Browsing by Author "Ercegovac, Maja (24821301800)"

Background/Objectives: Non-small cell lung carcinoma (NSCLC) is characterized by its diverse molecular profiles and varying responses to treatment, highlighting the importance of precision medicine in optimizing therapeutic outcomes. A promising approach involves using patient-derived cellular models, which provide insights into the unique biology of individual tumors and their responsiveness to treatment. Methods: We established short-term primary cell cultures from thirteen patients with NSCLC of different subtypes and stages, including both cancer and stromal cells. To evaluate the ex vivo cytotoxicity and selectivity of eight chemotherapeutics and erlotinib, we employed an immunoassay, and the results were analyzed using an automated imaging system. Scoring of the obtained results was also performed. The ex vivo responses to cisplatin, etoposide, and paclitaxel were correlated with the patients’ responses to therapy. We used Kaplan–Meier analysis to assess progression-free survival (PFS) differences among patient groups. Results: NSCLC cells exhibited significant variability in their responses to drugs, with stromal cells demonstrating greater sensitivity. Tumors at stages I-III responded to multiple treatments, whereas stage IV cells showed considerable resistance. Erlotinib effectively reduced cancer cell growth at lower doses but plateaued at higher concentrations. The immunoassay indicated 67% sensitivity and 100% specificity in predicting patient responses to chemotherapy. Sensitivity to etoposide and paclitaxel correlated with progression-free survival (PFS). Conclusions: A personalized treatment strategy, such as our immunoassay based on the ex vivo responses of cancer patients’ cells, can guide treatment decisions and, in some cases, serve as surrogate biomarkers for tumor types that lack actionable biomarkers. © 2025 by the authors.

Background/Objectives: Non-small cell lung carcinoma (NSCLC) is characterized by its diverse molecular profiles and varying responses to treatment, highlighting the importance of precision medicine in optimizing therapeutic outcomes. A promising approach involves using patient-derived cellular models, which provide insights into the unique biology of individual tumors and their responsiveness to treatment. Methods: We established short-term primary cell cultures from thirteen patients with NSCLC of different subtypes and stages, including both cancer and stromal cells. To evaluate the ex vivo cytotoxicity and selectivity of eight chemotherapeutics and erlotinib, we employed an immunoassay, and the results were analyzed using an automated imaging system. Scoring of the obtained results was also performed. The ex vivo responses to cisplatin, etoposide, and paclitaxel were correlated with the patients’ responses to therapy. We used Kaplan–Meier analysis to assess progression-free survival (PFS) differences among patient groups. Results: NSCLC cells exhibited significant variability in their responses to drugs, with stromal cells demonstrating greater sensitivity. Tumors at stages I-III responded to multiple treatments, whereas stage IV cells showed considerable resistance. Erlotinib effectively reduced cancer cell growth at lower doses but plateaued at higher concentrations. The immunoassay indicated 67% sensitivity and 100% specificity in predicting patient responses to chemotherapy. Sensitivity to etoposide and paclitaxel correlated with progression-free survival (PFS). Conclusions: A personalized treatment strategy, such as our immunoassay based on the ex vivo responses of cancer patients’ cells, can guide treatment decisions and, in some cases, serve as surrogate biomarkers for tumor types that lack actionable biomarkers. © 2025 by the authors.

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

Background and Objectives: Lung cancer is the second most common form of cancer in the world for both men and women as well as the most common cause of cancer-related deaths worldwide. The aim of this study is to summarize the radiological characteristics between primary lung adenocarcinoma subtypes and to correlate them with FDG uptake on PET-CT. Materials and Methods: This retrospective study included 102 patients with pathohistologically confirmed lung adenocarcinoma. A PET-CT examination was performed on some of the patients and the values of SUVmax were also correlated with the histological and morphological characteristics of the masses in the lungs. Results: The results of this analysis showed that the mean size of AIS-MIA (adenocarcinoma in situ and minimally invasive adenocarcinoma) cancer was significantly lower than for all other cancer types, while the mean size of the acinar cancer was smaller than in the solid type of cancer. Metastases were significantly more frequent in solid adenocarcinoma than in acinar, lepidic, and AIS-MIA cancer subtypes. The maximum standardized FDG uptake was significantly lower in AIS-MIA than in all other cancer types and in the acinar predominant subtype compared to solid cancer. Papillary predominant adenocarcinoma had higher odds of developing contralateral lymph node involvement compared to other types. Solid adenocarcinoma was associated with higher odds of having metastases and with higher SUVmax. AIS-MIA was associated with lower odds of one unit increase in tumor size and ipsilateral lymph node involvement. Conclusions: The correlation between histopathological and radiological findings is crucial for accurate diagnosis and staging. By integrating both sets of data, clinicians can enhance diagnostic accuracy and determine the optimal treatment plan. © 2024 by the authors.

The impact of tyrosine kinase inhibitors (TKIs) on multidrug resistance (MDR) in non-small cell lung carcinoma (NSCLC) is a critical aspect of cancer therapy. While TKIs effectively target specific signaling pathways of cancer cells, they can also act as substrates for ABC transporters, potentially triggering MDR. The aim of our study was to evaluate the response of 17 patient-derived NSCLC cultures to 10 commonly prescribed TKIs and to correlate these responses with patient mutational profiles. Using an ex vivo immunofluorescence assay, we analyzed the expression of the MDR markers ABCB1, ABCC1, and ABCG2, and correlated these data with the genetic profiles of patients for a functional diagnostic approach. NSCLC cultures responded differently to TKIs, with erlotinib showing good efficacy regardless of mutation burden or EGFR status. However, the modulation of MDR mechanisms by erlotinib, such as increased ABCG2 expression, highlights the challenges associated with erlotinib treatment. Other TKIs showed limited efficacy, highlighting the variability of response in NSCLC. Genetic alterations in signaling pathways associated with drug resistance and sensitivity, including TP53 mutations, likely contributed to the variable responses to TKIs. The relationships between ABC transporter expression, gene alterations, and response to TKIs did not show consistent patterns. Our results suggest that in addition to mutational status, performing functional sensitivity screening is critical for identifying appropriate treatment strategies with TKIs. These results underscore the importance of considering drug sensitivity, off-target effects, MDR risks, and patient-specific genetic profiles when optimizing NSCLC treatment and highlight the potential for personalized approaches, especially in early stages. © 2024 by the authors.

The impact of tyrosine kinase inhibitors (TKIs) on multidrug resistance (MDR) in non-small cell lung carcinoma (NSCLC) is a critical aspect of cancer therapy. While TKIs effectively target specific signaling pathways of cancer cells, they can also act as substrates for ABC transporters, potentially triggering MDR. The aim of our study was to evaluate the response of 17 patient-derived NSCLC cultures to 10 commonly prescribed TKIs and to correlate these responses with patient mutational profiles. Using an ex vivo immunofluorescence assay, we analyzed the expression of the MDR markers ABCB1, ABCC1, and ABCG2, and correlated these data with the genetic profiles of patients for a functional diagnostic approach. NSCLC cultures responded differently to TKIs, with erlotinib showing good efficacy regardless of mutation burden or EGFR status. However, the modulation of MDR mechanisms by erlotinib, such as increased ABCG2 expression, highlights the challenges associated with erlotinib treatment. Other TKIs showed limited efficacy, highlighting the variability of response in NSCLC. Genetic alterations in signaling pathways associated with drug resistance and sensitivity, including TP53 mutations, likely contributed to the variable responses to TKIs. The relationships between ABC transporter expression, gene alterations, and response to TKIs did not show consistent patterns. Our results suggest that in addition to mutational status, performing functional sensitivity screening is critical for identifying appropriate treatment strategies with TKIs. These results underscore the importance of considering drug sensitivity, off-target effects, MDR risks, and patient-specific genetic profiles when optimizing NSCLC treatment and highlight the potential for personalized approaches, especially in early stages. © 2024 by the authors.

Aim. The aim of this study was to evaluate the role of thoracic sonography in treatment of pleural effusions and to identify sonographic indicators for surgical intervention. Materials and Methods. This study included 378 patients with pleural effusions. US characteristics of effusions as the echo structure and pleural thickening were analyzed. Regarding the US finding, the diagnostic or therapeutic procedure was performed. Results. The study included 267 male and 111 female patients, an average of 56.7 years. Infection was the most frequent cause of effusion. Two hundred sixty-nine patients had loculated and 109 free pleural effusion. Most frequent echo structure of loculated effusion was complex septate, whereas free effusion was mostly anechoic. Successful obtaining of the pleural fluid without real-time guidance was in 88% and under real-time guidance in 99% patients (p < 0.012). There was no significant difference in success rate between free and loculated effusion and regarding the echo structure (p = 0.710 and 0.126, respectively). Complete fluid removal after serial thoracentesis or drainage was achieved in 86% patients. Forty-five patients with significantly thicker pleural peel and impairment of the diaphragmatic function than remaining of the group (p < 0.001) underwent surgery. Open thoracotomy and decortication was more frequently performed in patients with completely fixed diaphragm and complex, dominantly septated effusions. There is no significant difference in US parameters comparing to patients underwent VATS, but the number of VATS is too small for valid conclusion. Conclusion. Thoracic sonography is a very useful tool in the evaluation of clinical course and treatment options in patients with pleural effusions of a different origin. Copyright © 2018 Ruza Stevic et al.

Background: The prediction of postoperative respiratory function is necessary in identifying patients that are at greater risk of complications. There are not enough studies on the effect of the diaphragm on postoperative respiratory function prediction in lung cancer surgical patients. The objective of this study is to estimate the precision of machine learning methods in the prediction of respiratory function in the immediate postoperative period and how diaphragm function contributes to that prediction. Materials and methods: Our prospective study included 79 patients who underwent lung cancer surgery. Diaphragm function was estimated by its mobility measured both ultrasonographically and radiographically and by noninvasive muscle strength tests. We present a new machine learning multilayer regression metamodel, which predicts FEV1 for each patient based on preoperative measurements. Results: The proposed regression models are specifically trained to predict FEV1 in the immediate postoperative period and were proved to be highly accurate (mean absolute error in the range from 8 to 11%). Predictive models based on resected segments give two to three times less precise results. Measured FEV1 was 44.68% ± 14.07%, 50.95% ± 15.80%, and 58.0%1 ± 14.78%, and predicted postoperative (ppo) FEV1 was 43.85% ± 8.80%, 50.62% ± 9.28%, and 57.85% ± 10.58% on the first, fourth, and seventh day, respectively. By interpreting the obtained model, the diaphragm contributes to ppoFEV1 13.62% on the first day, 10.52% on the fourth, and 9.06% on the seventh day. Conclusion: The machine learning metamodel gives more accurate predictions of postoperative lung function than traditional calculations. The diaphragm plays a notable role in the postoperative FEV1 prediction. © 2023, The Author(s).