Hartmann JT, Hecker H, Kopp HG, Mayer F, Classen J, Königsrainer A, Wallwiener D, Bamberg M
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Transcript of Hartmann JT, Hecker H, Kopp HG, Mayer F, Classen J, Königsrainer A, Wallwiener D, Bamberg M
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Risk of radiation-induced sarcoma: Data of a population-Risk of radiation-induced sarcoma: Data of a population-based registry of 29.931 irradiated patientsbased 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 CenterComprehensive Cancer Center Tuebingen and Institute of Biometry, Hanover Medical School
CTOS, Miami 2009
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IntroductionIntroduction
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
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Catchment AreaCatchment Area
Area: 7500 km²
No. of new referrals per year: 4500-5000
Unterer Neckar
LB
MittlererOberrhein
Franken
Ost-Württemb.
SüdlicherOberrhein
FDS
CW
PF WN
ES GPBB
TÜRT
Donau-IllerBL
Schwarzwald-Baar-Heuberg
Hochrhein-
Bodensee-Oberschwaben
S
Bodensee
11%
5%
5%
1%
7%
4% 14%
5%
0%
17%
10%
2%4%
3%
1%
1%
0%2%
1%
3%
1%
covering the region South West Germany with a population of approximately 3 millions inhabitants.
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Selection criteria and statisticsSelection criteria and statisticsFor this analysis patients have been identified using the following selection criteria:
malignant primary tumorradiation within 6 months of primary diagnosissecondary tumor exceeding 1 year after diagnosis
29.931 patients had received radiation therapy between 1/1968 and 12/2006Irrespective of type of treatment (curatve vs. palliative), extent of disease, prognosis.
Statistics: univariate analysisCox proportional hazardcumulative IncidenceLogistic regression analysis
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Patients´ characteristics (n=29.931)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 25.8hematologic tumors, NHL, HD 3 354 11.2head and neck 3 045 10.2lung/thoracic 2 621 8.8Gastrointestinal 2 615 8.7female reproductive 2 326 7.7Prostate 1 878 6.3Brain 1 354 4.5genitourinary (other than prostate) 1 135 3.8Endocrine 1 067 3.6Sarcomas 1 016 3.4Cutaneous 735 2.5other malignancies 1 062 3.5
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Results: whole populationResults: whole population
36 patients with RIS were identified 1994 through 2006 representing 0.12% of 29.931 irradiated patients.
Median follow up:
96 months (95%CI, 92.9-99.1)
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Median age: 59 years (range, 5-74)female to male ratio was 2.3:1 Primary tumors were
breast cancer n=19lymphoma (incl. Hodgkin´s/NHL) n= 9head and neck cancer n= 4tumors of the female reproductive organs n= 2neuroblastoma n= 1seminoma 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).
Patients´characteristics: RIS cohort (n=36)Patients´characteristics: RIS cohort (n=36)
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Examples in breast cancer patientsExamples in breast cancer patients
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Results RIS patients (n=36)Results RIS patients (n=36)mode of primary therapy, including radiation sourcemode of primary therapy, including radiation source
Radiation Source N60Cobalt 23Electron 8Not available 5
Mode of Primary Therapy NRadiation alone 25Radiochemotherapy 1Sequential Chemotherapy 5Unknown 5
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Results: RIS patientsResults: RIS patientsradiation field and histologyradiation field and histology
The tumors arosewithin the radiation field in 29 caseson the border of the field in 6 casesout of field in a single case
The histologies of RIS werevascular tumors, e.g. angiosarcoma n = 12 pleomorphic sarcoma, not otherwise specified n = 10leiomyosarcoma n = 4fibrosarcoma n = 2osteosarcoma n = 2others n = 6
Significantly, angiosarcoma occurred in breast cancer (p<.01)
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Cumulative RIS incidence
Cumulative risks (95%CI) years0.2% (0.00-0.49) 10 0.9% (0.01-1.79) 2016.0% (0.01-33.8) 30
Cum
ulat
ive
1 m
inus
sur
viva
l fun
ctio
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Cumulative RIS incidence
Primary breast cancer vs. other
Cum
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1 m
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sur
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Latency period breast RIS: 100 mos (CI95%, 69-131)Non-breast cancer RIS: 224 mos (CI95%, 99-349)
p<.01
19 of 7.716 cases (0.246%)17 of 22.215 cases (0.076%)
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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)
Results: RIS patientsResults: RIS patients
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Factors influencing survival of RISFactors influencing survival of RISHistology: Angiosarcoma vs. otherHistology: Angiosarcoma vs. other
0 10 20 30 40 50 600
25
50
75
100Angiosarkom
Non-Angiosarkom
months
Prop
ortio
n su
rviv
ing
P=0.94
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Factors influencing survival of RISFactors influencing survival of RISBreast cancer vs. other primaryBreast cancer vs. other primary
0 10 20 30 40 50 600
25
50
75
100Breast cancer
Non-Breast cancer
months
Prop
ortio
n su
rviv
ing
P=0.50
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Factors influencing survival of RISFactors influencing survival of RISCompleteness ofCompleteness of resectionresection
0 10 20 30 40 50 600
25
50
75
100Resektion complete
Resektion incomplete
months
Prop
ortio
n su
rviv
ing
P=0.08
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ConclusionsConclusions
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
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Conclusions (cont.)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
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RIS after Radiation for RIS after Radiation for Breast CancerBreast Cancer, Case , Case CollectionsCollections
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 yrs0.9% at 20 yrs