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Keywords:

  • breast carcinoma;
  • spine metastases;
  • stereotactic radiosurgery;
  • CyberKnife

Abstract

  1. Top of page
  2. Abstract
  3. MATERIALS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. REFERENCES

BACKGROUND

The spine is the most common site of bony metastases in patients with osseous breast carcinoma metastases. Spine metastases are the source of significant pain and occasionally neurologic deficit in this patient population. Conventional external beam radiotherapy lacks the precision to allow delivery of large single-fraction doses of radiation and simultaneously limit the dose to radiosensitive structures such as the spinal cord. This study evaluated the clinical efficacy of the treatment of spinal breast carcinoma metastases with a single-fraction radiosurgical technique.

METHODS

In this prospective cohort evaluation, 68 breast carcinoma metastases to the spine in 50 patients were treated with a single-fraction radiosurgery technique with a follow-up period of 6–48 months, median 16 months. The most common indication for radiosurgery treatment was pain in 57 lesions, as a primary treatment modality in 8 patients, and for radiographic tumor progression, as a postsurgical boost, and for a progressive neurologic deficit in 1 patient each.

RESULTS

Tumor volume ranged from 0.8–197 cm3 (mean, 27.7 cm3). Maximum tumor dose was maintained at 15–22.5 Gy (mean, 19 Gy). No radiation-induced toxicity occurred during the follow-up period (6–48 mo). Long-term axial and radicular pain improvement occurred in 55 of 57 (96%) patients who were treated primarily for pain. Long-term radiographic tumor control was seen in all patients who underwent radiosurgery as their primary treatment modality, for radiographic tumor progression, or as a postsurgical treatment.

CONCLUSIONS

Spinal radiosurgery was found to be feasible, safe, and clinically effective for the treatment of spinal metastases from breast carcinoma. The results indicate the potential of radiosurgery in the treatment of patients with spinal breast metastases, especially those with solitary sites of spine involvement, to improve long-term palliation. Cancer 2005. © 2005 American Cancer Society.

Approximately 200,000 women develop breast carcinoma in the U.S. each year.1 Thirty percent of patients with breast carcinoma go on to develop metastatic disease. Bone metastases are the most common initial site of metastases, and the spine is the most common site of bony metastases in patients with osseous breast carcinoma metastases. In fact, metastatic disease from the breast is the most prevalent of all spinal tumors.2 Spine metastases are the source of significant pain and occasionally neurologic deficit in this patient population. These lesions are usually radiosensitive and are also often responsive to both hormonal as well as cytotoxic chemotherapy.3

The role of radiation therapy in the treatment of metastatic tumors of the spine is well established and is often the initial treatment modality.4–10 The goals of local radiation therapy in the treatment of spinal tumors have been palliation of pain, prevention of pathologic fractures, and halting progression of or reversing neurologic compromise.11 Surgery is usually reserved for spinal instability or subluxation, in patients with neurologic deficits despite other forms of therapy, and those with intractable pain attributable to an isolated lesion.12–15 Studies have previously determined the clinical efficacy of single-fraction therapy for painful bone metastases.16, 17 A primary factor that limits radiation dose for local vertebral tumor control with conventional radiotherapy is the relatively low tolerance of the spinal cord to radiation. Conventional external beam radiotherapy lacks the precision to deliver large single-fraction doses of radiation to the spine near radiosensitive structures such as the spinal cord. It is the low tolerance of the spinal cord to radiation that often limits the treatment dose to a level that is far below the optimal therapeutic dose.4, 18, 19 Radiotherapy may provide less than optimal clinical response because the total dose is limited by the tolerance of the spinal cord. Confinement of the radiation dose to the treatment volume, as is the case for intracranial radiosurgery using techniques such as the Gamma Knife, should increase the likelihood of successful tumor control at the same time that the risk of spinal cord injury is minimized.19–27

Radiosurgery is defined as the delivery of a highly conformal, large radiation dose to a localized tumor by a stereotactic approach.28 Since Hamilton et al.29 first described the possibility of a linear-accelerator-based spinal stereotactic radiosurgery in 1995, multiple centers have attempted to pursue large fraction conformal radiation delivery to spinal lesions using a variety of technologies.19, 22–36 Treatment of spinal lesions by stereotactic conformal radiotherapy and intensity-modulated radiation therapy (IMRT) have shown promising clinical results. Several clinical studies have described stereotactic radiosurgery (SRS) for the treatment of brain metastases specifically from breast carcinoma as an effective treatment associated with a low complication rate.37–42 Other researchers have previously shown the feasibility and clinical efficacy of spinal hypofractionated stereotactic body radiotherapy for breast metastases.19, 21–27, 43 Our previous work has demonstrated both the feasibility as well as the clinical efficacy of spinal radiosurgery for a variety of both benign and malignant lesions using an image-guided frameless SRS delivery system known as the CyberKnife Image-Guided Radiosurgery System (Accuray, Sunnyvale, CA).22–24, 26 The purpose of this study was to evaluate the clinical outcomes of radiosurgery for the treatment of metastases to the spine from breast carcinoma to see if such a radiosurgery technique parallels the efficacy that has been demonstrated for the treatment of intracranial breast metastases.

MATERIALS AND METHODS

  1. Top of page
  2. Abstract
  3. MATERIALS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. REFERENCES

This study involved the prospective evaluation of 68 lesions in 50 consecutive women with histologically proven breast carcinoma metastatic to the spine who were treated using the CyberKnife Image-Guided Radiosurgery System with the Dynamic Tracking System (DTS) 3.0 software. All patients were treated at the University of Pittsburgh Medical Center (Pittsburgh, PA) and the protocol was approved by the University of Pittsburgh's institutional review board. Spinal metastases were diagnosed by computed tomography (CT) and/or magnetic resonance imaging (MRI). Ages ranged from 36–77 years (mean, 56 yrs). Follow-up ranged from 6–48 months (median, 16 mos). Table 1 summarizes the characteristics of the treatment group. Table 2 summarizes the primary indications for spinal SRS that were used for patient selection for this study. The most common indication for treatment was pain in 57 patients, as a primary treatment modality in 8 patients, for asymptomatic radiographic tumor progression on serial imaging in 1 patient, and for postsurgical boost and progressive neurologic deficit in 1 patient each. The levels of involvement included 13 cervical, 25 thoracic, 14 lumbar, and 16 sacral.

Table 1. Characteristics of the Treatment Group (N = 68 lesions)
Characteristics 
Age in yrs 
Mean56
Range36–77
Patients with multiple lesions treated18
Prior external beam irradiation48
Levels treated 
 Cervical13
 Thoracic25
 Lumbar14
 Sacral16
Skull tracking13
Fiducial tracking55
Mean tumor volume (range, 0.8–97 cm3)27.7 cm3
Mean maximum tumor dose (range, 15–22.5 Gy)19 Gy
Mean volume of spinal canal dose > 8 Gy0.44 cm3
Mean volume of cauda equina dose > 8 Gy0.63 cm3
Table 2. Primary Indications for Spinal Stereotactic Radiosurgery for the Treatment Group (N = 68 lesions)
Pain57
Primary treatment modality8
Tumor progression on imaging1
Radiation boost after surgery1
Progressive neurologic deficit1

Forty-eight patients had previously undergone external beam irradiation that precluded further conventional irradiation to the involved level. In these 48 patients, prior irradiation was delivered using fractionation schedules ranging from 3 Gy × 10–2.5 Gy × 14. Radiosurgery was felt to be indicated to limit further radiation dose to the neural structures. Tumor dose was not decreased in a uniform manner in these previously irradiated patients. Instead, the maximum dose to the spinal cord or cauda equina was more strictly limited, constrained by the CyberKnife's inverse treatment planning system. The combination of a steep dose gradient and high conformability of the CyberKnife treatment allows for such high doses to be delivered so close to the adjacent critical structures (e.g., the spinal cord). Except in a single case, patients with myelopathy or cauda equina syndrome from direct tumor progression were not felt to be candidates for radiosurgery treatment. Exclusion criteria for CyberKnife treatment were: 1) evidence of overt spinal instability, or 2) neurologic deficit resulting from bony compression of neural structures. For evaluation of pain relief, a 10-point visual analog scale with intensity description was administered to all patients before radiosurgery and 1 month after radiosurgery. The last pain score was used to determine long-term pain control. Pain scores ranged from 0 (no pain) to 10 (the worst imaginable pain). Analgesic usage was also documented.

The CyberKnife consists of a 6 mV compact linear accelerator that is smaller and lighter in weight than linear accelerators used in conventional radiotherapy (Fig. 1).44–47 The smaller size allows it to be mounted on a computer-controlled six-axis robotic manipulator that permits a much wider range of beam orientations than can be achieved with conventional radiotherapy devices.19, 30, 48, 49 Two diagnostic X-ray cameras are positioned orthogonally (90° offset) to acquire real-time images of the patient's internal anatomy during treatment. The images are processed to identify radiographic features (skull bony landmarks or implanted fiducials) and then automatically compared with the patient's CT treatment planning study. The precise tumor position is communicated through a real-time control loop to a robotic manipulator that aligns the radiation beam with the intended target.50 An analysis of the accuracy of the CyberKnife radiosurgery system found that the machine has a clinically relevant accuracy of 1.1 ± 0.3 mm using a 1.25-mm CT slice thickness.49

thumbnail image

Figure 1. Patient setup on the CyberKnife treatment couch. The CyberKnife consists of a linear accelerator mounted on a six-axis robotic manipulator that permits a wide range of beam orientations. Note the amorphous silicon X-ray screen positioned orthogonally to the treatment couch. The patient is positioned supine with legs in an alpha cradle for comfort and to limit motion. The couch will move rostrally to place the fiducials between the amorphous silicon detectors.

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The CyberKnife spinal radiosurgery treatment consists of three distinct components: 1) CT image acquisition based on skull bony landmarks or implanted bone fiducials, 2) treatment planning, and 3) the treatment itself.50, 51 All cervical lesions down to C7 were tracked relative to skull bony landmarks. All patients with cervical lesions were fitted with a noninvasive molded aquaplast facemask that stabilized the head and neck on a radiographically transparent headrest. All other lesions were tracked relative to fiducial markers placed within the bone adjacent to the lesion. Because these implanted fiducials have a fixed relationship with the bone in which they are implanted, any movement in the vertebrae would be detected as movement in the fiducials, and this movement is detected and compensated for by the CyberKnife.

For cervical spine lesions, CT images were acquired using 1.25-mm-thick slices from the top of the skull to the bottom of the cervical spine. All other lesions underwent fluoroscopically guided percutaneous placement of four to six gold fiducial markers (Alpha-Omega Services, Bellflower, CA) into the pedicles immediately adjacent to the lesion to be treated using a standard Jamshidi Bone Marrow Biopsy Needle (Allegiance Healthcare, McGraw Park, IL) as previously described.51 The fiducial placement procedure was performed in the operating room in an outpatient setting before undergoing the planning CT. The patient was placed in a supine position in a conformal alpha cradle during CT imaging as well as during treatment. CT images were acquired using 1.25-mm-thick slices to include the lesion of interest as well as all fiducials and critical structures.

The second component of the CyberKnife treatment is the development of the radiosurgical treatment plan. In each case, the radiosurgical treatment plan was designed based on tumor geometry, proximity to spinal cord, and location. The prescription dose was independent of the tumor volume. For each case, the spinal cord and/or cauda equina was outlined as a critical structure. At the level of the cauda equina, the spinal canal was outlined. Therefore, at the level of the cauda equina the critical volume is the entire spinal canal and not actual neural tissue. The maximum dose was defined as the dose delivered to a single pixel. Given their relative radiosensitivity, a limit of 2 Gy was set as the maximum dose received by each of the kidneys.

The third component of the CyberKnife treatment is the actual treatment delivery. All treatments were performed using a single-fraction technique. The patients were placed on the CyberKnife treatment couch in a supine position with the appropriate immobilization device. Preoperative analgesics, sedation, or steroids were not routinely given. During the treatment, real-time digital X-ray images of the implanted fiducial markers were obtained. The location of the vertebral body being treated was established from these images and was used to determine tumor location as previously described. The patient was observed throughout the treatment by closed-circuit television. The mean treatment time (patient on the couch) was approximately 90 minutes.

RESULTS

  1. Top of page
  2. Abstract
  3. MATERIALS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. REFERENCES

Table 1 provides a summary of the clinical characteristics and treatment of the patient cohorts. The tumor dose was maintained at 12.5–22.5 Gy contoured to the edge of the target volume (mean, 19 Gy). The prescription dose was chosen based on currently used intracranial radiosurgery doses as well as the limitation of the maximum dose to the spinal cord as the primary critical structure for each treatment plan. The planning treatment volume (PTV) was defined as the gross tumor volume with no margin. The dose was prescribed to the 80% isodose line, which covered the PTV in all cases. Fifty-five cases (i.e., all lesions limited to the cervical spine) were treated using bony landmarks for image guidance. The remaining 13 cases (thoracic, lumbar, and sacral cases) were treated using fiducial tracking. Tumor volume ranged from 0.8–197.1 cm3 (mean, 27.7 cm3). There were no complications associated with the fiducial placement in this series. Table 2 describes the primary indications for spinal radiosurgery treatment for the patient cohort. During a follow-up ranging from 6–48 months (median, 16 mos), there were no clinically detectable neurologic signs that could be attributed to the acute or subacute radiation-induced cord damage. Posttreatment MRI revealed no changes suggestive of radiation-induced spinal cord injury.

Maximum doses were used for purposes of comparison. The doses delivered to tumors at the level of the spinal cord and the cauda equina were analyzed separately. The average maximum dose delivered to tumors of the cervical and thoracic spine (38 cases) at the level of the spinal cord was 19 Gy (range, 15–22.5 Gy). The average volume for these 38 cases was 16.2 cm3 (range, 0.8–62.7 cm3). The dose received by the spinal cord during the treatment ranged from a minimum of 6.5 Gy to a maximum of 13 Gy (mean, 10 Gy). The volume of the spinal cord or cauda equina receiving greater than 8 Gy was recorded for each patient. The spinal cord volume receiving greater than 8 Gy for these same patients ranged from 0.0–2.6 cm3 (mean, 0.44 cm3).

The average maximum dose delivered to tumors of the lumbar spine and sacrum (30 cases) at the level of the cauda equina was 20 Gy (range, 15–22.5 Gy). The mean volume for these 30 cases was 42.3 cm3 (range, 1.3–197.1 cm3), triple the mean volume of the tumors at the level of the spinal cord. The dose received by the cauda equina during the treatment ranged from a minimum of 1 Gy to a maximum of 17 Gy (mean, 10.5 Gy). The volume of the cauda equina receiving greater than 8 Gy for these same patients ranged from 0.0–2.9 cm3 (mean, 0.63 cm3). Within the cohort, no patient experienced an exacerbation of symptoms, hemorrhage, or new neurologic deficit in the immediate period after treatment. No patient developed radiation-induced myelopathy or radiculopathy during the follow-up period.

Fifty-seven cases were treated for significant pain from the treated lesion as the primary indication for radiosurgery. Fifty-five of the 57 (96%) cases reported long-term improvement in pain measured using a 10-point pain scale compared with pain described at the time of initial evaluation. The magnitude of improvement ranged from 0 (for the two patients considered failures) to 9 for complete resolution of pain (mean absolute improvement, 5 points). Patients were found to be on a large variety of different narcotic analgesics. Pain improvement at 1 month as well as last follow-up was compared with any change in analgesic dosage and accounted for. The two pain failures both had an increase in their narcotic dosage. Of the two patients considered pain failures, the first underwent radiosurgery for a sacral lesion (20 Gy, volume 42 cm3) and experienced only temporary relief of her pain. She had previously undergone conventional irradiation to the lesion with 1 year of subsequent pain relief. The second patient also underwent radiosurgery for a previously irradiated sacral lesion (20 Gy, volume 78 cm3). She experienced significant relief of her pain that partially recurred after 3 months.

In eight cases, spinal SRS was used as the primary treatment modality for the lesion. These lesions were usually asymptomatic lesions seen on imaging in patients who were undergoing fiducial implantation for other symptomatic lesions. Fiducials markers were implanted adjacent to these asymptomatic lesions to avoid a protracted course of external beam irradiation. Long-term radiographic control with local progression was seen in all 8 cases with follow-up of 3–40 months.

Spinal SRS was used in a single patient who had previously undergone an open surgical decompression followed by fractionated radiation therapy. Tumor progression of the L1 vertebral body tumor was seen on follow-up imaging without associated neurologic deficit or significant pain. Surgical reexploration was not felt to be indicated, and spinal radiosurgery was elected. In this patient, follow-up imaging after radiosurgery has demonstrated no further radiographic progression at 20 months.

In a single case, fiducials were implanted at the time of a T10 transthoracic corpectomy. The lesion had previously undergone fractionated radiation therapy. Radiosurgery was used as a postsurgical boost to the remaining tumor bed. Follow-up imaging of 15 months failed to demonstrate any tumor progression. One patient was treated for progressive neurologic deficit as her primary indication. The patient has developed progressive myelopathy but was not felt to be a candidate for open surgery. The tumor was treated with 1750 cGy. The patient experienced complete resolution of her neurologic deficits that has lasted for 12 months. None of the patients in this series went on to require open surgical intervention either for pain control or for progressive neurologic deficit.

Illustrative Case

The images in Figure 2 demonstrate a representative case of a 66-year-old woman with an original diagnosis of a T2, N0 infiltrating ductal carcinoma. She had been treated initially with a right segmental resection; 20 nodes were negative. The tumor was estrogen receptor/progesterone receptor (ER/PR) negative. She received radiation therapy to the right breast to a total dose of 61.2 Gy as well as four cycles of adjuvant 5-FU and methotrexate. She presented with back pain 6 years later and was found to have a T6 destructive lesion as her only site of metastatic disease. She was initially treated with 30 Gy external beam irradiation in 10 fractions to the lesion with temporary improvement of symptoms. Because of persistent symptoms interfering with her activities of daily living and preventing her from returning to work, she was referred for spinal radiosurgery. An MRI revealed a pathologic compression fracture with significant spinal canal compromise. A percutaneous fiducial placement was performed 1 week before radiosurgery. The treatment plan was designed to treat the tumor with a prescribed dose of 16 Gy that was calculated to the 80% isodose line. The maximum tumor dose was 20 Gy and the tumor volume was 10.3 cm3. The spinal canal received a maximum dose of 10 Gy. The volume of the spinal cord that received greater than 8 Gy was 0.3 cm3. The patient experienced complete pain relief within 1 month. Follow-up imaging 1 month after radiosurgery revealed a decrease in the amount of tumor within the spinal canal.

thumbnail image

Figure 2. A representative case of a 66-year-old woman with an isolated painful T6 metastasis previously treated with 30 Gy external beam irradiation in 10 fractions. Gadolinium-enhanced axial and sagittal MRI revealed a pathologic compression fracture with significant spinal canal compromise (A,B). Sagittal and axial projections of the isodose lines of the treatment plan (C,D). The 80% isodose line represents the prescribed dose of 16 Gy, the tumor volume was 10.3 cm3, and 0.3 cm3 of the spinal cord received greater than 8 Gy. Notice the conformability of the isodose line around the spinal cord. The patient experienced pain relief within 1 month. Follow-up imaging 1 month after radiosurgery revealed a decrease in the amount of tumor within the spinal canal with no evidence of further vertebral body collapse (E,F).

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DISCUSSION

  1. Top of page
  2. Abstract
  3. MATERIALS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. REFERENCES

Despite therapeutic advances during the past decade in the treatment of patients with localized breast carcinoma, half of these patients initially present with metastases or subsequently develop metastases.12 Bone metastases are the most common initial site of metastases, and the spine is the most common site of bony metastases in patients with osseous breast carcinoma metastases.2 The incidence of women with breast carcinoma who develop skeletal metastasis may be as high as 74%. Metastatic disease from the breast is the most prevalent of all spinal tumors. Venous drainage from the breast via the azygous veins and their communication to the paravertebral venous plexus accounts for the high percentage of thoracic spine metastases in patients with breast carcinoma.12

Because the survival time after the diagnosis of breast carcinoma is relatively long, the incidence of patients who are diagnosed with skeletal metastases is high. Furthermore, because of the long median survival after the development of bone metastases, patients are at high risk for skeletal complications.1 Compression of the spinal cord and spinal instability from spine metastases are a major cause of morbidity for these patients.9 Metastatic breast carcinoma often remains confined to the skeleton for a prolonged period of time, and patients with bone-only metastases may survive for several years. This is particularly true for tumors that express hormone receptors.52–54 Breast tumors that metastasize to bone have been shown to be more frequently estrogen receptor-positive and better differentiated than breast tumors that have metastasized to the lungs or liver.

Standard treatment options for spinal tumors include radiotherapy alone, radionuclide therapy, radiotherapy plus systemic chemotherapy, hormonal therapy, or surgical decompression and/or stabilization followed by radiotherapy.10 The goals of local radiation therapy in the treatment of these spinal tumors have been palliation of pain, prevention of pathologic fractures, and halting progression of or reversing neurologic compromise. When a spinal tumor causes compression of the spinal cord or other neural elements, surgical decompression is often necessary with or without spinal fixation based on the extent of spinal column destruction and instability of the spine. Indications for surgical treatment of metastatic disease of the spine include those patients with intractable pain, spinal instability, or progressive neurologic dysfunction secondary to dural compression in whom radiation therapy has failed.13–15 Patients with extensive bony destruction of the spinal column should be treated with surgical decompression and stabilization to correct or prevent progressive spinal deformity.

There has been a rapid increase in the use of radiosurgery as a treatment alternative for malignant tumors involving the spine.6, 8, 19, 28, 46 Recent technological developments, including imaging technology for 3D localization and pretreatment planning, the advent of IMRT, and a higher degree of accuracy in achieving target dose conformation while sparing normal surrounding tissue have allowed clinicians to expand radiosurgery applications to treat malignant vertebral body lesions within close proximity to the spinal cord and cauda equina.

In SRS, a high dose of radiation is delivered in a single fraction to a well-defined intracranial or extracranial target.1 Radiosurgery has been shown to be very effective for controlling intracranial malignancies.38, 55–60 Stereotactic radiosurgery has been demonstrated to be an effective treatment for brain metastases (including breast metastases), either with or without whole-brain radiation therapy, with an 85–95% control rate. The emerging technique of spinal radiosurgery represents a logical extension of the current state-of-the-art radiation therapy. Stereotactic radiosurgery for tumors of the spine has more recently been demonstrated to be accurate, safe, and efficacious.19, 22, 23, 25–33

The CyberKnife was first developed for the treatment of both benign and malignant intracranial lesions.48, 61, 62 Treatment outcome has been similar to the results of conventional frame-based radiosurgery.19 With the ability to treat lesions outside of the skull using fiducial tracking, a growing experience in the treatment of spinal lesions using the CyberKnife has emerged.19, 50, 63 Unlike conventional radiation therapy that delivers a full dose to both the vertebral body and the spinal cord, the CyberKnife can deliver a single high-dose fraction of radiation to the target tissue while sparing most of the adjacent spinal cord. The treatment plan can create a high gradient dose fall-off to the target tissue that should significantly reduce the possibility of radiation-induced myelopathy. This is a significant advantage to using SRS for treatment of spinal tumors. It therefore has the potential to significantly improve local control of spine metastases, which could translate into both more effective palliation, delaying progression of neurologic deficits requiring open surgical intervention, and potentially longer survival.

There is no large experience to date with spinal radiosurgery or hypofractionated radiotherapy that has developed optimal doses for these treatment techniques. Other centers, using intensity-modulated, near-simultaneous, CT image-guided stereotactic radiotherapy techniques have used doses of 6–30 Gy in one to five fractions.23, 24, 27 In our series, maximum tumor dose was maintained at 15–22.5 Gy delivered in a single fraction. The appropriate dose for spinal radiosurgery for metastatic breast carcinoma to the spine has not been determined. In this series, a maximum tumor dose of 20 Gy or 16 Gy to the tumor margin appeared to provide good tumor control with no radiation-induced spinal cord or cauda equina injury.

Spinal radiosurgery was found to be safe at doses comparable to those used for intracranial radiosurgery without the occurrence of radiation-induced neural injury. In the current series, there were no clinically or radiographically identifiable acute or subacute spinal cord damage attributed to the radiation dose, with a follow-up period long enough to have seen such events were they to occur.5, 64–69

The role of radiotherapy in the palliation of symptomatic bone metastases is well established. During the past two decades, several clinical trials have compared the relative efficacy of various dose-fractionation schedules in producing pain relief.17 The idea of single-fraction radiotherapy for symptomatic bone metastases is not new. Several studies, including a Radiation Therapy Oncology Group Phase III trial, as well as a meta-analysis, found no significant difference in complete and overall pain relief between single-fraction and multifraction palliative radiation therapy for bone metastases.16, 17 Most of these trials used 8 Gy in a single fraction. However, none of these trials were specifically evaluating spinal metastases. In addition, the prescribed doses that were delivered in our study were far greater than 8 Gy (median dose of 19 Gy), possibly translating into a more durable symptomatic response as well as local control. Furthermore, the issue of reirradiation could not be analyzed by the meta-analysis. In our study, 71% of the lesions had previously been irradiated. At our center, spinal radiosurgery is often used for cases that have previously undergone conventional fractionated radiotherapy. The greater conformability provided by spinal radiosurgery allows for the delivery of much larger prescribed doses while limiting the dose to the often previously irradiation spinal cord.

In this series, pain was the primary indication for radiosurgery treatment. This, of course, is different from the primary indication for intracranial radiosurgery for breast metastases. Ninety-six percent of patients reported improvement in their pain after radiosurgery treatment, accounting for the level of pain medication use. This is similar to the success reported by others using hypofractionated radiotherapy techniques.21–25, 43 Conventional external beam irradiation may provide less than optimal pain relief because the total dose is limited by the tolerance of adjacent tissues (e.g., spinal cord). In the two patients in this series who failed to achieve long-term pain improvement after radiosurgery, both lesions were within the sacrum. Posttreatment imaging revealed pathologic fractures of the sacrum, likely the cause of pain and the reason for radiosurgical failure. Unfortunately, such sacral fractures are not amenable to open surgical instrumentation techniques or closed fracture fixation using methylmethacrylate. Single-fraction spinal radiosurgery achieved rapid and durable pain control as well as radiologically documented tumor control in this patient population.

The mean maximum dose delivered to the tumors at the level of the cauda equina was 20 Gy, while the mean maximum dose delivered to the tumors at the level of the spinal cord was approximately 1 Gy lower, at 19 Gy. We feel somewhat more comfortable with treating lesions at the level of the cauda equina with higher doses even if it means a larger dose received by the cauda equina compared with the same dose delivered to the spinal cord. The maximum dose to the cauda equina has reached over 17 Gy without adverse consequences. However, the mean volume of lesions at the cauda equina level was 42 cm3 compared with 16.2 cm3 for those lesions at the spinal cord level. This tripling of tumor volume is not surprising, given the larger size of the lumbar vertebral bodies and sacrum compared with the cervical and thoracic vertebral bodies.

In eight cases, radiosurgery was used as the primary treatment for spinal metastases. In six cases, the patients had a second lesion that was symptomatic for which radiosurgery was felt to be appropriate. In these six cases, at the time of fiducial implantation, fiducials also were placed adjacent to the asymptomatic lesion. In the other two primary treatment cases, the lesions were found to be the first and only metastatic lesions discovered on bone scans as part of an investigation protocol follow-up. There are several advantages to using a radiosurgery technique as a primary treatment modality for spinal breast metastases. Early treatment of these lesions before the patient becoming symptomatic and the stability of the spine threatened has obvious advantages.25 This approach avoids the need to irradiate large segments of the spinal cord. Early SRS treatment of spinal lesions may obviate the need for extensive spinal surgeries for decompression and fixation in these already debilitated patients. It may also avoid the need to irradiate large segments of the spinal column, known to have a deleterious effect on bone marrow reserve in these patients. Avoiding open surgery as well as preserving bone marrow function facilitates continuous chemotherapy in this patient population. Furthermore, improved local control, such as has been the case with intracranial radiosurgery, could translate into more effective palliation and potentially longer survival.

One concern that has been raised regarding radiosurgery for spinal metastases is that adjacent levels are not included in the radiation field. One possibility is that the tumor can progress within the adjacent levels. In this series, there were no cases of tumor progression at the immediate adjacent levels, justifying the treatment of the involved spine only. Other authors have also found this not to be the case.33

An advantage to the patient of using single-fraction radiosurgery is that the treatment can be completed in a single day rather than over a course of several weeks, which is not inconsequential for patients with a limited life expectancy. The technique may be useful to capitalize on possible advantages of radiosensitizers. In addition, cancer patients may have difficulty with access to a radiation treatment facility for prolonged, daily fractionated therapy. A large single fraction of irradiation may be more radiobiologically advantageous to certain tumors such as breast carcinoma compared with prolonged fractionated radiotherapy. Clinical response such as pain or improvement of a neurologic deficit might also be more rapid with a radiosurgery technique. Finally, the procedure is minimally invasive compared with open surgical techniques and can be performed in an outpatient setting.

Careful follow-up will be necessary to ensure that delayed toxicity to normal tissues is not encountered in patients treated with spinal radiosurgery. As patients with breast carcinoma survive longer from more successful systemic treatment, delayed radiation toxicity will be more of a concern. The excellent symptomatic response as well as tumor control, associated with a lack of radiation-induced toxicity, has led us to conclude that 16 Gy prescribed to the 80% isodose line is an appropriate dose to use for the single-fraction treatment of spinal breast metastases.

Conclusions

This study demonstrated that single-fraction spinal SRS for breast carcinoma metastases is both safe and clinically effective. Spinal radiosurgery represents a logical extension of the current state-of-the-art radiation therapy. The major potential benefits of radiosurgical ablation of spinal metastases are relatively short treatment time in an outpatient setting combined with potentially better local control of the tumor with minimal risk of side effects. Such an outcome could translate into better palliation of symptoms and a longer survival period, while avoiding the significant morbidity associated with open surgical intervention. In addition, this technique allows for the treatment of lesions previously irradiated using conventional external beam irradiation. Spinal radiosurgery offers an important new therapeutic modality for the treatment of spinal breast metastases. Furthermore experience with higher irradiation doses as well as improved tumor imaging will likely lead to even better clinical outcomes.

REFERENCES

  1. Top of page
  2. Abstract
  3. MATERIALS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. REFERENCES
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