Introduction: Immunotherapy works by stimulating the immune system against cancer cells. Resistance to immunotherapy represents a significant challenge in the field of medical oncology. The mechanisms by which cancer cells evade immunotherapy are not well understood. Prior research suggested overexpression of prostaglandin E-2 (PGE-2) by cancer cells, which bind to EP-2 and EP-4 receptors on the tumor-specific cytotoxic T-lymphocytes (CTLs) and suppress their anticancer role. This immunosuppressive effect is involved in evading the programmed cell death-1 (PD-1)/programmed death-ligand 1 (PD-L1) blockade of immunotherapy, which fuels cancer cell growth and recurrence. Studies found that combining PGE-2 blockade and a PD-1 signaling inhibitor helped promote the anticancer immunity cells. If confirmed in a clinical setting, the above in vitro findings could be of great clinical significance.Methods: Given that aspirin (ASA) blocks PGE-2 production, this work aimed to evaluate whether ASA use with immunotherapy results in better outcomes than immunotherapy alone. We performed a retrospective chart review of 500 non-small cell lung cancer (NSCLC) patients aged 21 years or older treated with PD-1 and/or PD-L1 directed immunotherapy at St. Luke's University Health Network between July 2015 and July 2021. Relevant patient, disease, and treatment-related variables were collected, including ASA use (≥ 81 mg daily) and the type of immunotherapy. Bivariate analyses were conducted to determine which variables to include in a multivariable model.The four primary outcomes included survival at 18-months, both after diagnosis and starting immunotherapy, achieving complete remission (CR), and having a progressive disease (PD), as defined by RECIST (Response Evaluation Criteria in Solid Tumors) criteria. Secondary outcomes included therapyrelated toxicities and complications in the different treatment groups.Results: After bivariate analysis, no statistical significance was found for a difference in 18-month survival between ASA and non-ASA groups (50.3% vs 49.7%, p-value = 0.79). ASA with PD-L1 inhibitor showed a trend towards a higher likelihood of achieving CR [adjusted odds ratio (AOR) 1.85] with a p-value close to statistical significance (0.06). However, ASA with PD-L1 showed high statistical significance as an independent variable associated with a decreased likelihood of having PD (AOR 0.44, p < 0.001). These findings suggest that NSCLC patients receiving PD-L1 inhibitors could benefit more from daily ASA than patients treated with PD-1 inhibitors. Our study emphasizes using the Eastern Cooperative Oncology Group (ECOG) scoring of the performance status (PS) in NSCLC patients. Poorer PSwas associated with lower survival, decreased likelihood of CR, and more PD. Other variables associated with worse outcomes were advanced cancer stage at diagnosis and male gender. Low-PD-L1 expression in NSCLC was associated with an increased likelihood of survival; this could be of clinical significance, especially with previous studies su...

Introduction Radiation pneumonitis (RP) is a common dose-limiting toxicity of radiotherapy to the chest in lung cancer patients. Similarly, the revolutionary use of immune checkpoint inhibitors (ICIs) to treat lung cancer can be complicated by immune-related adverse events (irAEs), particularly checkpoint inhibitor pneumonitis (CIP). Our study aimed to assess the effect of immunotherapy, with and without radiotherapy, on pneumonitis and other outcomes. Methods We performed a retrospective chart review of 680 lung cancer patients treated with either radiotherapy, immunotherapy, or both at St. Luke's University Health Network to determine the incidence rates of pneumonitis. Then, a more extensive review of 346 patients was completed, 181 of whom had pneumonitis, to investigate risk factors and outcomes. Results All-grade pneumonitis incidence was 26.6% while more severe pneumonitis (grade 3 or higher) was 13%. Receiving programmed cell death-1 (PD-1) or ligand-1 (PD-L1) inhibitors, having squamous cell carcinoma (SCC), and having poorer performance status were independently and significantly associated with increased risk of pneumonitis, with AOR (adjusted odds ratios) of 8.32, 4.10, 2.91, and 1.71, respectively. Among those who had pneumonitis, more severe cases (grade 3 or higher) were related to immunotherapy, either alone (58.32%) or with radiation (55.7%), compared to radiation therapy alone (36.2%). Poorer performance status (defined as a higher Eastern Cooperative Oncology Group (ECOG) score) was the only covariate we found to be significantly and independently associated with reduced odds of 18-months survival. More of the patients treated with both lung radiation and immunotherapy had progressive disease (53.8%) compared to those treated with only radiation (30.4%) or immunotherapy (36.7). Progressive disease occurred more in patients with pneumonitis grade 3 or higher (48.3%) than those with no or low-grade pneumonitis (27.2%). Conclusion Receiving PD-L1 and PD-1 inhibitors, either with or without radiotherapy, was associated with a higher risk of more severe pneumonitis (PD-L1 > PD-1) than radiotherapy alone. Given its high incidence and complications, more about therapy-induced pneumonitis is yet to be studied. Learning more about pneumonitis' risk factors and complications is of great clinical importance, as it may result in better treatment planning and improved outcomes. Future studies are needed to investigate the suggested association between symptomatic pneumonitis and poorer response to treatment and whether SCC increases the risk of higher-grade pneumonitis.