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Urinary bladder cancer is the fourth most common cancer in men and the eighth in women, being an important public health issue. : Medical files of 155 patients (132M/ 23F) with urinary bladder cancer treated between 2006 and 2012 were retrospectively analyzed. The median age at diagnosis was 65 years (range: 19-85 years). Disease free survival (DFS) for patients with complete tumor resection receiving adjuvant treatment and progression free survival (PFS) for patients with post-operative residual disease was estimated. The distribution of the stage disease was: 50 patients (32.2%) stage II, 47 (30.3%) stage III, 58 (37.4%) stage IV. Radical cystectomy was performed in 56 patients (36.1%), while 99 patients (63.9%) underwent repeated transurethral resection of the urinary bladder tumor (TURBT). Postoperative treatment included multimodal therapy in 47 patients (30.3%) (chemotherapy and external beam radiation), external beam radiation alone in 57 patients (36.8%) and chemotherapy alone (methotrexate, vinblastine, doxorubicin, and cisplatin-MVAC or gemcitabine+platinum) in 51 patients (32.9%). After a median follow-up of 31 months (range: 3-79 months), 51 patients (32.9%) presented local recurrence, 32 patients (21%) distant recurrence (metastases), 10 patients (6.4%) both local and distant recurrence, and 62 patients (40%) were free of disease. The median duration until progression was 27 months. Despite the combined therapy approaches, urinary bladder carcinoma remains an aggressive disease, with a high relapse rate. Earlier diagnosis, aggressive radical surgery in intention to cure (cystectomy), and adjuvant multimodal treatment (radiotherapy and chemotherapy) are needed for survival improvement.

Urinary bladder cancer is the fourth most common cancer in men and the eighth in women, being an important public health issue. to assess the outcome of patients with urinary bladder cancer treated in an oncologic center. Medical files of 155 patients (132M/ 23F) with urinary bladder cancer treated between 2006 and 2012 were retrospectively analyzed. The median age at diagnosis was 65 years (range: 19-85 years). Disease free survival (DFS) for patients with complete tumor resection receiving adjuvant treatment and progression free survival (PFS) for patients with post-operative residual disease was estimated. Stage disease's distribution was: 50 patients (32.2%) stage II, 47 (30.3%) stage III, 58 (37.4%) stage IV. Radical cystectomy was performed in 56 patients (36.1%), while 99 patients (63.9%) underwent repeated transurethral resection of the urinary bladder tumor (TURBT). The postoperative treatment included multimodal therapy in 47 patients (30.3%) (chemotherapy and external beam radiation), external beam radiation alone in 57 patients (36.8%) and chemotherapy alone (methotrexate, vinblastine, doxorubicin, and cisplatin-MVAC or gemcitabine + platinum) in 51 patients (32.9%). After a median follow-up of 31 months (range: 3-79 months), 51 patients (32.9%) presented local recurrence, 32 patients (21%) distant recurrence (metastases), 10 patients (6.4%) both local and distant recurrence, and 62 patients (40%) were free of disease. The median duration until progression was of 27 months. Despite combined therapy approaches, urinary bladder carcinoma remains an aggressive disease, with high relapse rate. Earlier diagnosis and an aggressive radical surgery with the intention to cure (cystectomy), and adjuvant multimodal treatment (radiotherapy and chemotherapy) are needed for survival improvement.

Endobronchial and endotracheal metastases from extra-pulmonary solid tumors are rare. We reported the case of a patient diagnosed with endobronchial and endotracheal metastases from rectal adenocarcinoma. Patient P.G., 62 years old, was diagnosed with a rectal tumor in 2011, for which, a surgical intervention was performed (pT3 pN2a M0, stage IIIB). Afterwards, she underwent adjuvant chemotherapy and concomitant radiochemotherapy. In September 2013, the chest CT showed 2 nodules for which, an incomplete surgical resection was done and which were histopathologically diagnosed as metastases from rectal cancer. The patient continued the treatment with chemotherapy associated with Bevacizumab and after 6 months only Bevacizumab for maintenance. In June 2015, the chest CT pointed out a nodule in the right upper lobe and the bronchoscopy highlighted a 4-5 mm lesion at the level of the right primary bronchus, whose biopsy proved the rectal origin. Afterwards, another surgical intervention was performed. Unfortunately, the postoperative chest CT revealed an intratracheal tissue mass (11/ 7mm) and multiple metastases in the right lung. The bronchoscopy showed 2 endotracheal lesions, out of which one was biopsied (histopathological result of metastasis from rectal cancer). Despite the fact that chemotherapy was continued, other endobronchial lesions appeared. All of them were removed and the patient started radiotherapy on the tracheal area. Afterwards, she refused to continue chemotherapy. The last bronchoscopy highlighted one endobronchial and two endotracheal secondary malignant lesions. Endobronchial and endotracheal metastases must be taken into consideration in all the patients with a history of extra-pulmonary cancer. CT = computed tomography, MRI = magnetic resonance imaging, IMRT = intensity-modulated radiotherapy, ESMO = European Society for Medical Oncology, NCCN = National Comprehensive Cancer Network, iv = intravenous, PET - CT = Positron Emission Tomography - Computed Tomography.

Nowadays, rectal cancer is an important healthcare challenge that affects many thousands of people each year worldwide, being diagnosed especially after the age of 50 years. This study attempted to evaluate the oxidative stress in patients with rectal cancer. 30 patients from the \"Prof. Dr. Al. Trestioreanu\" Institute of Oncology in Bucharest were treated with neoadjuvant radiochemotherapy during 2014 and 2016 and were included in the clinical study. Blood samples were obtained in dynamics during the treatment. From the blood samples, the serum was separated and used to identify the biochemical oxidative stress parameters. Regarding the determination of lipid peroxides, albumin thiols, the cuprum oxidase activity of ceruloplasmin, the values registered in the dynamic of the treatment highlighted their increase to a maximum at the treatment's endpoint due to an important oxidative stress. Regarding the serum values for total antioxidants, the results pointed out the activation of the natural protection systems, which in time were overwhelmed, due to the installed oxidative stress. Part of the cytotoxic effect of radiotherapy was due to the production of oxidative stress. The cell was constantly exposed to the cytotoxic action of the reactive oxygen species. The obtained results indicated the dual relation to which the tumoral cell exposed itself and the installed oxidative stress, respectively, the oxidative stress being a cause or a consequence of the malign transformation. : CT = computed tomography, MRI = magnetic resonance imaging, ESMO = European Society for Medical Oncology, ECOG = performance status scale.

Triple-negative breast cancer (TNBC) has a poor prognosis, even in its early stages. In the absence of postoperative targeted treatments, intensive adjuvant chemotherapy regimens are proposed. For those favorable histologies, such as apocrine and adenoid cystic carcinoma, which frequently belong to TNBC, aggressive treatments are unnecessary. We retrospectively analyzed 631 cases of breast cancer, primary operated curatively, and followed up at our institution for at least 36 months to identify the bio-markers assessable by immunohistochemistry, to be proposed as prognostic score for tailoring adjuvant treatment to TNBC patients. The triple-negative phenotype was found in 85 patients (13.5%). Over a mean followup of 55.7 months, relapses occurred in 106 patients (16.8%), of which 18 (2.8%) were TNBC. Recurrence was directly correlated with Ki67 and cytokeratin 5/6 (CK5/6) immunoreactivity in all breast cancer patients ( =0.005), but only marginally with CK5/6 and epithelial cadherin (E-cad) expression in TNBC patients ( =0.07). Mean event-free survival (EFS) in TNBC patients was 85.52 months compared with 100.4 months in non-TNBC patients ( =0.228). The EFS of CK5/6-negative triple-negative patients was 68.84 months compared with 98.84 months in those who were CK5/6 positive (HR =5.08; =0.038). EFS differed among patients identified as double-positive for E-cad and CK5/6 (83.87 months), those expressing E-cad or CK5/6 (64.23 months), and those negative for both biomarkers (39.64 months). These preliminary results suggest that CK5/6 and E-cad are possible core biomarkers for a cost-effective prognostic evaluation of primary operable TNBC patients.

Weekly paclitaxel (Ptx) and q3w docetaxel (Dtx) are equivalent in adjuvant breast cancer treatment. Weekly Ptx is better tolerated than q3w Dtx and became the first choice in daily practice, even preoperatively. To compare the efficacy and safety of the two regimens, a retrospective analysis was performed in breast cancer patients (pts) referred for neoadjuvant, sequential, taxane-containing chemotherapy to the Institute of Oncology and Oncofort Clinic, Bucharest, between 2008 and 2017. Forty-seven cases were eligible, median age was 56 years (34-73 years), mainly stage IIIA-B (53.2%, 25 pts) and ductal invasive (70.2%, 33 pts) of which 24 pts (51%) received q3w Dtx and 23 pts (48.9%) weekly Ptx. The histological response rates were 62.5% (15 pts) and 73.7% (17 pts) (p=0.47), average dose-intensity was 87.7% and 96.7% (p=0.002) and grade III-IV toxicity rate was 12.5% and 13% (p=0.64), respectively. Pathologic response was correlated with immunophenotype, PgR expression, tumor size and backbone chemotherapy (p<0.05). Our study showed an improved efficacy of taxane's weekly administration, probably due to a better tolerance and a lower rate of dose-impairing toxicities.

This work aims at constraining the size, shape, and geometric albedo of the dwarf planet candidate 2002 MS4 through the analysis of nine stellar occultation events. Using multichord detection, we also studied the object's topography by analyzing the obtained limb and the residuals between observed chords and the best-fitted ellipse. We predicted and organized the observational campaigns of nine stellar occultations by 2002 MS4 between 2019 and 2022, resulting in two single-chord events, four double-chord detections, and three events with three to up to sixty-one positive chords. Using 13 selected chords from the 8 August 2020 event, we determined the global elliptical limb of 2002 MS4. The best-fitted ellipse, combined with the object's rotational information from the literature, constrains the object's size, shape, and albedo. Additionally, we developed a new method to characterize topography features on the object's limb. The global limb has a semi-major axis of 412 \\(\\pm\\) 10 km, a semi-minor axis of 385 \\(\\pm\\) 17 km, and the position angle of the minor axis is 121 \\(^\\circ\\) \\(\\pm\\) 16\\(^\\circ\\). From this instantaneous limb, we obtained 2002 MS4's geometric albedo and the projected area-equivalent diameter. Significant deviations from the fitted ellipse in the northernmost limb are detected from multiple sites highlighting three distinct topographic features: one 11 km depth depression followed by a 25\\(^{+4}_{-5}\\) km height elevation next to a crater-like depression with an extension of 322 \\(\\pm\\) 39 km and 45.1 \\(\\pm\\) 1.5 km deep. Our results present an object that is \\(\\approx\\)138 km smaller in diameter than derived from thermal data, possibly indicating the presence of a so-far unknown satellite. However, within the error bars, the geometric albedo in the V-band agrees with the results published in the literature, even with the radiometric-derived albedo.

Rilotumumab is a fully human monoclonal antibody that selectively targets the ligand of the MET receptor, hepatocyte growth factor (HGF). We aimed to assess the efficacy, safety, and pharmacokinetics of rilotumumab combined with epirubicin, cisplatin, and capecitabine, and to assess potential biomarkers, in patients with advanced MET-positive gastric or gastro-oesophageal junction adenocarcinoma. This multicentre, randomised, double-blind, placebo-controlled, phase 3 study was done at 152 centres in 27 countries. We recruited adults (aged ≥18 years) with unresectable locally advanced or metastatic gastric or gastro-oesophageal junction adenocarcinoma, an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, MET-positive tumours (≥25% of tumour cells with membrane staining of ≥1+ staining intensity), and evaluable disease, who had not received previous systemic therapy. Eligible patients were randomly assigned (1:1) via a computerised voice response system to receive rilotumumab 15 mg/kg intravenously or placebo in combination with open-label chemotherapy (epirubicin 50 mg/m2 intravenously; cisplatin 60 mg/m2 intravenously; capecitabine 625 mg/m2 orally twice daily) in 21-day cycles for up to ten cycles. After completion of chemotherapy, patients continued to receive rilotumumab or placebo monotherapy until disease progression, intolerability, withdrawal of consent, or study termination. Randomisation was stratified by disease extent and ECOG performance status. Both patients and physicians were masked to study treatment assignment. The primary endpoint was overall survival, analysed by intention to treat. We report the final analysis. This study is registered with ClinicalTrials.gov, number NCT01697072. Between Nov 7, 2012, and Nov 21, 2014, 609 patients were randomly assigned to rilotumumab plus epirubicin, cisplatin, and capecitabine (rilotumumab group; n=304) or placebo plus epirubicin, cisplatin, and capecitabine (placebo group; n=305). Study treatment was stopped early after an independent data monitoring committee found a higher number of deaths in the rilotumumab group than in the placebo group; all patients in the rilotumumab group subsequently discontinued all study treatment. Median follow-up was 7·7 months (IQR 3·6–12·0) for patients in the rilotumumab group and 9·4 months (5·3–13·1) for patients in the placebo group. Median overall survival was 8·8 months (95% CI 7·7–10·2) in the rilotumumab group compared with 10·7 months (9·6–12·4) in the placebo group (stratified hazard ratio 1·34, 95% CI 1·10–1·63; p=0·003). The most common grade 3 or worse adverse events in the rilotumumab and placebo groups were neutropenia (86 [29%] of 298 patients vs 97 [32%] of 299 patients), anaemia (37 [12%] vs 43 [14%]), and fatigue (30 [10%] vs 35 [12%]). The frequency of serious adverse events was similar in the rilotumumab and placebo groups (142 [48%] vs 149 [50%]). More deaths due to adverse events occurred in the rilotumumab group than the placebo group (42 [14%] vs 31 [10%]). In the rilotumumab group, 33 (11%) of 298 patients had fatal adverse events due to disease progression, and nine (3%) had fatal events not due to disease progression. In the placebo group, 23 (8%) of 299 patients had fatal adverse events due to disease progression, and eight (3%) had fatal events not due to disease progression. Ligand-blocking inhibition of the MET pathway with rilotumumab is not effective in improving clinical outcomes in patients with MET-positive gastric or gastro-oesophageal adenocarcinoma. Amgen.

The randomised phase 3 TURANDOT trial compared two approved bevacizumab-containing regimens for HER2-negative metastatic breast cancer in terms of efficacy, safety, and quality of life. The interim analysis did not confirm non-inferior overall survival (stratified hazard ratio [HR] 1·04; 97·5% repeated CI [RCI] –∞ to 1·69). Here we report final results of our study aiming to show non-inferior overall survival with first-line bevacizumab plus capecitabine versus bevacizumab plus paclitaxel for locally recurrent or metastatic breast cancer. In this multinational, open-label, randomised phase 3 TURANDOT trial, patients aged 18 years or older who had an Eastern Cooperative Oncology Group performance status 0–2 and measurable or non-measurable HER2-negative locally recurrent or metastatic breast cancer who had received no previous chemotherapy for locally recurrent or metastatic breast cancer were stratified and randomly assigned (1:1) using permuted blocks of size six to either bevacizumab plus paclitaxel (bevacizumab 10 mg/kg on days 1 and 15 plus paclitaxel 90 mg/m2 on days 1, 8, and 15 every 4 weeks) or bevacizumab plus capecitabine (bevacizumab 15 mg/kg on day 1 plus capecitabine 1000 mg/m2 twice daily on days 1–14 every 3 weeks) until disease progression, unacceptable toxicity, or withdrawal of consent. Stratification factors were oestrogen or progesterone receptor status, country, and menopausal status. The primary objective was to show non-inferior overall survival with bevacizumab plus capecitabine versus bevacizumab plus paclitaxel in the per-protocol population by rejecting the null hypothesis of inferiority (HR ≥1·33) using a stratified Cox proportional hazard model. This trial is registered with ClinicalTrials.gov, number NCT00600340. Between Sept 10, 2008, and Aug 30, 2010, 564 patients were randomised, representing the intent-to-treat population. The per-protocol population comprised 531 patients (266 in the bevacizumab plus paclitaxel group and 265 in the bevacizumab plus capecitabine group). At the final overall survival analysis after 183 deaths (69%) in 266 patients receiving bevacizumab plus paclitaxel and 201 (76%) in 265 receiving bevacizumab plus capecitabine in the per-protocol population, median overall survival was 30·2 months (95% CI 25·6–32·6 months) versus 26·1 months (22·3–29·0), respectively. The stratified HR was 1·02 (97·5% RCI –∞ to 1·26; repeated p=0·0070), indicating non-inferiority. The unstratified Cox model (HR 1·13 [97·5% RCI –∞ to 1·39]; repeated p=0·061) did not support the primary analysis. Intent-to-treat analyses were consistent with the per-protocol results. The most common grade 3 or worse adverse events were neutropenia (54 [19%] of 284 patients in the bevacizumab plus paclitaxel group vs 5 [2%] of 277 patients in the bevacizumab plus capecitabine group), hand–foot syndrome (1 [<1%] vs 43 [16%]), peripheral neuropathy (39 [14%] vs 1 [<1%]), leucopenia (20 [7%] vs 1 [<1%]), and hypertension (12 [4%] vs 16 [6%]). Serious adverse events were reported in 65 (23%) of 284 patients receiving bevacizumab plus paclitaxel and 68 (25%) of 277 receiving bevacizumab plus capecitabine. Deaths in two (1%) of 284 patients in the bevacizumab plus paclitaxel group were deemed by the investigator to be treatment-related. No treatment-related deaths occurred in the bevacizumab plus capecitabine group. Bevacizumab plus capecitabine represents a valid first-line treatment option for HER2-negative locally recurrent or metastatic breast cancer, offering good tolerability without compromising overall survival compared with bevacizumab plus paclitaxel. Although progression-free survival with the bevacizumab plus capecitabine combination is inferior to that noted with bevacizumab plus paclitaxel, we suggest that physicians should consider possible predictive risk factors for overall survival, individual's treatment priorities, and the differing safety profiles. Roche.

Coronavirus disease is a global pandemic with millions of confirmed cases and hundreds of thousands of deaths worldwide that continues to create a significant burden on the healthcare systems. The aim of this study was to determine the patient clinical and paraclinical profiles that associate with COVID-19 unfavourable outcome and generate a prediction model that could separate between high-risk and low-risk groups. The present study is a multivariate observational retrospective study. A total of 483 patients, residents of the municipality of Timișoara, the biggest city in the Western Region of Romania, were included in the study group that was further divided into 3 sub-groups in accordance with the disease severity form. Increased age (cOR=1.09, 95% CI: 1.06-1.11, p<0.001), cardiovascular diseases (cOR=3.37, 95% CI: 1.96-6.08, p<0.001), renal disease (cOR=4.26, 95% CI: 2.13-8.52, p<0.001), and neurological disorder (cOR=5.46, 95% CI: 2.71-11.01, p<0.001) were all independently significantly correlated with an unfavourable outcome in the study group. The severe form increases the risk of an unfavourable outcome 19.59 times (95% CI: 11.57-34.10, p<0.001), while older age remains an independent risk factor even when disease severity is included in the statistical model. An unfavourable outcome was positively associated with increased values for the following paraclinical parameters: white blood count (WBC; cOR=1.10, 95% CI: 1.05-1.15, p<0.001), absolute neutrophil count (ANC; cOR=1.15, 95% CI: 1.09-1.21, p<0.001) and C-reactive protein (CRP; cOR=1.007, 95% CI: 1.004-1.009, p<0.001). The best prediction model including age, ANC and CRP achieved a receiver operating characteristic (ROC) curve with the area under the curve (AUC) = 0.845 (95% CI: 0.813-0.877, p<0.001); cut-off value = 0.12; sensitivity = 72.3%; specificity = 83.9%. This model and risk profiling may contribute to a more precise allocation of limited healthcare resources in a clinical setup and can guide the development of strategies for disease management.