Download The Bone Scan Index - Clinical Cancer Research

Vol.
4, 1765-1772,
July
Clinical
1998
A New
Parameter
Prostate
Cancer:
Massimo
Imbriaco,
Henry
W.
Yusuf
Erdi,
Howard
for
The
Steven
Yeung,
Metastatic
Bone
Index’
Scan
relapse
M. Larson,2
Osama
R.
Ennpadam
Measuring
27
Mawlawi,
S. Venkatraman,
Medicine
Service
[M.
I., S. M. L., H. W. Y.,
0. R. M.,
H. I. S.], Department
of Medicine,
Genitourinary
Oncology
Service
[H. I. S.], Department
of Medical Physics tY. E.], and Department
of
Biostatistics
and Epidemiology
[E. S. V.], Memorial
Sloan-Kettering
Cancer Center, New York, New York 10021
scan
report,
this
method
The
is involved
of the
report
metastases
in terms
a part
prostate
and
early
prostate
age
cancer
lize
A cube
the
tumor
readers
(69 scans,
AIPC
with
of
had
range
bone
(<3%
as
(62 scans),
bone
scan
to late
involvement,
showed
a rapid
percent-
used
to stabi-
of
values
of interobserver
the cube
Intraobserver
variability
the same
coefficient
followed
has
was
suramin
at
cancer
of
as
Bone
of
payment
of
revised
publication
of page charges.
advertisement
indicate
3/27/98;
accepted
of this
article
This article
in accordance
with
proven
to be
must therefore
18 U.S.C.
be hereby
Section
1734
the
marked
by
solely
to
in part
by the Pepsico
2
To whom
requests
for reprints
Memorial
Foundation.
should
icine
Service,
Sloan-Kettering
Avenue,
New York, NY 10021. Phone:
E-mail: [email protected].
Cancer
at Nuclear
Center,
(212) 639-7373;
1 275
MedYork
Fax: (212) 717-
provides
of
treatment
pro-
Although
BSI appears
fur-
capable
involvement
more
of
by tu-
scanning
usually
(“hot
erated
porated
involvement
accelerated
bone
can
10%
and
mineral
detect
in
regions
that
by
about
veyed
photon
such
than
15
that
mm.
emission
computed
bone
is often
used
have
size.
1 cm3)
be
that
In
must
detected
in regard
to stage
made
cameras
rapid
the
entire
skeleton
The
same
instrument
tomography
tech-
as small
patients
Improvements
gamma
computed
scan
can
then,
of
is incorbased
on
in
(-
change
involvement.
scanning,
single-photon
emission
scan
agent
region
millimeters
of
An
site
is accel-
bone
as dual-headed
so
turnover
turnover
the
(1).
a Tc-
at the
mineral
It is not surprising
of bony
convenient
less
before
and
Modern
a few
volume
the bone
the course
of whole-body
in
only
50%
(2).
cancer,
instrumentation,
perform
are
large
radiographs
monitor
in bone
meth-
to bone
diphosphonate.
bone
turnover.
evi-
scan
camera
and the scanning
matrix
in this
an increase
a relatively
the
develops
because
near the metastatic
site
into the bone mineral
first
the bone
radiographic
methylene
in bone
dissem-
cancer
a gamma
spot”)
bone
in the detec-
example,
of prostate
uses
agent,
systemic
standard
and
have
providing
than
uptake
metastatic
and
For
spread
cancer
modality
frequently
sensitive
to the bones,
prostate
spread
spread.
the initial
bone
to spread
vascular
of increased
aminations
be addressed,
BSI
that the BSI
of bone.
from
bone-seeking
capable
Supported
die
area
to prostate
in part
defrayed
this fact.
I
3263:
4/10/98.
were
entering
scan
The
as the
assessment
suggest
is an effective
malignant
by plain
1/6/98;
of
metastasis,
demineralize
costs
a result
skeletal
contrast,
The
bone
99m
as
Received
who
of distant
niques
PSA
resnits
has a tendency
patients
scintigraphy
Modern
mini-
serial
It
3.3%.
slope
The
both the progression
of bony
as the response
to treatment.
ods for detecting
scans after a 2-year
of 0.97 (reader
1)
by
80%
tion
2), P < 0.001.
There
was a parallel
rise in
PSA in 24 patients
(105 scans)
treated
for
hydrocortisone
to
dence
BSI
was
gradual
increased.
involvement
of
(<3%)
equation.
the BSI
patients
of time
INTRODUCTION
ination.
(0-60%
of the
is necessary,
quantifying
mor as well
variability
root
for stratifying
21
progression
for quantitative
These
of
of
with an estimated
phase,
involvement
of tumor
distribution
a group
involvement
a more
parameter
not
cen-
in
The
when
was
in the
the
to a Gompertzian
approached
(i.e.,
as a function
early
growth
by AIPC.
for extent
ther study
fitted
of 43 days
new
be useful
tocols
metastases
from
from
ofskeletal
involvement
will
in AIPC,
time
a reproducible
in BSI
graphically.
in BSI rapidly
bone
change
was
metastases
Also,
of
AIPC
distributed
explored
exponential
doubling
percentage
up
involve-
of the
was
changes
In a group
by
matched
marrow.
the
was
was
that
bone
0.71).
early
but
1765
by
involvement
of
skeleton
in a manner
diagnosis
change
bone
distribution
the
adult
Prostate
(b) the com-
metastases
the
after
intraob-
skeletal
span
times
scans
the
prostate-specific
antiof bony metastases
of bony
entire
0.2-0.5
at Memorial
androgen-
(a)
skeleton
mid when the same reader
read
interval,
showing
a correlation
and 0.99 (reader
the BSI and the
of
the application
transformation
the
18 patients).
purpose
validation
of the BSI;
cancer
The
was
who
in BSI and
distribution
root
over
involvement).
between
The
and
determined:
of the entire
variance
in
of
as the regional
and
variability
D prostate
cancer.
or BSI)
the fraction
bones.
(AIPC),
We
(‘0 the rate of growth
of involvement
Index
under
four protocols
Center
for progressive,
interobserver
and
quantitative
extent
of disease
and monitoring
analyzed
263 bone scans
from 90
work-up.
stage
ment);
for
as well
in the
parison
between
a change
gen (PSA);
(c) the regional
in
estimates
of reproducibility
studied
Cancer
of their
Scan
BSI
the development
for determining
progression.
We
independent
Bone
by tumor,
is to describe
patients
being
Sloan-Kettering
a method
(the
cancer.
that
distribution
of BSI
disease
describe
interpretation
the skeleton
server
we
prostate
this
normal
tumor
In this
advanced
skeleton
the
patients
ABSTRACT
bone
tral
correlation,
limited
within
Research
Involvement
moment
with
BSI),
random
I. Scher
Nuclear
(Pearson’s
patients
<3%
and
Bone
Cancer
tomography.
significantly
in
that
staging
can
be
can
are
exsuralso
Single-
increases
Downloaded from clincancerres.aacrjournals.org on June 14, 2017. © 1998 American Association for Cancer
Research.
the
1766 BSI in Cancer
of the Prostate
sensitivity
of bone
the spine,
which
is a frequent
As
a rule
of thumb,
treatment
for
therapy,
prostate
a bone
ment
of bone
score
and
scanning
scan
(3),
cer,
better
if the
especially
metastatic
given
patient
tumors,
cancer,
such as external
beam
is performed
to rule out metastatic
radiation
involve-
tissue
improve
with
a high
is not
for bone
methods
metastases
are
of prostate
needed
to
more
can-
accurately
scan
total
skeleton
interpretation
that
(the
BSI).
this
scan
to compare
it with
role
the normal
adult
bone,
scans
the present
treatment
in the
use of bone
response
reflects
detection
scintigraphy
in prostate
an inherent
of tumor
cancer
limitation
involvement
as a way
is not optimal.
of bone
scintigraphy,
of
to monitor
way
physiology
which
this
is that
visual
is visualized.
as degener-
required,
scan.
Also,
going
most
corn-
or
standard
monly
report
Other
forms
of damage
trauma,
can
also
cause
methods
of
bone
scan
descriptive
a simple
to bone,
interpretation
method
but
is more
cause
it is subjective
and nonquantitative.
in which the healing
bone becomes
region
of
is appropriate
difficult
site
mimics
clinical
information
well as the PSA
changes
To
sions,
metastatic
about the treatment
level is essential
for
in the
scintigraphic
improve
the
some
objective
authors
methods
pattern
have
of
as counting
the number
the regional
distribution
developed
of lesions
in advanced
coalesce,
lesion
PSA
disease,
counting
has been
patients
with prostate
tatectomy,
radiation
shown
more
methods
response
methods
the lesions
are
to treatbecome
become
large
and
in monitoring
who have undergone
radical
and/or
hormonal
treatment
pros(7-9).
with
bone
from
ing
69
and
for
showing
patient.
gram
More
than
poorly
progression,
with
value
differentiated
do well-differentiated
PSA
levels
the tumor
burden,
varies
widely
from
tumors
tumors,
produce
and
serum
less
do
not
and for a
patient
to
PSA
levels
per
in a
scans
± 4) with
treatment
ruary
1994.
reviewers
studies,
bone
for
was
confirmed
stage
were
results
of the
the
three
observers
images
3
3 h and
together
To assess
18 patients
first
time
first
bone
were
mCi)
performed
3 h after
of Tc-99m
methylene
high-resolution
collimator
To provide
based
Variability
the bone
One hun-
publication
No.
cancer
other
were
to the
reviewers’
participated
re-read
1995,
was
by three
This
by two
the
readers
second
Feb-
as well
was
session
in which
on a
and
independent
readings.
in a training
69
age,
entered
1990
condition,
consensus.
variability,
and
were
patients’
10 images
In-
on
(mean
January
read
Scan
tested
patients
who
between
involveskeleton.
of Bone
variation
scans
to reach
intraobserver
in July
at
a quanti-
disease,
criteria.
on ICRP
1 8 consecutive
blinded
involved
was
ob-
bones in the body were listed by name.
expressed
as a fraction
of the weight of
D prostate
were
In all
by Iran-
measurements
Analysis.
at MSKCC
These
who
scans
AIPC.
involvement
of each bone by tumor was
the bone scan. The BSI was then calculated
the
the
about
The abbreviations
used are: PSA, prostate-specific
antigen; BSI, Bone
Scan Index: AIPC, androgen-independent
prostate
cancer; MSKCC,
Memorial
Sloan-Kettering
Cancer Center.
of patient
not
Bone scans were read by independent
to the patient’s
clinical
condition.
Intraobserver
The interobserver
protocol
An
were
by summing
the product
of the weight and the fractional
ment of each bone expressed
as percentages
of the entire
and
tumor
response.
scans
images
(and static images
when mdia dual-head
gamma
camera
(ADAC;
was determined
Interterpretation.
correlate
in absolute
terms
given tumor
size, the PSA
scans
a low-energy,
The fractional
visually
from
Although
PSA is probably
the best current
means for monitoring
tumor response
and progression,
this test also has limitations
in
monitoring
tumor response
in bone. Although
helpful
in detect-
a
whole-body
bone scintigraphy.
ranged
from 0 to 4 ng/ml.
(20
Quantitative
skeleton,
used
for our initial
sixty-three
cancer
Bone
dred fifty-eight
individual
The weight of each bone,
the entire
patho-
we
treated
for PSA
MBq
Whole-body
obtained
using
Scan
series
with
in this
to the
and
measure
of the extent of metastatic
bone
were analyzed
according
to the following
23 (10).
estimated
impossible.
value
Bone
tative
scans
and
cancer,
suitable
hundred
of prostate
a scan speed of 20 cm/mm.
reviewers
who were blinded
such
and assessing
(6). These
to be of clinical
cancer
therapy,
for
metastases,
in regard
being
samples
of 740
equipped
treatment
and
cases.
Two
Scintigraphy.
diphosphonate.
cated) were
of
carcinoma
METHODS
from each patient
before
serum PSA concentrations
Genesys)
le-
a larger
in some
tamed
Normal
injection
and accuracy
progression
study
the diagnosis
Bone
BSI
of
disease
To explore
proved
on 90 patients
Blood
an improved
was that digitized
biopsy.
iv.
the
tumor
years
during
in prostate
srectal
the
as
of
of bone
systems
of monitoring
lesion counting
become
reason,
therapy.
in the total skeleton
and once
may
is
in
of the patient
interpretation
of bone
of the metastases
delay
this
treatment
scoring
extent
difficult
to apply to the problem
ment. In part this is because
bone
tedious
status
proper
of the
assessing
For
during
monitoring
may
performed
patients,
soft-
to bone
metastatic
distribution.
which
we could
several
AND
were
by
the amount
prostate
response
method
Population.
Interpretation
an increase
involvement.
and
to describe
with
of
with
Patient
The flare phenomena
strongly
positive
in the
response.
can show
BSI
of the visual
MATERIALS
be-
for more
disease
the precision
metastases
of analysis,
back
both
by osseous
marrow
to bone
response
to therapy,
the PSA
bone
usually
in bones.
spread
tumor
is responding
that
physicians
of tumor
tumor
in monitoring
the diagnosis
of a favorable
treatment
difficult
because
the healing
bone
that
are
for detecting
to use
a tumor
intensity
bone
in that nuclear
medicine
record
of the detected
sites
This
(5),
such
a positive
was
involved
relevance
of
advantage
increased
for quantifying
in patients
of bone
method
correlation
study
to determine
biological
the tumor is not directly
visualized
but only indirectly,
because
it is the reaction
of the bone to the local invasion
by tumor that
ation
was
We sought
the
Also,
metastatic
technique
interpretation
In part
be
therefore,
of the present
determine
the amount
of tumor
present
at baseline
and to monitor the tumor’s
response
to therapy.
In contrast
to the important
of bone
can
of benign
tissue.
directly.
aim
bone
by the amount
prostate
levels
metastases;
monitored
The
be influenced
in residual
PSA
and bony
Gleason’s
(4).
also
hypertrophy
advanced
in patients
may
prostatic
localized
diagnostic
patient
in
involvement.
is to have
10 ng/ml
>
metastases,
site of initial
especially
a PSA3
As therapies
for detecting
they
done
as
after
that
last
graded
the
one scan
for each
of the
at 2-year
intervals
(the
time
in July
Downloaded from clincancerres.aacrjournals.org on June 14, 2017. © 1998 American Association for Cancer
Research.
1997).
A
Clinical
Cancer
Research
1767
“.3
*
#{149}1
.
.
r
Fig. 1 Typical
whole-body
bone scan in a patient with progressive
prostate
cancer,
ohtamed at four different intervals
after the first bone scan abnormality was observed in the right
ischium, showing progression.
,
;
.: :
1/24/90
BSI = 0.6%
simple
server
correlation’s
analysis
variability.
Comparison
Serial
used
to assess
the
function
intraob-
relapse.
bone
scans
patient).
of Changes
in Serial
A comparison
was
made
BSI
to Changes
between
changes
in
nentially
declining
in the
describe
solid
Twenty-four
for
of these
comparison
These
bone
patients
(an
scans
were
had
average
read
sufficient
of
by two
4.3
serial
bone
readers
and
Inter-
when
the
20,
moment
correlation
analysis
was
and BSI over time.
of Metastases
in
ment
by AIPC
(<3%
scans
of 27 patients
were
analyzed
skeleton,
and
adult
and
62
with
in
regard
bone
plotted
bone
and
adult
Limited
Bone
The
limited
bone
distribution
respect
Involve-
baseline
(1 1). A total
within
of
136
representation
lesions
the
of the
exponential
growth
Twenty-one
3% in a subsequent
and
the
patients
for
3%
were
AIPC who had a
or less and who
scan.
In all, a series
BSI
was
plorted
had
data
that
was
which
growth
patterns
obtained
describes
rate
(13)
relatively
1990.
When
of
as a
quite
change
no
The
2a
a patient
BSI.
slowly
the patient
bone
been
Variability
from
corresponding
progressed
phenomenon
Fig.
found
scan
scan
was
an expo-
and
appears
to
well.
prior
there
upper
change
is unlikely
developed
involvement
three
readers’
with
estimates
the BSI, and the abscissa
the average
of the three
The
initial
in
a rapidly
increasing
Also,
the scans
for easier
in
involvement
24,
management
as a cause
A typical
is shown
January
in April
scans.
AIPC
1991,
1990
in
to May
PSA,
which
showed
in the 2-month
period
was considerable
humerus
and right
interobserver
variability
shows the three readers’
bone
of BSI.
with
from
was ordered
from
to June 27, 1991,
lesions
in the right
were
of the distri-
skeleton.
obtained,
the bone
a marked
bone
involvement
to the distribution
who were being
treated
for which
the BSI was
were
to correlate
1 with
a follow-up
regional
a composite
of AIPC.
to above
scans
to
with
used
Skeleton).
AJPC
marrow
onto
of the normal
patients
scan
of the
in particular
Progression
progressed
(12),
Intraobserver
the
Pearson’s
changes
in PSA
Distribution
and
bone
Fig.
among
baseline
The
equation
tumor
whole-body
reA
bution
of observation.
RESULTS
scans!
there was a discrepancy
in BSI, a consensus
reading
was
corded.
There
was an average
of 28 PSA values
per patient.
found
of time
6127/91
BSI = 8.1%
PSA in 27 patients
with AIPC who participated
in a
protocol
with hydrocortisone
followed
by suramin
at
PSA
normal
4/23/91
BSI = 6.7%
fit to a Gompertzian
PSA.
BSI and
treatment
was
5/20/90
BSI = 0.7%
up
progression
hip. Because
to this
of the bone
scan
of the
there
point,
flare
progression.
of the test is shown
in Fig.
estimates
of the percentage
ordered
by the average
visualization.
The
2.
of
of the
ordinate
is
is the scan number,
ranked
in order of
readers’
scores.
As can be seen in Fig.
2, a and b, the average
BSI of the three readers
5 1 % in this series
of bone scans.
A typical
varied from
“super-scan”
Downloaded from clincancerres.aacrjournals.org on June 14, 2017. © 1998 American Association for Cancer
Research.
0 to
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1768 BSI in Cancer
of the Prostate
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vs. Others
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Mean
2 a, percentage
of bone involvement
as estimated
by the three readers with the scans ordered by the average of the three readers’ estimates
for
easier visualization
(x-axis, number of scan; y-axis, percentage
of bone involved by tumor). b, cube root transformation
of the percentage
of bone
involvement
as estimated
by the three readers. c, individual
readers’ (1-3) behavior as a function of the other two (i.e., every reader’s deviation
from
Fig.
the average
prostate
of the
cancer
other
two
would
variability
among
est values.
However,
is plotted
be in the range
readers
Fig.
and
between
observers.
this
somewhat
2b shows
that
simplifies
The
curve
of the
of 30-50%.
increases
mation
of the three readers’
involvement
stabilizes
the
analysis,
as a function
estimates
variance
average
The
root
the interpretation
for reader
of bone
range
of
of BSI
1 abruptly
high-
transfor-
of the percentage
over the entire
variation
goes
to zero
at scan 27 because
no reading
was available
here. Fig. 2c shows
the individual
reader’s
behavior
as a function
of the other two,
i. e.,
every
reader’
BSI of the other
5
BSI of the other
are scattered
systematic
There
deviation
two readers,
two
along
readers.
the y
difference
are
larger BSI
the average
some
trends
from
For
are
most
(x-axis),
the
root
as a function
the
0 line
between
that
the cube
plotted
readers
apparent;
values,
reader
3 tended
to have
of the other two readers.
part,
After
a period
coefficient
2 (Fig. 3b),
reader
his previous
reading
agreed
with
Thus, in summary,
moreover,
there
ibility
observations.
of intraobserver
Comparison
Serial
of Changes
PSA.
With
patients
had
the deviations
average
of 4.3
tends
to be
example,
a higher
value
small.
at the
than
27
published
patients
regard
with
bone
previously
in Serial
had
serial
bone
between
median
BSI determinations
change
(18-35%)
between
median
PSA
change
BSI
scans
These
form
even
after
to Changes
between
available,
scans
scans/patient).
in abstract
was
a
the reliability
of BSI
is excellent
reproduc-
to the comparison
AIPC
sufficient
variability
of 0.97 for reader
1
P < 0.001.
The same
of the BSI,
considerable
time gap.
has been characterized;
PSA,
any
the intraobserver
a correlation
for reader
of the average
that
of 2 years,
minimal,
showing
(Fig. 3a) and 0.99
of the average
indicating
for
two).
absolute
at the very
the cube
of the other
(14).
for
BSI
of which
comparison
results
The
in
and
24
(an
have
been
median
time
was 75 (47-1 10) days, with a 25%
between
studies.
The median
time
determinations
was I I (7-26)
between
values
per patient.
days, with
On average,
Downloaded from clincancerres.aacrjournals.org on June 14, 2017. © 1998 American Association for Cancer
Research.
a 6%
there
Clinical
a
Cancer
a
37x
y = 1 .01
R2
60
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80
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50
,
2
<
(I)
u
0
40
.
0
120
150
30
240
250
450
510
Time (Days)
20
b
10
45Oo
0
40
4000I
0
10
20
30
40
50
60
.35
-#{149}-PSA
)
70
3500
%
BSI
BSI(%)95
.
25
2500
‘4,
‘‘
y
=
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R2
+
0.9863
4 20
I
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I
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.
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.
10
1500’
40
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0)
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35
“.
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-
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4#{149}
3#{176}
:
500
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.5
0
20
--
.
100
0
200
300
-
400
0
500
600
700
T1m.(Dsys
10
Comparison
of BSI and PSA. a, patient with prostate
carcinoma
showing
a parallel increase
of the bone scan index and PSA levels
during a period of 2 years, with rise in BSI preceeding
PSA. b, patient
Fig. 4
0
10
20
30
40
50
60
with
BSI(%)95
Fig.
Intraobserver
variability
for reader I (a) and reader 2 (b) over a
period. R2 is the correlation
coefficient
for the comparison.
3
2-year
were
4.3 BSI
determinations
per patient
patient.
There was a generally
parallel
a strong
concordance
between
BSI
Pearson’s
moment
correlation
and
28 PSA
values
per
rise in PSA and BSI, with
and PSA change
with a
of 0.71
(P
0.0!).
<
Fig. 4 shows two examples
of how the BSI might be used
to monitor
response.
The change
in PSA and the BSI show a
similar
trend in these examples.
in PSA and the gradual
increase
prostate
showed
In Fig. 4a, the gradual
increase
in BSI paralleled
one another
carcinoma
a dramatic
crease
in both PSA
with rhenium-186.
group
with
more
of metastatic
who
to treatment
and
over
BSI
extensive
lesions
a total of
distribution
underwent
response
time.
tumor
involvement
on a model
projection
posterior
bution
is not random
in the
axial
of the
(Fig.
ribs
and
shows
normal
adult
4b, the
dramatic
interpreted
these results
the distribution
of early
as being
metastatic
tensive
red
in both PSA and BSI over time,
drop in PSA. At day 450, there
PSA
and
also
appeared
the
to correlate
Distribution
ment by AIPC
by Tumor.
skeleton
was
were
BSI.
being
better
In
with a much
was a marked
this
instance,
and showed
a
by the decrease
larger and earlier
upswing
in both
the
in progression
than
BSI
and
in response.
of Metastases
in Limited
Bone
with <3%
of the Skeleton
Initially
The distribution
of metastatic
lesions
studied
in a group of 27 patients
with
treated
These
27 patients
limited
disease,
under
had
BSI
in contrast
two
treatment
<3%
to the
and
protocols
were
balance
PSA
InvolveInvolved
within
AIPC
the
who
at MSKCC.
considered
of patients
with
a remarkable
bone
the
that the marrow
It can
The
normal
may
of AIPC tumor.
Rate of Progression
tocols
treated
for AIPC,
that
the distri-
the tumor
limbs.
with
The
clusters
metastatic
the distribution
(Fig.
consistent
tumor
marrow
were
in the anterior
distribution
be a particularly
There
shown
instead,
parallel
marrow
distribution
be seen
proximal
pattern
and
and the pattern
of
at the site of tumor
skeleton
Sa).
in the skeleton;
skeleton,
therapy
was determined.
136 lesions
in these
patients,
is shown
as a black dot placed
and
I 86
involvement.
in the skeleton
for about 6 months,
at which time there was a rapid increase
in
BSI involvement,
followed
later by an increase
in PSA. In Fig.
patient
underwent
rhenium-!86
therapy
response
to treatment,
as demonstrated
rhenium-
as demonstrated
by the deThe arrows
indicate treatment
Sb).
of the
We
have
with the view that
from AIPC
is coex-
in the
adult
favorable
and
suggests
environment
for
growth
gressing
during
serial
of prostate
cancer
from low-volume
progress
above
to have
bone
scan
in this
first
follow-up
of AIPC.
we evaluated
scan
studies.
In a group of three
patients
who were
Because
the
natural
propro-
history
is variable,
we defined
progression
as going
disease
(<3%
of skeletal
involvement)
to
3%
interval.
in a subsequent
Of the 21 follow-up
was
108
days
after
bone
bone
baseline,
scan,
scans,
with
regardless
of
the median
a range
Downloaded from clincancerres.aacrjournals.org on June 14, 2017. © 1998 American Association for Cancer
Research.
of
1770 BSI in Cancer
of the Prostate
100
a
.
.
.
.
.
(I)
4.
a?
0
500
1000
2000
1500
Deys
Progression
of bone involvement
by prostate cancer. Example
of progression
by BSI from early involvement
(<3%)
to late involveFig.
6
ment
ANT
of prostate
cancer
using
a Gompertzian
equation
model.
POST
b
data were determined
the residuals
using
The
0.00485;
was
by minimizing
the
the Levenberg-Marquardt
sum
fit parameters
were as follows:
and b
0.00254.
The progression
most
rapid
diminished
initially,
as more
and
time
then
elapsed
of the
method
there
with
is more
the
growth
from
the
growth,
growth
a Gompertzian
rapid
expansion
rate
a gradual
loss
gradually
index
growth
of tumor
reflecting
a more
of the AIPC tumor.
of
BSI0 = 3.3%;
a =
that was observed
scan.
corresponds
to a starting
doubling
time of 43
rapidly
diminished
with time. We have interpreted
to be consistent
squares
(15).
pattern
in the
This
days,
these
which
results
in which
early
phase
of
highly
favorable
environment
for
As time goes by, however,
there is
of favorable
conditions,
and
the
growth
slows.
DISCUSSION
We developed
the
approach
method
the BSI
should
should
measure
ANT
(‘
bone
monitoring
5 a, pattern of metastatic
bone disease
BSI. b, normal adult pattern of bone marrow
Fig.
in 27 patients
distribution.
with
<3%
extent
number
ogy
days.
The
BSI
patients
was plotted
all, 2 1 patients
and
plotted
in Fig.
growth
rate
at time
growth
rate
slows
baseline
scan.
The
scans
as a function
of the time
62 scans were analyzed,
6. The
of the form BSJ(t)
represents
the BSI
of all available
data
were
fitted
in this
group
of
after baseline.
and the data
In
are
to a Gompertzian
zero,
down,
parameters
b
and
represents
t is
in the
the
the
rate
time
in
equation
at which
days
that
after
best
number
of bony
in the
methods
the
become
the
when
simpler
metastases
based
prognosis.
the
patient
methods
five
categories
of lesions
on scoring
et a!.
based
scintigraphy.
at the
Such
extremes,
there
bone
of lesions
Because
is a
scanning
are not easily
in number
can actually
or grading
(6)
of pa-
of lesions,
increase
a
on the
a stratification
and
for
and
and the extent
Soloway
on the bone
lesions
is progressing.
based
17),
methodol-
and response
the number
the number
cancer.
tool
semiquantitative
number
when
relevant
(16,
Semiquantitative
on counting
Also,
metastases
involvement,
massive
(a)
the
(b)
as a valuable
in permitting
of bone
however.
confluent,
read
value
versus
with
automated,
into
in mind:
and
by prostate
In particular,
of disease
extent
lesions
in bone
involvement
goals
is biologically
accepted
(18).
do have
few
BSJ0
the
fit the
extent
techniques
correlation
equation
BSl0exp[a/b(l
exp(-bt))],
where
at time zero at the baseline,
a represents
the
tients
bone
two
automation;
that
developed
involvement
graded
i.e.,
have
for assessing
to
involvement
is widely
of tumor
of authors
of tumor
30-1770
of bone
scan
with
itself
information
to the pathophysiology
The
method
lend
of these
drop,
and
even
limitations,
schemes
Downloaded from clincancerres.aacrjournals.org on June 14, 2017. © 1998 American Association for Cancer
Research.
have
been
Clinical
proposed.
Knudson
skeletal
areas:
Patients
were
involved.
stratified
Other
simple
uptake,
diffuse
uptake
bone
scintigrams
using
fixed-size
landmarks.
These
principle,
but much
approaches,
are
readily
that
useful
such
made
none
with
other
clinically
The
of the skeleton
olding
approaches,
niques
developed
analysis,
we
are in the process
graphics
platform
This
method
assessed
ance,
made.
permit
shows
of metastases
readers
to the average
is acceptably
low.
Similarly,
the
the range
less
BSI
than
of 2-54%.
was
excellent
In considering
facts
natural
history
phatics
from
tate cancer,
of
three
Once
tumor
the tumor
distinct
the
should
evident
nodes
has spread
Prior
of individual
patients
the
bulk
of the
withdrawn.
cells
During
stop
unaffected
These
by the
cells
this
growing,
are
phase
and
could
be
between
based
1 and 2,
of 1.3%
of
significantly
of treatment,
treatment
sensitive
but
to
continue
other
with
cancer
is gradual
both
growth
to
the prostate
gland,
of metastatic
pros-
is composed
8.1
>5.1%
of cells
stage
in BSI
show
during
so
is
the androgen-sensiproliferate.
including
are
good
used,
the
for
and
is not sensitive
The
correlation
As
seen
appears
in Fig.
to be best
BSI is likely
enough
Furthermore,
based
disease
marrow
and
AIPC
during
of
the
in PSA
that
for rank
levels
BSI
changes
changes
is used
disease,
was
order
of the variable
on a statistical
individual
and during
patients
response
the
slower
to change.
However,
of PSA
responders
to systematically
biological
AIPC
we did
series.
correlates
of a match
a Gompertzian
into
months,
correlation
in these
in early
18.3
metastases,
correlation
interesting
of
group
as an indicator
the
type
in the present
on the BSI in terms
and
values
Although
of bony
significant
group
with
0.0079).
<
method
to absolute
to be significantly
a large
of
(P
between
in progressing
BSI
study
was highly
4, the
this phenomenon
the
the
correlation,
compared.
basis.
report,
progression.
The
correlation
poor
prednisone,
survivals
feature
moment
candi-
cancer,
we focused
on a comPSA is presently
considered
to
correlation
Pearson’s
be
BSI
for
1 9 1 patients
versus
of the BSI
progression.
may
of
respectively
marker
to have
of otherwise
group
median
different
disease
between
and
pattern
the
can
be drawn
the distribution
normal
of skeletal
of
adult
bone
involvement
by
progression.
normal
adult,
red
marrow
is found
in the
central
skeleton
(skull, thorax,
pelvis,
and spine) and the upper portion
of the femurs,
humeri
(Fig. 5). In the present
study, patients
with
low-volume
of the
cells
cancer
relapse
shown
who
divided
months,
the validity
a very
In the
androgen-
factors,
and
metastatic
by lym-
hematogeneously
to slowly
and
usually
of
do not normalize
prognosis
(24).
because
in this
corresponding
months,
not have
The
the androgen-independent
included
1.4-5.1%,
been
patients
liarozole
best
disease
is, like normal
prostatic
cells, androgen
dependent,
that the cells stop proliferating
and in fact die when androgen
tive
not
with
represents
BSI,
at this
are
in PSA
who
a poor
in a separate
be the
readers
(23).
Initially,
most pado respond
to androgen
tumor
select
therapies
treated
supPSA
by Sabbatini
et a!. (25) that
predictor
of the prognosis
two
prostate
of the
androgen-dependent,
help
example,
In assessing
in mind.
beyond
from studies
independent
will
also
patients
have
within
evolve.
evidence
have
individually
with
variability
to spread
and
sensitive,
and androgen-independent
tients
with advanced
prostate
cancer
because
1.4%,
15.5
validity
to treatment
phenotypes:
<
in the
often
increase
symptomatic
levels
aggressive
were
data
patients
be kept
prostate
tumor
lymph
who
study
evaluated
cancer
incurable.
withdrawal,
We
bones
to hormonal
of tumor
progressive
impact,
and
after treatment
and
For
whose
initially
cells
proliferate,
sites
involvement
by prostate
of BSI to PSA, because
of readers
difference
was
in PSA
very
prognosis.
a
microen-
of the
unresponsive
of bone
parison
reproducibility
intraobserver
before
major
prognostic
their PSA values
AIPC
of bone
readers
variability
as expected,
organ-confined
to locoregional
sites.
we
prostate
of clinically
it is essentially
tech-
variability.
how
about
progression,
distant
and,
the interobserver
certain
Thus,
In fact,
months
Changes
for
cells
as the tumor
clones
becomes
to rise.
a few
occurs.
bone
in some
is a rich
involvement
1771
shows
and
The
there
phenomenon,
androgen-independent
patients
(22).
The
and
important
where
growth.
tumor
such
Hence
a cube root
to stabilize
the van-
on a linear correlation
between
two readings
as shown in Fig. 3, is also small, with a mean
and
begin
is a reliable
was
the
dates
image
of the other
between
that the
pression
cancer
Research
expand.
amenable
assessment
in patients
three
marrow
bone
prostate
involvement.
space,
favors
and threshof threshold
BSI
is a secondary
It is also clear
is a powerful
quantitative
the
and
that
itself
at MSKCC
to increase
as the BSI increases.
was performed
empirically
the visual
is
adopted
computerized
that
so that a direct
comparison
In general,
it can be said
BSI over
net result
involvement
a method
developed
of the
in relationship
readers
be
be more
other
interpretation
variability
and appears
transformation
will
study
or progression
The
will
vironment
in the
why
as the most
site of metastatic
themselves
begins
can
been
to bone
to the marrow
levels
of transferring
this approach
from a silicon
to a more readily
accessible
PC environment.
quantitative
extent
cancer.
The
have
in
which
correlation
the sole
found
in part
As androgen-independent
simplified
about
explain
to spread
the bones,
at least
on segmentation
with
has been
preliminary
for
prostate
the
substances
may
are seeded
bone
to anatomical
on fractional
In fact,
believe
of BSI,
of
automated,
basis,
based
2
have
in serial
methods
is based
and
(21)
of changes
information.
in comparison
which
interpretation
scan
diagnostic
previously.
cases
et a!.
so that
semiquantitative
automation,
used
have
0 representing
information
on a bone-by-bone
to computerized
propensity
is lost in these
anatomical
on a large scale.
BSI method,
which
areas
relative
be easily
or progressing,
of these
of skeletal
carcinoma
placed
information
as the
involved
with
could
This
five
uptakes,
Jinnouchi
of interest
methods
marrow.
interpretation
for quantitation
in patients
stimulatory
skull.
into
bones,
or several
recently,
method
various
and
skeleton
0 to 2, with
single
More
regions
scan
from
1 representing
(20).
the
long
to the number
ranging
a different
bones
divided
pelvis,
for bone
system
normal
(19)
ribs,
according
methods
scoring
proposed
et a!.
vertebrae,
Cancer
tumors
(i.e.,
<3%
BSI)
displayed
a distribution
of
metastases
in a manner
corresponding
to the distribution
of the
normal
adult bone marrow.
This is supportive
of the notion
that
the initial
seeding
and
attachment
of the
tumor
cells
occur
within
the red marrow,
followed
adjacent
bone (2).
Finally,
the BSI has been
of time
AIPC,
6),
after
from
shows
diagnosis.
early
by expansion
graphically
The
progression
involvement
(<3%)
a relatively
rapid
increase
during
explored
of bone
to late
initially,
growth
to
as a function
scan
changes
involvement
followed
in
(Fig.
by
Downloaded from clincancerres.aacrjournals.org on June 14, 2017. © 1998 American Association for Cancer
Research.
a
1772 BSI in Cancer
of the Prostate
slowing
of expansion
The data as plotted
as time elapses
from baseline
match
well to a Gompertzian
growth,
which
rate
is the usual
and
Based
independent
changes
probably
6, it is possible
to make
During
the
tumor
when
slower,
months.
When
slower,
the process,
highly
scan
cancer
every
3
will
be
be sufficient
active
treatat
in situations
feature
rate
BSI
data
with
of bone
of 43 days
evaluating
of patient
that the BSI may prove
BSI
with
together,
the hypoth-
for bone
of treatment
management.
to be useful
by
new parameter
by AIPC.
Ac-
as a tool
monitoring
is
followed
Taken
and reliable
involvement
that
the dis-
by AIPC
or less,
are consistent
a valid
of bone
where
indicate
is coextensive
of involvement.
study
according
to their likelihood
based on total extent of tumor
therapy
Also,
is a
a known
scan
response
In addition,
for stratifying
patients
of response
to particular
therapies,
in bone, and thus help select the most
for the individual
147: 956-961,
patient.
F. R., Drach,
on initial
scan.
usefulness
of
therapy
of metastatic
S. S., and
serum
prostate
specific
prostate
cancer.
J. Urol.,
1992.
on Radiological
Protection.
Report of the
Man, ICRP Publication
23. New York:
S. M., and NeIp, W. B. The radiocolloid
disease. J. Surg. Oncol., 3: 685-687,
12. O’Donoghue,
growth characteristics
72: 325-339,
Cancer
T. G., Potts, S., Chappel,
antigen as a predictor
of
in localized prostate can-
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Downloaded from clincancerres.aacrjournals.org on June 14, 2017. © 1998 American Association for Cancer
Research.
A new parameter for measuring metastatic bone involvement by
prostate cancer: the Bone Scan Index.
M Imbriaco, S M Larson, H W Yeung, et al.
Clin Cancer Res 1998;4:1765-1772.
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