Browsing by Author "Plesinac-Karapandzic, Vesna (23474669800)"

Purpose: The toxicity of postoperative radiotherapy for cervical cancer affects patients’ quality of life. We evaluated acute toxicity in postoperative intensity-modulated radiotherapy (IMRT) and three-dimensional conformal radiotherapy (3DCRT) as well as the influence of dosimetric parameters and concomitant chemotherapy. Methods: A total of 45 patients with early operable cervical cancer underwent postoperative IMRT with 40-45 Gy. The control group of 50 patients was treated with 3DCRT. Brachytherapy and concomitant cisplatin chemotherapy were performed in all patients according to pathologic and histologic findings. The patients were monitored for acute gastrointestinal, urological and hematological toxicity classified according to the RTOG acute radiation morbidity scoring criteria. We also analyzed the influence of dosimetric parameters on acute toxicity. Results: Significant differences were found in overall acute toxicity (p=0.018), acute genitourinary toxicity (p=0.029), anemia (p=0.043) and neutropenia (p=0.027) but not in acute gastrointestinal toxicity between the IMRT and 3DCRT groups. In all patients, regarding chemotherapy administration, differences were found between the chemoradiotherapy and radiotherapy group as far as overall acute toxicity (CHRT vs RT; p=0.011) and hematological toxicity were concerned (p=0.001). Patients with ≥3 cycles of chemotherapy showed increased hematologic toxicity. In the IMRT group according to the administration of chemotherapy (chemoradiotherapy vs radiotherapy), statistically significant difference for leukopenia (p=0.009) was found and in the 3DCRT group for anemia (p=0.021) and neutropenia (p=0.029). According to chemotherapy administration (chemoradiotherapy vs radiotherapy), a statistically significant difference in leukopenia (p=0.009) was found in the IMRT group while in the 3DCRT group the differences were in anemia (p=0.021) and neutropenia (p=0.029). Conclusion: IMRT is associated with lower acute toxicity and better dosimetric parameters in organs at risk (OAR) compared to 3DCRT. Higher hematological toxicity occurred when concomitant chemotherapy was performed, regardless of RT technique. Further reduction of toxicity is expected with protocol and technical improvement and research of gene-related toxicity. © 2019 Zerbinis Publications. All rights reserved.

Purpose: The toxicity of postoperative radiotherapy for cervical cancer affects patients’ quality of life. We evaluated acute toxicity in postoperative intensity-modulated radiotherapy (IMRT) and three-dimensional conformal radiotherapy (3DCRT) as well as the influence of dosimetric parameters and concomitant chemotherapy. Methods: A total of 45 patients with early operable cervical cancer underwent postoperative IMRT with 40-45 Gy. The control group of 50 patients was treated with 3DCRT. Brachytherapy and concomitant cisplatin chemotherapy were performed in all patients according to pathologic and histologic findings. The patients were monitored for acute gastrointestinal, urological and hematological toxicity classified according to the RTOG acute radiation morbidity scoring criteria. We also analyzed the influence of dosimetric parameters on acute toxicity. Results: Significant differences were found in overall acute toxicity (p=0.018), acute genitourinary toxicity (p=0.029), anemia (p=0.043) and neutropenia (p=0.027) but not in acute gastrointestinal toxicity between the IMRT and 3DCRT groups. In all patients, regarding chemotherapy administration, differences were found between the chemoradiotherapy and radiotherapy group as far as overall acute toxicity (CHRT vs RT; p=0.011) and hematological toxicity were concerned (p=0.001). Patients with ≥3 cycles of chemotherapy showed increased hematologic toxicity. In the IMRT group according to the administration of chemotherapy (chemoradiotherapy vs radiotherapy), statistically significant difference for leukopenia (p=0.009) was found and in the 3DCRT group for anemia (p=0.021) and neutropenia (p=0.029). According to chemotherapy administration (chemoradiotherapy vs radiotherapy), a statistically significant difference in leukopenia (p=0.009) was found in the IMRT group while in the 3DCRT group the differences were in anemia (p=0.021) and neutropenia (p=0.029). Conclusion: IMRT is associated with lower acute toxicity and better dosimetric parameters in organs at risk (OAR) compared to 3DCRT. Higher hematological toxicity occurred when concomitant chemotherapy was performed, regardless of RT technique. Further reduction of toxicity is expected with protocol and technical improvement and research of gene-related toxicity. © 2019 Zerbinis Publications. All rights reserved.

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.

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.

Purpose; To estimate whether the computed tomography (CT) perfusion imaging could be useful to predict the pathological complete response (pCR) of esophageal cancer to the neoadjuvant chemoradiotherapy (NACRT). Methods: Twenty-seven patients with the advanced squamous cell esophageal carcinoma, who were treated with concomitant CRT (CIS/5-FU/LV and 45-50 Gy total radiation dose), were re-evaluated using CT examination, which included the low-dose CT perfusion study. CT perfusion series were analysed using the deconvolution-based CT perfusion software (Perfusion 3.0, GE), and color parametric maps of the blood flow (BF), blood volume (BV), mean transit time (MTT), and permeability surface area product (PS) were displayed. All patients were operated and histo-pathological analysis of the resected esophagus considered the gold standard for pathologic complete response (pCR). Results: BF post-NACRT BVpost-NACRT and PSpost-NACRT were significantly lower, and MTTpost-NACRT significantly higher in the pCR group. Mean (±SD), or median perfusion parameter values in the pCRs (11 patients) vs non-pCRs (16 patients) were: BFpost-NACRT 21.4±5.0 VS 86.0±29 ml/min/100 g (p<0.001), BV post-NACRT 1.3 vs 3.9 ml/100 g (p<0.001), MTTpost-NACRT 5.5 vs 3.7 s (p=0.018), and PSpost-NACRT 5.9 vs 9.8 ml/min/100 g (p=0.006). ROC analysis revealed that BFpost-NACRT (AUC=1.000), BVpost-NACRT (AUC=0.932), MTTpost-NACRT (AUC=0.801), and PS^HACRT (AUC=0.844) could predict the pCR (p<0.01), while maximal esophageal wall thickness could not (AUC=0.676, p=0.126). If we set a cut-off value of BFpost-NACRT<30.0 ml/min/100 g, pCR was predicted with sensitivity and specificity of 100%. Conclusion: CT perfusion imaging enables accurate prediction of pCR of esophageal carcinoma to neoadjuvant chemoradiotherapy.

Purpose; To estimate whether the computed tomography (CT) perfusion imaging could be useful to predict the pathological complete response (pCR) of esophageal cancer to the neoadjuvant chemoradiotherapy (NACRT). Methods: Twenty-seven patients with the advanced squamous cell esophageal carcinoma, who were treated with concomitant CRT (CIS/5-FU/LV and 45-50 Gy total radiation dose), were re-evaluated using CT examination, which included the low-dose CT perfusion study. CT perfusion series were analysed using the deconvolution-based CT perfusion software (Perfusion 3.0, GE), and color parametric maps of the blood flow (BF), blood volume (BV), mean transit time (MTT), and permeability surface area product (PS) were displayed. All patients were operated and histo-pathological analysis of the resected esophagus considered the gold standard for pathologic complete response (pCR). Results: BF post-NACRT BVpost-NACRT and PSpost-NACRT were significantly lower, and MTTpost-NACRT significantly higher in the pCR group. Mean (±SD), or median perfusion parameter values in the pCRs (11 patients) vs non-pCRs (16 patients) were: BFpost-NACRT 21.4±5.0 VS 86.0±29 ml/min/100 g (p<0.001), BV post-NACRT 1.3 vs 3.9 ml/100 g (p<0.001), MTTpost-NACRT 5.5 vs 3.7 s (p=0.018), and PSpost-NACRT 5.9 vs 9.8 ml/min/100 g (p=0.006). ROC analysis revealed that BFpost-NACRT (AUC=1.000), BVpost-NACRT (AUC=0.932), MTTpost-NACRT (AUC=0.801), and PS^HACRT (AUC=0.844) could predict the pCR (p<0.01), while maximal esophageal wall thickness could not (AUC=0.676, p=0.126). If we set a cut-off value of BFpost-NACRT<30.0 ml/min/100 g, pCR was predicted with sensitivity and specificity of 100%. Conclusion: CT perfusion imaging enables accurate prediction of pCR of esophageal carcinoma to neoadjuvant chemoradiotherapy.

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.

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.

Purpose: Within implementation of intensity-modulated radiotherapy (IMRT) in the postoperative irradiation of cervical cancer we evaluated and compared IMRT and threedimensional conformal radiotherapy (3DCRT) dosimetric parameters for target volumes and organs at risk (OAR). Methods: We randomized 95 patients with cervical cancer, UICC stage I-III, in groups depending of the type of external beam postoperative radiotherapy. Forty-five patients were treated with IMRT and 50 with 3DCRT. All patients underwent brachytherapy, and according to risk factors some of the patients had concomitant cisplatin chemotherapy. The study was done in a period of three years from December 2015. Analysis of dosimetric parameters for target volume coverage and OARs was performed. Results: IMRT plans showed better conformity compared to 3DCRT plans, represented with homogenity index and conformity index, with higher maximum dose (PTV105 and D2). Both plans achieved adequate planning target volume coverage described with PTV95. Statistically significant difference between groups was found for bladder, rectum and bowel high dose regions: bladder V45 (p=0.000), rectum V40 (p=0.043) and V45 (p=0.000), bowel V45 (p=0.000), and bone marrow dosimetric parameters V20-V45; all were better in IMRT plans. Significant difference was found for volume of patient body normal tissue receiving dose of 20Gy, which was higher in IMRT. Conclusion: IMRT is a highly conformal technique. Satisfactory target volume coverage was achieved with both techniques, with better sparing of OARs in the IMRT group. With this technique improvement, we expect better quality of life in cervical cancer patients with good prognosis. © 2019 Zerbinis Publications. All rights reserved.

Purpose: Within implementation of intensity-modulated radiotherapy (IMRT) in the postoperative irradiation of cervical cancer we evaluated and compared IMRT and threedimensional conformal radiotherapy (3DCRT) dosimetric parameters for target volumes and organs at risk (OAR). Methods: We randomized 95 patients with cervical cancer, UICC stage I-III, in groups depending of the type of external beam postoperative radiotherapy. Forty-five patients were treated with IMRT and 50 with 3DCRT. All patients underwent brachytherapy, and according to risk factors some of the patients had concomitant cisplatin chemotherapy. The study was done in a period of three years from December 2015. Analysis of dosimetric parameters for target volume coverage and OARs was performed. Results: IMRT plans showed better conformity compared to 3DCRT plans, represented with homogenity index and conformity index, with higher maximum dose (PTV105 and D2). Both plans achieved adequate planning target volume coverage described with PTV95. Statistically significant difference between groups was found for bladder, rectum and bowel high dose regions: bladder V45 (p=0.000), rectum V40 (p=0.043) and V45 (p=0.000), bowel V45 (p=0.000), and bone marrow dosimetric parameters V20-V45; all were better in IMRT plans. Significant difference was found for volume of patient body normal tissue receiving dose of 20Gy, which was higher in IMRT. Conclusion: IMRT is a highly conformal technique. Satisfactory target volume coverage was achieved with both techniques, with better sparing of OARs in the IMRT group. With this technique improvement, we expect better quality of life in cervical cancer patients with good prognosis. © 2019 Zerbinis Publications. All rights reserved.

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.

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.

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

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

Tamoxifen is a standard therapeutical treatment in patients with estrogen receptor positive breast carcinoma. However, less than 50% of estrogen receptor positive breast cancers do not respond to tamoxifen treatment whereas 40% of tumors that initially respond to treatment develop resistance over time. The underlying mechanisms for tamoxifen resistance are probably multifactorial but remain largely unknown. The primary aim of this study was to investigate the impact of PTEN tumor suppressor gene on acquiring resistance to tamoxifen by analyzing loss of heterozygosity (LOH) and immunohystochemical expression of PTEN in 49 primary breast carcinomas of patients treated with tamoxifen as the only adjuvant therapy. The effect of PTEN inactivation on breast cancer progression and disease outcome was also analyzed. Reduced or completely lost PTEN expression was observed in 55.1% of samples, while 63.3% of samples displayed LOH of PTEN gene. Inactivation of PTEN immunoexpression significantly correlated with the PTEN loss of heterozygosity, suggesting LOH as the most important genetic mechanism for the reduction or complete loss of PTEN expression in primary breast carcinoma. Most importantly, LOH of PTEN and consequential reduction of its immunoexpression showed significant correlation with the recurrence of the disease. Besides, our study revealed that LOH of PTEN tumor suppressor was significantly associated with shorter disease free survival, breast cancer specific survival and overall survival. In summary, our results imply that LOH of PTEN could be used as a good prognostic characteristic for the outcome of breast cancer patients treated with tamoxifen. © 2012 Landes Bioscience.

Tamoxifen is a standard therapeutical treatment in patients with estrogen receptor positive breast carcinoma. However, less than 50% of estrogen receptor positive breast cancers do not respond to tamoxifen treatment whereas 40% of tumors that initially respond to treatment develop resistance over time. The underlying mechanisms for tamoxifen resistance are probably multifactorial but remain largely unknown. The primary aim of this study was to investigate the impact of PTEN tumor suppressor gene on acquiring resistance to tamoxifen by analyzing loss of heterozygosity (LOH) and immunohystochemical expression of PTEN in 49 primary breast carcinomas of patients treated with tamoxifen as the only adjuvant therapy. The effect of PTEN inactivation on breast cancer progression and disease outcome was also analyzed. Reduced or completely lost PTEN expression was observed in 55.1% of samples, while 63.3% of samples displayed LOH of PTEN gene. Inactivation of PTEN immunoexpression significantly correlated with the PTEN loss of heterozygosity, suggesting LOH as the most important genetic mechanism for the reduction or complete loss of PTEN expression in primary breast carcinoma. Most importantly, LOH of PTEN and consequential reduction of its immunoexpression showed significant correlation with the recurrence of the disease. Besides, our study revealed that LOH of PTEN tumor suppressor was significantly associated with shorter disease free survival, breast cancer specific survival and overall survival. In summary, our results imply that LOH of PTEN could be used as a good prognostic characteristic for the outcome of breast cancer patients treated with tamoxifen. © 2012 Landes Bioscience.

Purpose: All breast cancer (BC) patients with detectable hormone receptors (HR) expression should be offered endocrine therapy (ET). In premenopausal patients, tamoxifen and/or ovarian suppression (OvS)/ablation (OA) may improve disease outcome. Alteration of phosphatase and tensin homolog (PTEN) signaling pathways could be one of the possible mechanisms of resistance to antiestrogen therapy. The purpose of this study was to investigate the association of PTEN protein expression with prognostic factors such as tumor histology and grade, estrogen receptor (ER) and progesterone receptor (PgR) status, human epidermal growth factor receptor 2 (HER2) and disease outcome in premenopausal patients with HR-positive early BCs treated with adjuvant OA. Methods: We analyzed a group of premenopausal early stages I/II HR-positive BC patients who had undergone radical mastectomy followed only with adjuvant OA by irradiation. ER and PgR contents were determined by classical biochemical dextran-coated charcoal (DCC) method, HER2 status by chromogen in situ hybridization (CISH) analysis and PTEN status by immunohistochemistry (IHC). Results: Sixty-six premenopausal patients included into this analysis were followed for a median of 17 years (range 1-29). Compared to PTEN-positive BCs, PTEN-negative BCs were significantly more frequently associated with lobular tumor histology (p<0.05), higher ER content (p<0.05), and had significantly decreased disease-free survival (DFS) and overall survival (OS) (p<0.01 for both) compared to patients with PTEN-positive BCs. Conclusions: It seems that PTEN status determined by protein expression may discriminate between subgroups with poor and good prognosis in premenopausal HR-positive BC patients receiving adjuvant OA. © 2018 Zerbinis Publications. All Rights Reserved.

Purpose: All breast cancer (BC) patients with detectable hormone receptors (HR) expression should be offered endocrine therapy (ET). In premenopausal patients, tamoxifen and/or ovarian suppression (OvS)/ablation (OA) may improve disease outcome. Alteration of phosphatase and tensin homolog (PTEN) signaling pathways could be one of the possible mechanisms of resistance to antiestrogen therapy. The purpose of this study was to investigate the association of PTEN protein expression with prognostic factors such as tumor histology and grade, estrogen receptor (ER) and progesterone receptor (PgR) status, human epidermal growth factor receptor 2 (HER2) and disease outcome in premenopausal patients with HR-positive early BCs treated with adjuvant OA. Methods: We analyzed a group of premenopausal early stages I/II HR-positive BC patients who had undergone radical mastectomy followed only with adjuvant OA by irradiation. ER and PgR contents were determined by classical biochemical dextran-coated charcoal (DCC) method, HER2 status by chromogen in situ hybridization (CISH) analysis and PTEN status by immunohistochemistry (IHC). Results: Sixty-six premenopausal patients included into this analysis were followed for a median of 17 years (range 1-29). Compared to PTEN-positive BCs, PTEN-negative BCs were significantly more frequently associated with lobular tumor histology (p<0.05), higher ER content (p<0.05), and had significantly decreased disease-free survival (DFS) and overall survival (OS) (p<0.01 for both) compared to patients with PTEN-positive BCs. Conclusions: It seems that PTEN status determined by protein expression may discriminate between subgroups with poor and good prognosis in premenopausal HR-positive BC patients receiving adjuvant OA. © 2018 Zerbinis Publications. All Rights Reserved.

Purpose: To investigate the influence of the vaginal packing volume on the registered dose parameters evaluated by radiography (2D) and computed tomography (CT) (3D) based brachytherapy planning in cervical cancer patients treated with postoperative radiotherapy. Methods: The postoperative radiotherapy was performed in 40 cervical cancer patients with increased risk for disease relapse. Both, radiography and CT based brachytherapy planning were done in all patients. Vaginal packing volume was evaluated by clinical target volume (CTV) uk , assessed on CT scans and analyzed according to the registered dose parameters: doses delivered to the organs at risk (OAR) and the defined CTV, using both planning methods. Results: CTV uk volume had statistically significant influence on CTV coverage with the prescribed brachytherapy doses D 90 (p<0.01) and D 100 (p<0.01), revealing a CTV uk cut-off value of 25.6 cm 3 . Dividing the patients into two groups according to the cutoff value, we found a statistical significance in the registered doses to the rectal wall and no significance in the bladder wall doses between the groups. Also, a statistically significant, negative correlation was found between CTV uk and following doses: R max (rho= -0.34, p<0.05), D 0.1cc (rho= -0.76, p<0.01), D 1cc (rho= -0.74, p<0.01) and D 2cc (rho= -0.72, p<0.01), D 90 (rho= -0.80, p<0.01), D 100 (rho= -0.7, p<0.01). Conclusion: If the brachytherapy vaginal packing is of a large volume (more than 25.6 cm 3 ), an asymmetric deformation of the proximal part of the vaginal cavity might appear, leading to inappropriate dose coverage of the CTV part of the vaginal mucosa. Also, making a vaginal packing volume larger than 25.6 cm 3 made no further reduction in the bladder dose, but it made a statistically significant further reduction in the rectal doses. © 2017 Zerbinis Publications. All rights reserved.

Purpose: To investigate the influence of the vaginal packing volume on the registered dose parameters evaluated by radiography (2D) and computed tomography (CT) (3D) based brachytherapy planning in cervical cancer patients treated with postoperative radiotherapy. Methods: The postoperative radiotherapy was performed in 40 cervical cancer patients with increased risk for disease relapse. Both, radiography and CT based brachytherapy planning were done in all patients. Vaginal packing volume was evaluated by clinical target volume (CTV) uk , assessed on CT scans and analyzed according to the registered dose parameters: doses delivered to the organs at risk (OAR) and the defined CTV, using both planning methods. Results: CTV uk volume had statistically significant influence on CTV coverage with the prescribed brachytherapy doses D 90 (p<0.01) and D 100 (p<0.01), revealing a CTV uk cut-off value of 25.6 cm 3 . Dividing the patients into two groups according to the cutoff value, we found a statistical significance in the registered doses to the rectal wall and no significance in the bladder wall doses between the groups. Also, a statistically significant, negative correlation was found between CTV uk and following doses: R max (rho= -0.34, p<0.05), D 0.1cc (rho= -0.76, p<0.01), D 1cc (rho= -0.74, p<0.01) and D 2cc (rho= -0.72, p<0.01), D 90 (rho= -0.80, p<0.01), D 100 (rho= -0.7, p<0.01). Conclusion: If the brachytherapy vaginal packing is of a large volume (more than 25.6 cm 3 ), an asymmetric deformation of the proximal part of the vaginal cavity might appear, leading to inappropriate dose coverage of the CTV part of the vaginal mucosa. Also, making a vaginal packing volume larger than 25.6 cm 3 made no further reduction in the bladder dose, but it made a statistically significant further reduction in the rectal doses. © 2017 Zerbinis Publications. All rights reserved.