(Radiographics. 2000;20:67-81.)
© RSNA, 2000
Unusual Radiologic Findings in the Thorax after Radiation Therapy1
Benoît Mesurolle, MD ,
Salah Dine Qanadli, MD ,
Myriam Merad, MD ,
François Mignon, MD ,
Pierre Baldeyrou, MD ,
Anne Tardivon, MD ,
Pascal Lacombe, MD and
Daniel Vanel, MD
1 From the Departments of Radiology (B.M., F.M., A.T., D.V.), Hematology (M.M.), and Medicine (P.B.), Institut Gustave-Roussy, 39 rue Camille Desmoulins, F-94805 Villejuif, France; and the Department of Radiology, Hôpital Ambroise Paré, Boulogne-Billancourt, France (S.D.Q., P.L.). Recipient of a Cum Laude award for a scientific exhibit at the 1998 RSNA scientific assembly. Received February 18, 1999; revision requested March 25 and received June 21; accepted June 21. Address reprint requests to B.M.
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Abstract
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Radiation therapy is used to treat many intrathoracic and chest wall malignancies. A variety of changes may occur after radiation therapy to the thorax. Radiation therapy produces dramatic effects in the lung. Pulmonary necrosis is an uncommon, severe, late complication of adjuvant postoperative radiation therapy. Bronchiolitis obliterans with organizing pneumonia is a distinct clinicopathologic entity characterized by patchy, migratory, peripheral air-space infiltrates. Radiation therapy can also cause spontaneous pneumothorax, mesothelioma, and lung cancer. In the mediastinum, radiation therapy may cause thymic cysts, calcified lymph nodes, and esophageal injuries. Cardiovascular complications of radiation therapy are often delayed and insidious. Premature coronary artery stenosis occurs after radiation therapy to the mediastinum. Radiation therapy may also give rise to calcifications of the ascending aorta, pericardial disease, valvular injuries, and conduction abnormalities. Women who undergo thoracic irradiation before the age of 30 years have a high risk of developing a second breast cancer. Radiation-induced sarcomas are an infrequent but well-recognized complication of radiation therapy. Other chest wall injuries due to radiation therapy are osteochondroma and rib or clavicle fractures. Knowledge of the imaging features of injuries caused by radiation therapy can prevent misinterpretation as recurrent tumor and may facilitate further treatment.
Index Terms: Radiations, injurious effects, complications of therapeutic radiology, 47.47, 50.47, 60.47 • Thorax, injuries, 47.47, 50.47, 60.47 Thorax, therapeutic radiology, 47.47, 50.47, 60.47
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Introduction
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Radiation therapy is used to treat many intrathoracic and chest wall malignancies, chiefly breast carcinoma, bronchogenic carcinoma, and lymphoma. Patients receive radiation therapy as part of their treatment for cure, for palliation, or in combination with surgery, chemotherapy, or both (1). Most patients remain asymptomatic with generally subclinical manifestations of radiation-related changes. Indeed, in recent years, the frequency of radiation-induced complications has decreased. However, as both the number of new cases of invasive cancers (lung and breast cancers) (1) and the number of survivors (Hodgkin disease) (2) increase, several late and unusual effects of treatment are becoming evident (Table). In addition, whereas some of the older diagnostic radiologists were trained in an age when certification in radiology included certification in therapeutic radiology, most of today's radiologists are unaware of several complications—notably the rare and delayed—related to radiation therapy.
In this article, unusual thoracic injuries after radiation therapy are discussed and illustrated. These injuries include lung injuries, mediastinal injuries, cardiovascular injuries, and chest wall injuries. Knowledge of the imaging features of such injuries can prevent misinterpretation as recurrent tumor and may facilitate further treatment.
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Lung Injuries
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Radiation therapy produces dramatic effects in the lung, which are traditionally divided into early and late stages. The early stage—radiation pneumonitis—occurs 1–3 months after treatment; the late stage—which is secondary to incompletely resolved radiation pneumonitis—occurs later and becomes stable 12–15 months after completion of radiation therapy (15). Radiologic changes are rare after a total dose of less than 30 Gy (to part of the lung), variably present after 30–40 Gy, and universally seen after more than 40 Gy (3). Many factors can alter the risk of developing radiation-related pulmonary damage. These include (a) prior irradiation; (b) chemotherapy (doxorubicin, actinomycin D, busulfan, bleomycin, and interferons); (c) a larger target volume, a higher total radiation dose and daily fraction size, and a shorter overall treatment time; and (d) withdrawal of steroid therapy. The lung target volume irradiated may be the most important factor (16); in the treatment of breast carcinoma, tangential ports are now used to minimize the volume of irradiated lung tissue. A reduction of at least 15%–20% of the total dose has been recommended when chemotherapy is administered concurrently (17).
Pulmonary or Bronchial Necrosis
Pulmonary necrosis is an uncommon, severe, late complication of adjuvant postoperative radiation therapy that occurs after high doses of radiation. In an unpublished study of 1,000 patients with apical lung carcinoma who were treated with upper lobectomy followed by chemotherapy and adjuvant radiation therapy, we found six patients who developed benign apical pleural or chest parenchymal necrosis (Fig 1). Two of these six patients also underwent parietal resection; four of them received 60 Gy, and two received 65 Gy. Cavitations occurred 1–7 years after radiation therapy. The diagnosis of tumor recurrence was excluded with surgery (n = 4) or follow-up (n = 2). Surgical exploration demonstrated a bronchopleural fistula in only one case. Two of the patients developed an associated infection. Usually, cavitations that occur within areas of fibrotic change during the treatment of lung carcinoma are considered to represent potential recurrent tumor or infection. However, these cases show that benign cavitations can also occur in the absence of recurrence (18). A combination of factors such as radiation therapy, chemotherapy, infection, and surgery contribute to this complication (19). Patients with lung cancer who receive postoperative radiation therapy to the lung have an increased risk of developing such complications.
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Figure 1a. Pulmonary necrosis in a 48-year-old man after postoperative radiation therapy (60 Gy) for upper right bronchogenic carcinoma. (a, b) Chest radiograph (a) and computed tomographic (CT) scan (b) obtained 1 year after radiation therapy show fibrotic changes in the apex of the right lung. (c, d) Chest radiograph (c) and CT scan (d) obtained 2 years after radiation therapy show a large cavity with a sequestrum. Surgical exploration and histologic examination revealed changes due to radiation necrosis. Neither a bronchial fistula nor an associated infection was identified.
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Figure 1b. Pulmonary necrosis in a 48-year-old man after postoperative radiation therapy (60 Gy) for upper right bronchogenic carcinoma. (a, b) Chest radiograph (a) and computed tomographic (CT) scan (b) obtained 1 year after radiation therapy show fibrotic changes in the apex of the right lung. (c, d) Chest radiograph (c) and CT scan (d) obtained 2 years after radiation therapy show a large cavity with a sequestrum. Surgical exploration and histologic examination revealed changes due to radiation necrosis. Neither a bronchial fistula nor an associated infection was identified.
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Figure 1c. Pulmonary necrosis in a 48-year-old man after postoperative radiation therapy (60 Gy) for upper right bronchogenic carcinoma. (a, b) Chest radiograph (a) and computed tomographic (CT) scan (b) obtained 1 year after radiation therapy show fibrotic changes in the apex of the right lung. (c, d) Chest radiograph (c) and CT scan (d) obtained 2 years after radiation therapy show a large cavity with a sequestrum. Surgical exploration and histologic examination revealed changes due to radiation necrosis. Neither a bronchial fistula nor an associated infection was identified.
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Figure 1d. Pulmonary necrosis in a 48-year-old man after postoperative radiation therapy (60 Gy) for upper right bronchogenic carcinoma. (a, b) Chest radiograph (a) and computed tomographic (CT) scan (b) obtained 1 year after radiation therapy show fibrotic changes in the apex of the right lung. (c, d) Chest radiograph (c) and CT scan (d) obtained 2 years after radiation therapy show a large cavity with a sequestrum. Surgical exploration and histologic examination revealed changes due to radiation necrosis. Neither a bronchial fistula nor an associated infection was identified.
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Bronchiolitis Obliterans with Organizing Pneumonia
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Classic radiation pneumonitis is characterized by alveolar areas of increased opacity confined to the treatment port (20). Radiologic abnormalities are seldom seen beyond the portal margin, although bilateral lymphocytic alveolitis is seen in bronchoalveolar lavage specimens after strictly unilateral breast irradiation (21). These findings suggest that radiation therapy gives rise to a lymphocyte-mediated hypersensitivity reaction. BOOP is a distinct clinicopathologic entity characterized by patchy, migratory, peripheral air-space infiltrates (22) (Fig 2). This syndrome differs from classic radiation pneumonitis because of the migration of the alveolar areas of increased opacity and the absence of significant sequelae. BOOP is characterized by ingrowth of polypoid fibroinflammatory granulation tissue from bronchioles into adjacent alveoli, where organizing pneumonia develops.
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Figure 2. BOOP in a 62-year-old woman with cough, dyspnea, and fever 2 months after radiation therapy to the right breast for breast carcinoma. CT scan of the chest obtained 9 months after completion of radiation therapy shows a lung infiltrate outside the radiation field. Surgical biopsy of the apical segment of the lower lobe was performed. Histologic analysis revealed the typical findings of BOOP. Corticosteroid therapy resulted in rapid clinical improvement and complete resolution of air-space areas of increased attenuation.
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To our knowledge, post–radiation therapy BOOP has been reported only in patients who underwent irradiation for breast cancer, not in patients treated for lung cancer. Because the radiation fields (tangential fields) used to treat breast cancer irradiate not only the breast but also the subpleural regions of the lung, where initial infiltrates are shown to arise, it is highly likely that radiation therapy is implicated in this disorder (22). Usually, BOOP occurs 6 weeks to 10 months after radiation therapy (4,23), although longer interim periods (18 years) have been reported (24). The clinical manifestations of BOOP include nonproductive cough, mild dyspnea, and low-grade fever. BOOP responds well to corticosteroids, but a relapse can occur when corticosteroid therapy is withdrawn too rapidly. Bronchoalveolar lavage shows a mixed cellular pattern with an increase in lymphocyte, neutrophil, and eosinophil counts (22).
The most common appearance at chest radiography and CT is patchy, bilateral, multifocal areas of consolidation or ground-glass infiltration, frequently in subpleural or peribronchial locations, with a characteristic migratory pattern (Fig 2). In 11 of 15 patients with BOOP related to radiation therapy for breast cancer, serial radiographs showed infiltrates arising in the irradiated area and spreading to nonirradiated areas (22). A single area of consolidation and a diffuse reticular pattern are less common appearances. BOOP rarely manifests as a solitary cavitating pulmonary nodule likely to be mistaken for a bronchial carcinoma. Indeed, to our knowledge, this appearance has never been reported in the follow-up of patients treated with radiation therapy (25).
Spontaneous Pneumothorax
Treatment-related pneumothorax has occasionally been reported in patients who received radiation therapy for a primary malignancy (26). Pezner et al (27) reported a frequency of spontaneous pneumothorax of 2% in patients with Hodgkin disease who were treated with mantle radiation therapy. The patients reported in the literature received more than 30 Gy of radiation (5). Pneumothorax can be recurrent, is rarely bilateral, and occurs 1 to 31 months after radiation therapy, with a mean time to onset of 16 months. It usually occurs in patients with radiologic evidence of postirradiation fibrosis. The volume is usually minimal to moderate, and most cases will reexpand without treatment (26).
Mesothelioma and Lung Cancer
Radiation-induced mesothelioma has been described (28). The interval between radiation therapy and the appearance of mesothelioma ranges from 5 to 41 years (median, 13.5 years) (29). Radiographic and CT features are nonspecific and consist of pleural effusion with or without pleura-based masses (28,29). Patients treated with irradiation for breast carcinoma are also considered to be at increased risk for development of lung cancer, particularly if they are smokers (30).
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Mediastinal Injuries
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Thymic Cysts
Thymic cysts may arise in patients who have undergone irradiation for Hodgkin disease or breast cancer (Fig 3). These cysts are thought to occur either secondarily to treatment of Hodgkin disease of the thymus or exclusively as a result of radiation effects on the thymus (31). They manifest as a stable or progressively enlarging cyst (32,33). The CT and MR imaging appearance is the same as that of a benign cyst (Fig 3). Irregular or thick-walled cysts should be regarded with suspicion and may necessitate biopsy.
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Figure 3a. Thymic cyst in a 55-year-old woman 15 years after radiation therapy for breast cancer. T2-weighted magnetic resonance (MR) image (a) and CT scan (b) show a thymic cyst (arrows).
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Figure 3b. Thymic cyst in a 55-year-old woman 15 years after radiation therapy for breast cancer. T2-weighted magnetic resonance (MR) image (a) and CT scan (b) show a thymic cyst (arrows).
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Calcified Lymph Nodes
Calcifications can arise in lymph nodes after radiation therapy for lymphoma. In Hodgkin disease, calcification of a nonenlarged mass after radiation therapy signifies a favorable response to therapy (31,34). Calcification generally begins about 1 year after treatment and may become increasingly dense over the years (6) (Fig 4). Awareness of this condition allows one to avoid confusion with the changes that typify granulomatous infection.
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Figure 4a. Lymph node calcifications in a 70-year-old woman after mediastinal irradiation for lymphoma. (a) Lateral chest radiograph obtained before radiation therapy shows a normal appearance (arrow). (b, c) Lateral chest radiographs obtained 13 years (b) and 28 years (c) after radiation therapy show mediastinal node calcification in the radiation field (arrows). The calcification increases in density over the years.
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Figure 4b. Lymph node calcifications in a 70-year-old woman after mediastinal irradiation for lymphoma. (a) Lateral chest radiograph obtained before radiation therapy shows a normal appearance (arrow). (b, c) Lateral chest radiographs obtained 13 years (b) and 28 years (c) after radiation therapy show mediastinal node calcification in the radiation field (arrows). The calcification increases in density over the years.
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Figure 4c. Lymph node calcifications in a 70-year-old woman after mediastinal irradiation for lymphoma. (a) Lateral chest radiograph obtained before radiation therapy shows a normal appearance (arrow). (b, c) Lateral chest radiographs obtained 13 years (b) and 28 years (c) after radiation therapy show mediastinal node calcification in the radiation field (arrows). The calcification increases in density over the years.
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Esophageal Injuries
The esophagus is frequently included in the radiation therapy field when patients are treated for thoracic or spinal cancers. Two radiologic patterns of esophageal damage have been recognized: abnormal peristalsis and stricture formation (35). Esophageal dysmotility occurs 4–12 weeks after radiation therapy (7). Strictures are uncommon but may occur 3–18 months after radiation therapy with a median interval of 6 months. They are usually smooth with tapered margins but may also have an irregular surface. A total dose of 50 Gy or more can lead to stricture formation. The prevalence of symptomatic benign strictures is probably under 2% at doses of 50 Gy or less and may rise to approximately 15% in patients treated with 60 Gy (36). However, esophageal strictures can occur even with low-dose radiation therapy when chemotherapy (doxorubicin) is administered (36).
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Cardiovascular Injuries
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Cardiovascular complications of radiation therapy are often delayed and insidious. They are reported to contribute significantly to morbidity and death due to intercurrent disease in long-term survivors of Hodgkin disease. This risk is higher in younger patients and in those who received mediastinal doses exceeding 30 Gy (37). Such radiation therapy techniques as use of a cobalt beam, preferential weighting of the anterior field, and large daily fractions have been implicated in the development of late cardiac toxic effects (38).
Vascular Injuries
Radiation-induced vasculopathy usually occurs after a lapse of about 10 years (39). Radiation injuries within the vascular tree most often affect the capillaries, sinusoids, small arteries, veins, and large arteries (8). When major damage (eg, thrombosis or rupture) is sustained by an elastic artery, the damage tends to be clinically significant (40,41). The only differentiating feature from radiation arteritis is that radiation-induced vasculopathy is limited to the radiation field. Stenoses and occlusions are more frequently reported than are perforations and pseudoaneurysms (42). Arterial bleeding from a radiation ulcer is potentially more life threatening (43). Mediastinal fibrosis produces obliteration of normal fat planes and anatomic landmarks, which is responsible for distortion and stricture of normal vessels (Figs 5, 6).
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Figure 5a. Vascular injury in a 36-year-old man after postoperative radiation therapy for bronchogenic carcinoma. Acute vena cava syndrome related to post-radiation therapy fibrosis occurred 5 years after completion of radiation therapy. (a) Posteroanterior chest radiograph shows chronic radiation changes with bilateral paramediastinal fibrosis. Note the metallic sternal prosthesis. (b) Phlebogram shows occlusion of the superior vena cava and left brachiocephalic vein, which led to venous thrombosis. (c, d) Angiograms show angioplasty (c) and placement of a Wallstent (d).
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Figure 5b. Vascular injury in a 36-year-old man after postoperative radiation therapy for bronchogenic carcinoma. Acute vena cava syndrome related to post-radiation therapy fibrosis occurred 5 years after completion of radiation therapy. (a) Posteroanterior chest radiograph shows chronic radiation changes with bilateral paramediastinal fibrosis. Note the metallic sternal prosthesis. (b) Phlebogram shows occlusion of the superior vena cava and left brachiocephalic vein, which led to venous thrombosis. (c, d) Angiograms show angioplasty (c) and placement of a Wallstent (d).
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Figure 5c. Vascular injury in a 36-year-old man after postoperative radiation therapy for bronchogenic carcinoma. Acute vena cava syndrome related to post-radiation therapy fibrosis occurred 5 years after completion of radiation therapy. (a) Posteroanterior chest radiograph shows chronic radiation changes with bilateral paramediastinal fibrosis. Note the metallic sternal prosthesis. (b) Phlebogram shows occlusion of the superior vena cava and left brachiocephalic vein, which led to venous thrombosis. (c, d) Angiograms show angioplasty (c) and placement of a Wallstent (d).
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Figure 5d. Vascular injury in a 36-year-old man after postoperative radiation therapy for bronchogenic carcinoma. Acute vena cava syndrome related to post-radiation therapy fibrosis occurred 5 years after completion of radiation therapy. (a) Posteroanterior chest radiograph shows chronic radiation changes with bilateral paramediastinal fibrosis. Note the metallic sternal prosthesis. (b) Phlebogram shows occlusion of the superior vena cava and left brachiocephalic vein, which led to venous thrombosis. (c, d) Angiograms show angioplasty (c) and placement of a Wallstent (d).
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Figure 6a. Vascular injury in a 69-year-old man after postoperative radiation therapy for thymoma. Coronal maximum intensity projection image (a) and coronal multiplanar reconstruction image (b) from CT scans show stenosis of the superior vena cava. Note the collateral network in a.
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Figure 6b. Vascular injury in a 69-year-old man after postoperative radiation therapy for thymoma. Coronal maximum intensity projection image (a) and coronal multiplanar reconstruction image (b) from CT scans show stenosis of the superior vena cava. Note the collateral network in a.
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Coronary Artery Disease
The effect of radiation on the coronary arteries continues to fuel debate. Coronary artery stenosis occurs after radiation therapy to the mediastinum, which is usually given for Hodgkin disease. Although studies indicate that the overall risk of a serious ischemic event in the coronary arteries is not increased in patients who received radiation therapy (44), more convincing are the reports of young patients with severe coronary artery disease in whom previous irradiation was the only feasible explanation for the development of premature coronary artery stenosis (9,45). Among survivors of Hodgkin disease, two studies found a threefold higher relative risk for coronary artery disease (46,47).
Stenosis generally affects the proximal portions of the coronary arteries (Fig 7). These sites are rarely stenotic in patients who were not treated with radiation therapy, but they are frequently stenotic in patients who received radiation therapy to the mediastinum. Postmortem examination of young adults treated with radiation therapy for Hodgkin disease has shown marked atherosclerotic disease at the ostia and proximal courses of the coronary arteries, which correspond to the anatomic area exposed to radiation therapy (48). Radiation therapy to the heart has also been associated with coronary artery spasm (49,50). It is not known whether concurrent use of chemotherapy will increase the risk of coronary artery disease (47).
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Figure 7. Premature coronary artery stenosis in a nonsmoking 27-year-old man 14 years after radiation therapy for stage IV Hodgkin disease. Selective left coronary arteriogram shows a subocclusive ostial stenosis of the left main coronary artery (arrow). (Courtesy of Rémy Pillière, MD, Hôpital Ambroise Paré, Boulogne-Billancourt, France.)
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A higher risk of fatal myocardial infarction has been reported 10–15 years after adjuvant radiation therapy for cancer of the left breast versus cancer of the right breast (51), but this finding is controversial.
The results of treatment appear to be the same in patients who did not undergo adjuvant radiation therapy, including those who underwent coronary bypass surgery (52).
Calcified Ascending Aorta
Radiation therapy may give rise to calcifications of the ascending aorta after radiation-induced aortitis (53). The calcification has a fine, sharp, and pencil-like outline. It is due to deposition of calcium salts in tissue as a sequela of a scarred intima or media after aortitis.
Pericardial Disease
The prevalence of post–radiation therapy pericarditis is 2%–6% and is very low when the radiation dose is below 40 Gy (10). The frequency of pericarditis is significantly greater when a higher radiation dose is delivered per fraction for Hodgkin disease (2). The most common form is pericardial effusion, which appears 12–18 months after completion of radiation therapy. The second form appears later, usually more than 48 months after radiation therapy, and manifests as chronic pericardial disease (10). Constriction is observed in 15%–20% of patients with pericarditis (54), but it may arise in the absence of a prior adverse pericardial event (52). The normal pericardium is thin, curvilinear, and 1–2 mm thick at CT (55). A pericardial thickness of 4 mm at CT or MR imaging is consistent with constriction (Fig 8). CT and MR imaging can provide information about impaired right ventricular diastolic filling when dilatation of the inferior vena cava and right atrium is demonstrated.
Valvular Injuries and Conduction Abnormalities
It is not clear whether radiation therapy causes structural alterations in valves (52). These abnormalities are probably related to radiation or due to myocardial fibrosis adjacent to valve rings, resulting in distortion and functional impairment. The mitral, aortic, and tricuspid valves are the most frequently affected. Changes in cardiac rhythm are rarely seen, but the odd event has been attributed to ischemic fibrosis affecting the conduction system. Atrioventricular block, albeit rare, is the most frequent conduction abnormality encountered. It tends to occur about 10 years after treatment (usually after a radiation dose of 40 Gy or greater) and requires insertion of a pacemaker in most cases (Fig 9) (11,54).
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Figure 9. Conduction abnormality in a 52-year-old woman 16 years after postoperative radiation therapy for cancer of the left breast. Radiograph shows a pacemaker, which was implanted to control cardiac arrhythmia. Note the post-radiation therapy changes in the left shoulder.
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Chest Wall Injuries
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"It is a paradox that radiations both cure and cause cancer" (56).
Breast Carcinoma
Women who undergo thoracic irradiation before the age of 30 years have a high risk of developing a second breast cancer. In the study of Bhatia et al (12), women treated for childhood Hodgkin disease had a risk of breast cancer 75 times greater than that of the general population. Breast sensitivity to radiation disappears if the first exposure occurs after 35 years of age. The mean interval between exposure and the development of breast cancer is 15–19 years. Data on the relationship between the radiation field and breast cancer are inconsistent. Yahalom et al (57) found a higher percentage of breast cancers in the inner quadrants (Fig 10); in the study of Dershaw et al (58), the main site was the upper outer quadrant, with equal distribution between the left and right breasts. Women who undergo thoracic irradiation before the age of 30 years should benefit from screening with mammography earlier than the general population. Any abnormal clinical or mammographic finding (Fig 10) should prompt a histologic examination.
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Figure 10a. Breast cancer in a 47-year-old woman who was treated for Hodgkin disease at the age of 23 years. At clinical examination, there was a palpable nodule in the upper inner quadrant of the right breast, which represented an infiltrating ductal carcinoma. (a) Lateral mammogram shows a spiculated area of increased opacity. (b) Original pretreatment photograph shows the radiation fields for treatment of the Hodgkin disease (breast dose, 8-49 Gy). The site of the future breast cancer (arrow) overlaps the radiation field.
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Figure 10b. Breast cancer in a 47-year-old woman who was treated for Hodgkin disease at the age of 23 years. At clinical examination, there was a palpable nodule in the upper inner quadrant of the right breast, which represented an infiltrating ductal carcinoma. (a) Lateral mammogram shows a spiculated area of increased opacity. (b) Original pretreatment photograph shows the radiation fields for treatment of the Hodgkin disease (breast dose, 8-49 Gy). The site of the future breast cancer (arrow) overlaps the radiation field.
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Sarcomas
Radiation-induced sarcomas are an infrequent but well-recognized complication of radiation therapy. They were demonstrated in an experimental study conducted by Marie et al (59) in 1910. The risk of post–radiation therapy sarcoma is very low relative to the beneficial effects of radiation therapy. The risk of radiation-induced sarcoma is not greater than the risk of death due to surgery or anesthesia (60). Radiation-induced sarcomas occur in approximately 0.1% or fewer of the patients who receive radiation therapy and survive 5 years (61). Such sarcomas can occur 3–30 years after completion of radiation therapy in either bone or soft tissue. Osteosarcoma is the most frequent variety occurring in bone (Fig 11), and malignant fibrous histiocytoma is the most common cell type arising in soft tissue (13).
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Figure 11a. Osteosarcoma in a 60-year-old man 15 years after postoperative radiation therapy (60 Gy) for bronchogenic carcinoma. (a) Clinical photograph shows a soft-tissue mass within the radiation field. (b) CT scan at the level of the sternal manubrium shows bone destruction and the soft-tissue mass.
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Figure 11b. Osteosarcoma in a 60-year-old man 15 years after postoperative radiation therapy (60 Gy) for bronchogenic carcinoma. (a) Clinical photograph shows a soft-tissue mass within the radiation field. (b) CT scan at the level of the sternal manubrium shows bone destruction and the soft-tissue mass.
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Diagnosis of Radiation-induced Bone Sarcoma.—Criteria for diagnosis of a radiation-induced sarcoma arising in bone are as follows (62): (a) a history of radiation therapy, (b) a neoplasm arising within the irradiated area, (c) a number of years of latency, and (d) histologic proof of sarcoma.
Factors Related to Radiation-induced Sarcomas.—A minimal dose, should one exist, has not been defined. Most patients included in earlier studies received orthovoltage radiation therapy. Today, most patients receive megavoltage radiation therapy. The energy attenuation in bone achieved with megavoltage radiation therapy should result in fewer radiation-induced soft-tissue sarcomas. It is not known whether chemotherapy compounds the risk of developing a radiation-induced sarcoma.
Imaging Appearance.—Radiation-induced sarcomas are aggressive, with a marked tendency toward local recurrence and distant metastasis (63). Salvage therapy could be successful in some patients, but early diagnosis is necessary (61). At radiography, radiation-induced sarcomas of bone do not differ from de novo sarcomas (64), appearing most frequently as an area of bone destruction on conventional radiographs. A radiation-induced sarcoma should be suspected when changes occur in the appearance of previously stable irradiated bone, particularly if an associated soft-tissue mass is present. At CT or MR imaging, a soft-tissue mass and bone destruction are the most common findings (Fig 11) (65). The differential diagnosis includes metastases, infection, and severe benign changes. Involvement of bone outside the treatment field indicates metastatic disease (Fig 12). Absence of a soft-tissue mass is the most helpful finding in distinguishing extensive benign changes from a radiation-induced sarcoma (Fig 13). Nevertheless, histologic proof is mandatory in all cases (Figs 12, 13).
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Figure 12a. Bone metastasis in a 51-year-old woman 10 years after radiation therapy for breast carcinoma. (a) CT scan of the chest shows destruction of the manubrium and a soft-tissue mass within the radiation field. (b) Sagittal T1-weighted MR images of the chest wall show an abnormal soft-tissue mass replacing the manubrium. The initial diagnosis was solitary bone metastasis or radiation-induced sarcoma. CT-guided
biopsy demonstrated a metastasis from breast carcinoma.
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Figure 12b. Bone metastasis in a 51-year-old woman 10 years after radiation therapy for breast carcinoma. (a) CT scan of the chest shows destruction of the manubrium and a soft-tissue mass within the radiation field. (b) Sagittal T1-weighted MR images of the chest wall show an abnormal soft-tissue mass replacing the manubrium. The initial diagnosis was solitary bone metastasis or radiation-induced sarcoma. CT-guided
biopsy demonstrated a metastasis from breast carcinoma.
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Figure 13a. Severe benign bone changes in an 8-year-old boy 6 years after radiation therapy for Ewing sarcoma of a rib. (a) CT scan obtained before radiation therapy shows a postoperative rib fracture (arrow). (b) CT scan of the chest shows an abnormal callus with an ossified soft-tissue mass. Histologic examination after open biopsy demonstrated a massive, calcified callus with radionecrosis. (c) Coronal T1-weighted spin-echo MR image shows hyperintense bone marrow, which corresponds to the radiation field (ie, posttherapy conversion of hematopoietic marrow to fatty marrow). (d) Coronal T1-weighted spin-echo MR image shows the abnormal callus (arrows).
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Figure 13b. Severe benign bone changes in an 8-year-old boy 6 years after radiation therapy for Ewing sarcoma of a rib. (a) CT scan obtained before radiation therapy shows a postoperative rib fracture (arrow). (b) CT scan of the chest shows an abnormal callus with an ossified soft-tissue mass. Histologic examination after open biopsy demonstrated a massive, calcified callus with radionecrosis. (c) Coronal T1-weighted spin-echo MR image shows hyperintense bone marrow, which corresponds to the radiation field (ie, posttherapy conversion of hematopoietic marrow to fatty marrow). (d) Coronal T1-weighted spin-echo MR image shows the abnormal callus (arrows).
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Figure 13c. Severe benign bone changes in an 8-year-old boy 6 years after radiation therapy for Ewing sarcoma of a rib. (a) CT scan obtained before radiation therapy shows a postoperative rib fracture (arrow). (b) CT scan of the chest shows an abnormal callus with an ossified soft-tissue mass. Histologic examination after open biopsy demonstrated a massive, calcified callus with radionecrosis. (c) Coronal T1-weighted spin-echo MR image shows hyperintense bone marrow, which corresponds to the radiation field (ie, posttherapy conversion of hematopoietic marrow to fatty marrow). (d) Coronal T1-weighted spin-echo MR image shows the abnormal callus (arrows).
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Figure 13d. Severe benign bone changes in an 8-year-old boy 6 years after radiation therapy for Ewing sarcoma of a rib. (a) CT scan obtained before radiation therapy shows a postoperative rib fracture (arrow). (b) CT scan of the chest shows an abnormal callus with an ossified soft-tissue mass. Histologic examination after open biopsy demonstrated a massive, calcified callus with radionecrosis. (c) Coronal T1-weighted spin-echo MR image shows hyperintense bone marrow, which corresponds to the radiation field (ie, posttherapy conversion of hematopoietic marrow to fatty marrow). (d) Coronal T1-weighted spin-echo MR image shows the abnormal callus (arrows).
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Osteochondroma
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Osteochondroma is the only benign bone tumor related to radiation therapy. The prevalence of radiation-induced osteochondromas is about 12% independent of the type of radiation therapy, whereas the prevalence of spontaneous osteochondromas is below 1% (66).
Rib and Clavicle Fractures
Rib fractures occur in approximately 1.8% of patients with breast cancer (14). Such fractures are associated with a higher radiation dose per fraction, with a higher dose (>50 Gy) to the whole breast, and with combination radiation therapy and CT. They are frequently multiple, spontaneous, and asymptomatic and may be slow to unite. Nonunion, resorption of fracture fragments (Figs 14, 15), and an abnormal callus—which may also simulate a radiation-induced sarcoma (Fig 13)—may be observed. Rib fractures more frequently involve the anterior aspect of the third, fourth, or fifth rib. They rarely occur within a year after completion of radiation therapy (14).
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Figures 14. Severe benign bone changes in a 37-year-old man 3 years after postoperative radiation therapy (65 Gy) for upper right bronchogenic carcinoma. Radiograph of the ribs and shoulder shows rib fractures with severe bone changes. Note the subcutaneous emphysema (arrows).
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Figure 15. Rib fracture in a 47-year-old woman 12 years after radiation therapy for inflammatory cancer of the left breast. Close-up radiograph shows a fracture of the anterior aspect of the left third rib with nonunion (arrow).
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Fractures of the clavicle are reported to affect 1%–6% of patients treated with orthovoltage radiation therapy. The fractures commonly arise in the middle or lateral third of the bone and are minimally symptomatic, if at all. They may progress to separation of the fragments with nonunion and occasionally to bone resorption (13).
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Conclusions
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Because radiation therapy plays a major role in the curative or palliative treatment of malignant disease, radiologists need to be aware of the spectrum of unusual complications, some of which may occur very late after completion of radiation therapy. Such complications can usually be diagnosed on the basis of their characteristic appearance at CT and knowledge of the radiation ports, radiation dose, and interval since therapy. As in all patients in whom long-term survival can be expected, vigilance regarding iatrogenic complications can lead to the prevention of potentially lethal complications, even long after apparent cure of the oncologic disease.
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Acknowledgments
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We thank Lorna Saint-Ange for editing the manuscript.
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Footnotes
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Abbreviation: BOOP = bronchiolitis obliterans with organizing pneumonia
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References
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|---|
-
Brady LW, Levitt SH. Radiation oncology in the 3rd millennium. Radiology 1998; 209:593-596.[Free Full Text]
-
Cosset JM, Henry-Amar M, Girinski T, Malaise E, Dupouy N, Dutreix J. Late toxicity of radiotherapy in Hodgkin's disease: the role of fraction size. Acta Oncol 1988; 27:123-129.[Medline]
-
Mosvas B, Raffin TA, Epstein AH, Link CJ, Jr. Pulmonary radiation injury. Chest 1997; 111:1061-1076.[Free Full Text]
-
Crestani B, Kambouchner M, Soler P, et al. Migratory bronchiolitis obliterans organizing pneumonia after unilateral radiation therapy for breast carcinoma. Eur Respir J 1995; 8:318-321.[Abstract]
-
Penniment MG, O'Brien PC. Pneumothorax following thoracic radiation therapy for Hodgkin's disease. Thorax 1994; 49:936-937.[Abstract]
-
Bereton HD, Johnson RE. Calcification in mediastinal lymph nodes after radiation therapy of Hodgkin's disease. Radiology 1974; 112:705-707.[Medline]
-
Lepke RA, Libshitz HI. Radiation-induced injury of esophagus. Radiology 1983; 148:375-378.[Abstract/Free Full Text]
-
Fajardo LF, Berthrong M. Vascular lesions following radiation. Pathol Annu 1988; 23:297-330.
-
Kopelson G, Herwig KJ. Coronary artery disease in cancer patients. Int J Radiat Oncol Biol Phys 1978; 4:895-906.[Medline]
-
Applefeld MM, Cole JF, Pollock SH, et al. The late appearance of chronic pericardial disease in patients treated by radiotherapy for Hodgkin's disease. Ann Intern Med 1981; 94:338-341.
-
Cohen SI, Bharati S, Glass J, Lev M. Radiotherapy as a cause of complete atrioventricular block in Hodgkin's disease: an electrophysiological-pathological correlation. Arch Intern Med 1981; 141:676-679.[Abstract]
-
Bhatia S, Robison LL, Oberlin O, et al. Breast cancer and other second neoplasms after childhood Hodgkin's disease. N Engl J Med 1996; 334:745-751.[Abstract/Free Full Text]
-
Libshitz HI. Radiation changes in bone. Semin Roentgenol 1994; 29:15-37.[Medline]
-
Pierce SM, Recht A, Lingos T, et al. Long-term radiation complications following conservative surgery and radiation therapy in patients with early stage breast cancer. Int J Radiat Oncol Biol Phys 1992; 23:915-923.[Medline]
-
Logan PM. Thoracic manifestations of external beam radiotherapy. AJR Am J Roentgenol 1998; 171:569-577.[Free Full Text]
-
Rubin P, Casarett GW. Clinical radiation pathology Philadelphia, Pa: Saunders, 1968; 428-470.
-
Roswit B, White DC. Severe radiation injuries of the lung. AJR Am J Roentgenol 1977; 129:127-136.[Abstract]
-
Mehta AC, Dweik RA. Necrosis of the bronchus: role of radiation. Chest 1995; 108:1462-1466.[Abstract/Free Full Text]
-
Redvanly RD, Hudgins PA, Gussack GS, Lewis M, Crocker IR. CT of muscle necrosis following radiation therapy in a patient with head and neck malignancy. AJNR Am J Neuroradiol 1992; 13:220-222.[Abstract]
-
Libshitz HI, Schuman LS. Radiation-induced pulmonary change: CT findings. J Comput Assist Tomogr 1984; 8:15-19.[Medline]
-
Roberts CM, Foulcher E, Zaunders JJ, et al. Radiation pneumonitis: a possible lymphocyte-mediated hypersensitivity reaction. Ann Intern Med 1993; 118:696-700.[Abstract/Free Full Text]
-
Crestani B, Valeyre D, Roden S, Wallaert B, Dalphin JC, Cordier JF. Bronchiolitis obliterans organizing pneumonia syndrome primed by radiation therapy to the breast. Am J Respir Crit Care Med 1998; 158:1929-1935.[Abstract/Free Full Text]
-
Mairovitz A, Besnier M, Diot P, et al. Bronchiolite oblitérante avec pneumonie organisée: une complication de la radiothérapie. Rev Pneumol Clin 1997; 53:207-209.[Medline]
-
Tobias ME, Plit M. Bronchiolitis obliterans with organizing pneumonia: a late complication of radiation therapy. AJR Am J Roentgenol 1993; 160:205-206.[Medline]
-
Murphy J, Schnyder P, Herold C, Flower C. Bronchiolitis obliterans organizing pneumonia simulating bronchial carcinoma. Eur Radiol 1998; 8:1165-1169.[Medline]
-
Rowinsky EK, Abeloff MD, Wharam MD. Spontaneous pneumothorax following thoracic irradiation. Chest 1985; 88:703-708.[Abstract/Free Full Text]
-
Pezner RD, Horak DA, Sayegh HO, Lipsett JA. Spontaneous pneumothorax in patients irradiated for Hodgkin's disease and other malignant lymphomas. Int J Radiat Oncol Biol Phys 1990; 18:193-198.[Medline]
-
Shannon VR, Nesbitt JC, Libshitz HI. Malignant pleural mesothelioma after radiation therapy for breast cancer. Cancer 1995; 76:437-441.[Medline]
-
Hofmann J, Mintzer D, Warhol MJ. Malignant mesothelioma following radiation therapy. Am J Med 1994; 97:379-382.[Medline]
-
Neugut AL, Murray T, Santos J. Increased risk of lung cancer after breast cancer radiation therapy in cigarette smokers. Cancer 1994; 73:1615-1620.[Medline]
-
Katz M, Piekarski JD, Bayle-Weisberger C, Laval-Jeantet M, Teillet F. Residual mediastinal mass following radiation therapy for Hodgkin's disease. Ann Radiol 1977; 20:667-672.
-
Baron RL, Sagel SS, Baglan RJ. Thymic cysts following radiation therapy for Hodgkin's disease. Radiology 1981; 141:593-597.[Free Full Text]
-
Qanadli S, Schemoul G, Barre O, Mulot RO, Chagnon S, Lacombe P. Kyste thymique après irradiation médiastinale pour cancer du sein. Rev d'Imagerie Med 1992; 4:839-841.
-
Rivero H, Gaisie G, Bender TM, Oh KS. Calcified mediastinal lymph nodes in Hodgkin's disease. Pediatr Radiol 1984; 14:11-13.[Medline]
-
Goldstein HM, Rogers LF, Fletcher GH, Dodd GD. Radiological manifestations of radiation-induced injury to the normal upper gastrointestinal tract. Radiolo
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Abstract
Introduction
