Clinical Investigations
Postradiation sarcomas: 20 cases and a literature review

Presented in part as a poster at the 13th National Congress of the South African Society of Radiotherapists, South Africa, April 22–26, 1990.
https://doi.org/10.1016/S0360-3016(99)00279-5Get rights and content

Abstract

Purpose: To analyze 20 cases of postradiation sarcoma (PRS) to determine dose levels at which this condition developed, the pathology of the initial and postradiation tumors, latency period, and outcome; and to review the literature and propose modified criteria for diagnosis.

Methods and Materials: Patient records were reviewed. Previous radiation fields and isodose charts were reconstructed to determine the dose received in the tissue in which the PRS subsequently developed.

Results: There were 16 female patients and 4 male patients. Mean age at the time of initial radiotherapy was 28 years. Mean latency was 14 years, with no difference in latency between the adult and pediatric group (t = 0.45, p = 0.37), but shorter latency in the retinoblastoma than in the nonretinoblastoma patients (t = 3.18, p = 0.003). The outcome was poor; 2 patients were alive and disease-free at 2 and 5 years. The 18 patients who died as a result of PRS had a median survival of 1 year.

Conclusion: PRSs are rare. Unnecessary radiation must be avoided. Cases should be reported with full details so that risk factors can be ascertained. PRSs usually arise in moderate to higher dose areas. Diagnostic criteria should allow soft tissue tumors and short latency.

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)

  • M.S Lemson et al.

    Post-radiation fibrosarcoma of the breast

    The Breast

    (1996)
  • M.B O’Neil et al.

    Radiation-induced soft-tissue fibrosarcoma: Surgical therapy and salvage. Ann Thorac Surg

    (1982)
  • J.C Chumas et al.

    High-grade pelvic sarcoma after radiation therapy for low-grade endometrial stromal sarcoma (case report)

    Gynecol Oncol

    (1990)
  • J.M Scully et al.

    Radiation-induced prostatic sarcomaA case report

    J Urol

    (1990)
  • J.J Senyszyn et al.

    Radiation-induced sarcoma after treatment of breast cancer

    Cancer

    (1970)
  • E.B Harvey et al.

    Second cancer following cancer of the breast in Connecticut, 1935–1982

    Monogr Natl Cancer Inst

    (1985)
  • M.A Bagshaw et al.

    Status of radiation treatment of prostate cancer at Stanford University

    Monogr Natl Cancer Inst

    (1998)
  • R.S Lavey et al.

    Impact of radiation therapy and/or chemotherapy on the risk for a second malignancy after breast cancer

    Cancer

    (1990)
  • R.J Mark et al.

    Postirradiation sarcomas

    Cancer

    (1994)
  • E Robinson et al.

    Clinical aspects of postirradiation sarcomas

    J Natl Cancer Inst

    (1988)
  • P.M Hatfield et al.

    Postirradiation sarcoma including 5 cases after x-ray therapy of breast carcinoma

    Radiology

    (1970)
  • T.A Wiklund et al.

    Analysis of a nationwide cancer registry material

    Cancer

    (1991)
  • A.T Tountas et al.

    Post-irradiation sarcoma of boneA perspective

    Cancer

    (1979)
  • F.P Li et al.

    Risk of second tumors in survivors of childhood cancer

    Cancer

    (1975)
  • H.B Soloway

    Radiation-induced neoplasms following curative therapy for retinoblastoma

    Cancer

    (1966)
  • R.E Haselow et al.

    Second neoplasms following megavoltage radiation in a pediatric population

    Cancer

    (1978)
  • R.P Weatherby et al.

    Postradiation sarcoma of boneReview of 78 Mayo Clinic cases

    Mayo Clin Proc

    (1981)
  • M.A Tucker et al.

    Bone sarcomas linked to radiotherapy and chemotherapy in children

    N Engl J Med

    (1987)
  • R.S Bell et al.

    Supervoltage radiotherapy in the treatment of difficult giant cell tumors of bone

    Clin Orthop

    (1983)
  • M.S Brady et al.

    Radiation-associated sarcoma of bone and soft tissue

    Arch Surg

    (1992)
  • W.B Laskin et al.

    Postradiation soft tissue sarcomasAn analysis of 53 cases

    Cancer

    (1988)
  • M Arlen et al.

    Radiation-induced sarcoma of bone

    Cancer

    (1971)
  • F.H Sim et al.

    Postradiation sarcoma of bone

    J Bone Joint Surg Am

    (1972)
  • W.G Cahan et al.

    Sarcoma arising in irradiated boneReport of 11 cases

    Cancer

    (1948)
  • W.H Turner et al.

    Sarcoma induced by radiotherapy after breast conservation surgery

    Br J Surg

    (1991)
  • S Hatlinghus et al.

    Sarcoma following irradiation for breast cancer

    Acta Radiol Oncol

    (1986)
  • F.M Enziriger et al.

    General considerations

  • H.E Johns et al.

    The measurement of absorbed dose

  • Shallet RJ. Use of computers for the calculation of dose from Iridium-192 implants. In: Hilaris BS, editor....
  • G Marus et al.

    Malignant glioma following radiotherapy for unrelated primary tumors

    Cancer

    (1986)
  • Williams PL, Warwick R, Dyson M, et al., editors. Gray's anatomy. 37th ed. Edinburgh: Churchill Livingstone;...
  • R.J Mark et al.

    Postirradiation sarcoma of the gynecologic tract

    Am J Clin Oncol

    (1996)
  • R.J Mark et al.

    Postirradiation sarcoma of the head and neck

    Cancer

    (1993)
  • J.Y Bobin et al.

    Radiation induced sarcomas following treatment for breast cancerPresentation of a series of 14 cases treated with an aggressive surgical approach

    J Surg Oncol

    (1994)
  • L Castro et al.

    Radiation induced bone sarcomas. Report of five cases

    Am J Roentgenol

    (1967)
  • T Davidson et al.

    Radiation-induced soft-tissue sarcoma

    Br J Surg

    (1986)
  • A Kuten et al.

    Postirradiation soft tissue sarcoma occurring in breast cancer patientsReport of seven cases and results of combination chemotherapy

    J Surg Oncol

    (1985)
  • J.G Lorigan et al.

    Radiation-induced sarcoma of boneCT findings in 19 cases

    Am J Roentgenol

    (1989)
  • V.D Pettit et al.

    Fibromatosis and fibrosarcoma following irradiation therapy

    Cancer

    (1954)
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