Relative Radiosensitivity of Metastatic Spine Disease

  • Waqar Haque
  • Bin S. TehEmail author


Up to 10% of all cancer patients developed metastatic disease in the bone. The purpose of the present report is to describe the radiosensitivity of metastatic disease to the spine. Tumor histology is the primary method that physicians use to determine radiation sensitivity. The most radiosensitive histologies include seminoma, myeloma, and lymphoma, while radioresistant histologies include melanoma, renal cell carcinoma, and sarcoma. The radiosensitivity of the cancer can guide management of patients with spinal metastatic disease, as conventionally fractionated radiation therapy may suffice for radiosensitive tumors. Higher, ablative doses can be delivered to radioresistant tumors using a specialized radiation technique called stereotactic body radiation therapy (SBRT) to overcome radioresistance. SBRT is able to overcome radioresistance by delivering a higher biologically effective dose to tumors while sparing surrounding normal tissue.


External beam radiation therapy Stereotactic body radiation therapy Bone metastases Biologically effective dose Radiation sensitivity 


  1. 1.
    Fornasier VL, Horne JG. Metastases to the vertebral column. Cancer. 1975;36:590–4.CrossRefPubMedGoogle Scholar
  2. 2.
    Grant R, Papadopoulos SM, Greenberg HS. Metastatic epidural spinal cord compression. Neurol Clin. 1991;9:825–41.PubMedCrossRefGoogle Scholar
  3. 3.
    Hatrick NC, Lucas JD, Timothy AR, et al. The surgical treatment of metastatic disease of the spine. Radiother Oncol. 2000;56:335–9.CrossRefPubMedGoogle Scholar
  4. 4.
    Laufer I, Rubin DG, Lis E, et al. The NOMS framework: approach to the treatment of spinal metastatic tumors. Oncologist. 2013;18:744–51.CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Johns HE, Cunningham JR. The physics of radiology. Springfield: Charles C Thomas; 1969.Google Scholar
  6. 6.
    Carrano AV. Chromosome aberrations and radiation-induced cell death: II. Predicted and observed cell survival. Mutat Res. 1973;17:355–66.CrossRefPubMedGoogle Scholar
  7. 7.
    Cornforth MN, Bedford JS. A quantitative comparison of potentially lethal damage repair and the rejoining of interphase chromosome breaks in low passage normal human fibroblasts. Radiat Res. 1987;111:385–405.CrossRefPubMedGoogle Scholar
  8. 8.
    Williams GT. Programmed cell death: apoptosis and oncogenesis. Cell. 1991;65:1097–8.CrossRefPubMedGoogle Scholar
  9. 9.
    Sinclair WK, Morton RA. X-ray sensitivity during the cell generation cycle of cultured Chinese hamster cells. Radiat Res. 1966;29:450–74.CrossRefPubMedGoogle Scholar
  10. 10.
    Hammond EM, Pires I, Giacca AJ. Chapter 2: DNA damage and repair. In: Libel S, Phillips TL, Hoppe RT, Roach M, editors. Textbook of radiation oncology. Philadelphia: Elsevier; 2010.Google Scholar
  11. 11.
    Hall EJ, Giaccia AJ. Radiobiology for the radiobiologist. 7th ed. Philadelphia: Lippincott Williams and Wilkins; 2012.Google Scholar
  12. 12.
    Tubiana M. Repopulation in human tumors. A biological background for fractionation in radiotherapy. Acta Oncol. 1988;27:83–8.CrossRefPubMedGoogle Scholar
  13. 13.
    Gray LH, Conger AD, Ebert M, Hornsey S, Scott OC. The concentration of oxygen dissolved in tissues at the time of irradiation as a factor in radiotherapy. Br J Radiol. 1953;26:638–48.CrossRefPubMedGoogle Scholar
  14. 14.
    Thomlinson RH, Gray LH. The histological structure of some human lung cancers and the possible implications for radiotherapy. Br J Cancer. 1955;9:539–49.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Gerweck LE, Vijayappa S, Kurimasa A, Ogawa K, Chen DJ. Tumor cell radiosensitivity is a major determinant of tumor response to radiation. Cancer Res. 2006;66:8352–5.CrossRefPubMedGoogle Scholar
  16. 16.
    Eschwege F, Bourhis J, Girinski T, et al. Predictive assays of radiation response in patients with head and neck squamous cell carcinoma: a review of the Institute Gustave Roussy experience. Int J Radiat Oncol Biol Phys. 1997;39:849–53.CrossRefPubMedGoogle Scholar
  17. 17.
    Bourhis J, Dendale R, Hill C, et al. Potential doubling time and clinical outcome in head and neck squamous cell carcinoma treated with 70 Gy in 7 weeks. Int J Radiat Oncol Biol Phys. 1996;35:471–6.CrossRefPubMedGoogle Scholar
  18. 18.
    Höckel M, Vorndran B, Schlenger K, Baussmann E, Knapstein PG. Tumor oxygenation: a new predictive parameter in locally advanced cancer of the uterine cervix. Gynecol Oncol. 1993;51:141–9.CrossRefPubMedGoogle Scholar
  19. 19.
    Brizel DM, Dodge RK, Clough RW, Dewhirst MW. Oxygenation of head and neck cancer: changes during radiotherapy and impact on treatment outcome. Radiother Oncol. 1999;53:113–7.CrossRefPubMedGoogle Scholar
  20. 20.
    Brahme A. Biologically optimized 3-dimensional in vivo predictive assay-based radiation therapy using positron emission tomography–computerized tomography imaging. Acta Oncol. 2003;42:123–36.CrossRefPubMedGoogle Scholar
  21. 21.
    Smith L, Qutob O, Watson MB, et al. Proteomic identification of putative biomarkers of radiotherapy resistance: a possible role for the 26S proteasome? Neoplasia. 2009;11(11):1194–207.CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Allal AS, Kähne T, Reverdin AK, et al. Radioresistance-related proteins in rectal cancer. Proteomics. 2004;4:2261–9.CrossRefPubMedGoogle Scholar
  23. 23.
    Skvortsova I, Skvortsov S, Stasyk T, et al. Intracellular signaling pathways regulating radioresistance of human prostate carcinoma cells. Proteomics. 2008;8:4521–33.CrossRefPubMedGoogle Scholar
  24. 24.
    Ramsamooj P, Kasid U, Dritschilo A. Differential expression of proteins in radioresistant and radiosensitive human squamous carcinoma cells. J Natl Cancer Inst. 1992;84:622–8.CrossRefPubMedGoogle Scholar
  25. 25.
    Chen X, Xu Y, Liao X, et al. Plasma miRNAs in predicting radiosensitivity in non-small cell lung cancer. Tumour Biol. 2016;37:11927–36.CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Rofstad EK. Radiation sensitivity in vitro of primary tumors and metastatic lesions of malignant melanoma. Cancer Res. 1992;52:4453–7.PubMedGoogle Scholar
  27. 27.
    Gerszten PC, Mendel E, Yamada Y. Radiotherapy and radiosurgery for metastatic spine disease: what are the options, indications, and outcomes? Spine. 2009;34:S78–92.CrossRefPubMedGoogle Scholar
  28. 28.
    Kyndi M, Sørensen FB, Knudsen H, et al. Estrogen receptor, progesterone receptor, HER-2, and response to postmastectomy radiotherapy in high-risk breast cancer: the Danish Breast Cancer Cooperative Group. J Clin Oncol. 2008;26:1419–26.CrossRefPubMedGoogle Scholar
  29. 29.
    Nguyen PL, Taghian AG, Katz MS, et al. Breast cancer subtype approximated by estrogen receptor, progesterone receptor, and HER-2 is associated with local and distant recurrence after breast-conserving therapy. J Clin Oncol. 2008;26:2373–8.CrossRefPubMedGoogle Scholar
  30. 30.
    Maranzano E, Latini P. Effectiveness of radiation therapy without surgery in metastatic spinal cord compression: final results from a prospective trial. Int J Radiat Oncol Biol Phys. 1995;32:959–67.CrossRefPubMedGoogle Scholar
  31. 31.
    Katagiri H, Takahashi M, Inagaki J, et al. Clinical results of nonsurgical treatment for spinal metastases. Int J Radiat Oncol Biol Phys. 1998;42:1127–32.CrossRefPubMedGoogle Scholar
  32. 32.
    Gilbert RW, Kim JH, Posner JB. Epidural spinal cord compression from metastatic tumor: diagnosis and treatment. Ann Neurol. 1978;3:40–51.CrossRefPubMedGoogle Scholar
  33. 33.
    Rades D, Fehlauer F, Schulte R, et al. Prognostic factors for local control and survival after radiotherapy of metastatic spinal cord compression. J Clin Oncol. 2006;24:3388–93.CrossRefPubMedGoogle Scholar
  34. 34.
    Steenland E, Leer JW, van Houwelingen H, et al. The effect of a single fraction compared to multiple fractions on painful bone metastases: a global analysis of the Dutch Bone Metastasis Study. Radiother Oncol. 1999;52:101–9.CrossRefPubMedGoogle Scholar
  35. 35.
    Hartsell WF, Scott CB, Bruner DW, et al. Randomized trial of short- versus long-course radiotherapy for palliation of painful bone metastases. J Natl Cancer Inst. 2005;97:798–804.CrossRefPubMedGoogle Scholar
  36. 36.
    Lutz S, Berk L, Chang E, et al. Palliative radiotherapy for bone metastases: an ASTRO evidence-based guideline. Int J Radiat Oncol Biol Phys. 2011;79:965–76.CrossRefPubMedGoogle Scholar
  37. 37.
    Sahgal A, Roberge D, Schellenberg D, et al. The Canadian Association of Radiation Oncology scope of practice guidelines for lung, liver and spine stereotactic body radiotherapy. Clin Oncol (R Coll Radiol). 2012;24:629–39.CrossRefGoogle Scholar
  38. 38.
    Brown PD, Brown CA, Pollock BE, Gorman DA, Foote RL. Stereotactic radiosurgery for patients with “radioresistant” brain metastases. Neurosurgery. 2002;51:656–65.PubMedGoogle Scholar
  39. 39.
    Yaeh A, Nanda T, Jani A, et al. Control of brain metastases from radioresistant tumors treated by stereotactic radiosurgery. J Neurooncol. 2015;124:507–14.CrossRefPubMedGoogle Scholar
  40. 40.
    Teh BS, Bloch C, Paulino AC, et al. Pathologic complete response in renal cell carcinoma brain metastases treated with stereotactic radiosurgery. Clin Genitourin Cancer. 2007;5:334–7.CrossRefPubMedGoogle Scholar
  41. 41.
    Gerszten PC, Burton SA, Ozhasoglu C, et al. Radiosurgery for spinal metastases: clinical experience in 500 cases from a single institution. Spine. 2007;32:193–9.CrossRefPubMedGoogle Scholar
  42. 42.
    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;71:484–90.CrossRefPubMedGoogle Scholar
  43. 43.
    Yamada Y, Cox B, Zelefsky MJ, et al. An analysis of prognostic factors for local control of malignant spine tumors treated with spine radiosurgery. Int J Radiat Oncol Biol Phys. 2011;81:S132–3.CrossRefGoogle Scholar
  44. 44.
    Redmond KJ, Lo SS, Soltys SG, et al. Consensus guidelines for postoperative stereotactic body radiation therapy for spinal metastases: results of an international survey. J Neurosurg Spine. 2017;26(3):299–306.CrossRefPubMedGoogle Scholar
  45. 45.
    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. 2014;18:207–14.CrossRefGoogle Scholar
  46. 46.
    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;15:1413–9.CrossRefPubMedPubMedCentralGoogle Scholar
  47. 47.
    Yang Z, Yang Y, Zhang Y, et al. Minimal access versus open spinal surgery in treating painful spine metastasis: a systematic review. World J Surg Oncol. 2015;13:68.CrossRefPubMedPubMedCentralGoogle Scholar
  48. 48.
    Ryu S, Pugh SL, Gerszten PC, et al. RTOG 0631 phase 2/3 study of image guided stereotactic radiosurgery for localized (1-3) spinal metastases: phase 2 results. Pract Radiat Oncol. 2014;4:76–81.CrossRefPubMedGoogle Scholar
  49. 49.
    Zuckerman SL, Laufer I, Sahgal A, et al. When less is more: the indications for MIS techniques and separation surgery in metastatic spine disease. Spine (Phila Pa 1976). 2016;41:S246–53.CrossRefGoogle Scholar
  50. 50.
    Ryu S, Rock J, Jain R, et al. Radiosurgical decompression of metastatic epidural compression. Cancer. 2010;116:2250–7.PubMedGoogle Scholar
  51. 51.
    Ryu S, Yoon H, Stessin A, et al. Contemporary treatment with radiosurgery for spinal metastasis and spinal cord compression in 2015. Radiat Oncol J. 2015;33:1–11.CrossRefPubMedPubMedCentralGoogle Scholar
  52. 52.
    Fowler JF. A review: the linear quadratic formula and progress in fractionated radiotherapy. Br J Radiol. 1989;62:679–5.CrossRefPubMedGoogle Scholar
  53. 53.
    Rofstad EK. Radiation biology of malignant melanoma. Review article. Acta Radiol Oncol. 1986;25:1–10.CrossRefPubMedGoogle Scholar
  54. 54.
    Brown JM, Carlson DJ, Brenner DJ. The tumor radiobiology of SRS and SBRT: are more than the 5 R’s involved? Int J Radiat Oncol Biol Phys. 2014;88:254–62.CrossRefPubMedPubMedCentralGoogle Scholar
  55. 55.
    Miller JA, Balagamwala EH, Angelov L, et al. Spine stereotactic radiosurgery with concurrent tyrosine kinase inhibitors for metastatic renal cell carcinoma. J Neurosurg Spine. 2016;25:766–74.CrossRefPubMedGoogle Scholar
  56. 56.
    Kroeze SGC, Fritz C, Hoyer M, et al. Toxicity of concurrent stereotactic radiotherapy and targeted therapy or immunotherapy: a systematic review. Cancer Treat Rev. 2017;53:25–37.CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Radiation Oncology DepartmentHouston Methodist HospitalHoustonUSA

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