Clinical networking results in continuous improvement of the outcome of patients with acute promyelocytic leukemia.

ABSTRACT: The introduction of all-trans retinoic acid combined with anthracyclines has significantly improved the outcomes for patients diagnosed with acute promyelocytic leukemia (APL), and this strategy remains the standard of care in countries in which arsenic trioxide is not affordable. However, data from national registries and real-world databases indicate that low- and middle-income countries (LMIC) still face disappointing results, mainly because of high induction mortality and suboptimal management of complications. The American Society of Hematology established the International Consortium on Acute Leukemias (ICAL) to address this challenge through international clinical networking. Here, we present the findings from the International Consortium on Acute Promyelocytic Leukemia study involving 806 patients with APL recruited from 2005 to 2020 in Brazil, Chile, Paraguay, Peru, and Uruguay. The induction mortality rate has notably decreased to 14.6% compared with the pre-ICAL rate of 32%. Multivariable logistic regression analysis revealed as factors associated with induction death: age of ≥40 years, Eastern Cooperative Oncology Group performance status score of 3, high-risk status based on the Programa Español de Tratamiento en Hematologia/Gruppo Italiano Malattie EMatologiche dell'Adulto classification, albumin level of ≤3.5 g/dL, bcr3 PML/RARA isoform, the interval between presenting symptoms to diagnosis exceeding 48 hours, and the occurrence of central nervous system and pulmonary bleeding. With a median follow-up of 53 months, the estimated 4-year overall survival rate is 81%, the 4-year disease-free survival rate is 80%, and the 4-year cumulative incidence of relapse rate is 15%. These results parallel those observed in studies conducted in high-income countries, highlighting the long-term effectiveness of developing clinical networks to improve clinical care and infrastructure in LMIC.

External validation and calibration of the HoLISTIC Consortium's advanced-stage Hodgkin lymphoma international prognostic index (A-HIPI) in the Brazilian Hodgkin lymphoma registry.

The Hodgkin lymphoma International Study for Individual Care (HoLISTIC) Consortium's A-HIPI model, developed in 2022 for advanced-stage classical Hodgkin lymphoma (cHL), predicts survival within 5 years amongst newly diagnosed patients. This study validates its performance in the Brazilian Hodgkin lymphoma registry. By 2022, the Brazilian HL registry included 1357 cHL patients, with a median 5-year follow-up. Probabilities for 5-year progression-free survival (PFS) and overall survival (OS) were calculated using A-HIPI-model equations. Discrimination (Harrell C-statistic/Uno C-statistic) and calibration measures assessed external validation and calibration. Lab values beyond the allowed range were excluded, mirroring the initial A-HIPI analysis. A total of 694 advanced-stage cHL patients met the original inclusion criteria (age 18-65 years, Stage IIB-IV). Median age was 31 years; 46.3% were females. Stage distribution was IIB (33.1%), III (27.4%), IV (39.5%). Bulky disease in 32.6%. Five-year PFS and OS were 68.4% and 86.0%, respectively. Harrell C-statistics were 0.60 for PFS and 0.69 for OS, and Uno C-statistics were 0.63 for PFS and 0.72 for OS. Calibration plots demonstrated well-calibrated predictions with calibration slopes of 0.91 and 1.03 for 5-year OS and PFS, respectively. Despite differing patient, clinical characteristics, and socioeconomic factors, the baseline prediction tool performed well in the Brazilian cohort, demonstrating adequate discrimination and calibration. This supports its reliability in diverse settings.

Impact of baseline and interim quantitative PET parameters on outcomes of classical Hodgkin Lymphoma.

Currently, analysis of interim PET (iPET) according to the Deauville score (DS) is the most important predictive factor in Hodgkin lymphoma (HL); however, there is room for improvement in its prognostic power. This study aimed to evaluate the prognostic value of quantitative PET analysis (maximum standard uptake value [SUVmax], total metabolic tumor volume [TMTV] and total lesion glicolysis [TLG]) at baseline (PET0) and iPET in a retrospective cohort of newly diagnosed classical HL. For positive iPET (+ iPET), the reduction of quantitative parameters in relation to PET0 (ΔSUVmax, ΔTMTV and ΔTLG) was calculated. Between 2011 and 2017, 234 patients treated with ABVD were analyzed. Median age was 30 years-old, 59% had advanced stage disease, 57% a bulky mass and 25% a + iPET (DS 4-5). At baseline, high TLG was associated with an increased cumulative incidence of failure (CIF) (p = 0.032) while neither SUVmax, TMTV or TLG were associated with overall survival (OS) or progression-free survival (PFS). In multivariate analysis, only iPET was associated with CIF (p < 0.001). Among ΔSUVmax, ΔTMTV and ΔTLG, only a ΔSUVmax ≥ 68.8 was significant for PFS (HR: 0.31, CI95%: 0.11-0.86, p = 0.024). A subset of patients with improved PFS amongst + iPET was identified by the quantitative (ΔSUVmax ≥ 68.8%) analysis. In this real-world Brazilian cohort, with prevalent high-risk patients, quantitative analysis of PET0 did not demonstrate to be prognostic, while a dynamic approach incorporating the ΔSUVmax to + iPET succeeded in refining a subset with better prognosis. These findings warrant validation in larger series and indicate that not all patients with + iPET might need treatment intensification.

Five-year survival of resectable stage IIIA non-small cell lung cancer in Brazil.

BACKGROUND: In stage IIIA non-small cell lung cancer (NSCLC), surgery plays a role in terms of multimodal treatment. Surgery rates have increased in recent years, mainly due to the combination of more accurate imaging tools, electromagnetic navigation bronchoscopy, robotic bronchoscopy, robotic surgery, and a wide range of challenging clinical scenarios to lead surgeons and oncologists to include surgery as an option in therapeutic management. OBJECTIVES: To assess the prognostic factors, the 5-year overall survival (OS) and cancer-specific survival (CSS) of patients with resectable stage III-NSCLC. METHODS: Patients' information was extracted from 76 Hospitals' Cancer Registry. OS and CSS were constructed using the Kaplan-Meier method, and the log-rank test was used to assess differences between curves. In addition, Cox regression was conducted to evaluate the patients' characteristics leading to better OS and CSS. RESULTS: Overall, 433 stage III NSCLC surgical patients followed over 19 years were included. The median age was 61.29 ± 9.62 years, 58.4% male, 50.1% with adenocarcinoma, 29.3% with squamous cell carcinoma, 3.7% with large-cell lung carcinoma, and 16,9% with other lung cancer types. The 5-year OS was 30.6% (95% confidence interval [CI]: 27.4-36.1), and the CSS was 35.0% (95% CI: 29.4-41.0). In the Cox multivariate regression, squamous cell carcinoma was associated with reduced OS (hazard ratio [HR]: 1.40; 95% CI: 1.07-1.83; p=0.014) and CSS (HR: 1.56; 95% CI: 1.17-2.08; p = 0.002), in comparison with adenocarcinoma. The 2015-2019 quinquennial had a 50% reduction in HR (0.49; 95% CI: 0.29-0.81; p = 0.006), and the 2010-2014 group had a 40% reduction (0.59; 95% CI: 0.42-0.83; p = 0.006) in comparison with the 2000-2004 patients' group. CONCLUSION: The OS and CSS of patients with resectable stage III NSCLC have improved over the past 19 years in our region. Squamous cell carcinoma was associated with increased mortality risk from any cause or specific cancer.

Risk adapted approach: How to treat splenic marginal zone lymphoma in resource-poor settings? - The real-life experience of a Brazilian cancer treatment center.

BACKGROUND: Splenic marginal zone lymphoma (SMZL) is a rare lymphoid B-cell malignant neoplasm with primary involvement of the spleen. It is a chronic disease, of indolent behavior and prolonged survival. However, 25% of cases have higher biological aggressiveness, propensity for histological transformation to high grade B-cell non-Hodgkin lymphoma and shortened survival. Recognition of these cases of reserved outcome is important for selecting a risk-adapted therapeutic approach in a resource-poor settings. METHODS: We described clinical and epidemiological characteristics, survival analysis and prognostic factors in a retrospective cohort of 39 SMZL patients, treated in Latin America. RESULTS: We observed a predominance of female (71.8%), median age of 63 years and higher incidence of B symptoms (56.4%) and extra-splenic involvement (87.1%) than in European and North-American series. With a median follow-up of 8.7 years (0.6-20.2 years), estimated 5-year overall survival (OS) and progression-free survival (PFS) were 76.9% and 63.7%, respectively. Factors with adverse prognostic impact on OS and PFS were Hb < 100 g/L, platelet count < 100 x 109/L, albumin < 3.5 g/dL, LDH > 480 U/L and high-risk Arcaini and SMZL/WG scores. Despite a relative low number of patients, no superiority was observed among the therapeutic regimens used including rituximab monotherapy, splenectomy and cytotoxic chemotherapy. CONCLUSION: Therefore, in resource-poor settings, where access to immunotherapy is not universal for all SMZL patients, we suggest that first-line should consist on rituximab therapy for elderly patients or with high surgical risk or with at least 1 risk factor identified in our study. Remainders can be safely managed with splenectomy.

FcγR2B B2.4 haplotype predicts increased risk of red blood cell alloimmunization in sickle cell disease patients.

BACKGROUND: Red blood cell (RBC) alloimmunization is an important transfusion complication which is prevalent among sickle cell disease (SCD) patients. Autoimmune diseases are a known risk factor for RBC alloimmunization, suggesting that autoimmunity and post-transfusion alloantibody development occur through similar physiopathological pathways. Polymorphisms in the FcγR2B gene have already been associated with several autoimmune disorders and hypothetically could be associated with RBC alloimmunization. Our goal was to evaluate if important polymorphisms of FcγR2B have an impact on the risk of RBC alloimmunization among SCD patients. STUDY DESIGN AND METHODS: This was a case-control study in which alloimmunized and non-alloimmunized SCD patients were compared in terms of the genotype frequency of the FcγR2B polymorphisms -386G/C, -120 T/A, and 695C/T, genotyped through direct Sanger sequencing. RESULTS: A total of 237 patients met the eligibility criteria, 120 cases (alloimmunized) and 117 controls (non-alloimmunized). RBC alloimmunization was associated with female sex (p < 0.001), lifetime number of RBC units transfused (p = 0.002) and 120 T/A FcγR2B genotype (p = 0.031). The FcγR2B promoter region haplotype 2B.4 (386C120A) was positively associated with RBC alloimunization (p = 0.045). The logistic regression (LR) model identified female sex (OR 10.03, CI 95% 5.16-19.49; p < 0.001) and FcγR2B 2B.4 haplotype (OR 4.55, CI95% 1.1118.65; p = 0.035) as independent predictors of RBC alloimmunization in SCD patients. CONCLUSION: SCD patients with the FcγR2B 2B.4 haplotype had over a fourfold higher risk for RBC alloimmunization. This highlights the role played by FcγR2B on RBC alloimmunization and may be helpful in identifying the immune responders.

Absolute monocyte count is a predictor of overall survival and progression-free survival in nodal peripheral T cell lymphoma.

Nodal peripheral T cell lymphomas (nPTCL) present aggressive clinical course, and its heterogeneous nature and poor prognosis with current therapeutic strategies make it a target for the development of new prognostic markers. Thus, we investigated tumor-associated macrophages (TAM) according to the number of cells expressing CD68 in biopsies and the absolute monocyte count (AMC) in peripheral blood of 87 patients with nPTCL. The median overall survival (OS) was 3 years (95% CI 1.3-8.4 years) and estimate 5 years OS of 43.3% (95% CI 32.5-53.7%). The median progression-free survival (PFS) was 1.5 years (95% CI 0.8-2.6 years) with estimate 5 years PFS of 29.2% (95% CI 19.7-39.3%). The cutoff for AMC was 1.5 × 109/L and the median OS for patients with AMC ≥ 1.5 × 109/L was 0.83 years versus 3.7 years for those with AMC < 1.5 × 109/L (HR 2.32, 95% CI 1.03-5.22, p = 0.035). The median PFS for patients with AMC ≥ 1.5 × 109/L was 0.50 years versus 1.5 years for those with AMC < 1.5 × 109/L (HR 2.25, 95% CI 1.05-4.78, p = 0.031). CD68 was evaluated in 26/87 (29.8%) patients with a median expression of 34% and positivity cutoff of 43%. CD68 expression was not associated with OS or PFS either with AMC values. Our findings suggest that the AMC of ≥ 1.5 × 109/L at diagnosis in peripheral blood is associated with poor prognosis in nPTCL. Further investigations in a larger cohort are required to better validate our results.

Prevalence, characteristics, and predictors of early termination of cardiovascular clinical trials due to low recruitment: insights from the ClinicalTrials.gov registry.

BACKGROUND: Early termination of clinical trials due to low recruitment represents an understudied challenge for clinical research. We aimed to describe characteristics of cardiovascular trials terminated because of low recruitment and identify the major predictors of such early termination. METHODS: We reviewed all cardiovascular clinical trials (7,042 studies) registered in ClinicalTrials.gov from February 29, 2000, to January 17, 2013, and assessed information about trials that were completed and those that were terminated early. Logistic regression models were developed to identify independent predictors of early termination due to low recruitment. RESULTS: Our search strategy identified 6,279 cardiovascular clinical trials, of which 684 (10.9%) were terminated prematurely. Of these halted trials, the main reason for termination was lower than expected recruitment (278 trials; 53.6%). When comparing trials that terminated early because of low recruitment with those that were completed, we found that studies funded by the National Institutes of Health or other US federal agencies (odds ratio [OR] 0.35, 95% confidence interval [CI] 0.14-0.89), studies of behavior/diet intervention (OR 0.35, 95% CI 0.19-0.65), and single-arm design studies (OR 0.57, 95% CI 0.42-0.78) were associated with a lower risk of early termination. University/hospital-funded (OR 1.52, 95% CI 1.10-2.10) and mixed-source-funded studies (OR 2.14, 95% CI 1.52-3.01) were associated with a higher likelihood of early termination due to lower than expected recruitment rates. CONCLUSIONS: Low recruitment represents the main cause of early termination of cardiovascular clinical trials. Funding source, type of intervention, and study design are factors associated with early termination due to low recruitment and might be good targets for improving enrollment into cardiovascular clinical trials.

Clinical characteristics and outcomes of Brazilian patients with duodenal-type follicular lymphoma: a multicenter retrospective study.

Duodenal-type follicular lymphoma (DFL) is a rare subtype classified by the 5th edition of the WHO and international consensus classifications of lymphoid neoplasms, typically presenting as localized disease with favorable outcomes. This multicenter retrospective study examines 53 Brazilian DFL patients with a median age of 58.2 years (33-85), with males comprising 50% (n = 27). According to Lugano GI tract classification, 40 patients (75%) were stage I. Median follow-up was 2.9 years (range 0.1-11). Incidental diagnosis occurred in 28 patients (52.8%) during routine endoscopy; 24 patients (45%) presented mild gastrointestinal symptoms. Treatments included watchful waiting (32 patients, 60.4%), rituximab monotherapy (15 patients, 28.3%), radiotherapy (three patients, 5.7%), and chemoimmunotherapy (three patients, 5.7%). Three patients experienced disease progression; watchful waiting showed three spontaneous remissions. No deaths occurred during follow-up. This study, the first from Latin America, demonstrates a good prognosis across treatments, highlighting Watchful waiting's effectiveness.

Impact of genetic background as a risk factor for atherosclerotic cardiovascular disease: A protocol for a nationwide genetic case-control (CV-GENES) study in Brazil.

Atherosclerotic Cardiovascular Disease (ASCVD) represents the leading cause of death worldwide, and individual screening should be based on behavioral, metabolic, and genetic profile derived from data collected in large population-based studies. Due to the polygenic nature of ASCVD, we aimed to assess the association of genomics with ASCVD risk and its impact on the occurrence of acute myocardial infarction, stroke, or peripheral artery thrombotic-ischemic events at population level. CardioVascular Genes (CV-GENES) is a nationwide, multicenter, 1:1 case-control study of 3,734 patients in Brazil. Inclusion criterion for cases is the first occurrence of one of the ASCVD events. Individuals without known ASCVD will be eligible as controls. A core lab will perform the genetic analyses through low-pass whole genome sequencing and whole exome sequencing. In order to estimate the independent association between genetic polymorphisms and ASCVD, a polygenic risk score (PRS) will be built through a hybrid approach including effect size of each Single Nucleotide Polymorphism (SNP), number of effect alleles observed, sample ploidy, total number of SNPs included in the PRS, and number of non-missing SNPs in the sample. In addition, the presence of pathogenic or likely pathogenic variants will be screened in 8 genes (ABCG5, ABCG8, APOB, APOE, LDLR, LDLRAP1, LIPA, PCSK9) associated with atherosclerosis. Multiple logistic regression will be applied to estimate adjusted odds ratios (OR) and 95% confidence intervals (CI), and population attributable risks will be calculated. Clinical trial registration: This study is registered in clinicaltrials.gov (NCT05515653).

Impact of allele-level HLA matching on outcomes after double cord blood transplantation in adults with malignancies.

In single unrelated cord blood transplantation (UCBT), an increasing number of HLA allele mismatches (MM) has been associated with inferior overall survival (OS) and attributed to higher transplant-related mortality (TRM). Previous studies on the role of allele-level HLA matching after double UCBT (dUCBT) showed conflicting results. In this study, we report the impact of allele-level HLA matching on the outcomes of a large dUCBT cohort. We included 963 adults with hematologic malignancies, with available allele-level HLA matching at HLA-A, -B, -C, and -DRB1, receiving dUCBT between 2006 to 2019. Assignment of donor-recipient HLA match was performed considering the unit with the highest disparity with the recipient. Three hundred ninety-two patients received dUCBT with 0 to 3 MM and 571 with ≥4 allele MM. For recipients of dUCBT with 0 to 3 MM, day-100 and 4-year TRM were 10% and 23%, respectively, compared with 16% and 36% for those with ≥4 MM. A higher degree of allele MM was also associated with the worse neutrophil recovery and lower incidence of relapse; no significant effect on graft-versus-host disease was observed. Patients receiving units with 0 to 3 MM had a 4-year OS of 54% compared with 43% for those receiving units with ≥4 MM. The inferior OS associated with higher HLA disparity was only partially mitigated by increased total nucleated cell doses. Our results confirm that allele-level HLA typing is a significant factor for OS after dUCBT, and units with ≥4 MM (≤4/8 HLA-matched) should be avoided if possible.

Rivaroxaban to prevent major clinical outcomes in non-hospitalised patients with COVID-19: the CARE - COALITION VIII randomised clinical trial.

Background: COVID-19 progression is associated with an increased risk of arterial and venous thrombosis. Randomised trials have demonstrated that anticoagulants reduce the risk of thromboembolism in hospitalised patients with COVID-19, but a benefit of routine anticoagulation has not been demonstrated in the outpatient setting. Methods: We conducted a randomised, open-label, controlled, multicentre study, evaluating the use of rivaroxaban in mild or moderate COVID-19 patients. Adults ≥18 years old, with probable or confirmed SARS-CoV-2 infection, presenting within ≤7 days from symptom onset with no clear indication for hospitalization, plus at least 2 risk factors for complication, were randomised 1:1 either to rivaroxaban 10 mg OD for 14 days or to routine care. The primary efficacy endpoint was the composite of venous thromboembolic events, need of mechanical ventilation, acute myocardial infarction, stroke, acute limb ischemia, or death due to COVID-19 during the first 30 days. ClinicalTrials.gov: NCT04757857. Findings: Enrollment was prematurely stopped due to sustained reduction in new COVID-19 cases. From September 29th, 2020, through May 23rd, 2022, 660 patients were randomised (median age 61 [Q1-Q3 47-69], 55.7% women). There was no significant difference between rivaroxaban and control in the primary efficacy endpoint (4.3% [14/327] vs 5.8% [19/330], RR 0.74; 95% CI: 0.38-1.46). There was no major bleeding in the control group and 1 in the rivaroxaban group. Interpretation: On light of these findings no decision can be made about the utility of rivaroxaban to improve outcomes in outpatients with COVID-19. Metanalyses data provide no evidence of a benefit of anticoagulant prophylaxis in outpatients with COVID-19. These findings were the result of an underpowered study, therefore should be interpreted with caution. Funding: COALITION COVID-19 Brazil and Bayer S.A.

NPAS3 demonstrates features of a tumor suppressive role in driving the progression of Astrocytomas.

Malignant astrocytomas, the most common primary brain tumors, are predominantly fatal. Improved treatments will require a better understanding of the biological features of high-grade astrocytomas. To better understand the role of neuronal PAS 3 (NPAS3) in diseases in human beings, it was investigated as a candidate for astrocytomagenesis based on the presence of aberrant protein expression in greater than 70% of a human astrocytoma panel (n = 433) and most notably in surgically resected malignant lesions. In subsequent functional studies, it was concluded that NPAS3 exhibits features of a tumor-suppressor, which drives the progression of astrocytomas by modulating the cell cycle, proliferation, apoptosis, and cell migration/invasion and has a further influence on the viability of endothelial cells. Of clinical importance, absence of NPAS3 expression in glioblastomas was a significantly negative prognostic marker of survival. In addition, malignant astrocytomas lacking NPAS3 expression demonstrated loss of function mutations, which were associated with loss of heterozygosity. While overexpressed NPAS3 in malignant glioma cell lines significantly suppressed transformation, the converse decreased expression considerably induced more aggressive growth. In addition, knockdown NPAS3 expression in a human astrocyte cell line in concert with the human papillomavirus E6 and E7 oncogenes induced growth of malignant astrocytomas. In conclusion, NPAS3 drives the progression of human malignant astrocytomas as a tumor suppressor and is a negative prognostication marker for survival.

Hospitalization for Primary Care-Sensitive Conditions in Adults and Its Impact on Hospital Care in São Paulo City, Brazil.

INTRODUCTION: Identifying conditions among all cause hospitalizations that could be prevented at the primary care level would allow the development of strategies to reduce the range of diseases treated in hospital and promote a more efficient utilization of resources. OBJECTIVE: We sought to evaluate hospitalizations for clinical conditions that are sensitive to primary care in adults. METHODS: Cross-sectional study with data captured in hospital electronic health records using the diagnosis related groups classification system. RESULTS: Primary care-sensitive conditions were associated with longer duration of hospitalization, older age, higher prevalence of female patients, higher complexity at admission and during hospitalization, and a higher risk of mortality as compared with other conditions not sensitive to primary care. CONCLUSION: A significant proportion of hospitalizations are due to causes sensitive to primary care. Hospitalizations due to primary care-sensitive conditions are associated with longer hospital stay, greater complexity and severity, and a higher risk of mortality.

Hydroxychloroquine versus placebo in the treatment of non-hospitalised patients with COVID-19 (COPE - Coalition V): A double-blind, multicentre, randomised, controlled trial.

Background: Previous Randomised controlled trials (RCT) evaluating chloroquine and hydroxychloroquine in non-hospitalised COVID-19 patients have found no significant difference in hospitalisation rates. However, low statistical power precluded definitive answers. Methods: We conducted a multicenter, double-blind, RCT in 56 Brazilian sites. Adults with suspected or confirmed COVID-19 presenting with mild or moderate symptoms with ≤ 07 days prior to enrollment and at least one risk factor for clinical deterioration were randomised (1:1) to receive hydroxychloroquine 400 mg twice a day (BID) in the first day, 400 mg once daily (OD) thereafter for a total of seven days, or matching placebo. The primary outcome was hospitalisation due to COVID-19 at 30 days, which was assessed by an adjudication committee masked to treatment allocation and following the intention-to-treat (ITT) principle. An additional analysis was performed only in participants with SARS-CoV-2 infection confirmed by molecular or serology testing (modified ITT [mITT] analysis). This trial was registered at ClinicalTrials.gov, NCT04466540. Findings: From May 12, 2020 to July 07, 2021, 1372 patients were randomly allocated to hydroxychloroquine or placebo. There was no significant difference in the risk of hospitalisation between hydroxychloroquine and placebo groups (44/689 [6·4%] and 57/683 [8·3%], RR 0·77 [95% CI 0·52-1·12], respectively, p=0·16), and similar results were found in the mITT analysis with 43/478 [9·0%] and 55/471 [11·7%] events, RR 0·77 [95% CI 0·53-1·12)], respectively, p=0·17. To further complement our data, we conducted a meta-analysis which suggested no significant benefit of hydroxychloroquine in reducing hospitalisation among patients with positive testing (69/1222 [5·6%], and 88/1186 [7·4%]; RR 0·77 [95% CI 0·57-1·04]). Interpretation: In outpatients with mild or moderate forms of COVID-19, the use of hydroxychloroquine did not reduce the risk of hospitalisation compared to the placebo control. Our findings do not support the routine use of hydroxychloroquine for treatment of COVID-19 in the outpatient setting. Funding: COALITION COVID-19 Brazil and EMS.

Real-Life Long-Term Cohort of Patients With Stage IIIA Non-Small-Cell Lung Cancer: Overall Survival Related to Patients' Characteristics and Multiple Treatment Models.

PURPOSE: This real-life cohort of patients describes the treatment patterns and compares the overall survival (OS) and hazard risk of utilization of multiple therapies. MATERIALS AND METHODS: Electronic medical registries of patients with stage III non-small-cell lung cancer (NSCLC) regularly attended in 72 hospitals were included. Univariate and multivariate analyses were conducted to evaluate the primary patients' characteristics leading to better OS and cancer-specific survival. RESULTS: A total of 3,363 patients with stage III NSCLC followed over 19 years were included in this study. The median age was 66.00 (58.00-72.00) years, 65% male, and 41.2% with squamous cell carcinoma followed by adenocarcinoma (34.6%) and undifferentiated carcinoma (13.1%) in clinical stage T3 (50.3%), T2 (29.3%), and T4 (12.3%). The median survival (in months) was 18.4 (95% CI, 16.9 to 19.5) in patients submitted to radiotherapy plus chemotherapy, 11.2 (95% CI, 10.5 to 12.1) to chemotherapy, 31.5 (95% CI, 25.9 to 37.7) to surgery plus chemotherapy, and 33.8 (95% CI, 28.3 to 47.8) to chemotherapy plus radiotherapy plus surgery. The median cancer-specific survival (in months) was 19.3 (95% CI, 17.9 to 20.9) in patients submitted to radiotherapy plus chemotherapy, 12.1 (95% CI, 11.1 to 12.9) to chemotherapy, 36.9 (95% CI, 29.6 to 43.2) to surgery plus chemotherapy, and 41.3 (95% CI, 32.1 to 61.3) to chemotherapy plus radiotherapy plus surgery. The patients treated with multiple chemotherapy plus radiotherapy followed by surgery had significantly better OS and lower mortality rates than those treated with other treatments (adjusted hazard ratio, 0.55; 95% CI, 0.45 to 0.66; P < .001). At the end of the study, 11.2% and 10.7% of the patients were living with and without cancer, respectively. CONCLUSION: Our real-life 19-year cohort study has shown that only 30.3% of the total patients with stage III NSCLC have been submitted to standard chemotherapy and radiotherapy treatment. This may show a substantial difference between the recruited clinical trials' patients and the real-life patients' characteristics in daily routine treatment.

Impact of Teleconsultation on Patients With Type 2 Diabetes in the Brazilian Public Health System: Protocol for a Randomized Controlled Trial (TELEconsulta Diabetes Trial).

BACKGROUND: Although the Brazilian Unified Health System (SUS) offers universal health coverage, access to quality care is often limited by social inequality and location. Although telemedicine has been shown to be an important tool in the efforts to overcome this problem, because it can provide access to specialist care and break the geographical barriers to health care, there are no national studies demonstrating its use in public health. OBJECTIVE: This study aims to test the hypothesis that remote consultation can be as effective as standard face-to-face consultation for type 2 diabetes mellitus in the Brazilian public health system and to assess the associated costs related to teleconsultation in public health scenarios, for patients referred from Primary Health Care units of the SUS for specialist care. METHODS: This is a pragmatic, phase 2, unicentric, open-label, noninferiority, blinded allocation, data-blinded, centrally randomized clinical trial. The inclusion criteria will be adults, both sexes, ≥18 years old, glycated hemoglobin (HbA1c) ≥8%. Outcomes will be evaluated by assessing symptoms, laboratory exams, anthropometric measurements, blood pressure, adverse events, and satisfaction level for 6 months. The costs of the teleconsultation will be assessed using the time-driven activity-based costing (TDABC) method to compare the costs with the face-to-face consultations. The noninferiority margin was set at 0.5%. Assuming an SD of 1.3% for both groups, true difference between the means of zero, and a type I error level of 5% (one-sided), it was estimated that 117 individuals per group would be necessary to achieve 90% power. Statistical analysis of the efficacy will be done using intention-to-treat and per-protocol approaches. RESULTS: The results from this trial will be reported according to the CONSORT guidelines. The trial was approved by the institutional review board on October 5, 2019. Data collection started in January 2019 and is expected to finish in 2022. At the time of manuscript submission, 18 participants were recruited. CONCLUSIONS: Our expectations are that providing remote access to health care will result in improvements in the health and quality of life of patients with type 2 diabetes and reduce costs and that both patients and clinicians will benefit from and be satisfied with this technology. TRIAL REGISTRATION: Registro Brasileiro de Ensaios Clínicos RBR-8gpgyd; https://ensaiosclinicos.gov.br/rg/RBR-8gpgyd. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/23679.

Disparity in the access to kidney transplantation for sensitized patients in the state of Sao Paulo-Brazil.

Highly sensitized (HS) patients accumulate on deceased donor kidney transplantation (DDKT) waitlists worldwide due to matching difficulty and inequity of allocation policies. Current situation of HS patients on KT waitlist in Brazil has not been published. All patients enrolled on the KT waitlist of the State of São Paulo from 2002 to 2017 were retrospectively assessed. Patients were divided into eight groups according to their degree of sensitization, PRA of 0%, >0-40%, >40-80%, >80-85%, >85-90%, >90-95%, >95-98% and > 98%. Cumulative incidence curves for transplantation or mortality/removal from waitlist were estimated by competing risk. Among 50,249 waitlisted candidates, 1247 prioritized, 2467 with age < 18 or > 75 years and 4152 submitted to living-donor KT were excluded from the analysis, remaining 42,383 patients. There were 29,664(70%) PRA 0%, 5611(13.2%) PRA > 0-40%, 3442(8.2%) PRA > 40-80%, 507(1.2%) PRA > 80-85%, 564(1.3%) PRA > 85-90%, 825(1.9%) PRA >90-95%, 859(2%) PRA > 95-98% and 911(2.2%) PRA > 98%. There was a progressive increase in the need of prioritization, waiting time for KT or on waitlist and time on dialysis as PRA increased (p < 0.001). Probability of DDKT clearly increased as PRA decreased so that PRA 0% candidates were much more likely to be transplanted compared to PRA > 98% patients(HR:13.02, p < 0.001). Waiting list mortality/removal was higher among PRA > 0-40%(HR1.05,p = 0.03), PRA > 90-95%(HR:1.10,p = 0.05), PRA > 95-98%(HR:1.26,p < 0.001) and PRA > 98%(HR:1.09,p = 0.05) patients compared to PRA zero candidates. HS patients in Sao Paulo-Brazil required greater prioritization due to lack of venous access, longer dialysis and waitlist times, lower probability of DDKT and higher rates of waitlist mortality/removal. We confirmed the disparity of access to KT among HS patients in Sao Paulo-Brazil, indicating the need of new strategies that optimize transplantation for this subcategory of patients.

Validation of a formula predictive of peripheral blood stem cell yield and successful collection in healthy allogeneic donors.

BACKGROUND: An efficient mobilization and collection of peripheral blood stem cells (PBSCs) are crucial to optimize engraftment in the recipient. We aim to validate a formula that predicted CD34+ cell yield and to describe variables that correlated with high yield mobilization and collection in healthy donors. METHODS: We retrospectively analyzed clinical and laboratory data from healthy donors who underwent PBSC collection from 2006 to 2015. The predicted number of collected cells was calculated using the following formula: Total number of CD34+ (cells×106/kg) yield=[(peripheral CD34+ cells/µL)×(0.43)/recipient body weight (kg)]×total liters processed. RESULTS: We evaluated 338 collections from 307 allogeneic PBSC donors. The predicted versus the observed number of CD34+ cells/kg collected yielded an r-value of 0.775 (0.726-0.816; p<0.0001). Overall, 55.7% donors had an acceptable mobilization level. Donors with a body weight <67kg were less likely to yield a satisfactory CD34+ cell count (OR=0.44; 95% CI 0.24-0.81), while a white blood cell (WBC) count >40×109/L (OR=3.69; 2.11-6.46) and platelet count ≥200×109/L (OR=2.09; 1.26-3.47) on the day of collection predicted a good level of mobilization. Predictors of a CD34+ cell yield/kg of ≥4×106 with only one apheresis session were: circulating CD34+ cells/µL >40 (OR=16; 6.94-36.93), hemoglobin ≥14g/dL (OR=3.40; 1.53-7.57), WBC >40×109/L (OR=4.61; 2.10-10.10) on the first collection day, and a positive delta weight between donor and recipient (OR=3.10; 1.36-7.06). CONCLUSION: The formula for predicting CD34+ cell yield is accurate and suggests the optimal length of time for successful leukapheresis. Validation of the predictors of successful mobilization will help to further refine PBSC leukapheresis procedures.