Steven A. Burton

Radiosurgery for spinal metastases: clinical experience in 500 cases from a single institution.

Study Design. A prospective nonrandomized, longitudinal cohort study. Objective. To evaluate the clinical outcomes of single-fraction radiosurgery as part of the management of metastatic spine tumors. Summary of Background Data. The role of stereotactic radiosurgery for the treatment of spinal lesions has previously been limited by the availability of effective target immobilization and target tracking devices. Large clinical experience with spinal radiosurgery to properly assess clinical experience has previously been limited. Methods. A cohort of 500 cases of spinal metastases underwent radiosurgery. Ages ranged from 18 to 85 years (mean 56). Lesion location included 73 cervical, 212 thoracic, 112 lumbar, and 103 sacral. Results. The maximum intratumoral dose ranged from 12.5 to 25 Gy (mean 20). Tumor volume ranged from 0.20 to 264 mL (mean 46). Long-term pain improvement occurred in 290 of 336 cases (86%). Long-term tumor control was demonstrated in 90% of lesions treated with radiosurgery as a primary treatment modality and in 88% of lesions treated for radiographic tumor progression. Twenty-seven of 32 cases (84%) with a progressive neurologic deficit before treatment experienced at least some clinical improvement. Conclusions. The results indicate the potential of radiosurgery in the treatment of patients with spinal metastases, especially those with solitary sites of spine involvement, to improve long-term palliation.

CyberKnife Frameless Stereotactic Radiosurgery for Spinal Lesions: Clinical Experience in 125 Cases

OBJECTIVE: The role of stereotactic radiosurgery for the treatment of intracranial lesions is well established. Its use for the treatment of spinal lesions has been limited by the availability of effective targe-immobilizing devices. Conventional external beam radiotherapy lacks the precision to allow delivery of large doses of radiation near radiosensitive structures such as the spinal cord. The CyberKnife (Accuray, Inc., Sunnyvale, CA) is an image-guided frameless stereotactic radiosurgery system that allows for the radiosurgical treatment of spinal lesions. This study evaluated the feasibility and effectiveness of the treatment of spinal lesions with a single-fraction radiosurgical technique using the CyberKnife. METHODS: The CyberKnife system uses the coupling of an orthogonal pair of x-ray cameras to a dynamically manipulated robot-mounted linear accelerator with six degrees of freedom that guides the therapy beam to the intended target without the use of frame-based fixation. Real-time imaging allows the tracking of patient movement. Cervical spine lesions were located and tracked relative to cranial bony landmarks lower spinal lesions were tracked relative to fiducial bone markers. In this prospective cohort evaluation of a spine radiosurgery technique, 125 spinal lesions in 115 consecutive patients were treated with a single-fraction radiosurgery technique (45 cervical, 30 thoracic, 36 lumbar, and 14 sacral). There were 17 benign tumors and 108 metastatic lesions. All dose plans were calculated on the basis of computed tomographic images acquired from 1.25-mm slices with an inverse treatment planning technique. Radiosurgical circular cones ranging in diameter from 5 to 40 mm were used. RESULTS: Tumor volume ranged from 0l3 to 232 cm 3 (mean, 27.8 cm 3 ). Seventy-eight lesions had received external beam irradiation previously. Tumor dose was maintained at 12 to 20 Cy to the 80% isodose line (mean, 14 Gy); canal volume receiving more than 8 Gy ranged from 0.0 to 1.7 cm 3 (mean, 0.2 cm 3 ). No acute radiation toxicity or new neurological deficits occurred during the follow up period (range, 9-30 mo median, 18 mo). Axial and radicular pain improved in 74 of 79 patients who were symptomatic before treatment. CONCLUSION: This is the first large prospective evaluation of this frameless imageguided spinal radiosurgery system. The Cyberknife system was found to be feasbile, safe, and effective. The major potential benetits of radiosurgical ablation of spinal lesions are short treatment time in an outpatient setting with rapid recovery and symptomatic response. This technique offers a successial therapeutic modality for the treatment of a variety of spinal lesions as a primary treatment or for lesions not amenable to open surgical techniques, in medically inoperable patients, in lesions located in previously irradiated sites or as an adjunct to surgery.

Combination kyphoplasty and spinal radiosurgery: a new treatment paradigm for pathological fractures

OBJECT Patients with symptomatic pathological compression fractures require spinal stabilization surgery for mechanical back pain control and irradiation for the underlying malignant process. The authors evaluated a treatment paradigm of closed fracture reduction and fixation involving kyphoplasty and subsequent spinal radiosurgery. METHODS Twenty-six patients (six men and 20 women, mean age 72 years) with pathological compression fractures (16 thoracic and 10 lumbar) were prospectively evaluated. Histological diagnoses included 11 lung, nine breast, four renal, one cholangiocarcioma, and one ocular melanoma. Seven lesions had received prior external-beam radiation therapy. All patients underwent kyphoplasty that involved the percutaneous transpedicular technique. Fiducial markers allowing for image guidance during CyberKnife treatment were placed, at time of the kyphoplasty, in the pedicles at adjacent levels. Patients underwent single-fraction radiosurgery (mean time after kyphoplasty 12 days) in an outpatient setting. The tumor dose was maintained at 16 to 20 Gy (mean 18 Gy) to the 80% isodose line. The treated tumor volume ranged from 12.7 to 37.1 cm3. No acute radiation-induced toxicity or new neurological deficit occurred during the follow-up period (range 11-24 months, median 16 months). Axial pain improved in 24 (92%) of 26 patients. CONCLUSIONS The combined kyphoplasty and spinal radiosurgery treatment paradigm was found to be clinically effective in patients with pathological fractures; there was no significant spinal canal compromise. In this technique two minimally invasive surgical procedures are combined to avoid the morbidity associated with open surgery while providing both immediate fracture fixation and administering a single-fraction tumoricidal radiation dose.

Stereotactic Body Radiotherapy for Recurrent Squamous Cell Carcinoma of the Head and Neck: Results of a Phase I Dose-Escalation Trial

PURPOSE To evaluate the safety and efficacy of stereotactic body radiotherapy (SBRT) in previously irradiated patients with squamous cell carcinoma of the head and neck (SCCHN). PATIENTS AND METHODS In this Phase I dose-escalation clinical trial, 25 patients were treated in five dose tiers up to 44 Gy, administered in 5 fractions over a 2-week course. Response was assessed according to the Response Evaluation Criteria in Solid Tumors and [(18)F]-fluorodeoxyglucose standardized uptake value change on positron emission tomography-computed tomography (PET-CT). RESULTS No Grade 3/4 or dose-limiting toxicities occurred. Four patients had Grade 1/2 acute toxicities. Four objective responses were observed, for a response rate of 17% (95% confidence interval 2%-33%). The maximum duration of response was 4 months. Twelve patients had stable disease. Median time to disease progression was 4 months, and median overall survival was 6 months. Self-reported quality of life was not significantly affected by treatment. Fluorodeoxyglucose PET was a more sensitive early-measure response to treatment than CT volume changes. CONCLUSION Reirradiation up to 44 Gy using SBRT is well tolerated in the acute setting and warrants further evaluation in combination with conventional and targeted therapies.

Delayed radiation-induced myelopathy after spinal radiosurgery.

OBJECTIVESpinal cord injury is arguably the most feared complication in radiotherapy and has historically limited the aggressiveness of spinal tumor treatment. We report a case series of 6 patients treated with radiosurgery who developed delayed myelopathy. METHODSBetween 1996 and 2005, 1075 patients with benign or malignant spinal tumors were treated by CyberKnife (Accuray, Inc., Sunnyvale, CA) robotic radiosurgery at Stanford University Medical Center and the University of Pittsburgh Medical Center. Patients were followed prospectively with clinical and radiographic assessments at 1- to 6-month intervals. A retrospective review identified patients who developed delayed radiation-induced myelopathy. Six patients (5 women, 1 man) with a mean age of 48 years (range, 25–61 years) developed delayed myelopathy at a mean of 6.3 months (range, 2–9 months) after spinal radiosurgery. Three tumors were metastatic; 3 were benign. The metastases were in the upper to midthoracic spine, whereas the benign tumors were partially in the cervical region. Three cases involved previous radiation therapy. RESULTSDose volume histograms were generated for target and critical structures. Clinical and dosimetric factors were analyzed for factors predictive of spinal cord injury. Specific dosimetric factors contributing to this complication could not be identified, but one-half of the patients with myelopathy received spinal cord biological equivalent doses exceeding 8 Gy. CONCLUSIONDelayed myelopathy after radiosurgery is uncommon with the dose schedules used in this case series. Radiation injury to the spinal cord occurred over a spectrum of dose parameters that prevented identification of specific dosimetric factors contributing to this complication. Primarily, biological equivalent dose estimates were not usable for defining spinal cord tolerance to hypofractionated dose schedules. We recommend limiting the volume of spinal cord treated above an 8-Gy equivalent dose, because half of the complications occurred beyond this level.OBJECTIVE Spinal cord injury is arguably the most feared complication in radiotherapy and has historically limited the aggressiveness of spinal tumor treatment. We report a case series of 6 patients treated with radiosurgery who developed delayed myelopathy. METHODS Between 1996 and 2005, 1075 patients with benign or malignant spinal tumors were treated by CyberKnife (Accuray, Inc., Sunnyvale, CA) robotic radiosurgery at Stanford University Medical Center and the University of Pittsburgh Medical Center. Patients were followed prospectively with clinical and radiographic assessments at 1- to 6-month intervals. A retrospective review identified patients who developed delayed radiation-induced myelopathy. Six patients (5 women, 1 man) with a mean age of 48 years (range, 25-61 years) developed delayed myelopathy at a mean of 6.3 months (range, 2-9 months) after spinal radiosurgery. Three tumors were metastatic; 3 were benign. The metastases were in the upper to midthoracic spine, whereas the benign tumors were partially in the cervical region. Three cases involved previous radiation therapy. RESULTS Dose volume histograms were generated for target and critical structures. Clinical and dosimetric factors were analyzed for factors predictive of spinal cord injury. Specific dosimetric factors contributing to this complication could not be identified, but one-half of the patients with myelopathy received spinal cord biological equivalent doses exceeding 8 Gy. CONCLUSION Delayed myelopathy after radiosurgery is uncommon with the dose schedules used in this case series. Radiation injury to the spinal cord occurred over a spectrum of dose parameters that prevented identification of specific dosimetric factors contributing to this complication. Primarily, biological equivalent dose estimates were not usable for defining spinal cord tolerance to hypofractionated dose schedules. We recommend limiting the volume of spinal cord treated above an 8-Gy equivalent dose, because half of the complications occurred beyond this level.

Single-fraction radiosurgery for the treatment of spinal breast metastases

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.

Radiosurgery for the treatment of spinal melanoma metastases

Background: The role of stereotactic radiosurgery in treating metastatic melanoma involving the spine has previously been limited. Conventional external beam radiotherapy lacks the precision to allow delivery of large single-fraction doses of radiation and simultaneously to limit the dose delivered to radiosensitive structures such as the spinal cord. This study evaluated the clinical efficacy of radiosurgery for the treatment of melanoma spinal metastases in 28 patients.Methods: Thirty-six melanoma spine metastases were treated with a single-session radiosurgery technique (1 cervical, 11 thoracic, 13 lumbar, and 11 sacral) with a follow-up period of 3–43 months (median 13 months). Tumor volume ranged from 4.1 to 153 cm3 (mean 47.6 cm3). Twenty-three of the 36 lesions had received prior external beam irradiation. Results: Maximum tumor dose was maintained at 17.5–25 Gy (mean 21.7 Gy). Spinal cord volume receiving >8 Gy ranged from 0.0 to 0.7 cm3 (mean 0.26 cm3); spinal canal volume at the cauda equina level receiving >8 Gy ranged from 0.0 to 3.5 cm3 (mean 0.98 cm3). No radiation-induced toxicity occurred during the follow-up period. Axial and radicular pain improved in 27 of 28 patients (96%) who were treated primarily for pain. Long-term tumor control was seen in 3 of 4 cases treated primarily for radiographic tumor progression. Two patients went on to require open surgical intervention for tumor progression resulting in neurological deficit. Conclusions: Spinal radiosurgery offers a therapeutic modality for the safe delivery of large dose fractions of radiation therapy in a single fraction for the management of spinal metastases in patients with advanced melanoma that are often poorly controlled with alternative conventional external beam radiation therapy, and is successful even in patients with previously irradiated lesions.

Stereotactic body radiotherapy in the treatment of advanced adenocarcinoma of the pancreas.

Objectives: The aim of the study was to assess the feasibility and safety of stereotactic body radiotherapy (SBRT) in patients with advanced pancreatic adenocarcinoma. Methods: We reviewed outcomes of 71 patients treated with SBRT for pancreatic cancer between July 2004 and January 2009. Forty patients (56%) had locally unresectable disease, 11 patients (16%) had local recurrence following surgical resection, 8 patients (11%) had metastatic disease, and 12 patients (17%) received adjuvant SBRT for positive margins. The median dose was 24 Gy (18–25 Gy), given in a single-fraction SBRT (n = 67) or fractionated SBRT (n = 4). Kaplan-Meyer survival analyses were used to estimate freedom from local progression (FFLP) and overall survival (OS) rates. Results: The median follow-up among surviving patients was 12.7 months (4–26 months). The median tumor volume was 17 mL (5.1–249 mL). The overall FFLP rates at 6 months/1 year were 71.7%/48.5%, respectively. Among those with macroscopic disease, FFLP was achieved in 77.3% of patients with tumor size <15 mL (n = 22), and 59.5% for ≥15 mL (n = 37) (P = 0.02). FFLP was achieved in 73% following 24 to 25 Gy, and 45% with 18 to 22 Gy (P = 0.004). The median OS was 10.3 months, with 6 month/1 year OS rates of 65.3%/41%, respectively. Grade 1–2 acute and late GI toxicity were seen in 39.5% of patients. Three patients experienced acute grade 3 toxicities. Conclusions: SBRT is feasible, with minimal grade ≥3 toxicity. The overall FFLP rate for all patients was 64.8%, comparable to rates with external beam radiotherapy. This shorter treatment course can be delivered without delay in adjuvant systemic therapy.

RADIOSURGERY FOR BENIGN INTRADURAL SPINAL TUMORS

OBJECTIVEThe role of stereotactic radiosurgery for the treatment of intracranial benign tumors is well established. There is less experience and more controversy regarding its use for benign tumors of the spine. This study evaluated the clinical efficacy of radiosurgery as part of the treatment paradigm of selected benign tumors of the spine. METHODSSeventy-three benign intradural extramedullary spinal tumors were treated with a radiosurgery technique and prospectively evaluated. Patient ages ranged from 18 to 85 years (mean age, 44 yr); the follow-up period was 8 to 71 months (median, 37 mo). Lesion location included 43 cervical, five thoracic, 19 lumbar, and six sacral. Tumor histology included neurofibroma (25 cases), schwannoma (35 cases), and meningioma (13 cases). Twenty-one cases were associated with neurofibromatosis Type 1, and nine patients had neurofibromatosis Type 2. Nineteen tumors (26%) had previously undergone open surgical resection, and six tumors (8%) had previously been treated with conventional external beam irradiation techniques. RESULTSSimilar radiation doses were prescribed for all three histopathologies. The maximum intratumoral dose was 1500 to 2500 cGy (mean, 2164 Gy). Tumor volume ranged from 0.3 to 93.4 cm3 (mean, 10.5 cm3; median, 4.11 cm3). Radiosurgery was used for the treatment of postsurgical radiographic progression in 18 cases; it was used as the primary treatment modality in 14 cases; it was used for treatment of radiographic tumor progression in nine cases; and it was used for the treatment of postsurgical residual tumor in two cases. Long-term pain improvement occurred in 22 out of 30 cases (73%). Long-term radiographic tumor control was demonstrated in all cases. Three patients experienced new symptoms attributed to radiation-induced spinal cord toxicity 5 to 13 months after treatment. CONCLUSIONSingle fraction radiosurgery was found to be clinically effective for the treatment of benign extramedullary spinal neoplasms. Although surgical extirpation remains the primary treatment option for most benign spinal tumors, radiosurgery was demonstrated to have short-term clinical benefits for the treatment of such lesions. The long-term efficacy of spinal radiosurgery for such tumors will be determined with longer follow-up periods. Its role in patients with neurofibromatosis will also be further defined with greater clinical experience.

Frameless stereotactic radiosurgery for recurrent head and neck carcinoma.

The aim of this study was to assess the feasibility and toxicity of stereotactic radiosurgery (CK-SRS) using the CyberKnife® Frameless Radiosurgery System (Accuray Inc., Sunnyvale, CA) in the management of recurrent squamous cell carcinoma of the head and neck region (SCCHN). Between November 2001 and February 2004, 22 patients with recurrent, previously irradiated SCCHN were treated with CK-SRS. The following endpoints were assessed post-CK-SRS: local control (LC), cause-specific survival (CSS), overall survival (OS), symptom relief, and acute and late toxicity. Kaplan-Meier survival analyses were used to estimate the LC, CSS, and OS rates. Clinical symptoms were graded as “improved,” “stable,” or “progressed” after CK-SRS. Acute and late toxicity were graded according to the National Cancer Institute Common Toxicity Criteria (CTC) scale, version 2.0. Seventeen patients were followed until their death. The median follow-up in the remaining five patients was 19 months (range 11–40 months). The median survival time for the entire cohort was 12 months from the time of CK-SRS. The 2-year LC, CSS, and OS rates were 26%, 26%, and 22%, respectively. After CK-SRS, symptoms were improved or stable in all but one patient who reported increasing pain. The treatment was well tolerated, with one case each of Grade 2 and 3 mucositis. There were no acute Grade 4 or 5 CTC toxicities. There were no late toxicities in this cohort. Frameless stereotactic radiosurgery for recurrent SCCHN is feasible and safe in the setting of high doses of prior irradiation. The majority of patients experienced palliation of disease without excess toxicity.