Pulmonary Complications of Cancer Therapy
Saumini Srinivasan, MD, MS
•Treatment of malignancies involves administration of chemotherapy and radiation therapy and/or the need for hematopoietic stem cell transplantation (HSCT).
•With the introduction of chemotherapy more than 60 years ago, prognosis in all childhood cancers has improved. Overall 5-year survival rates have increased from <30% in 1960 to >80% for all childhood cancers.
•Increased survival after childhood malignancies has resulted in increasing emergence and recognition of the pulmonary complications of these treatments.
•Patients with radiation pneumonitis most commonly present with fever, cough, and shortness of breath. At examination, they are tachypneic with audible crackles.
•Kyphosis and/or scoliosis can result from radiation involving the chest, abdomen, or spine, as well as from spinal tumors. Severe deformities require surgical correction.
•Plain chest radiographs are only useful when pulmonary involvement is extensive. Computed tomography (CT) can be used to detect small areas of fibrosis, as well as infiltrates, and demonstrates the mosaic pattern characteristic of obliterative bronchiolitis (bronchiolitis obliterans).
•Pulmonary function testing helps to identify the presence of obstructive or restrictive defects. Serial lung function testing is useful in monitoring pulmonary toxicity. In the growing child undergoing therapy for cancer, lung function testing can also be useful in detecting abnormal lung growth.
•Infections are a major cause of morbidity and mortality in children undergoing therapy for cancers.
•Several factors increase susceptibility to infections.
—Disruptions of mucocutaneous barriers provide a portal of entry for pathogens.
▪Indwelling catheters, endotracheal tubes and/or chest tubes
▪Chemotherapeutic agents, such as cytosine arabinoside and anthracyclines
▪Radiation delivered to the thorax and abdomen
▪Graft versus host disease in stem cell transplantation
—Depleted or abnormally functioning phagocytic cells occur from the malignancy or result from therapies.
▪Neutropenia results in increased susceptibility to bacterial infections (Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and several resistant gram-negative organisms).
▪Fungal infections (caused by Candida species, Aspergillus, Fusarium, and Zygomycetes) can also occur because of neutropenia.
▪The use of infliximab to treat graft versus host disease increases the risk of reactivation of Mycobacterium tuberculosis infection and the development of invasive aspergillosis.
▪Effect of impaired humoral and/or cell-mediated immunity: Hypogammaglobulinemia increases the susceptibility to infection by encapsulated bacteria, including Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis.
—Impaired cell-mediated immunity in patients with Hodgkin disease and in non-Hodgkin lymphoma makes patients more prone to fungal and viral infections, as well as intracellularly replicating bacteria like M tuberculosis and Listeria.
—Herpes simplex virus infections are commonly seen after allogeneic stem cell transplantation.
—The use of T cell–depleted marrow increases the risk for cytomegalovirus infection.
—Prolonged T cell depletion results in opportunistic infections like herpes zoster and Pneumocystis jirovecii pneumonia.
—Altered central nervous system function from tumors themselves or from opioid administration increases the risk of aspiration pneumonia. Aspirated organisms colonize, invade, and disseminate from the lungs. Reduced mucosal clearance from damage caused by antineoplastic therapy facilitates invasion and dissemination.
•Patients ≥6 months of age need to be immunized with the killed influenza vaccine once they have completed chemotherapy. For those who cannot receive this vaccine, everyone who comes into the home needs to be immunized.
•The routine childhood vaccine schedule should be started or resumed 3 months after the completion of chemotherapy.
Infectious Complications and the Upper and Lower Respiratory Tracts
•Anatomic alteration from radiation damage increases the susceptibility to ear infections.
•Treatment involves the use of broad-spectrum antibiotics for 10–14 days.
•Prolonged neutropenia increases the risk for fungal mastoiditis.
•Infections are usually bacterial or fungal.
•Acute sinusitis is usually caused by S pneumoniae, Moraxella catarrhalis, or H influenzae.
•Chronic sinusitis is usually caused by gram-negative bacteria (mainly P aeruginosa) or anaerobes. This is seen more commonly in nasopharyngeal carcinomas and in Burkitt lymphomas.
•Fungal sinusitis is seen in patients with acute leukemias, those with aplastic anemias, and stem cell transplant recipients. Causative organisms include Aspergillus, Zygomycetes, and Fusarium species.
Lower Respiratory Tract Infections
•Bacterial colonization of the upper respiratory tract serves as a source of pathogenic organisms for the lower respiratory tract.
•Pulmonary infiltrates on images can be infectious or noninfectious, as detailed in Table 84-1.
•Diagnosing pneumonia in an immunocompromised child is as follows.
—Imaging studies include chest radiography and chest CT. The latter is more sensitive. The presence of a halo sign (nodular or consolidated opacities surrounded by ground-glass attenuation) at chest CT indicates the possibility of infection by an invasive filamentous fungus, such as Aspergillus, Fusarium, or Scedosporium species.
—Nasopharyngeal aspirate samples are important in diagnosing viral infections.
—Bronchoscopy and bronchoalveolar lavage are highly sensitive for the diagnosis of P jirovecii pneumonia but are less so for other fungal infections.
|Table 84-1. Differential Diagnosis of Pulmonary Infiltrates During Therapy for Childhood Malignancies|
|Localized Infiltrates||Diffuse Infiltrates|
|Bacteria||Streptococcus pneumoniae, Moraxella species, Legionella, Mycobacteria, Nocardia||Mycobacteria, Chlamydia, Mycoplasma|
|Fungi||Cryptococcus, Histoplasma, Coccidioides, Aspergillus||Pneumocystis jirovecii, Cryptococcus, Histoplasma|
|Viruses||RSV, adenovirus, influenza, CMV||RSV, adenovirus, CMV, influenza, HSV, VZV|
|Drugs||Bleomycin, busulfan, cyclophosphamide, methotrexate, cytosine arabinoside|
|Radiation-induced conditions||Radiation pneumonitis|
|Bacteria||Gram-positive and gram- negative organisms, Mycobacteria, Legionella, Nocardia||Gram-positive and gram-negative organisms, Mycobacteria, Mycoplasma, Chlamydia, Legionella, Nocardia|
|Fungi||Pneumocystis jirovecii, Cryptococcus, Histoplasma||Aspergillus, Zygomycetes, Fusarium, Scedosporium|
|Viruses||RSV, adenovirus, influenza virus||RSV, adenovirus, influenza, HSV, VZV, CMV|
CMV, cytomegalovirus; HSV, herpes simplex virus; RSV, respiratory syncytial virus; VZV, varicella zoster virus.
—In P jirovecii pneumonia:
▪Patients present with fever, dry cough, and dyspnea and are tachypneic and hypoxic at examination.
▪Bronchoscopy and bronchoalveolar lavage are highly sensitive for detecting the causative organism.
Treatment of Infectious Complications
•Treatment is based on underlying etiologic origins.
•A neutropenic patient should be started on broad-spectrum antibiotic therapy.
—Nonresponsive patients require further evaluation, including bronchoscopy and bronchoalveolar lavage, followed, if needed, by lung biopsy.