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radiotherapy of bone metastases,Vakalis

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radiotherapy of bone metastases,Vakalis

  1. 1. Ακτινοθεραπεία Ξ. Βακάλης Ακτινοθεραπευτής Ογκολόγος Ιατρικού κέντρου Αθηνών
  2. 2. Disclosures  None
  3. 3. Metastatic Bone Disease Metastasis Sites –Vertebra (69%) – Pelvis (41%) –Femur (25%) –Hip (14%) Malawer, MM and Delaney, TF. Treatment of Metastatic Cancer to the Bone. In: Devita VT, Hellman S, Rosenberg SA (eds). Cancer: Principles and Practice of Oncology. 4th ed. Philadelphia: JB Lippincott; 1993:2225-2245.
  4. 4. Level of Metastases  Thoracic 70%  Lumbar 20%  Cervical 10%
  5. 5. Radiology: How to Evaluate  Imaging tests – X-ray – Bone scan  Sensitive, not specific.  False positives: trauma, arthritis, infection – CT (“CAT” scan) – PET scan – MRI scan  Bone biopsy – for confirmation  Blood tests – Calcium, alkaline phosphatase Bone Scan
  6. 6. Bone Scan A nuclear medicine bone scan would show bone mets as dark areas
  7. 7. PET scans may show the mets very clearly
  8. 8. PET scans can show bone mets that are in hard to see areas like the ribs or scapula
  9. 9. An MRI may show a bone met better than a regular X-ray
  10. 10. MRI imaging T1 T2
  11. 11. Clinical features of bony metastases  Bone pain  Pathological fracture  Nerve compression  Hypercalcaemia
  12. 12. APPROACH  Life expectancy  Biopsy – Histology to predict the response to non operative management  Stability  Clinical presentation – Pain and Neurological status
  13. 13. Treatment of bone metstasis Multi-disciplinary approach  Medical.  Surgical.  Radiotherapy.  Radionuclid.  Chemotherapy & Hormonal Therapy
  14. 14. Radiation Therapy 1. Localized irradiation 2. Hemibody irradiation
  15. 15. How does RT reduce pain ?  Cell kill – reduced tumor size and pressure effects  Endothelial damage of micro-vasculature – reduced blood flow.  Reduces edema  Reduces pain related neuro-transmitter concentrations  Bone – promotes re-mineralisation leading to structural stability.
  16. 16. Indications of Radiotherapy As Primary Treatment 1. Radiosensitive tumor not previously irradiated 2. Widespread spinal metastases with multilevel neural compression 3. Total neurological deficits below the level of compression > 48 hours 4. Patient’s condition (or prognosis) precludes surgery: high surgical risk or short life expectancy Penas-Prado M, Loghin ME. Spinal cord compression in cancer patients: review of diagnosis and treatment. Curr Oncol Rep. 2008 Jan;10(1):78- 85.
  17. 17. Radiotherapy Modalities  Conventional External Beam Radiotherapy (EBRT)  Intensity-modulated radiation therapy (IMRT)  Stereotactic radiotherapy  Stereotactic radiosurgery  Radioisotopes Finn MA, Vrionis FD, Schmidt MH. Spinal radiosurgery for metastatic disease of the spine. Cancer Control. 2007 Oct;14(4):405-11.
  18. 18. Radiation Results •Overall 85% response rate •Complete relief in 54% •50% respond by 2 weeks, 80% by 1 month •Median duration of pain relief 12-15 weeks •The Xrays or scans may take months to show improvement (Recalcification by 2-3 months)
  19. 19. Bone met at L2 Radiation field A typical course of radiation is 10 treatments ( in some cases it is necessary to go slower, 20 to 25)
  20. 20. Palliative xrt - bone metastases treatment planning M. Raphael Pfeffer,Oncology Institute, Chaim Sheba Medical Center  good margins – e.g. add 1-2 vertebrae on each side  include nearby asymptomatic lesions  avoid irradiating entire limb circumference  reduce irradiated volume of bowel/bladder  bone marrow toxicity
  21. 21. Fractionation regimens  8 Gy in 1 fraction  20 Gy in 5 fractions  24 Gy in 6 fractions  30 Gy in 10 fractions  Endpoints using pain relief, narcotic relief and quality of life measures show consistent similarity in the regimens
  22. 22. Single Vs Multi-Fraction
  23. 23. SYSTEMATIC REVIEW
  24. 24. Single fraction v multifraction more convenient less costly shorter time with acute side effects fear of high doses per fraction higher retreatment rate( 2-2,5 times higher) concern about toxicity in long-term survivors flare of bone pain maybe be higher
  25. 25. Single fraction v multifraction caution  Problematic retreatment  Previous treatment to the spine  Femoral axial cortical involvment > 3 cm  Surgical stabilization procedure  Spinal cord compression or radicular nerve pain
  26. 26. Re-irradiation Not covering the spinal cord – 1 x 8 Gy or 5 x 4Gy(Grade C) Covering the spinal cord – 8 x 2,5 Gy (Grade D)
  27. 27. Adjuvant Radiotherapy  Done after operative decompression  Patchell et al study  Wait 3 weeks for wound healing before starting radiation
  28. 28. Post-operative  Patient received 30Gy/10fx
  29. 29. Radiopharmaceuticals  Use of Radiopharmaceuticals does not obviate the need for EBRT.  Ideal for osteoblastic, multi-focal and wide-spread disease.
  30. 30. Hemi-body Irradiation  For multiple lesions, when facilities for radionuclide therapy is un-available.  More suited for lower hemibody than upper.  Ideally treated using 6MV photons or higher  Keep lung dose to < 6 Gy for upper HBI
  31. 31. Palliative xrt -single fraction half body iradiation  lower half body 8 Gy  upper half body 6 Gy  good short term palliation (~3 months)  onset of pain relief – Half Body xrt 50% @ 3 days, 100% @ 14 days – Focal XRT 50% @ 7 days, 80% @ 14 days Salazar Cancer 1986 M. Raphael Pfeffer,Oncology Institute, Chaim Sheba Medical Center
  32. 32. Bisphosphonates and RT  “Bisphosphonates and RT can be given concurrently.”  Synergistic effect – Zoledronic acid pauses the cells in G2M phase.  Use of Bisphosphonates does not obviate the need for RT.
  33. 33. IMRT, STEREOTACTIC RADIOSURGERY AND STEREOTACTIC RADIOTHERAPY – Deliver high doses safely – Possible to irradiate spine without affecting spinal cord *De Salles AA, Pedroso AG, Medin P, Agazaryan N, Solberg T, Cabatan-Awang C, et al: Spinal lesions treated with Novalis shaped beam intensity-modulated radiosurgery and stereotactic radiotherapy. J Neurosurg 101 (3 Suppl):435–440, 2004
  34. 34. Metastatic Spinal Cord Compression (MSCC)
  35. 35. Spinal Cord Syndrome
  36. 36. Epidemiology  40% of all cancer patients will develop metastatic spinal disease – 10-20% of these patients will develop spinal cord compression White AP, Kwon BK, Lindskog DM, Friedlaender GE, Grauer JN. Metastatic disease of the spine. J Am Acad Orthop Surg. 2006 Oct;14(11):587-98.
  37. 37. Signs & Symptoms Presents with as: Collapsed vertebral body Soft tissue mass in the spinal canal Symptoms  Increasing & unexplained pain in neck or spine  Any numbness/ weakness in arms or legs  Difficulty in walking and balancing  Problems with controlling & emptying bladder or bowels  Any muscle loss or lack of tendon reflex
  38. 38. Location
  39. 39. What happens to the patient in hospital? – they should start dexamethasone 16mg od if not already on it – urgent MRI scan of spine – if proven, urgent radiotherapy to cord compression area It is an oncologic emergency
  40. 40. Success rates of SCC treatment with Radiotherapy – depends on level of neurological function at presentation to radiotherapist – if patient is ambulatory – 70% retain ability to walk – if patient is paraparetic – 35% retain ability to walk – if patient is paraplegic – 5% retain ability to walk
  41. 41. Epidural Metastases and Spinal Cord Compression  < 24 hours of immobility - urgent treatment - 300 cGy x 10 fractions; although shorter courses can be used if needed (e.g. 400 cGy x 5) (Grade C).  Established paraplegia > 24 hours – radiotherapy is indicated for pain relief – single dose of 8 Gy (Grade C).
  42. 42. Multidisciplinary Care NOMS1,2  Neurologic  Oncologic  Mechanical Stability  Systemic disease  Systemic Therapy  Radiation Therapy  Surgery vs. 1Bilsky MH, Smith M. Surgical approach to epidural spinal cord compression. Hematology/Oncology Clinics of North America.;20(6):1307-1317, 2006 2Bilsky MH, Azeem S. The NOMS framework for decision making in metastatic cervical spine tumors. Current Opinions in Orthopedics 2007;18(3):263-269.
  43. 43. The role of surgery  Indicated if:  previous Radio Rx/ no response  Radioresistant tumor  life expectancy > three months  single site  unstable spine  no tissue diagnosis
  44. 44. The role of surgery + RT  RCT comparing surgery followed by RT vs. RT alone  Improvement in surgery + RT – Able to walk: 84% vs 57% – Median time able to walk: 122 vs 13 days – Continent: 156 vs 17 days – Regained ability to walk: (n= 32) 62% vs 19% – Survival: 126 vs 100 days Patchell, R, Tibbs, PA, Regine, WF, et al. A randomized trial of direct decompressive surgical resection in the treatment of spinal cord compression caused by metastasis (abstract). proc Am Soc Clin Oncol 2003; 22:1.
  45. 45. A meta-analysis of surgery versus conventional radiotherapy for the treatment of metastatic spinal epidural disease Neuro Oncol 2005 Jan. Klimo et al. Department of Neurosurgery, University of Utah, Salt Lake City, USA surgery 999 patients: radiation 543 patients surgical patients were 1.3 times more likely to be ambulatory after treatment and twice as likely to regain ambulatory function overall ambulatory success rates for surgery and radiation were 85% and 64% surgery should usually be the primary treatment with radiation given as adjuvant therapy
  46. 46. PostOp major wound complications (dehiscence or wound infection) 32% in the group that underwent radiotherapy before surgery 12% in the group of patients first treated by surgery.
  47. 47. Radiation field  Portal 8 cm wide  Centered on spine  Extends one to two vertebral bodies above and below the epidural metastasis
  48. 48. 3D
  49. 49. permits high dose delivery precisely to the target while minimizing exposure to normal tissues
  50. 50. permits high dose delivery precisely to the target while minimizing exposure to normal tissues
  51. 51. Radiosurgery Recommendations A strong recommendation can be made with low-quality evidence that radiosurgery should be considered over conventional fractionated radiotherapy for the treatment of solid tumor spine metastases in the setting of oligometastatic disease and/or radioresistant histology in which no relative contraindications exist. Gerszten PC, Mendel E, Yamada Y. Radiotherapy and radiosurgery for metastatic spine disease: What are the options, indications, and outcomes. Spine 34(22S):S78-92, 2009
  52. 52. Radiosurgery
  53. 53. Results of Radiosurgery Pain relief in 85 – 100% Improvement of neurologic symptoms in 75 – 92%
  54. 54. Cyberknife
  55. 55. CyberKnife frameless stereotactic radiosurgery for spinal lesions: clinical experience in 125 cases. Neurosurgery. 2004 Jul;55(1):89-98; 125 spinal lesions in 115 consecutive patients were treated with a single-fraction radiosurgery technique No acute radiation toxicity or new neurological deficits occurred and Axial and radicular pain improved in 74 of 79 (94%) patients who were symptomatic before treatment.
  56. 56. Combination kyphoplasty and spinal radiosurgery: a new treatment paradigm for pathological fractures. Gerszten. Neurosurg Focus 2005 Mar 15;18(3):e8. CyberKnife radiosurgery underwent single-fraction radiosurgery (at a mean of 12 days after kyphoplasty) in an outpatient setting. Axial pain improved in 24 (92%) of 26 patients during the follow-up period of 7 to 20 months.

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