Browsing by Author "Jovanovic, Dragana (58721901700)"

[No abstract available]

Objective: Under conditions in which palliative care has not yet become part of clinical practice, the differences in palliative care needs between patients with cancer and other life-limiting diseases can yield knowledge that will be very valuable for future planning. The aim of our investigation was to compare health-related quality of life (HRQoL) for patients with end-stage chronic obstructive pulmonary disease (COPD) and those with non-small-cell lung cancer (NSCLC) in Belgrade, Serbia. We also evaluated the influence of demographic, socioeconomic, and clinical factors on HRQoL for both patient groups. Method: This cross-sectional study included 100 NSCLC patients (stages IIIb and IV) and 100 patients with stage IV COPD. Measures included the SF-36 questionnaire, the EORTC QLQ-C30, the St. George's Respiratory Questionnaire, and the Beck Depression Inventory (BDI). Associations of demographic, socioeconomic, and clinical factors with QoL were examined using linear regression analyses. Results: The COPD group scored significantly lower compared to NSCLC patients in all SF-36 domains except for bodily pain. Additionally, a significantly higher level of depressive symptoms was observed in COPD patients. A worse physical QoL for COPD patients was independently associated with a longer duration of unemployment, a lack of wage earning, lower Karnofsky Performance Status (KPS) scores, and higher levels of depression. A worse mental QoL for COPD patients was related to a longer duration of disease, poorer KPS scores, and higher BDI scores. The independent variables significantly associated with worse physical and mental QoL of NSCLC patients were lower KPS and higher BDI scores. Significance of Results: A worse QoL, a significantly higher level of depressive symptoms, and adverse socioeconomic status in the COPD group imposes the need for development of more intensive psychosocial and community support for COPD patients during implementation of palliative care. Copyright © Cambridge University Press 2015.

Objective: Under conditions in which palliative care has not yet become part of clinical practice, the differences in palliative care needs between patients with cancer and other life-limiting diseases can yield knowledge that will be very valuable for future planning. The aim of our investigation was to compare health-related quality of life (HRQoL) for patients with end-stage chronic obstructive pulmonary disease (COPD) and those with non-small-cell lung cancer (NSCLC) in Belgrade, Serbia. We also evaluated the influence of demographic, socioeconomic, and clinical factors on HRQoL for both patient groups. Method: This cross-sectional study included 100 NSCLC patients (stages IIIb and IV) and 100 patients with stage IV COPD. Measures included the SF-36 questionnaire, the EORTC QLQ-C30, the St. George's Respiratory Questionnaire, and the Beck Depression Inventory (BDI). Associations of demographic, socioeconomic, and clinical factors with QoL were examined using linear regression analyses. Results: The COPD group scored significantly lower compared to NSCLC patients in all SF-36 domains except for bodily pain. Additionally, a significantly higher level of depressive symptoms was observed in COPD patients. A worse physical QoL for COPD patients was independently associated with a longer duration of unemployment, a lack of wage earning, lower Karnofsky Performance Status (KPS) scores, and higher levels of depression. A worse mental QoL for COPD patients was related to a longer duration of disease, poorer KPS scores, and higher BDI scores. The independent variables significantly associated with worse physical and mental QoL of NSCLC patients were lower KPS and higher BDI scores. Significance of Results: A worse QoL, a significantly higher level of depressive symptoms, and adverse socioeconomic status in the COPD group imposes the need for development of more intensive psychosocial and community support for COPD patients during implementation of palliative care. Copyright © Cambridge University Press 2015.

[No abstract available]

Background: In spite of the progress made in neoadjuvant therapy for operable non small-cell lung cancer (NSCLC), many issues remain unsolved, especially in locally advanced stage IIIA. Methods: Retrospective data of 163 patients diagnosed with stage IIIA NSCLC after surgery was analyzed. The patients were divided into two groups: a preoperative chemotherapy group including 59 patients who received platinum-etoposide doublet treatment before surgery, and an upfront surgery group including 104 patients for whom surgical resection was the first treatment step. Adjuvant chemotherapy or/and radiotherapy was administered to 139 patients (85.3%), while 24 patients (14.7%) were followed-up only. Results: The rate of N2 disease was significantly higher in the upfront surgery group (P < 0.001). The one-year relapse rate was 49.5% in the preoperative chemotherapy group compared to 65.4% in the upfront surgery group. There was a significant difference in relapse rate in relation to adjuvant chemotheraphy treatment (P = 0.007). The probability of relapse was equal whether radiotherapy was applied or not (P = 0.142). There was no statistically significant difference in two-year mortality (P = 0.577). The median survival duration after two years of follow-up was 19.6 months in the preoperative chemotherapy group versus 18.8 months in the upfront surgery group (P = 0.608 > 0.05). Conclusion: There was significant difference in preoperative chemotherapy group regarding relapse rate and treatment outcomes related to the lymph node status comparing to the upfront surgery group. Neoadjuvant/adjuvant chemo-therapy is a part of treatment for patients with stage IIIA NSCLC, but further investigation is required to determine optimal treatment. © 2017 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd

Thymic epithelial tumors (TETs) include several anterior mediastinal malignant tumours: thymomas, thymic carcinomas and thymic neuroendocrine cancers. There is significant variety in the biologic features and clinical course of TETs and many attempts have been made to identify target genes for successful therapy of TETs. Next generation sequencing (NGS) represents a huge advancement in diagnostics and these new molecular technologies revealed that thymic neoplasms have the lowest tumor mutation burden among all adult malignant tumours with a different pattern of molecular aberrations in thymomas and thymic carcinomas. As for the PD-L1 expression in tumor cells in thymoma and thymic carcinoma, it varies a lot in published studies, with findings of PD-L1 expression from 23% to 92% in thymoma and 36% to 100% in thymic carcinoma. When correlated PD-L1 expression with disease stage some controversial results were obtained, with no association with tumor stage in most studies. This is, at least in part, explained by the fact that several diverse PD-L1 immunohistochemical tests were used in each trial, with four different antibodies (SP142, SP263, 22C3, and 28-8), different definition of PD-L1 positivity and cutoff values throughout the studies as well. There is a huge interest in using genomic features to produce predictive genomic-based immunotherapy biomarkers, particularly since recent data suggest that certain tumor-specific genomic alterations, either individually or in combination, appear to influence immune checkpoint activity and better responses as the outcome, so as such in some cancer types they may complement existing biomarkers to improve the selection criteria for immunotherapy. © Journal of Thoracic Disease. All rights reserved.

This paper presents a rare case of an elderly patient treated with erlotinib for disseminated lung adenocarcinoma with poor performance status (Eastern Cooperative Oncology Group performance status [PS]3). This treatment led to a long duration of complete remission according to Response Evaluation Criteria in Solid Tumors 1.1 – almost 7 years (81 months) of progression-free survival (PFS) and overall survival (OS) of 10 years by March 2017. The treatment with erlotinib started in September 2008 and it was well tolerated with no adverse effects. Mutation analyses (real-time polymerase chain reaction method) revealed deletion of EGFR (epidermal growth factor receptor) gene and wild-type Kirsten-ras protein gene in exon 19. In May 2015, the patient relapsed with jaundice and enlarged lymph nodes of the liver hilum, with no other metastasis, PS 2. Biopsy confirmed metastasis of lung adenocarcinoma. EGFR molecular testing did not reveal T790M mutation. Treatment was continued with gemcitabine–cisplatin chemotherapy. A total of six cycles were administered with nearly complete response and Eastern Cooperative Oncology Group performance status 0. Further on, gemcitabine monotherapy has been administered with nearly complete response maintained and OS of 10 years by March 2017. This report describes an extremely rare case of a poor performance patient with advanced metastatic adenocarcinoma harboring EGFR mutation – deletion in exon 19 – who was receiving salvage erlotinib and had a complete response with 81 months of PFS followed by a relapse and subsequent chemotherapy which led to nearly complete response, with an OS of 10 years by March 2017. Such a complete response to tyrosine kinase inhibitor therapy in a poor PS patient, with long PFS and OS achieved, justifies tyrosine kinase inhibitor treatment approach in poor PS patients with EGFR-sensitizing tumors, and furthermore points to the feasibility of administering chemotherapy at the time of relapse. © 2017 Jovanovic et al.

Introduction: Thymomas and thymic carcinoma (TC) are the most common neoplasms localised in the thymus. These diseases are poorly understood, but progress made in next-generation sequencing (NGS) technology has provided novel data on their molecular pathology. Material and methods: Genomic DNA was isolated from formalin-fixed paraffin-embedded tumour tissue. We investigated somatic variants in 35 thymoma patients using amplicon-based TruSeq Amplicon Cancer Panel (TSACP) that covers 48 cancer related genes. We also analysed three samples from healthy individuals by TSACP platform and 32 healthy controls using exome sequencing. Results: The total number of detected variants was 4447, out of which 2906 were in the coding region (median per patient 83, range: 2–300) and 1541 were in the non-coding area (median per patient 44, range: 0–172). We identified four genes, APC, ATM, ERBB4, and SMAD4, having more than 100 protein-changing variants. Additionally, more than 70% of the analysed cases harboured protein-changing variants in SMAD4, APC, ATM, PTEN, KDR, and TP53. Moreover, this study revealed 168 recurrent variants, out of which 15 were shown to be pathogenic. Comparison to controls revealed that the variants we reported in this study were somatic thymoma-specific variants. Additionally, we found that the presence of variants in SMAD4 gene predicted shorter overall survival in thymoma patients. Conclusions: The most frequently mutated genes in thymoma samples analysed in this study belong to the EGFR, ATM, and TP53 signalling pathways, regulating cell cycle check points, gene expression, and apoptosis. The results of our study complement the knowledge of thymoma molecular pathogenesis. © 2020 Termedia & Banach.

Background: Idiopathic Pulmonary Fibrosis (IPF) is a lethal lung disease of unknown etiology. A major limitation in transcriptomic profiling of lung tissue in IPF has been a dependence on snap-frozen fresh tissues (FF). In this project we sought to determine whether genome scale transcript profiling using RNA Sequencing (RNA-Seq) could be applied to archived Formalin-Fixed Paraffin-Embedded (FFPE) IPF tissues. Results: We isolated total RNA from 7 IPF and 5 control FFPE lung tissues and performed 50 base pair paired-end sequencing on Illumina 2000 HiSeq. TopHat2 was used to map sequencing reads to the human genome. On average ~62 million reads (53.4% of ~116 million reads) were mapped per sample. 4,131 genes were differentially expressed between IPF and controls (1,920 increased and 2,211 decreased (FDR < 0.05). We compared our results to differentially expressed genes calculated from a previously published dataset generated from FF tissues analyzed on Agilent microarrays (GSE47460). The overlap of differentially expressed genes was very high (760 increased and 1,413 decreased, FDR < 0.05). Only 92 differentially expressed genes changed in opposite directions. Pathway enrichment analysis performed using MetaCore confirmed numerous IPF relevant genes and pathways including extracellular remodeling, TGF-beta, and WNT. Gene network analysis of MMP7, a highly differentially expressed gene in both datasets, revealed the same canonical pathways and gene network candidates in RNA-Seq and microarray data. For validation by NanoString nCounter® we selected 35 genes that had a fold change of 2 in at least one dataset (10 discordant, 10 significantly differentially expressed in one dataset only and 15 concordant genes). High concordance of fold change and FDR was observed for each type of the samples (FF vs FFPE) with both microarrays (r = 0.92) and RNA-Seq (r = 0.90) and the number of discordant genes was reduced to four. Conclusions: Our results demonstrate that RNA sequencing of RNA obtained from archived FFPE lung tissues is feasible. The results obtained from FFPE tissue are highly comparable to FF tissues. The ability to perform RNA-Seq on archived FFPE IPF tissues should greatly enhance the availability of tissue biopsies for research in IPF. © 2017 The Author(s).

Background: Promoter hypermethylation of tumor suppressor genes presents promising markers for lung cancer diagnosis and prognosis. The purpose of this study was to determine the association between the promoter hypermethylation of multiple genes and 5‑year survival rate in patients with Non‑small cell lung cancer (NSCLC). Materials and Methods: Primary tumor samples (n = 65), corresponding nonmalignant lung tissues (n = 65), and circulating blood were obtained from NSCLC patients who underwent curative surgery. Promoter methylation status in seven genes (RASSF1A, CDH13, MGMT, ESR1, DAPK, SOX1, and HOXA9) was quantified by using bisulfite pyrosequencing. Five‑year survival data were obtained by a clinician. Cox proportional hazards models were used to analyze the associations between gene methylation status and overall patient survival. Results: The 5‑year survival of the patients with SOX1 aberrant tumor methylation was found to be statistically significantly shorter than for those patients without aberrant tumor methylation (P = 0.01). This effect was independent of TNM stage. No significant survival differences were associated with aberrant methylation in other genes tested in either of the two tissue types. Conclusion: Our study shows that SOX1 promoter hypermethylation in NSCLC tumors is significantly associated with inferior survival, showing promise as a useful prognostic biomarker in patients with NSCLC. © 2021 Journal of Cancer Research and Therapeutics.

Background: Idiopathic pulmonary fibrosis (IPF) has common risk factors with cancer and significant similarities in the pathobiology process, both diseases having poor outcomes. Immune checkpoint PD-L1 has become the target of checkpoint inhibitory therapy that unleashes antitumor T cells and has revolutionized cancer treatment. This is a pilot study exploring membrane immune checkpoint PD-L1 expression in human IPF lung tissue samples and its soluble form, soluble PD-L1 (sPD-L1) plasma concentrations in IPF patients, in order to investigate potential role of PD-L1 as an IPF biomarker. © Journal of Thoracic Disease. All rights reserved.

Background: Thymomas belong to rare tumors giving rise to thymic epithelial tissue. There is a classification of several forms of thymoma: A, AB, B1, B2, B3, thymic carcinoma (TC) and thymic neuroendocrine thymoma. In this meta-analysis study, we have focused on thymoma using articles based on the disease's next-generation sequencing (NGS) genomic profiling. Materials and methods: We conducted a systematic review and meta-analysis of the prevalence of studies that discovered the genes and variants occurring in the less aggressive forms of the thymic epithelial tumors. Studies published before 12th December 2022 were identified through PubMed, Web of Science (WoS), and SCOPUS databases. Two reviewers have searched for the bases and selected the articles for the final analysis, based on well-defined exclusion and inclusion criteria. Results: Finally, 12 publications were included in the qualitative as well as quantitative analysis. The three genes, GTF2I, TP53, and HRAS, emerged as disease-significant in the observed studies. The Odds Ratio for all three extracted genes GTF2I (OR = 1.58, CI [1.51, 1.66] p < 0.00001), TP53 (OR = 1.36, CI [1.12, 1.65], p < 0.002), and HRAS (OR = 1.02, CI [1.00, 1.04], p < 0.001). Conclusions: According to obtained data, we noticed that the GTF2I gene exhibits a significant prevalence in the cohort of observed thymoma patients. Moreover, analyzing published articles NGS has suggested GTF2I, TP53, and HRAS genes as the most frequently mutated genes in thymoma that have pathogenic single nucleotide variants (SNV) and Insertion/Deletion (InDel), which contribute to disease development and progression. These variants could be valuable biomarkers and target points specific to thymoma. © 2023 Jelena Kostic Peric, Andja Cirkovic, Sanja Srzentic Drazilov, Natalija Samardzic, Vesna Skodric Trifunovic, Dragana Jovanovic, Sonja Pavlovic, published by Sciendo.

Sarcoidosis is an inflammatory granulomatous disease that is characterized by diverse organ system manifestations, a variable clinical course, and a predilection for affecting relatively young adults worldwide. Abnormalities on chest radiographs are detected in 85% to 95% of patients who have sarcoidosis. Approximately 20% to 50% of patients who have sarcoidosis present with respiratory symptoms, including dyspnea, cough, chest pain, and tightness of the chest. The clinical course and manifestations of pulmonary sarcoidosis are protean: spontaneous remission occurs in approximately two thirds of patients; up to 30% of patients have chronic course of the lung disease, resulting in progressive, (sometimes life-threatening) loss of lung function. Morbidity that correlates to sarcoidosis occurs in 1% to 4% of patients. © 2008 Elsevier Inc. All rights reserved.

Background: Cisplatin-induced peripheral neuropathy is a common complication of cisplatin therapy, which develops in most patients with lung cancer. There are no effective preventive measures and once it occurs there is no effective therapy, except symptomatic. In this study, we aimed to assess the effect of transcutaneous electrical nerve stimulation (TENS) therapy on the pain intensity and the quality of life of patients with cisplatin-induced neuropathy. Material and Methods: A prospective cohort study was performed from 2013 to 2018, at the Clinical Center of Serbia. After the initial evaluation of 106 newly diagnosed patients with lung cancer, 68 patients did not have peripheral neuropathy. These 68 patients continued in the study and started the cisplatin chemotherapy. Forty of these patients developed cisplatin-induced neuropathy, which was manifested by neuropathic symptoms and proven by ENG examination. All patients with cisplatin-induced neuropathy were treated with TENS therapy. Their neuropathic pain and quality of life were evaluated using the following questionnaires at diagnosis, after cisplatin therapy and after four weeks of TENS use: DN4, VAS scale, EORTC QLQ-C30 and FACT-L. Results: Two thirds (68%) of the patients with cisplatin-induced neuropathy were male and the majority were smokers (70%). Adenocarcinoma was the most common (38%), followed by squamous (33%) and small-cell carcinoma (28%). The application of TENS therapy had a positive effect on reducing the neuropathic pain and increasing the quality of life for patients with painful cisplatin-induced neuropathy. The VAS and DN4 scores significantly decreased after TENS therapy, in comparison to its values after cisplatin therapy (p < 0.001). After TENS therapy, patients had significantly higher values in most of the domains of EORTC QLQ-C30 and FACT- L, in comparison with the values after cisplatin therapy (p < 0.001). Conclusion: The application of TENS therapy has a positive effect on reducing neuropathic pain and increasing the quality of life for patients with lung cancer and cisplatin-induced neuropathy. © 2022 by the authors.

Introduction: Between February and November 2016, 17 tuberculosis (TB) cases were identified among high school students in Novi Pazar, Serbia. The objectives of our study were to describe the outbreak, to identify potential risk factors and to evaluate the applied control measures. Methodology: The outbreak was described by time, person and place. A retrospective cohort study was conducted. Attack rates, unadjusted relative risks (RR) and 95% confidence intervals (CI) were calculated. Multiple log-binomial regression analysis was performed to calculate adjusted RR. Results: Sixteen of the total 17 cases occurred among grade 3 students, AR 5.5%. Previous TB family history, (RR = 5.29; 95% CI = 1.63-17.12), spending time with a known TB case at school (RR = 5.38; 95% CI = 1.48-19.55) and exposure to secondhand smoke (RR = 3.37; 95% CI = 1.11-10.29) were all significantly and independently associated with the occurrence of TB. Conclusions: Delayed diagnosis and reporting resulted in delayed initiation of the contact investigation and non-identification of latent TB cases probably favored the occurrence of this outbreak in a low incidence country. Public health authorities should consider revising the existing guidelines, promoting inter-sectorial collaboration and increasing awareness of public health professionals. © 2019 Stosic et al.

Introduction: Between February and November 2016, 17 tuberculosis (TB) cases were identified among high school students in Novi Pazar, Serbia. The objectives of our study were to describe the outbreak, to identify potential risk factors and to evaluate the applied control measures. Methodology: The outbreak was described by time, person and place. A retrospective cohort study was conducted. Attack rates, unadjusted relative risks (RR) and 95% confidence intervals (CI) were calculated. Multiple log-binomial regression analysis was performed to calculate adjusted RR. Results: Sixteen of the total 17 cases occurred among grade 3 students, AR 5.5%. Previous TB family history, (RR = 5.29; 95% CI = 1.63-17.12), spending time with a known TB case at school (RR = 5.38; 95% CI = 1.48-19.55) and exposure to secondhand smoke (RR = 3.37; 95% CI = 1.11-10.29) were all significantly and independently associated with the occurrence of TB. Conclusions: Delayed diagnosis and reporting resulted in delayed initiation of the contact investigation and non-identification of latent TB cases probably favored the occurrence of this outbreak in a low incidence country. Public health authorities should consider revising the existing guidelines, promoting inter-sectorial collaboration and increasing awareness of public health professionals. © 2019 Stosic et al.