Introduction
Background
A late effect of ionizing radiation is the development of sarcoma within the field of irradiation, referred to as postradiation sarcoma (PRS). Ionizing radiation has had many varied uses in medicine. In early years, in addition to being used in the treatment of a variety of malignancies, radiation was used to treat benign conditions, such as acne, fungal infections, eczema, and various bone diseases.1,2,3,4,5,6,7,8
Advances in cancer treatment in recent years have included intensive multiagent chemotherapy and irradiation.9 Despite significant medical use of radiation therapy, PRS is an uncommon tumor. The overall incidence of PRS is less than 1% for patients with cancer who are treated with radiation and survive 5 years.9 Although the implication for individual patients is significant, little doubt exists that the benefits of ionizing radiation far outweigh the potential risks of developing sarcomas.
The diagnosis of PRS generally is based on the following criteria:
- The histologic features of the original lesion and PRS are completely different.
- PRS is located within the field of irradiation.
- Patients with cancer syndromes such as Li-Fraumeni and Rothmund-Thomson are excluded.
- The latent period (period between initiation of radiotherapy and histologic diagnosis of second neoplasm) is more than 4 years. Although arbitrary given the wide age range reported in the literature (4-55 y), a period of 4 years generally has been accepted as being the lower limit for the latent period.
Pathophysiology
PRS can occur with orthovoltage (low-energy) and megavoltage (high-energy) radiation. With orthovoltage radiation, the dosages are lower and the latent periods are longer. The threshold dose for PRS is not known, although in most published series, a dosage of 40-60 Gy is reported.2,10,11 Development of PRS also is influenced by other factors, including genetic tendency, influence of chemotherapeutic agents, and as yet unknown factors.Ionizing radiation is thought to act via genetic alterations, including mutations of p53 and retinoblastoma (Rb) genes. Experimental evidence shows p53 gene alterations or increased p53 messenger ribonucleic acid (mRNA) levels in murine PRS.12
Frequency
United States
If the criteria listed above are followed strictly, the overall incidence of PRS in patients who survive longer than 5 years following radiation therapy is about 0.1%.9 In one large series, the incidence was reported to be 0.11% following orthovoltage radiation therapy and 0.09% following megavoltage radiation therapy.9 In earlier published studies, many patients had received radiation therapy for benign bone and soft-tissue conditions. In contrast, other reports have shown larger numbers of patients who have received radiation therapy for malignancies such as breast cancer, lymphoma, and Ewing sarcoma.5,6,9,13 In a large retrospective study from the Mayo Clinic spread over several years (1933-1992), benign bone conditions were found to be the single largest group of index lesions in patients with PRS, followed by genitourinary malignancies (especially cervical cancers).9
Mortality/Morbidity
The reported 5-year survival rate for PRS has been extremely poor, ranging from 8.7-22%.10,11,14 The poor survival rate is thought to be due to a number of interrelated factors, as follows:
- Significant delay in diagnosis
- Large unresectable lesions
- Elderly
- Anaplastic nature of lesions
- Lack of effective adjuvant treatment
Race
A racial predilection has not been reported in the literature.
Sex
Predilection based on sex has not been reported. In the Mayo study, although the male-to-female ratio was 8:5, when sex-specific tumors (eg, breast, cervix, testis, ovary) were excluded, no difference based on sex was demonstrated.
Age
Patients of all ages are affected. In the Mayo study, which involved 130 patients, the average age at diagnosis of index lesion was 28.7 years (range 4 mo to 65 y).9 The mean age at diagnosis of PRS was 47.9 years (range 10.5-80.9 y). The latent period ranged from 4-55 years (average 17 y).
Clinical
History
Pain is the most common complaint and is abrupt and rapid in onset, relentless and progressive, constant, and worse at night. Pain usually is not relieved with aspirin or nonsteroidal anti-inflammatory drugs (NSAIDs). Mass (soft tissue or bone), bleeding, and pathologic fracture also are reported. Clinical factors that favor a diagnosis of PRS include the following:
- Sarcoma in bone or soft tissue appearing at an unusual age
- Sarcoma in bone or soft tissue at an unusual site
- Addition of intensive chemotherapy to irradiation
Physical
Physical findings are localized to the irradiation area. These usually are a mass (bony or soft tissue), tenderness, and/or a pathologic fracture.
Causes
Causes are discussed in detail in Pathophysiology. While ionizing radiation is the triggering factor (a dose of 40-60 Gy is thought to be the threshold dose), other factors (eg, genetic tendency, concomitant use of chemotherapeutic agents, as yet unknown factors) appear to be responsible for development of PRS.
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| Differential Diagnoses & Workup: Postradiation Sarcoma |
| Treatment & Medication: Postradiation Sarcoma |
| Follow-up: Postradiation Sarcoma |
| Multimedia: Postradiation Sarcoma |
| References |
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References
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Smith LM, Cox RS, Donaldson SS. Second cancers in long-term survivors of Ewing''s sarcoma. Clin Orthop. Jan 1992;(274):275-81. [Medline].
Cahan WG, Woodard HQ, Higinbotham NL, et al. Sarcoma arising in irradiated bone: report of eleven cases. 1948. Cancer. Jan 1 1998;82(1):8-34. [Medline].
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Taghian A, de Vathaire F, Terrier P, et al. Long-term risk of sarcoma following radiation treatment for breast cancer. Int J Radiat Oncol Biol Phys. Jul 1991;21(2):361-7. [Medline].
Strauss PG, Schmidt J, Pedersen L, et al. Amplification of endogenous proviral MuLV sequences in radiation- induced osteosarcomas. Int J Cancer. Apr 15 1988;41(4):616-21. [Medline].
Pitcher ME, Davidson TI, Fisher C, et al. Post irradiation sarcoma of soft tissue and bone. Eur J Surg Oncol. Feb 1994;20(1):53-6. [Medline].
Smith J. Radiation-induced sarcoma of bone: clinical and radiographic findings in 43 patients irradiated for soft tissue neoplasms. Clin Radiol. Mar 1982;33(2):205-21. [Medline].
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Brown J, Byers T, Thompson K, et al. A cancer journal for clinicians: nutrition during and after cancer treatment. In: A Guide for Informed Choices by Cancer Survivors. Vol 51. 2001.
Further Reading
Keywords
postradiation sarcoma, PRS, postirradiation sarcoma, radiation-induced sarcoma, osteosarcoma, fibrosarcoma, malignant fibrous histiocytoma, MFH, chondrosarcoma, angiosarcoma, Ewing sarcoma, malignant peripheral nerve sheath tumor, MPNST
