[en] Purpose: To determine the prognostic significance of pretreatment edema, lesion size and location on morbidity following stereotactic radiosurgery (SRS). Methods and Materials: Forty-seven evaluable patients with 63 lesions were treated on a 6-MV linear accelerator radiosurgery system at Memorial Sloan Kettering Cancer Center. All patients received a 10-mg intravenous bolus of dexamethasone sodium phosphate (Decadron) prior to SRS. Thirteen patients were treated for asymptomatic lesions while 34 were treated because of neurologic symptoms. The median dose delivered was 1800 cGy and the median prescription isodose curve was 85%. Pretreatment edema was measured on a transaxial T2-weighted MR image acquired within 1 month of the SRS. Results: Ten patients experienced morbidity as a result of their treatment. The complication rate was measured by neurologic events following SRS and was not significantly influenced by the extent of peritumoral edema. Lesion size was also unrelated to the development of post-treatment symptoms as assessed by the ease of tapering steroids. The only parameter found to influence post-SRS complications was lesion location. Four of six (66%) patients treated to lesions in the motor cortex suffered post-SRS seizure activity, whereas only 6 of 37 (16%) patients treated to lesions elsewhere in the brain parenchyma experienced seizure activity. Conclusion: The presence of pretreatment edema and lesion size are not predictors of post-SRS complication rates or the ability to taper Decadron. Lesion location is predictive of post-SRS seizure activity

[en] Purpose: To design and implement a noninvasive stereotactic immobilization technique with daily CT image-guided positioning to treat patients with paraspinal lesions accurately and to quantify the systematic and random patient setup errors occurring with this method. Methods and Materials: A stereotactic body frame (SBF) was developed for 'rigid' immobilization of paraspinal patients. The inherent accuracy of this system for stereotactic CT-guided treatment was evaluated with phantom studies. Seven patients with thoracic and lumbar spine lesions were immobilized with the SBF and positioned for 33 treatment fractions using daily CT scans. For all 7 patients, the daily setup errors, as assessed from the daily CT scans, were corrected at each treatment fraction. A retrospective analysis was also performed to assess what the impact on patient treatment would have been without the CT-based corrections (i.e., if patient setup had been performed only with the SBF). Results: The average magnitude of systematic and random errors from uncorrected patient setups using the SBF was approximately 2 mm and 1.5 mm (1 SD), respectively. For fixed phantom targets, the system accuracy for the SBF localization and treatment was shown to be within 1 mm (1 SD) in any direction. Dose-volume histograms incorporating these uncertainties for an intensity-modulated radiotherapy plan for lumbar spine lesions were generated, and the effects on the dose-volume histograms were studied. Conclusion: We demonstrated a very accurate and precise method of patient immobilization and treatment delivery based on a noninvasive SBF and daily image guidance for paraspinal lesions. The SBF provides excellent immobilization for paraspinal targets, with setup accuracy better than 2 mm (1 SD). However, for highly conformal paraspinal treatments, uncorrected systematic and random errors of 2 mm in magnitude can result in a significantly greater (>100%) dose to the spinal cord than planned, even though the planned target coverage may not change substantially. With daily CT guidance using the SBF, we showed that the maximal spinal cord dose is ensured to be within 10-15% of the planned value

[en] Because of the proximity of the spinal cord, effective radiotherapy of paraspinal tumors to high doses requires highly conformal dose distributions, accurate patient setup, setup verification, and patient immobilization. An immobilization cradle has been designed to facilitate the rapid setup and radiation treatment of patients with paraspinal disease. For all treatments, patients were set up to within 2.5 mm of the design using an amorphous silicon portal imager. Setup reproducibility of the target using the cradle and associated clinical procedures was assessed by measuring the setup error prior to any correction. From 350 anterior/posterior images, and 303 lateral images, the standard deviations, as determined by the imaging procedure, were 1.3 m, 1.6 m, and 2.1 in the ant/post, right/left, and superior/inferior directions. Immobilization was assessed by measuring patient shifts between localization images taken before and after treatment. From 67 ant/post image pairs and 49 lateral image pairs, the standard deviations were found to be less than 1 mm in all directions. Careful patient positioning and immobilization has enabled us to develop a successful clinical program of high dose, conformal radiotherapy of paraspinal disease using a conventional Linac equipped with dynamic multileaf collimation and an amorphous silicon portal imager

[en] Purpose: To report the esophageal toxicity from single-fraction paraspinal stereotactic radiosurgery (SRS) and identify dosimetric and clinical risk factors for toxicity. Methods and Materials: A total of 204 spinal metastases abutting the esophagus (182 patients) were treated with high-dose single-fraction SRS during 2003-2010. Toxicity was scored using the National Cancer Institute Common Toxicity Criteria for Adverse Events, version 4.0. Dose-volume histograms were combined to generate a comprehensive atlas of complication incidence that identifies risk factors for toxicity. Correlation of dose-volume factors with esophageal toxicity was assessed using Fisher’s exact test and logistic regression. Clinical factors were correlated with toxicity. Results: The median dose to the planning treatment volume was 24 Gy. Median follow-up was 12 months (range, 3-81). There were 31 (15%) acute and 24 (12%) late esophageal toxicities. The rate of grade ≥3 acute or late toxicity was 6.8% (14 patients). Fisher’s exact test resulted in significant median splits for grade ≥3 toxicity at V12 = 3.78 cm³ (relative risk [RR] 3.7, P=.05), V15 = 1.87 cm³ (RR 13, P=.0013), V20 = 0.11 cm³ (RR 6, P=0.01), and V22 = 0.0 cm³ (RR 13, P=.0013). The median split for D2.5 cm³ (14.02 Gy) was also a significant predictor of toxicity (RR 6; P=.01). A highly significant logistic regression model was generated on the basis of D2.5 cm³. One hundred percent (n = 7) of grade ≥4 toxicities were associated with radiation recall reactions after doxorubicin or gemcitabine chemotherapy or iatrogenic manipulation of the irradiated esophagus. Conclusions: High-dose, single-fraction paraspinal SRS has a low rate of grade ≥3 esophageal toxicity. Severe esophageal toxicity is minimized with careful attention to esophageal doses during treatment planning. Iatrogenic manipulation of the irradiated esophagus and systemic agents classically associated with radiation recall reactions are associated with development of grade ≥4 toxicity.

[en] Purpose: Image-guided intensity-modulated radiotherapy enables delivery of high-dose radiation to tumors close to the spinal cord. We report our experience with multifractionated regimens using image-guided intensity-modulated radiotherapy to treat gross paraspinal disease to doses beyond cord tolerance. Methods and Materials: We performed a retrospective review of 27 consecutive patients with partially resected or unresectable paraspinal tumors irradiated to >5,300 cGy in standard fractionation. Results: The median follow-up was 17.4 months (range, 2.1-47.3). Eighteen sarcomas, seven chordomas, and two ependymomas were treated. The median dose to the planning target volume was 6,600 cGy (range, 5,396-7,080) in 180- or 200-cGy fractions. The median planning target volume was 164 cm³ (range, 29-1,116). Seven patients developed recurrence at the treatment site (26%), and 6 of these patients had high-grade tumors. Three patients with recurrence had metastatic disease at the time of radiotherapy. The 2-year local control rate was 65%, and the 2-year overall survival rate was 79%. Of the 5 patients who died, 4 had metastatic disease at death. Twenty-three patients (84%) reported either no pain or improved pain at the last follow-up visit. Sixteen patients discontinued narcotic use after treatment (62.5%). Twenty-three patients (89%) had a stable or improved American Spine Injury Association score at the last follow-up visit. No patient experienced radiation-induced myelopathy. Conclusions: The dose to paraspinal tumors has traditionally been limited to respect cord tolerance. With image-guided intensity-modulated radiotherapy, greater doses of radiation delivered in multiple fractions can be prescribed with excellent target coverage, effective palliation, and acceptable toxicity and local control

[en] Purpose: To report tumor control and toxicity for patients treated with image-guided intensity-modulated radiotherapy (RT) for spinal metastases with high-dose single-fraction RT. Methods and Materials: A total of 103 consecutive spinal metastases in 93 patients without high-grade epidural spinal cord compression were treated with image-guided intensity-modulated RT to doses of 18-24 Gy (median, 24 Gy) in a single fraction between 2003 and 2006. The spinal cord dose was limited to a 14-Gy maximal dose. The patients were prospectively examined every 3-4 months with clinical assessment and cross-sectional imaging. Results: The overall actuarial local control rate was 90% (local failure developed in 7 patients) at a median follow-up of 15 months (range, 2-45 months). The median time to local failure was 9 months (range, 2-15 months) from the time of treatment. Of the 93 patients, 37 died. The median overall survival was 15 months. In all cases, death was from progression of systemic disease and not local failure. The histologic type was not a statistically significant predictor of survival or local control. The radiation dose was a significant predictor of local control (p = 0.03). All patients without local failure also reported durable symptom palliation. Acute toxicity was mild (Grade 1-2). No case of radiculopathy or myelopathy has developed. Conclusion: High-dose, single-fraction image-guided intensity-modulated RT is a noninvasive intervention that appears to be safe and very effective palliation for patients with spinal metastases, with minimal negative effects on quality of life and a high probability of tumor control

[en] Purpose: To examine the impact of dose on local failure (LF) rates in the re-treatment of recurrent paraspinal metastases with image-guided intensity-modulated radiotherapy (IG-IMRT). Methods and Materials: The records of patients with in-field recurrence after previous spine radiation (median dose, 30 Gy) who received salvage IG-IMRT with either five 4-Gy (20-Gy group, n = 42) or five 6-Gy (30-Gy group, n = 55) daily fractions between January 2003 and August 2008 were reviewed. Institutional practice was 20 Gy before April 2006, when it changed to 30 Gy. A total of 47 cases (48%) were treated adjuvantly, after surgery to decompress epidural disease. LF after IG-IMRT was defined radiographically. Results: The median follow-up was 12.1 months (range, 0.2-63.6 months). The 1-year cumulative incidences of LF after 20 Gy and 30 Gy IG-IMRT were 45% and 26%, respectively (p = 0.04). Of all treatment characteristics examined (20-Gy vs. 30-Gy dose group, dose to 95% of the planned and gross target volume, tumor size, histology, receipt of surgery, and interval between first and second radiation), only dose group had a significant impact on actuarial LF incidence (p = 0.04; unadjusted HR, 0.51; 95% CI, 0.27-0.96). There was no incidence of myelopathy. Conclusions: A significant decrease in LF after IG-IMRT with five 6-Gy fractions compared with five 4-Gy fractions was observed without increased risk of myelopathy. Until prospective data comparing stereotactic hypofractionated and single-fraction regimens become available, when reirradiating recurrent paraspinal metastases with IG-IMRT, administration of five 6-Gy daily fractions is reasonable.

[en] Purpose: The use of image-guided and stereotactic intensity-modulated radiotherapy (IMRT) techniques have made the delivery of high-dose radiation to lesions within close proximity to the spinal cord feasible. This report presents clinical and physical data regarding the use of IMRT coupled with noninvasive body frames (stereotactic and image-guided) for multifractionated radiotherapy. Methods and Materials: The Memorial Sloan-Kettering Cancer Center (Memorial) stereotactic body frame (MSBF) and Memorial body cradle (MBC) have been developed as noninvasive immobilizing devices for paraspinal IMRT using stereotactic (MSBF) and image-guided (MBC) techniques. Patients were either previously irradiated or prescribed doses beyond spinal cord tolerance (54 Gy in standard fractionation) and had unresectable gross disease involving the spinal canal. The planning target volume (PTV) was the gross tumor volume with a 1 cm margin. The PTV was not allowed to include the spinal cord contour. All treatment planning was performed using software developed within the institution. Isocenter verification was performed with an in-room computed tomography scan (MSBF) or electronic portal imaging devices, or both. Patients were followed up with serial magnetic resonance imaging every 3-4 months, and no patients were lost to follow-up. Kaplan-Meier statistics were used for analysis of clinical data. Results: Both the MSBF and MBC were able to provide setup accuracy within 2 mm. With a median follow-up of 11 months, 35 patients (14 primary and 21 secondary malignancies) underwent treatment. The median dose previously received was 3000 cGy in 10 fractions. The median dose prescribed for these patients was 2000 cGy/5 fractions (2000-3000 cGy), which provided a median PTV V100 of 88%. In previously unirradiated patients, the median prescribed dose was 7000 cGy (5940-7000 cGy) with a median PTV V100 of 90%. The median Dmax to the cord was 34% and 68% for previously irradiated and never irradiated patients, respectively. More than 90% of patients experienced palliation from pain, weakness, or paresthesia; 75% and 81% of secondary and primary lesions, respectively, exhibited local control at the time of last follow-up. No cases of radiation-induced myelopathy or radiculopathy have thus far been encountered. Conclusions: Precision stereotactic and image-guided paraspinal IMRT allows the delivery of high doses of radiation in multiple fractions to tumors within close proximity to the spinal cord while respecting cord tolerance. Although preliminary, the clinical results are encouraging

[en] Purpose: In the setting of high-dose single-fraction image-guided radiotherapy of spine metastases, the delivered dose is hypothesized to be a significant factor in local control. We investigated the dependence of local control on measures of dose insufficiency. Methods and Materials: The minimum doses received by the hottest 100%, 98%, and 95% (D_min, D₉₈, and D₉₅) of the gross target volume (GTV) were computed for 91 consecutively treated lesions observed in 79 patients. Prescribed doses of 18-24 Gy were delivered in a single fraction. The spinal cord and cauda equina were constrained to a maximum dose of 12-14 Gy and 16 Gy, respectively. A rank-sum test was used to assess the differences between radiographic local failure and local control. Results: With a median follow-up of 18 months, seven local failures have occurred. The distributions of GTV D_min, D₉₈, and D₉₅ for treatments resulting in local failure were found to be statistically different from the corresponding distributions of the patient group as a whole. Taking no account of histology, p values calculated for D_min, D₉₈, and D₉₅ were 0.004, 0.012, and 0.031, respectively. No correlations between local failure and target volume or between local failure and anatomic location were found. Conclusions: The results indicate that D_min, D₉₈, and D₉₅ may be important risk factors for local failure. No local failures in any histology were observed when D_min was >15 Gy, suggesting that this metric may be an important predictor of local control.

[en] Purpose: Implanted gold markers and megavoltage (MV) portal imaging are commonly used for setup verification of paraspinal tumors treated with high-dose, single-fraction radiotherapy. We investigated whether the use of kilovoltage cone-beam computed tomography (CBCT) imaging eliminates the need for marker implantation. Methods and Materials: Patients with paraspinal disease who were eligible for single-fraction stereotactic body radiotherapy were accrued to an institutional review board-approved protocol. Each of 16 patients underwent implantation of fiducial markers near the target. The markers were visible on the MV images. Three MV image pairs were acquired for each patient (initial, verification, and final) and were registered to the reference images. Every MV pair was complemented by a CBCT scan. CBCT image registration was performed automatically by maximizing the mutual information using a region of interest that excluded the markers. The corrections, as determined from the MV images, were compared with these from CBCT and were used for actual patient setup. Results: The mean and standard deviation of the absolute values of the differences between the CBCT and MV corrections were 1.0 ± 0.7, 1.0 ± 0.6, and 1.0 ± 0.8 mm for the left-right, anteroposterior, and superoinferior directions, respectively. The absolute differences between the corresponding pre- and post-treatment kilovoltage CBCT image registration were 0.6 ± 0.5, 0.6 ± 0.5, and 1.0 ± 0.8 mm. Conclusion: The setup corrections found using CBCT without the use of implanted markers were consistent with the marker registration on MV projections. CBCT has additional advantages, including better positioning precision and robust automatic three-dimensional registration, as well as eliminating the need for invasive marker implantation. We have adopted CBCT for the setup of all single-fraction paraspinal patients. Our data have also demonstrated that target displacements during treatment are insignificant