Answer:

Chemotherapy and high-dose stereotactic radiation have been used in the preoperative period after diagnosis and staging of lung cancer with an increase in survival when started in the early stages (IB-IIIA). In the past decade, the approach to chemotherapy has changed with an increased use of immunomodulators that affect the autoimmune response in favor of the organism. Lung cancer cells abound of programed death (PD)-1 and programmed death-ligand 1 (PD-L1) receptors, which upon activation, decrease the function of the killer T cells. Drugs that inhibit these receptors (also known as check point inhibitors, such as pembrolizumab, nivolumab, cemiplimab, atezolizumab, avelumab, and durvalumab) can increase the T-cell immune response toward cancer cells. This treatment modality has shown a very good oncologic response and outcome. However, a new toxic profile has emerged secondary to the overwhelming inflammation and autoimmune process, ranging from mild reaction to life-threatening conditions. Concerning side effects include skin reactions (diffuse rash), enteritis and diarrhea, hypothyroidism, hypophysitis, and adrenal insufficiency as well as hepatic insufficiency. Endocrine and hepatic side effects may be so severe to warrant delaying surgery to allow optimization. Grade 3 to 4 toxicity usually requires prednisone 1 to 2 mg/kg/day, gradually tapered to symptoms improvement and discontinuation of the immunotherapy. Anti-tumor necrosis factor- (TNF-) inhibitors are added in case of suboptimal response to steroids. Interstitial pneumonitis has been reported in patients receiving phosphoinositol 3-kinase inhibitors. When severe, it warrants intensive care unit admission and high-dose corticosteroids (1 to 2 mg/kg/day) with further immunosuppression in refractory cases. Cytokine release syndrome (CRS) can present with encephalopathy, mental status changes, and cerebellar disease. In this subpopulation, surgery should be delayed. CRS is a major concern in recipients of chimeric antigen receptor-modified T-cell lymphocytes and checkpoint inhibitors. Altered cerebellar function, mental status, and seizures have been described after its use.