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Sarah Chuzi,1 Fabio Tavora,2 Marcelo Cruz,3 Ricardo Costa,3 Young Kwang Chae,3 Benedito A Carneiro,3 Francis J Giles3 1Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA; 2Argos Laboratory, Messejana Heart and Lung Hospital, Fortaleza, Brazil; 3Developmental Therapeutics Program, Division of Hematology/Oncology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA Abstract: Immune checkpoint inhibitors, including cytotoxic T-lymphocyte antigen 4 (CTLA-4) and programmed cell death-1 (PD-1) inhibitors, represent an effective treatment modality for multiple malignancies. Despite the exciting clinical benefits, checkpoint inhibition is associated with a series of immune-related adverse events (irAEs), many of which can be life-threatening and result in significant treatment delays. Pneumonitis is an adverse event of special interest as it led to treatment-related deaths in early clinical trials. This review summarizes the incidence of pneumonitis during treatment with the different checkpoint inhibitors and discusses the prognostic significance of tumor type. The wide range of clinical, radiographic, and histologic characteristics of checkpoint inhibitor-related pneumonitis is reviewed and followed by guidance on the different management strategies. Keywords: immune checkpoint inhibitors, pneumonitis, anti-PD-1, anti-CTLA-4, immune-related adverse event

Ricardo Costa,1 Benedito A Carneiro,1,2 Sunandana Chandra,1,2 Sachin G Pai,1 Young Kwang Chae,1,2 Jason B Kaplan,1,2 Hannah B Garrett,1 Mark Agulnik,1,2 Peter A Kopp,3 Francis J Giles1,2 1Northwestern Medicine Developmental Therapeutics Institute, Robert H Lurie Comprehensive Cancer Center of Northwestern University, 2Division of Hematology and Oncology, Feinberg School of Medicine, 3Division of Endocrinology, Metabolism, and Molecular Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA Abstract: Thyroid cancer is the most common endocrine malignancy, with over 60,000 cases reported per year in the US alone. The incidence of thyroid cancer has increased in the last several years. Patients with metastatic differentiated thyroid cancer (DTC) generally have a good prognosis. Metastatic DTC can often be treated in a targeted manner with radioactive iodine, but the ability to accumulate iodine is lost with decreasing differentiation. Until recently, chemotherapy was the only treatment in patients with advanced thyroid cancer, which is no longer amenable to therapy with radioactive iodine. The modest efficacy and significant toxicity of chemotherapy necessitated the need for urgent advances in the medical field. New insights in thyroid cancer biology propelled the development of targeted therapies for this disease, including the tyrosine kinase inhibitor sorafenib as salvage treatment for DTC. In 2015, the US Food and Drug Administration approved a second tyrosine kinase inhibitor, lenvatinib, for the treatment of radioiodine-refractory thyroid cancer. Although associated with a significant progression-free survival improvement as compared to placebo in a large Phase III study (median progression-free survival 18.2 vs 3.6 months; hazard ratio 0.21; 99% confidence interval 0.14–0.31; P