Health Services Access Inequalities in Brazil Result in Poorer Outcomes for Stage III NSCLC-RELANCE/LACOG 0118.

Introduction: Stage III NSCLC is a heterogeneous disease, representing approximately one-third of newly diagnosed lung cancers. Brazil lacks detailed information regarding stage distribution, treatment patterns, survival, and prognostic variables in locally advanced NSCLC. Methods: RELANCE/LACOG 0118 is an observational, retrospective cohort study assessing sociodemographic and clinical data of patients diagnosed with having stage III NSCLC from January 2015 to June 2019, regardless of treatment received. The study was conducted across 13 cancer centers in Brazil. Disease status and survival data were collected up to June 2021. Descriptive statistics, survival analyses, and a multivariable Cox regression model were performed. p values less than 0.05 were considered significant. Results: We recruited 403 patients with stage III NSCLC. Most were male (64.0%), White (31.5%), and smokers or former smokers (86.1%). Most patients had public health insurance (67.5%), had stage IIIA disease (63.2%), and were treated with concurrent chemoradiation (53.1%). The median follow-up time was 33.83 months (95% confidence interval [CI]: 30.43-37.50). Median overall survival (OS) was 27.97 months (95% CI: 21.57-31.73), and median progression-free survival was 11.23 months (95% CI: 10.70-12.77). The type of treatment was independently associated with OS and progression-free survival, whereas the types of health insurance and histology were independent predictors of OS only. Conclusions: Brazilian patients with stage III NSCLC with public health insurance are diagnosed later and have poorer OS. Nevertheless, patients with access to adequate treatment have outcomes similar to those reported in the pivotal trials. Health policy should be improved to make lung cancer diagnosis faster and guarantee prompt access to adequate treatment in Brazil.

Induction Chemotherapy and Chemoradiotherapy Combined to ASA vs. Placebo for High-Risk Rectal Cancer: Results of a Randomized Trial.

INDUCTION: chemotherapy (IC) followed by chemoradiation (CRT) is an attractive approach in high-risk locally advanced rectal cancer. Additionally, ASA has shown potential to improve outcomes alongside CRT in rectal cancer. The ICAR trial aimed to evaluate the safety and efficacy of IC followed by CRT with or without ASA on MRI tumor response. METHODS: Single-center, double-blind, randomized phase II trial to evaluate induction treatment with CAPOX, followed by capecitabine-based chemoradiotherapy with ASA (arm 1) or placebo (arm 2) in high-risk stage II-III rectal adenocarcinoma staged by MRI. The primary endpoint was MRI tumor regression grade (mrTRG). Secondary endpoints were pathological response, surgical outcomes, postoperative complications, treatment tolerance, DFS, and OS. RESULTS: Between January 2018 and August 2019, 27 patients were eligible, 25 (92.5%) completed IC, and 23 patients were randomly assigned (12 to ASA group; 11 to placebo group). In the ASA arm, 3 pts (25%) presented distant disease progression at restaging. Seven patients (30.4%) had cCR after neoadjuvant treatment. All 13 patients submitted to surgery after neoadjuvant treatment underwent R0 resections except for 1 patient with positive CRM, and 12 patients (92.3%) had sphincter preservation. After a median follow-up of 34.9 months, the 2-year DFS was 83.1% and 3-year OS was 81.5%. CONCLUSION: There was good compliance in both treatment arms and encouraging cCR rate. ASA during CRT was safe but failed to improve on MRI tumor response. The study was closed due to the absence of benefits.

Outcome of Patients With Breast Cancer Treated in a Private Health Care Institution in Brazil.

PURPOSE: Middle-income countries like Brazil often have a dichotomous health care system in which patients may be treated in either public or private institutions that differ substantially in terms of level of access to diagnostic and therapeutic procedures. PATIENTS AND METHODS: This was a prospective, observational study to assess real-world data in 1,230 female patients with breast cancer who were treated in a private health care institution between 2012 and 2016 in Brazil. RESULTS: Breast cancer in these patients mostly was diagnosed at early (79.0% stages I or II) or locally advanced (16.1% stage III) stages. The primary tumor was resected in 89.0% of cases, most often through breast-conserving surgery (55.1%). Patients with locally advanced disease received more aggressive therapy (eg, higher rates of mastectomy, axillary dissection and chemotherapy use) than patients with early-stage disease. The estimated 2-year overall survival (OS) was 95.3%. Survival was significantly longer among patients with stage I or II disease (2-year OS, 97.9% and 97.5%, respectively) than those with stage III or IV disease (89.4% and 69.5%, respectively; P < .01). Tumor grade was also correlated with OS in the overall cohort ( P = .05); triple-negative status was only prognostic for patients with stage III disease ( P < .01). CONCLUSION: The data provided aid understanding of the current scenario of breast cancer presentation and treatment in the Brazilian private health care system and may serve as a foundation to guide resource allocation. Our results reinforce the need to pursue adequate access to cancer care in low- and middle-income countries to optimize patient outcome.

Diagnostic accuracy and reproducibility of pleural and lung ultrasound in discriminating cardiogenic causes of acute dyspnea in the emergency department.

Dyspnea is a common symptom in patients admitted to the Emergency Department (ED), and discriminating between cardiogenic and non-cardiogenic dyspnea is often a clinical dilemma. The initial diagnostic work-up may be inaccurate in defining the etiology and the underlying pathophysiology. The aim of this study was to evaluate the diagnostic accuracy and reproducibility of pleural and lung ultrasound (PLUS), performed by emergency physicians at the time of a patient's initial evaluation in the ED, in identifying cardiac causes of acute dyspnea. Between February and July 2007, 56 patients presenting to the ED with acute dyspnea were prospectively enrolled in this study. In all patients, PLUS was performed by emergency physicians with the purpose of identifying the presence of diffuse alveolar-interstitial syndrome (AIS) or pleural effusion. All scans were later reviewed by two other emergency physicians, expert in PLUS and blinded to clinical parameters, who were the ultimate judges of positivity for diffuse AIS and pleural effusion. A random set of 80 recorded scannings were also reviewed by two inexperienced observers to assess inter-observer variability. The entire medical record was independently reviewed by two expert physicians (an emergency medicine physician and a cardiologist) blinded to the ultrasound (US) results, in order to determine whether, for each patient, dyspnea was due to heart failure, or not. Sensitivity, specificity, and positive/negative predictive values were obtained; likelihood ratio (LR) test was used. Cohen's kappa was used to assess inter-observer agreement. The presence of diffuse AIS was highly predictive for cardiogenic dyspnea (sensitivity 93.6%, specificity 84%, positive predictive value 87.9%, negative predictive value 91.3%). On the contrary, US detection of pleural effusion was not helpful in the differential diagnosis (sensitivity 83.9%, specificity 52%, positive predictive value 68.4%, negative predictive value 72.2%). Finally, the coexistence of diffuse AIS and pleural effusion is less accurate than diffuse AIS alone for cardiogenic dyspnea (sensitivity 81.5%, specificity 82.8%, positive predictive value 81.5%, negative predictive value 82.8%). The positive LR was 5.8 for AIS [95% confidence interval (CI) 4.8-7.1] and 1.7 (95% CI 1.2-2.6) for pleural effusion, negative LR resulted 0.1 (95% CI 0.0-0.4) for AIS and 0.3 (95% CI 0.1-0.8) for pleural effusion. Agreement between experienced and inexperienced operators was 92.2% (p < 0.01) and 95% (p < 0.01) for diagnosis of AIS and pleural effusion, respectively. In early evaluation of patients presenting to the ED with dyspnea, PLUS, performed with the purpose of identifying diffuse AIS, may represent an accurate and reproducible bedside tool in discriminating between cardiogenic and non-cardiogenic dyspnea. On the contrary, US detection of pleural effusions does not allow reliable discrimination between different causes of acute dyspnea in unselected ED patients.

Estudo de fase II com doses fracionadas diárias de etoposide oral em pacientes com câncer de mama estádio IV refratário a múltiplos esquemas quimioterápicos / Phase II study of fractionated daily doses of oral etoposide in patients with stage IV breast cancer refractory to multiple chemotherapy regimens

O etoposide é um inibidor da topoisomerase II capaz de produzir respostas objetivas em cerca de 10% das pacientes com câncer de mama metastático após a falha a esquemas convencionais. A administração oral de doses fracionadas de etoposide produz um aumento significativo do tempo de exposição dos tecidos em níveis terapêuticos deste agente, aumentando o seu índice terapêutico. Neste artigo, são descritos os resultados de um ensaio clínico de fase II com etoposide oral em doses fracionadas diárias em 20 mulheres com câncer de mama metastático refratário a múltiplos esquemas quimioterápicos. Foram elegíveis pacientes entre 18-75 anos de idade, desempenho clínico entre 0-2 (ECOG), diagnóstico histopatológico de câncer de mama, doença metastática visceral, sem disfunção de órgãosvitais e sem envolvimento do Sistema Nervoso Central (SNC). A assinatura de um documento de consentimento pelapaciente, segundo as normas da CONEP e do Comitê de Ética da Instituição, era condição necessária para inclusão.O conteúdo da ampola de etoposide para uso endovenoso foi administrado por via oral na dose de 20mg/m2 a cadaoito horas, diluído em veículo ácido (suco de laranja ou uva), diariamente por 14 dias, seguido de sete dias deintervalo. A cada 21 dias, as pacientes foram reavaliadas quanto à toxicidade (critério do NCI-CTC) e, a cada doisciclos (42 dias), quanto à resposta tumoral (critério da RECIST). As pacientes foram tratadas até a progressão, toxicidade limitante ou desejo próprio de interromper o tratamento. Foram incluídas 20 pacientes no estudo, tendo sido analisado um total de 55 ciclos de tratamento, com uma mediana de dois ciclos por paciente (1-10). Os efeitosadversos mais observados foram: náusea (36%), vômitos (24%), mucosite (16%) e neutropenia (14%). Neutropenia febril ocorreu em apenas um caso (2%). Não foram documentadas respostas objetivas. Entretanto, 9 pacientes apresentaram doença estável (45%), algumas com duração prolongada (30+, 21+ e...

Etoposide is an inhibitor of the nuclear topoisomerase II enzyme, which produces objective tumor responses inabout 10% of patients with metastatic breast cancer failing to standard chemotherapy regimens. Fractionatedoral administration of etoposide causes significant increase in tissue drug exposure, leading to a better therapeuticindex. In this paper, the outcomes of a Phase II trial of fractionated oral daily doses of etoposide conducted in20 women with metastatic breast cancer, who progressed following multiple chemotherapy regimens, are described. Eligible patients were those between 18-75 years old, ECOG performance status between 0-2, confirmed histopathological diagnosis of breast cancer, presence of visceral involvement, no vital organs dysfunction and no CNS involvement. A written informed consent was required, in accordance with the local IRB and theMinistry of Health of Brazil. The content of an ampoule for IV use was administered orally, at the dose of 20mg/m2, every eight hours, diluted in a low pH fluid (orange or grape juice), daily for 14 consecutive days,followed by a 7-day rest. Patients were reviewed every 21 days for toxicity (NCI-CTC criteria), and every 42days for tumoral response (RECIST criteria). Patients were treated until tumor progression, dose-limiting toxicityor own desire to interrupt the treatment. Twenty patients were included in the trial, and a total of 55 treatment cycles administered with a median of two cycles per patient (1-10) was evaluated. The most common side-effects were nausea (36%), vomiting (24%), mucositis (16%) and neutropenia (14%). Febrile neutropenia was documented in one case (2%) only. No objective response was documented. However, nine patients showed stable disease (45%), in some cases with prolonged duration (30+, 21+ and 18 weeks). The median duration of stable disease was 15 weeks (9-30+). In summary, this daily fractionated regimen of oral etoposide was welltolerated, producing...