Clinical outcomes of an intraoperative surgical margin assessment using the fresh frozen section method in patients with invasive breast cancer undergoing breast-conserving surgery - a single center analysis.

Breast conserving treatment (BCT) is a safe standard therapeutic method in patients with early invasive breast cancer. However, it is associated with an increased risk of residual neoplastic tissues in surgical margins. The aim of this study was to assess the outcome of the use of the intraoperative pathologic analysis by the frozen section (FS) method for evaluation of the extent of the primary lumpectomy. The study concerns a retrospective analysis of a group of 1102 patients who underwent BCT between Jan 2015 and Dec 2016. The assessment focused on the frequency of the intraoperative pathologic analysis of the primary lumpectomy extent (fresh frozen section method). The influence of the BCT specimen analysis method on the free margins width, as well as the rate and the cause of reoperation were evaluated. The intraoperative lumpectomy evaluation was performed in 45.8% (505/1102) of patients (Group I), while in the remaining 54.2% of the cases it was decided to abandon this procedure (Group II). Although in 72 (14.3%) patients the intraoperative analysis gave negative results, the margins contained residual tumor tissue (vs. 16.9% in Group II). In Group I, conversion from the previously planned BCT to mastectomy was necessary in 5.9% (30/505) patients (vs. 9.7% in Group II). The duration of surgery was 48.9 ± 17.3 minutes (Group I) and 42.9 ± 13.6 minutes (Group II). In patients undergoing BCT, the use of the intraoperative pathologic analysis by the FS method resulted in a reduction of the total number of reoperations performed due to residual tumor found in the margins following the primary lumpectomy. However, it statistically significantly extended the duration of the surgery.

Osteopontin And Angiogenic Factors As New Biomarkers Of Prostate Cancer.

PURPOSE: The novel biomarkers that would identify patients at risk for relapse and metastatic spread are needed. The aim of this study was the evaluation of serum levels of osteopontin (OPN) and tumor endogenous angiogenic factors such as vascular-endothelial growth factor (VEGF), vascular-endothelial growth factor receptor 2 (VEGF R2), endostatin, angiostatin and thrombospondin 1, in prostate cancer (PC) patients. MATERIAL AND METHODS: Blood concentrations of the analyzed parameters were determined in 40 prostate cancer patients eligible for radiotherapy as well as in the control group consisted of 25 volunteers. Commercial ELISA kits were used for the analysis. RESULTS: Significantly higher levels of OPN (101.49 ng/mL vs 59.88 ng/mL; P<.001), endostatin (252.60 ng/mL vs. 223.55 ng/mL; P=.043), angiostatin (47 ng/mL vs. 13 ng/mL; P=.047), VEGF (262.1 pg/mL vs. 138.0 pg/mL; P=.056) and VEGF R2 (11188.81 pg/mL vs. 9377.50 pg/mL; P=.047) were detected in PC patients compared with the control group. In PC patients we showed a positive correlation between OPN level and TNM clinical stage(R=0.36; P=.02) and negative correlation between OPN level and hemoglobin concentration (R=-0.33; P=.04). CONCLUSION: The study showed higher levels of the angiogenic factors in PC patients compared with the control group and identified OPN as an indicator of the PC clinical stage as well as a decreased hemoglobin level.

15O-H2O PET/CT as a tool for the quantitative assessment of early post-radiotherapy changes of heart perfusion in breast carcinoma patients.

OBJECTIVE: Studies examining radiation-induced heart toxicity in breast cancer patients are inconclusive. The aim of this study was to prospectively and quantitatively asses myocardial blood flow (MBF) with, for the first time, 15O-H2O PET/CT as a marker of heart damage in irradiated breast cancer patients. METHODS: 15 breast cancer patients receiving intact breast or chest wall irradiation were included in the analysis (six with right-sided and nine with left-sided breast cancer). They underwent 15O-H2O PET/CT before radiotherapy (RT) and 2 and 8 months after RT. MBF was quantitatively assessed at rest and under stress conditions in 17 heart segments distinguished according to the American Ultrasound Association classification. Regional MBF values were derived in each of the coronary artery territories. RESULTS: MBF decreased in 53% and increased in 33% of cases 2 months after RT in both left-sided and right-sided breast cancer patients. Stress testing was more sensitive than at-rest testing, demonstrating decreased perfusion in the segments supplied by the left anterior descending coronary artery (LAD) [5.41 ± 1.74 vs 4.52 ± 1.82 ml (g*min)-1; p = 0.018], which persisted at 6 months [5.41 ± 1.74 vs 4.40 ± 1.38 ml (g*min)-1; p = 0.032] and a decrease in global heart perfusion [5.14 ± 1.49 vs 4.46 ± 1.73 ml (g*min)-1; p = 0.036]. A minimal radiation dose applied to the LAD correlated with MBF changes observed 2 months after RT (r = -0.57; p = 0.032). Radiological findings were not correlated with clinical symptoms of heart toxicity. CONCLUSION: 15O-H2O PET/CT is safe and effective for the early detection and quantitative analysis of subclinical post-RT changes in heart perfusion in breast cancer patients. The LV segments supplied by the LAD are the main site of MBF changes. A minimum radiation dose deposited in the LAD may be a predictor of radiation-induced heart toxicity. Advances in knowledge: This is the first time that 15O-H2O PET/CT has been used to assess MBF after RT and the first granular description of the distribution of blood flow changes after breast cancer RT.

Fertility impairment in radiotherapy.

Infertility as a result of antineoplastic therapy is becoming a very important issue due to the growing incidence of neoplastic diseases. Routinely applied antineoplastic treatments and the illness itself lead to fertility disorders. Therapeutic methods used in antineoplastic treatment may cause fertility impairment or sterilization due to permanent damage to reproductive cells. The risk of sterilization depends on the patient's sex, age during therapy, type of neoplasm, radiation dose and treatment area. It is known that chemotherapy and radiotherapy can lead to fertility impairment and the combination of these two gives an additive effect. The aim of this article is to raise the issue of infertility in these patients. It is of growing importance due to the increase in the number of children and young adults who underwent radiotherapy in the past. The progress in antineoplastic therapy improves treatment results, but at the same time requires a deeper look at existential needs of the patient. Reproductive function is an integral element of self-esteem and should be taken into account during therapy planning.

The Sum of Tumour-to-Brain Ratios Improves the Accuracy of Diagnosing Gliomas Using 18F-FET PET.

Gliomas are common brain tumours, but obtaining tissue for definitive diagnosis can be difficult. There is, therefore, interest in the use of non-invasive methods to diagnose and grade the disease. Although positron emission tomography (PET) with 18F-fluorethyltyrosine (18F-FET) can be used to differentiate between low-grade (LGG) and high-grade (HGG) gliomas, the optimal parameters to measure and their cut-points have yet to be established. We therefore assessed the value of single and dual time-point acquisition of 18F-FET PET parameters to differentiate between primary LGGs (n = 22) and HGGs (n = 24). PET examination was considered positive for glioma if the metabolic activity was 1.6-times higher than that of background (contralateral) brain, and maximum tissue-brain ratios (TBRmax) were calculated 10 and 60 min after isotope administration with their sums and differences calculated from individual time-point values. Using a threshold-based method, the overall sensitivity of PET was 97%. Several analysed parameters were significantly different between LGGs and HGGs. However, in a receiver operating characteristics analysis, TBR sum had the best diagnostic accuracy of 87% and sensitivity, specificity, and positive and negative predictive values of 100%, 72.7%, 80%, and 100%, respectively. 18F-FET PET is valuable for the non-invasive determination of glioma grade, especially when dual time-point metrics are used. TBR sum shows the greatest accuracy, sensitivity, and negative predictive value for tumour grade differentiation and is a simple method to implement. However, the cut-off may differ between institutions and calibration strategies would be useful.

The role of postoperative radiotherapy in prostate cancer patients.

AIM OF THE STUDY: The aim of the study was to evaluate the effectiveness of postoperative radiotherapy in prostate cancer patients with unfavorable prognostic factors. MATERIAL AND METHODS: In the years 2002-2008, 121 consecutive prostate cancer patients underwent radical prostatectomy and postoperative radiotherapy. The median dose was 64 Gy (range: 60-72 Gy). Biochemical and clinical progression-free survival were estimated. Univariate and multivariate analyses were used to analyze clinicopathological variables associated with treatment failure. RESULTS: The median follow-up was 27 months. Three-year bPFS was 72%. On univariate analysis it was influenced by: extracapsular tumor extension (60% vs. 75%, p = 0.0232), seminal vesicles invasion (52% vs. 85%, p = 0.00041), Gleason score ≥ 7 (65% vs. 86%, p = 0.044) and the use of hormonal therapy (50% vs. 80%, p = 0.0058). On multivariate analysis bPFS was associated with: TNM stage (HR = 3.19), postoperative hormonal therapy (HR = 2.6), total irradiation dose (HR = 0.82) and the maximum pretreatment level of prostate-specific antigen (PSA) (HR = 0.95). Three-year cPFS was 84%. On univariate analysis it was influenced by: preoperative PSA level > 10 ng/ml (75% vs. 90%, p = 0.04), vascular-nerve bundles involvement (63% vs. 88%, p = 0.0031), adjacent organs infiltration (50% vs. 85%, p = 0.018) and the use of postoperative hormonal therapy (62% vs. 90%, p = 0.02). On multivariate analysis cPFS was associated with: TNM stage (HR = 2.68), postoperative hormonal therapy (HR = 3.61) and total irradiation dose (HR = 0.78). CONCLUSIONS: Postoperative radiotherapy in patients with unfavorable prognostic factors provides good biochemical and local control. Total irradiation dose and postoperative hormonal therapy are important treatment factors influencing prognosis.

The side effects of hormonal therapy at the patients with prostate cancer.

Prostate cancer is one of most frequent malignant tumours at men. The androgen-deprivation therapy is the part of cancer treatment. It could be used both in the early stage of prostate cancer and in the bone metastates. From this reason the antiandrogen drugs waste systematically grows. Unfortunately androgen-deprivation therapy has numerous side effects such as: the inferior quality of live, sexual disturbances, the fatigue, the anaemia, the bone mineral density loss and the increase of the risk of breaks the bone, the increase of body mass, insulinresistance, hypercholesterolemia, the increase risk of cardiac disorders. The aim of this article is the introduction of the reader with possibly complications androgen-deprivation therapy and with possibilities in diagnosis and treatment.

Comparative analysis of biological profiles of benign prostate hyperplasia and prostate cancer as potential diagnostic, prognostic and predictive indicators.

The prognosis in prostate cancer depends on several clinical-morphological factors, such as Gleason score, pTNM and preoperative PSA level. Reliable biological markers are being sought to supplement clinical-morphological data in order to better predict prognosis and to select an individualized therapeutic option. The aim of this study was a comparative analysis of the expression of biological markers, such as Hif-1α, bcl-2, p53, Ki-67, cyclin D1 and CD44 in BPH and prostate cancer, as well as examining their association with standard prognostic factors in prostate cancer. The immunohistochemical analysis was made on 82 formalin-fixed, paraffin- embedded tissue blocks: 43 prostate cancer specimens derived from patients who had undergone radical resection, and 39 prostate bioptates derived from patients with BPH. A positive correlation was demonstrated between Gleason score and the expression of both Hif-1α (R = 0.32, p 〈 0.05) and Ki-67 (R = 0.30, p 〈 0.05). Additionally, a negative correlation was demonstrated between tumor stage (pTNM) and bcl-2 expression (R = -0.35, p 〈 0.05). Hif-1α as a hypoxia marker and Ki-67 as a proliferation marker, both correlated with Gleason score, may constitute important additional prognostic indicators in prostate cancer patients.

Psoriasis exacerbation after hormonotherapy in prostate cancer patient-Case report.

Psoriasis, as the most common inflammatory skin disorder, affects about 2-3% of the world's population. Many non-dermatological conditions have been linked with psoriasis, including cardiovascular diseases, depression, inflammatory bowel disorders, and some cancers, i.e. lung, colon and kidney cancers. Among systemic factors are endocrine and metabolic disturbances as well as many drugs. Erythrodermic psoriasis, the most severe form of the disease, is characterized by diffuse erytrema and scaling, often accompanied by fever, chills, and malaise. A 57-year-old Caucasian man was admitted for curative radiation therapy of adenocarcinoma of the prostate after 3 months of initial hormonal therapy. The management comprised the combined androgen blockade (CAB). On admission the patient reported escalation of psoriasis symptoms, which he had been treated for since 2002. Due to a mild course of the disease he had not required any systemic treatment ever before, even during aggravation periods. The last exacerbation started appearing a month after hormonal therapy implementation. The cutaneous eruptions, already existing, become larger with new foci revealing, mainly on upper and lower limbs. During radiotherapy planning, there appeared a diffuse erythema and scaling on hands and feet with accompanying pruritis. We decided to start the previously planned radiation therapy which included the prostate gland with 1.5 cm margin and provided for the total dose of 72 Gy in 36 fractions. The irradiation was conducted with the four-field technique using a megavoltage linear accelerator. During radiotherapy we photo-documented skin lesions. To our best knowledge hormone therapy (androgen deprivation) of prostate cancer patients has not been reported as an aggravating factor. Thus, the aim of our work is to present the case of a prostate cancer patient who experienced psoriasis exacerbation after implementation of hormonal blockade as a neoadjuvant oncological treatment.

Response of U87 glioma xenografts treated with concurrent rapamycin and fractionated radiotherapy: possible role for thrombosis.

BACKGROUND AND PURPOSE: Rapamycin, a highly specific mTOR inhibitor, has shown anti-proliferative and anti-angiogenic properties, as well as an enhancement in tumour growth delay when used in combination with radiation in mouse xenograft models. Our goal was to determine if rapamycin can also have a positive effect on the local tumour control achieved by radiotherapy. MATERIALS AND METHODS: Nude mice bearing U87 glioblastoma xenografts were treated with concomitant rapamycin and radiotherapy over a 5 day fractionation schedule. Animals received graded total doses ranging from 24 to 100 Gy. Experimental endpoints were tumour growth delay and local tumour control. In addition, histological evaluation of tumour sections was performed to examine changes occurring within the tumour microenvironment as a result of treatment. Analysis of proliferation, mTOR signalling, hypoxia, and vessel thrombosis was conducted. RESULTS: As a single agent, rapamycin reduced the in vitro growth of U87 cells by 70% and caused a 4 day growth delay of tumour xenografts. In combination with radiation, no further increase in tumour growth delay was observed when compared to radiation alone. The tumour control dose 50% (TCD(50)) was 46.8 Gy (95% CI 41; 53 Gy) in tumours treated with radiation alone and was slightly but not significantly lower at 42.8 Gy (95% CI 36; 49 Gy) after simultaneous treatment with rapamycin. Histological evaluation revealed evidence of elevated hypoxia following rapamycin treatment that may be due to vessel thrombosis. CONCLUSIONS: The influence of rapamycin on thrombosis and tumour hypoxia may be a confounding factor limiting its effectiveness in combination with radiotherapy.