International Journal of Radiation Oncology*Biology*Physics
Clinical InvestigationsPostradiation sarcomas: 20 cases and a literature review
Introduction
A simple cause and effect relationship between irradiation and oncogenesis has not been established (1). However, statistical evidence for a relationship between irradiation and oncogenesis does exist 2, 3, 4, and although not all clinical studies support radiotherapy as a risk factor for second tumor development 5, 6, the weight of the evidence suggests that radiotherapy does increase the relative risk of subsequent sarcomas and second cancers (7). Neither the risk nor the incidence of postradiation sarcoma (PRS) can be accurately calculated due to the rarity of the condition, the potentially long latency period between irradiation and the development of a sarcoma, and possibly, the failure to recognize and report sarcomas occurring in radiation fields 8, 9, 10. Overall, the incidence of PRS has been estimated at less than 1% 7, 8, 11. Tountas et al. (12) reported that PRS of the bone occurred in 0.02% of irradiated patients and in 0.035% of 5-year survivors. In a review of 25,724 cases of breast cancer, it was found that the relative risk of soft tissue sarcoma was higher in patients who had received radiotherapy, although some of these sarcomas were related to lymphoedema of the arm (2).
The cumulative probability of a new malignancy in patients treated for pediatric cancer has been reported as 12%, and as 17% in those who received radiotherapy, with 42% of the tumors arising in radiation fields being sarcomas (13).
The incidence of PRS may be increasing as radiotherapy is used more often in the treatment of a wide spectrum of malignant diseases, and with more patients surviving longer after treatment for the original malignancy 8, 14. The expected reduction in risk with the change from orthovoltage to megavoltage radiotherapy (15) has not been seen 16, 17, although malignant transformation of giant cell tumors has been reported to occur less often with modern techniques 18, 19, 20.
PRS remains a serious long-term complication of radiotherapy. The criteria for its diagnosis remain a matter of debate 21, 22, 23, 24. Radiotherapy regimens in patients who have developed PRSs are seldom fully described 10, 25. Dose levels at which the tumors are most likely to occur have not been clearly established 12, 26, 27, 28.
Our report reviews cases of PRS, including “malignant mixed Mullerian tumors” (MMMT), presenting to the radiation oncology departments of our own and affiliated hospitals, or known to have occurred in patients initially treated in these hospitals. We have included cases in our report if sarcomas developed in fields of previous radiotherapy, and regardless of the period of latency. The term PRS has been used as previously done 11, 16. We propose a modification of Cahan’s criteria (26) for bone sarcomas to include soft tissue sarcomas and which will exclude fewer true postradiation sarcomas from the postradiation category. We establish as accurately as possible the dose levels at which the tumors developed.
Section snippets
Methods and materials
Material included in the study related to 20 patients who had developed sarcomas in a previous radiotherapy field with histology differing from that of the primary tumor. As the computerized database available did not allow a method of ensuring that all cases were included in this study, and not all patients were initially irradiated at this or the associated institutions, the incidence rate for PRS could not be calculated.
Clinical notes, diagrams, photographs of the postradiation tumors, and
Results
Results are shown in Table 1 Three examples of radiation field and isodose reconstruction are shown in Fig. 1, Fig. 2, and 3.
The 20 patients (16 female, 4 male) who fulfilled our criteria presented with PRS between September 1972 and June 1992. Their mean age at the time of radiotherapy for the initial tumor was 28 years, with the 6 patients under the age of 15 having a mean age of 4 years, and the 14 adults having a mean age of 38 years. The three retinoblastoma patients had a mean age of
Criteria for diagnosis
In 1948, in the first volume of the journal Cancer, Cahan et al. (26) reported on PRS in irradiated bone. Their criteria for case selection (quoted below) have been the basis of diagnosis of PRS since then:
“1.
There must have been microscopic or roentgenographic evidence of the nonmalignant nature of the initial bone condition.
2.
Irradiation must have been given and the sarcoma that subsequently developed must have arisen in the area included within the radiotherapeutic beam.
3.
A relatively long,
Acknowledgements
We thank the Departments of Radiation Oncology, Groote Schuur, Frere and Livingstone Hospitals, and H. Ball, D. Dent, R. Duffett, M. Garb, S. Giles, E. Hering, H. Hogg, J. Hough, S. Isaacs, P. Johnson, S. King, V. Mawson, M. Renan, and M. Wyeth.
References (98)
- et al.
Increased incidence of sarcoma in patients treated for testicular seminoma
Eur J Cancer
(1993) - et al.
Long-term risk of sarcoma following radiation treatment for breast cancer
Int J Radiat Oncol Biol Phys
(1991) - et al.
Sarcoma of bone following therapeutic irradiation for breast carcinoma
Int J Radiat Oncol Biol Phys
(1986) - et al.
Long term follow-up of efficacy and safety of megavoltage radiotherapy in high-risk giant cell tumors of bone
Int J Radiat Oncol Biol Phys
(1995) - et al.
Radiation therapy in the treatment of difficult giant cell tumors
Int J Radiat Oncol Biol Phys
(1989) - et al.
Sarcomas following radiation therapy for breast cancerA report of three cases and a review of the literature
Int J Radiat Oncol Biol Phys
(1995) - et al.
Postradiation sarcoma of bone and soft tissues
Orthop Clin North Am
(1977) - et al.
Post-irradiation soft tissue sarcoma
Eur J Cancer
(1995) - et al.
Aggressive management of second primary tumors in survivors of hereditary retinoblastoma
Int J Radiat Oncol Biol Phys
(1989) - et al.
Contralateral breast cancer and other second malignancies in patients treated by breast-conserving therapy with radiation
Int J Radiat Oncol Biol Phys
(1988)
Post-radiation fibrosarcoma of the breast
The Breast
Radiation-induced soft-tissue fibrosarcoma: Surgical therapy and salvage. Ann Thorac Surg
High-grade pelvic sarcoma after radiation therapy for low-grade endometrial stromal sarcoma (case report)
Gynecol Oncol
Radiation-induced prostatic sarcomaA case report
J Urol
Radiation-induced sarcoma after treatment of breast cancer
Cancer
Second cancer following cancer of the breast in Connecticut, 1935–1982
Monogr Natl Cancer Inst
Status of radiation treatment of prostate cancer at Stanford University
Monogr Natl Cancer Inst
Impact of radiation therapy and/or chemotherapy on the risk for a second malignancy after breast cancer
Cancer
Postirradiation sarcomas
Cancer
Clinical aspects of postirradiation sarcomas
J Natl Cancer Inst
Postirradiation sarcoma including 5 cases after x-ray therapy of breast carcinoma
Radiology
Analysis of a nationwide cancer registry material
Cancer
Post-irradiation sarcoma of boneA perspective
Cancer
Risk of second tumors in survivors of childhood cancer
Cancer
Radiation-induced neoplasms following curative therapy for retinoblastoma
Cancer
Second neoplasms following megavoltage radiation in a pediatric population
Cancer
Postradiation sarcoma of boneReview of 78 Mayo Clinic cases
Mayo Clin Proc
Bone sarcomas linked to radiotherapy and chemotherapy in children
N Engl J Med
Supervoltage radiotherapy in the treatment of difficult giant cell tumors of bone
Clin Orthop
Radiation-associated sarcoma of bone and soft tissue
Arch Surg
Postradiation soft tissue sarcomasAn analysis of 53 cases
Cancer
Radiation-induced sarcoma of bone
Cancer
Postradiation sarcoma of bone
J Bone Joint Surg Am
Sarcoma arising in irradiated boneReport of 11 cases
Cancer
Sarcoma induced by radiotherapy after breast conservation surgery
Br J Surg
Sarcoma following irradiation for breast cancer
Acta Radiol Oncol
General considerations
The measurement of absorbed dose
Malignant glioma following radiotherapy for unrelated primary tumors
Cancer
Postirradiation sarcoma of the gynecologic tract
Am J Clin Oncol
Postirradiation sarcoma of the head and neck
Cancer
Radiation induced sarcomas following treatment for breast cancerPresentation of a series of 14 cases treated with an aggressive surgical approach
J Surg Oncol
Radiation induced bone sarcomas. Report of five cases
Am J Roentgenol
Radiation-induced soft-tissue sarcoma
Br J Surg
Postirradiation soft tissue sarcoma occurring in breast cancer patientsReport of seven cases and results of combination chemotherapy
J Surg Oncol
Radiation-induced sarcoma of boneCT findings in 19 cases
Am J Roentgenol
Fibromatosis and fibrosarcoma following irradiation therapy
Cancer
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