Immune checkpoint inhibitors (ICI), such as anti-PD-1 agents, have become part of the standard of care treatment of advanced non-small cell lung cancer (NSCLC). Predictive biomarkers are needed to identify patients that benefit from anti-PD-1 treatments. Tumor infiltrating lymphocytes (TILs) and PD-L1 are major players in the ICI mechanism of action. In this study, we assess the impact of real-world clinicopathological variables, including TILs and PD-L1, on anti-PD-1 efficacy. Methods: We performed a monocenter retrospective study in advanced NSCLC treated with nivolumab or pembrolizumab between January 2015 and February 2019. The impact of baseline clinical and pathological variables was assessed by univariate and multivariate models. TILs, defined as CD8+T-cells, and PD-L1 were scored in tumor and stroma, and correlated with progression free survival (PFS) and overall survival (OS). Results: We included 366 patients of whom 141 were assessed for tumor and stromal TILs. The median follow-up time was 487 days. In the whole cohort, PFS was associated with high tumor PD-L1, high albumin and good performance. OS was associated with low LDH, high albumin, good performance and 'first-line treatment'. In the TILs subcohort, stromal TILs had the strongest impact on PFS and OS. Stromal TILs were a stronger marker for PFS and OS than tumoral TILs, tumoral PD-L1 or stromal PD-L1. Remaining factors for PFS and OS were albumin and albumin with LDH, respectively. Conclusions: This real-world study on clinicopathological features shows that stromal CD8 + TILs were the strongest predictor for PFS and OS in patients with advanced NSCLC on anti-PD-1 therapy. Other predictors for PFS and OS included albumin and albumin together with LDH, respectively. This study highlights the pivotal role of the stromal compartment in the mechanisms of action of ICI, and the need for further studies aiming to overcome this stromal firewall.
Purpose of reviewAlthough respiratory viruses are common triggers of asthma exacerbation, it is unknown whether this also applies to infection with SARS-CoV-2. Indeed, patients with asthma and allergy appear underrepresented in large reports of COVID-19 cases worldwide. In this review, we evaluate existing literature on this topic and potential underlying mechanisms for any interrelationship between asthma and COVID-19. Recent findingsData from several preclinical and clinical reports suggest a lower susceptibility for COVID-19 in patients with underlying type 2 airway inflammation including asthma that may be related to a reduced expression of ACE2 and TMPRSS2 receptors for SARS-CoV-2. Corticosteroids further decrease expression of the ACE2 and TMPRSS2 receptors, hence may also have a protective effect against infection with SARS-CoV-2. In addition, some studies suggest that the reported improvement in asthma control and a reduction in asthma exacerbations during the COVID-19 pandemic may be related to improvement in adherence to controller therapy and reduced exposure to triggers, such as other respiratory viruses and air pollutants. Recent data point towards differential susceptibility for COVID-19 among asthma patients based on their phenotype and/or endotype. On the basis of existing evidence, continuation with controller therapies is recommended for all patients with asthma. For patients with severe uncontrolled asthma infected by SARS-CoV-2, adjustment of controllers and biologics should be based on a multidisciplinary decision.
It is unknown what treatment goals patients and oncologists have before starting systemic treatment. In total, 266 patients with metastatic lung cancer and their prescribing oncologists (n [ 23) were included. Patients and oncologist set quality of life, life prolongation, decreased tumor, and cure as treatment goals, but concordances of treatment goals were low. Clear communication about treatment goals should be integrated into clinical care. Background: Metastatic lung cancer is an incurable disease that can be treated with systemic therapy. These treatments might prolong survival and reduce symptoms, but they may also cause serious adverse effects. We studied the treatment goals of patients with metastasized lung cancer and their oncologists before starting systemic therapy, concordance between patients' and oncologists' goals, and feasibility of these goals. Patients and Methods: This research was conducted between November 2016 and April 2018 in 1 academic and 5 nonacademic hospitals across the Netherlands. A total of 266 patients with metastatic lung cancer and their prescribing oncologists (n ¼ 23) filled out a questionnaire about their treatment goals and the estimated feasibility of these goals before treatment was started. Additional interviews were conducted with patients and oncologists. Results: Patients and oncologists reported quality of life (respectively, 45% and 72%), life prolongation (45% and 55%), decrease in tumor size (39% and 66%), and cure (19% and 2%) as treatment goals. The interviews showed that the latter appeared to be often as motivation to stay alive. Concordances between patients' and oncologists' treatment goals were low (ranging from 24% to 33%). Patients had slightly higher feasibility scores than oncologists (6.8 vs. 5.8 on a 10-point scale). Educational level, age, religious views, and performance status of patients were associated with treatment goals. Conclusion: Patients and oncologists set various goals for the treatment they receive/prescribe. Low concordance might exist because different goals are set or because the patient misunderstands something. Clear communication about treatment goals should be integrated into clinical care.
Introduction Treatment patterns in stage III NSCLC can vary considerably between countries. The PACIFIC trial reported improvements in progression-free and overall survival with adjuvant durvalumab after concurrent chemoradiotherapy (CCRT). We studied treatment decision-making by three Dutch regional thoracic multidisciplinary tumor boards between 2015 and 2019, to identify changes in practice when adjuvant durvalumab became available. Methods Details of patients presenting with stage III NSCLC were retrospectively collected. Both CCRT and multimodality schemes incorporating planned surgery were defined as being radical-intent treatment (RIT). Results Of 855 eligible patients, most (95%) were discussed at a thoracic multidisciplinary tumor board, which recommended a RIT in 63% (n = 510). Only 52% (n = 424) of the patients finally received a RIT. Predictors for not recommending RIT were age greater than or equal to 70 years, WHO performance score greater than or equal to 2, Charlson comorbidity index greater than or equal to 2 (excluding age), forced expiratory volume in 1 second less than 80% of predicted value, N3 disease, and period of diagnosis. Between 2015 to 2017 and 2018 to 2019, the proportion of patients undergoing CCRT increased from 34% to 42% ( p = 0.02) and use of sequential chemoradiotherapy declined (21%–16%, p = 0.05). Rates of early toxicity and 1-year mortality were comparable for both periods. After 2018, 57% of the patients who underwent CCRT (90 of 159) received adjuvant durvalumab. Conclusions After publication of the PACIFIC trial, a significant increase was observed in the use of CCRT for patients with stage III NSCLC with rates of early toxicity and mortality being unchanged. Since 2018, 57% of the patients undergoing CCRT went on to receive adjuvant durvalumab. Nevertheless, approximately half of the patients were still considered unfit for a RIT.
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