Richard M Gore,
University of Chicago Pritzker School of Medicine, USA
Title: Pulmonary complications of molecular targeted therapy
Biography
Biography: Richard M Gore,
Abstract
Introduction: Over the last 10years, the management of cancer patients has been revolutionized by the advances in molecular targeted therapy and immunotherapy with significant benefits for patient outcomes and comfort. These therapies, however, are associated with new toxicities and complications that can be mild, moderate or life-threatening; may require alteration or cessation of therapy, or simulate disease progression. In this presentation, the various classes of molecular targeted and immunotherapy associated with pulmonary complications are reviewed and the drug associated injuries and their differential diagnosis are presented.
Pneumonitis: Drug-induced pneumonitis develops in up to 10% of patients on immunotherapy and remains a diagnosis of exclusion that must be differentiated from infection and malignant lung infiltration. Five different patterns have been described on CT: Ground glass opacities with preserved bronchovascular markings; increased interstitial markings, interlobular septal thickening, peribronchovascular infiltration, subpleural reticulation, and honeycomb pattern in severe cases ; cryptogenic organizing pneumonia-like, with discrete patchy or confluent consolidation with or without air bronchograms, predominantly peripheral or subpleural in location; non-specific, with a mixture of nodular and other subtypes, not clearly fitting into other subtype classifications.
Bronchiolitis obliterans: There is myxoid fibrous tissue filling the distal bronchioles and extending into alveolar ducts and associated with inflammatory cells. On CT imaging findings include bilateral regions of patchy consolidation or small irregular nodular opacities, bronchial wall thickening and dilation, and small pleural effusions.
Radiation recall pneumonitis: This is an inflammatory reaction in previously irradiated areas of lung producing well-defined areas of alveolar consolidation, ground-glass opacities or infiltrates corresponding to the radiation portals. This pneumonitis usually presents 3-4months following radiotherapy and the patient presents with cough and dyspnea.
Pulmonary veno-occlusive disease: Progressive occlusion of postcapillary pulmonary venules leads to increased pulmonary resistance, pulmonary hypertension, and right ventricular failure. CT findings include diffuse ground-glass opacification, septal thickening, peribronchial thickening, soft tissue edema around the hila and mediastinum, small pleural effusions, and dilatation of the central pulmonary arteries.
Sarcoid-like granulomatous reactions: Intrathoracic lymphadenopathy simulating sarcoidosis develops in up to 10% of patients following ipilimumab and nivolumab therapy. The adenopathy may manifest and newly enlarged lymph nodes or enlargement of pre-existing lymph nodes that occur in isolation or associated with bilateral upper lobe and middle lobe predominant ground-glass opacities, parenchymal consolidations and/or irregular nodules. Most patients are asymptomatic and biopsy show non-caseating granulomas with elevated CD4: CD8 levels. Extrathoracic diffuse adenopathy and cutaneous non-caseating granulomas have also been described.
Pseudoprogression: Immunotherapy often may initially provoke infiltration of cytotoxic T lymphocytes and other immune cells into the tumor bed. This may cause an increase in tumor size or the development of new lesions as an early response. Pseudoprogression is defined as ≥ a 25% increase in tumor burden that is not seen on repeat imaging performed 4 weeks or more after the initial study. Mixed immune-related responses or pseudoprogression are quite problematic in assessing treatment response using RECIST criteria.