The role of immunotherapy in early-stage and metastatic NSCLC.

In the past decade we have seen new advances and thus remarkable progress in the therapeutic options for non-small cell lung cancer (NSCLC). Among cytostatic therapies with new approaches in molecularly targeted therapies, we see new developments in a wide range of applications for immunotherapies. In this review we discuss the new potential modalities for the use of immune checkpoint inhibitors (ICIs) in the frontlines, including in early-stage (perioperative) and metastatic settings. The perioperative use of ICIs in both neoadjuvant and adjuvant settings may show benefits for patients. In early-stage NSCLC (from stage IIB and above) a multimodality approach is recommended as the gold standard for the treatment. After surgical resection platinum-based adjuvant chemotherapy has been the standard of care for many years. Based on the benefit of disease-free survival, the approval of adjuvant atezolizumab and adjuvant pembrolizumab was a significant breakthrough. In the metastatic setting, the use of immune checkpoint inhibitors with chemotherapy, regardless of PD-L1 expression or ICI alone (PD-L1 expression equal to or greater than 50%) also improves overall survival and progression-free survival.

Decreasing incidence and mortality of lung cancer in Hungary between 2011 and 2021 revealed by robust estimates reconciling multiple data sources.

Objective: Hungary has repeatedly been shown to have the highest cancer-related mortality and incidence in Europe. Despite lung cancer being the most abundant malignant diagnosis in Hungary, numerous concerns have been raised recently regarding the bias inherent to reported incidence estimates. Re-analysis of reimbursement claims has been suggested previously by our group as an alternative approach, offering revised figures of lung cancer incidence between 2011 and 2016. Leveraging on this methodology, we aimed at updating Hungarian lung cancer incidence estimates with an additional 5 years (2017-2021), including years affected by the COVID-19 pandemic. Additionally, we also attempted to improve the robustness of estimates by taking additional characteristics of the patient pathway into account. Methods: Lung cancer patients between 2011 and 2021 were identified based on reimbursement-associated ICD-10 codes, histology codes and time patterns. Multiple query architectures were tested for sensitivity and compared to official estimates of the Hungarian National Cancer Registry (HNCR). Epidemiological trends were estimated by Poisson-regression, corrected for age and sex. Results: A total of 89,948 lung cancer patients diagnosed in Hungary between 2011 and 2021 have been identified by our study. In 2019 alone, 7,887 patients were diagnosed according to our optimized query. ESP2013 standardized rate was estimated between 92.5/100,000 (2011) and 78.4/100,000 (2019). In 2019, standardized incidence was 106.8/100,000 for men and 59.7/100,000 for women. Up until the COVID-19 pandemic, lung cancer incidence was decreasing by 3.18% (2.1%-4.3%) yearly in men, while there was no significant decrease in women. Young age groups (40-49 and 50-59) featured the largest improvement, but women aged 60-79 are at an increasing risk for developing lung cancer. The COVID-19 pandemic resulted in a statistically significant decrease in lung cancer incidence, especially in the 50-59 age group (both sexes). Conclusion: Our results show that using an optimized approach, re-analysis of reimbursement claims yields robust estimates of lung cancer incidence. According to this approach, the incidence rate of male lung cancer is declining in Hungary, in concordance with the trend observed for lung cancer mortality. Among women aged 60-79, the incidence of lung cancer has risen, requiring more attention in the near future.

Large-Scale Plasma Proteome Epitome Profiling is an Efficient Tool for the Discovery of Cancer Biomarkers.

Current proteomic technologies focus on the quantification of protein levels, while little effort is dedicated to the development of system approaches to simultaneously monitor proteome variability and abundance. Protein variants may display different immunogenic epitopes detectable by monoclonal antibodies. Epitope variability results from alternative splicing, posttranslational modifications, processing, degradation, and complex formation and possesses dynamically changing availability of interacting surface structures that frequently serve as reachable epitopes and often carry different functions. Thus, it is highly likely that the presence of some of the accessible epitopes correlates with function under physiological and pathological conditions. To enable the exploration of the impact of protein variation on the immunogenic epitome first, here, we present a robust and analytically validated PEP technology for characterizing immunogenic epitopes of the plasma. To this end, we prepared mAb libraries directed against the normalized human plasma proteome as a complex natural immunogen. Antibody producing hybridomas were selected and cloned. Monoclonal antibodies react with single epitopes, thus profiling with the libraries is expected to profile many epitopes which we define by the mimotopes, as we present here. Screening blood plasma samples from control subjects (n = 558) and cancer patients (n = 598) for merely 69 native epitopes displayed by 20 abundant plasma proteins resulted in distinct cancer-specific epitope panels that showed high accuracy (AUC 0.826-0.966) and specificity for lung, breast, and colon cancer. Deeper profiling (≈290 epitopes of approximately 100 proteins) showed unexpected granularity of the epitope-level expression data and detected neutral and lung cancer-associated epitopes of individual proteins. Biomarker epitope panels selected from a pool of 21 epitopes of 12 proteins were validated in independent clinical cohorts. The results demonstrate the value of PEP as a rich and thus far unexplored source of protein biomarkers with diagnostic potential.

Patterns of erythropoiesis-stimulating agent use for chemotherapy-induced anemia in lung cancer: results of a retrospective Hungarian real-life clinical data analysis.

OBJECTIVE: Lung cancer carries a relatively high risk of chemotherapy-induced anemia, one of the most frequent hematological complications. Previous data show a lack of optimal anemia correction in patients with chemotherapy-induced anemia. This paper analyzes real-life data considering the prevalence and severity of chemotherapy-induced anemia, together with the frequency and efficacy of erythropoietin treatment of anemia in Hungarian lung cancer patients. RESEARCH DESIGN AND METHODS: Data of 482 patients with histological or cytological confirmed lung cancer receiving chemotherapy were collected retrospectively between 1 January and 31 December, 2008. In all, 83 (17%) of them developed chemotherapy-induced moderate to severe anemia (44.6% male, 55.4% female; mean age 70 ± 8.6 years; NSCLC 67.5%, small cell lung cancer 32.5%). RESULTS: More than 50% of the patients suffering from moderate to severe chemotherapy-induced anemia (hemoglobin below 10 g/dl) did not receive erythropoietin treatment. Chemotherapy had to be postponed due to anemia in 32.26% of the patients receiving erythropoietin supplementation, while this was seen in 41.94% of the group without erythropoietin treatment (p < 0.05). In patients not receiving erythropoietin, the severity of anemia increased, while erythropoietin treated patients maintained acceptable hemoglobin levels after the end of the chemotherapy. CONCLUSIONS: The data draws attention to the fact that nowadays chemotherapy-induced anemia is not treated according to current guidelines in many lung cancer cases in Hungary.