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Monitoring for and management of delayed complications after cancer therapy


KEY POINTS

  • Several different delayed pulmonary complications can occur after chemotherapy, radiation therapy, and stem cell transplantation.

  • Pulmonary fibrosis is the most common delayed parenchymal process and needs to be distinguished from organizing pneumonia, which may develop months after therapy and, unlike fibrosis, is usually reversible with steroids.

  • Obliterative bronchiolitis is a rare but serious complication that develops several months to years after hematopoietic stem cell transplantation in patients with chronic graft versus host disease; initially it may be asymptomatic, recognizable only on screening spirometry and with a variable response to immunosuppressive treatment.

  • Bronchiectasis may develop as a result of fibrosis or recurrent infection and, when symptomatic, requires a combination of respiratory hygiene (e.g., inhaled bronchodilators and mucolytics, mechanical mucus clearance maneuvers) and antimicrobials for management.

  • Pulmonary arterial hypertension is associated with certain pharmacologic cancer agents, particularly with dasatinib and, less commonly, with other tyrosine kinase inhibitors (bosutinib, nilotinib, ponatinib) and cancer therapeutics such as alemtuzumab, bevacizumab, gemcitabine, leflunomide, mitomicin, ruxolitinib, and thalidomide.

  • Pulmonary venoocclusive disease is a rare complication of cytotoxic and myeloablative therapies and can easily be missed owing to its subtle presentation suggestive of mild congestive heart failure.

  • Pleural effusions are common in patients with cancer with the differential diagnosis including complications of cancer therapy (e.g., dasatinib), malignant pleural effusion, volume overload, and congestive heart failure.

  • Secondary intrathoracic malignancies, including lung cancer and posttransplant lymphoproliferative neoplasm, may arise several months to years after cancer therapy.

Introduction

The lungs are a common site of neoplastic involvement—both primary and metastatic. Moreover, given the large surface area of the alveolar–capillary interface, lungs are a common site for idiosyncratic drug toxicities that often are difficult to distinguish from infections, postsurgical inflammatory or radiation therapy (RT) associated processes, and neoplastic involvement itself. Pulmonary complications of cancer treatment may occur during (early) or after (delayed) therapy. Delayed complications include diseases of lung parenchyma (pneumonitis, pulmonary fibrosis), airways (obliterative bronchiolitis, bronchiectasis), vasculature (pulmonary hypertension, pulmonary venoocclusive disease), pleural (serositis, effusion), neuromuscular system (weakness, diaphragm paralysis), and secondary malignancy (Central Illustration).

Parenchymal disease

Parenchymal lung disease has been reported with a variety of chemotherapeutic and biologic agents (e.g., bleomycin, mitomycin-C, carmustine, busulfan, and cyclophosphamide. Bleomycin lung toxicity is one of the most common and best characterized. Bleomycin-induced pneumonitis (BIP) may occur during therapy or after 6 months or more. Common symptoms include dyspnea, cough, and fever. Imaging usually demonstrates interstitial infiltrates and/or opacities. Patients with BIP tend to respond to corticosteroids starting at 0.5 to 1.0 mg/kg/day of prednisone or equivalent for a month followed by a taper over 3 to 6 months. BIP can progress to pulmonary fibrosis and is associated with an increased mortality among testicular cancer survivors. Other chemotherapies associated with the late complication of pulmonary fibrosis include busulfan, carmustine, and lomustine. Corticosteroid treatment has little benefit in pulmonary fibrosis, except potentially during an acute exacerbation.

RT-induced pneumonitis typically occurs several months after completion of therapy for lung, breast, and esophageal cancers as well as bone metastases, Hodgkin and non-Hodgkin lymphoma, or total body irradiation for leukemia. Symptoms are similar to those of drug-induced pneumonitis. With the exception of breast radiation-induced organizing pneumonia, airspace opacities occur within the field of radiation. Steroids may be helpful in expediting resolution of symptoms. Radiation-induced pulmonary fibrosis develops between 6 and 24 months after therapy. Some patients may be asymptomatic, whereas others may present with progressive dyspnea and cough. Pulmonary function tests demonstrate a restrictive deficit and diffusion impairment. Steroids are of little benefit in RT-induced fibrosis.

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