Skin
Thickness
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HERMAN
in the Therapeutically
I. LIBSHITZ,’
ELEANOR
D.
MONTAGUE,2
AND
measurements thicknesses
Skin thickening of the breasts of 22 women undergoing excision biopsy of a breast cancer and subsequent radiation therapy to 5,000 rad Is considered. The skin thickness of the treated breast returned to normal in 17 of 22 patIents studied. Of the 17, nearly 60% returned to normal in 2 years, over 80% in 3 years, and the rest by 4 years. The period of follow-up was less than 4 years In the five patients with residual skin thickening. The alterations in skin thickness are consistent with the histopathologic changes seen in radiation dermatitis.
in the
portion between equality.
Prior
reports
have
shown
that
can
However, ing
we
have
radiation
therapy
pathologic This
was
the
receiving
excision
thickness
and
Institute
who
had
cancer
and subsequent
tumors
ranged
keeping
radiation
the
dermatitis. to accurately
wedge
therapy
Hospital
excision All
but
six
and The
recurrent
disease
or distant
metastases
on follow-up;
postoperative edema possible unappreciated
in skin Patients to avoid
Bolus
areas
(3)
of moist
the boost intensity between
77030. Address 2Department Am J Roentgenol © 1 978 American
reprint
requests
of Radiotherapy,
mammary
to the internal
was
depending used
on
the
to increase
with nonbolus
and friction
The desired
the
treatment
(inframammary
skin
reaction
dry desquamation,
desquamation
are
acceptable.
at the
but small
The
addition
of
the overall
reaction. No correlation could be made of the skin reaction and the resulting skin
thickness.
and to exclude spread.
October
University
dose
(voltage
alternated
is pigmented
of the skin the intensity
Radiographic timing
in table
(i.e.,
1
other
a possible could cause the original
Findings
of mammograms
the
thicknesses The skin
after revision
internal
to the area of the scar does not change
0.1 mm intervals. Repeat measurements showed error of 0.1 mm for any single measurement. This a possible compound error of 0.4 mm in comparing
Radiology,
is usually
in the areas of warmth
occurred within 36
Diagnostic
was given to the
and
rad tumor
tail of the breast).
and
The measurements of skin thickness were made in the same relative position in the same view of both breasts. All measurements were made with a Baush & Lomb measuring magnifier (cat. no. 81-34-35) with a 10 mm long metric scale, engraved at
April 5, 1977; accepted
4,500
particularly
following
Department:of
supraclavicular
sulcus
The
,
with 80Co irradiation
and
delivering
end of treatment
Measurements
Received
a
for the first week. Generally at the third treatment week, stippled erythema begins which progresses into homogenous erythema,
thickness of the two breasts with greater than a 0.3 mm possible changes related to
in the involved breast changes of lymphangitic
fields
skin dose.
skin thickness measurements possible at the same relative position in both breasts on the same view of the breast; and (4) less than 0.3 mm difference prior to radiation therapy. difference were excluded
axilla,
or low voltage electrons are used thickness of the area to be treated). Tissue equivalent bolus material
had
excision of the primary tumor before referral to this institution. None had had disturbance of the axilla, either from biopsy or axillary dissection, prior to irradiation. In an attempt to limit the cause of any alteration in skin thickness to those of radiation change alone, we included 22 patients based on the following criteria: (1) mammograms available from both before and after radiation therapy and complete clinical follow-up was available; (2) no evidence of locally
that
cancel out, a difference of 0.3 mm of both breasts was accepted as
the midbreast level or the excised tumor depth if it is a peripherally located primary tumor. At completion of 5,000 rad tumor dose in 5 weeks, a reduced appositional field is used to deliver an additional 1 000 rad in 5 days to the excision scar with an adequate margin. Either #{176}Co
of their
were reviewed.
in diameter.
Assuming
skin mm
contour of the midportion of the breast is utilized to establish isodose distributions made with and without bolus. The daily dose is calculated to deliver 1 000 rad tumor dose per week at
in women
therapy.
at M. D. Anderson
mammograms.
The 0.1
mammary nodes at a depth of 3 cm; the remainder had internal mammary node treatment included in the tangential portals. The medial and lateral fields are treated daily. The transverse
Methods
undergone
2 to 6 cm
with
pretreatment
delivered
breast,
mammary
follow-
of breast
radiation
and
of all patients
Tumor
in
in radiation
JR.’
nodes. A tumor dose of 5,000 rad was delivered in 5 weeks (25 fractions) to each area. Portals included medial and lateral tangential fields treating the breast, an anterior supraclavicularaxillary portal, and a posterior axillary portal opposing the low and central axilla. Seventeen patients had separate internal
thickening
thickening
in an attempt
in skin
from
skin
PAULUS,
Therapy
Radiotherapy
cancer of the breast to the breast [1].
resolve,
undertaken
Subjects
The records
the
described
changes
local
that may
changes
review
define
noted
skin
D.
of this error would the thicknesses
Radiation
More women are now receiving excision biopsy and radiation therapy as primary treatment of their breast to that seen in inflammatory result from radiation therapy
DAVID
Breast
of both breasts with subsequent ones. the two breasts averaged less than
of
difference
entire
cancers. similar
Irradiated
completion
The
.
within
skin
0.3 within months
three
and
thickness
mm)
the
of radiation in
of the
17
of
status
therapy breasts
the
22
of the
skin
is shown was
equal
patients.
This
24 months in 10 of the 22 patients, in four, and within 48 months in the
patients.
The
average
time
at
which
skin
were noted to be equal was 23 months. thickness was noted to be equal on the
first
17, 1977.
of Texas
System
Cancer
Center,
M. D. Anderson
Hospital
and
Tumor
Institute,
Houston,
Houston,
Texas
Texas
to H. I. Libshitz. University
130:345-347, February Roentgen Ray Society
of Texas
1978
System
Cancer
Center,
345
M. D. Anderson
Hospital
and
Tumor
Institute,
0361 -803X/78/0200
-
77030.
0345 $02.00
LIBSHITZ
Downloaded from www.ajronline.org by 138.210.33.74 on 11/12/15 from IP address 138.210.33.74. Copyright ARRS. For personal use only; all rights reserved
346
follow-up study in eight patients. The range was 10-18 months (average, 13 months). Nine patients in whom the skin thickness returned to normal had inequality of skin thickness on at least one interval study. The time of the return to normal thickness ranged from 20 to 47 months (average, 34 months). The interval mammograms at which skin thickness was unequal ranged from 7 to 35 months (average, 18 months). Representative cases are shown in figures 1 and 2. In the five patients in whom equality of skin thickness TABLE
1
Time of Mammogram Time Case
and 5km ness
and Skin Status
Thick-
Time
ce
No.
and Skin
Thickness
No. Unequal
Equal
unequal
Equal
28-30
1
10-12
12
.
. .
.
2
10-12
13
.
.
.
.
3 4
13-15 13-15
14 15
.
.
.
.
.
.
.
.
5
16-18
16
. .
.
.
10-12, 16-18 10-12, 22-24 19-21 10-12 19-21
6
16-18
17
.
.
.
10-12,
.
31-33 34-36
40-42 40-42 46-48
34-36
7 8 9
,,...,
16-18
18
.
16-18 19-21
19 20
. .
10-12
7-9
...
. .
.
.
10-12
.
.
. .
.
.
1-3,
.
.
.
.
.
.
....
13-15 10
.
11
...
.
.
.
10-12 7-9
22-24 25-27
Mont ha after completion
21 22
. . ....
of radia tion therapy.
.
.
31-33 13-15,3133, 40-42
ET AL. was not seen, the 33, and 41 months. ness was unequal grams at 15 and 33 ity.
periods of follow-up were 9, 1 1 , 13, The patient in whom the skin thickat 41 months had interval mammomonths which also showed inequal-
Discussion
In a previous report by one of us (HI. Libshitz) in a different series of patients, postinnadiation skin thickening had been noted in all patients [1]. Complete nesolution had not been seen, but the skin thickening diminished with time in several patients. In a review of patients with inoperable breast cancer, Nisce et al. [2] noted no patients in whom skin thickening completely disappeared. Bloomer et al. [3] reported variable skin thickening at less than 6 months and observed its presence after 6 months. However they did not specifically state in which patients these changes occurred non did they report any cases in which the skin returned to normal. The findings in this series are in keeping with the histopathologic description of radiation dermatitis. Lever [4] described an early (acute) stage and a late (chronic) stage of radiation dermatitis, the late or chronic stage occurring from a few months to years after the radiation therapy. Histopathologically, early radiation dermatitis shows intracellular and extracellular edema of the epidermis. An inflammatory infiltrate is present in the denmis and may permeate the epidermis. The collagen bundles also show edema. With the resolution of these acute changes, the skin becomes atrophic in late on chronic radiation dermatitis.
Fig . 1 . - Magnified craniocaudad view of left breast (A) and untreated right breast (B) both obtained 18 months after radiotherapy. No difference
in
skin
thickness
Photograph
of right
to facilitate
comparison.
is apparent. breast
reversed
SKIN
A
THICKNESS
IN IRRADIATED
347
BREASTS
B
C
..
_.?
Downloaded from www.ajronline.org by 138.210.33.74 on 11/12/15 from IP address 138.210.33.74. Copyright ARRS. For personal use only; all rights reserved
“1.-i’
:“-
-
..
-
‘‘
.
/
.
I ‘
/
5,.4
/
I
f
1
I
, , ,
-.,
‘-
,;..
‘i’; Fig. 2.-A, Magnified craniocaudad view of left breast 19 months after radiotherapy showing slight skin thickening. B, Similar view of left breast 42 months after radiotherapy showing return of skin to normal thickness. Compare similar view of untreated right breast obtained at same time (C). Photograph of right breast reversed to facilitate comparison.
Patients in our series had no evidence of skin involvement of their breast cancers non of local or distant recurrence following radiation therapy. Thus our findings are in keeping with the pathologic changes descnibed in radiation dermatitis. During the stage of acute radiation dermatitis, differentiation from lymphangitic involvement would be quite difficult. However, it becomes apparent that most of the patients treated to 5,000 rad following excision biopsy will, in time, have resolution of the skin changes caused by radiation thenapy. Of the 17 patients followed to resolution of the skin changes, 10 (59%) resolved within 2 years, 14 (82%) by the end of 3 years, and all 17 patients after 4 years. Patients in whom equality of the skin thickness has not occurred have been followed up to 41 months. The use of bolus and the occurrence of desquamation (moist or dry) seemed to have little relation to the final resolution of thickening. The only possible exception is the one patient followed 41 months whose skin changes have not returned to normal and in whom bolus was used for 45% of the tumor dose. In no other patient was bolus used for over 30% of the tumor dose. To our knowledge, this is the first study of skin thick-
ness changes due only to radiation therapy. Because a greater number of women are refusing radical mastectomy
and
requesting
excision
apy, the opportunity was changes due to radiation one of the classic findings noma, recognition that irradiation follow a definite distinguishing between change and lymphangitic
biopsy
and
radiation
ther-
presented to define the skin alone. While skin thickening is in inflammatory breast carcithe skin changes caused by temporal pattern may aid in acute radiation-induced skin spread.
REFERENCES 1 . Libshitz
HI, Southard ME: Mammography following primary radiation therapy for carcinoma of the breast. Am J Roentgenol 120:62-66, 1974 2. Nisce LZ, Snyder RE, Chu FCH: The role of mammography in
evaluating
radiation response of inoperable primary Radiology 110:85-88, 1974 3. Bloomer WD, Berenberg AL, Weissman BN: Mammography of the definitively irradiated breast. Radiology 118:425-
breast
cancer.
428, 1976 4. Lever WF: Histopatho/ogy cott,
1967
of the Skin. Philadelphia,
Lippin-
Thickness
Downloaded from www.ajronline.org by 138.210.33.74 on 11/12/15 from IP address 138.210.33.74. Copyright ARRS. For personal use only; all rights reserved
HERMAN
in the Therapeutically
I. LIBSHITZ,’
ELEANOR
D.
MONTAGUE,2
AND
measurements thicknesses
Skin thickening of the breasts of 22 women undergoing excision biopsy of a breast cancer and subsequent radiation therapy to 5,000 rad Is considered. The skin thickness of the treated breast returned to normal in 17 of 22 patIents studied. Of the 17, nearly 60% returned to normal in 2 years, over 80% in 3 years, and the rest by 4 years. The period of follow-up was less than 4 years In the five patients with residual skin thickening. The alterations in skin thickness are consistent with the histopathologic changes seen in radiation dermatitis.
in the
portion between equality.
Prior
reports
have
shown
that
can
However, ing
we
have
radiation
therapy
pathologic This
was
the
receiving
excision
thickness
and
Institute
who
had
cancer
and subsequent
tumors
ranged
keeping
radiation
the
dermatitis. to accurately
wedge
therapy
Hospital
excision All
but
six
and The
recurrent
disease
or distant
metastases
on follow-up;
postoperative edema possible unappreciated
in skin Patients to avoid
Bolus
areas
(3)
of moist
the boost intensity between
77030. Address 2Department Am J Roentgenol © 1 978 American
reprint
requests
of Radiotherapy,
mammary
to the internal
was
depending used
on
the
to increase
with nonbolus
and friction
The desired
the
treatment
(inframammary
skin
reaction
dry desquamation,
desquamation
are
acceptable.
at the
but small
The
addition
of
the overall
reaction. No correlation could be made of the skin reaction and the resulting skin
thickness.
and to exclude spread.
October
University
dose
(voltage
alternated
is pigmented
of the skin the intensity
Radiographic timing
in table
(i.e.,
1
other
a possible could cause the original
Findings
of mammograms
the
thicknesses The skin
after revision
internal
to the area of the scar does not change
0.1 mm intervals. Repeat measurements showed error of 0.1 mm for any single measurement. This a possible compound error of 0.4 mm in comparing
Radiology,
is usually
in the areas of warmth
occurred within 36
Diagnostic
was given to the
and
rad tumor
tail of the breast).
and
The measurements of skin thickness were made in the same relative position in the same view of both breasts. All measurements were made with a Baush & Lomb measuring magnifier (cat. no. 81-34-35) with a 10 mm long metric scale, engraved at
April 5, 1977; accepted
4,500
particularly
following
Department:of
supraclavicular
sulcus
The
,
with 80Co irradiation
and
delivering
end of treatment
Measurements
Received
a
for the first week. Generally at the third treatment week, stippled erythema begins which progresses into homogenous erythema,
thickness of the two breasts with greater than a 0.3 mm possible changes related to
in the involved breast changes of lymphangitic
fields
skin dose.
skin thickness measurements possible at the same relative position in both breasts on the same view of the breast; and (4) less than 0.3 mm difference prior to radiation therapy. difference were excluded
axilla,
or low voltage electrons are used thickness of the area to be treated). Tissue equivalent bolus material
had
excision of the primary tumor before referral to this institution. None had had disturbance of the axilla, either from biopsy or axillary dissection, prior to irradiation. In an attempt to limit the cause of any alteration in skin thickness to those of radiation change alone, we included 22 patients based on the following criteria: (1) mammograms available from both before and after radiation therapy and complete clinical follow-up was available; (2) no evidence of locally
that
cancel out, a difference of 0.3 mm of both breasts was accepted as
the midbreast level or the excised tumor depth if it is a peripherally located primary tumor. At completion of 5,000 rad tumor dose in 5 weeks, a reduced appositional field is used to deliver an additional 1 000 rad in 5 days to the excision scar with an adequate margin. Either #{176}Co
of their
were reviewed.
in diameter.
Assuming
skin mm
contour of the midportion of the breast is utilized to establish isodose distributions made with and without bolus. The daily dose is calculated to deliver 1 000 rad tumor dose per week at
in women
therapy.
at M. D. Anderson
mammograms.
The 0.1
mammary nodes at a depth of 3 cm; the remainder had internal mammary node treatment included in the tangential portals. The medial and lateral fields are treated daily. The transverse
Methods
undergone
2 to 6 cm
with
pretreatment
delivered
breast,
mammary
follow-
of breast
radiation
and
of all patients
Tumor
in
in radiation
JR.’
nodes. A tumor dose of 5,000 rad was delivered in 5 weeks (25 fractions) to each area. Portals included medial and lateral tangential fields treating the breast, an anterior supraclavicularaxillary portal, and a posterior axillary portal opposing the low and central axilla. Seventeen patients had separate internal
thickening
thickening
in an attempt
in skin
from
skin
PAULUS,
Therapy
Radiotherapy
cancer of the breast to the breast [1].
resolve,
undertaken
Subjects
The records
the
described
changes
local
that may
changes
review
define
noted
skin
D.
of this error would the thicknesses
Radiation
More women are now receiving excision biopsy and radiation therapy as primary treatment of their breast to that seen in inflammatory result from radiation therapy
DAVID
Breast
of both breasts with subsequent ones. the two breasts averaged less than
of
difference
entire
cancers. similar
Irradiated
completion
The
.
within
skin
0.3 within months
three
and
thickness
mm)
the
of radiation in
of the
17
of
status
therapy breasts
the
22
of the
skin
is shown was
equal
patients.
This
24 months in 10 of the 22 patients, in four, and within 48 months in the
patients.
The
average
time
at
which
skin
were noted to be equal was 23 months. thickness was noted to be equal on the
first
17, 1977.
of Texas
System
Cancer
Center,
M. D. Anderson
Hospital
and
Tumor
Institute,
Houston,
Houston,
Texas
Texas
to H. I. Libshitz. University
130:345-347, February Roentgen Ray Society
of Texas
1978
System
Cancer
Center,
345
M. D. Anderson
Hospital
and
Tumor
Institute,
0361 -803X/78/0200
-
77030.
0345 $02.00
LIBSHITZ
Downloaded from www.ajronline.org by 138.210.33.74 on 11/12/15 from IP address 138.210.33.74. Copyright ARRS. For personal use only; all rights reserved
346
follow-up study in eight patients. The range was 10-18 months (average, 13 months). Nine patients in whom the skin thickness returned to normal had inequality of skin thickness on at least one interval study. The time of the return to normal thickness ranged from 20 to 47 months (average, 34 months). The interval mammograms at which skin thickness was unequal ranged from 7 to 35 months (average, 18 months). Representative cases are shown in figures 1 and 2. In the five patients in whom equality of skin thickness TABLE
1
Time of Mammogram Time Case
and 5km ness
and Skin Status
Thick-
Time
ce
No.
and Skin
Thickness
No. Unequal
Equal
unequal
Equal
28-30
1
10-12
12
.
. .
.
2
10-12
13
.
.
.
.
3 4
13-15 13-15
14 15
.
.
.
.
.
.
.
.
5
16-18
16
. .
.
.
10-12, 16-18 10-12, 22-24 19-21 10-12 19-21
6
16-18
17
.
.
.
10-12,
.
31-33 34-36
40-42 40-42 46-48
34-36
7 8 9
,,...,
16-18
18
.
16-18 19-21
19 20
. .
10-12
7-9
...
. .
.
.
10-12
.
.
. .
.
.
1-3,
.
.
.
.
.
.
....
13-15 10
.
11
...
.
.
.
10-12 7-9
22-24 25-27
Mont ha after completion
21 22
. . ....
of radia tion therapy.
.
.
31-33 13-15,3133, 40-42
ET AL. was not seen, the 33, and 41 months. ness was unequal grams at 15 and 33 ity.
periods of follow-up were 9, 1 1 , 13, The patient in whom the skin thickat 41 months had interval mammomonths which also showed inequal-
Discussion
In a previous report by one of us (HI. Libshitz) in a different series of patients, postinnadiation skin thickening had been noted in all patients [1]. Complete nesolution had not been seen, but the skin thickening diminished with time in several patients. In a review of patients with inoperable breast cancer, Nisce et al. [2] noted no patients in whom skin thickening completely disappeared. Bloomer et al. [3] reported variable skin thickening at less than 6 months and observed its presence after 6 months. However they did not specifically state in which patients these changes occurred non did they report any cases in which the skin returned to normal. The findings in this series are in keeping with the histopathologic description of radiation dermatitis. Lever [4] described an early (acute) stage and a late (chronic) stage of radiation dermatitis, the late or chronic stage occurring from a few months to years after the radiation therapy. Histopathologically, early radiation dermatitis shows intracellular and extracellular edema of the epidermis. An inflammatory infiltrate is present in the denmis and may permeate the epidermis. The collagen bundles also show edema. With the resolution of these acute changes, the skin becomes atrophic in late on chronic radiation dermatitis.
Fig . 1 . - Magnified craniocaudad view of left breast (A) and untreated right breast (B) both obtained 18 months after radiotherapy. No difference
in
skin
thickness
Photograph
of right
to facilitate
comparison.
is apparent. breast
reversed
SKIN
A
THICKNESS
IN IRRADIATED
347
BREASTS
B
C
..
_.?
Downloaded from www.ajronline.org by 138.210.33.74 on 11/12/15 from IP address 138.210.33.74. Copyright ARRS. For personal use only; all rights reserved
“1.-i’
:“-
-
..
-
‘‘
.
/
.
I ‘
/
5,.4
/
I
f
1
I
, , ,
-.,
‘-
,;..
‘i’; Fig. 2.-A, Magnified craniocaudad view of left breast 19 months after radiotherapy showing slight skin thickening. B, Similar view of left breast 42 months after radiotherapy showing return of skin to normal thickness. Compare similar view of untreated right breast obtained at same time (C). Photograph of right breast reversed to facilitate comparison.
Patients in our series had no evidence of skin involvement of their breast cancers non of local or distant recurrence following radiation therapy. Thus our findings are in keeping with the pathologic changes descnibed in radiation dermatitis. During the stage of acute radiation dermatitis, differentiation from lymphangitic involvement would be quite difficult. However, it becomes apparent that most of the patients treated to 5,000 rad following excision biopsy will, in time, have resolution of the skin changes caused by radiation thenapy. Of the 17 patients followed to resolution of the skin changes, 10 (59%) resolved within 2 years, 14 (82%) by the end of 3 years, and all 17 patients after 4 years. Patients in whom equality of the skin thickness has not occurred have been followed up to 41 months. The use of bolus and the occurrence of desquamation (moist or dry) seemed to have little relation to the final resolution of thickening. The only possible exception is the one patient followed 41 months whose skin changes have not returned to normal and in whom bolus was used for 45% of the tumor dose. In no other patient was bolus used for over 30% of the tumor dose. To our knowledge, this is the first study of skin thick-
ness changes due only to radiation therapy. Because a greater number of women are refusing radical mastectomy
and
requesting
excision
apy, the opportunity was changes due to radiation one of the classic findings noma, recognition that irradiation follow a definite distinguishing between change and lymphangitic
biopsy
and
radiation
ther-
presented to define the skin alone. While skin thickening is in inflammatory breast carcithe skin changes caused by temporal pattern may aid in acute radiation-induced skin spread.
REFERENCES 1 . Libshitz
HI, Southard ME: Mammography following primary radiation therapy for carcinoma of the breast. Am J Roentgenol 120:62-66, 1974 2. Nisce LZ, Snyder RE, Chu FCH: The role of mammography in
evaluating
radiation response of inoperable primary Radiology 110:85-88, 1974 3. Bloomer WD, Berenberg AL, Weissman BN: Mammography of the definitively irradiated breast. Radiology 118:425-
breast
cancer.
428, 1976 4. Lever WF: Histopatho/ogy cott,
1967
of the Skin. Philadelphia,
Lippin-
