Impact of PD-L1 Expression on the Overall Survival of Patients With Non-small Cell Lung Cancer Treated With Single-agent Pembrolizumab.

BACKGROUND/AIM: Cemiplimab in patients with non-small cell lung cancer (NSCLC) with PD-L1 (programmed death ligand type 1) expression ≥50% showed a significant improved overall survival (OS) with increasing expression of PD-L1. To our knowledge there exist no similar data published for pembrolizumab regarding the increased OS in relation to the PD-L1 expression. Therefore, the objective of our study was to determine whether improvement in OS reflects increased expression levels of PD-L1 (≥50%) in patients with NSCLC. PATIENTS AND METHODS: Retrospective data from 9 Czech and 1 Polish comprehensive oncology Centers were used. All patients with stage IV NSCLC and PD-L1 expression ≥50% treated with pembrolizumab in daily practice were included. The groups of patients according to the expression of PD-L1 were determined as follows: PD-L1 50-59%, 60-69%, 70-79%, 80-89% and 90-100%. The log-rank test and the Cox regression model were used to compare survival between study groups. RESULTS: A total of 617 patients were included in the study. We did not observe a statistically significant difference in OS between groups of patients with different levels of PD-L1 expression in the pooled comparison (p=0.445). Furthermore, we did not observe a statistically significant difference even when comparing OS in patients with PD-L1expression of 50-59% (reference) with the group of other patients according to the level of expression of PD-L1 in the Cox regression model including the effect covariates. CONCLUSION: PD-L1 expression showed no significant effect on OS in patients with NSCLC with PD-L1≥50% treated with pembrolizumab.

Omission of staging PET/CT linked to reduced survival in stage III non-small cell lung cancer: insights from the LUCAS project real-world data.

Background: Stage III non-small cell lung cancer (NSCLC) is a highly heterogeneous stage due to its subgroups (IIIA-IIIC) comprising both resectable and unresectable tumors. Accurate determination of the extent of the disease is essential for excluding stage IV and choosing the optimal treatment regimen. Whole body positron emission tomography and computed tomography scan (PET/CT) is recommended as an initial staging imaging in locally advanced NSCLC. Despite international guidelines for NSCLC diagnosis and treatment, they are not always adhered to due to various reasons. Even in such a groundbreaking study, the phase 3 trial PACIFIC investigating the efficacy of durvalumab as consolidation therapy in patients with stage III NSCLC PET/CT was not mandatory. With the premise that whole body PET/CT of the trunk is essential for diagnosing stage III NSCLC, we performed a retrospective study evaluating the relationship of the use of PET/CT versus conventional staging with CT of the chest and abdomen, in terms of survival. Methods: This retrospective study of stage III NSCLC patients used the Czech lung cancer registry LUCAS, which was established in June 2018. As of the data export (up to February 9, 2022), a total of 703 patients were eligible for the analysis. Overall survival (OS) was compared using Kaplan-Meier analysis and a Cox regression model. Continuous variables were tested using the Mann-Whitney test, and categorical variables using the Pearson's Chi-square or Fisher's exact test. Results: A total of 703 patients were included in the cohort with an average age of 69 years. PET/CT was performed on 354 patients, and conventional staging using chest and abdominal CT on 349 patients. The median OS among patients with PET/CT was 20.9 months [95% confidence interval (CI): 18.1-23.7], and it was statistically significantly higher (P<0.001) than among patients without PET/CT, where the median OS was 9.0 months (95% CI: 7.3-10.6). The observed effect of PET/CT was also statistically significant when comparing individual stages (IIIA, IIIB, IIIC). The multivariate Cox model confirmed the use of PET/CT as an independent prognostic factor. The most common reason for omission of PET/CT was the local or time unavailability of the examination. Conclusions: Omission of PET/CT can mean a significant decrement in survival for the patients in stage III NSCLC, likely due to poor staging and suboptimal treatment. Routine use of PET/CT is strictly recommended for the optimal management of stage III NSCLC patients even outside the high-income countries.

Comparison of the efficacy of cisplatin and carboplatin in combination with etoposide in firstline treatment of extensive-stage small cell lung cancer in real-world practice in the Czech Republic - a retrospective analysis of patients from the LUCAS project.

BACKGROUND: Patients with extensive-stage small-cell lung cancer (ES-SCLC) have a poor prognosis. The standard palliative treatment for four decades has been chemotherapy as a combination of etoposide with carboplatin or cisplatin, and in recent years, immunotherapy in addition. AIMS: To determine whether there is a difference in the efficacy of palliative chemotherapy as cisplatin or carboplatin in combination with etoposide in patients with ES-SCLC in real-world practice in the Czech Republic. METHODS: This was a retrospective analysis of a cohort of 348 patients from the LUCAS project with ES-SCLC. 79 were treated with etoposide plus cisplatin and 265 were treated with etoposide plus carboplatin. Kaplan-Meier curves and the Cox regression model were used for analysis. RESULTS: No statistically significant difference in median overall survival (mOS) or median progression free survival (mPFS) was found between groups or between patients grouped according to age and performance status (PS) in mOS. The Cox regression result was similar. CONCLUSION: This study shows that cisplatin and carboplatin do not differ in efficacy in a given indication, thus when choosing a treatment, the physician should consider the expected toxicity in a particular patient, assessing the patient's general condition and comorbidities.

Rethinking risk prediction: The role of albumin and other parameters in implant-associated complications after hip or knee arthroplasty.

BACKGROUND: Total hip (THA) or knee (TKA) arthroplasty is still a traumatic and challenging operation that induces inflammation, with a particularly high risk of acute-phase reaction. The aim of this study was to predict the likelihood of implant-associated complications during the preoperative and postoperative course. METHODS: The prospective observational, non-interventional study of patients diagnosed with primary knee or hip osteoarthrosis undergoing THA or TKA during the study period was conducted. The inflammatory and malnutrition parameters were collected for each patient one day before surgery, two days after surgery, and in outpatient follow-up. RESULTS: Of 159 patients analysed, 12 developed implant-associated complications. The albumin, prealbumin, Intensive Care Infection Score (ICIS), Nutritional Risk Index, and white blood cell counts were found to be potential predictors. Notably, preoperative albumin levels significantly differed between groups with and without complications (P-value = 0.042). CONCLUSION: Our study definitively shows that WBC, prealbumin, Nutritional Risk Index, ICIS as a novel marker, and significantly albumin, outperform C-reactive protein in predicting implant-associated complications in hip and knee arthroplasty.

Inflammatory blood parameters as prognostic factors for implant-associated infection after primary total hip or knee arthroplasty: a systematic review.

BACKGROUND: Implant-associated infection (IAI) is a potential complication following total hip (THA) or knee arthroplasty (TKA). The initial phase of the inflammatory process can be measured by applying one of the inflammatory blood parameters (IBP). This systematic review aims to assess the response of IBP to trauma caused by orthopedic surgery and evaluate the clinical utility of quantitative measurements of IBP as prognostic factors for infection. METHODS: All studies indexed in Ovid MEDLINE (PubMed), Ovid EMBASE, the Cochrane Library and the ISI Web of Science databases, from inception until January 31, 2020, were analyzed. Studies included were those on adults who underwent THA or TKA with minimum follow up of 30 days after surgery. In addition to minimum follow up, data on the prognostic factors for pre- or post-THA/TKA IAI were mandatory. The Quality Assessment of Diagnostic Accuracy tool (version 2) (QUADAS-2) and Standards for Reporting of Diagnostic Accuracy Studies guideline 2015 (STARD) were used for quality assessment. RESULTS: Twelve studies fulfilled the inclusion and exclusion criteria. C-reactive protein was analyzed in seven studies, interleukin-6 in two studies and erythrocyte sedimentation rate in eight studies. White blood cell count and procalcitonin were analyzed in the only study. The overall quality of included studies was low. A potential for other cytokines (IL-1ra, IL-8) or MCP-1 was observed. CONCLUSIONS: This is the first systematic review of IBP response to orthopedic surgery which identified some IBP for pre/post-operative screening, despite insufficient data supporting their prognostic potential for patient risk stratification.

Inflammatory blood parameters as prognostic factors for surgical site infection after primary hip or knee arthroplasty: a systematic review protocol.

INTRODUCTION: Surgical site infection (SSI) is a potential complication of surgical procedure. SSI after implant surgery is a disaster both for patients and surgeons. Although predictive tools for SSI are available, none of them estimate early infection based on inflammatory blood parameters. The inflammatory process can be measured using several parameters including interleukin-6, C reactive protein, neutrophil to lymphocyte ratio, white cell count, erythrocyte sedimentation rate or procalcitonin. This systematic review aims to determine whether inflammatory blood parameters could be used as significant predictive factors for SSI after primary hip or knee arthroplasty. METHODS AND ANALYSIS: A systematic review of randomised controlled trials, cross-sectional studies, case-control studies and cohort studies, published in English, will be searched in the following electronic bibliographic databases: MEDLINE, Embase, PubMed, Cochrane Central Register of Controlled Trials and Web of Science. Studies performed in adult patients of all ages who underwent knee or hip arthroplasty, studies containing data on the risk/prognostic factors for preknee or postknee or hip arthroplasty SSI and studies with a minimum follow-up of 30 days after surgery will be included. A standardised form will be used to extract data from the included studies comprising study characteristics, participant characteristics, details of the intervention, study methodology and outcomes. Quality Assessment of Diagnostic Accuracy tool, second version, and Standards for Reporting of Diagnostic Accuracy Studies checklist will be used to assess risk of bias. Heterogeneity will be assessed using Cochran χ² statistic and I2 statistics where applicable. Grading of Recommendations Assessment, Development and Evaluation and Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidance will be used to report findings. ETHICS AND DISSEMINATION: No ethics approval is required. The findings will be disseminated at national and international scientific sessions, also to be published in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42020147925.