This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Background Intensity-modulated stereotactic radiotherapy achieves improvements in the ability to produce conformal stereotactic dose distributions by modulation of the intensity of individually delivered beamlets of radiation. Image-guided intensity-modulated stereotactic radiotherapy has emerged as a new treatment option in the multidisciplinary management of metastatic and locally advanced cancers.Methods From July 2009 to February 2010, 34 patients with metastatic and locally advanced cancers were treated with an image-guided intensity-modulated stereotactic radiation system, Axesse (Elekta, Crawley, England). The patient position was verified using CBCT of the Elekta Axesse. Patient setup errors were calculated using automatic image registration of the planning CT scan and verification CBCT scan using the Elekta XVI software. Errors were corrected on-line before each treatment.ResultsThe group mean errors were ? 1 mm and ? 1°. Radiologic complete response was achieved in 8 patients (23.5%). Radiologic partial response was achieved in 25 patients (73.6%). Development of new intracranial lesion was noted in one patient with brain metastasis from lung cancer (2.9%). Radiologic local control was achieved in 33 patients (97.1%). Clinical symptom improvement, including relief of pain and other symptoms, was achieved in all patients.Conclusion Image-guided intensity-modulated stereotactic radiotherapy used in the treatment of patients with metastatic and locally advanced cancer appears to be safe and effective both in terms radiographic tumor control and pain relief. Clinical trials providing standards on treatment parameters, physics quality assurance benchmarks, and tools to measure outcomes are warranted.
Recently, significant progress has been made in advancing the state-of-the-art in stereotactic radiosurgery (SRS) and stereotactic radiotherapy (SRT) treatment delivery through the adoption of intensity modulated radiosurgery/therapy (IMRS/IMRT) approaches [1-3]. IMRS/IMRT achieves improvements in the ability to produce conformal stereotactic dose distributions by modulation of the intensity of individually delivered beamlets of radiation [4-6]. The ability to deliver modulated beamlets of radiation is implemented by use of multileaf collimators (MLC) to segment the large linac-produced radiation beam into small beamlets, or pencil beams. Intensity, or dose, is modulated by varying the amount of time that one pencil beam is exposed, relative to the others [7-9].Linear accelerators capable of kilovoltage cone-beam computed tomography (CBCT) imaging and intensity modulated dose delivery are used in radiotherapy to improve treatment guidance while achieving highly conformal dose distributions [9-13].Image-guided intensity-modulated stereotactic radiotherapy has emerged as a new treatment option in the multidisciplinary management of metastatic and locally advanced cancers [9, 14-16].Sahgal et al. published a comprehensive review concerning the emerging technique of stereotactic body radiosurgery for spinal metastases [17]. Using state-of-the-art image-guided intensity-modulated stereotactic approach, radiotherapy can be focused more precisely. It can be used to treat metastatic and locally advanced cancers in which the conventional apÂproach would not allow delivery of adequate radiation doses to the planning target volume (PTV) in combination with sparing of normal tissue [15, 18, 19].The present study reports the preliminary results of intensity-modulated stereotactic radiotherapy and daily cone-beam computed tomography (CBCT)-based image guidance with on-line correction of setup errors for patients with metastatic and locally advanced cancers.
From July 2009 to February 2010, 34 patients with metastatic and locally advanced cancers were treated with an image-guided intensity-modulated stereotactic radiation system, Axesse (Elekta, Crawley, England). Patient characteristics are shown in Table 1. Median age of the patients was 63 years (range, 38 to 89 years). Twenty-three patients were male and 11 patients were female. Karnofsky performance status (KPS) score was 90-100 in 21 patients, 70-80 in 13 patients. Sixteen patients had locally advanced cancers in which tumor volumes were very large and adjacent to critical structures, 7 patients had limited brain metastases, 3 patients had complicated and extensive vertebral metastases in which the critical structure, spinal cord, was involved, and 8 patients had metastatic diseases other than brain and vertebral metastases. Site of radiotherapy was brain (n = 7), head and neck (n = 3), thorax (n = 6), abdomen (n = 6), pelvis (n = 6) and skeletal system (n = 6), respectively. Site of primary tumor was head and neck (n = 4), lung (n =11), liver (n = 5), rectum (n = 3), uterine cervix (n = 3), prostate (n = 2), urinary bladder (n = 2) and others (n = 4), respectively (Table1).Immobilization of the patientsThe patients were immobilized with a vacuum pillow for treatment of tumors of the brain, head and neck region. This system was attached to a stereotactic localization device HeadFIX (Medical Intelligence, The Elekta Group).For treatment of thoracic, abdominal and pelvic tumors, a customized total body vacuum cushion (BodyFIX, Medical Intelligence, The Elekta Group) was used [20]. The double vacuum was applied for all treatment fractions to minimize intrafraction patient motion [21].Treatment planningThe Pinnacle treatment planning system (Philips, ADAC, Milpitas, CA) was used for treatment planning. Step-and-shoot IMRT plans were generated for an Elekta Axesse equipped with the beam modulator with a 4-mm leaf width.For head and neck tumors, the target volume was defined after registration of the planning magnetic resonance imaging to the planning CT scan. The gross target volume (GTV) was defined as the gross extent of tumor shown by imaging studies. The clinical target volume (CTV) surrounded the gross target volume (GTV) with additional margin of at least 5 mm depending on the anatomical relationship of adjacent structures and of potential microscopic spread. The planning target volume (PTV) surrounded the clinical target volume (CTV) with additional margin of 3 mm. A total dose of 70-72 Gy was prescribed to the isodose line that encompassed at least 95% of the PTV, and 50-65 Gy to the regional lymph nodes at risk of potential microscopic spread. Dose was delivered at 1.8-2.0 Gy/fraction/day, 5 days a week [22].For patients with brain metastases, the whole brain radiation therapy (WBRT) was delivered followed by stereotactic radiosurgery to metastatic lesions (24, 25). The WBRT dosage schedule was 30 Gy in 10 fractions over 2 weeks. For metastatic lesions, the target volume was defined after registration of the magnetic resonance imaging scan to the planning CT scan. The planning target volume (PTV) for metastatic lesions surrounded the gross target volume (GTV) with additional margin of 2 mm [23]. The dosage schedule of stereotactic radiosurgery to metastatic lesions was described as follows. For metastases up to 2.0 cm in diameter, metastases larger than 2 cm but equal to or less than 3 cm, and metastases larger than 3 cm and less than 4 cm, a dose of 24 Gy, 18 Gy, and 15 Gy was prescribed to the isodose line that encompassed at least 95% of the PTV respectively [24, 25].For patients with complicated vertebral metastases, the target volume was defined after registration of the magnetic resonance imaging scan to the planning CT scan. The affected parts of the vertebrae were delineated as the gross target volume (GTV). For coverage of areas with potential microscopic disease, additional margin of at least 5 mm around the GTV defined the clinical target volume (CTV). The whole vertebra was defined as the CTV if significant parts of vertebral body and vertebral arch were affected simultaneously. PTV was generated with additional margin around the CTV. The PTV was not allowed to overlap the spinal canal but touched it in all cases. The spinal canal was contoured as the critical structures, rather than the spinal cord, to allow for the safety margin [26, 27]. A total dose of 30 Gy was prescribed to the isodose line that encompassed at least 95% of the PTV. The dosage schedule was 30 Gy in 5 fractions over 1 week.For patients with metastatic diseases other than brain and vertebral metastases, a total dose of 30 Gy was prescribed to the isodose line that encompassed at least 95% of the PTV. The dosage schedule was 30 Gy in 5 fractions over 1 week.IGRT protocolBefore every treatment fraction, 3D volume imaging was performed. The patient position was verified using CBCT of the Elekta Axesse. Patient setup errors were calculated using automatic image registration (correlation coefficient algorithm) of the planning CT scan and verification CBCT scan using the Elekta XVI software. Errors were corrected on-line before each treatment. Combined translational and rotational errors were corrected using a robotic treatment table with 6 degrees freedom of movement (HexaPOD evo RT System, Medical Intelligence, The Elekta Group).Translational and rotational setup errors were evaluated. The group mean error was defined as the average of all systematic errors; Σ was defined as the standard deviation of the systematic errors. The root-mean-square of the random errors was calculated as Ï. Errors were calculated separately for all three axes: lateral (leftâright), longitudinal (superoinferior), and vertical (anteroposterior) [27-29].
Setup errorsPatient setup errors were calculated using 760 CBCT studies acquired before treatment. The results were summarized in Table 2. The group mean errors of Axesse in combination with a HexaPOD robotic treatment table were ? 1 mm (translational) and ? 1°(rotational). The systematic positioning errors (translational) of Axesse in combination with a HexaPOD robotic treatment table were 2.87 mm anteroposteriorly, 2.26 mm laterally, and 2.77 mm superoinferiorly; while the systematic positioning errors (rotational) were 0.79° anteroposteriorly, 0.85° laterally, and 0.79° superoinferiorly. These translational errors and rotational errors were corrected online before each treatment fraction.There were no rotational errors that exceeded the motion range of the robotic HexaPOD (3° around all three axes).Clinical responseThe follow-up period ranged from 1.3 to 7.8 months (median 3.7 months). During radiotherapy, patients were evaluated once a week. After completion of radiotherapy, patients were evaluated every 1-2 months for the first year. Physical examination was performed at each follow-up visit. A post-treatment CT or MRI scan was obtained 1-3 months after completion of radiotherapy and then every 6 months or when clinically indicated.Complete response was defined as total radiologic disappearance of all lesions. Partial response was defined as greater than a 50% decrease in size of all lesions. Stable disease was defined as a 0-50% decrease in size of all lesions. Local control was defined as a complete response, partial response, or stable disease. Progressive disease was defined as an increase in the size of any lesion or the development of new lesions. The radiologic reappearance of tumor constituted recurrent disease [24].Radiologic complete response was achieved in 8 patients (23.5%). Radiologic partial response was achieved in 25 patients (73.6%). Development of new intracranial lesion was noted in one patient with brain metastasis from lung cancer (2.9%). Therefore, radiologic local control was achieved in 33 patients (97.1%).Clinical symptom improvementClinical symptom improvement, including relief of pain and other symptoms, was achieved in all patients.Acute and late toxicitiesAcute and late toxicities were graded according to the Radiation Therapy Oncology Group (RTOG) radiation morbidity scoring criteria [30].Acute toxicities were mild in most of the patients. Grade 1 toxicity was observed in 23 patients (67.7%). Grade 2 toxicity was observed in 10 patients (29.4%). One patient (2.9%) with locally advanced head and neck cancer treated with a total dose of 72 Gy in 36 fractions developed grade 3 moist desquamation of the skin. An absence of grade 4 toxicity was noted.Normal tissue effects occurring more than 90 days after irradiation, or acute toxicities persisting beyond 90 days were scored as late toxicities. During the limited follow-up period, no grade 3 of greater late toxicity was observed. The patient with grade 3 moist desquamation of the skin developed grade 2 induration of the skin and subcutaneous tissue.
Radiotherapy is essential for the appropriate management of patients with metastatic and locally advanced cancer and constitutes nearly 50% of the modern radiation therapy workload [31].Brain metastases occur in 20â40% of patients with systemic cancer; 30â40% present with a single metastasis. Prognosis for these patients is poor with a median survival time of 1â2 months with corticosteroids, which can be extended to 6 months with whole brain radiation therapy (WBRT), and some investigators report that survival can be further extended when WBRT is preceded by surgical resection. Radiosurgery is a technique that involves single treatment radiation precisely focused at intracranial targets. Radiosurgery is frequently used to treat brain metastases and is sometimes preferred as a less invasive alternative to surgery [24].Approximately 40% of cancer patients may develop metastatic disease involving the vertebral spine [32], and metastatic spinal cord compression occurs in 5-10% of all cancer patients [33]. Radiotherapy is accepted as a key treatment of painful bony metastases and metastatic spinal cord compression. Standard treatment regimens vary from a single dose of 8 Gy to protracted fractionation for a dose ? 40 Gy [27].Conventional palliative treatment usually consists of a single direct or parallel-opposed beam arrangement for each treatment site. This type of treatment provides no avenue for dose conformation in three dimensions.Studies have demonstrated that CT-based imaging and planning of palliative radiotherapy is superior to that with conventional approaches that use clinical mark-ups or fluoroscopy [34, 35].Numerous locally advanced or recurrent tumors that are very large and that have complex geometric configurations are difficult to treat with conventional approaches, especially when adjacent to critical structures [15].In order to adequately treat these situations of metastatic or locally advanced cancer using state-of-the-art image-guided intensity-modulated stereotactic radiotherapy, recent work has investigated streamlining the radiotherapy process, including online planning of radiation therapy using kilovoltage cone-beam CT and external treatment planning and verify and record systems [36]. The Ottawa Hospital Cancer Center investigated the framework which integrates the processes of treatment planning, image guidance, verify and record, and delivery of intensity-modulated radiation therapy [15, 37].The system error analyses of various image-guided intensity-modulated stereotactic radiotherapy apparatus are discussed. Using the patient-based measurements of Cyberknife (Accuray Inc., Sunnyvale, California), the average Xsight tracking error component was 0.49 ± 0.22 mm [38] and the alignment of the treatment dose with target volume was within ± 1 mm [39].Using the patient-based measurements, precision of the Novalis (Brain Lab Inc., Munich, Germany) defined as the degree of variation between the isocenter location by fusing images taken at the time portal imaging to that at the time of CT simulation was 1.36 ± 0.11 mm [40].Using the patient-based measurements, the standard deviation of interfraction isocenter displacement of TomoTherapy HiArt helical tomotherapy (TomoTherapy Inc., Madison, Wisconsin) was ±4.0 mm anteroposteriorly, ±4.1 mm laterally, and ±4.3 mm superoinferiorly [41].Using the patient-based measurements, the systematic positioning errors (translational) of Synergy S (Elekta, Crawley, England) in combination with a HexaPOD robotic treatment table were 2.0 mm anteroposteriorly, 2.7 mm laterally, and 2.9 mm superoinferiorly; while the systematic positioning errors (rotational) were 1.2° anteroposteriorly, 1.1° laterally, and 1.2° superoinferiorly. The group mean errors of Synergy S in combination with a HexaPOD robotic treatment table were ? 1 mm (translational) and ? 1°(rotational) [27]. In our series, the systematic positioning errors (translational) of Axesse in combination with a HexaPOD robotic treatment table were 2.87 mm anteroposteriorly, 2.26 mm laterally, and 2.77 mm superoinferiorly; while the systematic positioning errors (rotational) were 0.79° anteroposteriorly, 0.85° laterally, and 0.79° superoinferiorly. The group mean errors of Axesse in combination with a HexaPOD robotic treatment table were ? 1 mm (translational) and ? 1° (rotational). The results were similar to that of Guckenberger et al.During conventional palliative treatment, 1.5 -2.5 cm margins around the areas of tumors were used in delivery of radiotherapy. With an image-guided intensity-modulated stereotactic approach, small margins (0.5-1.0 cm) around the areas of tumors were used in treatment planning [15]. The dose distributions achieved a much more homogeneous dose to PTV and minimize dose to the adjacent normal tissues. The setup errors were small during treatment with application of the following techniques: daily CBCT- based image guidance, robotic correction of setup errors in 6 degrees freedom of movement, and effective intrafraction immobilization of the patients [42, 43].In the review article of Sahgal et al., local control for unirradiated patients with spinal metastases was achieved in 67/77 (87%) tumors treated, and in 23/24 (96%) reirradiated patientsâ tumors [17]. Andrews et al. reported that the local control of brain metastatic lesions was 41/50 (82%) in the whole brain radiotherapy plus radiosurgery group [24]. In our study, local control rate was defined according to progression or recurrence by imaging. Radiologic local control was achieved in 33/34 patients (97.1%). The results were similar to the above series.In the referenced literature, both acute and late toxicity were mild or moderate [22, 24, 27, 44-47]. In our study, similar results of toxicities were noted.With these favorable results, image-guided intensity-modulated stereotactic radiotherapy is feasible for the treatment of patients with metastatic and locally advanced cancer.Some limitations of this study need to be considered in the interpretation of our data. The shortcomings of this study included the limited number of patients, the heterogeneity of the patient cohort, short follow-up and the retrospective nature of the analysis.
Image-guided intensity-modulated stereotactic radiotherapy used in the treatment of patients with metastatic and advanced cancer appears to be safe and effective both in terms radiographic tumor control and pain relief [15, 17, 27]. It is anticipated that obstacles to the routine practice of image-guided intensity-modulated stereotactic radiotherapy will gradually be overcome. Clinical trials providing standards on treatment parameters, physics quality assurance benchmarks, and tools to measure outcomes are warranted.
1.  Benedict SH, Cardinale RM, Wu Q, Zwicker RD, Broaddus WC, Mohan R. Intensity-modulated stereotactic radiosurgery using dynamic micro-multileaf collimation. Int J Radiat Oncol Biol Phys 2001; 50: 751-58.2. Yin FF, Ryu S, Ajlouni M, Zhu J, Yan H, Guan H, Faber K, Rock J, Abdalhak M, Rogers L, Rosenblum M, Kim JH. A technique of intensity-modulated radiosurgery (IMRS) for spinal tumors. Med Phys 2002; 29: 2815-22.3. Fuss M, Salter BJ, Sadeghi A, Vollmer DG, Hevezi JM, Herman TS. Fractionated stereotactic intensity-modulated radiotherapy (FS-IMRT) for small acoustic neuromas. Med Dosim 2002; 27: 147-54.4. Dogan N, Leybovich LB, King S, Sethi A, Emami B. Improvement of treatment plans developed with intensity-modulated radiation therapy for concave-shaped head and neck tumors. Radiology 2002; 223: 57-64.5. Fiorino C, Broggi S, Corletto D, Cattaneo GM, Calandrino R. Conformal irradiation of concave-shaped PTVs in the treatment of prostate cancer by simple 1D intensity-modulated beams. Radiother Oncol 2000; 55: 49-58.6. Ten Haken RK, Lawrence TS. The clinical application of intensity-modulated radiation therapy. Semin Radiat Oncol 2006; 16: 224-31.7. Salter BJ, Fuss M, Sarkar V, Wang B, Rassiah-Szegedi P, Papanikolaou N, Hollingshaus S, Shrieve DC. Optimization of isocenter location for intensity modulated stereotactic treatment of small intracranial targets. Int J Radiat Oncol Biol Phys 2009; 73: 546-55.8. Lawson JD, Wang JZ, Nath SK, Rice R, Pawlicki T, Mundt AJ, Murphy K. Intracranial application of IMRT based radiosurgery to treat multiple or large irregular lesions and verification of infra-red frameless localization system. Neurooncol 2010; 97: 59-66.9. Wang JZ, Rice R, Mundt A, Sandhu A, Murphy K. Image-guided stereotactic spine radiosurgery on a conventional linear accelerator. Med Dosim 2010; 35: 53-62.10. Oldham M, Létourneau D, Watt L, Hugo G, Yan D, Lockman D, Kim LH, Chen PY, Martinez A, Wong JW. Cone-beam-CT guided radiation therapy: A model for on-line application. Radiother Oncol 2005; 75: 271-8.11. Letourneau D, Keller H, Sharpe MB, Jaffray DA. Integral test phantom for dosimetric quality assurance of image guided and intensity modulated stereotactic radiotherapy. Med Phys 2007; 34: 1842-9.12. Polat B, Guenther I, Wilbert J, Goebel J, Sweeney RA, Flentje M, Guckenberger M. Intra-fractional uncertainties in image-guided intensity-modulated radiotherapy (IMRT) of prostate cancer. Strahlenther Onko. 2008; 184: 668-73.13. Kim S, Jin H, Yang H, Amdur RJ. A study on target positioning error and its impact on dose variation in image-guided stereotactic body radiotherapy for the spine. Int J Radiat Oncol Biol Phys 2009; 73: 1574-9.14. Shiu AS, Chang EL, Ye JS, Lii M, Rhines LD, Mendel E, Weinberg J, Singh S, Maor MH, Mohan R, Cox JD. Near simultaneous computed tomography image-guided stereotactic spinal radiotherapy: an emerging paradigm for achieving true stereotaxy. Int J Radiat Oncol Biol Phys 2003; 57: 605-13.15. Samant R, Gerig L, Montgomery L, Macrae R, Fox G, Nyiri B, Carty K, Macpherson M. The emerging role of IG-IMRT for palliative radiotherapy: a single-institution experience. Curr Oncol 2009; 16: 40-5.16. Breneman JC, Steinmetz R, Smith A, Lamba M, Warnick RE. Frameless image-guided intracranial stereotactic radiosurgery: clinical outcomes for brain mstastases. Int J Radiat Oncol Biol Phys 2009; 74: 702-6.17. Sahgal A, Larson DA, Chang EL. Stereotactic body radiosurgery for spinal metastases: A critical review. Int J Radiat Oncol Biol Phys 2008; 71: 652-65.18. Gibbs IC, Kamnerdsupaphon P, Ryu MR, Dodd R, Kiernan M, Chang SD, Adler JR Jr. Image-guided robotic radiosurgery for spinal metastases. Radiother Oncol 2007; 82: 185-90.19. Chang EL, Shiu AS, Mendel E, Mathews LA, Mahajan A, Allen PK, Weinberg JS, Brown BW, Wang XS, Woo SY, Cleeland C, Maor MH, Rhines LD. Phase I/II study of stereotactic body radiotherapy for spinal metastasis and its pattern of failure. J Neurosurg Spine 2007; 7: 151-60.20. Nevinny-Stickel M, Sweeney RA, Bale RJ, Posch A, Auberger T, Lukas P. Reproducibility of patient positioning for fractionated extracranial stereotactic radiotherapy using a double-vacuum technique. Strahlenther Onkol 2004; 180: 117-22.21. Guckenberger M, Meyer J, Wilbert J, Richter A, Baier K, Mueller G, Flentje M. Intra-fractional uncertainties in cone-beam CT based image-guided radiotherapy (IGRT) of pulmonary tumors. Radiother Oncol 2007; 83: 57-64.22. Münter MW, Thilmann C, Hof H, Didinger B, Rhein B, Nill S, Schlegel W, Wannenmacher M, Debus J. Stereotactic intensity modulated radiation therapy and inverse treatment planning for tumors of the head and neck region: clinical implementation of the step and shoot approach and first clinical results. Radiother Oncol 2003; 66: 313-21.23. Lagerwaard FJ, van der Hoorn EAP, Verbakel WFAR, Haasbeek CJA, Slotman BJ, Senan S. Whole-brain radiotherapy with simultaneous integrated boost to multiple brain metastases using volumetric modulated arc therapy. Int J Radiat Oncol Biol Phys 2009; 75: 253-9.24. Andrews DW, Scott CB, Sperduto PW, Flanders AE, Gaspar LE, Schell MC, Werner-Wasik M, Demas W, Ryu J, Bahary JP, Souhami L, Rotman M, Mehta MP, Curran WJ Jr. Whole brain radiation therapy with or without stereotactic radiosurgery boost for patients with one to three brain metastases: phase III results of the RTOG 9508 randomised trial. Lancet 2004; 363: 1665-72.25. Aoyama H, Shirato H, Tago M, Nakagawa K, Toyoda T, Hatano K, Kenjyo M, Oya N, Hirota S, Shioura H, Kunieda E, Inomata T, Hayakawa K, Katoh N, Kobashi G. Stereotactic radiosurgery plus whole-brain radiation therapy vs stereotactic radiosurgery alone for treatment of brain metastases: a randomized controlled trial. JAMA 2006; 295: 2483-91.26. Breen SL, Craig T, Bayley A, O'Sullivan B, Kim J, Jaffray D. Spinal cord planning risk volumes for intensity-modulated radiation therapy of head-and-neck cancer. Int J Radiat Oncol Biol Phys 2006; 64: 321-5.27. Guckenberger M, Goebel J, Wilbert J, Baier K, Richter A, Sweeney RA, Bratengeier K, Flentje M. Clinical outcome of dose-escalated image-guided radiotherapy for spinal metastases. Int J Radiat Oncol Biol Phys 2009; 75: 828-35.28. van Herk M. Errors and margins in radiotherapy. Semin RadiatOncol 2004; 14: 52-64.29. Guckenberger M, Meyer J, Vordermark D, Baier K, Wilbert J, Flentje M.. Magnitude and clinical relevance of translational and rotational patient setup errors: A cone-beam CT study. Int J Radiat Oncol Biol Phys 2006; 65: 934-42.30. Cox JD, Stetz J, Pajak TF. Toxicity criteria of the Radiation Therapy Oncology Group (RTOG) and the European Organization for Research and Treatment of Cancer (EORTC). Int J Radiat Oncol Biol Phys 1995; 31: 1341-6.31. Chow E, Danjoux C, Wong R, Szumacher E, Franssen E, Fung K, Finkelstein J, Andersson L, Connolly R. Palliation of bone metastases: a survey of patterns of practice among Canadian radiation oncologists. Radiother Oncol 2000; 56: 305-14.32. Wong DA, Fornasier VL, MacNab I. Spinal metastases: The obvious, the occult, and the impostors. Spine 1990; 15: 1-4.33. Rades D, Stalpers LJ, Veninga T, Schulte R, Hoskin PJ, Obralic N, Bajrovic A, Rudat V, Schwarz R, Hulshof MC, Poortmans P, Schild SE. Evaluation of five radiation schedules and prognostic factors for metastatic spinal cord compression. J Clin Oncol 2005; 23: 3366-75.34. Haddad P, Cheung F, Pond G, Easton D, Cops F, Bezjak A, McLean M, Levin W, Billingsley S, Williams D, Wong R. Computerized tomographic simulation compared with clinical mark-up in palliative radiotherapy: a prospective study. Int J Radiat Oncol Biol Phys 2006; 65: 824-9.35. McJury M, Fisher PM, Pledge S, Brown G, Anthony C, Hatton MQ, Conway J, Robinson MH. The impact of virtual simulation in palliative radiotherapy for non-small-cell lung cancer. Radiother Oncol 2001; 59: 311-8.36. Létourneau D, Wong R, Moseley D, Sharpe MB, Ansell S, Gospodarowicz M, Jaffray DA. Online planning and delivery technique for radiotherapy of spinal metastases using cone-beam CT: image quality and system performance. Int J Radiat Oncol Biol Phys 2007; 67: 1229-37.37. MacPherson M, Montgomery L, Fox G, Carty K, Gerig L, MacRae R, Grimard L, Clark BG, Samant R. On-line rapid palliation using helical tomotherapy: A prospective feasibility study. Radiotherapy and Oncology 2008; 87: 116-8.38. Ho AK, Fu D, Cotrutz C, Hancock SL, Chang SD, Gibbs IC, Maurer CR Jr, Adler JR Jr. A study of the accuracy of cyberknife spinal radiosurgery using skeletal structure tracking. Neurosurgery 2007; 60: ONS147-56.39. Ryu SI, Chang SD, Kim DH, Murphy MJ, Le QT, Martin DP, Adler JR Jr. Image-guided hypo-fractionated stereotactic radiosurgery to spinal lesions. Neurosurgery 2001; 49: 838-46.40. Ryu S, Fang Yin F, Rock J, Zhu J, Chu A, Kagan E, Rogers L, Ajlouni M, Rosenblum M, Kim JH. Image-guided and intensity-modulated radiosurgery for patients with spinal metastasis. Cancer 2003; 97: 2013-8.41. Mahan SL, Ramsey CR, Scaperoth DD, Chase DJ, Byrne TE. Evaluation of image-guided helical tomotherapy for the retreatment of spinal metastasis. Int J Radiat Oncol Biol Phys 2005; 63: 1576-83.42. Guckenberger M, Meyer J, Wilbert J, Baier K, Sauer O, Flentje M. Precision of image-guided radiotherapy (IGRT) in six degrees of freedom and limitations in clinical practice. Strahlenther Onkol 2007; 183: 307-13.43. Meyer J, Wilbert J, Baier K, Guckenberger M, Richter A, Sauer O, Flentje M. Positioning accuracy of cone-beam computed tomography in combination with a HexaPOD robot treatment table. Int J Radiat Oncol Biol Phys 2007; 67: 1220-8.44. Chang EL, Shiu AS, Mendel E, Mathews LA, Mahajan A, Allen PK, Weinberg JS, Brown BW, Wang XS, Woo SY, Cleeland C, Maor MH, Rhines LD. Phase I/II study of stereotacticbody radiotherapy for spinal metastasis and its pattern of failure. J Neurosurg Spine 2007; 7: 151-60.45. Yamada Y, Lovelock DM, Yenice KM, Bilsky MH, Hunt MA, Zatcky J, Leibel SA. Multifractionated image-guided and stereotactic intensity-modulated radiotherapy of paraspinal tumors: A preliminary report. Int J Radiat Oncol Biol Phys 2005; 62: 53-61.46. Sahgala A, Choua D, Amesa C, Maa L, Chuanga C, Lamborna K, Huang K, Chin CT, Weinstein P, Larson D. Proximity of spinous/paraspinous radiosurgery metastatic targets to the spinal cord versus risk of local failure. Int J Radiat Oncol Biol Phys 2007; 69: S243.47. Degen JW, Gagnon GJ, Voyadzis JM, McRae DA, Lunsden M, Dieterich S, Molzahn I, Henderson FC. CyberKnife stereotactic radiosurgical treatment of spinal tumors for pain control and quality of life. J Neurosurg Spine 2005; 2: 540-9.