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Risk of radiation-induced sarcoma: Data of a populationbased registry of 29.931 irradiated patients
Hartmann JT, Hecker H, Kopp HG, Mayer F, Classen J, Königsrainer A,
Wallwiener D, Bamberg M
Medical Center, Radiooncology, General-, Visceral Surgery and Transplantation,
Gynecology
Interdisciplinary Sarcoma Center
Comprehensive Cancer Center Tuebingen and
Institute of Biometry, Hanover Medical School
CTOS, Miami 2009
Introduction
Radiation-induced sarcoma (RIS) is a rare complication of radiation
therapy for any cause
With increasing numbers of patients receiving radiotherapy, data
concerning the incidence and treatment outcome of RIS are urgently
needed
The Surveillance, Epidemiology, and End Results Program of the South
West German Comprehensive Cancer Center, Tuebingen University
registry, was sreened for patients with RIS
Catchment Area
Unterer Neckar
0%
Area:
Franken
2%
Mittlerer
Oberrhein
1%
LB
PF
WN
3%
1%
2%
S
CW
BB
11%
5%
FDS
TÜ
17%
4%
Südlicher
Oberrhein
0%
4%
BL
10%
Ost-Württemb.
ES
7%
1%
Hochrhein3%
Bodensee
No. of new referrals per year:
4500-5000
GP
1%
RT
14%
Donau-Iller
1%
SchwarzwaldBaar-Heuberg
5%
7500 km²
BodenseeOberschwaben
5%
covering the region South West
Germany with a population of
approximately 3 millions inhabitants.
Selection criteria and statistics
For this analysis patients have been identified using the following selection criteria:
malignant primary tumor
radiation within 6 months of primary diagnosis
secondary tumor exceeding 1 year after diagnosis
29.931 patients had received radiation therapy between 1/1968 and 12/2006
Irrespective of type of treatment (curatve vs. palliative), extent of disease, prognosis.
Statistics:
univariate analysis
Cox proportional hazard
cumulative Incidence
Logistic regression analysis
Patients´ characteristics (n=29.931)



median age was 58 years (SD, ±16; range, 0-98)
Gender: male/female: 46 / 54%
Irradiated tumor types:
N pts
breast cancer
7 723
hematologic tumors, NHL, HD
3 354
head and neck
3 045
lung/thoracic
2 621
Gastrointestinal
2 615
female reproductive
2 326
Prostate
1 878
Brain
1 354
genitourinary (other than prostate) 1 135
Endocrine
1 067
Sarcomas
1 016
Cutaneous
735
other malignancies
1 062
%
25.8
11.2
10.2
8.8
8.7
7.7
6.3
4.5
3.8
3.6
3.4
2.5
3.5
Results: whole population
Median follow up:
96 months (95%CI, 92.9-99.1)
36 patients with RIS were identified
1994 through 2006
representing 0.12% of 29.931
irradiated patients.
Patients´characteristics: RIS cohort (n=36)
Median age: 59 years (range, 5-74)
female to male ratio was 2.3:1
Primary tumors were
breast cancer
n=19
lymphoma (incl. Hodgkin´s/NHL)
n= 9
head and neck cancer
n= 4
tumors of the female reproductive organs
n= 2
neuroblastoma
n= 1
seminoma
n= 1
median of delivered total radiation dose per patient was 50 Gy (range,
35 to 72 Gy).
median time interval from start of irradiation to detection of RIS was 137
mos (CI95%, 105-169).
Examples in breast cancer patients
Results RIS patients (n=36)
mode of primary therapy, including radiation source
Radiation Source
60Cobalt
N
23
Electron
Not available
8
5
Mode of Primary Therapy
Radiation alone
N
25
Radiochemotherapy
Sequential Chemotherapy
Unknown
1
5
5
Results: RIS patients
radiation field and histology
The tumors arose
within the radiation field in 29 cases
on the border of the field in 6 cases
out of field in a single case
The histologies of RIS were
vascular tumors, e.g. angiosarcoma
n = 12
pleomorphic sarcoma, not otherwise specified
n = 10
leiomyosarcoma
n= 4
fibrosarcoma
n= 2
osteosarcoma
n= 2
others
n= 6

Significantly, angiosarcoma occurred in breast cancer
(p<.01)
Cumulative 1 minus survival function
Cumulative RIS incidence
Cumulative risks (95%CI)
0.2%
(0.00-0.49)
0.9%
(0.01-1.79)
16.0% (0.01-33.8)
years
10
20
30
Cumulative RIS incidence
Cumulative 1 minus survival function
Primary breast cancer vs. other
Latency period
breast RIS:
Non-breast cancer RIS:
p<.01
19 of 7.716 cases (0.246%)
17 of 22.215 cases (0.076%)
100 mos (CI95%, 69-131)
224 mos (CI95%, 99-349)
Results: RIS patients
Latency period
Breast vs. non-breast cancer: 100 mos (CI95%, 69-131) vs 224 mos, (CI95%, 99-349),
p<.01
age <49 year with 224 mos (95%CI, 107-341) vs age 50-69 years with 100.0 months
(95%CI, 67-133), (p<.0001)
trend: men, 255 mos (95%CI, 108-402) vs women, 114 mos (91-137) p=.058
Factors predicting RIS occurrence (logistic regression):
age >70 years: HR: 3.04 (95%CI, 1.58-5.85, p=.001)
breast cancer: HR: 2.17 (95%, 1.11-4.21, p=.02)
RIS treatment and outcome analysis:
Most cases in a localized stage (34 out of 36)
complete surgical removal 59% (n=19), R I n=8, R II n=4.
13 patients free of disease during median f/u period of 11 mos (range, 0-51)
Factors influencing survival of RIS
Histology: Angiosarcoma vs. other
Proportion surviving
100
Angiosarkom
Non-Angiosarkom
75
50
25
0
0
10
20
30
months
40
50
60
P=0.94
Factors influencing survival of RIS
Breast cancer vs. other primary
Proportion surviving
100
Breast cancer
Non-Breast cancer
75
50
25
0
0
10
20
30
months
40
50
60
P=0.50
Factors influencing survival of RIS
Completeness of resection
Proportion surviving
100
Resektion complete
Resektion incomplete
75
50
25
0
0
10
20
30
months
40
50
60
P=0.08
Conclusions
Radiation induced secondary sarcoma (RIS) is a rare event within
a 20-year period
10- and 20-year cumulative incidence of RIS were below 1%
Risk is steadily increasing 20 years after application of radiation
Age (>70 years) at the time of the first cancer diagnosis and
breast cancer primary associated with elevated RIS risk
Women (e.g. breast cancer patients) and elderlies had shorter
latency period
Conclusions (cont.)
Angio- or pleomorphic sarcomas, NOS, are the most common RIS
subentities
With lag period between initial treatment and RIS occurrence, the
need for long-term follow-up becomes evident
Follow-up of previously irradiated breast cancer patients include
examination of irradiated regions with a high level of suspicion if
cutaneous atypical vascular lesions
Factor associated with outcome for RIS is a early stage disease
RIS is treated the same as non-radiation induced sarcoma
RIS after Radiation for Breast Cancer, Case
Collections
Author
Year
N pts
5y-OS
Cum. Incidence of RIS
Zucali et al. [29]
1994
3
-
-
Brady et al. [7]
1993
48
29%
-
Taghian et al. [9]
1991
11
Med.S. = 2.4 y
0.2% at 10 years
Schulz et al. [15]
1999
3
-
-
Yap et al. [18]
2002
87
27-35%
0.09% at 15 years
This series
2008
11
28
0.2% at 10 yrs
0.9% at 20 yrs