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PURPOSE: We evaluated the prevalence of immune-related adverse events and anti-tumor efficacy in advanced/metastatic urothelial carcinoma following immune-checkpoint inhibitors (ICIs) treatment. METHODS: We conducted a multicenter retrospective study of patients with advanced/metastatic urothelial carcinoma treated with ICIs in four Spanish institutions. irAEs were classified using Common Terminology Criteria for Adverse Event (CTCAE) v.5.0 guidelines. The primary endpoint was overall survival (OS). Other endpoints were overall response rate (ORR) and progression-free survival (PFS). irAEs were evaluated as a time-dependent covariate to avoid immortal time bias. RESULTS: A total of 114 patients were treated with ICIs between May 2013 and May 2019, 105 (92%) of whom received ICIs as monotherapy. irAEs of any grade were experienced in 56 (49%) patients and 21 (18%) patients had grade ≥ 3 toxicity. The most frequent irAEs were gastrointestinal and dermatological toxicities, reported in 25 (22%) and 20 (17%) patients, respectively. Patients with grade 1-2 irAEs had significantly longer OS compared to those without grade 1-2 irAEs (median 18.2 vs. 8.7 months, HR = 0.61 [95% CI 0.39-0.95], p = 0.03). No association with efficacy was observed for patients with grade ≥ 3 irAEs. No difference in PFS was observed after adjusting for the immortal time bias. ORR was higher in patients who developed irAEs (48% vs 17%, p < 0.001). CONCLUSIONS: Our findings suggest that development of irAEs was associated with higher ORR, and patients who developed grade 1-2 irAEs had longer OS. Prospective studies are necessary to confirm our findings.
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Antineoplásicos Imunológicos , Carcinoma de Células de Transição , Neoplasias da Bexiga Urinária , Humanos , Inibidores de Checkpoint Imunológico/efeitos adversos , Estudos Retrospectivos , Estudos Prospectivos , Carcinoma de Células de Transição/tratamento farmacológico , Prevalência , Antineoplásicos Imunológicos/efeitos adversosRESUMO
This study aimed to perform a metaanalysis comparing the efficacy and safety of gefitinib in combination with chemotherapy versus gefitinib alone in patients with advanced NonSmall Cell Lung Cancer (NSCLC). We searched databases for clinical studies that reported the efficacy or safety of gefitinib plus chemotherapy in comparison with gefitinib alone. Raw data from included studies were extracted and pooled to calculate the Odds Ratio (OR) for Objective Response Rate (ORR) and Disease Control Rate (DCR), the Hazard Ratio (HR) for Progression-Free Survival (PFS) and Overall Survival (OS), and OR for complication ≥ Grade 3. A total of 10 studies containing 1,528 patients with NSCLC were identified and included in the analysis. Gefitinib plus chemotherapy showed significantly better efficacy in improving ORR (OR = 1.54; 95% CI [Confidence Interval], 1.13â2.1; p = 0.006), DCR (OR = 1.62; 95% CI 1.14â2.29; p = 0.007), PFS (HR=1.67; 95% CI 1.45â1.94; p < 0.001) and OS (HR = 1.49; 95% CI 1.2â1.87; p < 0.001) as compared with gefitinib alone. Consistent results were observed in the sub-population with positive EGFR mutation. The combination of gefitinib with chemotherapy had a significantly higher risk of complication (≥ Grade 3) with an OR of 3.29 (95% CI 2.57â4.21; p < 0.001). The findings in the present study suggest that the combination of gefitinib with chemotherapy can provide better disease response and survival outcomes for patients with advanced NSCLC.
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Antineoplásicos , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Antineoplásicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/genética , Gefitinibe/efeitos adversos , Mutação , Intervalo Livre de Progressão , Inibidores de Proteínas Quinases/uso terapêuticoRESUMO
Abstract This study aimed to perform a meta-analysis comparing the efficacy and safety of gefitinib in combination with chemotherapy versus gefitinib alone in patients with advanced Non-Small Cell Lung Cancer (NSCLC). We searched databases for clinical studies that reported the efficacy or safety of gefitinib plus chemotherapy in comparison with gefitinib alone. Raw data from included studies were extracted and pooled to calculate the Odds Ratio (OR) for Objective Response Rate (ORR) and Disease Control Rate (DCR), the Hazard Ratio (HR) for Progression-Free Survival (PFS) and Overall Survival (OS), and OR for complication ≥ Grade 3. A total of 10 studies containing 1,528 patients with NSCLC were identified and included in the analysis. Gefitinib plus chemotherapy showed significantly better efficacy in improving ORR (OR = 1.54; 95% CI [Confidence Interval], 1.13‒2.1; p = 0.006), DCR (OR = 1.62; 95% CI 1.14‒2.29; p = 0.007), PFS (HR=1.67; 95% CI 1.45‒1.94; p < 0.001) and OS (HR = 1.49; 95% CI 1.2‒1.87; p < 0.001) as compared with gefitinib alone. Consistent results were observed in the sub-population with positive EGFR mutation. The combination of gefitinib with chemotherapy had a significantly higher risk of complication (≥ Grade 3) with an OR of 3.29 (95% CI 2.57‒4.21; p < 0.001). The findings in the present study suggest that the combination of gefitinib with chemotherapy can provide better disease response and survival outcomes for patients with advanced NSCLC.
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BACKGROUND: Stress, burnout, and mental health problems such as depression and anxiety are common, and can significantly impact workplaces through absenteeism and reduced productivity. To address this issue, organizations must first understand the extent of the difficulties by mapping the mental health of their workforce. Online surveys are a cost-effective and scalable approach to achieve this but typically have low response rates, in part due to a lack of interactivity. Chatbots offer one potential solution, enhancing engagement through simulated natural human conversation and use of interactive features. OBJECTIVE: The aim of this study was to explore if a text-based chatbot is a feasible approach to engage and motivate employees to complete a workplace mental health assessment. This paper describes the design process and results of a pilot implementation. METHODS: A fully automated chatbot ("Viki") was developed to evaluate employee risks of suffering from depression, anxiety, stress, insomnia, burnout, and work-related stress. Viki uses a conversation style and gamification features to enhance engagement. A cross-sectional analysis was performed to gain first insights of a pilot implementation within a small to medium-sized enterprise (120 employees). RESULTS: The response rate was 64.2% (77/120). In total, 98 employees started the assessment, 77 of whom (79%) completed it. The majority of participants scored in the mild range for anxiety (20/40, 50%) and depression (16/28, 57%), in the moderate range for stress (10/22, 46%), and at the subthreshold level for insomnia (14/20, 70%) as defined by their questionnaire scores. CONCLUSIONS: A chatbot-based workplace mental health assessment seems to be a highly engaging and effective way to collect anonymized mental health data among employees with response rates comparable to those of face-to-face interviews.
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AIM: The aim of this study was to assess treatment modalities, treatment response, toxicity profile, disease progression and outcomes in 14 patients with a confirmed diagnosis of primary cutaneous T-cell lymphoma (PCTCL) treated with total skin electron beam therapy (TSEBT). BACKGROUND: Primary cutaneous lymphomas (PCLs) are extranodal non-Hodgkin lymphomas originating in the skin without evidence of extracutaneous disease at diagnosis. Despite advances in systemic and local therapy options, the management of advanced stages remains mostly palliative. MATERIALS AND METHODS: This is a retrospective study of patients with PCTCL, diagnosed and treated in a reference center in Mexico City, analyzing treatment modalities, response to treatment, long-term outcome, and mortality. RESULTS: Eight males (57%) and 6 (43%) females were identified. Most patients were stage IVA (nâ¯=â¯5, 36%) followed by stage IB and IIB (28.5% and 21.4%, respectively). Eleven patients received the low-dose RT scheme (12â¯Gy), 1 patient, the intermediate-dose RT scheme (24â¯Gy), and 2 patients, the conventional-dose RT scheme (36â¯Gy). Mean follow-up time was 4.6 years. At first follow-up examination, 6-8 weeks after radiotherapy, the overall response rate (ORR) for the cohort was 85%. The median PFS for the whole cohort was 6 months. CONCLUSION: This study reinforces the role of TSEBT when compared with other treatment modalities and novel agents. Low-dose TSEBT is now widely used because of the opportunity for retreatment.
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BACKGROUND: Previous studies have identified that patients with EGFR mutations tend to have better responses to targeted therapy, as well as chemotherapy; however, the effect of genetic alterations in terms of radiotherapy (RT)-related outcomes has not been fully assessed. We studied the impact of common non-small cell lung cancer (NSCLC) genetic alterations (EGFR, ALK and KRAS) in relation to objective response rate (ORR) to RT in patients with brain metastases. METHODS: From 2009-2015, 153 patients with an available genotyping status were treated with whole-brain irradiation (WBI) before receiving systemic therapy. Primary outcome was ORR; secondary outcomes included intracranial progression-free survival (IPFS) and overall survival (OS). RESULTS: Overall, ORR was 47.1%. ORR to RT varied significantly according to molecular status: EGFR (64.5%) ALK (54.5%) KRAS (20%) and WT (35.4%) (P = 0.001). EGFR mutation was the only independently associated factor for response to WBI (RR 3.52 [95% CI 1.6-7.7]; P = 0.002). Median IPFS was 10.8 months [95% CI 8.2-13.5] overall; however, IPFS also varied significantly according to molecular status: EGFR (18.2 months), ALK (18.4 months), KRAS (6.0 months) and WT (8.7 months) (P < 0.0001). OS for EGFR, ALK, KRAS and WT patients was 36.6, 32.2, 15.5 and 22.4 months, respectively (P = 0.014). Intracranial-ORR (HR 0.4 [95% CI 0.2-0.6], P < 0.001) and mutation status (HR 0.7 [95% CI 0.6-0.9], P < 0.042) were independently associated with a higher OS. CONCLUSIONS: RT response varies as per tumor molecular status. The presence of EGFR mutations favors the organ-specific response to RT, and is associated with longer OS in patients with NSCLC and BM. KEY POINTS: This study addressed for the first time the difference in radiotherapy-related outcomes in patients with different genotypes of non-small cell lung cancer (NSCLC) before they received systemic therapy. Results show that response to radiotherapy varies as per tumor molecular status, particularly EGFR-mutated tumors, have a favorable response to radiotherapy, contrary to KRAS-mutated tumors.
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Quinase do Linfoma Anaplásico/genética , Neoplasias Encefálicas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Regulação Neoplásica da Expressão Gênica/efeitos da radiação , Mutação , Proteínas Proto-Oncogênicas p21(ras)/genética , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/mortalidade , Adenocarcinoma de Pulmão/patologia , Adenocarcinoma de Pulmão/radioterapia , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/secundário , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Receptores ErbB/genética , Feminino , Seguimentos , Rearranjo Gênico , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/radioterapia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Radioterapia/mortalidade , Taxa de SobrevidaRESUMO
OBJECTIVES: To systematically review the literature and compare response rates (RRs) of web surveys to alternative data collection methods in the context of epidemiologic and public health studies. METHODS: We reviewed the literature using PubMed, LILACS, SciELO, WebSM, and Google Scholar databases. We selected epidemiologic and public health studies that considered the general population and used two parallel data collection methods, being one web-based. RR differences were analyzed using two-sample test of proportions, and pooled using random effects. We investigated agreement using Bland-and-Altman, and correlation using Pearson's coefficient. RESULTS: We selected 19 studies (nine randomized trials). The RR of the web-based data collection was 12.9 percentage points (p.p.) lower (95% CI = - 19.0, - 6.8) than the alternative methods, and 15.7 p.p. lower (95% CI = - 24.2, - 7.3) considering only randomized trials. Monetary incentives did not reduce the RR differences. A strong positive correlation (r = 0.83) between the RRs was observed. CONCLUSIONS: Web-based data collection present lower RRs compared to alternative methods. However, it is not recommended to interpret this as a meta-analytical evidence due to the high heterogeneity of the studies.
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Pesquisa Biomédica , Coleta de Dados/métodos , Internet , Saúde Pública , Inquéritos e Questionários , Humanos , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
BACKGROUND: Fluoropyrimidines form the chemotherapy backbone of advanced and metastatic colorectal cancer (CRC). These drugs are frequently associated with toxicity events that result in dose adjustments and even suspension of the treatment. The thymidylate synthase (TYMS) gene is a potential marker of response and toxicity to fluoropyirimidines as this enzyme is the molecular target of these drugs. Our aim was to assess the association between variants of TYMS with response and toxicity to fluoropyrimidines in patients with CRC in independent retrospective and prospective studies. METHODS: Variants namely rs45445694, rs183205964, rs2853542 and rs151264360 of TYMS were genotyped in 105 CRC patients and were evaluated to define their association with clinical response and toxicity to fluoropyrimidines. Additionally, the relationship between genotypes and tumor gene expression was analyzed by quantitative polymerase chain reaction. RESULTS: The 2R/2R (rs45445694) was associated with clinical response (p=0.05, odds ratio (OR)=3.45) and severe toxicity (p=0.0014, OR=5.21, from pooled data). Expression analysis in tumor tissues suggested a correlation between the 2R/2R genotype and low TYMS expression. CONCLUSIONS: The allele 2R (rs45445694) predicts severe toxicity and objective response in advanced CRC patients. In addition, the alleles G(rs2853542) and 6bp-(rs151264360) are independent predictors of response failure to chemotherapy. This is the first study made on a Latin American population that points out TYMS gene variants have predictive values for response and toxicity in patients with CRC treated with fluoropyrimidine-based chemotherapy.
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Capecitabina/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Fluoruracila/uso terapêutico , Timidilato Sintase/genética , Alelos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Capecitabina/efeitos adversos , Neoplasias do Colo , Feminino , Fluoruracila/efeitos adversos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Compostos Organoplatínicos/uso terapêutico , Oxaliplatina , Polimorfismo Genético , Estudos Prospectivos , Estudos Retrospectivos , Resultado do Tratamento , População Branca/genéticaRESUMO
ABSTRACT OBJECTIVE To describe the response rate and characteristics of people who either took part or not in from the Study of Cardiovascular Risks in Adolescents (ERICA) , according to information subsets. METHODS ERICA is a school-based, nation-wide investigation with a representative sample of 12 to 17-year-old adolescents attending public or private schools in municipalities with over 100,000 inhabitants in Brazil. Response rate of eligible subjects were calculated according to macro-regions, sex, age, and type of school (public or private). We also calculated the percentages of replacement schools in comparison with the ones originally selected as per the sample design, according to the types of schools in the macro-regions. The subjects and non-subjects were compared according to sex, age, and average body mass indices (kg/m2). RESULTS We had 102,327 eligible adolescents enrolled in the groups drawn. The highest percentage of complete information was obtained for the subset of the questionnaire (72.9%). Complete information regarding anthropometric measurements and the ones from the questionnaire were obtained for 72.0% of the adolescents, and the combination of these data with the 24-hour dietary recall were obtained for 70.3% of the adolescents. Complete information from the questionnaire plus biochemical blood evaluation data were obtained for 52.5% of the morning session adolescents (selected for blood tests). The response percentage in private schools was higher than the one in public schools for most of the combination of information. The ratio of older and male adolescents non-participants was higher than the ratio among participants. CONCLUSIONS The response rate for non-invasive procedures was high. The response rate for blood collection – an invasive procedure that requires a 12-hour fasting period and the informed consent form from legal guardians – was lower. The response rate observed in public schools was lower than in the private ones, and that may reflect lower school frequency of registered students.
RESUMO OBJETIVO Descrever o percentual de resposta e características de participantes e não-participantes no Estudo de Riscos Cardiovasculares em Adolescentes (ERICA) segundo subconjuntos de informações. MÉTODOS O ERICA é um inquérito de base escolar de abrangência nacional com amostra representativa de adolescentes, de 12 a 17 anos de idade, que estudam em escolas públicas ou privadas de municípios com mais de 100 mil habitantes de todo o Brasil. Foram calculadas frequências de participação (de elegíveis) por macrorregiões, sexo, idade, e tipo de escola (pública ou privada). Foram calculados também os percentuais de escolas substitutas das selecionadas na origem do desenho amostral, de acordo com o tipo de escola nas macrorregiões. Os participantes e não-participantes foram comparados segundo sexo, idade e média de índice de massa corporal (kg/m2). RESULTADOS Estavam cadastrados nas turmas sorteadas 102.327 adolescentes elegíveis. O maior percentual de informações completas foi obtido para o subconjunto do questionário (72,9%). Informações completas das medidas antropométricas e do questionário foram obtidas em 72,0% dos adolescentes, e a combinação dessas informações com recordatório alimentar de 24h, em 70,3%. Informações completas do questionário mais avaliação bioquímica do sangue foram obtidas em 52,5% dos adolescentes do turno da manhã (elegíveis para exame de sangue). O percentual de resposta nas escolas privadas foi maior do que a das escolas públicas para a maioria das combinações de informações. A proporção de adolescentes não participantes do sexo masculino e mais velhos foi maior do que entre os participantes. CONCLUSÕES O percentual de resposta para procedimentos não invasivos foi elevado. Para a coleta de sangue, procedimento invasivo, com necessidade de jejum de 12 horas e de consentimento escrito dos responsáveis, a participação foi menor. O percentual de participação observado nas escolas públicas foi menor do que nas particulares, podendo refletir menor frequência escolar dos alunos cadastrados.