
Int J Radiat Oncol Biol Phys
(2007) - et al.
Dose-volume effects in the rat cervical spinal cord after proton irradiation
Int J Radiat Oncol Biol Phys
(2002) - et al.
Regional differences in radiosensitivity across the rat cervical spinal cord
Int J Radiat Oncol Biol Phys
(2005) - et al.
The effect of small radiation doses on the rat spinal cord: The concept of partial tolerance
Int J Radiat Oncol Biol Phys
(1983) - et al.
The tolerance of primate spinal cord to re-irradiation
Int J Radiat Oncol Biol Phys
(1993) - et al.
Extent and kinetics of recovery of occult spinal cord injury
Int J Radiat Oncol Biol Phys
(2001) - et al.
Long-term recovery kinetics of radiation damage in rat spinal cord
Int J Radiat Oncol Biol Phys
(1997) The radiation dose-response of the human spinal cord
Int J Radiat Oncol Biol Phys
(2008)
Radiation tolerance of the cervical spinal cord
Int J Radiat Oncol Biol Phys
The incidence of myelitis after irradiation of the cervical spinal cord
Int J Radiat Oncol Biol Phys
Basis for new strategies in postoperative radiotherapy of bronchogenic carcinoma
Int J Radiat Oncol Biol Phys
Split course radiation in inoperable carcinoma of the bronchus
Eur J Cancer
Radiation myelitis and survival in the radiotherapy of lung cancer
Int J Radiat Oncol Biol Phys
Myelopathy following radiotherapy of bronchial carcinoma with large single fractions: A retrospective study
Int J Radiat Oncol Biol Phys
Radiation myelopathy: Estimates of risk in 1048 patients in three randomized trials of palliative radiotherapy for non-small cell lung cancer. The Medical Research Council Lung Cancer Working Party
Clin Oncol (R Coll Radiol)
Proposal of human spinal cord reirradiation dose based on collection of data from 40 patients
Int J Radiat Oncol Biol Phys
A phase II study of primary reirradiation in squamous cell carcinoma of head and neck
Radiother Oncol
Retreatment of the spinal cord with palliative radiotherapy
Int J Radiat Oncol Biol Phys
Update of human spinal cord reirradiation tolerance based on additional data from 38 patients
Int J Radiat Oncol Biol Phys
Intensity-modulated radiation therapy for the spine at the University of California, Irvine
Med Dosim
Reirradiation of primary CNS tumors
Int J Radiat Oncol Biol Phys
Neurological damage in patients irradiated twice on the spinal cord: A morphologic and electrophysiological study
Radiother Oncol
Proximity of spinous/paraspinous radiosurgery metastatic targets to the spinal cord versus risk of local failure
Int J Radiat Oncol Biol Phys
Stereotactic body radiotherapy for lesions of the spine and paraspinal regions
Int J Radiat Oncol Biol Phys
Radiation tolerance of the immature rat spinal cord
Radiother Oncol
Radiation tolerance and fractionation sensitivity of the developing rat cervical spinal cord
Int J Radiat Oncol Biol Phys
Radiation response of the rat cervical spinal cord after irradiation at different ages: Tolerance, latency and pathology
Int J Radiat Oncol Biol Phys
The effect of intraspinal cytosine arabinoside on the re-irradiation tolerance of the cervical spinal cord of young and adult rats
Eur J Cancer
Effect of intra-peritoneal fludarabine on rat spinal cord tolerance to fractionated irradiation
Radiother Oncol
Sequential radiotherapy and Adriamycin in the management of bronchogenic carcinoma: The question of additive toxicity
Int J Radiat Oncol Biol Phys
Radiation myelopathy following transplantation and radiotherapy for non-Hodgkin's lymphoma
Int J Radiat Oncol Biol Phys
Fatal radiation myelopathy after high-dose busulfan and melphalan chemotherapy and radiotherapy for Ewing's sarcoma: A review of the literature and implications for practice
Clin Oncol (R Coll Radiol)
Radiation response of the central nervous system
Int J Radiat Oncol Biol Phys
Cited by (419)
Neurological complications of modern radiotherapy for head and neck cancer
2024, Radiotherapy and OncologyPractice and principles of stereotactic body radiation therapy for spine and non-spine bone metastases
2024, Clinical and Translational Radiation OncologyPredictive Factors Associated With Radiation Myelopathy in Pediatric Patients With Cancer: A PENTEC Comprehensive Review
2024, International Journal of Radiation Oncology Biology PhysicsPENTEC Organ-Specific Report: Brain and Brain Stem Necrosis After Reirradiation for Recurrent Childhood Primary Central Nervous System Tumors: A PENTEC Comprehensive Review
2024, International Journal of Radiation Oncology Biology Physics