Summary
Objective
Obstructive sleep apnea (OSA) is a common medical problem with numerous comorbidities and high costs. Since the introduction of the Epworth sleepiness scale (ESS), excessive daytime ...sleepiness (EDS) has been considered the most common and prominent symptom of OSA. Aim of this study was to re-evaluate the ESS for detection of OSA in a population at risk compared to the gold standard overnight polysomnography (PSG).
Methods
A total of 266 patients (mean age 57.9 ± 11.6 years; 189 men and 77 women), referred to our sleep laboratory for probable OSA, were given ESS followed by an overnight PSG. The ESS values were compared to PSG apnea hypopnea index (AHI) with sensitivity (SE), specificity (SP), positive predictive value (PPV), negative predictive value (NPV) and diagnostic accuracy (DA) calculated for ESS. The positive cut-off value for ESS was ≥ 10 and for AHI ≥ 5.
Results
Only 92 (34.6%) subjects had a positive ESS. An OSA was diagnosed by PSG in 213 (80.1%) subjects: 46 having mild, 37 moderate and 130 severe apnea. Most subjects with positive ESS (88.0%) were found to have OSA but most subjects with a negative ESS (75.9%) were also positive for OSA (42% with AHI ≥ 30). The area under the receiver operating characteristic (ROC) curve for ESS was 0.60 (95% confidence interval, CI 0.54–0.66;
p
= 0.020) with SE 38.0%, SP 79.3%, PPV 88.0%, NPV 24.1% and DA 46.2%.
Conclusion
It was found that excessive daytime sleepiness, measured by ESS, is not a valuable screening tool for OSA, especially when the test is negative. Other screening tests that involve additional parameters, beside daytime sleepiness alone, should be considered.
Although the median age at diagnosis of non-small cell lung cancer (NSCLC) is 70 years, a subset of patients with NSCLC present at a younger age (<40 years). Little is known about the time-trends in ...incidence of NSCLC in the young, their characteristics and outcomes.
The surveillance, epidemiology, and end results database was used to extract NSCLC cases from 1978 to 2010. Yearly incidence rates in various age groups, race, site of disease, histology, treatment patterns, and outcomes were assessed. We modeled Kaplan-Meyer survival curves stratified by age of presentation.
Young patients represented 0.6% of incident NSCLC from 1978 to 2010. The incidence of young NSCLC declined significantly during this time-period. Young NSCLCs had a higher proportion of women (51%), Asians or Pacific Islanders (14%), adenocarcinoma histology (59%) and were more likely to present with distant metastases (68%). The young had better all cause and lung cancer-specific survival than the older patients (median survival for localized, regional, and distant disease: not reached, 28, 9 vs. 46, 17, 5 months; p < 0.001 for all groups). Male sex, non-adenocarcinoma histology, and main bronchial primary were independent negative prognostic factors among the young. In contrast to the overall population, black race was a poor prognostic factor among the young.
The incidence of NSCLC in the young decreased from 1978 to 2010. The clinical characteristics of NSCLC in the young, including demographic distribution, treatment, and outcomes are different from those observed in the older patients.
Receptor tyrosine kinases (RTKs) are transmembrane receptors of great clinical interest due to their role in disease. Historically, therapeutics targeting RTKs have been identified using in vitro ...kinase assays. Due to frequent development of drug resistance, however, there is a need to identify more diverse compounds that inhibit mutated but not wild-type RTKs. Here, we describe MaMTH-DS (mammalian membrane two-hybrid drug screening), a live-cell platform for high-throughput identification of small molecules targeting functional protein-protein interactions of RTKs. We applied MaMTH-DS to an oncogenic epidermal growth factor receptor (EGFR) mutant resistant to the latest generation of clinically approved tyrosine kinase inhibitors (TKIs). We identified four mutant-specific compounds, including two that would not have been detected by conventional in vitro kinase assays. One of these targets mutant EGFR via a new mechanism of action, distinct from classical TKI inhibition. Our results demonstrate how MaMTH-DS is a powerful complement to traditional drug screening approaches.
BRAF and cMET exon 14 skipping are rare mutations of NSCLC. The treatment sequence in these cases for the first and second line is not clear. An international registry was created for patients with ...advanced NSCLC harboring BRAF or cMET exon 14 skipping mutations, diagnosed from January 2017 to June 2022. Clinicopathological and molecular data and treatment patterns were recorded. Data on 58 patients, from eight centers across five countries, were included in the final analysis. We found that 40 patients had the cMET exon 14 skipping mutation and 18 had the BRAF V600E mutation. In total, 53 and 28 patients received first- and second-line treatments, respectively, among which 52.8% received targeted therapy (TT) in the first line and 53.5% in the second line. The overall response rate (ORR) and disease control rate (DCR) for first-line treatment with TT vs. other treatment such as immune checkpoint inhibitors ± chemotherapy (IO ± CT) were 55.6% vs. 21.7% (p = 0.0084) and 66.7% vs. 39.1% (p = 0.04), respectively. The type of treatment in first-line TT vs. other affected time to treatment discontinuation (TTD) was 11.6 m vs. 4.6 m (p= 0.006). The overall survival for the whole group was 15.4 m and was not statistically affected by the type of treatment (19.2 m vs. 13.5 m; p = 0.83).
BackgroundThe most effective method and length of time for administering adjuvant immunotherapy after surgery for non-small cell lung cancer (NSCLC) are still unknown. Various clinical trials have ...utilized diverse strategies for adjuvant treatment. In this case, we explore the potential benefits of neoadjuvant immunotherapy combined with chemotherapy in managing locally advanced lung squamous carcinoma, which often poses challenges for treatment. This multimodal approach aims to downstage tumors and optimize surgical outcomes.Case DescriptionFollowing a diagnosis of stage IIIB lung cancer, the patient underwent three cycles of neoadjuvant therapy using sintilimab, Abraxane, and Lobaplatin, resulting in a significant 45% reduction in tumor size. Subsequently, a right lower lobe lobectomy and systematic lymphadenectomy were performed using a uniportal video-assisted thoracic surgery (VATS) approach. Postoperative analysis revealed negative lymph nodes, with only a 5-mm residual tumor in the tumor bed, downstaging the cancer to IA1. Remarkably, the patient experienced a smooth recovery without any postoperative complications. One cycle of adjuvant therapy was administered following the operation to further support the patient's recovery and minimize the risk of disease recurrence. This comprehensive treatment approach underscores the importance of neoadjuvant therapy in optimizing surgical outcomes and improving long-term prognosis for patients with locally advanced lung cancer.ConclusionsFor patients with stage III locally advanced lung squamous carcinoma, the combination of Sintilimab and Platinum-based drugs can be used as a neoadjuvant therapy which can reduce the difficulty of the operation.
Lung cancer is the leading cause of cancer-related deaths worldwide. Despite growing efforts for its early detection by screening populations at risk, the majority of lung cancer patients are still ...diagnosed in an advanced stage. The management of lung cancer has dramatically improved in the last decade and is no longer based on the “one-fits-all” paradigm or the general histological classification of non-small cell versus small cell lung cancer. Emerging options of targeted therapies and immunotherapies have shifted the management of lung cancer to a more personalized treatment approach, significantly influencing the clinical course and outcome of the disease. Molecular biomarkers have emerged as valuable tools in the prognosis and prediction of therapy response. In this review, we discuss the relevant biomarkers used in the clinical management of lung tumors, from diagnosis to prognosis. We also discuss promising new biomarkers, focusing on non-small cell lung cancer as the most abundant type of lung cancer.
Croatian National Cancer Patient Experience Survey Karabatić, Sandra; Šajnić, Andreja; Pleština, Sanja ...
International journal of environmental research and public health,
07/2022, Volume:
19, Issue:
14
Journal Article
Peer reviewed
Open access
Background: Cancer patients’ experiences of the healthcare system, care, and treatment are increasingly viewed as important in order to inform and improve quality of care, patient safety, and ...treatment efficacy. Understanding patient experience is a key step in moving toward patient-centred care. The aims of this study were to determine the experience of cancer patients in Central and Eastern European countries and to identify the needs and perspectives of oncological patients during the cancer treatment. In this paper, results from Croatia are presented. Methods: A sixty-nine item online survey was translated by native-language participating countries. Only registered members (subjects with confirmed cancer diagnosis) of the national patient oncology associations in each participating country were allowed to access and complete the online questionnaire (n = 16,458). Data were collected between October 2018 to February 2019. The Croatian Coalition of Health Associations enabled the authors of this paper to use the collected data from a sample of the Croatian participants (n = 2460) for the purposes of publication. Results: Two-thirds (67.3%) of the respondents reported satisfaction with the length of time needed for getting tests done. Bad news was delivered sensitively to 52.97% of the participants, and 52.76% received a cancer treatment plan. During the hospitalisation, 45.93% responded that they did not find someone from the hospital staff whom they could talk to about their worries and fears, and 57.48% were not given any contact information in case of concerns about their condition or treatment following the discharge. Regarding the patients’ preferences, needs, and values, 60.81% of the respondents felt that the greatest improvement would be to perform all services in one place, and 55.28% felt that improvement would be achieved through a multidisciplinary team coordinated by one person. Conclusions: The study reveals domains that need to be addressed in the overall Croatian healthcare system for oncology patients. Based on the obtained data, we can conclude that there is a large need for improvement in patient experience on the oncology pathway.
Chronic obstructive pulmonary disease (COPD) and lung cancer (LC) are closely related diseases associated with smoking history and dysregulated immune response. However, not all smokers develop the ...disease, indicating that genetic susceptibility could be important. Therefore, the aim of this study was to search for the potential overlapping genetic biomarkers, with a focus on single nucleotide polymorphisms (SNPs) located in the regulatory regions of immune-related genes. Additionally, the aim was to see if an identified SNP has potentially an effect on proinflamma-tory cytokine concentration in the serum of COPD patients. We extracted summary data of variants in 1511 immune-related genes from COPD and LC genome-wide association studies (GWAS) from the UK Biobank. The LC data had 203 cases, patients diagnosed with LC, and 360 938 controls, while COPD data had 1 897 cases and 359 297 controls. Assuming 1 association/gene, SNPs with a
-value < 3.3 × 10
were considered statistically significantly associated with the disease. We identified seven SNPs located in different genes (
) to be associated with the COPD risk and two with the LC risk (
), with statistical significance. We also identified two SNPs located in the
gene associated with LC (rs2386841;
= 1.86 × 10
) and COPD (rs11256442;
= 9.79 × 10
) but with lower significance. Functional studies conducted on COPD patients showed that RNA expression of IL2RA, IFNγ and related proinflammatory cytokines in blood serum did not correlate with a specific genotype. Although results presented in this study do not fully support our hypothesis, it is worth to mention that the identified genes/SNPs that were associated with either COPD or LC risk, all were involved in the activation of the NF-κB transcription factor which is closely related to the regulation of the inflammatory response, a condition associated with both pathologies.
EGFR exon 20 (EGFR Ex20) insertion mutations in non-small cell lung cancer (NSCLC) are insensitive to traditional EGFR tyrosine kinase inhibitors (TKIs). Mobocertinib is the only approved TKI ...specifically designed to target EGFR Ex20. We performed an international, real-world safety and efficacy analysis on patients with EGFR Ex20-positive NSCLC enrolled in a mobocertinib early access program. We explored the mechanisms of resistance by analyzing postprogression biopsies, as well as cross-resistance to amivantamab. Data from 86 patients with a median age of 67 years and a median of two prior lines of treatment were analyzed. Treatment-related adverse events (TRAEs) occurred in 95% of patients. Grade ≥3 TRAEs were reported in 38% of patients and included diarrhea (22%) and rash (8%). In 17% of patients, therapy was permanently discontinued, and two patients died due to TRAEs. Women were seven times more likely to discontinue treatment than men. In the overall cohort, the objective response rate to mobocertinib was 34% (95% CI, 24-45). The response rate in treatment-naïve patients was 27% (95% CI, 8-58). The median progression-free and overall survival was 5 months (95% CI, 3.5-6.5) and 12 months (95% CI, 6.8-17.2), respectively. The intracranial response rate was limited (13%), and one-third of disease progression cases involved the brain. Mobocertinib also showed antitumor activity following EGFR Ex20-specific therapy and vice versa. Potential mechanisms of resistance to mobocertinib included amplifications in MET, PIK3CA, and NRAS. Mobocertinib demonstrated meaningful efficacy in a real-world setting but was associated with considerable gastrointestinal and cutaneous toxicity.
Squamous cell lung carcinoma (SqCLC) is associated with high mortality and limited treatment options. Identification of therapeutic targets and prognostic biomarkers is still lacking. This research ...aims to analyze the transcriptomic profile of SqCLC samples and identify the key genes associated with tumorigenesis, overall survival (OS), and a profile of the tumor-infiltrating immune cells. Differential gene expression analysis, pathway enrichment analysis, and Gene Ontology analysis on RNA-seq data obtained from FFPE tumor samples (
= 23) and healthy tissues (
= 3) were performed (experimental cohort). Validation of the results was conducted on publicly available gene expression data using TCGA LUSC (
= 225) and GTEx healthy donors' cohorts (
= 288). We identified 1133 upregulated and 644 downregulated genes, common for both cohorts. The most prominent upregulated genes were involved in cell cycle and proliferation regulation pathways (MAGEA9B, MAGED4, KRT, MMT11/13), while downregulated genes predominately belonged to immune-related pathways (DEFA1B, DEFA1, DEFA3). Results of the survival analysis, conducted on the validation cohort and commonly deregulated genes, indicated that overexpression of HOXC4 (
< 0.001), LLGL1 (
= 0.0015), and SLC4A3 (
= 0.0034) is associated with worse OS in early-stage SqCLC patients. In contrast, overexpression of GSTZ1 (
= 0.0029) and LILRA5 (
= 0.0086) was protective, i.e., associated with better OS. By applying a single-sample gene-set enrichment analysis (ssGSEA), we identified four distinct immune subtypes. Immune cell distribution suggests that the memory T cells (central and effector) and follicular helper T cells could serve as important stratification parameters.
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