856

Radiation-Induced Sarcomas after Radiotherapy for

Breast Carcinoma
A Large-Scale Single-Institution Review

Youlia M. Kirova, M.D.1 BACKGROUND. Sarcomas are a rare complication of radiotherapy for breast carci-
Jacques R. Vilcoq, M.D.1 noma and patients have a poor prognosis. The incidence, histology, and manage-
Bernard Asselain, M.D.2 ment of patients with sarcomas were reviewed in the current study.
Xavier Sastre-Garau, M.D.3 METHODS. The authors reviewed the records of 16,705 patients with breast carci-
Alain Fourquet, M.D.1 noma. Of these, 13,472 (81%) were treated with megavoltage radiotherapy and 3233
were treated without at the Institute Curie (Paris, France) between 1981 and 1997.
1
Department of Radiation Oncology, Institut Curie, Median doses of 50 –55 grays (Gy) in 25–27 fractions were delivered to the whole
Paris, France. breast over a period of 5–5.5 weeks (2 Gy/day, 5 weekly fractions) followed, when
2
Department of Biostatistics, Institut Curie, Paris, indicated, by a 16 –26-Gy boost to the tumor or tumor bed. Treatment of radiation-
France. induced sarcomas (RIS) consisted mostly of radical surgery and chemotherapy.
3 RESULTS. Overall, 35 patients developed sarcomas. Of these, 27 fulfilled the Cahan
Department of Pathology, Institut Curie, Paris,
France. criteria. The median follow-up was 9.3 years (range, 1–22.4 years). The latency
period ranged from 3 years to 20.3 years. Thirteen sarcomas were located in the
breast, 5– in the chest wall, 3 in the sternum, 2 in the supraclavicle, 1 in the scapula,
and 3 in the axilla. Histologic evaluation identified 13 angiosarcomas, 3 osteosar-
comas, 5 undifferentiated sarcomas, 1 malignant fibrous histiocytoma, 2 leiomy-
osarcomas, 1 fibrosarcoma, 1 rhabdomyosarcoma, and 1 myosarcoma. The cumu-
lative RIS incidence was 0.07% (⫾ 0.02) at 5 years, 0.27% (⫾ 0.05) at 10 years, and
0.48% (⫾ 0.11) at 15 years. Standardized incidence ratios were 10.2 (95% confi-
dence interval, 9.03–11.59) for irradiated patients and 1.3 (0.3–3.6) for nonirradi-
ated patients. Of the 27 patients, 15 died of sarcoma within 1 month to 14.5 years
(mean, 34.2 ⫾ 0.7 months). The 5-year actuarial survival rate after diagnosis of RIS
was 36% (⫾ 0.11).
CONCLUSIONS. The current study confirmed the rarity of RIS. However, it showed
that the risk increased with time. Therefore, careful, long-term follow-up of pa-
tients treated with radiotherapy is needed for early detection and efficacious
treatment of these malignancies. Cancer 2005;104:856 – 63.
© 2005 American Cancer Society.

Presented at European Society for Therapeutic

KEYWORDS: radiation-induced sarcoma, breast carcinoma, long-term risk, second
Radiology and Oncology 23, Amsterdam, The
Netherlands, October 24 –28, 2004. malignant neoplasms.

The authors thank C. Gautier for helping with data

management.

Address for reprints: Youlia M. Kirova, M.D.,

Department of Radiation Oncology, Institut Curie,
26 Rue d’Ulm, 75248 Paris, Cedex 05, France;
Fax: (011) 331-44-32-46-16; E-mail: youlia.
kirova@curie.net
Received December 27, 2004; accepted April 4,
2005.
A djuvant radiotherapy (RT) to the breast plays a significant role in
preventing local disease recurrence in women treated for early-
stage breast carcinoma. This fact is supported by multiple clinical
trials demonstrating that adjuvant RT decreases the risk of local
disease recurrence and increases the rate of breast preservation, and
actually the rules of adjuvant breast irradiation are clearly estab-
lished.1– 8
Sarcomas are a rare, but recognized, complication of RT for
breast carcinoma, and are associated with poor prognosis.9 –19 The

© 2005 American Cancer Society

DOI 10.1002/cncr.21223
Published online 24 June 2005 in Wiley InterScience (www.interscience.wiley.com).

first description of a bone sarcoma after RT of a breast
tumor was reported by Beck in 1922,12 and Warren
and Sommer in 193620 reported a soft tissue sarcoma
in the breast treatment volume. In 1948, Cahan et al.21
defined the criteria for the diagnosis of radiation-in-
duced sarcoma.
Since that time, some studies have reported the
incidence of RIS after RT for different cancers.9 –23 To our
knowledge, there are several reports of RIS after breast
carcinoma treatment, but most of the reported series
comprise a limited number of patients.9 –13,22,26 – 43
The current article reports and discusses the inci-
dence, management, and treatment outcome of RIS
after RT for patients with breast carcinoma at the
Institut Curie (Paris, France) during the period from
1981 to 1997. This is a large series (⬎ 16,700 patients
with breast carcinoma) from a single institution.
MATERIALS AND METHODS
We reviewed retrospectively the records for a popula-
tion of 16,705 patients treated for nonmetastatic
breast carcinoma at the Institut Curie between 1981
and 1997. Of these 16,705 patients, 13,472 received RT
and 3233 were treated without RT. Of the 13,472 pa-
tients treated with RT, 2347 patients underwent mas-
tectomy followed by RT and 11,125 had conservative
treatment (2529 patients underwent RT alone, 8596 –
underwent lumpectomy and RT). The patients who
underwent RT were irradiated using high-energy pho-
tons of a cobalt unit and/or linear accelerator, either
before or after surgery, or were treated exclusively
with RT. Median doses of 50 –55 grays (Gy) were de-
livered to the whole breast over 5– 6 weeks (4 –5 weekly
fractions) followed, when indicated, by a 16 –26-Gy
boost to the tumor or tumor bed. After mastectomy,
high-energy electrons were used to treat the chest
wall. The treatment modalities of our RIS population
of patients are shown in Table 1. The recommenda-
tions of the 29th and 50th reports from the Interna-
tional Commission on Radiation Units were com-
plied.44 We used either a standard tangential field
technique or a technique with the patient in the lateral
decubitus position.45,46 Some patients received an ad-
ditional RT dose delivered to the tumor site, axilla, and
internal mammary lymph nodes, using a direct 9 –12-
megavolt electron beam.
To diagnose RIS, we used the criteria established
by Cahan et al.21: 1) history of RT, 2) asymptomatic
latency period of several years, 3) occurrence of sar-
coma within a previously irradiated field, and 4) his-
tologic confirmation of the sarcomatous nature of the
postirradiation lesion. After reviewing the records, we
noted clinical and primary tumor characteristics, RT
history, RIS site, histology, treatment, and outcome.
Sarcomas after Breast Irradiation/Kirova et al. 857
Statistical Methods
Cumulative incidence rates were calculated using
Kaplan–Meier estimates. Annual incidence rates
were derived from the number of cases of RIS re-
ferred to the person-years at risk in the cohort.
Person-years at risk were calculated from the date of
diagnosis of breast carcinoma to the date of diag-
nosis of RIS for patients with RIS or to the date of
death or last follow-up for the patients without
RIS. Relative risks (RR) were calculated by a com-
parison of the incidence rates of sarcomas (RIS and
other sarcomas) in the RT and non-RT cohorts, and
95% confidence intervals (95% CI) were calculated
using the Breslow–Day method.47 Sarcoma inci-
dence rates in the two cohorts (RT and non-RT)
were then compared with the incidence of sarcomas
in the French population, estimated from the data
of five regional registries.48 Because the entire pop-
ulation is not covered in France, we considered an
average incidence rate of 2.7 per 100,000 (this rate
was more or less constant for patients ages 45–70
years).
RESULTS
Of the 16,705 patients, 35 patients developed sarco-
mas, 27 of whom developed RIS and fulfilled the cri-
teria established by Cahan et al.21 Eight patients did
not fulfill these criteria as follows: two had Stewart–
Treves syndrome (STS), and were excluded from the
analysis, and six patients had other histologic types
and different sites of sarcoma. In the group of 3233
patients with breast carcinoma who did not receive
irradiation, 1 patient had a sarcoma.
The median follow-up for all patients treated with
RT was 9.4 years, and was 8.9 years for patients who
did not receive RT and 9.3 years (range, 1–22.4 years)
for the patients with RIS. The median patient age at
the time of diagnosis of breast carcinoma was 56.2
years for the entire study population, as follows: 54.1
years for patients who received RT, 60.3 years for
patients who did not receive RT, and 57 years (range,
36 –74 years) for patients with RIS.
Table 1 gives the characteristics of the primary
breast tumors and their treatment in 27 patients pre-
senting with RIS. The median dose to the treatment
volume where sarcomas developed was 53 Gy (range,
45– 66 Gy).
The cumulative RIS incidence was 0.07% (⫾ 0.02)
at 5 years, 0.27% (⫾ 0.05) at 10 years, and 0.48% (⫾
0.11) at 15 years (Fig. 1). The standardized incidence
ratio (SIR) was 10.2 (95% CI, 9.03–11.59) for the irra-
diated population compared with the general popula-
tion and 1.3 (95% CI, 0.3–3.6) for patients with breast
858 CANCER August 15, 2005 / Volume 104 / Number 4

TABLE 1
Patient and Tumor Characteristics: Treatment at Breast Carcinoma Diagnosis

Age
Patient no. (yrs) Tumor stage Histology (grade) Treatment besides RT RT source RT dose (Gy)

1 61 T1-N1b M0 DAC (III) Lumpectomy ⫹ LND 60

Co Breast 51; tumor site 60; LN 47–50
2 38 T2-N0-M0 Medullary carcinoma Lumpectomy ⫹ LND; Mastectomy for 60
Co Breast 46; tumor site 61
disease recurrence
60
3 46 T4b-N1b M0 DAC Chemotherapy (FAC) Co Breast 50; tumor 65; axilla 55; SLN 48; IMC 47.5
4 66 T4b-N1a M0 DAC (I) Mastectomy ⫹ LND 60
Co Breast 50; tumor 63; axilla 50; SLN 50; IMC 41
60
5 52 T2-N1-M0 DAC (III) Chemotherapy (AC) Co Breast 50; tumor 64; axilla 60; SLN 43; IMC 47.5
60
6 56 T2-N0-M0 DAC (II) Lumpectomy Co Breast 50; tumor 74; axilla 55; IMC 35
60
7 61 T2-N0-M0 DAC No Co Breast 50; tumor 64; axilla 60; SLN 45; IMC 45
8 51 T2-Nx-M0 DAC Mastectomy ⫹ LND 60
Co ⫹ e- Breast 50; tumor 63; axilla 50; SLN 50; IMC 41
9 45 T2-N1-M0 DAC (II) Chemotherapy (FAC) Mastectomy 60
Co ⫹ e- Breast 47; tumor 69; axilla 60; SLN45; IMC 50
⫹ LND for disease recurrence
10 44 T1-N0-M0 DAC (I) ⫹ DCIS Lumpectomy 60
Co ⫹ e- Breast 54; axilla 43; SLN 40; IMC 50
11 36 T1-N0-M0 DAC (II) Lumpectomy ⫹ LND ⫹ FAC 60
Co Breast 58; tumor site 66; -LN 45
12 58 T2-N0-M0 DAC (I) Lumpectomy 60
Co ⫹ e- Breast 55; tumor site 66; LN 45
13 57 T2-N1-M0 DAC Lumpectomy ⫹ LND 60
Co ⫹ e- Breast 55; tumor site 66; -LN 45
14 63 T2-N1-M0 DAC (III) Lumpectomy ⫹ LND ⫹ FAC X6MV ⫹ e- Breast 54; LN 45
15 57 T2-N0-M0 DAC (II) Lumpectomy ⫹ LND 60
Co Breast 54; IMC 45
16 68 Tx-N0-M0 LAC Lumpectomy ⫹ LND 60
Co ⫹ e- Breast 55; tumor site 66; LN 45
17 52 T1-N0-M0 DAC (II) Lumpectomy ⫹ LND 60
Co Breast 52;
18 60 T2-N0-M0 DAC (II) Lumpectomy ⫹ LND 60
Co Breast 50; tumor site 64; IMC 45
19 74 T1N0-M0 DAC (II) Lumpectomy ⫹ LND 60
-Co Breast 53; IMC 45
20 72 T2-N1-M0 DAC (II) Lumpectomy ⫹ LND 60
-Co Breast 52; axilla 45; SLN 45
21 59 T2-N0-M0 DAC (III) Lumpectomy ⫹ LND 60
-Co Breast 52; axilla 45; SLN 45
22 69 mT1-N0 M0 DAC (III) Wide lumpectomy ⫹ LND 60
-Co ⫹ e- Breast 50; tumor site 74; IMC 45
23 41 T2-N0-M0 LAC (II) Lumpectomy ⫹ LND ⫹ paclitaxel ⫹ 60
-Co ⫹ e- Breast 50; tumor site 66; IMC 50
doxorubicin
24 50 T3N1M0 DAC (II) Tamoxifen ⫹ castration 60
-Co Breast 56; tumor 75; axilla 65; SLN45; IMC 45
25 61 T1N0M0 LAC (I) No 60
-Co ⫹ Ir 192 Breast 54; tumor site 69; IMC 45
26 70 T2N0M0 DAC (I) Lumpectomy ⫹ LND 60
-Co Breast 50; tumor site 60
27 45 T2N1M0 DAC (II) Lumpectomy ⫹ LND ⫹ FAC 60
-Co Breast 50; tumor site 60; LN 45

RT: radiotherapy; Gy: gray; DAC: ductal adenocarcinoma; LND: lymph node dissection; 60CO: cobalt-60; LN: lymph node; FAC: 5-fluorouracil/doxorubicin/cyclophosphamide; SLN: sentinel lymph node; IMC: internal
mammary chain; AC: doxorubicin/cyclophosphamde; e-: MV: megavolt; DCIS: ductal carcinoma in situ; LAC: lobular adenocarcinoma; IR 192;

carcinoma who did not receive RT compared with the Whenever possible, patients underwent wide excision
general population’s risk (reference French cohort). of the sarcoma, mastectomy for patients with breast
The SIR of irradiated patients compared with nonirra- RIS, and chemotherapy with MAID (sodium mercap-
diated patients was 3.45 (95% CI, 0.088 –19.28), and toethanesulfonate, doxorubicin, ifosphamide, and
the RR was 8 (95% CI, 4.98 –12.7). dacarbazine). One patient (Patient 4) received RT be-
Data relating to RIS are shown in Table 2. At the cause of undefined resection margins. Two other pa-
time of a RIS diagnosis, all patients were free of tients were reirradiated (Patients 5 and 8) as part of
breast carcinoma. The median age at the time of their treatment (one patient for positive surgical re-
diagnosis of RIS was 63 years (range, 47– 82 years). section margins and one patient as a palliative modality
The latency period ranged from 3 years to 20.3 years. after recurrence of the sarcoma). Thalidomide was used
There were 13 breast sarcomas, 5 sarcomas of the if age and performance status precluded MAID use and
chest wall, 3 sternal lesions, 2 supraclavicular le- for second-line and third-line treatment (Patients 16 and
sions, 1 scapular lesion, and 3 sarcomas of the axilla. 20). Two patients underwent periclavicular surgery (Pa-
Histology was as follows: 13 angiosarcomas (48%), 3 tients 5 and 21).Twelve patients were still alive at the
osteosarcomas, 5 undifferentiated sarcomas, 1 ma- time of last follow-up, 8 of whom were free of disease
lignant fibrous histiocytoma (MFH), 2 leiomyosar- after radical treatment (Patients 7, 10, 13, 21, 23, 25, 26,
comas, 1 fibrosarcoma, 1 rhabdomyosarcoma, and 1 and 27); 3 patients were receiving chemotherapy and
myosarcoma. had stable disease (Patients 16, 17, and 19); and 1 patient
RIS treatment modalities are also given in Table 2. was awaiting surgery (Patient 22).

FIGURE 1. Cumulative radiation-induced sarcoma (RIS) incidence in the
Institute Curie series.
Of the 27 patients, 15 died of their sarcoma within
1 month to 14.5 years (mean, 34.2 ⫾ 0.7 months). The
5-year actuarial survival rate after diagnosis of RIS was
36% (⫾ 0.11).
DISCUSSION
The current study reports the incidence, management,
and treatment outcome of patients with RIS after RT
for breast carcinoma at our institute between 1981–
1997. To our knowledge, the current study is the larg-
est series (⬎ 16,700 studied patients) published to date
from a single institution. However, the limited number
of patients presenting with RIS did not permit us to
study different risk factors.
Table 3 shows the published RIS incidence rates
after treatment for breast carcinoma. Strict compar-
isons among studies are difficult because of differ-
ences in study inclusion criteria (RIS, STS, primary
breast sarcomas) and because of differences in the
nature of the data reported.9 –21 The current study
had a median follow-up period of 9.3 years. Our
cumulative RIS incidence was highly similar to those
reported in an earlier single-center French study
comprising a smaller population of patients22 and in
a recent large-scale study on registry data.23
Although RT increases the absolute risk of a sar-
coma, other factors such as chronic lymphedema were
found to be related to the increased risk of sar-
coma.49,50 To our knowledge, Stewart and Treves49
were the first to describe cases of angiosarcoma oc-
curring in lymphoedematous extremities after radical
mastectomy.
In the current study, the latency period ranged
from 3 years to 20.3years. The range overlaps with the
reported range of 2–50 years for breast irradiation.9 – 43
Shorter latency periods have been attributed to the
use of megavoltage rather than orthovoltage RT.51 In
Sarcomas after Breast Irradiation/Kirova et al. 859
the Institut Gustave Roussy series of 11 patients, 9
developed RIS after megavoltage RT and only 2 after
total body irradiation was delivered using orthovolt-
age.22 It is unclear to what extent our use of megavolt-
age may have affected latency time. All our patients
underwent megavoltage RT.
RIS incidence is considered to be a function of
RT dose.42,43 Most reports of RIS after breast irradi-
ation have been concerned with doses of 60 – 80 Gy44
with a minimal dose of 10 Gy in standard fraction-
ation. We delivered a somewhat lower dose of 50 –55
Gy over 5– 6 weeks followed by a 16 –26-Gy boost,
when indicated. Karlsson et al.25 found that the risk
for sarcomas other than angiosarcomas increased
linearly with the integral dose to 150 –200 J and
stabilized at higher energies. The odds ratio was
2.4 (95% CI, 1.4 – 4.2) for an energy of 50 J, equiva-
lent to the RT of the breast after breast-conserving
surgery.
Of 27 patients with RIS in the current study, 24
had soft tissue sarcomas. They included 13 angio-
sarcomas (48%). The ratio of angiosarcoma is in line
with reported rates of angiosarcomas after breast
carcinoma treatment by irradiation.27,29,30,41,46 –53
The use of megavoltage has been associated with an
increased incidence of RT-induced bone sarco-
mas,54 but we only encountered three bone sarco-
mas. Hardy et al.57 predominantly found bone sar-
comas and fibrosarcomas of the chest wall. Souba et
al.58 found 7 bone sarcomas and 6 MFHs among 16
patients with RIS. MFHs are rare tumors, often char-
acterized by an aberration in 7cen-q22 (38% of
postirradiation MFHs).57– 62 Our incidence of MFH
(1 of 27 patients with RIS) was lower than in other
studies.55,63– 67 For instance, Laskin et al.68 detected
36 MFHs among 53 patients with RIS.
The standard treatment is surgery, but RIS are
often located in areas precluding radical surgery.
Two of our patients underwent periclavicular sur-
gery as already described by others.70,71 At the time
of last follow-up, 1 of these patients had died,
whereas the other was disease free after 53 months.
Twelve patients underwent mastectomy and the
majority were disease-free survivors. Our results
with chemotherapy confirm that response to such
treatment tends to be poor.9,22,32,65,72,73 Kuten et
al.73 reported seven patients with RIS after irradia-
tion for breast carcinoma who were treated with a
standard four-drug combination. Only 2 patients
achieved partial disease remission, lasting 2 and 3
months, respectively. All 7 patients died within 6 –36
months of an RIS diagnosis.73 To our knowledge,
treatments using nonconventional methods such as
860 CANCER August 15, 2005 / Volume 104 / Number 4

TABLE 2
Patient and RIS Characteristics: Treatment and Outcome

Patient Age at RIS Latency Survival

No. diagnosis (yrs) (yrs) Site Histology (grade) Treatment (mos)

1 82 11.5 Axilla Undifferentiated sarcoma CT ⫻ 6 cycles ⫹ palliative care 9

(3)
2 49 10.5 Chest wall, skin lesion Angiosarcoma Wide local excision (3⫻) for local disease 46
recurrence ⫹ CT
3 57 11.5 Breast Undifferentiated sarcoma Wide local excision ⫹ 3 types of CT for 57
disease progression)
4 70 3.5 Chest wall MFH Wide excision ⫹ RT (e- 55 Gy) 174
5 60 8.1 Axilla Undifferentiated Neoadjuvant CT ⫹ periclavicular surgery 17
leiomyosarcoma ⫹ desarticulation ⫹ palliative RT after
local disease recurrence
6 63 6.5 Chest wall Fibrosarcoma (2) Wide excision 22
7 81 20.3 Supraclavicle area ⫹ Undifferentiated CT ⫹ mastectomy 4⫹ (alive)
breast leiomyosarcoma
8 55 4.4 Chest wall Undifferentiated sarcoma Wide excision then RT ⫹ CT after disease 16
recurrence/metastatic disease
9 59 14 Sternum Osteosarcoma Wide resection (sternectomy) ⫹ CT 17
10 53 8.5 Breast Angiosarcoma Mastectomy 104⫹ (DF)
11 48.5 12.3 Scapular lesion Rhabdomyosarcoma CT for metastatic disease 12
12 61 3 Clavicular area Myosarcoma Local excision ⫹ CT for disease 16
recurrence
13 72 15 Breast Angiosarcoma Mastectomy 16⫹ (DF)
14 70 7.5 Breast Angiosarcoma (3) Mastectomy 2
15 64 6.9 Sternocostal lesion Undifferentiated CT then wide excision (sternectomy) ⫹ 28
osteosarcoma CT
16 76 7.2 Breast Angiosarcoma (2–3) Mastectomy then thalidomide for disease 56⫹ (SD)
recurrence
17 57 4.7 Breast Angiosarcoma (3) Mastectomy then CT (2 disease 74⫹ (SD)
recurrences)
18 68 8.6 Sternum Osteosarcoma CT 1
19 81 6.5 Breast Angiosarcoma (3) Mastectomy then re-excision after disease 33⫹ (SD)
recurrence
20 79 7 Breast Angiosarcoma (2) Mastectomy then re-excision after 4 21
disease recurrence ⫹ thalidomide
21 63 3.9 Supraclavicular area Undifferentiated sarcoma CT then periclavicular surgery 53⫹ (DF)
(amputation)
22 77 7.3 Breast Angiosarcoma (3) Awaiting mastectomy 3⫹ (alive)
23 47 5.3 Breast Angiosarcoma (3) Mastectomy then CT 7⫹ (DF)
24 62 11 Axilla and chest wall Undifferentiated sarcoma CT 32
25 76 14 Breast Angiosarcoma Mastectomy 13⫹ (DF)
26 78 8.5 Breast Angiosarcoma Mastectomy 9⫹ (DF)
27 53 7 Breast Angiosarcoma (3) Mastectomy ⫹ CT 11⫹ (DF)

RIS: radiation-induced sarcoma; CT: chemotherapy; MFH: malignant fibrous histiocytoma; Gy: grays; RT: radiotherapy; DF: disease-free; SD: stable disease.

a combination of RT and hyperthermia have not study, the 5-year actuarial survival rate after diagnosis
been the subject of extended studies. of RIS was 36% (⫾ 0.11).
RIS tend to be diagnosed at an advanced stage, RT for breast carcinoma can induce malignant
which might explain the poor prognosis of patients. sarcoma after a latency period of several years.
Recent molecular biology analyses of 27 RIS speci- The risk is extremely low for the individual pa-
mens by genomic hybridization suggest that gains at tient, but is slightly increased as the number of
7q or 8q are associated with a poor prognosis or large long-term survivors increases. RIS are associated
tumors.69 Taghian et al.22 reported a mean survival with a poor overall prognosis. The treatment for
period of 2.4 years (4 months–9 years). In the current most patients is late and ineffective. Therefore,
 Sarcomas after Breast Irradiation/Kirova et al. 861

TABLE 3
Incidence of RIS after Breast Carcinomma Treatment

Incidence
Type of Total no. of Total no. of No. of Incidence without
References retrospective study patients sarcomas RIS (95% CI) after RT RT Risk

Yap et al., 200223 Registry data (SEER) 274,572 263 87 0.9 ⫾ 0.2/1000 cases at 15 0.1 ⫾ 0.1/ 0.32–15 yrs
yrs 1000 cumulative riska
cases 50% in-fielda
at 15
yrs
Huang and Cohort (SEER) 194,798 135 54 STS SIR: 26.2 (16.5–41.4) 2.1 1.3 RR: 15.9 RR 2.2
Mackillop, (angiosarcoma) 2.5
200124 (1.1–3.5) (other
sarcomas)
Karlsson et al. Swedish Cancer 122,991 40 angiosarcomas SIR: 1.9 (1.5–2.2) AR: 1.3/104
199825 Register (case– 76 other person-yrs
control study) sarcomas
including STS
Cozen et al., 199926 Los Angeles registry 20 upper OR: 11.6 (1.7–5.8)
(case–control extremity 48
study) chest
Marchal et al. French cancer 18,115 9 angiosarcomas 5 cases/10,000 (⫽ prevalence for healthy
199927 centers (without breasts)
Curie)
Current study Single center 16,705 13,472 with 36 Cumulative RIS SIR: 1.3 RR: 8 (4.98–12.7)
Institut Curie RT 3,233 incidence: 0.07% (0.3–
without RT (⫾0.2) at 5 yrs, 0.27% 3.6)
(⫾0.05) at 10 yrs and
0.48% (⫾0.11) at 15
yrs.
Blanchard et al., Single center (?) ??? 34
200228 (Mayo Clinic)
Taghian et al., Single center 6-919 9 in field Cumulative index: 0.2% at
199122 (Institut Gustave 2 STS 10 yrs, 0.43% at 20 yrs,
Roussy - IGR) and 0.78% at 30 yrs
Zucali et al., 199430 Single center 3,295 3 STS
(Milan)
Doherty et al., Single center 3,199 4
198631 (Ontario)
Pierce et al., 199232 Single center 1,624 3
(Boston)

RIS: radiation-induced sarcoma; 95% CI: 95% confidence interval; RT: radiotherapy; SEER: Surveillance, Epidemiology and End Results program; SIR: standardized incidence ratio; RR: relative risk; STS: Stewart–Treves
syndrome; AR: absolute risk; OR: odds ratio; SML: secondary malignancies.

careful, long-term follow-up is needed for early de-
tection.
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