Immunotherapy for combined pulmonary fibrosis and emphysema with advanced lung cancer: two case reports and a concise review

Background: It is unclear whether immunotherapy for combined pulmonary fibrosis and emphysema (CPFE) with advanced lung cancer (CPFE-LC) is safe.Case Description: We reported on two cases of primary CPFE-LC, where the initial focus was on the lung cancer and not on the CPFE. The two patients underwent surgical resections of the lung cancer, and were placed on a combination of immunotherapy and chemotherapy after progressive lung cancer was observed. One patient showed a worsening of respiratory symptoms with increased consolidation and ground-glass shadows, and an increased extent of honeycombing and other fibrosis on high-resolution computed tomography (HRCT) (>10%). He suffered acute exacerbations of interstitial lung disease (AE-ILD) after successful treatment with radiotherapy and follow-up immunotherapy and developed a progressivefibrosing phenotype. The other patient had a tumor that had shrunk with no progression of the CPFE fibrosis. The two patients died of AE-ILD and tumor invasion, respectively.Conclusions: Immunotherapy combined with comprehensive therapy may provide benefits for patients with CPFE-LC to a certain extent. However, immune-related adverse effects may limit the use of immunotherapy in CPFE-LC, and the choice of immunotherapy should be cautious in CPFE-LC with a history of radiation pneumonitis or AE-ILD.