Immunophenotyping of peripheral blood in NSCLC patients discriminates responders to immune checkpoint inhibitors.

PURPOSE: Immune checkpoint inhibitors (ICIs) dramatically changed the prognosis of patients with NSCLC. Unfortunately, a reliable predictive biomarker is still missing. Commonly used biomarkers, such as PD-L1, MSI, or TMB, are not quite accurate in predicting ICI efficacy. METHODS: In this prospective observational cohort study, we investigated the predictive role of erythrocytes, thrombocytes, innate and adaptive immune cells, complement proteins (C3, C4), and cytokines from peripheral blood of 224 patients with stage III/IV NSCLC treated with ICI alone (pembrolizumab, nivolumab, and atezolizumab) or in combination (nivolumab + ipilimumab) with chemotherapy. These values were analyzed for associations with the response to the treatment and survival endpoints. RESULTS: Higher baseline Tregs, MPV, hemoglobin, and lower monocyte levels were associated with favorable PFS and OS. Moreover, increased baseline basophils and lower levels of C3 predicted significantly improved PFS. The levels of the baseline immature granulocytes, C3, and monocytes were significantly associated with the occurrence of partial regression at the first restaging. Multiple studied parameters (n = 9) were related to PFS benefit at the time of first restaging as compared to baseline values. In addition, PFS nonbenefit group showed a decrease in lymphocyte count after three months of therapy. The OS benefit was associated with higher levels of lymphocytes, erythrocytes, hemoglobin, MCV, and MPV, and a lower value of NLR after three months of treatment. CONCLUSION: Our work suggests that parameters from peripheral venous blood may be potential biomarkers in NSCLC patients on ICI. The baseline values of Tregs, C3, monocytes, and MPV are especially recommended for further investigation.

Serious Immune-related Adverse Events Are Associated With Greater Efficacy of Nivolumab Therapy Against Non-small Cell Lung Cancer.

BACKGROUND/AIM: The aim of this study was to investigate possible association between adverse events of nivolumab therapy and the effectiveness of treatment in patients with non-small cell lung cancer (NSCLC). Focusing on serious adverse events (i.e., those of grade ≥3), we evaluated overall survival (OS), progression-free survival (PFS), as well as objective response rate (ORR) to treatment. PATIENTS AND METHODS: We retrospectively analyzed a set of patients from the TULUNG database of NSCLC treated with nivolumab in eight oncology centers. We evaluated OS data based upon this set. To reduce possible bias, we further evaluated a subgroup of patients treated at the University Hospital in Pilsen, where the occurrence of adverse events, PFS, and ORR were independently examined by two experienced physicians. Survival statistics were evaluated using the Kaplan-Meier method and Cox analysis. RESULTS: We observed significantly greater OS, PFS, and ORR in the group of patients experiencing adverse events upon nivolumab treatment versus in those patients without such events. Although the univariable model analyzing the data set of all patients demonstrated higher OS in patients with serious adverse events, only a nonsignificant trend was observed in the Cox multivariable model. In a subgroup of patients with PFS and ORR evaluation, we did observe significant, favorable effects for patients having had serious adverse effects. CONCLUSION: Patients experiencing severe adverse events show a tendency toward better OS, PFS, and ORR compared to patients without or having only mild adverse events with nivolumab treatment.

Comparison of Chemotherapeutic Regimens Frequently Used in Metastatic Non-squamous NSCLC Treatment.

BACKGROUND/AIM: Platinum-based chemotherapy with pemetrexed or paclitaxel/bevacizumab are regimens used in combination with checkpoint inhibitors in non-squamous non-small cell lung cancer (NSCLC) treatment. We conducted a real-world study to compare the outcomes of these chemotherapeutic regimens. PATIENTS AND METHODS: We investigated 1,534 patients with advanced non-squamous NSCLC treated with platin/pemetrexed (n=1212) or platin/paclitaxel/bevacizumab (n=322) in 9 cancer centres in the Czech Republic. RESULTS: The regimen containing platin/paclitaxel/bevacizumab showed significantly better overall response rate (ORR) compared to the platin/pemetrexed [40.8% vs. 32.7% (p=0.008)] in the overall population and [55.0% vs. 38.8% (p=0.002)] in the Eastern Cooperative Oncology Group performance status 0 group. There was no significant improvement in progression-free survival (PFS) and overall survival (OS) in either of these two groups of patients. CONCLUSION: In our real-world data analysis, patients treated with platin/paclitaxel/bevacizumab had better overall response rate (ORR), but not PFS or OS. Thus, both treatment regimens are similarly effective. Their selection should therefore be based on the potential side effects.

Impact of Concomitant Medication Administered at the Time of Initiation of Nivolumab Therapy on Outcome in Non-small Cell Lung Cancer.

AIM: To investigate potential association between administration of corticosteroids, antibiotics, probiotics, proton pump inhibitors, non-steroidal anti-inflammatory drugs (NSAID), statins and metformin and outcome in patients with non-small cell lung cancer (NSCLC) treated with nivolumab. PATIENTS AND METHODS: A total of 224 patients with advanced NSCLC treated at nine comprehensive cancer centers were analyzed in this national retrospective study. Survival statistics were evaluated using Kaplan-Meier method and Cox analysis. RESULTS: Only corticosteroid use had a significant negative effect on the objective response rate. In the univariate analysis, there was no significant effect of the studied concomitant medications on the efficacy of nivolumab. In a subsequent multifactorial analysis, a possible positive effect of the concomitant use of NSAID at the initiation of nivolumab treatment was revealed. CONCLUSION: The results of the present retrospective exploratory analysis underscore the importance of knowing the exact type of concomitant medication, the route of administration, the dose of medication, and the region of the ongoing study. The present data indicated a significantly higher rate of progression in patients treated with corticosteroids and the possible positive effect of NSAID use at the initiation of nivolumab treatment.

The Role of Airway and Endobronchial Ultrasound in Perioperative Medicine.

Recent years have witnessed an increased use of ultrasound in evaluation of the airway and the lower parts of the respiratory system. Ultrasound examination is fast and reliable and can be performed at the bedside and does not carry the risk of exposure to ionizing radiation. Apart from use in diagnostics it may also provide safe guidance for invasive and semi-invasive procedures. Ultrasound examination of the oral cavity structures, epiglottis, vocal cords, and subglottic space may help in the prediction of difficult intubation. Preoperative ultrasound may diagnose vocal cord palsy or deviation or stenosis of the trachea. Ultrasonography can also be used for confirmation of endotracheal tube, double-lumen tube, or laryngeal mask placement. This can be achieved by direct examination of the tube inside the trachea or by indirect methods evaluating lung movements. Postoperative airway ultrasound may reveal laryngeal pathology or subglottic oedema. Conventional ultrasound is a reliable real-time navigational tool for emergency cricothyrotomy or percutaneous dilational tracheostomy. Endobronchial ultrasound is a combination of bronchoscopy and ultrasonography and is used for preoperative examination of lung cancer and solitary pulmonary nodules. The method is also useful for real-time navigated biopsies of such pathological structures.