Late side effects of 3T MRI-guided 3D high-dose rate brachytherapy of cervical cancer : Institutional experiences.

PURPOSE: This article reports experiences with 3T magnetic resonance imaging(MRI)-guided brachytherapy (BT) for cervical cancer focusing on late side effects. METHODS: Between June 2012 and March 2017 a total of 257 uterovaginal BT administrations were performed in 61 consecutive patients with inoperable cervical cancer. All patients were treated with BT combined with external beam radiotherapy. RESULTS: The mean HR-CTV (high risk-clinical target volume) D90 was 87 ± 5.1 Gy equivalent dose corresponding to the conventional fractionation using 2 Gy per fraction (EQD2, range 70.7-97.9 Gy). The mean doses in OAR (organs at risk), namely rectum, sigmoid and bladder were D2 cm3rectum = 62.6 ± 6.9 Gy EQD2 (range 38.2-77.2 Gy), D2 cm3sigmoid = 66.2 ± 6.8 Gy EQD2 (43.2-78.6 Gy) and D2 cm3bladder = 75.1 ± 8.3 Gy EQD2 (58.2-92.6 Gy). There were no signs of late gastrointestinal (GI) toxicity in 49 patients, grade 3 toxicity was seen in 2 patients and grade 4 toxicity in 3 patients. There were no signs of late genitourinary (GU) toxicity in 41 patients, grade 3 toxicity was seen in 4 patients and no signs of grade 4 toxicity were seen. After the treatment, 60 patients (98.4%) achieved locoregional remission. In 54 patients (88.5%) the remission was complete, whereas in 6 patients (9.8%) remission was partial. CONCLUSION: The use of 3T MRI-guided BT leads to achievement of high rates of local control with limited late morbidity as demonstrated in this series of patients.

Prognostic value of c-MET in head and neck cancer: A systematic review and meta-analysis of aggregate data.

OBJECTIVES: The hepatocyte growth factor (HGF)/mesenchymal-epithelial transition factor (c-MET) ligand/receptor axis has been implicated in pathogenesis of malignant diseases including squamous cell carcinoma of the head and neck (SCCHN). Overexpression of c-MET has been reported as a common molecular abnormality in SCCHN, although its prognostic and predictive value remains to be validated. METHODS: We systematically searched literature for studies evaluating c-MET expression on immunohistochemistry in newly diagnosed, non-metastatic SCCHN. The c-MET expressing cases were classified into three categories according to predefined cut-off values for positivity. Our aim was to assess the prevalence of c-MET expression and its relationship with selected clinicopathological variables. RESULTS: Twenty-eight studies with 2019 cases were included. Relative frequencies of c-MET expression above cut-off levels I, II, and III were 81.8%, 63.8%, and 46.2%, respectively. Differences between these three values were statistically significant (p<1.0×10-6). Above cut-off level II, c-MET positivity was associated with worse overall survival (p=4.0×10-6), positive nodal status (p=1.0×10-4), higher disease stage (p=7.0×10-4), older age (p=2.1×10-3), disease recurrence (p=2.0×10-2), and primary tumour localization in the oral cavity (p=2.3×10-2). Above cut-off level III, c-MET positivity was associated with worse disease-free or progression-free survival (p=9.0×10-6), p16 negativity (p=2.4×10-4), worse overall survival (p=4.0×10-4), positive epidermal growth factor receptor (EGFR) status (p=7.2×10-4), and larger primary tumours (p=4.6×10-3). CONCLUSION: In SCCHN, immunohistochemical overexpression of c-MET above cut-off levels III and particularly II was associated with inferior survival outcomes and advanced disease. Moreover, it represents a promising predictive biomarker for c-MET targeting, yet the optimal scoring method remains to be defined.

The impact of PET/CT scanning on the size of target volumes, radiation exposure of organs at risk, TCP and NTCP, in the radiotherapy planning of non-small cell lung cancer.

AIM: To compare radiotherapy plans made according to CT and PET/CT and to investigate the impact of changes in target volumes on tumour control probability (TCP), normal tissue complication probability (NTCP) and the impact of PET/CT on the staging and treatment strategy. BACKGROUND: Contemporary studies have proven that PET/CT attains higher sensitivity and specificity in the diagnosis of lung cancer and also leads to higher accuracy than CT alone in the process of target volume delineation in NSCLC. MATERIALS AND METHODS: Between October 2009 and March 2012, 31 patients with locally advanced NSCLC, who had been referred to radical radiotherapy were involved in our study. They all underwent planning PET/CT examination. Then we carried out two separate delineations of target volumes and two radiotherapy plans and we compared the following parameters of those plans: staging, treatment purpose, the size of GTV and PTV and the exposure of organs at risk (OAR). TCP and NTCP were also compared. RESULTS: PET/CT information led to a significant decrease in the sizes of target volumes, which had the impact on the radiation exposure of OARs. The reduction of target volume sizes was not reflected in the significant increase of the TCP value. We found that there is a very strong direct linear relationship between all evaluated dosimetric parameters and NTCP values of all evaluated OARs. CONCLUSIONS: Our study found that the use of planning PET/CT in the radiotherapy planning of NSCLC has a crucial impact on the precise determination of target volumes, more precise staging of the disease and thus also on possible changes of treatment strategy.

The relationship between some soluble osteogenic markers, angiogenic cytokines/other biological parameters and the stages of multiple myeloma evaluated according to the Durie-Salmon and International Prognostic Index stratification systems.

BACKGROUND: The aim of the present paper was to examine the correlation between serum concentrations of 12 soluble biological markers and stages of myeloma evaluated according to the Durie-Salmon (D-S) and International Prognostic Index (IPI) stratification systems. METHODS: We analyzed a non-pretreated group of 179 patients with MM stratified according to D-S and IPI. Serum levels of soluble biological markers were evaluated using ELISA, REA and quantitative sandwich enzymatic immunoassays. The data were analyzed using the Kruskal-Wallis and Mann-Whitney U tests. RESULTS: The staging system according to D-S revealed a highly significant relationship between all stages (I-III) in case of beta(2)-m (p<0.0001) and sTK (p<0.001), in sICTP a significant difference was found only in stages II vs III (p<0.001) and I vs III (p<0.001), in case of sCD(138) (syndecan-1) in stages I vs II (p = 0.006) and I vs III (p<0.001), in sVEGF only in stages I vs III (p = 0.006). In substages A vs B we found a significant difference in case of beta2-m (p<0.0001), sTK (p = 0.041), sICTP (p 0.0001), sOSP (p = 0.008), sHGF (p<0.001), sCD138 (p = 0.001) and sFas (p= 0.001). The relationship between other factors and stages and substages according to D-S appeared nonsignificant. The IPI system showed a highly significant relationship between all 3 categories (1-3) in case of beta(2)-m (p<0.001), sTK (p<0.0001) and sICTP (p<0.0001), while in sHGF only in stages 2 vs 3 (p<0.0001) and 1 vs 3 (p<0.0001). In 4 parameters there were only discrete differences in 1 vs 3: sPINP (p= 0.036), sOSP (p= 0.002), sCD(138) (p = 0.03) and sFas (p=0.012), in the remaining markers the analysis was negative. CONCLUSIONS: A highly convincing relationship between myeloma stages and serum levels was found only in beta(2)-m, sTK, sICTP and partly also in sCD(138) (syndecan-1) and sHGF. More favourable was the IPI stratification system.

The correlation of serum immunoglobulin free light chain levels and selected biological markers in multiple myeloma.

AIMS: the presented study is aimed at the evaluation of correlation of free light chains serum levels - kappa, lambda and their relation (K/L ratio) and serum levels of selected biological markers in a group of patients with multiple myeloma examined at the time of the diagnosis. METHODS: 102 patients with multiple myeloma were included in this prospective study. Free light chains serum levels were determined by Freelite Binding Site system, for determination of serum levels of selected parameters the following methods were used: REA thymidinekinase (TK), RIA (beta(2)microglobulin (beta(2)m), ICTP, PINP), enzymoimmunoassay (sIL-6R, sVCAM-1, sICAM-1, sOPG) and quantitative enzymatic immunoassay (sHGF, sVEGF, sSyndecan-1 (sSyn-1) a sFas). RESULTS: There was found a correlation in the kappa-group of the dominant kappa chain and serum readings of beta(2)m (r = 0.344, p = 0.005), TK (r = 0.263, p = 0.035), ICTP (r = 0.402, p = 0.001), PINP (r = 0.264, p = 0.039), sOPG (r = 0.328, p = 0.028), sSyn-1 (r = 0.255, p = 0.046) and sFas (r = 0.418, p = 0.001). In case of K/L ratio there was found a statistically significant association of levels of beta(2)m (r = 0.316, p = 0.01), TK (r = 0.274, p = 0.027), ICTP (r = 0.346, p = 0.006), PINP (r = 0.261, p = 0.042), sSyn-1 (r = 0.283, p = 0.026) and sFas (r = 0.377, p = 0.002). In the lambda-group the analysis confirmed mutual dependence of the dominant lambda chain levels on beta(2)m (r = 0.476, p = 0.003), ICTP (r = 0.375, p = 0.022), sVCAM-1 (r = 0.383, p = 0.019), sHGF (r = 0.441, p = 0.006) and sFas (r = 0.334, p = 0.040). In addition we ascertained a correlation of L/K ratio and levels of beta(2)m (r = -0.473, p = 0.003), TK (r = -0.412, p = 0.011), ICTP (r = -0.331, p = 0.045), PINP (r = -0.409, p = 0.012), sHGF (r = -0.357, p = 0.028), sSyn-1 (r = -0.449, p = 0.005) a sFas (r = - 0.371, p = 0.022). CONCLUSIONS: The study confirmed mutual correlation of FLC serum levels and the levels of several selected biological markers, in particular beta(2)m, TK, ICTP, PINP, sSyn-1 a sFas at time of the diagnosis. It referred to the mutual relation of bone marrow microenvironment, biological qualities of clonal plasmocytes and the intensity of the free light chains production by the tumour cell population.

Retrospective analysis of 25 women with malignant cystosarcoma phyllodes--treatment results.

PURPOSE: Mastectomy without axillary dissection should be the standard treatment in patients with malignant form of cystosarcoma phyllodes. The role of postoperative radiotherapy and chemotherapy remains to be fully established. We evaluate treatment results in a group of patients with cystosarcoma phyllodes (CP) treated at our Institute. PATIENTS AND METHODS: In this report we analyze treatment outcome in 25 patients with malignant cystosarcoma phyllodes treated at Masaryk Memorial Cancer Institute between 1970 and 1995. Mean tumor size was 10 cm in diameter. All patients underwent surgery. Subsequently, 17 patients (68%) received radiotherapy on the breast or chest wall. RESULTS: Median follow-up was 139.5 months. Local recurrence was observed in 16% of all patients and all patients with local recurrence died. Time to local relapse after surgery was 4-11 months. Distant metastases occurred in 5 patients. All patients with local recurrence had distant metastases. Dissemination occurred 3-19 months after local recurrence. Five-year survival of all patients was 80%. CONCLUSION: A specific protocol for the treatment of cystosarcoma phyllodes is missing, probably due to rarity of the disease. The treatment of local recurrent disease remains unsuccessful in most CP patients. We recommend postoperative irradiation on the chest wall in patients with malignant form of CP, because adjuvant radiotherapy decreased the incidence of local relapse in our group of patients.

Monitoring of bone resorption and bone formation in multiple myeloma.

The article deals with the clinical value of monitoring of serum markers of osteoresorption (ICTP) and bone formation (PICP) in multiple myeloma. In a group of patients treated by conventional chemotherapy and group of patients treated by high dose chemotherapy with autologous peripheral blood stemm cell transplantation (APBSTC).