Radiation Effects in the Musculoskeletal System

History and Radiation Sources

Since the discovery of X-rays by Wilhelm Conrad Roentgen in 1895 and the discovery of radioactivity by Henri Becquerel in 1896, many medical uses of radiation have been developed, both diagnostic and therapeutic. Patients can be exposed to radiation by external or internal sources. External radiation sources include imaging exams like conventional radiography, computed tomography and fluoroscopy, as well as external radiation therapy. Internal sources of radiation include radionuclides administered orally, intravenously, or by inhalation, as may be used either for diagnostic nuclear medicine or therapeutically, for example, I 131 administered for thyroid cancer or brachytherapy for prostate cancer.

Now, in the early years of the twenty-first century, by far the most common source of large amounts of radiation exposure seen in medical practice is radiation therapy, which is almost exclusively used for malignant tumors; about 50% of oncologic patients will receive radiation therapy at some stage of their treatment. The aim of the radiation therapy is to eliminate or control the tumor. To ensure adequate treatment, the radiation plan must include both the tumor and a rim of apparently normal surrounding tissue to include undetected tumor extensions. Including the surrounding tissue increases the volume of tissue exposed to radiation. The tolerable dose to the normal tissues within the radiation treatment field determines the maximum dose of radiation that can be delivered to the tumor.

Radiation therapy can have numerous deleterious side effects. These deleterious effects are divided into early effects and late effects. Early effects occur during or within a few weeks after the course of radiation therapy. They include radiodermatitis and wound-healing problems. Early effects that persist long after completion of radiotherapy are termed consequential effects. Examples of these are skin ulceration and fibrosis, neuropathy, joint stiffness, myositis, and muscle spasms, the combination of which has been termed radiation fibrosis syndrome. Late effects appear months to years after completion of radiation therapy. Examples of late effects involving the musculoskeletal system include radiation osteitis, radiation-induced fracture, and radiation-induced sarcomas.

All subsequent discussions will consider the late effects of radiation in the musculoskeletal system and will assume external radiotherapy as the source; however, the effects of radiation are the same, independent of the source.

Anatomy

Any site that has been irradiated may exhibit either the beneficial effects or the deleterious side effects of radiation therapy. Some of the most commonly treated cancers, their common associated musculoskeletal late effects, and the relevant anatomic locations include the following:

• Head and neck cancer; jaw and clavicles; radiation osteonecrosis

• Breast and lung cancer; clavicle, ribs, scapula, and axilla; radiation osteonecrosis, brachial-plexus neuropathy

• Metastases or myeloma; spine; marrow replacement by fat; insufficiency fractures; spinal cord injury

• Gynecologic or colon cancers; pelvis and proximal femurs; pelvic ring insufficiency fractures, femoral head fractures or avascular necrosis, lumbar-plexus neuropathy

• Bone and soft-tissue sarcomas of extremities: long-bone radiation osteonecrosis and radiation-induced fractures

• Pediatric population; bone growth disturbances (limb length discrepancies, scoliosis), osteochondroma induction

Pathology

Radiation late effects are a diverse group of tissue reactions that vary from patient to patient, depending both on the specifics of the radiotherapy received (dose, number of fractions, volume exposed) and individual susceptibility (genetics, association of the radiation therapy with chemotherapy or surgery, other comorbidities).

Radiation osteonecrosis, also called radiation osteitis, develops in irradiated bone as a result of the death of cells (osteocytes, osteoblasts, osteoclasts, marrow precursors, and endothelial cells), degradation of collagen fibers, inflammatory tissue reaction, and damage to blood vessels. The vascular damage results in capillary thrombosis and fibrosis, and the combination of cell death and vascular compromise leads to progressive bone resorption, chronic hypoperfusion and hypoxia, and impaired remodeling, which ultimately result in insufficiency fractures with high rates of delayed healing or nonunion.

Osteochondroma is the most common benign bone tumor arising with radiation exposure. It occurs only in patients irradiated in childhood and is both radiographically and histologically identical to osteochondroma occurring spontaneously. Patients receiving total-body irradiation may develop several osteochondromas. Other benign tumors occur rarely as a result of radiation.

Radiation-induced sarcomas occur in both bone and soft tissue. In 1948, Cahan and colleagues published a series of cases of radiation-induced sarcoma and suggested criteria for distinguishing radiation-induced sarcomas from their spontaneously occurring counterparts. These criteria included a benign primary disease; a history of therapeutic radiation with the sarcoma arising within the radiated field; a long asymptomatic latent period, with 5 years being used for their cases; and histologic proof of the sarcoma. These criteria were later altered by other writers to allow for the prior existence of a primary malignancy that histologically differed significantly from the subsequent sarcoma. Some writers have suggested 4 years as a minimal latency, and Kohn and Fry, in a literature review published in 1984, found a median latency period of 10 to 12 years. Various histologic types of sarcoma occur after radiation therapy, with different series of studied cases producing different occurrence rates. Osteosarcoma and malignant fibrous histiocytoma are the two most common varieties. Kim and colleagues, in 1978, found spindle cell sarcoma to be the most common radiation-induced soft tissue sarcoma, with osteosarcoma the most common in bone. Sarcoma induction may also be linked to chemotherapy with cyclophosphamide and other alkylating agents. The likelihood of tumor induction increases with radiation dose up to 60 Gy. Pathology of radiation-induced neoplasms is identical to that of spontaneously occurring neoplasms.

Manifestations of the Disease

Beneficial Effects

Radiation may be used either for cure or for palliation and is used in the treatment of primary musculoskeletal lesions, such as soft tissue sarcomas, and of primary tumors arising in other organ systems, such as breast cancer and lung cancer. In systemic disease, such as lymphoma, disseminated metastatic tumor, or multiple myeloma, radiation therapy may be used palliatively against especially troublesome sites of disease. Desired goals may include shrinkage of the tumor, elimination of micrometastases, and, in the case of skeletal lesions, reconstitution of functional bone.

When radiation successfully addresses a bone tumor, there may be radiographically evident healing ( Fig. 41-1 ). Chemotherapy is often used in conjunction with radiation, and both may contribute to the healing effect. Responses that may indicate healing include the filling-in of lytic lesions with sclerotic or normal-appearing bone, normalization of signal intensity at MRI, or development of a sclerotic rim around a lytic lesion.

Side Effects in Soft Tissue

Radiography

With time, dystrophic calcifications may form in soft tissues. As radiation therapy techniques have changed over the decades, these dystrophic calcifications are becoming less common, but they are still encountered in clinical practice, particularly in patients who completed radiation therapy in the 1980s or earlier ( Fig. 41-2 ).

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