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- Symptom Clusters in Patients With Advanced Cancer: a Prospective Longitudinal Cohort Study to Examine Their Stability and Prognostic SignificancePublication . Simão, D; Barata, P; Alves, M; Papoila, AL; Oliveira, S; Lawlor, PThis study's purpose was to assess symptom cluster (SC) stability during disease progression and determine their strength of association with survival in patients with advanced cancer . Consecutively eligible patients with advanced cancer not receiving cancer-specific treatment and referred to a Tertiary Palliative Care Clinic were enrolled in a prospective cohort study. At first consultation (D0) and in subsequent consultations at day 15 (D15) and day 30 (D30), patients rated 9 symptoms through the Edmonton Symptom Assessment System scale (0-10) and 10 others using a Likert scale (1-5). Principal components factor analysis with varimax rotation was used to determine SCs at each consultation. Of 318 patients with advanced cancer, 301 met eligibility criteria with a median age of 69 years (range 37-94). Three SCs were identified: neuro-psycho-metabolic (NPM), gastrointestinal, and sleep impairment, with some variations in their constitution over time. Exploratory factor analysis accounted for 40% of variance of observed variables in all SCs. Shorter median survival was observed continuously for NPM cluster (D0 23 vs. 58 days, P < .001; D15 41 vs. 104 days, P=.004; D30 46 vs. 114 days, P = .002), although the presence of 2 or more SCs on D0 and D15 also had prognostic significance (D0: 21 vs. 45 days, P = .005; D30: 50 vs. 96 days, P = .040). In a multivariable model, NPM cluster (D0 hazard ratio estimate: HR 1.64; 95%CI, 1.17-2.31; P = .005; D15 HR: 2.51; 95%CI, 1.25-5.05; P = .009; D30 HR: 3.9; 95%CI, 1.54-9.86; P = .004) and hospitalization (D0 HR: 2.27; 95%CI, 1.47-3.51; P < .001; D15 HR: 2.43; 95%CI, 1.18-5.01; P = .016; D30 HR: 3.41; 95%CI, 1.35-8.62; P = .009) were independently and significantly associated with worse survival. Three clinically relevant SCs were identified, and their constitution had small variations, maintaining a stable set of nuclear symptoms through disease progression. Presence of the NPM cluster and hospitalization maintained their prognostic value over time.
- Reviewing Treatment Options for Advanced Renal Cell Carcinoma: Is There Still a Place for Tyrosine Kinase Inhibitor (TKI) Monotherapy?Publication . Fontes-Sousa, M; Magalhães, H; Oliveira, A; Carneiro, F; Palma dos Reis, F; Silvestre Madeira, P; Meireles, SRenal cell carcinoma (RCC) comprises a highly heterogeneous group of kidney tumours built upon distinct genetic- and epigenetic-driven mechanisms and molecular pathways. Therefore, responsiveness to treatment is considerably variable across patients, adding an extra layer of complexity to the already challenging therapeutic decision process. The last decade brought an unprecedented shift in the medical approach to advanced or metastatic RCC; in fact, immunotherapy-based combinations have significantly transformed the therapeutic arsenal and clinical outcomes of these patients. These strategies were quickly adopted by international guidelines committees as the new standards of care. However, this enhanced efficacy comes at the expense of tolerability, with a predictable negative impact on patients' quality of life. Moreover, subgroup and post hoc analyses of the major clinical trials have shown that not all patients benefit equally from these innovative approaches. In this context, a group of experts on kidney cancer met and discussed the state of the art in the field, with a special emphasis on the appropriateness of using monotherapy with an anti-angiogenesis tyrosine kinase inhibitor (TKI) to treat specific subgroups of patients with RCC. This article reviews the main topics that were considered to be pertinent for that discussion and establishes the profile of patients for whom TKI monotherapy remains a sensible frontline option by avoiding overtreatment and an unnecessary exposure to treatment-related toxicity.
- Personalized Medicine: Paradigm Shift in ALK Positive Non-Small Cell Lung Cancer: a Case ReportPublication . Barreira, JV; Leão Mendes, J; Parmanande, ABackground: Since the identification of multiple therapeutic targets, as is the case of anaplastic lymphoma kinase (ALK) translocation, the paradigm of treating patients with non-small cell lung cancer (NSCLC) has improved. In order to guarantee the possibility of longer survival outcomes with a better quality of life we must invest in the determination, in suitable time, of the consensual biomarkers and in the availability of the best treatments to our patients. Case presentation: We present a case of a caucasian male in his fifth decade of life, non-smoker, who highlights the complex journey of ALK-positive patients. This particular case, demonstrates the efficacy and tolerability of the new ALK target therapies, allowing our patients to maintain their routines without compromising the effectiveness of the therapy. Conclusion: Focusing on the reality of ALK positive patients and the impact that this therapy has on the daily lives of our patients, we can contribute to the awareness of this specific pathology.
- Hyperleukocytosis in Solid Tumors: a Rare Paraneoplastic Syndrome Associated with Poor PrognosisPublication . Ferrão, J; Sardinha, M; Dutra, EHematological paraneoplastic syndromes are fairly uncommon. While mild leukocytosis in solid tumors is well reported, white blood cell (WBC) count over 50,000 u/L, described as paraneoplastic leukemoid reaction (PLR), is not. Indeed, when found, it is usually associated with a higher burden of disease, tumor activity and worse clinical outcomes. We report the case of a challenging and burdensome diagnosis of a presumptive hematological paraneoplastic syndrome in a patient with a locally advanced lung cancer admitted in the Internal Medicine ward. After the end of chemotherapy, clinical and laboratory benefit was observed; however, the aggressive course of the disease became clear, with progression and downhill course that was unresponsive to treatment.
- Myocardial Work Brings New Insights into Left Ventricular Remodelling in Cardio-Oncology PatientsPublication . Vaz Ferreira, V; Mano, T; Cardoso, I; Coutinho Cruz, M; Branco, LM; Almeida-Morais, L; Timóteo, AT; Galrinho, A; Castelo, A; Garcia Brás, P; Simão, D; Sardinha, M; Gonçalves, A; Cruz Ferreira, RSerial transthoracic echocardiographic (TTE) assessment of 2D left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS) are the gold standard screening methods for cancer therapeutics-related cardiac dysfunction (CTRCD). Non-invasive left ventricular (LV) pressure-strain loop (PSL) provides a novel method of quantifying myocardial work (MW) with potential advantages to evaluate the impact of cardiotoxic treatments on heart function. We prospectively assessed breast cancer female patients undergoing cancer therapy through serial monitoring by 2D and 3D TTE. Patients were evaluated at T0, T1 and T2 (before, 4-6 and 12-14 months after starting therapy, respectively). Through PSL analysis, MW indices were calculated. A total of 122 patients, with a mean age of 54.7 years, who received treatment with anthracyclines (77.0%) and anti-HER2 (75.4%) were included. During a mean follow-up of 14.9 ± 9.3 months, LVEF and GLS were significantly diminished, and 29.5% developed CTRCD. All MW indices were significantly reduced at T1 compared with baseline and tended to return to baseline values at T2. Global work index and global work efficiency showed a more pronounced variation in patients with CTRCD. The presence of more than one cardiovascular risk factor, obesity and baseline left atrium volume were predictors of changes in MW parameters. In conclusion, breast cancer treatment was associated with LV systolic dysfunction as assessed by MW, with its peak at 4-6 months and a partial recovery afterwards. Assessment of myocardial deformation parameters allows a more detailed characterization of cardiac remodelling and could enhance patient screening and selection for cardioprotective therapeutics.
- What Has Changed During the COVID-19 Pandemic? - The Effect on an Academic Breast Department in PortugalPublication . Simão, D; Sardinha, M; Reis, AF; Spencer, AS; Luz, R; Oliveira, SIntroduction: One year ago, Portugal entered its first lockdown because of the coronavirus disease-2019 (COVID-19) pandemic. The impact of this on delays in cancer diagnosis and treatment is a major concern, which may negatively affect the outcomes of these patients. Materials and methods: This retrospective, single-center analysis compared the clinical and pathological characteristics of breast cancer (BC) patients referred to a medical oncology first appointment between March 2020 and 2021, with the same period in the previous year. Results: Strikingly, there was a 40% reduction in the number of BC patients during lockdown. However, there was a statistically significant increase in the proportion of metastatic BC patients admitted for the first time for systemic therapy (13.6% vs. 28.9%, p = 0.003). Additionally, a statistically significant increase in the number of patients with bilateral early BC at diagnosis after March 2020 was found (7.2% vs. 1.9%, p = 0.043). Conclusion: These findings support international recommendations for an accelerated restoration of BC screening, to reduce incidence of advanced breast cancer at diagnosis and mitigate the expected impact of the COVID-19 pandemic on patients with cancer. Further work is needed to examine in detail the impact of measures to manage the COVID-19 pandemic on breast cancer outcomes.
- Managing Severe Dysgeusia and Dysosmia in Lung Cancer Patients: a Systematic Scoping ReviewPublication . Spencer, AS; Silva Dias, D; Capelas, ML; Pimentel, F; Santos, T; Neves, PM; Mäkitie, A; Ravasco, PIntroduction: Lung cancer (LC) is highly prevalent worldwide, with elevated mortality. In this population, taste and smell alterations (TSAs) are frequent but overlooked symptoms. The absence of effective therapeutic strategies and evidence-based guidelines constrain TSAs' early recognition, prevention and treatment (Tx), promoting cancer-related malnutrition and jeopardizing survival outcomes and quality of life. Objectives: To systematically review the literature on TSAs in LC patients, understand the physiopathology, identify potential preventive and Tx strategies and to further encourage research in this area. Methods: Literature search on English language articles indexed to PubMed, CINALH, SCOPUS and Web of Science using MeSH terms "Lung neoplasms","Dysgeusia", "Olfaction Disorders", "Carcinoma, Small Cell","Carcinoma, Non- Small-Cell Lung "Adenocarcinoma of Lung","Carcinoma, Large Cell", and non-MeSH terms "Parageusia", "Altered Taste", "Smell Disorder", "Paraosmia", "Dysosmia","Lung Cancer" and "Oat Cell Carcinoma". Results: Thirty-four articles were reviewed. TSAs may follow the diagnosis of LC or develop during cancer Tx. The estimated prevalence of self-reported dysgeusia is 35-38% in treatment-naïve LC patients, and 35-69% in those undergoing Tx, based on studies involving LC patients only.One prospective pilot trial and 1 RCT demonstrated a clinically significant benefit in combining flavor enhancement, smell and taste training and individualized nutritional counselling; a systematic review, 1 RCT and 1 retrospective study favored using intravenous or oral zinc-based solutions (150mg 2-3 times a day) for the prevention and Tx of chemotherapy (CT) and radiotherapy (RT) -induced mucositis and subsequent dysgeusia. Conclusions: This is the first review on dysgeusia and dysosmia in LC patients to our knowledge. We propose combining taste and smell training, personalized dietary counselling and flavor enhancement with oral zinc-based solutions (150mg, 2-3 times a day) during CT and/or RT in this population, in order to prevent and help ameliorate Tx-induced dysgeusia and mucositis. However due to study heterogeneity, the results should be interpreted with caution. Developing standardized TSA measurement tools and performing prospective randomized controlled trials to evaluate their effect are warranted.
- Full Recovery of a Stage IV Cancer Patient Facing COVID-19 PandemicPublication . Parmanande, A; Simão, D; Sardinha, M; Palma dos Reis, AF; Spencer, AS; Barreira, JV; Luz, RCoronavirus disease 2019 (COVID-19), first recognized in Wuhan, China, was recently declared a global pandemic by the World Health Organization (WHO). Advanced age and comorbid disease, well-known characteristics in the solid tumor population, have been reported as risk factors for severe disease and death. Cancer-related immunosuppression and its treatments also seem to play an active role in the prognosis, response, and clinical outcomes of these patients. The most effective combination therapy for COVID-19 is still under investigation, and the use of corticosteroids is controversial. Although, as a group, metastatic cancer patients are often considered not to be good candidates for ICU treatment, the individual prognosis should always come into consideration, even in a context of high pressure on medical facilities. We report the case of a stage IV prostate cancer patient infected with SARS-CoV-2 who required ICU admission and recovered from COVID-19 infection. Further studies are needed in order to identify accurate clinical prognostic criteria and provide the best treatment for these challenging patients.
- Unknown Primary Merkel Cell Carcinoma With Cutaneous SpreadPublication . Barreira, JV; Valejo Coelho, M; Ribeiro, C; Semedo, MThe authors present the case of a woman in the seventh decade of life with medical history of: left nephrectomy for renal tuberculosis and non-Hodgkin's lymphoma treated with chemotherapy (QT) and radiotherapy. She presented with a 2-month history of non-tender, left inguinal lymph node enlargement. Positron Emission Tomography (PET)-CT -scanshowed hypermetabolic inguinal and retroperitoneal lymphadenopathies, no primary tumour. On the second dermatological examination a pink, 2 cm plaque on the anterior left knee was noted. The histopathological analysis revealed Merkel cell carcinoma. The patient underwent two lines of systemic QT, with life-threatening toxicities limiting treatment. Followed overwhelming disease progression with lymphoedema and numerous skin metastases in the left lower limb. The patient received palliative care until death. The rare incidence of such neoplasia and its uncommon clinical presentation justifies reporting this case and highlights the importance of multidisciplinary teams in the management of cancer patients.
- Three-Dimensional Speckle-Tracking Echocardiography for the Global and Regional Assessments of Left Ventricle Myocardial Deformation in Breast Cancer Patients Treated with AnthracyclinesPublication . Coutinho Cruz, M; Branco, LM; Portugal, G; Galrinho, A; Timóteo, AT; Rio, P; Ilhão Moreira, R; Mendonça, T; Leal, A; Gameiro, F; Duarte Oliveira, S; Luz, R; Cruz Ferreira, RBackground: Assessment of 2D/3D left ventricular ejection fraction (LVEF) and 2D global longitudinal strain (GLS) is the gold standard for diagnosing cancer therapeutics-related cardiac dysfunction (CTRCD). Although 3D speckle-tracking echocardiography (STE) has several advantages, it is not used in this setting. Methods: 105 breast cancer patients who underwent serial echocardiographic assessment during anthracycline therapy were included. STE was used to estimate 2D GLS, 3D GLS, 3D global circumferential strain (GCS), 3D global radial strain (GRS), and 3D global area strain (GAS). CTRCD was defined as an absolute decrease in 2D/3D LVEF > 10% to a value < 54% or a relative decrease in 2D GLS > 15%. Results: 24 patients developed CTRCD. There was a significant worsening of all 3D strain parameters during chemotherapy. 3D strain regional analysis showed impaired contractility in the anterior, inferior, and septal walls. Variations of 3D GRS and 3D GCS were associated with a higher incidence of CTRCD and the variation of 3D GRS was an independent predictor of CTRCD. Variations of 3D GCS and 3D GRS had a good discrimination for predicting CTRCD, with optimal cutoff values of - 34.2% for 3D GCS and - 34.4% for 3D GRS. These variations were observed 45 and 23 days before the diagnosis of CTRCD, respectively. Conclusion: Variations of 3D strain parameters were predictive of and preceded CTRCD, and thus have added value over currently recommended 2D/3D LVEF and 2D GLS. Routine application of this technique should be considered to offer targeted monitoring and timely initiation of cardioprotective treatment.
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