Complications in the Oncologic Patient: Chest

Introduction

With advances in cancer therapy, iatrogenic diseases of the chest are increasingly encountered. They are predominated by those affecting the lungs, which are an important cause of patient morbidity and mortality. In the cancer patient, iatrogenic pulmonary disease could be as a result of chemotherapy, radiation therapy (RT), or stem cell transplantation (SCT). Recognizing these patterns of disease is important because the radiologist may be the first to notice these changes, which at times may be reversible if identified in a timely manner.

Chemotherapy-Induced Noninfectious Lung Disease

The problem of drugs adversely affecting the lungs remains a major challenge to all primary care physicians. Symptoms are usually nonspecific, with patients presenting with dyspnea, nonproductive cough, and fever, which can begin weeks to years after the medication is first taken. Unfortunately, drug-induced respiratory disease remains a disease of exclusion, because the majority of drugs responsible for this effect cannot be identified by any specific test. Diagnosis requires a high index of suspicion, because infection, radiation pneumonitis, and recurrence of the underlying disease can manifest clinically and radiographically in a similar manner. There is underreporting of drug toxicity, and thus, the true incidence of drug-induced respiratory disease is unknown, although it is estimated to be less than 10%. To complicate matters, only a few patients are treated with single drugs. Thus, how much of an observed reaction is related to one agent or another versus synergy with other drugs, oxygen, or radiation often remains unknown. Prompt diagnosis of drug-induced lung toxicity is important, because early drug-induced lung injury will often regress with cessation of the therapy or with initiation of steroid therapy before pulmonary fibrosis is able to develop. For an updated list of generic drugs, types of reaction, and radiologic manifestations with references, the reader is referred to the routinely updated website Pneumotox ( www.pneumotox.com ). In this reference and in Table 40.1 , the reader will find some of the effects of drugs on other chest structures such as those causing pleural effusions, lymphadenopathy, or cardiomyopathy.

The lungs have a limited number of histopathologic responses to injury (see Table 40.1 ) that mimic many other pulmonary conditions. The radiologic appearance of drug toxicity corresponds to the histopathologic finding. Owing to these nonspecific findings, diagnosis relies on correlation with clinical, laboratory, and radiologic information. Even bronchoalveolar lavage (BAL) can only suggest an iatrogenic cause by helping to exclude infection and malignancy. Sometimes, cell composition in the lavage and elevation of a specific population (e.g., lymphocytes, neutrophils, or eosinophils) may suggest a more specific diagnosis.

As an aid for interpretation of the chest images, it is helpful to divide drug toxicity into acute and delayed presentation. Acute-onset, chemotherapy-induced lung injury is usually caused by noncardiogenic pulmonary edema/diffuse alveolar damage, hypersensitivity-type reaction, or pulmonary hemorrhage and occurs after the initial dose of chemotherapy. Radiographic findings usually include diffuse or scattered ground-glass opacities (GGOs) or consolidative opacities with or without septal thickening ( Fig. 40.1 ).

Delayed-onset, chemotherapy-induced lung injury usually presents more than 2 months after the completion of treatment or during prolonged treatment and is often caused by chronic interstitial pneumonia, which can lead to fibrosis. The more common histologic patterns seen are usual interstitial pneumonia (UIP) or nonspecific interstitial pneumonia (NSIP). The pattern most commonly encountered is that of NSIP, which appears as bilateral lower lobe–predominant heterogeneous or consolidative opacities on chest radiographs, and initially as scattered GGOs or consolidative opacities with lower lobe predominance on thin-section chest computed tomography (CT) ( Fig. 40.2 ). Although intralobular septal thickening and traction bronchiectasis can be seen with NSIP, when present, these findings are much more likely to be from UIP. Organizing pneumonia with fibromyxoid connective tissue plugs that fill distal airspaces, as well as terminal or respiratory bronchioles, is another nonacute form of drug toxicity. When associated with a known causative agent, this finding should be termed bronchiolitis obliterans organizing pneumonia (BOOP) caused by the name of the drug (e.g., BOOP caused by amiodarone). Radiographic findings of drug-induced BOOP on chest radiographs are bilateral scattered heterogeneous or consolidative opacities in a peripheral distribution, and on chest CT there are unilateral or bilateral areas of consolidation, with either peripheral or the more typical peribronchovascular distribution and a lower lobe predominance. Rarely, BOOP may have a nodular appearance that can be confused with metastatic disease.

When clinical suspicion for drug toxicity is high, thin-section CT should be performed, especially in conjunction with a normal chest film, so that treatment can be initiated for reversal of the process. Often, however, these findings are detected incidentally on routine follow-up chest CT scans. Radiologists may thus be the first to suspect drug toxicity and must alert the clinician to this possibility before end-stage fibrosis develops.

Chemotherapy-Induced Infectious Lung Disease

Drugs that are used to combat cancer target dividing cells, affect the bone marrow, and cause a decrease in neutrophils that results in infections. Other drugs that are often used to treat hematologic malignancies in conjunction with chemotherapeutic agents have immunosuppressive properties. Corticosteroids cause a broad suppression of the immune system. Diagnosis of pneumonia depends on clinical symptomatology with radiographic findings. The type of pathogen producing the pneumonia, whether bacterial, viral, or fungal, depends mainly on the patient’s immune status and the combination therapy they received. Given the inability of the severely immunocompromised patient (e.g., SCT recipients or prolonged neutropenia in patients with hematologic malignancies) to mount an adequate inflammatory response, the classic radiographic findings of each type of pneumonia may differ from those found in immunocompetent patients, and chest films may even appear normal. CT may disclose more subtle changes, such as minimal GGOs, bronchial thickening, or nodules, and in select cases may show the typical appearance for a specific group of pathogens. Such findings may lead to the correct selection of antibiotic therapy and improved outcomes.

Bacterial Pneumonia

The main source of pathogens is the patient’s endogenous flora. With the introduction of extended-spectrum beta-lactams, there has been a decrease in bloodstream infections because of gram-negative rod bacteremia and an increase in infections because of gram-positive cocci, although nosocomial bacterial pneumonias are still predominated by gram-negative rods. There is a low predictive yield to determination of the type of bacterial pneumonia from the chest radiographic or even chest CT appearance in the immunocompromised patient population. In SCT recipients, bacterial pneumonia most commonly manifests as pulmonary nodules (81%), in a tree-in-bud distribution, lower lobe predominant, asymmetrically distributed consolidation (69%), and GGOs (35%), usually symmetrically distributed. The majority of patients demonstrate a combination of these findings (73%), with another 15% of patients having pulmonary nodules only and 12% consolidation only on CT ( Fig. 40.3 ).

Viral Pneumonia

DNA viruses such as herpes simplex, varicella, and cytomegalovirus (CMV) have long been recognized as causing severe respiratory infections in patients with hematologic malignancies. These patients are also exposed to community seasonal respiratory viruses such as adenovirus or influenza A, which can be life-threatening in such immunocompromised patients. Radiographically, one viral infection cannot be differentiated from another. They tend to be symmetrically distributed in the lung, usually with lower lobe predominance and a combination of GGOs or consolidative airspace disease ( Fig. 40.4 ) in addition to small centrilobular nodules and consolidative opacities. The mortality rate can be high, and early diagnosis is essential because early treatment improves survival. Of this group, airspace disease is the most common finding, seen in 90% of patients with CT-documented pneumonia. The early changes of lower lobe–predominant peribronchial thickening and peribronchial GGOs or tree-in-bud opacities are more readily appreciated on a lateral plain film or, with greater sensitivity, by chest CT, although early bacterial pneumonia may have a similar appearance.