Browsing by Author "Babovic, Nada (6602584307)"

Aims: As numerous signalling molecules regulate effector functions of peripheral blood lymphocytes (PBLs) that have an important anti-tumour activity, the aim of this study was to analyse their level in patients with metastatic melanoma (MM) compared with healthy controls (HCs). Methods: Peripheral blood mononuclear cells (PBMCs) of 36 MMs and 28 HCs were analysed for the level of perforin, interferon-regulating transcription factor-1 (IRF-1), DAP10 and Src homology 2 domain-containing tyrosine phosphatase-1 by reverse transcriptase PCR, level of phosphorylated signal transducers and activators of transcription (pSTAT)-1, pSTAT-4, pSTAT-5 by western blot and interferon (IFN)-γ production by ELISA. The expression of activating NKG2D and inhibitory killer immunoglobulin-like receptors (KIR), CD158a and CD158b, on PBL, CD3-CD56+ natural killer (NK) cells and CD3+CD8+ cytotoxic T lymphocytes (CTLs), as well as the percentage of CD14+HLA-DR-cells in PBMC were estimated by flow cytometry. Results: Patients with MM, compared with HCs, had significantly lower level of cytotoxic molecule perforin and decreased IFN-γ production, as well as lower level of pSTAT-1, pSTAT-4, pSTAT-5 and IRF-1 signalling molecules in PBMC. Furthermore, MM had decreased expression of activating NKG2D receptor on PBL and NK cells and low level of its DAP10 signalling molecule contrary to no changes in KIR expression on all investigated cells. These results could be associated with increased percentage of immunosuppressive CD14+HLA-DR-myeloid-derived suppressor cells detected in patients with MM. Conclusions: The altered signalling molecules of PBL could represent biomarkers of impaired cytotoxic and immunoregulatory function of these cells, indicating melanoma-associated immunosuppression that facilitates tumour progression.

Background: The emerging new standard of care for metastatic clear cell renal carcinoma (mRCC) becomes a challenge when access to new drugs is limited. In Serbia, sunitinib and pazopanib are the only available first-line therapies. The second-line treatment for mRCC has never been and is still not available. We aimed to assess overall survival (OS) in patients with mRCC who received first-line sunitinib or pazopanib when access to second-line treatment was not available. Methods: This retrospective observational study analyzed data from a nationally representative cohort of 759 patients who started on first-line sunitinib or pazopanib between 1 January 2012 and 30 June 2019, in 4 centers in Serbia. The data cut-off date was 31 December 2019. Key eligibility criteria were clear cell RCC histology, measurable metastatic disease, performance status 0 or 1, and the Memorial Sloan Kettering Cancer Center favorable or intermediate prognosis. The primary outcome was OS from the start of first-line treatment to death or data cut-off date. Results: The study population included 759 patients with mRCC who started with first-line sunitinib (n = 673; [88.7%]) or pazopanib (n = 86; [11.3%]). Overall, the mean age was 61.0 ± 9.7 years at treatment baseline, and 547 (72%) were men. mRCC was primarily diagnosed in 230 (30%) patients, and most of them underwent cytoreductive nephrectomy prior to systemic therapy (n = 181 [79%]). Additional treatment of metastases prior to and/or during treatment was used in 169 patients (22.3%). Grade 3 and 4 adverse events occurred in 168 (22.1%) and 47 patients (6.2%), respectively, and treatment was permanently stopped because of toxicity in 41 (6.9%). The OS was calculated from the start of first-line treatment, and the median follow-up was 14 months (range, 0–97). The median OS in the entire cohort was 17 months (95% CI, 14.6–19.4). Conclusions: With only available sunitinib and pazopanib in first-line treatment, modest improvements are seen in the overall survival of patients with mRCC in real world clinical practice. In circumstances of limited availability of cancer medicines, our results can contribute to accelerating patient access to novel cancer therapies that have been shown to prolong survival in mRCC. Copyright © 2022 Nikic, Babovic, Dzamic, Salma, Stojanovic, Matkovic, Pejcic, Juskic and Soldatovic.

Background: The emerging new standard of care for metastatic clear cell renal carcinoma (mRCC) becomes a challenge when access to new drugs is limited. In Serbia, sunitinib and pazopanib are the only available first-line therapies. The second-line treatment for mRCC has never been and is still not available. We aimed to assess overall survival (OS) in patients with mRCC who received first-line sunitinib or pazopanib when access to second-line treatment was not available. Methods: This retrospective observational study analyzed data from a nationally representative cohort of 759 patients who started on first-line sunitinib or pazopanib between 1 January 2012 and 30 June 2019, in 4 centers in Serbia. The data cut-off date was 31 December 2019. Key eligibility criteria were clear cell RCC histology, measurable metastatic disease, performance status 0 or 1, and the Memorial Sloan Kettering Cancer Center favorable or intermediate prognosis. The primary outcome was OS from the start of first-line treatment to death or data cut-off date. Results: The study population included 759 patients with mRCC who started with first-line sunitinib (n = 673; [88.7%]) or pazopanib (n = 86; [11.3%]). Overall, the mean age was 61.0 ± 9.7 years at treatment baseline, and 547 (72%) were men. mRCC was primarily diagnosed in 230 (30%) patients, and most of them underwent cytoreductive nephrectomy prior to systemic therapy (n = 181 [79%]). Additional treatment of metastases prior to and/or during treatment was used in 169 patients (22.3%). Grade 3 and 4 adverse events occurred in 168 (22.1%) and 47 patients (6.2%), respectively, and treatment was permanently stopped because of toxicity in 41 (6.9%). The OS was calculated from the start of first-line treatment, and the median follow-up was 14 months (range, 0–97). The median OS in the entire cohort was 17 months (95% CI, 14.6–19.4). Conclusions: With only available sunitinib and pazopanib in first-line treatment, modest improvements are seen in the overall survival of patients with mRCC in real world clinical practice. In circumstances of limited availability of cancer medicines, our results can contribute to accelerating patient access to novel cancer therapies that have been shown to prolong survival in mRCC. Copyright © 2022 Nikic, Babovic, Dzamic, Salma, Stojanovic, Matkovic, Pejcic, Juskic and Soldatovic.