Vol 27, No 1 (2022)
Review paper
Published online: 2022-01-24

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Stereotactic radiotherapy for bone oligometastases

Caterina Colosimo1, Francesco Pasqualetti2, Cynthia Aristei3, Simona Borghesi4, Letizia Forte5, Marcello Mignogna1, Donatella Badii5, Manrico Bosio5, Fabiola Paiar2, Sara Nanni4, Silvia Bertocci4, Luciana Lastrucci5, Silvana Parisi6, Gianluca Ingrosso3
Rep Pract Oncol Radiother 2022;27(1):40-45.


About 60–90% of cancer patients are estimated to develop bone metastases, particularly in the spine.

Bone scintigraphy, computed tomography (CT) and magnetic resonance imaging (MRI) are currently used to assess metastatic bone disease; positron emission tomography/computed tomography (PET/CT) has become more widespread in clinical practice because of its high sensitivity and specificity with about 95% diagnostic accuracy. The most common and well-known radiotracer is 18F-fluorodeoxyglucose (18FDG); several other PET-radiotracers are currently under investigation for different solid tumors, such as 11C or 18FDG-choline and prostate specific membrane antigen (PSMA)-PET/CT for prostate cancer. In treatment planning, standard and investigational imaging modalities should be registered with the planning CT so as to best define the bone target volume. For target volume delineation of spine metastases, the International Spine Radiosurgery Consortium (ISRC) of North American experts provided consensus guidelines. Single fraction stereotactic radiotherapy (SRT) doses ranged from 12 to 24 Gy; fractionated SRT administered 21–27 Gy in 3 fractions or 20–35 Gy in 5 fractions. After spine SRT, less than 5% of patients experienced grade ≥ 3 acute toxicity. Late toxicity included the extremely rare radiation-induced myelopathy and a 14% risk of de novo vertebral compression fractures.

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  1. Joyce JA, Pollard JW. Microenvironmental regulation of metastasis. Nat Rev Cancer. 2009; 9(4): 239–252.
  2. Coleman RE. Clinical features of metastatic bone disease and risk of skeletal morbidity. Clin Cancer Res. 2006; 12(20 Pt 2): 6243s–6249s.
  3. Bury T, Barreto A, Daenen F, et al. Fluorine-18 deoxyglucose positron emission tomography for the detection of bone metastases in patients with non-small cell lung cancer. Eur J Nucl Med. 1998; 25(9): 1244–1247.
  4. Jacobson AF, Shapiro CL, Van den Abbeele AD, et al. Prognostic significance of the number of bone scan abnormalities at the time of initial bone metastatic recurrence in breast carcinoma. Cancer. 2001; 91(1): 17–24, doi: 10.1002/1097-0142(20010101)91:1<17::aid-cncr3>3.0.co;2-k.
  5. Niikura N, Liu J, Hayashi N, et al. Treatment outcome and prognostic factors for patients with bone-only metastases of breast cancer: a single-institution retrospective analysis. Oncologist. 2011; 16(2): 155–164.
  6. D'Angelillo RM, Francolini G, Ingrosso G, et al. Consensus statements on ablative radiotherapy for oligometastatic prostate cancer: A position paper of Italian Association of Radiotherapy and Clinical Oncology (AIRO). Crit Rev Oncol Hematol. 2019; 138: 24–28.
  7. Lecouvet FE, Geukens D, Stainier A, et al. Magnetic resonance imaging of the axial skeleton for detecting bone metastases in patients with high-risk prostate cancer: diagnostic and cost-effectiveness and comparison with current detection strategies. J Clin Oncol. 2007; 25(22): 3281–3287.
  8. Yilmaz MH, Ozguroglu M, Mert D, et al. Diagnostic value of magnetic resonance imaging and scintigraphy in patients with metastatic breast cancer of the axial skeleton: a comparative study. Med Oncol. 2008; 25(3): 257–263.
  9. Rybak LD, Rosenthal DI. Radiological imaging for the diagnosis of bone metastases. Q J Nucl Med. 2001; 45: 53–64.
  10. Taoka T, Mayr NA, Lee HJ, et al. Factors influencing visualization of vertebral metastases on MR imaging versus bone scintigraphy. AJR Am J Roentgenol. 2001; 176(6): 1525–1530.
  11. Messiou C, Cook G, deSouza NM. Imaging metastatic bone disease from carcinoma of the prostate. Br J Cancer. 2009; 101(8): 1225–1232.
  12. Greco C, Clifton Ling C. Broadening the scope of image-guided radiotherapy (IGRT). Acta Oncol. 2008; 47(7): 1193–1200.
  13. Taira AlV, Herfkens RJ, Gambhir SS, et al. Detection of bone metastases: assessment of integrated FDG PET/CT imaging. Radiology. 2007; 243(1): 204–211.
  14. Ozülker T, Küçüköz Uzun A, Ozülker F, et al. Comparison of (18)F-FDG-PET/CT with (99m)Tc-MDP bone scintigraphy for the detection of bone metastases in cancer patients. Nucl Med Commun. 2010; 31(6): 597–603.
  15. Song JW, Oh YM, Shim TS, et al. Efficacy comparison between (18)F-FDG PET/CT and bone scintigraphy in detecting bony metastases of non-small-cell lung cancer. Lung Cancer. 2009; 65(3): 333–338.
  16. Nitsch S, Hakenberg OW, Heuschkel M, et al. Evaluation of Prostate Cancer with 11C- and 18F-Choline PET/CT: Diagnosis and Initial Staging. J Nucl Med. 2016; 57(Suppl 3): 38S–42S.
  17. Pasqualetti F, Cocuzza P, Coraggio G, et al. Long-Term PSA Control with Repeated Stereotactic Body Radiotherapy in a Patient with Oligometastatic Castration-Resistant Prostate Cancer. Oncol Res Treat. 2016; 39(4): 217–220.
  18. Fodor A, Lancia A, Ceci F, et al. Oligorecurrent prostate cancer limited to lymph nodes: getting our ducks in a row : Nodal oligorecurrent prostate cancer. World J Urol. 2019; 37(12): 2607–2613.
  19. Cox BW, Spratt DE, Lovelock M, et al. International Spine Radiosurgery Consortium consensus guidelines for target volume definition in spinal stereotactic radiosurgery. Int J Radiat Oncol Biol Phys. 2012; 83(5): e597–e605.
  20. Gerszten PC, Burton SA, Ozhasoglu C, et al. Radiosurgery for spinal metastases: clinical experience in 500 cases from a single institution. Spine (Phila Pa 1976). 2007; 32(2): 193–199.
  21. Nguyen QN, Shiu AS, Rhines LD, et al. Management of spinal metastases from renal cell carcinoma using stereotactic body radiotherapy. Int J Radiat Oncol Biol Phys. 2010; 76(4): 1185–1192.
  22. Guckenberger M, Mantel F, Gerszten PC, et al. Safety and efficacy of stereotactic body radiotherapy as primary treatment for vertebral metastases: a multi-institutional analysis. Radiat Oncol. 2014; 9: 226.
  23. Wang XS, Rhines LD, Shiu AS, et al. Stereotactic body radiation therapy for management of spinal metastases in patients without spinal cord compression: a phase 1-2 trial. Lancet Oncol. 2012; 13(4): 395–402.
  24. Park HJ, Griffin RJ, Hui S, et al. Radiation-induced vascular damage in tumors: implications of vascular damage in ablative hypofractionated radiotherapy (SBRT and SRS). Radiat Res. 2012; 177(3): 311–327.
  25. Heron DE, Rajagopalan MS, Stone B, et al. Single-session and multisession CyberKnife radiosurgery for spine metastases-University of Pittsburgh and Georgetown University experience. J Neurosurg Spine. 2012; 17(1): 11–18.
  26. Ryu S, Pugh SL, Gerszten PC, et al. RTOG 0631 Phase II/III Study of Image-Guided Stereotactic Radiosurgery for Localized (1-3) Spine Metastases: Phase II Results. Int J Radiat Oncol Biol Phys. 2011; 81(2): S131–S132.
  27. Ahmed KA, Stauder MC, Miller RC, et al. Stereotactic body radiation therapy in spinal metastases. Int J Radiat Oncol Biol Phys. 2012; 82(5): e803–e809.
  28. Zelefsky MJ, Yamada Y, Greco C, et al. Phase 3 Multi-Center, Prospective, Randomized Trial Comparing Single-Dose 24 Gy Radiation Therapy to a 3-Fraction SBRT Regimen in the Treatment of Oligometastatic Cancer. Int J Radiat Oncol Biol Phys. 2021; 110(3): 672–679.
  29. Zeng KL, Sahgal A, Tseng CL, et al. Prognostic Factors Associated With Surviving Less Than 3 Months vs Greater Than 3 Years Specific to Spine Stereotactic Body Radiotherapy and Late Adverse Events. Neurosurgery. 2021; 88(5): 971–979.
  30. Zelefsky MJ, Greco C, Motzer R, et al. Predictors of local control after single-dose stereotactic image-guided intensity-modulated radiotherapy for extracranial metastases. Int J Radiat Oncol Biol Phys. 2011; 79(4): 1151–1157.
  31. Zelefsky MJ, Greco C, Motzer R, et al. Tumor control outcomes after hypofractionated and single-dose stereotactic image-guided intensity-modulated radiotherapy for extracranial metastases from renal cell carcinoma. Int J Radiat Oncol Biol Phys. 2012; 82(5): 1744–1748.
  32. Yamada Y, Bilsky MH, Lovelock DM, et al. High-dose, single-fraction image-guided intensity-modulated radiotherapy for metastatic spinal lesions. Int J Radiat Oncol Biol Phys. 2008; 71(2): 484–490.
  33. Siva S, Louie AV, Warner A, et al. Pooled analysis of stereotactic ablative radiotherapy for primary renal cell carcinoma: A report from the International Radiosurgery Oncology Consortium for Kidney (IROCK). Cancer. 2018; 124(5): 934–942.
  34. Ryu S, Rock J, Jain R, et al. Radiosurgical decompression of metastatic epidural compression. Cancer. 2010; 116(9): 2250–2257.
  35. Anand AK, Venkadamanickam G, Punnakal AU, et al. Hypofractionated stereotactic body radiotherapy in spinal metastasis — with or without epidural extension. Clin Oncol (R Coll Radiol). 2015; 27(6): 345–352.
  36. Garg AK, Shiu AS, Yang J, et al. Phase 1/2 trial of single-session stereotactic body radiotherapy for previously unirradiated spinal metastases. Cancer. 2012; 118(20): 5069–5077.
  37. Tao R, Bishop AJ, Brownlee Z, et al. Stereotactic Body Radiation Therapy for Spinal Metastases in the Postoperative Setting: A Secondary Analysis of Mature Phase 1-2 Trials. Int J Radiat Oncol Biol Phys. 2016; 95(5): 1405–1413.
  38. Al-Omair A, Masucci L, Masson-Cote L, et al. Surgical resection of epidural disease improves local control following postoperative spine stereotactic body radiotherapy. Neuro Oncol. 2013; 15(10): 1413–1419.
  39. Gerszten PC, Germanwala A, Burton SA, et al. Combination kyphoplasty and spinal radiosurgery: a new treatment paradigm for pathological fractures. Neurosurg Focus. 2005; 18(3): e8–301.
  40. Laufer I, Iorgulescu JB, Chapman T, et al. Local disease control for spinal metastases following "separation surgery" and adjuvant hypofractionated or high-dose single-fraction stereotactic radiosurgery: outcome analysis in 186 patients. J Neurosurg Spine. 2013; 18(3): 207–214.
  41. Hanna GG, McDonald F, Murray L, et al. UK Consensus on Normal Tissue Dose Constraints for Stereotactic Radiotherapy. Clin Oncol (R Coll Radiol). 2018; 30(1): 5–14.
  42. Pan HY, Allen PK, Wang XS, et al. Incidence and predictive factors of pain flare after spine stereotactic body radiation therapy: secondary analysis of phase 1/2 trials. Int J Radiat Oncol Biol Phys. 2014; 90(4): 870–876.
  43. Chiang A, Zeng L, Zhang L, et al. Pain flare is a common adverse event in steroid-naïve patients after spine stereotactic body radiation therapy: a prospective clinical trial. Int J Radiat Oncol Biol Phys. 2013; 86(4): 638–642.
  44. Khan L, Chiang A, Zhang L, et al. Prophylactic dexamethasone effectively reduces the incidence of pain flare following spine stereotactic body radiotherapy (SBRT): a prospective observational study. Support Care Cancer. 2015; 23(10): 2937–2943.
  45. Sahgal A, Atenafu EG, Chao S, et al. Vertebral compression fracture after spine stereotactic body radiotherapy: a multi-institutional analysis with a focus on radiation dose and the spinal instability neoplastic score. J Clin Oncol. 2013; 31(27): 3426–3431.
  46. Fisher CG, Di Pa, Ryken TC. et al.. A novel classification system for spinal instability in neoplastic disease: an evidence-based approach and expert consensus from the Spine Oncology Study Group. Spine , Philadelphia 2010: E1221–E1229.
  47. Fisher CG, Schouten R, Versteeg AL, et al. Reliability of the Spinal Instability Neoplastic Score (SINS) among radiation oncologists: an assessment of instability secondary to spinal metastases. Radiat Oncol. 2014; 9: 69.
  48. Lee SH, Tatsui CE, Ghia AJ, et al. Can the spinal instability neoplastic score prior to spinal radiosurgery predict compression fractures following stereotactic spinal radiosurgery for metastatic spinal tumor?: a post hoc analysis of prospective phase II single-institution trials. J Neurooncol. 2016; 126(3): 509–517.
  49. Nguyen TK, Sahgal A, Dagan R, et al. Stereotactic Body Radiation Therapy for Nonspine Bone Metastases: International Practice Patterns to Guide Treatment Planning. Pract Radiat Oncol. 2020; 10(6): e452–e460.
  50. Spencer KL, van der Velden JM, Wong E, et al. Systematic Review of the Role of Stereotactic Radiotherapy for Bone Metastases. J Natl Cancer Inst. 2019; 111(10): 1023–1032.