Avelumab as First-Line Maintenance Treatment in Locally Advanced or Metastatic Urothelial Carcinoma.

This work provides a summary of guideline recommendations and an expert position on the use of maintenance avelumab therapy based on a review of current international clinical practice guidelines for locally advanced or metastatic urothelial carcinoma (UC). A PubMed literature search was conducted in March 2022 (updated in July 2023) to identify guidelines for locally advanced or metastatic UC. An expert panel (four oncologists and one urologist) reviewed the guidelines and clinical evidence, and discussed practical questions regarding the use of avelumab maintenance therapy in this clinical setting. The National Comprehensive Cancer Network, European Association of Urology and European Society for Medical Oncology guidelines recommend first-line cisplatin-containing chemotherapy for cisplatin-eligible patients, carboplatin-gemcitabine for cisplatin-ineligible patients who are fit for carboplatin, or immunotherapy with programmed death ligand-1 (PD-L1) inhibitors (e.g. atezolizumab) in platinum-ineligible patients. Maintenance avelumab is recommended in patients with response/stable disease following chemotherapy (regardless of PD-L1 status). In patients who relapse after/during chemotherapy, options include immunotherapy, erdafitinib [in those with fibroblast growth factor receptor (FGFR) mutations], enfortumab vedotin or further chemotherapy. The expert panel provided the following practical guidance: (1) consider maintenance avelumab in all eligible patients; (2) continue avelumab until disease progression/unacceptable toxicity; (3) ideally, administer six cycles of platinum-based chemotherapy prior to maintenance avelumab; (4) perform radiological evaluation after four chemotherapy cycles and prior to maintenance avelumab; (5) carboplatin-gemcitabine followed by maintenance avelumab is preferred in cisplatin-ineligible patients (regardless of PD-L1 expression), but consider first-line immunotherapy in PD-L1-positive patients and platinum-ineligible patients (regardless of PD-L1 status); and (6) for patients who relapse on avelumab, second-line options include enfortumab vedotin, FGFR inhibitors (in those with FGFR mutations) or clinical trial inclusion. In conclusion, avelumab maintenance therapy is recommended following platinum-based chemotherapy in all eligible patients with locally advanced or metastatic UC, continued until disease progression or unacceptable toxicity.

The Role of Cyclin-Dependent Kinase 4/6 Inhibitors Treatment in Oligometastatic Breast Cancer: A Case Report on a Possible Curative Intent Strategy.

A small but important subset of patients with metastatic breast cancer has an oligometastatic disease. Some of these patients are highly responsive to systemic therapy and have the potential to achieve complete remission with treatment. However, it remains to be clarified the best locoregional and systemic treatment strategy for such patients and what features can determine whose patients are the best candidates. We also don't know what will be the role of cyclin-dependent kinase 4/6 inhibitors in those cases. We report the case of a 41-year-old woman with HR-positive/HER2-negative oligometastatic breast cancer who, after an excellent response to systemic treatment with palbociclib, anastrozole, and goserelin, underwent breast surgery and liver metastasectomy. After completing three years of systemic treatment, the CDK inhibitor was discontinued, maintaining the hormone therapy. The patient remained under regular follow-up with no evidence of disease after eight months.

Metastatic Castration-Resistant Prostate Cancer with BRCA2 Mutation: The Challenge Incorporating PARP Inhibitors and Platinum in Treatment Sequencing.

Prostate cancer is the second most frequent malignancy in men worldwide. Despite the improvement in survival achieved by increasingly early diagnosis and advances in treatment, it is still associated with high mortality. Because of its molecular heterogeneity, there is a need to identify genetic alterations in order to apply targeted therapies. Increasing evidence suggests that the PARP inhibitor olaparib could have a significant synthetic lethal effect in prostate cancer with homologous recombination defects, such as BRCA1/2 mutations. It is not yet known if, under these circumstances, platinum-based chemotherapy induces higher response rates in prostate cancer. We present the case of a patient with BRCA2-mutated metastatic castration-resistant prostate cancer whose treatment sequence included carboplatin and olaparib. LEARNING POINTS: Metastatic castration-resistant prostate cancer (mCRPC) remains a lethal disease despite significant progress in treatment.The BRCA2 mutation is associated with worse survival and so timely genetic screening is important.Studies are needed to identify the best therapeutic sequencing strategy for mCRPC harbouring homologous recombination repair defects, which includes PARP inhibitors and platinum.

Metastatic castration-resistant prostate cancer and the challenge of a patient with chronic kidney disease in hemodialysis

At a time when the population shows increasing longevity, entities such as cancer and chronic kidney disease (CKD) are more frequently connected. In the United States, approximately 6% of the patients on hemodialysis have cancer. The challenge to manage oncologic patients with CKD in a hemodialytic program represents a great shortage of available information on the choice of the best drug, timing, dosage adjustments, dialysis method, and treatment safety. We present the case of a patient with prostate cancer and terminal CKD in hemodialysis, and the treatment sequence after the development of resistance to hormonal blockade therapy, which included docetaxel, enzalutamide, and radium-223.

Metastatic castration-resistant prostate cancer and the challenge of a patient with chronic kidney disease in hemodialysis.

At a time when the population shows increasing longevity, entities such as cancer and chronic kidney disease (CKD) are more frequently connected. In the United States, approximately 6% of the patients on hemodialysis have cancer. The challenge to manage oncologic patients with CKD in a hemodialytic program represents a great shortage of available information on the choice of the best drug, timing, dosage adjustments, dialysis method, and treatment safety. We present the case of a patient with prostate cancer and terminal CKD in hemodialysis, and the treatment sequence after the development of resistance to hormonal blockade therapy, which included docetaxel, enzalutamide, and radium-223.

O Cuidado de enfermagem na prevenção das flebites / Nursing care in the prevention of phlebitis

A flebite é uma complicação com elevada taxa de incidência hospitalar (Mangerote et al. 2011; Urbanetto et al. 2011; Infusion Nurses Society, 2011). As suas consequências são graves para a saúde da pessoa, implicando ainda custos económicos acrescidos. Apesar do conhecimento disponível sobre os vários fatores de risco e sobre as boas práticas recomendadas na prevenção da infeção associada ao cateter venoso, reconhece-se que os resultados tardam em melhorar e se constituem como um desafio para os enfermeiros, Como principais objetivos definiram-se: identificar a percentagem de flebites na venopunção periférica nos doentes internados num serviço de área médica de um hospital central e analisar alguns fatores de risco de flebite. Desenvolveu-se um estudo observacional, descritivo-correlacional. Os dados recolhidos durante 76 dias, através de uma grelha de observação incluíram, entre outras variáveis, as relacionadas com o doente (género e idade), com a medicação (antibioterapia, terapêutica de manutenção e polimedicação) e com os cuidados de enfermagem na inserção e otimização do CVP (calibre, local, higienização das mãos do enfermeiro, desinfetante da pele, fixação, tempo de permanência). Incluíram-se 175 CVP (em 75 doentes), cujos critérios principais foram terem sido introduzidos apenas no serviço de internamento, em doentes adultos. Verificou-se uma taxa de flebite de 37,4% (Grau I ? 6,7%; Grau II ? 17,9%; Grau III ? 9,7%; Grau IV ? 3,1%). A análise das variáveis em estudo permitiu identificar a coexistência de vários fatores de risco, no entanto apenas o tipo de solução desinfetante do local a puncionar revelou correlação estatisticamente significativa com o desenvolvimento de flebite (menor taxa com Álcool 70% do que com Clorohexidina 2%). Os resultados deste estudo fornecem bases para a reflexão sobre os fatores de risco modificáveis, contribuindo para a promoção de estratégias e medidas de melhoria da taxa de flebite.

Prognostic value of MGMT promoter methylation in glioblastoma patients treated with temozolomide-based chemoradiation: a Portuguese multicentre study.

Glioblastoma (GBM) is the most common and aggressive primary brain tumor. The identification of novel molecular prognostic markers of GBM has recently been an area of great interest in neuro-oncology. The methylation status of the MGMT gene promoter is currently a promising molecular prognostic marker, but some controversial data have precluded its clinical use. We analyzed MGMT methylation by methylation-specific PCR in 90 GBM patients from four Portuguese hospitals, uniformly treated with radiotherapy combined with concomitant and adjuvant temozolomide (Stupp protocol). The Kaplan-Meier method was used to construct survival curves, and the log-rank test and a Cox-regression model were used to analyze patient survival. The methylation status of MGMT was successfully determined in 89% (80/90) of the tumors. The frequency of tumoral MGMT promoter methylation was 47.5%. The median overall survivals (OSs) were 16 months (95% CI 12.2-19.8) and 13 months (95% CI 13.3-18.7) for patients whose tumors had a methylated or unmethylated MGMT, respectively. Univariate and multivariate analyses did not show any statistically significant association between MGMT methylation status and patient OS (P=0.583 by the log-rank test; P=0.617 by the Cox-regression test) or progression-free survival (P=0.775 by the log-rank test; P=0.691 by the Cox-regression test). None of the patient clinical features were significantly correlated with survival. This is the first study to report the frequency of MGMT methylation among Portuguese GBM patients. Our data did not show statistically significant associations between MGMT promoter methylation and the outcome of GBM patients treated with temozolomide. Additional robust prospective studies are warranted to clarify whether the MGMT status should be used in clinical decisions.

Evaluation of HER2 in breast cancer: reality and expectations.

BACKGROUND: The introduction of drugs, whose mechanisms of action are directed against specific molecules involved in cancer initiation and/or progression, has changed the daily workup of breast cancer patients. At present, HER2 expression and/or amplification should be evaluated in every primary invasive breast cancer either at the time of diagnosis or at the time of recurrence, mostly to guide selection of trastuzumab in the adjuvant and/or metastatic setting. The adequate selection of patients is an essential step for indication of anti-HER2 therapy. OBJECTIVE: This review focuses on the state of the art for HER2 evaluation in breast cancer, as well as expectations regarding future molecular assays based on mechanisms of resistance to HER2-driven therapy. METHODS: Data were obtained by searching the PubMed database, including the terms 'HER2', 'in situ hybridisation', 'immunohistochemistry', 'trastuzumab', 'breast cancer', 'therapy', 'resistance' and 'tyrosine-kinase inhibitors', with a preference for updated publications. CONCLUSION: Pathologists have a central role in the selection of patients who will benefit from anti-HER-based therapies, with a responsibility to obtain the most reliable results for immunohistochemistry and in situ hybridisation techniques. Pre-analytical variables, such as type of fixative and time of fixation, are critical to guarantee consistent and quality assays, as well as to facilitate interpretation and decrease interobserver variability. Rigorous quality control and centralisation of techniques/interpretation of results are recommended to guarantee consistent assays.