SOnc - Artigos publicados em revistas indexadas na Pubmed/Medline
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- Non-Small Cell Lung Cancer: Screening, Diagnosis, and StagingPublication . Ferreira, J. P.; Magalhães, M.; Rocha, E.; Marques, F.Lung cancer is the leading cause of cancer deaths worldwide. Tobacco consumption is the primary cause of lung cancer, accounting for more than 85% 90% of all lung cancer deaths. Non-small cell lung cancer accounts for about 85% of all lung cancers. Several studies have shown that low-dose helical CT of the lung detects more nodules and lung cancers, including early-stage cancers, than does chest radiography. The National Lung Cancer Screening Trial results show that three annual rounds of low-dose CT screening reduce mortality from lung cancer. Despite the great debate around lung cancer screening, recently the National Comprehensive Cancer Network has come out in favor of lung cancer screening in an updated set of guidelines. All patients who present with suspect lung cancer should have a complete and meticulous history and physical examination performed to identify symptoms or physical findings suggestive of locally extensive or metastatic disease, assess pulmonary health status, identify significant comorbidities, and assess overall health status. Tissue sampling is required to confirm a diagnosis in all patients with suspected lung cancer. Non-surgical approaches, surgical approaches, or both may be used to obtain a tissue sample. Evaluation of the mediastinal lymph nodes is a key step in the further staging of the patient. The best way of evaluating mediastinal lymph nodes is still a matter of debate. The tumor node metastasis (TNM) International Staging System provides useful prognostic information and is used to stage all patients with non-small cell lung cancer. Recent trials added new data on screening and diagnostic approach. Those data will be reviewed in this paper.
- Metastatic Testicular Germ Cell Tumor or a Chemoresponsive Liver Hemangioma?Publication . Ferreira, J.; Magalhães, M.; Esteves, D.; Marques, F.Testicular germ cell tumors are the most common solid organ malignancy in young adult men. The presence of non-pulmonary visceral metastasis is an independent factor that places such patients into the higher risk group. Hepatic hemangiomas are the most common tumors of the liver and are entirely benign. Overlap between these entities may occur, particularly when metastases are hypervascular. We describe a case of a 27-year-old man with a testicular germ cell tumor and a nodule in the right hepatic lobe suggestive of hemangioma. After three cycles of chemotherapy, a size reduction in the hepatic nodule was confirmed, and this lesion was removed. Pathology revealed a fibrosing hemangioma. In this case report, the authors discuss the possible mechanisms for the hemangioma chemotherapy response.
- HIV and HPV infections and ocular surface squamous neoplasia: systematic review and meta-analysisPublication . Carreira, H.; Coutinho, F.; Carrilho, C.; Lunet, N.BACKGROUND: The frequency of ocular surface squamous neoplasias (OSSNs) has been increasing in populations with a high prevalence of infection with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) and infection with human papillomavirus (HPV). We aimed to quantify the association between HIV/AIDS and HPV infection and OSSN, through systematic review and meta-analysis. METHODS: The articles providing data on the association between HIV/AIDS and/or HPV infection and OSSN were identified in MEDLINE, SCOPUS and EMBASE searched up to May 2013, and through backward citation tracking. The DerSimonian and Laird method was used to compute summary relative risk (RR) estimates and 95% confidence intervals (95% CI). Heterogeneity was quantified with the I(2) statistic. RESULTS: HIV/AIDS was strongly associated with an increased risk of OSSN (summary RR=8.06, 95% CI: 5.29-12.30, I(2)=56.0%, 12 studies). The summary RR estimate for the infection with mucosal HPV subtypes was 3.13 (95% CI: 1.72-5.71, I(2)=45.6%, 16 studies). Four studies addressed the association between both cutaneous and mucosal HPV subtypes and OSSN; the summary RR estimates were 3.52 (95% CI: 1.23-10.08, I(2)=21.8%) and 1.08 (95% CI: 0.57-2.05, I(2)=0.0%), respectively. CONCLUSION: Human immunodeficiency virus infection increases the risk of OSSN by nearly eight-fold. Regarding HPV infection, only the cutaneous subtypes seem to be a risk factor.
- Single Jejunum Metastasis from Breast Cancer Arising Twelve Years after the Initial TreatmentPublication . Paiva, C.; Garcia, J.; Silva, C.; Araújo, A.; Araújo, A.; Santos, M.Metastatic involvement of gastrointestinal tract from breast cancer is a rare event. We report the case of a 61-year-old woman presenting with bowel obstruction, related to metastasis of a primary breast cancer she had 12 years earlier (a triple-negative invasive ductal carcinoma treated with surgery and chemotherapy). Bowel obstruction was caused by a 20-centimeter tumor in the jejunum, involving also the transverse colon. The patient underwent en bloc resection of tumor with jejunum and transverse bowel segment and received adjuvant chemotherapy with carboplatin and paclitaxel. Twenty months later, she was alive without disease recurrence.
- Exosomes isolation and characterization in serum is feasible in non-small cell lung cancer patients: critical analysis of evidence and potential role in clinical practicePublication . Taverna, S.; Giallombardo, M.; Gil-Bazo, I.; Carreca, A.; Castiglia, M.; Chacártegui, J.; Araujo, A.; Alessandro, R.; Pauwels, P.; Peeters, M.; Rolfo, C.Exosomes are nano-sized vesicles of endolysosomal origin, released by several cytotypes in physiological and pathological conditions. Tumor derived exosomes, interacting with other cells of the tumor microenvironment, modulate tumor progression, angiogenic switch, metastasis, and immune escape. Recently, extracellular vesicles were proposed as excellent biomarkers for disease monitoring and prognosis in cancer patients. Non-small cell lung cancer (NSCLC) has a poor 5-year survival rate due to the delay in the detection of the disease. The majority of patients are diagnosed in an advanced disease stage. Exosomes might be promising beneficial tools as biomarker candidates in the scenario of NSCLC, since they contain both, proteins and miRNAs. The clinical case reported in this manuscript is a proof of concept revealing that NSCLC exosomes and sorted miRNAs might constitute, in a near future, novel biomarkers. This review summarizes the role of exosomes in NSCLC, focusing on the importance of exosomal microRNAs in lung cancer diagnosis and prognosis.
- Exosomes genetic cargo in lung cancer: a truly Pandora's boxPublication . Reclusa, P.; Sirera, R.; Araujo, A.; Giallombardo, M.; Valentino, A.; Sorber, L.; Bazo, I.; Pauwels, P.; Rolfo, C.Lung cancer is a highly lethal disease. Targeted therapies have been developed in last years, however survival rates are not improving due to the delay in the diagnosis, making biomarkers one of the most interesting fields of study in cancer. Liquid biopsy has raised as an alternative to tissue biopsy due to improvements in analytical techniques for circulating tumor cells (CTCs), cell free DNA and exosomes. Among all, exosomes have raised as one of the most promising tools to understand the tumor due to their stability in the blood and their similarity to the cells of origin. In the last years, different alterations have been described inside the exosomes derived from non-small cell lung cancer (NSCLC) cells mirroring the processes inside these tumoral cells, such as EGFR mutation, translocations or microRNA (miRNA) deregulation. All these studies have opened the window to a new world of possibilities in the study of tumor biomarkers.
- Evidence-Based Treatment Options in Recurrent and/or Metastatic Squamous Cell Carcinoma of the Head and NeckPublication . Argiris, A,; Harrington, K,; Tahara, M,; Schulten, J,; Chomette, P,; Castro, A,; Licitra, L.The major development of the past decade in the first-line treatment of recurrent and/or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN) was the introduction of cetuximab in combination with platinum plus 5-fluorouracil chemotherapy (CT), followed by maintenance cetuximab (the "EXTREME" regimen). This regimen is supported by a phase 3 randomized trial and subsequent observational studies, and it confers well-documented survival benefits, with median survival ranging between approximately 10 and 14 months, overall response rates between 36 and 44%, and disease control rates of over 80%. Furthermore, as indicated by patient-reported outcome measures, the addition of cetuximab to platinum-based CT leads to a significant reduction in pain and problems with social eating and speech. Conversely, until very recently, there has been a lack of evidence-based second-line treatment options, and the therapies that have been available have shown low response rates and poor survival outcomes. Presently, a promising new treatment option in R/M SCCHN has emerged: immune checkpoint inhibitors (ICIs), which have demonstrated favorable results in second-line clinical trials. Nivolumab and pembrolizumab are the first two ICIs that were approved by the US Food and Drug Administration. We note that the trials that showed benefit with ICIs included not only patients who previously received ≥1 platinum-based regimens for R/M SCCHN but also patients who experienced recurrence within 6 months after combined modality therapy with a platinum agent for locally advanced disease. In this review, we outline the available clinical and observational evidence for the EXTREME regimen and the initial results from clinical trials for ICIs in patients with R/M SCCHN. We propose that these treatment options can be integrated into a new continuum of care paradigm, with first-line EXTREME regimen followed by second-line ICIs. A number of ongoing clinical trials are comparing regimens with ICIs, alone and in combination with other ICIs or CT, with the EXTREME regimen for first-line treatment of R/M SCCHN. As we eagerly await the results of these trials, the EXTREME regimen remains the standard of care for the first-line treatment of R/M SCCHN.
- Angiogenesis in NSCLC: is vessel co-option the trunk that sustains the branches?Publication . Coelho, A.; Gomes, M.; Catarino, R.; Rolfo, C.; Lopes, A.; Medeiros, R.; Araújo, A.The critical role of angiogenesis in tumor development makes its inhibition a valuable new approach in therapy, rapidly making anti-angiogenesis a major focus in research. While the VEGF/VEGFR pathway is the main target of the approved anti-angiogenic molecules in NSCLC treatment, the results obtained are still modest, especially due to resistance mechanisms. Accumulating scientific data show that vessel co-option is an alternative mechanism to angiogenesis during tumor development in well-vascularized organs such as the lungs, where tumor cells highjack the existing vasculature to obtain its blood supply in a non-angiogenic fashion. This can explain the low/lack of response to current anti-angiogenic strategies. The same principle applies to lung metastases of other primary tumors. The exact mechanisms of vessel co-option need to be further elucidated, but it is known that the co-opted vessels regress by the action of Angiopoietin-2 (Ang-2), a vessel destabilizing cytokine expressed by the endothelial cells of the pre-existing mature vessels. In the absence of VEGF, vessel regression leads to tumor cell loss and hypoxia, with a subsequent switch to a neoangiogenic phenotype by the remaining tumor cells. Unravelling the vessel co-option mechanisms and involved players may be fruitful for numerous reasons, and the particularities of this form of vascularization should be carefully considered when planning anti-angiogenic interventions or designing clinical trials for this purpose. In view of the current knowledge, rationale for therapeutic approaches of dual inhibition of Ang-2 and VEGF are swiftly gaining strength and may serve as a launchpad to more successful NSCLC anti-vascular treatments.
- Predictive clinical model of tumor response after chemoradiation in rectal cancerPublication . Santos, M.; Silva, C.; Rocha, A.; Nogueira, C.; Castro-Poças, F.; Araujo, A.; Matos, E.; Pereira, C.; Medeiros, R.; Lopes, C.Survival improvement in rectal cancer treated with neoadjuvant chemoradiotherapy (nCRT) is achieved only if pathological response occurs. Mandard tumor regression grade (TRG) proved to be a valid system to measure nCRT response. The ability to predict tumor response before treatment may significantly have impact the selection of patients for nCRT in rectal cancer. The aim is to identify potential predictive pretreatment factors for Mandard response and build a clinical predictive model design. 167 patients with locally advanced rectal cancer were treated with nCRT and curative surgery. Blood cell counts in peripheral blood were analyzed. Pretreatment biopsies expression of cyclin D1, epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF) and protein 21 were assessed. A total of 61 single nucleotide polymorphisms were characterized using the Sequenom platform through multiplex amplification followed by mass-spectometric product separation. Surgical specimens were classified according to Mandard TRG. The patients were divided as: "good responders" (Mandard TRG1-2) and "poor responders" (Mandard TGR3-5). We examined predictive factors for Mandard response and performed statistical analysis. In univariate analysis, distance from anal verge, neutrophil lymphocyte ratio (NLR), cyclin D1, VEGF, EGFR, protein 21 and rs1810871 interleukin 10 (IL10) gene polymorphism are the pretreatment variables with predictive value for Mandard response. In multivariable analysis, NLR, cyclin D1, protein 21 and rs1800871 in IL10 gene maintain predictive value, allowing a clinical model design.
- Real-world data from the Portuguese Nivolumab Expanded Access Program (EAP) in previously treated Non Small Cell Lung Cancer (NSCLC)Publication . Figueiredo, A.; Almeida, M.A.; Almodovar, M.T.; Alves, P.; A, Araujo; Araújo, D.; Barata, F.; Barradas, L.; Barroso, A.; Brito, U.; Camacho, E.; Canário, D.; Cardoso, T.; Chaves, A.; Costa, L.; Cunha, J.; Duarte, J.; Estevinho, F.; Felizardo, M.; Fernandes, J.P.; Ferreira, L.; Ferreira, L.; Fidalgo, Paula; Freitas, C.; Garrido, P.; Gil, N.; Hasmucrai, D.; Jesus, E.; Lopes, J.A.; de Macedo, J.E.; Meleiro, A.; Neveda, R.; Nogueira, F.; Pantorotto, M.; Parente, B.; Pego, A.; Rocha, M.; Roque, J.; Santos, C.; Saraiva, J.; Silva, E.; Silva, S.; Simões, S.; Soares, M.; Teixeira, E.; Timóteo, T.; Hespanhol, V.Objective: The main aim of the study was to evaluate the efficacy and safety profile of Nivolumab, an immune-checkpoint-inhibitor antibody, in advanced, previously treated, Non-Small Cell Lung Cancer (NSCLC) patients, in a real world setting. Methods: We performed a retrospective, multicentre data analysis of patients who were included in the Portuguese Nivolumab Expanded Access Program (EAP). Eligibility criteria included histologically or citologically confirmed NSCLC, stage IIIB and IV, evaluable disease, sufficient organ function and at least one prior line of chemotherapy. The endpoints included Overall Response Rate (ORR), Disease Control Rate (DCR), Progression Free Survival (PFS) and Overall Survival (OS). Safety analysis was performed with the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), version 4.0, and immune-related Adverse Events (irAEs) were treated according to protocol treatment guidelines. Tumour response was assessed using the Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1. Data was analysed using SPSS, version 21.0 (IBM Statistics). Results: From June 2015 to December 2016, a total of 229 patients with advanced NSCLC were enrolled at 30 Portuguese centres. Clinical data were collected up to the end of July 2018. The baseline median age was 64 years (range 37-83) and the majority of patients were males (70.3%) and former/current smokers (69.4%). Patients with non-squamous histology predominated (88.1%), and 67.6% of the patients had received 2 or more prior lines of chemotherapy. Out of 229 patients, data was available for 219 patients (3 patients did not start treatment, while data was unavailable in 7 patients); of the 219 patients, 15.5% were not evaluated for radiological tumour assessment, 1.4% had complete response (CR), 21% partial response (PR), 31% stable disease (SD) and 31.1% progressive disease (PD). Thus, the ORR was 22.4% and DCR was 53.4% in this population. At the time of survival analysis the median PFS was 4.91 months (95% CI, 3.89-6.11) and median OS was 13.21 months (95% CI, 9.89-16.53). The safety profile was in line with clinical trial data. Conclusions: Efficacy and safety results observed in this retrospective analysis were consistent with observations reported in clinical trials and from other centres.
