External-beam Radiation Therapy for Skeletal Metastases
External-beam Radiation Therapy for Skeletal Metastases
Overall toxicity after spinal SBRT is rare. Major late toxicity associated with spinal SBRT includes radiation myelopathy due to spinal cord necrosis, vertebral body compression fracture, and brachial plexopathy. In most cases, progressive neurologic deficits are usually due to tumor progression. Myelopathy due to a radiation injury is uncommonly reported in the literature.
Benzil et al treated 31 patients with 35 metastatic lesions; 2 patients had transient radiculitis. Gibbs et al reported the Stanford experience with 74 patients and 102 lesions; 50 patients had prior radiotherapy. Patients were treated variably with 16 to 25 Gy in 1 to 5 fractions, with a dose per fraction of 7 to 20 Gy. Radiosurgery-related neurotoxicity was observed in 3 patients, without significant recovery. Two noted to have had antiangiogenic or epidermal growth factor receptor inhibitor therapy within 2 months of developing clinical myelopathy.
Ryu et al retrospectively reviewed the toxicity and cumulated dose-volume histogram data for patients treated with single-fraction radiosurgery, with the dose range from 8 to 18 Gy (mean, 14.3 Gy). None of the patients had received prior spinal radiotherapy. The authors concluded that the partial-volume tolerance of the spinal cord is at least 10 Gy to 10% of the spinal cord volume 6 mm above and below the target. This dose constraint has gained wide acceptance and is applied in the current ongoing RTOG spinal radiosurgery trial.
Sahgal et al studied dosimetric data from 5 cases of radiation-induced myelopathy after SBRT. Mathematical modeling of the dose to the thecal sac suggested a stricter dose constraint to prevent myelopathy after SBRT. The study recommended a 10-Gy maximum point dose to the thecal sac when planning for single-fraction SBRT. For multifraction SBRT, the group suggested the mean normalized 2-Gy–equivalent biologically effective dose (nBED 2/2) of 30 to 35 Gy to the thecal sac.
A recent publication from the quantitative analysis of normal tissue effects in the clinic (QUANTEC) comprehensively reviewed literature on radiation dose tolerances of a variety of normal tissues. For the spinal cord, the available literature suggested the risk of radiation-induced myelopathy is less than 1% when the maximum dose to the partial spinal cord is limited to 13 Gy for single-fraction treatment and 20 Gy for 3-fraction– hypofraction treatment. Further investigation is needed to delineate dose constraints for spinal SBRT.
Reirradiation and overall tolerance of the spinal cord after conventional radiotherapy are under active investigation. In a separate report examining tolerance of the spinal cord to reirradiation using SBRT 5 months or more after conventional palliative radiotherapy, Sahgal et al concluded that nBED 2/2 of the maximal dose to the thecal sac should be kept at 20 to 25 Gy while the total maximal point dose nBED 2/2 does not exceed 70 Gy. The SBRT dose to the thecal sac should be limited to less than 50% of the total nBED. The analysis emphasized that the dose from the initial course of radiotherapy should be taken into account. Although the data are preliminary and retrospective, these proposed guidelines permit safe SBRT planning and allow future research to refine more precise constraints for the spinal cord.
As previously mentioned, a higher rate of fracture associated with SBRT was reported by Rose et al from the Memorial Sloan-Kettering Cancer Center. The dose used was significantly higher than the experiences from other institutions (mean, 24 Gy; range, 18 to 25 Gy). Several other institutions treated patients with a mean dose of 16 Gy, with no increased risk of fracture. At this time, whether there is a dose-response relationship that influences the fracture risk is not well understood. The current RTOG study evaluating radiosurgery for spinal oligometastasis with a single fraction of 16 Gy may provide prospective evaluation of the fracture risk.
Another rare toxicity after cervical or upper thoracic spinal SBRT is brachial plexopathy. Reports of this toxicity in the literature are limited. A relatively recent publication, which focused on patients with lung cancer treated with SBRT, highlighted the risk of this delayed radiation toxicity. The risk of grades 2–4 plexopathy increased significantly when the maximal dose to the brachial plexus exceeded 26 Gy in 3 or 4 fractions.
Toxicity After SBRT to the Spine
Overall toxicity after spinal SBRT is rare. Major late toxicity associated with spinal SBRT includes radiation myelopathy due to spinal cord necrosis, vertebral body compression fracture, and brachial plexopathy. In most cases, progressive neurologic deficits are usually due to tumor progression. Myelopathy due to a radiation injury is uncommonly reported in the literature.
Benzil et al treated 31 patients with 35 metastatic lesions; 2 patients had transient radiculitis. Gibbs et al reported the Stanford experience with 74 patients and 102 lesions; 50 patients had prior radiotherapy. Patients were treated variably with 16 to 25 Gy in 1 to 5 fractions, with a dose per fraction of 7 to 20 Gy. Radiosurgery-related neurotoxicity was observed in 3 patients, without significant recovery. Two noted to have had antiangiogenic or epidermal growth factor receptor inhibitor therapy within 2 months of developing clinical myelopathy.
Ryu et al retrospectively reviewed the toxicity and cumulated dose-volume histogram data for patients treated with single-fraction radiosurgery, with the dose range from 8 to 18 Gy (mean, 14.3 Gy). None of the patients had received prior spinal radiotherapy. The authors concluded that the partial-volume tolerance of the spinal cord is at least 10 Gy to 10% of the spinal cord volume 6 mm above and below the target. This dose constraint has gained wide acceptance and is applied in the current ongoing RTOG spinal radiosurgery trial.
Sahgal et al studied dosimetric data from 5 cases of radiation-induced myelopathy after SBRT. Mathematical modeling of the dose to the thecal sac suggested a stricter dose constraint to prevent myelopathy after SBRT. The study recommended a 10-Gy maximum point dose to the thecal sac when planning for single-fraction SBRT. For multifraction SBRT, the group suggested the mean normalized 2-Gy–equivalent biologically effective dose (nBED 2/2) of 30 to 35 Gy to the thecal sac.
A recent publication from the quantitative analysis of normal tissue effects in the clinic (QUANTEC) comprehensively reviewed literature on radiation dose tolerances of a variety of normal tissues. For the spinal cord, the available literature suggested the risk of radiation-induced myelopathy is less than 1% when the maximum dose to the partial spinal cord is limited to 13 Gy for single-fraction treatment and 20 Gy for 3-fraction– hypofraction treatment. Further investigation is needed to delineate dose constraints for spinal SBRT.
Reirradiation and overall tolerance of the spinal cord after conventional radiotherapy are under active investigation. In a separate report examining tolerance of the spinal cord to reirradiation using SBRT 5 months or more after conventional palliative radiotherapy, Sahgal et al concluded that nBED 2/2 of the maximal dose to the thecal sac should be kept at 20 to 25 Gy while the total maximal point dose nBED 2/2 does not exceed 70 Gy. The SBRT dose to the thecal sac should be limited to less than 50% of the total nBED. The analysis emphasized that the dose from the initial course of radiotherapy should be taken into account. Although the data are preliminary and retrospective, these proposed guidelines permit safe SBRT planning and allow future research to refine more precise constraints for the spinal cord.
As previously mentioned, a higher rate of fracture associated with SBRT was reported by Rose et al from the Memorial Sloan-Kettering Cancer Center. The dose used was significantly higher than the experiences from other institutions (mean, 24 Gy; range, 18 to 25 Gy). Several other institutions treated patients with a mean dose of 16 Gy, with no increased risk of fracture. At this time, whether there is a dose-response relationship that influences the fracture risk is not well understood. The current RTOG study evaluating radiosurgery for spinal oligometastasis with a single fraction of 16 Gy may provide prospective evaluation of the fracture risk.
Another rare toxicity after cervical or upper thoracic spinal SBRT is brachial plexopathy. Reports of this toxicity in the literature are limited. A relatively recent publication, which focused on patients with lung cancer treated with SBRT, highlighted the risk of this delayed radiation toxicity. The risk of grades 2–4 plexopathy increased significantly when the maximal dose to the brachial plexus exceeded 26 Gy in 3 or 4 fractions.
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