Taxanes in adjuvant chemotherapy for early breast cancer.

Adjuvant polychemotherapy improves diseasefree survival and overall survival in women with early breast cancer. A meta-analysis by the Early Breast Cancer Trialists' Collaborative Group (EBCTCG) reported that over 15 years there had been a reduction in recurrence and death in women younger than 50 years who had received adjuvant polychemotherapy [1]. A smaller but still highly significant reduction in the risk of recurrence and death was observed for women aged 50–69 years who received the same treatment. The effect of adjuvant chemotherapy on recurrence was noted mainly during the first 5 years after randomization. The magnitude of effect within this 5-year period was 2.5-times greater for women aged under 50 years compared with women aged 50–59 years. The EBCTCG meta-analysis also compared regimens that contain anthracyclines with no chemotherapy or with the oral combination of cyclophosphamide, methotrexate and 5-fluorouracil (CMF) [1]. The most widely investigated regimens that contain anthracyclines were a combination of cyclophosphamide and 5-fluorouracil with either doxorubicin or epirubicin. The EBCTCG study found that allocation to approximately 6 months of anthracycline-based polychemotherapy reduced the yearly death rate from breast cancer by approximately 38% for women younger than 50 years of age at diagnosis and by approximately 20% for women aged 50–69 years at diagnosis

Neuroendocrine tumor presenting like lymphoma: a case report

INTRODUCTION: Neuroendocrine tumors are a rare but diverse group of malignancies that arise in a wide range of organ systems, including the mediastinum. Differential diagnosis includes other masses arising in the middle mediastinum such as lymphoma, pericardial, bronchogenic and enteric cysts, metastatic tumors, xanthogranuloma, systemic granuloma, diaphragmatic hernia, meningocele and paravertebral abscess. CASE PRESENTATION: We present a case of 42-year-old Caucasian man with a neuroendocrine tumor of the middle-posterior mediastinum and liver metastases, which resembled a lymphoma on magnetic resonance imaging. CONCLUSION: The differential diagnosis in patients with mediastinal masses and liver lesions should include neuroendocrine tumor

REGISTRI: Regorafenib in first-line of KIT/PDGFRA wild type metastatic GIST: a collaborative Spanish (GEIS), Italian (ISG) and French Sarcoma Group (FSG) phase II trial

Wild type GIST; Biomarker; Clinical trialGIST de tipo salvaje; Biomarcador; Ensayo clínicoGIST de tipus salvatge, Biomarcador; Assaig clínicBackground Approximately 15% of adult GIST patients harbor tumors that are wild-type for KIT and PDGFRα genes (KP-wtGIST). These tumors usually have SDH deficiencies, exhibit a more indolent behavior and are resistant to imatinib. Underlying oncogenic mechanisms in KP-wtGIST include overexpression of HIF1α high IGFR signaling through the MAPK pathway or BRAF activating mutation, among others. As regorafenib inhibits these signaling pathways, it was hypothesized that it could be more active as upfront therapy in advanced KP-wtGIST. Methods Adult patients with advanced KP-wtGIST after central confirmation by NGS, naïve of systemic treatment for advanced disease, were included in this international phase II trial. Eligible patients received regorafenib 160 mg per day for 21 days every 28 days. The primary endpoint was disease control rate (DCR), according to RECIST 1.1 at 12 weeks by central radiological assessment. Results From May 2016 to October 2020, 30 patients were identified as KP-wtGIST by Sanger sequencing and 16 were confirmed by central molecular screening with NGS. Finally, 15 were enrolled and received regorafenib. The study was prematurely closed due to the low accrual worsened by COVID outbreak. The DCR at 12 weeks was 86.7% by central assessment. A subset of 60% experienced some tumor shrinkage, with partial responses and stabilization observed in 13% and 87% respectively, by central assessment. SDH-deficient GIST showed better clinical outcome than other KP-wtGIST. Conclusions Regorafenib activity in KP-wtGIST compares favorably with other tyrosine kinase inhibitors, especially in the SDH-deficient GIST subset and it should be taken into consideration as upfront therapy of advanced KP-wtGIST.GEIS, Bayer and SELNET. SELNET has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement Nº. 825806

Patterns of tumor response in canine and feline cancer patients treated with electrochemotherapy: preclinical data for the standardization of this treatment in pets and humans

Electrochemotherapy (ECT) is a novel anticancer therapy that is currently being evaluated in human and pet cancer patients. ECT associates the administration of an anti-tumor agent to the delivery of trains of appropriate waveforms. The increased uptake of chemotherapy leads to apoptotic death of the neoplasm thus resulting in prolonged local control and extended survival. In this paper we describe the histological features of a broad array of spontaneous tumors of companion animals receiving pulse-mediated chemotherapy. Multivariate statistical analysis of the percentage of necrosis and apoptosis in the tumors before and after ECT treatment, shows that only a high percentage of necrosis and apoptosis after the ECT treatment were significantly correlated with longer survivals of the patients (p < 0.0001 and p = 0.004, respectively). Further studies on this topic are warranted in companion animals with spontaneous tumors to identify new molecular targets for electrochemotherapy and to the develop new therapeutical protocols to be translated to humans

The effects of enzalutamide and abiraterone on skeletal related events and bone radiological progression free survival in castration resistant prostate cancer patients: An indirect comparison of randomized controlled trials

Two new drugs, the CYP17 inhibitor abiraterone acetate and the androgen receptor (AR) antagonist enzalutamide, have recently shown to prolong OS prior chemotherapy or in docetaxel treated mCRPC patients, using steroidal therapy or placebo as control group. Updated analyses underlined the role of these new agents on two prostate-specific endpoints as radiographic progression-free survival (rPFS) and time to first skeletal-related event (tSRE). On the basis of these reports, we made an indirect comparison between abiraterone and enzalutamide. We obtained a clinically but not significant difference favouring enzalutamide over abiraterone in terms of rPFS (HR 0.48, 95% CI 0.22â1.02). No significant difference was shown in term of tSRE (HR 0.99, 95% CI 0.83â1.17). In conclusion, abiraterone and enzalutamide have both demonstrated to significantly delay the bone progression resulting in similar improvements in bone-related endpoints in patients with mCRPC

Clinical impact of first-line bevacizumab plus chemotherapy in metastatic colorectal cancer of mucinous histology: a multicenter, retrospective analysis on 685 patients

In metastatic colorectal cancer (MCRC), mucinous histology has been associated with poor response rate and prognosis. We investigated whether bevacizumab combined with different chemotherapy regimens may have an impact on clinical outcomes of MCRC patients with mucinous histology

Biological and clinical effects of abiraterone on anti-resorptive and anabolic activity in bone microenvironment

Abiraterone acetate (ABI) is associated not only with a significant survival advantage in both chemotherapy-naive and -treated patients with metastatic castration-resistant prostate cancer (mCRPC), but also with a delay in time to development of Skeletal Related Events and in radiological skeletal progression. These bone benefits may be related to a direct effect on prostate cancer cells in bone or to a specific mechanism directed to bone microenvironment. To test this hypothesis we designed an in vitro study aimed to evaluate a potential direct effect of ABI on human primary osteoclasts/osteoblasts (OCLs/OBLs). We also assessed changes in bone turnover markers, serum carboxy-terminal collagen crosslinks (CTX) and alkaline phosphatase (ALP), in 49 mCRPC patients treated with ABI.Our results showed that non-cytotoxic doses of ABI have a statistically significant inhibitory effect on OCL differentiation and activity inducing a down-modulation of OCL marker genes TRAP, cathepsin K and metalloproteinase-9. Furthermore ABI promoted OBL differentiation and bone matrix deposition up-regulating OBL specific genes, ALP and osteocalcin. Finally, we observed a significant decrease of serum CTX values and an increase of ALP in ABI-treated patients.These findings suggest a novel biological mechanism of action of ABI consisting in a direct bone anabolic and anti-resorptive activity

TECNOGRAN: TODO PISO SERÁ PALCO. TODA PAREDE, MURAL. E A CIDADE INTEIRA, POESIA.

Este caso apresenta a Tecnogran, empresa paranaense de revestimentos de alto tráfego atuante no segmento de pisos para supermercados, shopping centers, áreas externas, obras públicas e de acessibilidade. O caso descreve o histórico, as características da organização e do setor, abordando impasses enfrentados pela Tecnogran: pressões por preço e demandas de mercado. A empresa é líder no mercado nacional e, apesar disso, encontra dilemas ao buscar se consolidar como inovadora frente a seus concorrentes. O caso é analisado sob as perspectivas das teorias: Estratégias Genéricas e Vantagem Competitiva Ambiental; Teoria Baseada em Recursos; e Teoria de Recursos, Processos e Valores na Inovação. O caso apresenta também as respostas da empresa: inovações em produtos e serviços, e alterações em processos produtivos para manutenção de sua liderança no mercado nacional. As informações para a elaboração do caso foram obtidas por entrevistas semiestruturadas com os gestores da Tecnogran e por dados secundários, tais como publicações, documentos da empresa e sites. Este caso de ensino poderá ser utilizado nas disciplinas de Administração Estratégica, Gestão da Inovação, Marketing e disciplinas correlatas, em cursos de graduação e pós-graduação com foco em negócios de empresas. Os principais objetivos educacionais são: sensibilizar alunos para perceber as estratégias empresariais; analisar os modelos de gestão em busca de vantagem competitiva; identificar modelos estratégicos organizacionais; assinalar a relação entre competências organizacionais e vantagem competitiva sustentável; e compreender a importância e os desafios da inovação para as organizações

Amalgame: Cosmological Constraints from the First Combined Photometric Supernova Sample

Future constraints of cosmological parameters from Type Ia supernovae (SNe Ia) will depend on the use of photometric samples, those samples without spectroscopic measurements of the SNe Ia. There is a growing number of analyses that show that photometric samples can be utilised for precision cosmological studies with minimal systematic uncertainties. To investigate this claim, we perform the first analysis that combines two separate photometric samples, SDSS and Pan-STARRS, without including a low-redshift anchor. We evaluate the consistency of the cosmological parameters from these two samples and find they are consistent with each other to under $1\sigma$. From the combined sample, named Amalgame, we measure $\Omega_M = 0.328 \pm 0.024$ with SN alone in a flat $\Lambda$CDM model, and $\Omega_M = 0.330 \pm 0.018$ and $w = -1.016^{+0.055}_{-0.058}$ when combining with a Planck data prior and a flat $w$CDM model. These results are consistent with constraints from the Pantheon+ analysis of only spectroscopically confirmed SNe Ia, and show that there are no significant impediments to analyses of purely photometric samples of SNe Ia.Comment: Submitting to MNRAS; comments welcom