Risk of radiation-induced sarcoma: Data of a population-based registry of 29.931 irradiated patients

1
Risk of radiation-induced sarcoma Data of a
population-based 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

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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

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Catchment Area

• Area 7500 km²
• No. of new referrals per year
  4500-5000

covering the region South West Germany with a
population of approximately 3 millions
inhabitants.
4
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

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Patients characteristics (n29.931)

• median age was 58 years (SD, 16 range, 0-98)
• Gender male/female 46 / 54
• Irradiated tumor types N pts
• breast cancer 7 723 25.8
• hematologic tumors, NHL, HD 3 354 11.2
• head and neck 3 045 10.2
• lung/thoracic 2 621 8.8
• Gastrointestinal 2 615 8.7
• female reproductive 2 326 7.7
• Prostate 1 878 6.3
• Brain 1 354 4.5
• genitourinary (other than prostate) 1 135 3.8
• Endocrine 1 067 3.6
• Sarcomas 1 016 3.4
• Cutaneous 735 2.5
• other malignancies 1 062 3.5

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Results whole population
Median follow up 96 months (95CI, 92.9-99.1)
36 patients with RIS were identified 1994
through 2006 representing 0.12 of 29.931
irradiated patients.
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Patientscharacteristics RIS cohort (n36)

• Median age 59 years (range, 5-74)
• female to male ratio was 2.31
• Primary tumors were
• breast cancer n19
• lymphoma (incl. Hodgkins/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).

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Examples in breast cancer patients
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Results RIS patients (n36)mode of primary
therapy, including radiation source
Radiation Source N
60Cobalt 23
Electron 8
Not available 5

Mode of Primary Therapy N
Radiation alone 25
Radiochemotherapy 1
Sequential Chemotherapy 5
Unknown 5
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Results RIS patientsradiation 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 (plt.01)

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Cumulative RIS incidence
Cumulative 1 minus survival function
Cumulative risks (95CI) years 0.2
(0.00-0.49) 10 0.9 (0.01-1.79) 20 16.0
(0.01-33.8) 30
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Cumulative RIS incidence Primary breast cancer
vs. other
Cumulative 1 minus survival function
Latency period breast RIS 100 mos (CI95,
69-131) Non-breast cancer RIS 224 mos (CI95,
99-349) plt.01 19 of 7.716 cases (0.246) 17 of
22.215 cases (0.076)
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Results RIS patients

• Latency period
• Breast vs. non-breast cancer 100 mos (CI95,
  69-131) vs 224 mos, (CI95, 99-349), plt.01
• age lt49 year with 224 mos (95CI, 107-341) vs age
  50-69 years with 100.0 months (95CI, 67-133),
  (plt.0001)
• trend men, 255 mos (95CI, 108-402) vs women,
  114 mos (91-137) p.058
• Factors predicting RIS occurrence (logistic
  regression)
• age gt70 years HR 3.04 (95CI, 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 (n19), R I n8, R
  II n4.
• 13 patients free of disease during median f/u
  period of 11 mos (range, 0-51)

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Factors influencing survival of RISHistology
Angiosarcoma vs. other
P0.94
15
Factors influencing survival of RISBreast cancer
vs. other primary
P0.50
16
Factors influencing survival of RISCompleteness
of resection
P0.08
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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 (gt70 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.)

• 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 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