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- Adjuvant Hyperthermic Intravesical Chemotherapy in Intermediate- and High-Risk Non-muscle Invasive Bladder CancerPublication . Magalhães, Joana C; Sousa, Maria João; Basto, Raquel; Fraga, Teresa; Gomes, Inês; Fernandes, Catarina; Mariano, Mónica; Paulo, Judy; Madeira, Pedro; Sousa, GabrielaIntroduction: Non-muscle invasive bladder cancer (NMIBC) is a frequently diagnosed neoplasm, which is typically managed with transurethral resection of bladder tumor (TURBT) eventually followed by intravesical therapies. Bacillus Calmette-Guérin (BCG) is used as first-line adjuvant treatment in high- (HR) and intermediate-risk (IR) NMIBC, although, in the latter, mitomycin C (MMC) may also be used. Multiple limitations to the use of BCG encouraged the search for therapeutic alternatives. In this context, hyperthermic intravesical chemotherapy with MMC (HIVEC-MMC) emerged as a promising therapy in the adjuvant setting for NMIBC. The aim of our study was to evaluate the tolerability, compliance, and survival outcomes of HIVEC-MMC in patients with IR- and HR-NMIBC. Material and methods: This was a single-center retrospective analysis of IR- and HR- NMIBC patients who received HIVEC-MMC after TURBT between August 2018 and August 2022. Levels of risk stratification were defined using the European Association of Urology (EAU) criteria. The protocol consisted of four weekly HIVEC-MMC instillations (induction) followed by six monthly instillations (maintenance). The primary outcomes were to evaluate the tolerability and compliance with the HIVEC-MMC protocol and secondary outcomes were disease-free survival (DFS) and overall survival (OS). For the purpose of statistical analysis, methods of descriptive statistics, survival analysis (Kaplan-Meier estimation), and multivariate analysis (Cox regression, and binary logistic regression) were used. Results: Fifty-seven patients were enrolled with a median age of 67.9 (34.4-83.5) years old. In this cohort, 40 patients (70.2%) had primary tumors. At the time of referral for HIVEC-MMC, the majority of the patients had IR-NMIBC (n= 33, 57.9%). A total of 41 patients (71.9%) completed the HIVEC-MMC protocol. Disease recurrence and adverse events (AEs) were the most common reasons to stop the protocol. After a median follow-up of 31 months (95% CI, 5.0-54.0), 32 patients (61.4%) were disease-free, 22 (38.6%) experienced recurrent disease and six patients (10.5%) died, although only one death was directly attributable to bladder cancer. The median DFS was 42 months (95% CI, 28.0-56.0). Completion of the HIVEC-MMC maintenance phase protocol stood as a predictive factor for DFS (44 months, 95% CI 29.1-58.9 vs. 14 months, 95% CI 0.0-29.6, p < 0.001; HR 4.48, 95% CI 1.65-12.15). The median OS was not reached; the 24- and 48-month OS were 92.6% and 82.7%, respectively. EAU risk group, ECOG-PS, and completion of HIVEC protocol were found to be significant predictive factors of OS but lost their significance on multivariate analysis. However, if we exclude those who experienced recurrence during the maintenance phase protocol, treatment completion had a significant positive impact on OS (HR: 42.8, 95% CI 1.75-1045.072, p= 0.021). Conclusions: Our study suggests that HIVEC is a secure and well-tolerated treatment with promising efficacy data, making this therapeutic approach a feasible option in IR- and HR-NMIBC patients, mainly in those who cannot tolerate or have contraindications to BCG therapy, but also as an alternative during BCG shortages.
- 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.
- O cancro no concelho de Santa Maria da FeiraPublication . Araujo, A.
- A Challenge Called Ogilvie´s SyndromePublication . Soares Miranda, Luisa; Silva Gonçalves, Carla; Silva, Ezequiel; Ferreira, Álvaro; Araújo Correia, João; Cruz, Ana RitaOgilvie´s syndrome is a colonic dilation without any existing mechanical obstruction. The risk factors that cause it are not completely understood, but if untreated, the distension can result in rupture or ischaemic bowel perforation. Additionally, the existing guidelines do not agree with each other about the next steps if conservative treatment fails. We report the case of a 71-year-old woman in whom Ogilvie´s syndrome was particularly difficult to manage, and with it, we try to add clinical data to a field with scarce evidence.
- Classic DMARD’s, biologic drugs and cancer riskPublication . Araujo, A.
- Clinical practice: approaching the reality of individual patientsPublication . Araujo, A.
- Diagnóstico e Tratamento do Cancro do Pulmão: Estado da ArtePublication . Araujo, A.
- Evaluation of Current Antiemetic Therapy Response in Patients Undergoing MEC or HEC Regimens in PortugalPublication . A, Araujo; Tavares, Nuno; Faria, Ana Luísa; Gomes, Rosa; Mendonça, Joana Carvalho; Parente, Bárbara; Capela, Andreia; Barata, Fernando; Macedo, AnaChemotherapy-induced nausea and vomiting (CINV) negatively impact cancer patients' quality of life and treatment outcomes. This study evaluated the achievement of complete response to CINV prophylaxis during the first five days after chemotherapy in adult outpatient cancer clinics with solid malignant tumours receiving Moderate or Highly Emetogenic Chemotherapy (MEC or HEC) in Portugal. During the study, patients completed three evaluations, and nausea severity and CINV impact on patients' daily life was assessed. A complete response (no emetic episodes, no use of rescue antiemetic medication, and no more than mild nausea) was observed in 72% of the cycles (N = 161) throughout the five days after chemotherapy. Amongst the patient population, 25% classified their CINV episodes as severe. Though more than half of the patients achieved a complete response, suggesting that a therapeutic effort is being made to minimise this side effect, the overall scenario is barely optimistic. Significantly, new CINV-control measures in MEC/HEC patients should be adopted, specifically avoiding the single use of dexamethasone and 5-HT3 and raising awareness of using NK1-RAs. Thus, it is critical to improve CINV prophylactic treatment and implement practical international antiemetic guidelines in Portuguese clinical practice, envisaging the improvement of supportive care for cancer patients.
- 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.
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