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BackgroundCurrent smokers undergoing lobectomy are at greater risk of complications than are former smokers. The Society of Thoracic Surgeons (STS) composite score for rating program performance for lobectomy adjusts for smoking status, a modifiable risk factor. This study examined variability in the proportion of current smokers undergoing lobectomy among STS database participants. Additionally, the study determined whether each participant's rating changed if smoking was excluded from the risk adjustment model.MethodsThis is a retrospective analysis of the STS cohort used to develop the composite score for rating program performance for lobectomy. The study summarized the variability among STS database participants for performing lobectomy on current smokers and compared star ratings developed from models with and without smoking status.ResultsThere were 24,912 patients with smoking status data: 23% current smokers, 62% former smokers, and 15% never smokers. There was significant variability among participants in the proportion of current smokers undergoing lobectomy (3% to 48.6%; P < .001). Major morbidity or mortality (composite) was greater in current smokers (12.1%) than in former smokers (8.6%) and never smokers (4.2%) (P < .001). Using the current risk adjustment model, participant star ratings were as follows: 1 star, n = 6 (3.2%); 2 stars, n = 170 (91.4%); and 3 stars, n = 10 (5.4%). When smoking status was excluded from the model, 1 participant shifted from a 2-star to a 3-star program.ConclusionsThere is substantial variability among STS database participants with regard to the proportion of current smokers undergoing lobectomy. However, exclusion of smoking status from the model did not significantly affect participant star rating.

In this article, we summarize results from the ongoing phase 3 CheckMate 816 clinical study that were published in The New England Journal of Medicine in 2022. The goal of CheckMate 816 was to find out if nivolumab, an immunotherapy that activates a person's immune system (the body's natural defense system) to fight cancer, plus chemotherapy works better than chemotherapy alone when given before surgery in people with non–small-cell lung cancer (NSCLC) that can be removed surgically (resectable NSCLC). Adults who had not previously taken medications to treat NSCLC and whose cancer could be removed with surgery were included in CheckMate 816. During this study, a computer randomly assigned the treatment each person would receive before surgery for NSCLC. In total, 179 people were randomly assigned to receive nivolumab plus chemotherapy, and 179 people were randomly assigned to receive chemotherapy alone. The researchers assessed whether people who received nivolumab plus chemotherapy lived longer without the cancer geting worse or coming back and whether there were any cancer cells left in the tumor and lymph nodes removed by surgery. The researchers also assessed how adding nivolumab to chemotherapy affected the timing and outcomes of surgery and whether the combination of these drugs was safe. Researchers found that people who took nivolumab plus chemotherapy lived longer without the cancer getting worse or coming back compared with those who took chemotherapy alone. More people in the nivolumab plus chemotherapy group had no cancer cells left in the tumor and lymph nodes removed by surgery. Most people went on to have surgery in both treatment groups; the people who took nivolumab plus chemotherapy instead of chemotherapy alone had less extensive surgeries and were more likely to have good outcomes after less extensive surgeries. Adding nivolumab to chemotherapy did not lead to an increase in the rate of side effects compared with chemotherapy alone, and side effects were generally mild and manageable. Results from CheckMate 816 support the benefit of using nivolumab plus chemotherapy before surgery for people with resectable NSCLC. Clinical Trial Registration: NCT02998528 (ClinicalTrials.gov) [ABSTRACT FROM AUTHOR]

Purpose: Co-mutations of the Kirsten rat sarcoma virus (KRAS) and serine/threonine kinase 11 (STK11) genes in advanced non-small cell lung cancer (NSCLC) are associated with immune checkpoint blockade (ICB) resistance. Although neoadjuvant chemoimmunotherapy is now a standard-of-care treatment for resectable NSCLC, the clinical and immunologic impacts of KRAS and STK11 co-mutations in this setting are unknown., Experimental Design: We evaluated and compared recurrence-free survival of resectable KRAS-mutated NSCLC tumors, with or without co-occurring STK11 mutations, treated with neoadjuvant ICB. Single-cell transcriptomics was performed on tumor-infiltrating T cells from seven KRASmut/STK11wt tumors and six KRAS and STK11 co-mutated (KRASmut/STK11mut) tumors., Results: Relative to KRASmut/STK11wt tumors, KRASmut/STK11mut exhibited significantly higher recurrence risk. Single-cell transcriptomics showed enhanced oxidative phosphorylation with evidence of decreased prostaglandin E2 signaling and increased IL-2 signaling in CD8+ tumor-infiltrating lymphocytes (TIL) from KRASmut/STK11mut tumors, a finding that was mirrored in KRASwt tumors that relapsed. TILs from KRASmut/STK11mut tumors expressed high levels of molecules associated with tumor residence, including CD39 and ZNF683 (HOBIT)., Conclusions: These divergent T-cell transcriptional fates suggest that T-cell maintenance and residence may be detrimental to antitumor immunity in the context of neoadjuvant ICB for resectable NSCLC, regardless of KRAS mutation status. Our work provides a basis for future investigations into the mechanisms underpinning prostaglandin E2 signaling and IL-2 signaling as they relate to T-cell immunity to cancer and to divergent clinical outcomes in KRASmut/STK11mut NSCLC treated with neoadjuvant ICB., (©2024 The Authors; Published by the American Association for Cancer Research.)

Purpose: Neoadjuvant anti-PD-1 therapy has shown promise for resectable non-small cell lung cancer (NSCLC). We reported the first phase I/II trial of neoadjuvant nivolumab in resectable NSCLC, finding it to be safe and feasible with encouraging major pathological responses (MPR). We now present 5-year clinical outcomes from this trial, representing to our knowledge, the longest follow-up data for neoadjuvant anti-PD-1 in any cancer type., Patients and Methods: Two doses of nivolumab (3 mg/kg) were administered for 4 weeks before surgery to 21 patients with Stage I-IIIA NSCLC. 5-year recurrence-free survival (RFS), overall survival (OS), and associations with MPR and PD-L1, were evaluated., Results: With a median follow-up of 63 months, 5-year RFS and OS rates were 60% and 80%, respectively. The presence of MPR and pre-treatment tumor PD-L1 positivity (TPS ≥1%) each trended toward favorable RFS; HR, 0.61 [95% confidence interval (CI), 0.15-2.44] and HR, 0.36 (95% CI, 0.07-1.85), respectively. At 5-year follow-up, 8 of 9 (89%) patients with MPR were alive and disease-free. There were no cancer-related deaths among patients with MPR. In contrast, 6/11 patients without MPR experienced tumor relapse, and 3 died., Conclusions: Five-year clinical outcomes for neoadjuvant nivolumab in resectable NSCLC compare favorably with historical outcomes. MPR and PD-L1 positivity trended toward improved RFS, though definitive conclusions are limited by cohort size., (©2023 The Authors; Published by the American Association for Cancer Research.)

Background: Neoadjuvant or adjuvant chemotherapy confers a modest benefit over surgery alone for resectable non-small-cell lung cancer (NSCLC). In early-phase trials, nivolumab-based neoadjuvant regimens have shown promising clinical activity; however, data from phase 3 trials are needed to confirm these findings., Methods: In this open-label, phase 3 trial, we randomly assigned patients with stage IB to IIIA resectable NSCLC to receive nivolumab plus platinum-based chemotherapy or platinum-based chemotherapy alone, followed by resection. The primary end points were event-free survival and pathological complete response (0% viable tumor in resected lung and lymph nodes), both evaluated by blinded independent review. Overall survival was a key secondary end point. Safety was assessed in all treated patients., Results: The median event-free survival was 31.6 months (95% confidence interval [CI], 30.2 to not reached) with nivolumab plus chemotherapy and 20.8 months (95% CI, 14.0 to 26.7) with chemotherapy alone (hazard ratio for disease progression, disease recurrence, or death, 0.63; 97.38% CI, 0.43 to 0.91; P = 0.005). The percentage of patients with a pathological complete response was 24.0% (95% CI, 18.0 to 31.0) and 2.2% (95% CI, 0.6 to 5.6), respectively (odds ratio, 13.94; 99% CI, 3.49 to 55.75; P<0.001). Results for event-free survival and pathological complete response across most subgroups favored nivolumab plus chemotherapy over chemotherapy alone. At the first prespecified interim analysis, the hazard ratio for death was 0.57 (99.67% CI, 0.30 to 1.07) and did not meet the criterion for significance. Of the patients who underwent randomization, 83.2% of those in the nivolumab-plus-chemotherapy group and 75.4% of those in the chemotherapy-alone group underwent surgery. Grade 3 or 4 treatment-related adverse events occurred in 33.5% of the patients in the nivolumab-plus-chemotherapy group and in 36.9% of those in the chemotherapy-alone group., Conclusions: In patients with resectable NSCLC, neoadjuvant nivolumab plus chemotherapy resulted in significantly longer event-free survival and a higher percentage of patients with a pathological complete response than chemotherapy alone. The addition of nivolumab to neoadjuvant chemotherapy did not increase the incidence of adverse events or impede the feasibility of surgery. (Funded by Bristol Myers Squibb; CheckMate 816 ClinicalTrials.gov number, NCT02998528.)., (Copyright © 2022 Massachusetts Medical Society.)