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Browsing by Author "Stojanovic-Rundic, Suzana (23037160700)"

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    Analyzing the post-contrast attenuation of the esophageal wall on routine contrast-enhanced MDCT examination can improve the diagnostic accuracy in response evaluation of the squamous cell esophageal carcinoma to neoadjuvant chemoradiotherapy in comparison with the esophageal wall thickness
    (2019)
    Djuric-Stefanovic, Aleksandra (16021199600)
    ;
    Jankovic, Aleksandra (57205752179)
    ;
    Saponjski, Dusan (57193090494)
    ;
    Micev, Marjan (7003864533)
    ;
    Stojanovic-Rundic, Suzana (23037160700)
    ;
    Cosic-Micev, Milena (6506607823)
    ;
    Pesko, Predrag (7004246956)
    Purpose: To evaluate the accuracy of the multidetector computed tomography (MDCT) in the response evaluation of the esophageal squamous cell carcinoma (ESCC) to neoadjuvant chemoradiotherapy (nCRT) by analyzing the thickness and post-contrast attenuation of the esophageal wall after the nCRT. Methods: Contrast-enhanced (CE)-MDCT examinations in portal venous phase of one hundred patients with locally advanced ESCC who received nCRT and underwent esophageal resection and histopathology assessment of tumor regression grade (TRG) were retrospectively analyzed by measuring the maximal thickness and mean density of the esophageal wall in the segment involved by tumor and visually searching for hyperdense foci within it. Diagnostic performance was evaluated using the ROC analysis. Results: Average attenuation of the esophageal wall had stronger diagnostic performance for predicting pathologic complete regression (pCR) (AUC = 0.994; p < 0.001) in relation to maximal esophageal wall thickness (AUC = 0.731; p < 0.001). Maximal esophageal wall thickness ≤ 9 mm and average attenuation of the esophageal wall ≤ 64 HU predicted pCR with the sensitivity, specificity, and overall accuracy of 62.5%, 77.9%, and 73%, and 96.9%, 98.5%, and 98%, respectively. Combination of both cutoff values enabled correct assessment of pCR with the 100% accuracy. Visual detection of the hyperdense focus within the esophageal wall predicted pCR with the sensitivity, specificity, and overall accuracy values of 100%, 94.1%, and 96%, respectively. Conclusion: Visual analysis and measurement of post-contrast attenuation of the esophageal wall after the nCRT can improve diagnostic accuracy of MDCT in the response evaluation of the ESCC to nCRT in comparison with measuring the esophageal wall thickness. © 2019, Springer Science+Business Media, LLC, part of Springer Nature.
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    Analyzing the post-contrast attenuation of the esophageal wall on routine contrast-enhanced MDCT examination can improve the diagnostic accuracy in response evaluation of the squamous cell esophageal carcinoma to neoadjuvant chemoradiotherapy in comparison with the esophageal wall thickness
    (2019)
    Djuric-Stefanovic, Aleksandra (16021199600)
    ;
    Jankovic, Aleksandra (57205752179)
    ;
    Saponjski, Dusan (57193090494)
    ;
    Micev, Marjan (7003864533)
    ;
    Stojanovic-Rundic, Suzana (23037160700)
    ;
    Cosic-Micev, Milena (6506607823)
    ;
    Pesko, Predrag (7004246956)
    Purpose: To evaluate the accuracy of the multidetector computed tomography (MDCT) in the response evaluation of the esophageal squamous cell carcinoma (ESCC) to neoadjuvant chemoradiotherapy (nCRT) by analyzing the thickness and post-contrast attenuation of the esophageal wall after the nCRT. Methods: Contrast-enhanced (CE)-MDCT examinations in portal venous phase of one hundred patients with locally advanced ESCC who received nCRT and underwent esophageal resection and histopathology assessment of tumor regression grade (TRG) were retrospectively analyzed by measuring the maximal thickness and mean density of the esophageal wall in the segment involved by tumor and visually searching for hyperdense foci within it. Diagnostic performance was evaluated using the ROC analysis. Results: Average attenuation of the esophageal wall had stronger diagnostic performance for predicting pathologic complete regression (pCR) (AUC = 0.994; p < 0.001) in relation to maximal esophageal wall thickness (AUC = 0.731; p < 0.001). Maximal esophageal wall thickness ≤ 9 mm and average attenuation of the esophageal wall ≤ 64 HU predicted pCR with the sensitivity, specificity, and overall accuracy of 62.5%, 77.9%, and 73%, and 96.9%, 98.5%, and 98%, respectively. Combination of both cutoff values enabled correct assessment of pCR with the 100% accuracy. Visual detection of the hyperdense focus within the esophageal wall predicted pCR with the sensitivity, specificity, and overall accuracy values of 100%, 94.1%, and 96%, respectively. Conclusion: Visual analysis and measurement of post-contrast attenuation of the esophageal wall after the nCRT can improve diagnostic accuracy of MDCT in the response evaluation of the ESCC to nCRT in comparison with measuring the esophageal wall thickness. © 2019, Springer Science+Business Media, LLC, part of Springer Nature.
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    Curative intent for unresectable advanced squamous cell esophageal cancer: Overall survival after chemoradiation
    (2017)
    Arsenijevic, Tatjana (6508074168)
    ;
    Nikitovic, Marina (6602665617)
    ;
    Plesinac-Karapandzic, Vesna (23474669800)
    ;
    Stojanovic-Rundic, Suzana (23037160700)
    ;
    Gavrilovic, Dusica (8849698200)
    ;
    Micev, Marjan (7003864533)
    ;
    Pesko, Predrag (7004246956)
    Purpose: To analyse the overall survival (OS) of patients with locally advanced, unresectable esophageal cancer treated with chemoradiation (CRT) with or without surgery. Methods: CRT was administered to 63 patients with locally advanced (T3-4, N0-1), initially unresectable squamous cell esophageal cancer. After the assessment of tumor response to treatment, medically fit patients converted to operable stage were subjected to surgery. Regular follow-up was performed every 3 months during first 2 years, and then every 6 months. Results: All 63 patients completed the whole radiotherapy course. Forty patients (63%) received complete 4 cycles of chemotherapy. In the remaining 23 patients (37%) chemotherapy was interrupted due to toxicity. Clinical response to CRT was: complete response (CR) in 4 patients (6%), partial response (PR) in 27 (43%), stable disease (SD) in 22 (35%) patients, and 10 patients (16%) had disease progression (PD). After reevaluation, 23 patients (15 PR and 8 SD after CRT) underwent surgery (37%), all with R0 resection. OS in the whole group was 53% at one year, and 36% at two years. OS was significantly better in the operated group of patients than in the non-operated group. No statistically significant difference in OS was observed comparing operated to CR patients with no surgery (70 vs 50%). In the non-operated group of patients there was no difference in OS between CR, PR, and SD patients. Conclusions: With appropriate selection, patients with advanced squamous cell esophageal cancer should be considered for potentially effective treatment. © 2017 Zerbinis Publications. All rights reserved.
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    Curative intent for unresectable advanced squamous cell esophageal cancer: Overall survival after chemoradiation
    (2017)
    Arsenijevic, Tatjana (6508074168)
    ;
    Nikitovic, Marina (6602665617)
    ;
    Plesinac-Karapandzic, Vesna (23474669800)
    ;
    Stojanovic-Rundic, Suzana (23037160700)
    ;
    Gavrilovic, Dusica (8849698200)
    ;
    Micev, Marjan (7003864533)
    ;
    Pesko, Predrag (7004246956)
    Purpose: To analyse the overall survival (OS) of patients with locally advanced, unresectable esophageal cancer treated with chemoradiation (CRT) with or without surgery. Methods: CRT was administered to 63 patients with locally advanced (T3-4, N0-1), initially unresectable squamous cell esophageal cancer. After the assessment of tumor response to treatment, medically fit patients converted to operable stage were subjected to surgery. Regular follow-up was performed every 3 months during first 2 years, and then every 6 months. Results: All 63 patients completed the whole radiotherapy course. Forty patients (63%) received complete 4 cycles of chemotherapy. In the remaining 23 patients (37%) chemotherapy was interrupted due to toxicity. Clinical response to CRT was: complete response (CR) in 4 patients (6%), partial response (PR) in 27 (43%), stable disease (SD) in 22 (35%) patients, and 10 patients (16%) had disease progression (PD). After reevaluation, 23 patients (15 PR and 8 SD after CRT) underwent surgery (37%), all with R0 resection. OS in the whole group was 53% at one year, and 36% at two years. OS was significantly better in the operated group of patients than in the non-operated group. No statistically significant difference in OS was observed comparing operated to CR patients with no surgery (70 vs 50%). In the non-operated group of patients there was no difference in OS between CR, PR, and SD patients. Conclusions: With appropriate selection, patients with advanced squamous cell esophageal cancer should be considered for potentially effective treatment. © 2017 Zerbinis Publications. All rights reserved.
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    Dose Escalation in Neoadjuvant Chemoradiotherapy for Rectal Cancer: Short-Term Efficacy and Toxicity of VMAT–SIB vs. 3D-CRT
    (2025)
    Stojanovic-Rundic, Suzana (23037160700)
    ;
    Marinkovic, Mladen (57222259689)
    ;
    Stanojevic, Aleksandra (58309472800)
    ;
    Gavrilovic, Dusica (8849698200)
    ;
    Jankovic, Radmila (57192010824)
    ;
    Maksimovic, Natasa (12772951900)
    ;
    Tomasevic, Aleksandar (56630429500)
    ;
    Petrasinovic, Predrag (57212480305)
    ;
    Radenkovic, Sandra (36615697100)
    ;
    Cavic, Milena (39760938900)
    Background and Objectives: The standard treatment for locally advanced rectal cancer (LARC) includes neoadjuvant chemoradiotherapy (nCRT), followed by surgery with or without adjuvant chemotherapy (CT). This study evaluated the efficacy and safety of dose-escalated radiotherapy (RT) using the volumetric modulated arc therapy–simultaneous integrated boost (VMAT–SIB) technique in patients with LARC compared to 3D conformal radiotherapy (3D-CRT). Materials and Methods: This study prospectively enrolled 75 patients with LARC. All patients received nCRT using VMAT–SIB, delivering a tumor dose (TD) of 54 Gy in 25 fractions, with concomitant CT following the 5-fluorouracil and leucovorin (5-FU–LV) protocol. To compare the treatment outcomes and toxicity associated with the increased RT dose, a retrospective cohort of 62 patients treated with the 3D-CRT technique was analyzed. The 3D-CRT group received a TD of 50.4 Gy in 28 fractions with the same CT. Outcomes, including pathological complete response (pCR), tumor regression grade (TRG), and sphincter preservation rates, were compared. Results: Among operated patients, the group treated with VMAT–SIB demonstrated improved rates of pCR (20.6% vs. 8.9%), with a statistically significant trend (p = 0.06). Sphincter-preserving surgeries were performed in 49 out of 63 operated patients (77.8%) in the VMAT–SIB group, compared to 35 out of 56 (62.5%) in the 3D-CRT group. Analysis of the definitive postoperative stage revealed a significantly higher prevalence of lower T categories (T0–2) (p < 0.01), negative N status (p < 0.05), and lower stages (I + II) (p < 0.05) in patients treated with the intensified RT approach. However, no significant differences in acute toxicity were observed. Conclusions: The implementation of intensified treatment with a higher dose using the VMAT–SIB technique demonstrated significant benefits in downsizing and downstaging compared to the standard treatment approach. These findings support its integration into clinical practice. However, further prospective, multi-center studies are needed to validate these results and assess long-term outcomes. © 2025 by the authors.
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    Evaluation of Cyclin D1 expression by western blotting methods and immunohistochemistry in breast cancer patients
    (2021)
    Radenkovic, Sandra (36615697100)
    ;
    Konjevic, Gordana (56008692300)
    ;
    Nikitovic, Marina (6602665617)
    ;
    Stojanovic-Rundic, Suzana (23037160700)
    ;
    Plesinac-Karapandzic, Vesna (23474669800)
    ;
    Milovic-Kovacevic, Marijana (15136517400)
    ;
    Jurisic, Vladimir (6603015144)
    Purpose: Considering that cyclin D1 had a prognostic and clinical value for breast cancer patients, adequate measurement of cyclin D1 is necessary. Methods: In this investigation, we detect cyclin D1 expression in tumour and peritumoral tissue of breast cancer patients by Western blotting method and by immunohistochemistry. Results: Cyclin D1 expression decreased significantly with each advanced clinical stage of disease and tumour size. Also, patients without lymph node involvement, with positive hormone receptors and Luminal A type of tumours had significantly increased the expression of cyclin D1. We show that cyclin D1 expression correlates with longer RFS in the entire group of patients, in the group of ER-positive and in the group of HER2-negative patients. Patients who were both ER and cyclin D1 positive had a better prognosis. Conclusion: Taken together, our results showing correlation of cyclin D1 with clinical stage, tumour size and lymph nodes, suggest that cyclin D1 expression detected by Western blotting could be considered as an additional marker for the staging of breast cancer, as well as a marker for longer RFS and survival in ER-positive breast cancer patients. © 2021 Zerbinis Publications. All rights reserved.
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    Evaluation of Cyclin D1 expression by western blotting methods and immunohistochemistry in breast cancer patients
    (2021)
    Radenkovic, Sandra (36615697100)
    ;
    Konjevic, Gordana (56008692300)
    ;
    Nikitovic, Marina (6602665617)
    ;
    Stojanovic-Rundic, Suzana (23037160700)
    ;
    Plesinac-Karapandzic, Vesna (23474669800)
    ;
    Milovic-Kovacevic, Marijana (15136517400)
    ;
    Jurisic, Vladimir (6603015144)
    Purpose: Considering that cyclin D1 had a prognostic and clinical value for breast cancer patients, adequate measurement of cyclin D1 is necessary. Methods: In this investigation, we detect cyclin D1 expression in tumour and peritumoral tissue of breast cancer patients by Western blotting method and by immunohistochemistry. Results: Cyclin D1 expression decreased significantly with each advanced clinical stage of disease and tumour size. Also, patients without lymph node involvement, with positive hormone receptors and Luminal A type of tumours had significantly increased the expression of cyclin D1. We show that cyclin D1 expression correlates with longer RFS in the entire group of patients, in the group of ER-positive and in the group of HER2-negative patients. Patients who were both ER and cyclin D1 positive had a better prognosis. Conclusion: Taken together, our results showing correlation of cyclin D1 with clinical stage, tumour size and lymph nodes, suggest that cyclin D1 expression detected by Western blotting could be considered as an additional marker for the staging of breast cancer, as well as a marker for longer RFS and survival in ER-positive breast cancer patients. © 2021 Zerbinis Publications. All rights reserved.
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    Exploring novel genetic and hematological predictors of response to neoadjuvant chemoradiotherapy in locally advanced rectal cancer
    (2023)
    Marinkovic, Mladen (57222259689)
    ;
    Stojanovic-Rundic, Suzana (23037160700)
    ;
    Stanojevic, Aleksandra (58309472800)
    ;
    Ostojic, Marija (57222464617)
    ;
    Gavrilovic, Dusica (8849698200)
    ;
    Jankovic, Radmila (57192010824)
    ;
    Maksimovic, Natasa (12772951900)
    ;
    Stroggilos, Rafael (57210317036)
    ;
    Zoidakis, Jerome (6506081730)
    ;
    Castellví-Bel, Sergi (57193218784)
    ;
    Fijneman, Remond J. A. (55879267200)
    ;
    Cavic, Milena (39760938900)
    Introduction: The standard treatment for locally advanced rectal cancer (LARC) is neoadjuvant chemoradiotherapy (nCRT). To select patients who would benefit the most from nCRT, there is a need for predictive biomarkers. The aim of this study was to evaluate the role of clinical, pathological, radiological, inflammation-related genetic, and hematological parameters in the prediction of post-nCRT response. Materials and methods: In silico analysis of published transcriptomics datasets was conducted to identify candidate genes, whose expression will be measured using quantitative Real Time PCR (qRT-PCR) in pretreatment formaline-fixed paraffin-embedded (FFPE) samples. In this study, 75 patients with LARC were prospectively included between June 2020—January 2022. Patients were assessed for tumor response in week 8 post-nCRT with pelvic MRI scan and rigid proctoscopy. For patients with a clinical complete response (cCR) and initially distant located tumor no immediate surgery was suggested (“watch and wait” approach). The response after surgery was assessed using histopathological tumor regression grading (TRG) categories from postoperative specimens by Mandard. Responders (R) were defined as patients with cCR without operative treatment, and those with TRG 1 and TRG 2 postoperative categories. Non-responders (NR) were patients classified as TRG 3-5. Results: Responders group comprised 35 patients (46.6%) and NR group 53.4% of patients. Analysis of published transcriptomics data identified genes that could predict response to treatment and their significance was assessed in our cohort by qRT-PCR. When comparison was made in the subgroup of patients who were operated (TRG1 vs. TRG4), the expression of IDO1 was significantly deregulated (p < 0.05). Among hematological parameters between R and NR a significant difference in the response was detected for neutrophil-to-monocyte ratio (NMR), initial basophil, eosinophil and monocyte counts (p < 0.01). According to MRI findings, non-responders more often presented with extramural vascular invasion (p < 0.05). Conclusion: Based on logistic regression model, factors associated with favorable response to nCRT were tumor morphology and hematological parameters which can be easily and routinely derived from initial laboratory results (NMR, eosinophil, basophil and monocyte counts) in a minimally invasive manner. Using various metrics, an aggregated score of the initial eosinophil, basophil, and monocyte counts demonstrated the best predictive performance. Copyright © 2023 Marinkovic, Stojanovic-Rundic, Stanojevic, Ostojic, Gavrilovic, Jankovic, Maksimovic, Stroggilos, Zoidakis, Castellví-Bel, Fijneman and Cavic.
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    Exploring novel genetic and hematological predictors of response to neoadjuvant chemoradiotherapy in locally advanced rectal cancer
    (2023)
    Marinkovic, Mladen (57222259689)
    ;
    Stojanovic-Rundic, Suzana (23037160700)
    ;
    Stanojevic, Aleksandra (58309472800)
    ;
    Ostojic, Marija (57222464617)
    ;
    Gavrilovic, Dusica (8849698200)
    ;
    Jankovic, Radmila (57192010824)
    ;
    Maksimovic, Natasa (12772951900)
    ;
    Stroggilos, Rafael (57210317036)
    ;
    Zoidakis, Jerome (6506081730)
    ;
    Castellví-Bel, Sergi (57193218784)
    ;
    Fijneman, Remond J. A. (55879267200)
    ;
    Cavic, Milena (39760938900)
    Introduction: The standard treatment for locally advanced rectal cancer (LARC) is neoadjuvant chemoradiotherapy (nCRT). To select patients who would benefit the most from nCRT, there is a need for predictive biomarkers. The aim of this study was to evaluate the role of clinical, pathological, radiological, inflammation-related genetic, and hematological parameters in the prediction of post-nCRT response. Materials and methods: In silico analysis of published transcriptomics datasets was conducted to identify candidate genes, whose expression will be measured using quantitative Real Time PCR (qRT-PCR) in pretreatment formaline-fixed paraffin-embedded (FFPE) samples. In this study, 75 patients with LARC were prospectively included between June 2020—January 2022. Patients were assessed for tumor response in week 8 post-nCRT with pelvic MRI scan and rigid proctoscopy. For patients with a clinical complete response (cCR) and initially distant located tumor no immediate surgery was suggested (“watch and wait” approach). The response after surgery was assessed using histopathological tumor regression grading (TRG) categories from postoperative specimens by Mandard. Responders (R) were defined as patients with cCR without operative treatment, and those with TRG 1 and TRG 2 postoperative categories. Non-responders (NR) were patients classified as TRG 3-5. Results: Responders group comprised 35 patients (46.6%) and NR group 53.4% of patients. Analysis of published transcriptomics data identified genes that could predict response to treatment and their significance was assessed in our cohort by qRT-PCR. When comparison was made in the subgroup of patients who were operated (TRG1 vs. TRG4), the expression of IDO1 was significantly deregulated (p < 0.05). Among hematological parameters between R and NR a significant difference in the response was detected for neutrophil-to-monocyte ratio (NMR), initial basophil, eosinophil and monocyte counts (p < 0.01). According to MRI findings, non-responders more often presented with extramural vascular invasion (p < 0.05). Conclusion: Based on logistic regression model, factors associated with favorable response to nCRT were tumor morphology and hematological parameters which can be easily and routinely derived from initial laboratory results (NMR, eosinophil, basophil and monocyte counts) in a minimally invasive manner. Using various metrics, an aggregated score of the initial eosinophil, basophil, and monocyte counts demonstrated the best predictive performance. Copyright © 2023 Marinkovic, Stojanovic-Rundic, Stanojevic, Ostojic, Gavrilovic, Jankovic, Maksimovic, Stroggilos, Zoidakis, Castellví-Bel, Fijneman and Cavic.
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    Factors influencing participation in breast cancer opportunistic screening in Belgrade, Serbia
    (2018)
    Jovicevic, Ana (6504029125)
    ;
    Ristic, Svetlana (56343123800)
    ;
    Mandic, Vera (57202817742)
    ;
    Jovicevic, Dragana (57202815606)
    ;
    Rajovic, Tatjana (57200209947)
    ;
    Stojanovic-Rundic, Suzana (23037160700)
    ;
    Pekmezovic, Tatjana (7003989932)
    Purpose: To assess the motivation and barrier factors influencing participation of women in opportunistic breast cancer screening in Belgrade, Serbia, and to detect changes in these factors over time. Methods: A cross-sectional study has been carried out at the Institute for Oncology and Radiology of Serbia in 2009 and 2016 among women aged 40 to 69 years from Belgrade who came at the Institute for opportunistic breast cancer screening. The demographic characteristics, data regarding breast exams practices, screening motivators and barriers and sources of information on breast cancer were collected by self-administered questionnaire. Results: The questionnaire was completed by 478 women in 2009 and 453 in 2016, with increase in women reporting regular mammograms or at least one previous mammogram (from 30.1% to 58.6%, p=0.000). In 2009, the most frequent motivating factors were health maintenance (36%), friend’s advice, TV, cancer in the family or fear of breast cancer; in 2016, advice from gynecologist (significant increase from 10.9% to 37.7%, p=0.000), health maintenance, family cancer and fear of cancer. The most frequent reasons for not going to exams regularly were absence of breast problems, crowded doctor’s offices and no family breast cancer. Conclusions: These findings provide information on motivation and barrier factors that may influence women’s decision to participate in opportunistic breast cancer screening. Those factors have changed over time and the role of physicians has increased significantly. Further exploration of motivating and barrier factors and the extent of their association with actual women’s behavior would be helpful for the development of interventions to improve organized and opportunistic screening participation. © 2018 Zerbinis Publications. All rights reserved.
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    Factors influencing participation in breast cancer opportunistic screening in Belgrade, Serbia
    (2018)
    Jovicevic, Ana (6504029125)
    ;
    Ristic, Svetlana (56343123800)
    ;
    Mandic, Vera (57202817742)
    ;
    Jovicevic, Dragana (57202815606)
    ;
    Rajovic, Tatjana (57200209947)
    ;
    Stojanovic-Rundic, Suzana (23037160700)
    ;
    Pekmezovic, Tatjana (7003989932)
    Purpose: To assess the motivation and barrier factors influencing participation of women in opportunistic breast cancer screening in Belgrade, Serbia, and to detect changes in these factors over time. Methods: A cross-sectional study has been carried out at the Institute for Oncology and Radiology of Serbia in 2009 and 2016 among women aged 40 to 69 years from Belgrade who came at the Institute for opportunistic breast cancer screening. The demographic characteristics, data regarding breast exams practices, screening motivators and barriers and sources of information on breast cancer were collected by self-administered questionnaire. Results: The questionnaire was completed by 478 women in 2009 and 453 in 2016, with increase in women reporting regular mammograms or at least one previous mammogram (from 30.1% to 58.6%, p=0.000). In 2009, the most frequent motivating factors were health maintenance (36%), friend’s advice, TV, cancer in the family or fear of breast cancer; in 2016, advice from gynecologist (significant increase from 10.9% to 37.7%, p=0.000), health maintenance, family cancer and fear of cancer. The most frequent reasons for not going to exams regularly were absence of breast problems, crowded doctor’s offices and no family breast cancer. Conclusions: These findings provide information on motivation and barrier factors that may influence women’s decision to participate in opportunistic breast cancer screening. Those factors have changed over time and the role of physicians has increased significantly. Further exploration of motivating and barrier factors and the extent of their association with actual women’s behavior would be helpful for the development of interventions to improve organized and opportunistic screening participation. © 2018 Zerbinis Publications. All rights reserved.
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    Methylenetetrahydrofolate reductase polymorphic variants C677T and A1298C in rectal cancer in Slavic population: significance for cancer risk and response to chemoradiotherapy
    (2023)
    Stanojevic, Aleksandra (58309472800)
    ;
    Spasic, Jelena (57195299847)
    ;
    Marinkovic, Mladen (57222259689)
    ;
    Stojanovic-Rundic, Suzana (23037160700)
    ;
    Jankovic, Radmila (57192010824)
    ;
    Djuric, Ana (56878876600)
    ;
    Zoidakis, Jerome (6506081730)
    ;
    Fijneman, Remond J. A. (55879267200)
    ;
    Castellvi-Bel, Sergi (57193218784)
    ;
    Cavic, Milena (39760938900)
    Background: Methylenetetrahydrofolate reductase (MTHFR) single nucleotide polymorphisms (SNPs) have been suggested as risk, prognostic, and predictive factors for colorectal cancer in various populations, but have not been validated so far. The aim of this study was to examine the association of MTHFR C677T (rs1801133) and A1298C (rs1801131) single nucleotide polymorphisms with the risk of rectal cancer as well as the response to neoadjuvant chemoradiotherapy (nCRT) based on 5-Fluorouracil (5-FU)/leucovorin (LV) in the locally advanced setting. Patients and methods: This case-control study included 119 healthy controls and 97 patients with locally advanced rectal cancer (LARC). For MTHFR genotyping, restriction fragment length polymorphism analysis (PCR-RFLP) was employed. Results: In silico analysis highlighted that SNPs C677T and A1298T correlate with MTHFR gene expression, and that gene expression profile correlates with cancer risk and stage. Using dominant and recessive models, it was found that the MTHFR 677CC vs. 677CT+677TT have increased risk of cancer development (odds ratio (OR): 2.27; 95% confidence interval (CI): 1.30–3.95, p = 0.002) as well as 677CC+677CT compared to 677TT (OR: 4.18, 95% CI: 1.16–14.99, p = 0.014). MTHFR 1298AA also shown increased risk for cancer development compared to 1298AC+1298CC (OR:2.0, 95% CI: 1.20–3.59, p = 0.035) Statistical analysis of combined genotypes highlighted the protective role of CT/AC combined genotype (OR: 3.15 95% CI: 1.576–6.279, p = 0.002) while the CC/AA genotype showed an increased risk for rectal cancer development (OR: 2.499, 95% CI: 1.246–5.081, p = 0.016) The carriers of the 677C/1298A haplotype had the highest risk for developing rectal cancer (OR: 1.74; 95% CI: 1.198–2.530, p = 0.002) while the 677T/1298C haplotype seems to provide a protective effect. (OR: 0.44; 95%CI 0.248–0.795, p = 0.003). No significant association with response to chemoradiotherapy was found. Conclusion: Our data point to MTHFR 667C allele and 1298A alleles as low-penetrance risk factors for rectal cancer in our population. To the best of our knowledge, this is the first study of this type performed on the Slavic population in the Western Balkan, as various population-based factors might also be significant our findings can be used for future meta-analyses and the construction of genetic cancer risk prediction panels. Copyright © 2024 Stanojevic, Spasic, Marinkovic, Stojanovic-Rundic, Jankovic, Djuric, Zoidakis, Fijneman, Castellvi-Bel and Cavic.
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    Methylenetetrahydrofolate reductase polymorphic variants C677T and A1298C in rectal cancer in Slavic population: significance for cancer risk and response to chemoradiotherapy
    (2023)
    Stanojevic, Aleksandra (58309472800)
    ;
    Spasic, Jelena (57195299847)
    ;
    Marinkovic, Mladen (57222259689)
    ;
    Stojanovic-Rundic, Suzana (23037160700)
    ;
    Jankovic, Radmila (57192010824)
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    Djuric, Ana (56878876600)
    ;
    Zoidakis, Jerome (6506081730)
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    Fijneman, Remond J. A. (55879267200)
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    Castellvi-Bel, Sergi (57193218784)
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    Cavic, Milena (39760938900)
    Background: Methylenetetrahydrofolate reductase (MTHFR) single nucleotide polymorphisms (SNPs) have been suggested as risk, prognostic, and predictive factors for colorectal cancer in various populations, but have not been validated so far. The aim of this study was to examine the association of MTHFR C677T (rs1801133) and A1298C (rs1801131) single nucleotide polymorphisms with the risk of rectal cancer as well as the response to neoadjuvant chemoradiotherapy (nCRT) based on 5-Fluorouracil (5-FU)/leucovorin (LV) in the locally advanced setting. Patients and methods: This case-control study included 119 healthy controls and 97 patients with locally advanced rectal cancer (LARC). For MTHFR genotyping, restriction fragment length polymorphism analysis (PCR-RFLP) was employed. Results: In silico analysis highlighted that SNPs C677T and A1298T correlate with MTHFR gene expression, and that gene expression profile correlates with cancer risk and stage. Using dominant and recessive models, it was found that the MTHFR 677CC vs. 677CT+677TT have increased risk of cancer development (odds ratio (OR): 2.27; 95% confidence interval (CI): 1.30–3.95, p = 0.002) as well as 677CC+677CT compared to 677TT (OR: 4.18, 95% CI: 1.16–14.99, p = 0.014). MTHFR 1298AA also shown increased risk for cancer development compared to 1298AC+1298CC (OR:2.0, 95% CI: 1.20–3.59, p = 0.035) Statistical analysis of combined genotypes highlighted the protective role of CT/AC combined genotype (OR: 3.15 95% CI: 1.576–6.279, p = 0.002) while the CC/AA genotype showed an increased risk for rectal cancer development (OR: 2.499, 95% CI: 1.246–5.081, p = 0.016) The carriers of the 677C/1298A haplotype had the highest risk for developing rectal cancer (OR: 1.74; 95% CI: 1.198–2.530, p = 0.002) while the 677T/1298C haplotype seems to provide a protective effect. (OR: 0.44; 95%CI 0.248–0.795, p = 0.003). No significant association with response to chemoradiotherapy was found. Conclusion: Our data point to MTHFR 667C allele and 1298A alleles as low-penetrance risk factors for rectal cancer in our population. To the best of our knowledge, this is the first study of this type performed on the Slavic population in the Western Balkan, as various population-based factors might also be significant our findings can be used for future meta-analyses and the construction of genetic cancer risk prediction panels. Copyright © 2024 Stanojevic, Spasic, Marinkovic, Stojanovic-Rundic, Jankovic, Djuric, Zoidakis, Fijneman, Castellvi-Bel and Cavic.
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    New objective method in reporting the breast cosmesis after breast-conservative treatment based on nonstandardized photographs: The Objective Breast Cosmesis Scale
    (2016)
    Soror, Tamer (6506443190)
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    Kovács, György (56063378500)
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    Kovács, Ádám (26324952900)
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    Seibold, Nina (54384259100)
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    Melchert, Corinna (16203741900)
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    Baumann, Kristin (24471246200)
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    Wenzel, Eike (56427688300)
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    Stojanovic-Rundic, Suzana (23037160700)
    Purpose Subjective scoring is the most widely used approach in reporting the cosmetic outcome after breast-conservative therapy. This work introduces an objective system to document the breast cosmetic changes using nonstandardized photographs without scale calibration. Methods and Materials Two hundred twenty-eight photographs of 114 breast cancer patients were analyzed. Baseline photographs were taken after breast-conservation surgery and before partial breast irradiation. Further photographs were taken during followup. The photographs were taken with a frontal view of the patient and without any skin marks for scaling. The baseline and the last followup photographs were analyzed by measuring certain anatomic distances (representing the nipple displacement and the asymmetry in breast dimensions and contour) to calculate the objective breast cosmesis score (OBCS). The measurements represent the nipple displacement and the asymmetry in breast dimensions and contour. Same photographs were scored subjectively by a multidisciplinary team (MDT) using the Harvard breast cosmesis scale. The patient-reported self-scoring was also recorded. Results The MDT results were favorable (excellent∖good) in 72.3% of the photographs and adverse in 27.7%. Agreement among the MDT members was strong (intraclass correlation coefficient = 0.798, p < 0.001, 95% CI: 0.753–0.937, Cronbach's alpha = 0.809). The patient self-scoring was satisfactory in 82.5% of the cases and nonsatisfactory in 17.5%. The results of the OBCS ranged between 0.0 and 20.4 with a median value of 4.5. There was a strong significant correlation between the OBCS and both the MDT subjective scoring (p < 0.001) and the patient self-scoring (p < 0.001). Conclusions The OBCS seems to be eligible for the objective assessment of cosmesis after breast-conservative therapy using nonstandardized photographs without scale calibration. © 2016 American Brachytherapy Society
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    p21 does, but p53 does not predict pathological response to preoperative chemoradiotherapy in locally advanced rectal cancer
    (2017)
    Stojanovic-Rundic, Suzana (23037160700)
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    Jankovic, Radmila (57192010824)
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    Micev, Marjan (7003864533)
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    Nikolic, Vladimir (36980401100)
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    Popov, Ivan (7202086682)
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    Gavrilovic, Dusica (8849698200)
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    Plesinac-Karapandzic, Vesna (23474669800)
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    Djuric-Stefanovic, Aleksandra (16021199600)
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    Krivokapic, Zoran (55503352000)
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    Radulovic, Sinisa (7005858810)
    Purpose: Preoperative chemoradiotherapy (CRT) is the standard treatment option in locally advanced rectal cancer. The tumor response is assessed through tumor and nodal downstaging and the tumor regression grade. Currently, there is no method to predict a tumor response to CRT. We aimed to evaluate whether p21 and p53 expressions could be a reliable predictors of pathological response to CRT. Methods: Fifty patients with locally advanced rectal cancer were treated with preoperative radiotherapy combined with mitomycin C and capecitabine. p21 and p53 immu-mohistochemical staining was performed on pretreatment biopsies and the results were compared with tumor regression according to grading systems by Dworak (TRG grades) and by Wheeler (RCRG grades). Results: Testing RCRG grades in relation to p21 expression showed statistically significant difference (p=0.021). RCRG 3 (poor response) was more frequent in the group of patients with low p21. According to Dworak, grade 4 (complete regression) was more frequent in the group of patients with positive p21 expression (p=0.032). Significant difference in p21 expression in grade 4 group compared with all other grade groups was also found (p=0.007). Patients with immune expression of p21 had significantly higher percentage of complete regression in comparison to the patients with low expression of p21. We haven’t found any correlation between p53 expression and histopathological (HP) as well as regression grades. Conclusion: According to both grading systems, our results suggest that p53 expression does not, but p21 expression does predict pathological response to preoperative CRT. © 2017 Zerbinis Publications. All rights reserved.
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    p21 does, but p53 does not predict pathological response to preoperative chemoradiotherapy in locally advanced rectal cancer
    (2017)
    Stojanovic-Rundic, Suzana (23037160700)
    ;
    Jankovic, Radmila (57192010824)
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    Micev, Marjan (7003864533)
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    Nikolic, Vladimir (36980401100)
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    Popov, Ivan (7202086682)
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    Gavrilovic, Dusica (8849698200)
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    Plesinac-Karapandzic, Vesna (23474669800)
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    Djuric-Stefanovic, Aleksandra (16021199600)
    ;
    Krivokapic, Zoran (55503352000)
    ;
    Radulovic, Sinisa (7005858810)
    Purpose: Preoperative chemoradiotherapy (CRT) is the standard treatment option in locally advanced rectal cancer. The tumor response is assessed through tumor and nodal downstaging and the tumor regression grade. Currently, there is no method to predict a tumor response to CRT. We aimed to evaluate whether p21 and p53 expressions could be a reliable predictors of pathological response to CRT. Methods: Fifty patients with locally advanced rectal cancer were treated with preoperative radiotherapy combined with mitomycin C and capecitabine. p21 and p53 immu-mohistochemical staining was performed on pretreatment biopsies and the results were compared with tumor regression according to grading systems by Dworak (TRG grades) and by Wheeler (RCRG grades). Results: Testing RCRG grades in relation to p21 expression showed statistically significant difference (p=0.021). RCRG 3 (poor response) was more frequent in the group of patients with low p21. According to Dworak, grade 4 (complete regression) was more frequent in the group of patients with positive p21 expression (p=0.032). Significant difference in p21 expression in grade 4 group compared with all other grade groups was also found (p=0.007). Patients with immune expression of p21 had significantly higher percentage of complete regression in comparison to the patients with low expression of p21. We haven’t found any correlation between p53 expression and histopathological (HP) as well as regression grades. Conclusion: According to both grading systems, our results suggest that p53 expression does not, but p21 expression does predict pathological response to preoperative CRT. © 2017 Zerbinis Publications. All rights reserved.
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    Performance and Dimensionality of Pretreatment MRI Radiomics in Rectal Carcinoma Chemoradiotherapy Prediction
    (2024)
    Marinkovic, Mladen (57222259689)
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    Stojanovic-Rundic, Suzana (23037160700)
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    Stanojevic, Aleksandra (58309472800)
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    Tomasevic, Aleksandar (56630429500)
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    Jankovic, Radmila (57192010824)
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    Zoidakis, Jerome (6506081730)
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    Castellví-Bel, Sergi (57193218784)
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    Fijneman, Remond J. A. (55879267200)
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    Cavic, Milena (39760938900)
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    Radulovic, Marko (57200831760)
    (1) Background: This study aimed to develop a machine learning model based on radiomics of pretreatment magnetic resonance imaging (MRI) 3D T2W contrast sequence scans combined with clinical parameters (CP) to predict neoadjuvant chemoradiotherapy (nCRT) response in patients with locally advanced rectal carcinoma (LARC). The study also assessed the impact of radiomics dimensionality on predictive performance. (2) Methods: Seventy-five patients were prospectively enrolled with clinicopathologically confirmed LARC and nCRT before surgery. Tumor properties were assessed by calculating 2141 radiomics features. Least absolute shrinkage selection operator (LASSO) and multivariate regression were used for feature selection. (3) Results: Two predictive models were constructed, one starting from 72 CP and 107 radiomics features, and the other from 72 CP and 1862 radiomics features. The models revealed moderately advantageous impact of increased dimensionality, with their predictive respective AUCs of 0.86 and 0.90 in the entire cohort and 0.84 within validation folds. Both models outperformed the CP-only model (AUC = 0.80) which served as the benchmark for predictive performance without radiomics. (4) Conclusions: Predictive models developed in this study combining pretreatment MRI radiomics and clinicopathological features may potentially provide a routine clinical predictor of chemoradiotherapy responders, enabling clinicians to personalize treatment strategies for rectal carcinoma. © 2024 by the authors.
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    pSTAT3 expression associated with survival and mammographic density of breast cancer patients
    (2019)
    Radenkovic, Sandra (36615697100)
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    Konjevic, Gordana (56008692300)
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    Gavrilovic, Dusica (8849698200)
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    Stojanovic-Rundic, Suzana (23037160700)
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    Plesinac-Karapandzic, Vesna (23474669800)
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    Stevanovic, Predrag (24315050600)
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    Jurisic, Vladimir (6603015144)
    Background: Constitutive activation of STAT3 have been shown in several tumor types including breast cancer. We investigate STAT3 expresion as possible molecular marker for breast cancer early detection, as well as prognostic factor for determination of tumor agressiveness. Methods: In this study we measure p(Y705)STAT3 expression in tumor and adjacent tissue of breast cancer patients by Western blot. For relapse-free survival (RFS) and overall survival (OS) we used Log-Rank test. Results: We show that average expression of p (Y705) STAT3 in tumor tissue is higher compared to adjacent tissue. Moreover, we found that patients with HER2 positive receptors had significantly higher pSTAT3 expression compared to HER2 negative patients. We showed that patients with high mammographic density had significantly higher tumor expression of pSTAT3 compared to patients with low mammographic density. Also, we show that pSTAT3 expression correlates with longer RFS in the entire group of patients, as well as in the group of ER positive, in lymph node positive and in older group of breast cancer patients (with age over 50). Furthermore, in the entire group of patients, in ER positive, in lymph node positive and in older group of patient, high expression of pSTAT3 showed a better survival than low expression of pSTAT3. Conclusion: Considering that the expression of pSTAT3 is associated with longer RFS and survival, it can be used as prognostic tools for determination of group of breast cancer patients with low-risk. © 2018 Elsevier GmbH
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    pSTAT3 expression associated with survival and mammographic density of breast cancer patients
    (2019)
    Radenkovic, Sandra (36615697100)
    ;
    Konjevic, Gordana (56008692300)
    ;
    Gavrilovic, Dusica (8849698200)
    ;
    Stojanovic-Rundic, Suzana (23037160700)
    ;
    Plesinac-Karapandzic, Vesna (23474669800)
    ;
    Stevanovic, Predrag (24315050600)
    ;
    Jurisic, Vladimir (6603015144)
    Background: Constitutive activation of STAT3 have been shown in several tumor types including breast cancer. We investigate STAT3 expresion as possible molecular marker for breast cancer early detection, as well as prognostic factor for determination of tumor agressiveness. Methods: In this study we measure p(Y705)STAT3 expression in tumor and adjacent tissue of breast cancer patients by Western blot. For relapse-free survival (RFS) and overall survival (OS) we used Log-Rank test. Results: We show that average expression of p (Y705) STAT3 in tumor tissue is higher compared to adjacent tissue. Moreover, we found that patients with HER2 positive receptors had significantly higher pSTAT3 expression compared to HER2 negative patients. We showed that patients with high mammographic density had significantly higher tumor expression of pSTAT3 compared to patients with low mammographic density. Also, we show that pSTAT3 expression correlates with longer RFS in the entire group of patients, as well as in the group of ER positive, in lymph node positive and in older group of breast cancer patients (with age over 50). Furthermore, in the entire group of patients, in ER positive, in lymph node positive and in older group of patient, high expression of pSTAT3 showed a better survival than low expression of pSTAT3. Conclusion: Considering that the expression of pSTAT3 is associated with longer RFS and survival, it can be used as prognostic tools for determination of group of breast cancer patients with low-risk. © 2018 Elsevier GmbH
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    The role of haematological parameters in predicting the response to radical chemoradiotherapy in patients with anal squamous cell cancer
    (2021)
    Stojanovic-Rundic, Suzana (23037160700)
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    Marinkovic, Mladen (57222259689)
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    Cavic, Milena (39760938900)
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    Karapandzic, Vesna Plesinac (36092731000)
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    Gavrilovic, Dusica (8849698200)
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    Jankovic, Radmila (57192010824)
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    De Voer, Richarda M. (58265981000)
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    Castellvi-Bel, Sergi (57193218784)
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    Krivokapic, Zoran (55503352000)
    Background: Historically, the treatment of choice for anal cancer had been abdominoperineal resection (APR). Radical radiotherapy with concurrent 5-fluorouracil plus mitomycin C chemotherapy was later established as standard therapy, although with a failure rate of 20-30%. The aim of this study was to evaluate the outcomes after radical chemoradiotherapy (CRT), prognostic and predictive factors and patterns of failure. Patients and methods: This study included 47 patients treated with radical CRT for patohistologicaly confirmed anal squamous cell carcinoma. Analysed haematological parameters included: Neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and haemoglobin level. The final logistic regression model included treatment break period. Tumour response was assessed at 24 weeks from CRT completion. Follow-up was performed every 3 months during the first two years, and every 6 months thereafter. Results: A complete clinical response (CR) was detected in 30 patients (63.8%). Patients who did not achieve a 6-months CR and those who had a CR after 6 months but then relapsed were referred to surgical treatment. With combined CRT and surgical salvage treatment the CR rate was 80.9%. Patients with CR after 6 months had significantly longer disease-free survival (DFS), progression-free survival (PFS), and overall survival (OS). A significant effect on the 6-month response was confirmed for PLR (p = 0.03). Conclusions: Important prognostic factors associated with CR were baseline haemoglobin level and period of treatment interruptions. Potential haematological prognostic factors could be PLR and NLR, which can be routinely determined by low-cost and minimally invasive methods. © 2021 Suzana Stojanovic-Rundic, Mladen Marinkovic, Milena Cavic, Vesna Plesinac Karapandzic, Dusica Gavrilovic, Radmila Jankovic, Richarda M. de Voer, Sergi Castellvi-Bel, Zoran Krivokapic, published by Sciendo.
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