Document 6447026

OSTEOSARCOMA
IN
A STUDY
C. H. G.
PRICE,
H. G. WILLERT,
BRISTOL,
FRANKFURT,
z.
A study
present
aetiological
The
PRAGUE,
is presented
and
K. ZHUBER,
M.
MATJOVSK’,
in children
English
ENGLAND,
GERMANY,
six
fifteen
European
M.
IMMENKAMP,
125 CASES
of age.
treatment
of treatment
These
cenfres.
cases
There
9 per
after
cent
MuNIch,
in a group
have
been
is a slight
feature
is the very high proportion
of tumours
two and a half and five year disease-free
survival
a further
metastasis
W. KEYL,
and
VIENNA,
P. GROH,
MUNSTER-WESTFALEN,
and results
years
M. SALZER,
SALZER-KUNTSCHIK,
CZECHOSLOVAKIA,
of the aetiology
under
OF
CHILDREN
of 125 proven
from
osteosarcomas
the
preponderance,
records
but
two
of one
the
striking
of the long bones
of the limbs (96 per cent).
rates were respectively
15 and 12 per cent,
still living,
but under observation
for less than two and a half years.
and a half years is very unusual,
but no child with a tumour
of an axial
this length of time.
Although
the differences
in the results
valid, the largest number of long survivors
GERMANY,
GERMANY
collected
male
AUSTRIA,
HAMBURG,
with
Evidence
of
or girdle bone
lived
the lowest
rate
of local
tumour
recurrences.
rates
1972).
for
clinical
trials
Although
and
behaves
there
Whether
or
by
therapy
there
age
are
which
at onset
(Price
few
reports
this
aggressive
1966;
are
amputation
in
the
figures
for
cases
results
these
collected
two
available
of
the
methods
world
amputation
( 19 1 of 903
patients)
cent
(I 19 of 501
without
operation.
of
is between
two
1974).
by
with
after
and
This
and
a rate
three
cases
figure
excludes
of 238
per
with
or
per
tumour:
annual
in the
incidence
million
population
tumours
related
Dr C. H. G. Price, F.R.C.Path.
Research
Fellow
in Pathology,
Royal Infirmary,
Bristol,
BS2 8HW, England.
Dr K. Zhuber
hk
. Wiener
Knochengeschwulstregister,
Dr M
Sal7er
Professor
M.
P.
Z.
W.
VOL.
sc
I
H. G. Willert,
The
have
Trifaud
radiotherapy
is not a common
United
Kingdom
the
the
No. 3, AUGUST
Spitalgasse
4, Osterreich.
lnterdisziplin#{228}re Arbeitsgemeinschaft
1975
ablation
is
age
group
difficult.
The
is derived
tumours
were
a study
of
bone
or
treatment
any
other
centre
is able,
to collect
records
of a sufficiently
to be adequate
for detailed
analysis.
under
review,
this
problem
present
series of 125 childhood
from
seven
centres
(Table
I).
histologically
proven.
of the aetiology
and
to
information
AND
concerning
the seven contributing
These,
together
with
sections,
were
This
results
paper
of treatment.
children
were
were
under
knowledge
sarcomas
METHODS
patients
was
centres
on detailed
the radiographs
examined
ensuring
agreement
any
doubtful
cases,
in Vienna
on diagnosis.
125 examples
accepted
for
in children
so
of
and
in Bristol,
All
age.
To
the largest
far
from
thus
After
elimination
of osteosarcoma
evaluation.
fifteen
years
this represents
entered
questionnaires.
and histological
reported.
the
of
in
children
the best of our
series
of osteoNo
histological
grading
of tumours
was carried
out ; nor was any distinction
made
between
osteoblastic,
chondroblastic,
fibroblastic,
anaplastic
or other
variants
of osteosarcoma.
University
of Bristol,
Pathologisch-Anatomisches
Knochentumoren
Immenkamp,
Orthop#{228}dische Universit#{228}ts Klinik,
M#{252}nster-Westfalen,
Groh,
Orthop#{228}dische Universit#{228}ts Klinik,
Homburg,
Saar, BRD.
Mat#{235}jovsk, Erste Orthopadische
Universit#{228}ts Klinik,
Prag, CSSR.
Keyl, Orthop#{228}dische Universit#{228}ts Klinik,
M#{252}nchen, BRD.
57-B,
disease
no single
PATIENTS
by selective
free of active
Comparative
at all ages immediate
survival
rate of 21 per cent
compared
patients)
Osteosarcoma
south-west
a restricted
of radio-
of treatment
literature
prompt
in adjuvant
treatment.
support for immediate
amputa-
method
about
six months
then
shown
to be
are still deplorable.
for osteosarcoma
gave a five years’
Meary
Dr
Dr
Dr
Dr
All
tumour
by immediate
Hospital
different
from
(1972):
treated
Westminster
at
time,
ofcases
is even more
osteosarcomas
presents
patients
Thus
With
that
prognosis
Paget’s
dysplasia.
evidence
influence
in
followed
disease,
antecedent
bone
is some
1973),
the
either
in a reasonable
large number
can
manner
in
crude
in children.
(Price
that
cited.
or more patients
ranging
1971 ; Trifaud
and Meary
cent
that
Jeifree
precise
of fifty
for osteosarcoma
the five years’
methods
(Ohno
groups
be a factor
been
indicate
of the new adjuvant
designed
10 to 25 per
tion
which
carefully
from
Price
are discussed
with certain advantages
in the light of recent advances
with childhood
osteosarcoma
certainly
provides
strong
survival
the
Reasons
employed
are not statistically
which method
also provided
the treatment
of choice,
perhaps
The past situation
in connection
The bad results
of treatment
patients
of all ages are well known,
may
of the different
methods
of treatment
had been treated
by early amputation,
Frankfurt,
Hon.
Secretary,
lnstitut
Bristol
der
Bone
Universit#{228}t.
Tumour
A-l090
Registry,
Wien,
BRD.
BRD.
341
342
C.
H.
G.
PRICE
ET
TABLE
LIST
AL
I
OF CONTRIBUTING
CENTRES
Number
Contributors
Price, C. H. G.
Zhuber,
K.,
Salzer-Kuntschik,
and Salzer,
M.
Willert,
M.
Bristol
Bone
Tumour
Registry
49
Vienna
Bone
Tumour
Registry
36
Interdisciplinary
Committee
German Republic
H. G.
on Bone
Orthopaedic
University
P.
Orthopaedic
Republic
University
Mat#{235}jovsk, Z.
Orthopaedic
University
Clinic,
Prague,
Keyl,
Orthopaedic
University
Clinic,
Munich,
lmmenkamp,
Groh,
M.
W.
of
cases
Centre
* These
cases were collected
(Prim.
Doz. Dr W. Becker);
by: the
ZUrich
Clinic,
Frankfurt,
M#{252}nster,West
Clinic,
Orthopaedic
Clinic,
(Dr M. Cserhati);
Tumours,
Homburg.
German
Saar,
West
I8
Republic
West
12
German
4
Czechoslovakia
West
University
the Surgical
4
German
.5
Republic
of Frankfurt
(Dr
Clinic,
University
N. Sarfert):
Heidelberg
of Heidelberg
(Dr M.
Pieper).
Age and sex-Table
by age and sex.
and
there
was
advancing
girls,
a steady
age
fifteenth
II shows
youngest
The
to
years.
increase
a
the
of tumour
in the
maximum
There
reflecting
the distribution
child was
were
usual
sixty-six
small
of the
four
years
cases
old,
incidence
fourteenth
boys
and
with
and
in
over
four
this
series
times
as common
other
they
as compared
at all ages
fifty-nine
preponderance
are
4) tumours
at sites
common
in children;
(Price
and
with
I 7 per
Jeffree
1973).
AGE
SEX
AND
Males
DISTRIBUTION
Females
AND
In assessment
SURVIVAL
Less
than 24
Total
(years)
24-5
Over
5
1
-6
2
2
1
3
-
1
The
-
1
3
-8
3
2
5
-9
4
5
9
1
-
-10
5
7
12
2
-
-Il
7
9
16
I
-12
7
6
13
1
1
-13
9
9
18
2
I
-14
II
12
23
-15
14
9
23
Totals
66
59
125
2
-
I
site
distribution
of
points
presented
occurred
should
of tumours-Figure
the
be
in the
in the
region
I shows
primary
noted:
long
1) 96
of the
TREATMENT
2
2
4
13
the
per
of the
knee
skeletal
The
following
cent
of the tumours
limbs;
2) 68 per cent
; 3) tumours
of the
of treatment
it is necessary
definitive
of cure may be
been taken
as the
is, the number
at five years
from
treatment.
vast
majority
of children
and
It
have
long
bone
they die from distant
Figure
2 shows
the
manifestation
whose
clinical
is not
sufficient
following
tumours
metastaseschronological
of lung metastases
and radiographic
information
points
should
unusual
to find
evidence
for this
be noted:
of metastatic
thirty
months
(one out of seventy-seven)
tases are unusual
(Fig. 2).
Although
present
results
at two and a half years,
tumours.
bones
osteosarcoma
to be
I) 50
per cent of the children
(thirty-eight
out of seventy-seven)
were known to have metastases
at five months;
and 2) it
2
4
II
of
records
provided
determined.
The
I
shows
Anatomical
for
however,
to wait so long as this before
attemptevaluate
and compare
the results
of treatment.
distribution
of the first
for seventy-five
children
was
2
of the results
(here 96 per cent),
usually
pulmonary.
-7
-
OF
commencement
essential,
ing to
1
-
cent
to define
the time when
the assumption
justified.
In the past this has usually
five years’ crude
survival
percentage-that
living with or without
evident
disease
the
0-4
-5
arm;
II
Survival
Years
of the
long bones
are unonly 4 per cent in
males.
EVALUATION
TABLE
as tumours
than
the
comprise
leg
that
at that
time
seventy-six
spread
after
and late metasit is not usual
to
the present
study
of the
seventy-seven
patients
(98 per cent) had evident
metastases.
Thus,
after
two and a half years in most cases a cure may be anticipated,
since
for long-bone
tumours
direct
invasion
of
vital organs
is a rarity.
The disease-free
and crude
survival
curves
for longbone tumours
(1973)
support
THE
at all ages published
this assertion.
JOURNAL
OF
BONE
by
AND
Price
JOINT
and
Jeffree
SURGERY
OSTEOSARCOMA
Fiu.
343
IN CHILDREN
I
Site of primary
FIG.
tumour.
RESU
As
might
there
patients
or
time
T,rnss(ir
months)
dICer
FIG.
57-B,
with
seven
contributory
centres
were
treated
by a combination
during
which
by either
of both.
this
series
For
All the
radiotherapy
or operation,
Owing
to the prolonged
of cases
has
been
collected
disjnosis
2
First appearance
of pulmonary
metastasis
in seventy-seven
patients.
No information:
twenty
patients:
alive, no metastasis:
twenty-eight
patients;
50 per cent have metastases
at five months;
98 per cent at
thirty months.
VOL.
be expected,
LTS
was much variety
in the methods
of treatment.
reason
these are given in detail
in Table
III.
this
z
3
Results
of treatment
related
to site of primary
tumour.
Black
circles:
dead with metastasis
within
two and a half years of the
start oftreatment.
Stippled
circles:
alive without
metastasis.
Upper
figure: over two and a halfyears;
lower figure: under two and a half
years.
(**Metastases
evident
at eight years.)
No. 3. AUGUST
1975
(for instance,
the
1972) some patients
after
1956, mainly
differing
regimes
Bristol
group
extended
received
orthovoltage
megavoltage
therapy
of treatment
have
been
from
1946 to
irradiation,
but
was given.
The
combined
into
344
C. H. G.
five
categories
variations
Age
specified
within
in Table
III, with
only
group.
I I indicates
that survivors
each
and survival-Table
appear
at any
younger
age:
as compared
as compared
Tumour
site
children
were
half
there
years
is no
with
girls.
and
survival
alive
older
minor
children,
nor
(thirteen
for
for
AL
cases unsuitable
largest
group
may
difference
ET
boys
(Fig.
and
the
free
3)-Seventeen
from
two
and
of
disease
a half
at two
years
the
OF TUMOUR,
a
one
children
therapy
METHOD
Site
Femur
Tibia
fifty-seven)
was
delayed
(Groups
composed
none
was
These
AND
1 . Biopsy
and
Survival
Humerus
Alive-no
metastasis
(years after start of
and
13
2
10
7
-
1
2
14
6
-
2
3
6
1
3
5
3
11
55
30
9
45
21
radical
with
metastases
No metastasis
2years
I
metastasis
2i to 5 years
No
metastasis
over
corrected
1
Metastases
cent
all had
and
long-bone
survival
12 per
-
tumour
of the
tibia,
and
(two)
and
survived
tumour
metastases.
of
somewhat
proximal
the
5
24-5
5 or
more
4
6
Under
metastasis
2
40
28
2
-
-
20
16
1
-
-
25
19
4
4
21
21
--
3
-
2
1
1
5
3
-
figures
1
19
13
4
3
17
2
2
5
125
97
11
4
13
2
14
I
5
97
lOper
3per
l2per
cent
cent
cent
-
and
one
children
with
they
with
for arm
--
but
had
been
under
ten
(Table
with a
of the
with
observation
years
to
be
those
being
with nine out
children
were
for
less
1*
corrected
are
for other
not
77percent
11
lOpercent
4
3 percent
13
12 percent
patients
statistically
2
-
still living.
significant
(p
<
0. 1) ; neverthe-
less,
immediate
appears
to give
ablation
of
the best results.
the tumour-bearing
limb
None
of the five children
with
at
than
tumours
sites
other
the
long
disease-free
at two and a half years (Fig.
Local recurrence
of primary
tumour-After
amputation
(two).
One
years
with a
to five
2
ences
respec-
of proximal
as compared
of survival
-
percentages
seventeen
and
then
succumbed
that the prognosis
may
tumours
two and a half years.
Treatment
and survival-The
Table Ill avoid the delineation
I
a tumour
tumours
---
1
included
middle
part of the humerus
free from
disease
for eight
incidence
1
-
being
-
2
1
These
-
1
Survival
four out of nineteen
for the arm compared
of eighty-six
for the leg. A further
eleven
alive,
-
4
--
of the knee region
surviving
one child
femur,
four
the distal
radius,
It is interesting
better
leg,
6
-
4
cent.
tumours
of the eighty-five
with tumours
III, Fig. 3). There
were also
also
Totals
4
1
at 8 years.
disease-free
15 per
children
--
5 years
*
of the
2
under
No
part
child
bones
with
biopsy
Totals
distal
Ulna
ProximalMiddle
Dead
and radiotherapy
5. Operation-not
tively
Other
ablation
4. Radiotherapy
and
and radiotherapy
years
Distal
20
and ablation
Dead
Proximal
1
later
3. Biopsy
Distal
Radius,
ablation
forthwith
2. Biopsy
differ-
treatment)
middle
.
radio-
SURVIVAL
of tumour
and
of treatment
by
group
Proximal
Method
twenty-
111
OF TREATMENT
and fibula
for two
ofthe
treatment
4) survived.
patients
(Groups
by radio-
survived
4), but
definitive
(Group
of
surgery
treated
ablation
3 and
whose
alone
It may be seen that the
two and a half years
or early ablative
out of forty-two
or without
a halfyears
TABLE
SITE
of
with
and
five
for comparison.
survivors
over
with immediate
2). Two patients
125
and
and
of
out
treated
1 and
therapy
with
or more,
significant
PRICE
of forty-six
operative
amputated
an event
radiotherapy
only
two
patients
so treated.
investigation
limb
had
Possibly
and
avoidable.
seven
Of
recurrence
out
more
elaborate
pre-
examination
theatre
might
twenty-seven
recurred
was
a local
immediate
in the operating
bones
3, Table
III).
transfemoral
of an
make
tumours
locally.
This
figure
to that reported
by Lee and Mackenzie
(1964)
tumour
tissue of possible
viability
in tumours
after radiotherapy.
such
given
is similar
for residual
amputated
than
DISCUSSION
subdivisions
adopted
of many small groups
in
of
The
in
results
a group
reported
here
of 1 25 children
TIlE
JOURNAL
ofthe
treatment
indicate
OF
BONE
that
AND
of osteosarcorna
the prognosis
JOINT
SURGERY
may
OSTEOSARCOMA
be
even
worse
five years’
that
of
a
there
between
the
is
of
free
of
avoids
and
the
there
are
cartilaginous
tumours
of
the
recurrences
arm.
after
implies
that the essentialfirst
be complete
control
practical
purposes,
most
promising
months
on
under
close
trial include
now
With
method
therapy
for occult micrometastases
nevertheless,
there
have been
telangiectatic
tumour
proportion
the
of
primary
as
(Jaffe,
metastatic
risk.
utterly
local
time
is the effective
prevention
there
can be no doubt
principle
in any
curative
ofthe primary
tumour.
this can only be effected
hood
regime
At present,
the
in
for
and
ablation.
is all the
of
most
may
value
of this
Cortes
et al. 1974).
is likely
to be most
is completely
and
it is employed
at the
These
points
earliest
again
chemochild-
figure
here reported.
In
of long-bone
tumours
are
potentially
treatment,
to significant
are
rather
than
with selective
trial of this new adjuvant
urgent
for patients
during
of which
lead
chemo-
yet be assessed;
early
reports
of prompt
amputation,
regime
of radiotherapy
The
more
Most
and
Acid
rescue
in a
(Cortes,
Holland,
Bodey,
Sinkovics,
Etcubanas,
Long,
1974;
progress.
antimetastatic
tory and
results.
Bishop
when
for
is chemo-
after the diagbe continued
cannot
encouraging
the high
mortality
the high proportion
children,
effective
by amputation.
and
The
adjuvant
treatment
the primary
tumour
in favour
protracted
also
1974).
patient’s
with
view
must
Traggis
removed
in
delayed
therapy
the
problem
metastases,
Leavitt
this
when
arguments
the more
method
Although
Frei,
Obviously,
effective
tumour
the
and
have
expert
supervision.
at least
Adriamycin
high-dose
Methotrexate
with
Folinic
pulsed
multi-drug
plan
of treatment
Wang
and Glidewell
1974;
Gottlieb,
Rodriguez
and Burgess
1974; Wilbur,
patient
there
treatment
method
as possible
This
should
Glatstein
amputation
or
urgent
of
twelve
schemes
must
be emphasised
also
that
the
tumour
tissue
anywhere
in the body
continuation
ultimate
and
and destruction
The
study
of adjuvant
Hospital
its employcontracture
for
immediate
and
it
of active
analytical
operations.
higher
radiotherapy
supports
of choice,
persistence
for
method
is probably
unsuitable
and
is more
appropriate
for
The
of this
developments
Westminster
for
flexion
mutilating
or
Moreover,
the
young
children
difference
the latter
new
therapy,
commenced
as soon
nosis
has been
established.
1974).
ifthe
the time
several
osteosarcoma.
of twenty-
considerations.
but
structure.
for very
out
(Steward
tumour,
the proponents
ofthe
certain
contra-indications
fungation,
fracture,
markedly
likewise
this
been
Manchester
amputation
unsuccessful
matches
significant
other
from
During
corrected
alternative
treatment
or radiotherapy
fol-
amputation
mortality
the
three
years
two
by selective
disease,
many
five
statistically
of
months
Nevertheless,
regime
admit
ment-tumour
by
in which
for
is no
The
of I 2 per cent
collected
immediate
a high
persons.
rate
Registry,
results
at six
such
group
survived
Whereas
regimes
older
survival
Tumour
children
lowed
for
similar
Children’s
eight
than
disease-free
345
IN CHILDREN
such
curable
trials
are
improvements
with
manda-
in future
With cases contributed
by seven treatment
centres,
it becomes
quite impossible
to express
the authors’
thanks
individually
to the many
colleagues
who,
by referring
their cases,
have furnished
the information
on which
this analytical
study
is based.
Nevertheless,
acknowledgment
is here recorded
of this prolonged
essential
collaboration.
Technical,
clerical
and other staff concerned
are thanked
for their services.
Valuable
help was given with the Bristol series by Dr E. Michelinakis,
Dr G. M. Jeifree and Mrs J. E. Nutt, in collecting
the case records
and in the extraction
of information
from the questionnaires.
The Bristol Bone Tumour
Registry
is supported
financially
by the Cancer
Research
Campaign.
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