This study is a retrospective chart review and analysis of the electronic medical records of adult patients diagnosed with stage III NSCLC at Parkview Health from 2019-2021 and treated with pembrolizumab as initial treatment plus sequential consolidation chest radiation (CXRT). NSCLC patients with high PD-L1 expression, but additional studies are (Rac)-PT2399 needed to confirm this hypothesis. strong class=”kwd-title” Key Words: Non-small cell lung malignancy, stage III- pembrolizumab, consolidation chest radiation, BDNF poor overall performance status Introduction Lung malignancy is the number one cause of cancer-associated mortality in the United States, and the 5-12 months overall survival rate for non-small cell lung malignancy (NSCLC) has remained poor (Duma et al., 2019; American Malignancy Society. 2021). For over a decade, the preferred treatment and standard of care for unresectable stage III NSCLC has been concurrent chemoradiation (Auprin et al., 2010). Previous clinical trials exhibited that concurrent chemoradiation was superior to sequential chemoradiation in terms of overall survival in patients with locally advanced NSCLC, albeit with increased acute esophageal toxicity (Auprin et al., 2010; M?rth et al., 2014). However, this therapy is usually indicated primarily for patients with good overall performance status, and factors such as old age, co-morbidities, and poor overall performance status make it difficult for other patients to tolerate the toxicity of chemotherapy. For example, in a study of 31 NSCLC patients with poor overall performance status (PS 2) receiving platinum combination chemotherapy, those with a malnourished nutritional status according to the Glasgow Prognostic Score were unable to complete as many chemotherapy cycles as those in the well-nourished group and experienced poorer outcomes in terms of response rate, median progression-free survival (PFS), and median overall survival (Fujio et al., 2019). Thus, immunotherapy, specifically immune checkpoint inhibitors with better tolerability, must be considered for this patient population as an alternative approach. Immune checkpoint inhibitors targeting the programmed death receptor-1 (PD-1) / programmed death-ligand 1 (PD-L1) axis have demonstrated efficacy in the treatment of a variety of cancers, including NSCLC. Pembrolizumab is usually a monoclonal antibody (mAb) which targets and blocks PD-1, and it is indicated as a single agent in patients with advanced/metastatic NSCLC tumors expressing PD-L1 (tumor proportion score (TPS) 1%) (Paz-Ares et al., 2018; Reck et al., 2016; Amrane et al., 2020, Mok et al., 2019). More specifically, pembrolizumab is usually indicated in patients without EGFR or ALK genomic aberrations in stage III disease where patients cannot receive surgical resection or definitive chemoradiation (i.e., chemotherapy with concurrent radiotherapy), as well as in patients with EGFR or ALK mutations that have continued disease progression even with FDA-approved therapy. Several randomized clinical (Rac)-PT2399 trials support the use of pembrolizumab for locally advanced or metastatic, PD-L1-expressing NSCLC as it has been shown to help increase overall survival, PFS, and (Rac)-PT2399 response compared to chemotherapy alone (Paz-Ares et al., 2018; Reck et al., 2016; Amrane et al., 2020, Mok et al., 2019). This study is usually a retrospective case series of adult ( 18 years old) patients with stage III NSCLC diagnosed at Parkview Health from 2019-2021 who were treated with pembrolizumab plus radiotherapy. We hypothesize that immunotherapy and radiation without chemotherapy may provide good disease control and tolerability in patients with unresectable stage III NSCLC that cannot be treated with chemoradiation. Materials and Methods em Study design /em This study was examined and approved by the Institutional Review Table at Parkview Health. This study is usually a retrospective chart review and analysis of the electronic medical records of adult patients diagnosed with stage III NSCLC at Parkview Health from 2019-2021 and treated with pembrolizumab as initial treatment plus sequential consolidation chest radiation (CXRT). As there is no prospective study design, this study.