Society management

Computed tomography chest diagnosis, management of drug-related pneumonitis: a position paper from the Fleischner Society

The Fleischner Society has published a position paper on the role of chest computed tomography (CT) diagnosis of drug-related pneumonia (PRP) in patients treated with molecular targeting therapies and immune checkpoint inhibitors. The article, which was published in a recent edition of CHEST, provides key information on imaging models useful for diagnosing DRP and predicting the associated prognosis.

DRP related agents

An international and multidisciplinary panel of the Fleischner Society, comprising experts in lung cancer, interstitial lung disease and radiology, described the main molecular targeting agents and immunotherapies associated with DRP in this position paper. According to the literature, DRP has been reported in patients treated with epidermal growth factor receptor (EGFR) tyrosine kinase (TKI) inhibitors, including gefitinib. A cited meta-analysis indicated that the overall incidence of DRP in patients with non-small cell lung cancer (NSCLC) treated with EGFR-TKI therapy is 1.12% for all grades.


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Patients with DRP are also frequently treated with mTOR (mechanistic target of rapamycin) inhibitors, such as everolimus and temsirolimus, often for the purpose of renal carcinoma. Previous management guidelines suggest that asymptomatic patients with mTOR-induced pneumonia as well as radiologic changes can only continue to take their mTOR inhibitor therapy without dose adjustment at the discretion of the treating physician. However, patients should be aware of signs of worsening, which may lead to changes in treatment with mTOR inhibitors.

Anaplastic lymphoma kinase inhibitors for the treatment of NSCLC have been reported to be associated with severe acute pneumonitis. A meta-analysis cited in the Fleischner Society position paper suggests that the overall incidence of pneumonia in patients with advanced NSCLC treated with anaplastic lymphoma kinase inhibitors is 2.14% for all grades.

Rituximab, a monoclonal antibody depleting B cells, has also been associated with DRP. Additionally, the position paper notes that several immunotherapy agents have been associated with DRP. DRP-associated immune checkpoint inhibitors, according to the literature, include ipilimumab, nivolumab, pembrolizumab, aitzolizumab, and durvalumab.

Imaging features

The Fleischner Society panel noted that DRP is primarily diagnosed on routine CT scans for the management of follow-up cancer. A CT model of DRP described in the article includes a radiologic model of nonspecific interstitial pneumonia, which shows diffuse or uneven areas of frosted glass opacity. Typically, there is a predominance of the peripheral and lower lung area in this pattern. The anomalies are often bilateral and symmetrical with predominant involvement of the lower and peripheral lungs.

The radiologic pattern of organized pneumonia is another imaging feature in DRP and is characterized by areas of consolidation typically found in the peripheral or peribronchovascular distribution. This pattern appears to occur in patients treated with immunotherapy, EGFR-TKI, mTOR inhibitors, and anaplastic lymphoma kinase inhibitors.

In contrast, a pattern of radiologically hypersensitive pneumonitis usually occurs after treatment with gefitinib or erlotinib, mTOR inhibitors, and immune checkpoint inhibitors. This pattern features small, ill-defined centrilobular nodules with or without extensive areas of lobular areas or frosted glass opacity.

A radiologic model of diffuse alveolar injury (DAD) also shows bilateral areas of frosted glass opacity as well as “airspace-dependent consolidation with traction bronchiectasis” on the chest CT scan, which increases with the progression of disease. The radiologic DAD profile may occur in patients treated with EGFR-TKIs, immune checkpoint inhibitors, or anaplastic lymphoma kinase inhibitors. In many cases, this pattern is associated with serious clinical outcomes.

The panel also described the radiologic pattern of simple pulmonary eosinophilia as a “simple pulmonary eosinophilia pattern” characterized by “non-segmental consolidation or ground glass opacity which may be unilateral or bilateral”. The prognosis associated with this CT model is generally excellent, with spontaneous resolution commonly seen within 4 weeks.

Proposal of diagnostic criteria

Based on the previously proposed diagnostic criteria for DRP as well as the challenges associated with stopping and restarting a drug in certain settings, the Fleischner Society panel provides the following diagnostic criteria for DRP:

  • Newly identified pulmonary parenchymal opacities on CT / chest x-ray (common bilateral non-segmental distribution)
  • Temporal association of presentation with onset of systemic therapy
  • Exclusion of other possible / probable causes

Management

In terms of management, the panel stressed the importance of early diagnosis and rapid cessation of the offending agent. A multidisciplinary approach to care could be based on discussions between clinicians, pathologists and radiologists. The panel also highlighted the use of glucocorticoids as a common method to resolve lung damage, especially in severe cases of DRP. Patients with severe DRP often require hospitalization, at least for initial treatment and subsequent monitoring. Other supportive management measures include the use of supplemental oxygen as well as the support of a non-invasive and / or invasive mechanical ventilator.

Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of author disclosures.

Reference

Johkoh T, Lee KS, Nishino M, et al. Thoracic CT diagnosis and clinical management of drug-related pneumonia in patients receiving molecular targeting agents and immune checkpoint inhibitors: a position paper from the Fleischner Society. CHEST. Published online January 9, 2021. doi: 10.1016 / j.chest.2020.11.027