Bone Pain Palliation

~., .
Metastatic Bone Disease
W Primary tumor
Breast
Prostate
Lung
Thyroid
W Primary sites
Vertebra (69%)
Pelvis (41%)
Femur (25%)
Skull (14%)
Mechanism of Metastasis
W Primary tumor growth allows for expansion of tumor beyond confines of cell
W ells or groups of cells detach from primary site
W ells are transported by way of hematologic or lymphatic channels (bone
metastasis spread by hematologic mechanism)
W Tumor cells withstand human defense mechanisms within circulatory system
Metastatic Bone Disease:
Signs and Symptoms
W Localized Pain
W initially intermittent
W unrelated to activity
W eventually continuous
and unrelenting
W ost no pain
W detected only by
radiography or bone
scintigraphy
W found secondary to
pathologic fracture
%herapeutic Options
W xternal Beam
Radiation Therapy
W Spot therapy
W Partial Body therapy: good therapy option if single
metastasis occur - 80% of patients will have pain relief
W alleviation of pain relief usually unmasks pain in another
area
W Side effects: myelosupression (limits usefulness); partial
body radiation - damage to whole organ systems (G,
Lung, Bone arrow)
%herapeutic Options
W Surgery
W prosthetic placement
W internal fixation devices (screws)
W polymethylmethacrylate (P)
W provides stability and relieves pain
W promotes ambulation
W usually is associated with radiation therapy to further inhibit
tumor growth and to decrease risk of further fracture
%herapeutic Options
W ormonal Therapy
strogen nti-androgens
nti-strogen astration
Used in patients with Breast or Prostate ancer
W hemotherapy
20-80% response rate - sustained for months
Single or combination therapy
Toxicity high
%herapeutic Options
W Biphosphonates
W tidronate (Didronel
R
)
W Pamidronate (redia
R
)
W nhibits bone resorption - helps to build up osteoid layer in bone
W Shown to delay onset of "skeletal complications when used in
patients with metastatic disease
NaO P P ONa
O O
O O
O
N
2
Pamidronate
NaO P P ONa
O O
O O
O
e
tidronate
%herapeutic Options
W Pain edication
W Non-narcotic: NSDS, PP, S for mild pain
W eak opioids: PP + codeine for mild to moderate pain
W Strong opioids: orphine, Oxycodone for severe pain
W Tricyclic antidepressants, steroids, and other adjuvant
agents can be used
!ain Medications
W only 10-50% of patients will achieve adequate
relief from pain with pharmacologic intervention
W patients have risk of addiction and overdosage
W scheduled dosing essential - prn dosing is for
breakthrough pain only
W changes in disease state influence drug selection
!ain Medications
W MiId to Moderate !ain (1-3): Non-opioids are the first choice of
treatment for mild to moderate pain. This includes medication
such as acetaminophen (Tylenol) or a non-steriodal anti-
inflammatory drug, such as ibuprofen.
W Moderate to Severe !ain (4-6) Patients with moderate to severe
pain who have not responded to the first step should receive an
opioid. These medications may include codeine, hydrocodone,
dilhydrocodiene, oxycodone, propoxyphene, and tramadol.
cetaminophen or a nonsteriodal may be added.
W Severe !ain (7-10) Patients with severe pain or patients whose
pain has not been relieved by the previous recommendations will
usually receive a stronger opioid. Opioids for severe pain may
include morphine, oxycodone, hydromorphone, methadone,
levophanol, or fentanyl. non-opioid medication such as aspirin,
acetaminophen, or ibuprofen may be added in some cases.
Nuclide HalI-liIe Energy Maximum Gammma SpeciIic
(days) (MeV) Range (mm) (keV) Activity

90
Y 2.66 2.27 12.0 ---- high
149
Pm 2.21 1.07 5.0 286 (3) low/medium
153
Sm 1.95 0.80 3.0 103 (28) low/medium
166
Ho 1.1 1.6 8.0 81 (6.3) high
177
Lu 6.7 0.497 1.5 208 (28) medium/high
186
Re 3.7 1.02 5.0 137 (9) reactor
188
Re 0.71 2.12 11.0 155 (15) reactor/generator
212
Bi 1.0 h 7.8 (-) 70 3m 2.25 (.
-
, 64) generator
#adionucIides for %herapy
Radiopharmaceuticals for Radiopharmaceuticals for
Bone Pain Treatment Bone Pain Treatment
Metastatic Bone Disease
IdeaI #adiopharmaceuticaI
W Symptomatically treat patient pain
W Therapeutic "cure for metastatic cancer
W Rapid extraction from circulation
W Slow if any turnover from diseased site
W Rapid excretion of any unbound drug
W Uptake in hydroxyapatite crystal only, not
throughout entire tissue (bone marrow)
Metastatic Bone Disease
IdeaI #adiopharmaceuticaI
W ost radiation deposited in diseased area
with little radiation to other tissues
W Physical half-life allowing delivery of large
amounts of radiation in short period of time
(ideally - short T
1/2
physical)
W Biologic half-life allowing deposition of a
large dose of radiation in the desired area
(ideally - long T
1/2
biologic)
Metastatic Bone Disease
IdeaI #adiopharmaceuticaI
conomical
Readily available
hemically stable
mageable gamma emission
UNFORTUNTLY, T DL
RDOPRUTL DOS NOT ST!!
pproved
#adiopharmaceuticaIs
W Sr-89
W T1/2: 50.5 days
W Dose: 4 mi (148 Bq)
W missions: 1.4 eV Beta
W xcretion: 2/3 renal and 1/3 fecal
W Trade Name: etastron
tm
mersham ealth
Strontium-89
W a
++
analog
W arried to bone tissue where it undergoes ion
exchange to form Sr
10
(PO
4
)
6
(O)
2
(Strontium
hydroxyapatite)
W Sr
89
remains in metastatic sites for up to 100 days,
but only 14 days in normal bone
W Over time, Sr
89
becomes imbedded more deeply in
the bone matrix
W Lesion to normal bone ratio of 10:1
W Retreatment in 3 months if needed - second doses
usually effective if the 1st injection was successful
Strontium-89
Strontium-89
W Patient should have platelet count > 60,000 and
B > 2400
W Delayed onset of pain relief, usually 7 to 20 days
W Rapid injection may produce "flushing reaction
(calcium like)
W Transient increase in bone pain at 36 to 72 hours
after injection
Strontium-89
W Usual onset of pain relief is 2 to 3 weeks after
injection, however, some patients will experience
relief within days of administration
W 10 to 20 % of patients will experience a "flare
reaction - an increase in pain in the few days
following injection
W Duration of effect varies from 1 to 15 months -
average effect is 3 to 6 months
Strontium-89 dministration
W Dose: 4 mi (148 Bq)
(40-60 ui/kg) (1480
- 2200 kBq/kg)
W dminister by slow V
injection over 1-2 minutes
W ncrease fluid to minimize
radiation exposure
W xpiration: 28 days after
calibration
W Release criteria
Strontium-89 Side Effects
W yelosuppression
Thrombocytopenia -
-usually see a 20 to 50% decrease in platelet count
-nadir occurs at 5 to 6 weeks
-partial to complete recovery in 12 weeks
-Leukopenia
W "FIare" and "FIushing" reactions
Strontium-89: Benefits
W Single dose therapy
W Therapy can be performed on an
outpatient basis
W Long shelf-life allows for increased
availability - easily shipped and stored
if needed
Strontium-89 Disadvantages
W Benefit of the "Self-burial phenomenon may be counteracted
by the radiation effect of the high energy Beta particle
W Difficult to accurately monitor the absorbed dose since there is
no gamma photon
W ontamination can be significant problem due to long half-life
W Storage of radioactive waste extended due to long half-life
"uadramet
%M
W Radionuclide: Sm-153
W T1/2: 46.27 hours
W Dose: 1 mi/kg (37 Bq/kg)
W missions: 640 keV Beta, 710
keV Beta, 810 keV Beta and 103
keV Gamma
W xcretion: 100% renal
W Trade Name: Quadramet
tm
Berlex Pharmaceuticals
N
153
Sm-DTP
O
P
O
O
O
O
O
N
O
P
O
O
O
O
O
Sm
P P
O
2
O
2
"uadramet for Bone !ain
Quadramet: average penetration is 1.7 mm in bone and 3.1 mm in
soft tissue, ensuring that surrounding normal tissue receive minimal
radiation exposure. yelosuppression is generally reversible; most
patients' blood counts reach nadir at 3-5 weeks and generally return
to pretreatment levels 8 weeks after administration.
Samarium-153
W omplexed by DTP (ethylenediaminetetramethylene
phosphonic acid) - stable, with good bone uptake
W Taken up in hydroxyapatite crystal through binding to
calcium ions - similar to uptake of Tc-99m bone agents
(chemiabsorption)
W Greater than 50% of the injected activity localizes in the
bone within 2 to 3 hours - average bone uptake is 65.5%
Samarium-153
W 35% of injected dose is excreted in the urine
- most during the first 6 hours after injection
W Lesion to normal bone ratio of 5:1
W 75% of total radiation dose is delivered
within the first 4 days following
administration
W Retreatment based on patient hematologic
status and incidence of pain
Samarium-153
W Patient should have platelet count > 60,000 and
B > 2400
W Pain relief can be seen as early as 7 days -
maximum pain relief at 3-4 weeks
W Duration of pain relief can last 4 months or more
W 7% of patients experience a flare reaction within
the first 72 hours after injection
Samarium-153 dministration
W Dose: 1 mi/kg (37 Bq/kg)
W dministered by slow V
injection over at least 1 minute
W Patient should ingest at least
500 ml of water prior to study
to aid in elimination
W xpiration: 48 hours after
calibration or 8 hours after
thawing
W Release criteria
Samarium-153: Side Effects
W yelosuppression
Thrombocytopenia
Leukopenia
Decreased emoglobin
- 40-50% decrease
- nadir at 3-5 weeks post injection
- recovery to baseline by 8 weeks
W Flare reaction
W ypocalcemia
Samarium-153 Side Effects
W Disseminated ntravascular oagulation
W Patients with certain cancers have increased
incidence of D
W Platelet counts should be monitored weekly
until adequate bone marrow function returns,
watching for signs of D
Samarium-153: Benefits
W Delivers a large radiation dose over a short
period of time
W Short half-life allows for treatment of
metabolically active tumors
W Radiation dose to bone marrow less than Sr
89
-
thought to be due to lower energy beta
emission and "patchy absorption of dose by
the bone marrow
Samarium-153: Benefits
W 103 kv Gamma photon allows for
localization and verification of uptake - can
match to Tc-99m Bone scan to monitor
therapy
Pain Pain- -relieving effect relieving effect
DeveIopment of the pain-
reIieving effect (mean values,
based on a pain scale)
There are patients who are free of
pain even in the 20th, 30th or 40th
week.
Samarium-153: Disadvantages
W Product requires storage at temperatures
below freezing - must thaw to use
W Shorter half-life poses limitations on shipping
and storage
W Gamma photon increases radiation exposure
to others - radiation safety concern
W Production related contaminant
!harmaceuticaI Care
W onitor Blood Levels - Side ffects
Related to Bone arrow Depression
W onitor Pain edication Use
W Become nvolved in Pain edication
Utilization and Dosing
W nform Patient about Radioactivity and
Precautions to Take
W omfort and Quality of Life ssues
%hyroid %herapy
Diseases of the %hyroid GIand
Hyperthyroid and %hyroid Cancer
GO OF %HE#!
Destroy the proper amount of thyroid tissue
#adioisotope of Choice?
hy I-131
W Spectrum of beta () emissions which can be
used therapeutically
W 364 kv gamma () photon which allows imaging
W 8.05 day half-life
W dministered orally
W -131 Beta () radiation causes
Fibrosis and destruction of thyroid tissue
Decreased mass of functional thyroid tissue
I-131 #adiation has a short
Iength of traveI
verage
path
length of
travel
0.8 mm to
1.0 mm
Damage is
generally
confined to
the thyroid
gland itself
ength of %herapy Varies
W dministered as a
single treatment
W ctual damage to
thyroid tissue will be
given over a long
period of time
ill take weeks to
months for effective
treatment
%herapeutic Outcomes Vary
W UTYROD
Desired state following
treatment
Patient releases the
appropriate levels of
thyroid hormones
chieving euthyroidism
with radioactive iodine
therapy is RR
W yperthyroid
Dose was
underestimated
Patient still has
undesirable symptoms
Treatment produces an
insufficient decrease in
overactive tissue
%herapeutic Outcomes Vary
W ypothyroid
Overestimation of
therapy dose
Patient will require long
term pharmacologic
treatment (hormone
replacement) to
maintain correct state
FRLY OON
OUTO
%reatment of Hyperthyroidism
W Patient should have results of previous iodine
uptake study (% Uptake) for determination of dose
W Review patient medication to remove any
interfering medications and other potential
interferences
Should have been done at time of uptake study
ust watch if there is a delay between uptake and
treatment
W ust know:
Uptake percentage from prior uptake study
eight of thyroid gland
W ay also palpate gland to determine size
W Normal weight of thyroid gland = 20 grams
%o CaIcuIate %herapy Dose
LNGT DT GT
Done for each lobe of the gland ("guesstimate
from appearance on images)
W ant to dose the patient
with 7000 to 20000 rads
This is equivalent to
40-240 ui/gram tissue
ost physicians use 100 -
150 ui / gram tissue
W 100 ui = "fresh thyroid
(no other treatment)
W 150 ui = "medicated
(pt disease treated with
PTU / tapazole)
EXM!E
24 hour uptake 52%
Goal dose: 100 ui/gm
Thyroid weight Rt 4.5 x 1.5 x 1.5
Lt 4.0 x 2.5 x 1.5
hat is the Desired Dose?
alculate size of thyroid gland
(multiply to find area)
Rt = 4.5 x 1.5 x 1.5 10.125 g
Lt = 4.0 x 2.5 x 1.5 15 g
TOTL 25.125 g
hat is the Desired Dose?
DOS = (gland weight) x (goal dose)
( uptake as decimal)
DOS = (25.125 g) x (100 ui / g)
( 0.52)
DOS = 4832 ui = 4.8 mi
ength to SuccessfuI %reatment
W oderate doses 9 - 29 mi
Generally takes 6 - 12 months for complete
treatment
Patient will probably require hormone replacement
therapy
W Low doses 1 - 8 mi
Takes 12 - 24 months for complete treatment
ay require more than one dose
W Occurs in ~ 13000 people annually
W ore common in females than males
W 3% - 10% of autopsied patients are
found to have thyroid cancer upon
death
W ~ 1000 deaths projected annually
from thyroid
I-131 %herapy in %hyroid Cancer
Papillary, Follicular, edullary and
Undifferentiated
&suaI %reatment
Surgical
removal of the
NTR
thyroid gland
#adioactive Iodine %herapy is used to:
W blate thyroid tissue remnants
W ncrease visualization of and improve treatment of
metastatic disease
W Doses depend on type and extent of disease
Post surgical remnant ablation 10 - 100 mi
Localized metastatic disease 75 - 150 mi
dvanced metastatic disease 150 - 300 mi
Recurrent thyroid cancer 100 - 200 mi
W Dose based on physician preference
W ay require multiple doses
W ay take months to years to be effective
Side Effects of %reatment
W Sore throat
W hange in taste
W eadache
W oarseness
W Fatigue
W Nausea/vomiting
W Bone marrow
depression
W Leukemia (?)
!ost %reatment Instructions
W Discharge will be dependent on
a variety of factors
ctivity administered
Dose rate (external)
Patient specific variables
( % uptake, renal function)
Family criteria
Discharge Instructions
W Limit close contact
specially with children or pregnant women
Sleep in separate beds, etc for 3-5 days
W -131 will be excreted in sweat, saliva, urine
Patient should use separate eating utensils,
towels, etc
Use caution for approximately 1 week
Discharge Instructions
W void pregnancy!!
Both before and after treatment
Fetal thyroid will take up -131 also
W No breast feeding
-131 will be excreted in breast milk
nfant thyroid ablated by thyroid
uptake