Prevention of nausea and vomiting in patients undergoing oral anticancer therapies for solid tumors

Copyright © 2015 Ana Lúcia Costa et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Chemotherapy-induced nausea and vomiting (CINV) is still a common and debilitating side effect despite recent advances in its prevention and treatment. The intrinsic emetogenicity of chemotherapy agents allowed grouping into four risk groups (high, moderate, low, and minimal risk of emetogenicity). The prevention of acute and delayed CINV for intravenous agents and one day regimens is well studied, although, there are few data about management of CINV induced by oral cytotoxic agents and targeted therapies, usually administered in extended regimens of daily oral use. Until now treatment of nausea and vomiting caused by oral antineoplastic agents remains largely empirical. The level of evidence of prophylactic antiemetics recommended for these agents is low. There are differences in the classification of emetogenic potential of oral antineoplastic agents between the international guidelines and different recommendations for prophylactic antiemetic regimens. Herein we review the evidence for antiemetic regimens for the most used oral antineoplastic agents for solid tumors and propose antiemetic regimens for high to moderate risk and low to minimal risk of emetogenicity.info:eu-repo/semantics/publishedVersio

Enhanced biomethane production by co-digestion of mixed sewage sludge and dephenolised two-phase olive pomace

Original articleIn this study, co-digestion of mixed sewage sludge from a wastewater treatment plant (WWTP) and partially dephenolised twophase olive pomace (DOP) as a co-substrate was addressed with the aim of improving the biodigestibility of both substrates. The introduction of DOP into WWTP anaerobic digester facilities could significantly increase biomethane production and enhance the sustainability of both activities. An improvement in the system’s performance was supported by stability parameters: total alkalinity increased and stabilised with the addition of 5% v/v DOP, and the specific energy loading rate was maintained at 0.177 ± 0.03 d−1, which indicated better buffer capacity and stability in the bioreactor, and the possibility of enhancing the organic loading rate. In terms of average daily biogas production rate, an increase of 39% was achieved, up to 0.39 ± 0.11 L L−1d−1. Moreover, there was a 40% and 37% improvement in specific methane production and methane production rate, respectively, up to 0.28 ± 0.02 L CH4 g TVS −1 and 0.26 ± 0.08 L L−1d−1. In addition, the proposed strategy leads to an energy saving of 20,328.6 kWh year−1 at the WWTP as a result of the electric energy production surplus, corresponding to an annual saving of €3293.23info:eu-repo/semantics/publishedVersio

Bone metastasis risk factors in breast cancer

Copyright: © the authors; licensee ecancermedicalscience. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Bone is the single most frequent site for bone metastasis in breast cancer patients. Patients with bone-only metastasis have a fairly good prognosis when compared with patients with visceral disease. Nevertheless, cancer-induced bone disease carries an important risk of developing skeletal related events that impact quality of life (QoL). It is therefore particularly important to stratify patients according to their risk of developing bone metastasis. In this context, several risk factors have been studied, including demographic, clinicopathological, genetic, and metabolic factors. Most of them show conflicting or non-definitive associations and are not validated for clinical use. Nonetheless, tumour intrinsic subtype is widely accepted as a major risk factor for bone metastasis development and luminal breast cancer carries an increased risk for bone disease. Other factors such as gene signatures, expression of specific cytokines (such as bone sialoprotein and bone morphogenetic protein 7) or components of the extracellular matrix (like bone crosslinked C-telopeptide) might also influence the development of bone metastasis. Knowledge of risk factors related with bone disease is of paramount importance as it might be a prediction tool for triggering the use of targeted agents and allow for better patient selection for future clinical trials.info:eu-repo/semantics/publishedVersio

Chemoradiotherapy completion and neutropenia risk in HIV patients with cervical cancer

Copyright © 2018 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. http://creativecommons.org/licenses/by/4.0Cervical cancer (CC) is one of the acquired immunodeficiency syndrome (AIDS) defining diseases and the human immunodeficiency virus (HIV) infection is thought to relate with increased acute toxicity of chemoradiotherapy (CRT). We investigated the effect of HIV status in the incidence of neutropenia associated with cisplatin-based CRT for CC and its impact in treatment completion. This is a single-center retrospective cohort study. Data collection was performed for all the consecutive stage Ib-IV CC women treated with cisplatin-based CRT from 2012 to 2016, and with known HIV status. Sixty-one patients were included, 6 were HIV+. HIV+ patients had a higher risk of neutropenia at any cycle during cisplatin CRT [adjusted odds ratio (OR) 7.3, 95% confidence interval (95% CI) 1.02–52.3; P = .05]. Despite the absolute differences, mean neutrophil count was nonsignificantly lower in HIV+ women, both at baseline [4455/μL (interquartile range, IQR: 1830–6689) vs 6340 (IQR: 1720–18,970) for HIV−, P = .98] and at the end of treatment [1752/μL (IQR: 1100–2930) vs 3147/μL (IQR: 920–18,390) in HIV−; P = .06]. Moreover, when considering the effect of time, CRT seems to induce a consistent drop of neutrophils in both groups (P = .229). No febrile neutropenia events occurred. In HIV+ women, there were more CT cycle delays (P = .013), patients were more prone to use granulocyte colony-stimulating factor (G-CSF; HIV+ 40.0% vs HIV− 4.0%; P = .04) and less likely to complete at least 5 cycles of cisplatin (P = .02). All patients received adequate dose of pelvic RT, regardless of HIV status. HIV+ patients have a significantly increased risk of neutropenia during CRT treatment for CC and are less likely to complete chemotherapy with cisplatin.info:eu-repo/semantics/publishedVersio

Preference for the fixed-dose combination of pertuzumab and trastuzumab for subcutaneous injection in patients with HER2-positive early breast cancer (PHranceSCa): a randomized, open-label phase II study

Aim The aim of the study was to assess patient preference for the fixed-dose combination of pertuzumab and trastuzumab for subcutaneous injection (PH FDC SC) in patients with HER2-positive early breast cancer in PHranceSCa (NCT03674112). Materials and methods Patients who completed neoadjuvant P + H + chemotherapy + surgery were randomised 1:1 to three intravenous (IV) P + H cycles followed by three cycles of PH FDC SC or vice versa (crossover) and then chose subcutaneous (SC) injection or IV infusion to continue up to 18 cycles (continuation). Assessments were via patient and healthcare professional (HCP) questionnaires. Results One hundred and sixty patients were randomised (cut-off: 24 February 2020); 136 (85.0%, 95% confidence interval: 78.5–90.2%) preferred SC; 22 (13.8%) preferred IV; 2 (1.3%) had no preference. The main reasons for SC preference were reduced clinic time (n = 119) and comfort during administration (n = 73). One hundred and forty-one patients (88.1%) were very satisfied/satisfied with SC injection versus 108 (67.5%) with IV infusion; 86.9% chose PH FDC SC continuation. HCP perceptions of median patient treatment room time ranged from 33.0–50.0 min with SC and 130.0–300.0 min with IV. Most adverse events (AEs) were grade 1/2 (no 4/5s); serious AE rates were low. AE rates before and after switching were similar (cycles 1–3 IV → cycles 4–6 SC: 77.5% → 72.5%; cycles 1–3 SC → cycles 4–6 IV: 77.5% → 63.8%). Conclusion Most patients strongly preferred PH FDC SC over P + H IV. PH FDC SC was generally well tolerated, with no new safety signals (even when switching), and offers a quicker alternative to IV infusion

Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK.

BACKGROUND: A safe and efficacious vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), if deployed with high coverage, could contribute to the control of the COVID-19 pandemic. We evaluated the safety and efficacy of the ChAdOx1 nCoV-19 vaccine in a pooled interim analysis of four trials. METHODS: This analysis includes data from four ongoing blinded, randomised, controlled trials done across the UK, Brazil, and South Africa. Participants aged 18 years and older were randomly assigned (1:1) to ChAdOx1 nCoV-19 vaccine or control (meningococcal group A, C, W, and Y conjugate vaccine or saline). Participants in the ChAdOx1 nCoV-19 group received two doses containing 5 × 1010 viral particles (standard dose; SD/SD cohort); a subset in the UK trial received a half dose as their first dose (low dose) and a standard dose as their second dose (LD/SD cohort). The primary efficacy analysis included symptomatic COVID-19 in seronegative participants with a nucleic acid amplification test-positive swab more than 14 days after a second dose of vaccine. Participants were analysed according to treatment received, with data cutoff on Nov 4, 2020. Vaccine efficacy was calculated as 1 - relative risk derived from a robust Poisson regression model adjusted for age. Studies are registered at ISRCTN89951424 and ClinicalTrials.gov, NCT04324606, NCT04400838, and NCT04444674. FINDINGS: Between April 23 and Nov 4, 2020, 23 848 participants were enrolled and 11 636 participants (7548 in the UK, 4088 in Brazil) were included in the interim primary efficacy analysis. In participants who received two standard doses, vaccine efficacy was 62·1% (95% CI 41·0-75·7; 27 [0·6%] of 4440 in the ChAdOx1 nCoV-19 group vs71 [1·6%] of 4455 in the control group) and in participants who received a low dose followed by a standard dose, efficacy was 90·0% (67·4-97·0; three [0·2%] of 1367 vs 30 [2·2%] of 1374; pinteraction=0·010). Overall vaccine efficacy across both groups was 70·4% (95·8% CI 54·8-80·6; 30 [0·5%] of 5807 vs 101 [1·7%] of 5829). From 21 days after the first dose, there were ten cases hospitalised for COVID-19, all in the control arm; two were classified as severe COVID-19, including one death. There were 74 341 person-months of safety follow-up (median 3·4 months, IQR 1·3-4·8): 175 severe adverse events occurred in 168 participants, 84 events in the ChAdOx1 nCoV-19 group and 91 in the control group. Three events were classified as possibly related to a vaccine: one in the ChAdOx1 nCoV-19 group, one in the control group, and one in a participant who remains masked to group allocation. INTERPRETATION: ChAdOx1 nCoV-19 has an acceptable safety profile and has been found to be efficacious against symptomatic COVID-19 in this interim analysis of ongoing clinical trials. FUNDING: UK Research and Innovation, National Institutes for Health Research (NIHR), Coalition for Epidemic Preparedness Innovations, Bill & Melinda Gates Foundation, Lemann Foundation, Rede D'Or, Brava and Telles Foundation, NIHR Oxford Biomedical Research Centre, Thames Valley and South Midland's NIHR Clinical Research Network, and AstraZeneca

Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK

Background A safe and efficacious vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), if deployed with high coverage, could contribute to the control of the COVID-19 pandemic. We evaluated the safety and efficacy of the ChAdOx1 nCoV-19 vaccine in a pooled interim analysis of four trials. Methods This analysis includes data from four ongoing blinded, randomised, controlled trials done across the UK, Brazil, and South Africa. Participants aged 18 years and older were randomly assigned (1:1) to ChAdOx1 nCoV-19 vaccine or control (meningococcal group A, C, W, and Y conjugate vaccine or saline). Participants in the ChAdOx1 nCoV-19 group received two doses containing 5 × 1010 viral particles (standard dose; SD/SD cohort); a subset in the UK trial received a half dose as their first dose (low dose) and a standard dose as their second dose (LD/SD cohort). The primary efficacy analysis included symptomatic COVID-19 in seronegative participants with a nucleic acid amplification test-positive swab more than 14 days after a second dose of vaccine. Participants were analysed according to treatment received, with data cutoff on Nov 4, 2020. Vaccine efficacy was calculated as 1 - relative risk derived from a robust Poisson regression model adjusted for age. Studies are registered at ISRCTN89951424 and ClinicalTrials.gov, NCT04324606, NCT04400838, and NCT04444674. Findings Between April 23 and Nov 4, 2020, 23 848 participants were enrolled and 11 636 participants (7548 in the UK, 4088 in Brazil) were included in the interim primary efficacy analysis. In participants who received two standard doses, vaccine efficacy was 62·1% (95% CI 41·0–75·7; 27 [0·6%] of 4440 in the ChAdOx1 nCoV-19 group vs71 [1·6%] of 4455 in the control group) and in participants who received a low dose followed by a standard dose, efficacy was 90·0% (67·4–97·0; three [0·2%] of 1367 vs 30 [2·2%] of 1374; pinteraction=0·010). Overall vaccine efficacy across both groups was 70·4% (95·8% CI 54·8–80·6; 30 [0·5%] of 5807 vs 101 [1·7%] of 5829). From 21 days after the first dose, there were ten cases hospitalised for COVID-19, all in the control arm; two were classified as severe COVID-19, including one death. There were 74 341 person-months of safety follow-up (median 3·4 months, IQR 1·3–4·8): 175 severe adverse events occurred in 168 participants, 84 events in the ChAdOx1 nCoV-19 group and 91 in the control group. Three events were classified as possibly related to a vaccine: one in the ChAdOx1 nCoV-19 group, one in the control group, and one in a participant who remains masked to group allocation. Interpretation ChAdOx1 nCoV-19 has an acceptable safety profile and has been found to be efficacious against symptomatic COVID-19 in this interim analysis of ongoing clinical trials

Exploring genomic copy number variation analysis to stratify recurrence risk of early-stage breast carcinoma

Tese de mestrado, Oncobiologia, Universidade de Lisboa, Faculdade de Medicina, 2019BACKGROUND Adjuvant chemotherapy (CT) reduces the risk of relapse in early breast cancer (BC); however, there is uncertainty about its benefit in intermediate risk patients. Molecular profiling tests help guiding clinical decision. METHODS We performed a non-interventional, retrospective, cohort study, with 48 intermediate risk BC patients, using a copy number variation (CNV) assay to characterize intermediate risk early BC, stratify relapse risk and predict CT benefit. For positive control we also analyzed 9 patients in the node-positive cohort, 10 in the epidermal growth factor eceptor 2 (HER2) positive cohort and 3 in the triple negative cohort. The median follow-up in the intermediate risk cohort was 108.57 months. RESULTS We confirmed CNV analysis is feasible in archival formalin-fixed paraffinembedded tumor specimens and its robustness and analytical validity with digital droplet polymerase chain reaction analysis. Among intermediate risk BC patients, an inverse correlation was detected between CNV scores and relapse-free survival (RFS) (p=0.253 for CNVScore and EventsMajorScore, and p=0.466 for EventsScore). Multivariate analysis identified CNVScore, EventsScore, EGFR CNV, CDKN1A CNV and JUN CNV as variables significantly associated with a decrease in RFS. In the multinomial logistic regression, anthracycline-based CT improved RFS for all tested variables when compared with no anthracycline (p=0.102). Through multinomial logistic regression, we developed a prognostic model, including log2 EGFR CNV and log2 CCND1 CNV, achieving a p-value of 0.002 and a goodness of fit by Pearson correlation of 0.983. This model separated patients in those with a high (>15%) risk and those with a low (£15%) risk of relapse or death. Starting from this model, we developed a potentially predictive model of benefit of adjuvant CT that stratified patients in groups with low (less than 2.5% RFS gain), intermediate (2.5-5% RFS gain) and high benefit (more than 5% RFS gain) from adjuvant third generation CT. We also applied this model to lymph node-positive patients and confirmed it performed as expected, indicating its clinical validity. CONCLUSIONS CNV analysis-based models provide not only prognostic information, but potentially also predictive information about adjuvant CT benefit in intermediate risk early BC patients. This approach should be further investigated.INTRODUÇÃO O cancro da mama (CM) é a neoplasia mais comum na mulher em todo o mundo e apresenta-se na maioria dos casos em estádio precoce ou localmente avançado. Neste contexto a abordagem terapêutica recomendada e multidisciplinar e multimodal, incluindo cirurgia, radioterapia e terapêutica sistémica, da qual faz parte a quimioterapia (QT) adjuvante. A QT adjuvante reduz o risco de recidiva e a mortalidade por CM, mas está associada a riscos e toxicidades não desprezáveis, pelo que a relação risco-benefício em doentes de risco intermédio deve ser ponderada. Os testes de perfil molecular existentes ajudam a guiar a decisão clínica, mas apresentam múltiplas limitações. MÉTODOS Realizámos um estudo observacional, de coorte retrospetiva, com 48 doentes diagnosticadas com CM de risco intermédio, empregando a análise da variação do número de cópias (VNC) para caracterizar os CM de risco intermédio, estratificar o risco de recidiva e prever o benefício da QT adjuvante. Para controlo positivo, foram incluídas 9 doentes na coorte com envolvimento ganglionar axilar, 10 na coorte com recetor do fator de crescimento epidérmico tipo 2 positivo e 3 na coorte triplo negativo. A mediana de tempo de vigilância na coorte de risco intermedio foi 108,57 meses. RESULTADOS Confirmámos que a análise da VNC é viável em amostras de tumor fixadas em formalina e embebidas em parafina, bem como a sua robustez e validade analítica com digital droplet polymerase chain reaction. Na coorte de risco intermédio foi detetada uma correlação inversa entre as pontuações de modelos baseados na VNC e a sobrevivência livre de recidiva (SLR) (p=0,253 para o CNVScore e o EventsMajorScore, e p=0,466 para o EventsScore). A análise multivariada identificou o CNVScore, o EventsScore, a VNC dos genes EGFR, CDKN1A e JUN como variáveis significativamente associadas a uma diminuição na RFS. Na regressão logística multinomial, a QT baseada em antraciclina melhorou a SLR para todas as variáveis testadas quando comparada com nenhuma antraciclina (p=0,102). Através de regressão logística multinomial, foi desenvolvido um modelo prognóstico, incluindo o log2 da VNC do gene EGFR e do gene CCND1, alcancando um p=0,002 e um ajuste de qualidade pela correlação de Pearson de 0,983. Este modelo separou as doentes em 2 grupos: alto risco (>15%) e baixo risco (£15%) de recidiva ou morte. A partir deste, desenvolvemos um modelo potencialmente preditivo de benefício da QT adjuvante que estratificou as doentes em grupos com baixo (menos de 2,5% de ganho de SLR), intermédio (2,5-5% de ganho de SLR) e alto beneficio (mais de 5% de ganho de SLR) com QT de terceira geração adjuvante. Também aplicamos este modelo a doentes com envolvimento ganglionar axilar e confirmamos o desempenho esperado, sugerindo a sua validade clínica. CONCLUSÕES Modelos baseados na análise da VNC proporcionam informação prognóstica e potencialmente preditiva do benefício da QT adjuvante em doentes com CM precoce de risco intermédio. Esta abordagem é promissora e merece investigação subsequente.Financiado pelo Fundo IMM - Laço, a caminho da cur

Levels of Circulating Fibroblast Growth Factor 23 (FGF23) and Prognosis in Cancer Patients with Bone Metastases

The fibroblast growth factor (FGF) signaling pathway plays a key role in tumorigenesis and is recognized as a potential therapeutic target. In this study, the authors aimed to assess the impact of serum FGF23 levels in the prognosis of patients with cancer and bone metastases from solid tumors. A cohort of 112 patients with cancer and metastatic bone disease were treated with bone-targeted agents (BTA). Serum baseline FGF23 was quantified by ELISA and dichotomized in FGF23high and FGF23low groups. Additionally, the association between FGF23 and overall survival (OS) and time to skeletal-related events (TTSRE) was investigated. Baseline characteristics were balanced between groups, except for the median urinary N-terminal telopeptide (uNTX) level. After a median follow-up of 26.0 months, a median OS of 34.4 and 12.2 months was found in the FGF23low and FGF23high groups, respectively (multivariate HR 0.18, 95% CI 0.07⁻0.44, p = 0.001; univariate HR 0.27, p = 0.001). Additionally, TTSRE was significantly longer for patients with FGF23low (13.0 vs. 2.0 months, p = 0.04). Overall, this study found that patients with FGF23low at baseline had longer OS and TTSRE. Further studies are warranted to define its role as a prognostic biomarker and in the use of drugs targeting the FGF axis