ERS 2022: Diagnosis and Management of Pneumonitis in Lung Cancer Systemic Therapy
In this session, the panel of experts provided an overview of the incidence and specific patterns of lung toxicity associated with immune-checkpoint inhibitors and discussed the clinical presentation, pathogenesis, diagnosis, and treatment of pulmonary toxicity associated with antineoplastic agents and the potential biomarkers that could guide clinical reasoning in immune-related toxicities.
The first talk focused on immune-checkpoint inhibitors-related pneumonitis in lung cancer and its diagnosis and management. Immune checkpoint inhibitors (ICIs) have transformed the therapeutic management of many metastatic cancers over the past decade, especially advanced non-small cell lung carcinoma (NSCLC) without oncogenic addition. Immune checkpoint inhibitor-related pneumonitis (ICI-P) is uncommon (<5%) during cancer immunotherapy; however, it is the most common pulmonary complication observed with ICI. ICI-P is more common in patients with NSCLC than in other cancers. Despite the low fatality rate, ICI-P is the leading cause of ICI-related deaths. Immunotherapy (IO) is included in almost all first-line standard regimens and at any stage of lung cancer (LC). ICI-related pneumonitis is observed in 2.6-4.8% of the cases, but frequency increases in cases of IO-IO combinations. Therefore, the risk must be better evaluated in other combinations, i.e., surgery, radiotherapy, and chemotherapy. Underlying respiratory disease, functional respiratory reserve, Asian population, and other risk factors should be known. Management should be based on early detection, IO interruption, and corticosteroids.
The next talk discussed pulmonary toxicity associated with antineoplastic therapy. Targeted anticancer therapies act by interfering with defined molecular entities and/or biologic pathways. Therefore, these targets may include tumour control and regression when adequately inhibited. An increasing number of targeted therapies are available for +/- 50% of patients with NSCLC. Pulmonary complications of targeted therapies often mimic certain ILDS seen in the general population. The most seen specific patterns of pneumonitis associated with targeted therapies are nonspecific interstitial pneumonitis (NSIP), organizing pneumonia (OP), and diffuse alveolar damage (DAD). Some new cases have reported transient asymptomatic pulmonary opacities (TAPOs), a milder form of lung reaction to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) that may manifest at imaging only. It is described in up to 20% of patients with NSCLC treated with osimertinib. They usually resolve without treatment during continued osimertinib with a median duration of 6 weeks. The risk of pneumonitis to osimertinib may be increased in patients previously treated with ICIs. New drugs can pose new challenges. In general, pulmonary toxicities require a high index of suspicion combined with comprehensive knowledge of specific pulmonary side effects of each drug. A complete diagnostic workup in patients presenting with a new or worsening respiratory complaint is necessary during treatment with targeted therapies.
The last talk focused on diagnosing and managing radiation-induced lung injury (RILI). Thoracic radiation therapy is vital in treating patients with breast, lung, thymic and oesophagal malignancies and mediastinal lymphomas. RILI is a well-known complication of radiation therapy (RT) to the chest. Patients with RILI may present nonspecifically, with symptoms ranging from asymptomatic to life-threatening disease. There are various grading scales for the severity of radiation-induced pneumonitis (RIP) and radiation-induced lung fibrosis (RILF), including late events, normal tissue task force-subjective, objective, management, analytic (LENT-SOMA), southwest cancer chemotherapy study group (SWOG). The most widely used clinical grading scales include radiation therapy oncology group (RTOG) and common terminology criteria for adverse events (CTCAE) version 5.0 (v5.0). A new RIP grading scale has been developed based on CT imaging and correlated with radiotherapeutic parameters. The majority of the patients with RILI show no clinical symptoms. Most symptoms commonly occur in the first 3-12 weeks post-RT. No standard laboratory test can identify RILI unequivocally. The goal is the prevention of RIP. Educating patients and healthcare personnel about the risk factors is essential: no effective treatments or established guidelines for RILF. Pirfenidone and nintedanib are the approved antifibrotic treatments for idiopathic pulmonary fibrosis (IPF). Trials are ongoing for the treatment of RILI with these drugs.
European Respiratory Society (ERS) International Congress 2022, 3rd-6th Sept. 2022, Barcelona
