palliation

1. Palliation of Bone Metastases
Dr. Ali Azher, MD
Radiation Oncology
The Gujarat Cancer & Research Institute
BJ Medical College, Ahmedabad, Gujarat
aliazhermuhammed@gmail.com

2. Introduction
• Common cause of pain
• Detrimental to quality of life
• Incidence of Bone mets
– Breast & Prostate – 70%
– Lung
– Thyroid, melanoma, kidney
– GI primary sites – only 3-15%
– Hematologic malignancies like myeloma &
lymphoma

3. • Poor prognosis
– In months rather than years
– Bone Mets from Lung cancer 6 months

4. Sites of Mets
• Axial skeleton
– Most common site
– Frequently occuring in spine, pelvis & ribs
– Lumbar spine is the most frequent site
• Appendicular skeleton
– Proximal femurs are the most common site
– Humeral lesions also occur
• Acral sites (feets & hands)
– Rarely involved

6. • Scapular mets – more frequently from renal
primaries
• Skull involvement is more frequent in breast
• Tibia, fibula, acral sites – lung
• Toes – genitourinary primaries

7. Symptoms
• Slowly progressive insidious pain
• Fairly well localized pain
• Pain worse at night
• Pain from femur/acetabulum worsen with
ambulation or weight bearing
• pain from inferior ischium/sacrum – worse
with sitting
• May radiate to other areas

8. Pathology
• Metastases most often occur in red marrow
• Red marrow is highest concentration in
skull/axial skeleton
• Hematogenous spread
• Direct extension (mandibular involvement by
oral cavity cancers)

9. Types
• Osteolytic
– Myeloma
• Osteolytic appearing
– Breast & Lung
• Osteoblastic
– Prostate & Thyroid

10. Evaluation
• History & Physical Examination
• Firm palpation & point tenderness
• Evaluation of entire skeletal system
• CNS examination
• Plain radiograph
• Tc-99m bone scintigraphy
– Screening patients at risk
– Indicator of osteoblastic activity

11. • CT scan
– Not useful for screening
– Defining the extent of cortical destruction & risk
of pathological fracture
• MRI
– Better to assess bone marrow involvement
– Involvement of neurovascular structures
– More sensitive (91-100%) in vertebral body region

12. • PET
– Useful in highly metabolic osteolytic bone mets
– Limitation in skull area where intense physiologic
uptake may obscure small skull mets

13. Management
• Medications
• Radiation
• Radiopharmaceuticals
• Surgical

14. Medication
• Pain Scale
• WHO Analgesic ladder

15. Radiation
• Effective in painful mets

16. RTOG 74-02
• Patients with solitary bone mets
– 40.5Gy/15# vs 20Gy/5#
• Patients with multiple painful mets
– 30Gy/10#
– 15Gy/5#
– 20Gy/5#
– 25Gy/5#

17. Conclusion
• Higher dose for optimal palliation
• 40.5Gy for solitary
• 30Gy for multiple

18. Single dose Vs Longer course
• Dutch trial
• Patients with breast/prostate/lung cancers
• 8Gy in single fraction
• 24Gy in 6 #
• Spine & pelvis common sites of treatment
• No difference in overall response

19. • Two significant differences
– Pathological fracture
– Retreatment rates
• Higher likelihood of retreatment in single
treatment group
Arm Pathological fracture Retreatment rates
8Gy 4% 25%
24Gy 2% 7%

20. • RTOG 9714
– Patients with painful mets from breast or prostate
– 8Gy in single #
– 30Gy/10#
– No significant difference in response
– No difference in rate of pathological fractures
– Rate of retreatment higher in 8Gy arm

21. Conclusions
• Single-dose treatments of 8 Gy provide similar pain
relief to longer treatment regimens
• The retreatment rates are higher after short-course
treatment
• Response rates are lower when scored by the patient
instead of by the treating physician.
• Response rates are better when the initial pain scores
are lower, that is, when the patients are treated for
moderate pain rather than severe pain.
• There is no consistent dose–response relationship for
palliation of bone metastases.

22. • 8Gy
– Poor PS
– Difficulty in ambulation
– Extensive nonosseous
mets
– Short life expectancy <
3months
– Less expensive
• 30Gy/10#
– Good PS
– Bone only mets
– Longer life expectancy
– To minimize the risk of
retreatment
Single large fraction may cause flare
reaction (temporary increase in pain)
Managed with steroids / anti
inflammatory medications

23. Bisphosphonates
• May improve the outcome in terms of both
pain and bone healing
• Monthly ibadronate

24. Multiple osseous metastases
• Wide spread disease
• Two techniques
– Hemibody irradiation
– Intravenous radiopharmaceuticals

25. Hemi Body Irradiation
• Wide field radiation
• Used to treat large portion of the body
• Typically the field does not cover half of the
body
• More accurately treats about one third of the
body

26. • Treatment volumes
– Upper HBI
• Thorax & abdomen
• From the neck to top of iliac crests
– Mid body HBI
• Abdomen & Pelvis
• From the diaphragm to ischial tuberosities
– Lower HBI
• Top of the pelvis to inferior portion of femur

27. • Doses
– Maximum tolerated dose (MTD)
• Middle & lower – 8Gy
• Upper – 6Gy
The risk of radiation pneumonitis with upper HBI
This is the dose limiting toxicity of upper HBI

28. • IAEA study
– 3 Gy twice daily for 2 days (12 Gy total) or 3 Gy
daily for 5 days (15 Gy total) was more effective
than 4 Gy daily for 2 days

29. • Premedications
– dexamethasone, 8 to 16 mg, and ondansetron, 8
to 16 mg, 1 hour before treatment with HBI

30. Radiopharmaceuticals
• Calcium analogs will preferentially accumulate
in bone, especially in areas of active bone
turnover
• A radioactive isotope that is a β-emitter or
low-energy γ-source will allow localized
treatment in the areas minimizing side effects
and giving an excellent therapeutic ratio.
• The radiopharmaceuticals are given in a single
injection that is easily administered.

31. • The first radiopharmaceutical used for
treatment of bone metastases was
phosphorous-32 (P-32).
• Unacceptable bone marrow toxicity.
Strontium-89 (Sr-89) pure β-emitter with an
energy of 1.4 MeV and a half-life of 50.6 days.
• Samarium-153 (Sm-153) is primarily a β-
emitter but also has a component of gamma
emission, which is useful for imaging
purposes.

32. • The Sm-153 ethylenediamine tetra-
methylenephosphonic acid (EDTMP) is
concentrated in areas of high bone turnover
• physical half-life of Sr-153 is 46.3 hours, but
the biologic half-life is much shorter because
about half of the compound is excreted in the
urine within 8 hours of injection.

33. • Newer isotopes
– rhenium-186
– rhenium-188
– tin-117m.
– All of these isotopes accumulate in areas of
osteoblastic activity

34. Study of Sr-89
• Sr-89 versus placebo in 126 men with metastatic
prostate cancer
• The patients were randomized after involved-field
radiation therapy in a double-blind fashion to 400
MBq of Sr-89 versus placebo.
• No statistically significant difference in the primary
end point of pain relief
• There were several secondary end points that were
improved with the Sr-89.
• More patients were able to discontinue pain
medications (17% vs. 2%)

35. • Sr-89 versus EBRT
• Patients were randomized to Sr-89 200 MBq
versus HBI of 8 Gy to the lower hemibody or 6
Gy to the upper hemibody.
• There was no difference in pain relief, toxicity,
or median survival between the groups.

36. Samarium-153
• It is chelated with ethylenediamine tetra-
methylenephosphonic acid to form Sm-153
EDTMP, a compound that is preferentially
taken up in newly formed bone.
• The unbound remainder of the drug is rapidly
cleared via urinary excretion.
• 1.0-mCi/kg dose gave significant improvement
in pain relief

37. • Transient marrow suppression was seen, with
a nadir at 4 to 6 weeks and recovery by 8
weeks; this primarily manifested as grade ≥3
neutropenia

38. Radium-223
• It emits alpha particles and selectivity targets
bone metastases.
• Radium-223 is the only bone-directed
radionuclide, which has shown improvement
not only in pain and quality of life but also in
overall survival.

39. Patient Selection
• Primarily for metastases that have an
osteoblastic component.
• If a Tc-99m nuclear medicine bone scan shows
localized areas of increased uptake, then
radiopharmaceutical treatment is likely to be
of benefit.
• An advantage of radioisotope treatment is
that it can be combined with other modalities,
such as external-beam radiation therapy or
chemotherapy.

40. • Because the targets of treatment are similar,
treatment with bisphosphonates should not
be given simultaneously with radioisotopes
because this may reduce the efficacy of both
medications.