(Radiographics. 1999;19:283-297.)
© RSNA, 1999
Complications of Cancer Therapy in Children: A Radiologist's Guide
Marguerite T. Parisi, MD, MSEd1,2,
Jana L. Fahmy, MD1,
Cornelia K. Kaminsky, MD1 and
Marcio H. Malogolowkin, MD3
1 Departments of Radiology (M.T.P., J.F., C.K.K.)
2 Pediatrics (M.T.P.), Childrens Hospital Los Angeles, 4650 Sunset Blvd, Los Angeles, CA 90027 and the University of Southern California School of Medicine
3 Department of Pediatrics, University of California Los Angeles (M.H.M.).
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Abstract
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As advances in cancer therapy improve the prognosis of patients with childhood malignancies, awareness of the consequences of treatment methods assumes increasing importance. All cancer treatment modalities are associated with toxic effects, and the spectrum of therapy-induced complications involves all organ systems. Radiologists have a pivotal role in detecting these sequelae, which can be categorized by the affected organ system and by whether they occur (a) at diagnosis or during initial therapy or (b) after the completion of treatment. The first group consists of oncologic emergencies, infectious complications, and irritant effects. Oncologic emergencies can be further categorized as space-occupying lesions (eg, superior vena cava syndrome or spinal cord compression), vascular abnormalities (eg, hyperleukocytosis, anemia, coagulopathy), and metabolic emergencies (eg, tumor lysis syndrome). Common complications developing after completion of treatment include leukoencephalopathy and neurocognitive defects; cataract formation; cardiomyopathy and congestive heart failure; hepatic dysfunction, fibrosis, and cirrhosis; radiation enteritis; renal dysfunction or failure; scoliosis and short stature; hypothyroidism; gonadal dysfunction; graft-versus-host disease; and development of secondary malignancies. Physician awareness of these complications will permit more effective patient surveillance, which may afford patients the opportunity for earlier intervention in these situations and improved quality of life.
Index Terms: Chemotherapy, complications, **.46 • Radiations, injurious effects, complications of therapeutic radiology, **.47 • Radiations, injurious effects, neoplastic, **.47 • Therapeutic radiology, in infants and children, **.47
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INTRODUCTION
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With the exception of accidents, childhood cancer is the most common cause of death in persons under 15 years of age (excluding the neonatal period) in the United States (1,2). In this country, approximately 6,000 new cases of childhood cancer—or 126 cases per million children less than 15 years of age—are diagnosed annually. Although incidence rates have remained stable, advances in the treatment of childhood malignancies have resulted in dramatically increased rates of patient survival. Currently, 60%–75% of children with cancer are being cured (2). By the year 2000, approximately one of 1,000 adults between the ages of 20 and 29 years will be a survivor of childhood cancer (3).
Because antineoplastic therapy affects both tumor and normal cells, all cancer treatment modalities are associated with toxic effects (both short and long term), which range from mild to debilitating, and affect all organ systems. As survival rates increase, detection of these complications grows in importance.
Each modality employed in a therapeutic regimen against cancer has a different mechanism of action. The use of multimodality and multidrug therapy is believed to decrease the emergence of resistant cell lines. Surgery and radiation therapy work locally and regionally. Chemotherapy, the backbone of most therapeutic regimens, works systemically. Both chemotherapy and radiation therapy are most effective when cells are either rapidly growing, reproducing, or less differentiated, all of which are typically (but not exclusively) characteristics of malignant cells.
The purpose of this article is to familiarize the radiologist with the spectrum and radiologic appearances of complications relating to cancer therapy. Potential sequelae of cancer therapy can be predicted, in part, from the type of treatment received (4,5). Occurrence and severity of toxic effects encountered appear directly related to the cumulative dose of chemotherapeutic drugs or radiation therapy (total and fractionated) administered and the age of the child at the time of treatment (4–7). Concomitant use of radiation therapy and chemotherapy potentiates adverse effects.
Sequelae can be characterized by the organ affected. The Table summarizes the potential complications of cancer therapy in specific organ systems. Alternatively, complications of cancer therapy can be categorized by their time of occurrence relative to the discontinuance of treatment. Neglia and Nesbit (5) proposed a three-stage categorization of complications: early (occurring before 5 years after the cessation of therapy), intermediate (occurring between 5 and 20 years), and very late (occurring after 20 years). Unfortunately, the time of onset of many of the complications of cancer therapy varies widely, and there is much overlap between these three categories. Consequently, for ease of conceptualization and categorization, we use the following classification: (a) problems occurring at diagnosis or during initial therapy (including oncologic emergencies, infectious complications, and irritant effects) and (b) problems occurring after completion of therapy (ie, early and late complications in specific organ systems, graft-versus-host disease, complications following therapeutic surgical interventions, and the development of secondary malignancies).
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PROBLEMS OCCURRING AT DIAGNOSIS OR DURING THERAPY
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Oncologic Emergencies
Three types of oncologic emergencies occur at the time of diagnosis (8–10): (a) space-occupying lesions (eg, superior vena cava syndrome, spinal cord compression, brain herniation, massive hepatomegaly), (b) emergencies caused by abnormalities of blood and blood vessels (eg, hyperleukocytosis, coagulopathy, anemia, leukopenia, cerebrovascular accidents), and (c) metabolic emergencies (eg, tumor lysis syndrome, hypercalcemia). Although these conditions are technically not complications of therapy, radiologists need to recognize these potentially life-threatening entities, which require immediate attention.
Superior vena cava syndrome refers to the signs and symptoms caused by compression of the superior vena cava by an anterior mediastinal mass such as occurs in non-Hodgkin or Hodgkin lymphoma (Fig 1), lymphoblastic lymphoma, or the acute leukemias (acute lymphoblastic lymphoma [ALL] or acute nonlymphoblastic lymphoma) (11). In children with cancer, central line occlusion may be a secondary cause of the syndrome. Patients often complain of headache and dizziness. Facial swelling, including papilledema and jugular venous distention, may be present. Symptoms of tracheal compression (shortness of breath, wheezing, stridor, or cyanosis) may predominate in children. Cardiac arrest or respiratory failure can occur, particularly in patients receiving sedatives or undergoing general anesthesia.
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Figure 1a. Superior vena cava syndrome and subsequent resolution in a 5-year-old patient with non-Hodgkin lymphoma who presented with respiratory distress and facial swelling. (a) Axial computed tomographic (CT) scan at diagnosis shows tracheal and vascular compression by a large, anterior mediastinal mass. (b) Normal axial CT scan obtained after initial therapy highlights the extent of prior abnormalities.
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Figure 1b. Superior vena cava syndrome and subsequent resolution in a 5-year-old patient with non-Hodgkin lymphoma who presented with respiratory distress and facial swelling. (a) Axial computed tomographic (CT) scan at diagnosis shows tracheal and vascular compression by a large, anterior mediastinal mass. (b) Normal axial CT scan obtained after initial therapy highlights the extent of prior abnormalities.
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Spinal cord compression occurs with an overall prevalence of 3%–5% in children with cancer (12). Cord compression most often is epidural and results from extension of a primary tumor (eg, neuroblastoma, Ewing sarcoma, non-Hodgkin lymphoma, or Hodgkin lymphoma) (Fig 2), but it can also be a manifestation of disease recurrence (Fig 3). Because irreversible neurologic damage, including paralysis, sensory loss, and sphincter incontinence, can occur if cord compression is prolonged, the radiologist's role is pivotal in detecting and treating this condition. MR imaging is the study of choice for detecting cord compression (13).
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Figure 2. Figures 2, 3. (2) Spinal cord compression in a patient with a primitive neuroectodermal tumor. Sagittal T2-weighted magnetic resonance (MR) image obtained at diagnosis shows a dropped metastasis causing cord compression (arrow). (3) Spinal cord compression in a 16-year-old patient with relapsed ALL. Sagittal fast spin-echo T2-weighted MR image shows diffuse bone marrow infiltration by tumor. Thrombocytopenia with hemorrhage (arrow) results in nerve root compression.
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Figure 3. Figures 2, 3. (2) Spinal cord compression in a patient with a primitive neuroectodermal tumor. Sagittal T2-weighted magnetic resonance (MR) image obtained at diagnosis shows a dropped metastasis causing cord compression (arrow). (3) Spinal cord compression in a 16-year-old patient with relapsed ALL. Sagittal fast spin-echo T2-weighted MR image shows diffuse bone marrow infiltration by tumor. Thrombocytopenia with hemorrhage (arrow) results in nerve root compression.
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Massive hepatomegaly from tumor infiltration (stage IVs neuroblastoma, ALL, and lymphoma) may cause fatal respiratory and cardiovascular compromise, liver failure, or disseminated intravascular coagulation (14). Obstruction of the genitourinary tract by tumor (Fig 4) merits mention, since underlying renal abnormalities including hydronephrosis increase the risk of chemotherapy-induced toxic effects in the kidneys (15).
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Figure 4a. Hydronephrosis and urinary tract obstruction in a 2-month-old infant with prostatic rhabdomyosarcoma. Axial CT scans demonstrate mass effect caused by the tumor (arrows), which results in hydronephrosis (a) and encasement and anterior displacement of the bladder (b in b).
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Figure 4b. Hydronephrosis and urinary tract obstruction in a 2-month-old infant with prostatic rhabdomyosarcoma. Axial CT scans demonstrate mass effect caused by the tumor (arrows), which results in hydronephrosis (a) and encasement and anterior displacement of the bladder (b in b).
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Hyperleukocytosis, which is defined as a leukocyte count greater than 100,000/mm3, is associated with early morbidity and death, either from leukostasis in the pulmonary or cerebral vasculature (with resultant hypoxemia, dyspnea, right ventricular failure, or stroke) or from the metabolic complications of tumor lysis syndrome (8,9,16).
Anemia and thrombocytopenia (associated with bone marrow failure) can be seen with malignant infiltration of the marrow from such tumors as ALL or following cytotoxic therapy. Thrombocytopenia from impaired production of platelets or from increased platelet consumption such as occurs in sepsis can result in hemorrhage (Fig 3). The risk of hemorrhage is greatest when the platelet count is less than 5,000/mm3.
Tumor lysis syndrome (17) encompasses a spectrum of metabolic abnormalities, including hypocalcemia, hyperuricemia, hyperkalemia, hyperphosphatemia, and renal failure resulting from spontaneous or induced tumor necrosis. Tumor lysis syndrome is most commonly seen in patients with Burkitt lymphoma and T-cell ALL and may manifest radiologically with nephromegaly (Fig 5) or renal stone formation with obstructive uropathy.
Infectious Complications
Infectious complications are one of the most significant causes of morbidity and death in the pediatric cancer patient (18). Development of infection can be related to one or more of the following conditions: compromised mechanical barriers, neutrophilic dysfunction (both quantitative and qualitative), impaired cell-mediated and humoral immunity, and splenic dysfunction (10). These defects may be caused by either the underlying malignancy or antineoplastic therapy.
The single most important determinant of a patient's susceptibility to bacterial and fungal pathogens is the absolute granulocyte count (AGC). The risk of infection increases as a function of both degree and duration of neutropenia (19). When the AGC is less than 500/mm3, the prevalence of infection rises to 30%, compared with 5% when the AGC is greater than 500/mm3 (20).
Infections in the pediatric cancer patient or bone marrow transplant recipient typically manifest themselves in classic time increments. When the granulocytopenic patient first becomes febrile, bacteria, including gram-positive and gram-negative organisms, are isolated in 85% of cases. Morbidity and mortality increase when infection is caused by gram-negative organisms or in the presence of polymicrobial sepsis (21,22). One such serious infection in the granulocytopenic patient is typhlitis (Fig 6). The radiologic manifestations of typhlitis include pneumatosis, diffuse bowel wall thickening, pericolonic fluid, and thickening of fascial planes. If untreated, typhlitis can rapidly progress to hemorrhage or bowel perforation.
Fungi typically cause infection in those patients with severe (AGC < 100/mm3) and prolonged (>2 weeks) granulocytopenia (22). Additional risk factors for development of disseminated fungal disease include prolonged hospitalization, administration of broad spectrum antibiotics, chemotherapy- or radiation therapy–induced mucosal damage, and steroid administration. Candida and Aspergillus species are the organisms most frequently identified (Figs 7, 8).
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Figure 8a. Candidal infection that developed during initial therapy in a 6-year-old patient with high-risk ALL who presented with respiratory distress. (a) Chest radiograph at diagnosis shows an anterior mediastinal mass, tracheal compression from superior vena cava syndrome, and bilateral pleural effusions. Initial cranial CT scan (not shown) was normal. (b) Axial CT scan of the head, which was obtained because of the patient's complaints of headaches during initial therapy, reveals the development of hydrocephalus, ventriculitis with ventricular wall enhancement, and multiple enhancing candidal abscesses.
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Figure 8b. Candidal infection that developed during initial therapy in a 6-year-old patient with high-risk ALL who presented with respiratory distress. (a) Chest radiograph at diagnosis shows an anterior mediastinal mass, tracheal compression from superior vena cava syndrome, and bilateral pleural effusions. Initial cranial CT scan (not shown) was normal. (b) Axial CT scan of the head, which was obtained because of the patient's complaints of headaches during initial therapy, reveals the development of hydrocephalus, ventriculitis with ventricular wall enhancement, and multiple enhancing candidal abscesses.
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Viral pathogens account for the greatest proportion of infections in children in remission and are encountered as frequently as bacterial infections during relapse (23). Varicella-zoster virus, cytomegalovirus, herpes simplex virus, and measles virus are the most frequently encountered viral pathogens.
Visceral dissemination of varicella-zoster virus occurs in 33% of immunosuppressed patients and, if untreated, carries a 25% mortality rate. Pneumonia, the most common and serious form of visceral involvement, manifests radiographically as bilateral nodular infiltrates occurring 3–7 days after the onset of skin lesions. Bacterial superinfection with distant seeding can manifest as multifocal osteomyelitis (Fig 9).
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Figure 9a. Disseminated varicella-zoster infection in a 5-year-old patient who was undergoing consolidation therapy for ALL. Radiograph of the chest (a) reveals bilateral nodular infiltrates typical of varicella-zoster pneumonia. Bacterial superinfection with distant seeding is manifested as multifocal osteomyelitis involving the proximal right humerus (arrow in a) and the right tibia and fibula (b).
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Figure 9b. Disseminated varicella-zoster infection in a 5-year-old patient who was undergoing consolidation therapy for ALL. Radiograph of the chest (a) reveals bilateral nodular infiltrates typical of varicella-zoster pneumonia. Bacterial superinfection with distant seeding is manifested as multifocal osteomyelitis involving the proximal right humerus (arrow in a) and the right tibia and fibula (b).
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Irritant Effects
Several complications occurring during therapy are the direct result of irritation caused by chemotherapy or radiation therapy. In the peripheral nervous system, use of intrathecal methotrexate—either alone or combined with radiation therapy—can produce a myelopathy (Fig 10) characterized by paraplegia; fortunately, this complication is rare and often reversible (24). Likewise, chemotherapy-induced pancreatitis (Fig 11) with or without pseudocyst formation can be seen (25).
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Figure 10. Neuritis of the spine in a 6-year-old patient treated with radiation therapy and multiple intrathecal chemotherapeutic agents for ALL. Axial contrast material–enhanced MR image of the lumbar spine demonstrates diffuse enlargement of all anterior nerve roots (one of which is identified with an arrow).
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COMPLICATIONS OCCURRING AFTER INITIAL THERAPY
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Late Complications in Specific Organ Systems
In the central nervous system, both chemotherapy and radiation therapy can induce leukoencephalopathy (Fig 12) and neurocognitive defects. The severity of these complications is greatest in those patients who received high-dose therapy or who were very young (<5 years of age) at the time of treatment. Other reported neurologic complications include radiation necrosis, cerebrovascular accidents, and mineralizing angiopathy, all of which are rare and typically associated with high-dose radiation therapy (24,26–29). Hearing loss related to chronic administration of cisplatin (30) and cataracts that develop after orbital or cranial irradiation for rhabdomyosarcoma and leukemia, respectively, are among the late sequelae noted in the peripheral nervous system (5,31). Unfortunately, cataract formation is seen in as many as 90% of patients who receive more than 750 rad (7.5 Gy) to the lens and occurs within 12–18 months after therapy.
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Figure 12. Leukoencephalopathy in a 2-year-old patient who received high-dose intrathecal methotrexate therapy for ALL. Axial T2-weighted MR image demonstrates periventricular white matter changes of leukoencephalopathy.
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A multitude of late complications, related to the use of chemotherapy, radiation therapy, or both, occurs in the cardiac system (Table). Disabling conditions or early death can result. As many as 65% of survivors of childhood ALL were found to have progressive cardiac abnormalities, including cardiomyopathy and congestive heart failure (Fig 13), 1–15 years after anthracycline therapy (32). The risk of toxic effects to the heart increases dramatically as the cumulative dose of anthracyclines administered rises (above 550 mg/m2) (32,33). Other risk factors for the development of anthracycline toxicity include female gender, younger age at time of treatment, and higher rates of administration (33). Concomitant use of radiation therapy potentiates adverse effects of anthracycline.
Major late sequelae of both chemotherapy and radiation therapy in the gastrointestinal tract include hepatic dysfunction, fibrosis, and cirrhosis (6). Chronic effects of radiation therapy in the gastrointestinal tract may be seen in up to 36% of long-term survivors and can include radiation enteritis with malabsorption, strictures (Fig 14), and obstruction (34).
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Figure 14. Esophageal perforation in a 20-year-old patient who underwent neck irradiation for multiple endocrine neoplasia syndrome. Single view from an upper gastrointestinal study demonstrates an esophageal stricture with perforation (arrow).
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Impaired renal function or renal failure are among the late effects of cancer therapy in the genitourinary system. This failure may result from progressive glomerular dysfunction caused by chemotherapeutic agents, such as ifosfamide (5,15,35,36), carboplatin, or cisplatin, or may be due to radiation nephritis (6). Treatment with cyclophosphamide, ifosfamide, or both may cause hemorrhagic cystitis at the time of or years after completion of therapy. In patients treated with concomitant radiation therapy to the pelvis, bladder fibrosis can occur (4).
Although most organ systems are affected by both chemotherapy and radiation therapy, the musculoskeletal and endocrine systems are primarily affected by irradiation. Late sequelae of radiation therapy in the musculoskeletal system include osteoporosis, avascular necrosis, leg length discrepancy, scoliosis (Fig 15), and short stature (4–7,37). Short stature can also result from growth hormone deficiency, which occurs in up to 80% of patients who received cranial irradiation (28). Although hypothyroidism is the most common abnormality reported after irradiation to the neck (5), hyperthyroidism, thyroid nodules (Fig 16), and carcinomas can also occur (38). Gonadal dysfunction may be temporary or permanent and is induced by both radiation therapy and chemotherapeutic agents. Age at treatment, gender, and cumulative dose administered affect the risk of gonadal damage (4,6).
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Figure 15. Scoliosis in a 17-year-old patient who underwent resection of and radiation therapy for a left adrenal neuroblastoma in infancy. Radiograph depicts scoliosis, as well as the surgical clips from the previous resection.
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Figure 16. Hypothyroidism in a 21-year-old patient who underwent radiation therapy for Hodgkin lymphoma. Scintiscan obtained with iodine-123 demonstrates an enlarging thyroid mass with cold nodules (arrows). Analysis of a biopsy specimen from the mass revealed multinodular goiter without carcinoma.
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Acute Graft-versus-Host Disease
Acute graft-versus-host disease is a significant complication of bone marrow transplantation and can occur in acute or chronic forms. Patients with ALL, lymphoma, and neuroblastoma are particularly at risk. Major target organs are the skin, liver, and gastrointestinal tract. Radiologic findings include nonspecific air-fluid levels, bowel wall thickening, bowel dilatation, pneumatosis (Fig 17), and ascites.
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Figure 17. Acute graft-versus-host disease in a 1-year-old patient who underwent bone marrow transplantation for ALL. Abdominal radiograph demonstrates diffuse pneumatosis, one radiographic finding of graft-versus-host disease.
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Complications of Therapeutic Surgical Interventions
Therapeutic surgical interventions, such as staging laparotomy, diagnostic biopsy, and tumor resections, increase the cancer patient's risk of developing intestinal adhesions or obstruction (39,40). Such complications can occur days to years following the surgical intervention.
Intussusception following biopsy or resection has been reported in conjunction with Wilms tumor (Fig 18) and is typically seen within 1 month of the procedure (40,41). An increased susceptibility to overwhelming infection by encapsulated organisms can occur after splenectomy, and the risk of infection is compounded by concomitant use of chemotherapy. Cosmetic, functional, and psychologic abnormalities can develop as a result of amputation for malignant bone tumors. Figure 19 shows the development of a diaphragmatic hernia following resection of a neuroblastoma.
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Figure 18a. Ileal obstruction in a 4-year-old patient following biopsy for bilateral Wilms tumors. (a) Axial CT scan at diagnosis shows bilateral, noncalcified renal masses. (b) Image from a kidney, ureter, and bladder study reveals small bowel obstruction due to an ileoileal intussusception that developed 3 weeks after biopsy.
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Figure 18b. Ileal obstruction in a 4-year-old patient following biopsy for bilateral Wilms tumors. (a) Axial CT scan at diagnosis shows bilateral, noncalcified renal masses. (b) Image from a kidney, ureter, and bladder study reveals small bowel obstruction due to an ileoileal intussusception that developed 3 weeks after biopsy.
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Figure 19a. Diaphragmatic hernia in a patient who had undergone resection of a left adrenal neuroblastoma in infancy. (a) Axial CT scan at diagnosis shows a calcified mass in the left adrenal gland. (b) Routine axial surveillance CT scan obtained several years after tumor resection shows an asymptomatic diaphragmatic hernia (arrow).
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Figure 19b. Diaphragmatic hernia in a patient who had undergone resection of a left adrenal neuroblastoma in infancy. (a) Axial CT scan at diagnosis shows a calcified mass in the left adrenal gland. (b) Routine axial surveillance CT scan obtained several years after tumor resection shows an asymptomatic diaphragmatic hernia (arrow).
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Development of Secondary Malignancies
Few complications are as devastating as the development of a secondary malignancy (Figs 20–22). Such tumors usually develop within 20 years of the primary diagnosis and have an overall prevalence of 3%–12% (42,43). Leukemia, bone and other soft-tissue sarcomas, and thyroid cancer are the most common secondary malignancies reported.
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Figure 20a. Radiation therapy–induced scoliosis and secondary malignancy in an 18-year-old patient who had undergone surgery and irradiation of the neck and spine for neurofibromatosis. Years after spinal fusion for radiation-induced scoliosis, the patient presented with a painful left shoulder mass. (a) Radiograph of the left shoulder revealed a calcified, destructive mass originating from the scapula, which prompted CT and bone scan evaluation. (b) Bone scan demonstrates uptake in the mass. Analysis of the biopsy specimen confirmed osteogenic sarcoma.
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Figure 20b. Radiation therapy–induced scoliosis and secondary malignancy in an 18-year-old patient who had undergone surgery and irradiation of the neck and spine for neurofibromatosis. Years after spinal fusion for radiation-induced scoliosis, the patient presented with a painful left shoulder mass. (a) Radiograph of the left shoulder revealed a calcified, destructive mass originating from the scapula, which prompted CT and bone scan evaluation. (b) Bone scan demonstrates uptake in the mass. Analysis of the biopsy specimen confirmed osteogenic sarcoma.
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Figure 22a. Figures 21, 22. (21) Secondary osteogenic sarcoma in a 15-year-old patient who had undergone enucleation of the left globe for bilateral retinoblastomas in infancy. (a) Coronal CT scan (bone window) demonstrates a new calcified soft-tissue mass in the previous radiation field (arrows). (b) Chest CT scan reveals pulmonary metastases from the mass, which proved to be osteogenic sarcoma. (22) Secondary leukemia with renal involvement in a 6-year-old patient previously treated for a Wilms tumor. (a) Axial CT scan at diagnosis (age 3 years) shows a mass arising from the left kidney (arrows). (b) Axial surveillance CT scan, obtained about 3 years after left nephrectomy with complete tumor resection, reveals marked enlargement of the right kidney with inhomogeneous contrast enhancement. Biopsy results demonstrated the development of secondary leukemia with renal involvement.
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Figure 22b. Figures 21, 22. (21) Secondary osteogenic sarcoma in a 15-year-old patient who had undergone enucleation of the left globe for bilateral retinoblastomas in infancy. (a) Coronal CT scan (bone window) demonstrates a new calcified soft-tissue mass in the previous radiation field (arrows). (b) Chest CT scan reveals pulmonary metastases from the mass, which proved to be osteogenic sarcoma. (22) Secondary leukemia with renal involvement in a 6-year-old patient previously treated for a Wilms tumor. (a) Axial CT scan at diagnosis (age 3 years) shows a mass arising from the left kidney (arrows). (b) Axial surveillance CT scan, obtained about 3 years after left nephrectomy with complete tumor resection, reveals marked enlargement of the right kidney with inhomogeneous contrast enhancement. Biopsy results demonstrated the development of secondary leukemia with renal involvement.
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Children who received cranial irradiation at 5 years of age or younger are most susceptible to the development of secondary brain tumors. An increased risk of secondary breast and thyroid cancer has been noted in patients treated for Hodgkin lymphoma and in those who underwent neck irradiation (44,45). Patients with genetic predisposition to tumors (eg, bilateral retinoblastomas, the genetic form of Wilms tumor, neurofibromatosis type 1) have a markedly increased risk of secondary tumor development. For example, the prevalence of secondary tumors in patients with bilateral retinoblastomas can be as high as 90% at 30 years after treatment (37,45,46). An increased risk of developing secondary solid tumors has also been documented in survivors of bone marrow transplantation. In these patients, the risk of developing a secondary solid tumor was greatest in those who were less than 10 years of age at transplantation, in those who received higher doses of total body irradiation, and in those surviving longer than 10 years after transplantation (47). Unfortunately, treatment-induced tumors are more aggressive than naturally occurring tumors and are highly refractory to therapy (43,48).
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SUMMARY
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As advances in therapy improve the prognosis of patients with childhood malignancies, awareness of the medical consequences of treatment methods assumes increasing importance. Failure to recognize oncologic emergencies occurring at diagnosis or during initial therapy may lead to early morbidity and death. As time elapses following therapy, late effects of treatment can negatively affect both the quality and duration of survival.
This article provides a structural framework for categorizing the complications of cancer therapy based on both time of occurrence and affected organ system. Physician awareness of these complications will permit more effective patient surveillance and result in earlier detection of adverse consequences of cancer treatment. This may afford patients the opportunity for earlier intervention in these situations and improved quality of life. The continued documentation of the toxic effects of therapy may better enable identification of causative agents and permit therapeutic modifications to decrease the negative impact without affecting patient survival.
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Figure 21a. Figures 21, 22. (21) Secondary osteogenic sarcoma in a 15-year-old patient who had undergone enucleation of the left globe for bilateral retinoblastomas in infancy. (a) Coronal CT scan (bone window) demonstrates a new calcified soft-tissue mass in the previous radiation field (arrows). (b) Chest CT scan reveals pulmonary metastases from the mass, which proved to be osteogenic sarcoma. (22) Secondary leukemia with renal involvement in a 6-year-old patient previously treated for a Wilms tumor. (a) Axial CT scan at diagnosis (age 3 years) shows a mass arising from the left kidney (arrows). (b) Axial surveillance CT scan, obtained about 3 years after left nephrectomy with complete tumor resection, reveals marked enlargement of the right kidney with inhomogeneous contrast enhancement. Biopsy results demonstrated the development of secondary leukemia with renal involvement.
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Figure 21b. Figures 21, 22. (21) Secondary osteogenic sarcoma in a 15-year-old patient who had undergone enucleation of the left globe for bilateral retinoblastomas in infancy. (a) Coronal CT scan (bone window) demonstrates a new calcified soft-tissue mass in the previous radiation field (arrows). (b) Chest CT scan reveals pulmonary metastases from the mass, which proved to be osteogenic sarcoma. (22) Secondary leukemia with renal involvement in a 6-year-old patient previously treated for a Wilms tumor. (a) Axial CT scan at diagnosis (age 3 years) shows a mass arising from the left kidney (arrows). (b) Axial surveillance CT scan, obtained about 3 years after left nephrectomy with complete tumor resection, reveals marked enlargement of the right kidney with inhomogeneous contrast enhancement. Biopsy results demonstrated the development of secondary leukemia with renal involvement.
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Acknowledgments
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The authors thank Doreen Keough, MS, LS, for her assistance in the preparation of the manuscript.
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Footnotes
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Address reprint requests to M.T.P.
2** indicates multiple body systems.
Abbreviations: AGC = absolute granulocyte count
ALL = acute lymphoblastic lymphoma
CME FEATURE This article meets the criteria for 1.0 credit hour in category 1 of the AMA Physician's Recognition Award. To obtain credit, see the questionnaire on pp 472–480.
LEARNING OBJECTIVES After reading this article and taking the test, the reader will be:
• Able to identify the major complications of cancer therapy in children.
• Familiar with two methods of categorizing the complications of cancer therapy in children.
• Able to identify factors that appear directly related to both the occurrence and severity of toxic effects encountered following cancer therapy.
• Familiar with several oncologic emergencies that can occur at time of diagnosis in the pediatric cancer patient.
Received for publication April 6, 1998.
Revision received May 7, 1998. August 18, 1998.
Accepted for publication August 18, 1998.
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Abstract
INTRODUCTION
