1. Ακτινοθεραπεία
Ξ. Βακάλης
Ακτινοθεραπευτής Ογκολόγος
Ιατρικού κέντρου Αθηνών

2. Disclosures
 None

4. 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.

5. Level of Metastases
 Thoracic 70%
 Lumbar 20%
 Cervical 10%

6. 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

7. Bone Scan
A nuclear medicine
bone scan would
show bone mets as
dark areas

8. PET scans may show the mets
very clearly

9. PET scans can
show bone
mets that are
in hard to see
areas like the
ribs or scapula

10. An MRI may show a bone met
better than a regular X-ray

11. MRI imaging
T1 T2

12. Clinical features of bony metastases
 Bone pain
 Pathological fracture
 Nerve compression
 Hypercalcaemia

13. APPROACH
 Life expectancy
 Biopsy – Histology to predict the response
to non operative management
 Stability
 Clinical presentation – Pain and Neurological
status

14. Treatment of bone metstasis
Multi-disciplinary approach
 Medical.
 Surgical.
 Radiotherapy.
 Radionuclid.
 Chemotherapy & Hormonal Therapy

15. Radiation Therapy
1. Localized irradiation
2. Hemibody irradiation

16. 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.

17. 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.

18. 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.

19. 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)

20. 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)

22. 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

24. 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

25. Single Vs Multi-Fraction

26. SYSTEMATIC REVIEW

28. 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

31. 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

32. 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)

33. Adjuvant Radiotherapy
 Done after operative decompression
 Patchell et al study
 Wait 3 weeks for wound healing before
starting radiation

34. Post-operative
 Patient received
30Gy/10fx

35. Radiopharmaceuticals
 Use of Radiopharmaceuticals does not obviate
the need for EBRT.
 Ideal for osteoblastic, multi-focal and wide-spread
disease.

37. 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

38. 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

40. 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.

41. 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

43. Metastatic Spinal Cord Compression (MSCC)

44. Spinal Cord Syndrome

45. 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.

46. 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

47. Location

48. 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

49. 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

50. 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).

51. 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.

52. The role of surgery
 Indicated if:
 previous Radio Rx/ no response
 Radioresistant tumor
 life expectancy > three months
 single site
 unstable spine
 no tissue diagnosis

53. 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.

55. 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

56. 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.

57. Radiation field
 Portal 8 cm wide
 Centered on spine
 Extends one to two vertebral bodies above and
below the epidural metastasis

58. 3D

62. permits high dose delivery precisely to the target
while minimizing exposure to normal tissues

63. permits high dose delivery precisely to the target
while minimizing exposure to normal tissues

64. 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

66. Radiosurgery

69. Results of Radiosurgery
Pain relief in 85 – 100%
Improvement of neurologic symptoms in 75 – 92%

72. Cyberknife

73. 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.

75. 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.