Deterministic linkage for improving follow-up time in a Brazilian population-based cancer registry.

Population-based cancer registries (PBCR) are the primary source of cancer incidence and survival statistics. The loss to follow-up of these patients is concerning since it reduces the reliability of any statistical analysis. The linkage techniques have been increasingly used to improve data quality in various information systems. The linkage was performed between the databases of the PBCR-Barretos and the mortality database of the state of São Paulo. To evaluate the improvement in the follow-up time of patients, the comparability of the two databases, pre- and post linkage, was made. Three analyses were performed: a comparative analysis of the absolute number of deaths, a comparative analysis of the follow-up time of patients and the survival analysis. After linkage, there was an increase of 813 deaths. The follow-up time of patients was extended and observed in most types of tumours. The comparability of the survival analyses at both time points also showed a decrease in survival probabilities for all tumour types. Deterministic linkage is effective in updating the vital status of registered patients, improving patient follow-up time, and maintaining good quality data from PBCRs, consequently producing more reliable rates, as seen for the survival analyses.

Tobacco smoking changes during the first pre-vaccination phases of the COVID-19 pandemic: A systematic review and meta-analysis.

Background: Globally, tobacco smoking remains the largest preventable cause of premature death. The COVID-19 pandemic has forced nations to take unprecedented measures, including 'lockdowns' that might impact tobacco smoking behaviour. We performed a systematic review and meta-analyses to assess smoking behaviour changes during the early pre-vaccination phases of the COVID-19 pandemic in 2020. Methods: We searched Medline/Embase/PsycINFO/BioRxiv/MedRxiv/SSRN databases (January-November 2020) for published and pre-print articles that reported specific smoking behaviour changes or intentions after the onset of the COVID-19 pandemic. We used random-effects models to pool prevalence ratios comparing the prevalence of smoking during and before the pandemic, and the prevalence of smoking behaviour changes during the pandemic. The PROSPERO registration number for this systematic review was CRD42020206383. Findings: 31 studies were included in meta-analyses, with smoking data for 269,164 participants across 24 countries. The proportion of people smoking during the pandemic was lower than that before, with a pooled prevalence ratio of 0·87 (95%CI:0·79-0·97). Among people who smoke, 21% (95%CI:14-30%) smoked less, 27% (95%CI:22-32%) smoked more, 50% (95%CI:41%-58%) had unchanged smoking and 4% (95%CI:1-9%) reported quitting smoking. Among people who did not smoke, 2% (95%CI:1-3%) started smoking during the pandemic. Heterogeneity was high in all meta-analyses and so the pooled estimates should be interpreted with caution (I2 >91% and p-heterogeneity<0·001). Almost all studies were at high risk of bias due to use of non-representative samples, non-response bias, and utilisation of non-validated questions. Interpretation: Smoking behaviour changes during the first phases of the COVID-19 pandemic in 2020 were highly mixed. Meta-analyses indicated that there was a relative reduction in overall smoking prevalence during the pandemic, while similar proportions of people who smoke smoked more or smoked less, although heterogeneity was high. Implementation of evidence-based tobacco control policies and programs, including tobacco cessation services, have an important role in ensuring that the COVID-19 pandemic does not exacerbate the smoking pandemic and associated adverse health outcomes. Funding: No specific funding was received for this study.

Role of Genetic Ancestry in 1,002 Brazilian Colorectal Cancer Patients From Barretos Cancer Hospital.

Background: Colorectal cancer (CRC) is the third most frequent and the second deadliest cancer worldwide. The ethnic structure of the population has been gaining prominence as a cancer player. The purpose of this study was to determine the genetic ancestry of Brazilian CRC patients. Moreover, we intended to interrogate its impact on patients' clinicopathological features. Methods: Retrospective observational cohort study with 1,002 patients with CRC admitted from 2000 to 2014 at Barretos Cancer Hospital. Following tumor DNA isolation, genetic ancestry was assessed using a specific panel of 46 ancestry informative markers. Survival rates were obtained by the Kaplan-Meier method, and the log-rank test was used to compare the survival curves. Multivariable Cox proportional regression models were used to estimate hazard ratios (HRs). Results: We observed considerable admixture in the genetic composition, with the following average proportions: European 74.2%, African 12.7%, Asian 6.5%, and Amerindian 6.6%. The multivariate analysis for cancer-specific survival showed that clinical stage, lymphovascular invasion, and the presence of recurrence were associated with an increased relative risk of death from cancer (p < 0.05). High African proportion was associated with younger age at diagnosis, while high Amerindian proportion was associated with the mucinous histological subtype. Conclusions: This represents the larger assessment of genetic ancestry in a population of Brazilian patients with CRC. Brazilian CRC patients exhibited similar clinicopathological features as described in Western countries. Impact: Genetic ancestry components corroborated the significant admixture, and importantly, patients with high African proportion develop cancer at a younger age.

Incidence and mortality of myeloid malignancies in children, adolescents and Young adults in Brazil: A population-based study.

BACKGROUND: Myeloid malignancies (MM) are heterogeneous when it comes to incidence rates and pathogenesis. These variation rates are important to generate hypotheses on causal aetiology. This study aimed to describe incidence and mortality patterns of MM among children, adolescents and young adults (cAYA) in Brazil and to evaluate trends in incidence and mortality rate overtime. METHODS: Data were extracted from a dataset of 15 Population-based Cancer Registries located in five Brazilian geographical regions and calculated by age-specific, crude, and age-standardized incidence (ASR) and mortality rates per million persons. Joinpoint regression analyses were performed for trends evaluations, regionally. Annual Percent Change (APC) and Average Annual Percent Change (AAPC) were also estimated. RESULTS: The overall ASR for incidence and mortality of MM in Brazil was 14.57 and 8.83 per million, respectively. The AML (non-APL AML and APL) incidence rate is 8.18 per million, whereas other MM subtypes altogether have an incidence rate of 2.62 per million, and not otherwise specified (NOS) is 3.70 per million. The analysis of incidence trends (AAPC) showed a significant decline in Manaus (-5.6%) and São Paulo (-4.7%), and a significant increase was observed in Fortaleza (5.8%). Mortality trends steadily declined in all registries, with significant declines occurring in Goiânia (-1.5%), Belo Horizonte (-2.3%), São Paulo (-2.5%), Curitiba (-2.8%) and Porto Alegre (-4.1%). CONCLUSION: Our findings showed differences in the incidence and mortality rates of MM in cAYA in Brazil, geographically. Infants-AML have the highest incidence within the cAYA population (17.42 per million). There was a substantial decrease in mortality rate observed, which was interpreted as an improvement in MM recognition and therapeutic approach.

IS THERE A SAFE TUMOR SIZE FOR IDENTIFICATION OF BREAST CARCINOMA WITHOUT AXILLARY NODE METASTASIS? / Há um tamanho seguro para a identificação do carcinoma mamário sem metástase linfonodal?

Objective: To evaluate the rate of absence of axillary pathological involvement in patients with clinically negative axilla, submitted to axillary lymphadenectomy (AL). Method: Retrospective longitudinal study, which clinically evaluated patients without axillary metastasis (cN0), who underwent oncologic treatment from 1998 to 2001. Patients were selected at clinical stage I to III. The axillary pathological impairment ratio was correlated with tumor size and clinical stage T and TNM. We also evaluated the locoregional and axillary (local) recurrences. Results: 519 clinically cN0 patients were selected. All were submitted to AL, with a mean of 18 lymph nodes dissected and 3.2 compromised. The axillary metastatic rate was 47.2%. Tumor size and clinical stage were associated with the presence of axillary lymph node metastasis (p<0.001). The axillary involvement was of 78.6% for tumors between 6.1 to 8 cm, and of 100% for tumors larger than 8.1 cm. Forty patients were T4- TNM, where the impairment rate was 57.5%. The specific survival at 120 months was 71.1%, with locoregional recurrence rate of 6.9% (n=36) and local rate of 0.4% (n=2). Conclusion: In patients submitted to axillary lymphadenectomy, the axillary recurrence was extremely low. There are patients with tumors greater than 5 cm, smaller than 8 cm, and selected T4-TNM without metastasis in axilla. Further studies are necessary to evaluate sentinel lymph node dissection in this selected group, but it is unacceptable for tumors larger than 8.1 cm

Objetivo: Avaliar a taxa de ausência de comprometimento anatomopatológico axilar em pacientes com axila clinicamente negativa, submetidas à linfadenectomia axilar (LA). Método: Estudo retrospectivo longitudinal que avaliou pacientes clinicamente com ausência de metástase axilar (N0), submetidas a tratamento oncológico no período de 1998 a 2001. Selecionaram-se pacientes no estádio clínico de I a III. Avaliou-se a relação entre a taxa de comprometimento anatomopatológico axilar, o tamanho do tumor e o estádio clínico T e TNM. Avaliou-se também o risco de recidiva locorregional (RLR) e de recidiva local axilar (RLA). Resultados: 519 pacientes clinicamente N0 foram selecionadas. Todas foram submetidas à LA, com o número médio de 18 linfonodos dissecados e 3,2 comprometidos. A taxa de doença metastática axilar foi de 47,2%. O tamanho do tumor e o estádio clínico estiveram associados à presença de metástase linfonodal axilar (p<0.001). Tumores de 6,1 a 8 cm apresentaram 78,6% de comprometimento, e em tumores maiores que 8,1 cm essa taxa foi de 100%. Quarenta pacientes eram T4-TNM, nos quais a taxa de comprometimento foi de 57,5%. A sobrevida específica aos 120 meses foi de 71,1%, a taxa de RLR foi de 6,9% (n=36) e a RLA de 0,4% (n=2). Conclusão: Em pacientes submetidas à linfadenectomia axilar, a taxa de recorrência axilar foi extremamente baixa. Há pacientes com tumores maiores que 5 cm e menores que 8 cm, T4-TNM, em que a axila se mostrou sem doença metastática axilar. Fazem-se necessários mais estudos prospectivos para avaliar a dissecção do linfonodo sentinela em casos selecionados de tumores T3 e T4 clínico, sendo a dissecção inaceitável para tumores com tamanho superior a 8,1 cm.

Overall survival and time trends in breast and cervical cancer incidence and mortality in the Regional Health District (RHD) of Barretos, São Paulo, Brazil.

BACKGROUND: Breast and cervical cancers represent a significant cause of morbidity and mortality among women. The purpose of this study was to analyse the survival and time trends in two of the most common female cancers in the Regional Health District (RHD) of Barretos, São Paulo, Brazil. METHODS: From 2000 through 2015, we calculated the breast and cervical cancer incidence and mortality rates per 100,000 women who were age-standardized to the world population. We obtained the time trends using the Joinpoint Regression software. We estimated the overall survival rates using the Kaplan-Meier methods. RESULTS: The age-standardized rates (ASR) for incidence of breast cancer increased annually, with an average annual percentage change (AAPC) of 4.3 (95% Confidence Interval (CI): 2.4 to 6.3) for invasive breast cancer and 10.2 (95% CI: 6.1 to 14.5) for in situ breast cancer. The mortality rates for invasive breast cancer decreased with an AAPC of 0.2 (95% CI: -1.9 to 2.4). The ASR incidence of invasive cervical cancer showed an AAPC of - 1.9 (95% CI: -4.7 to 0.9). For in situ cases, the ASR showed an AAPC of 9.3 (95% CI: 3.3 to 15.7). The ASR mortality for cervical cancer showed an AAPC of - 5.3 (95% CI: -9.5 to - 0.8). The Kaplan-Meier analysis indicated 5-year overall survival rates of 74.3% for breast cancer and 70.7% for cervical cancer. CONCLUSIONS: The incidence of in situ and invasive breast cancer is increasing, while the mortality rates remain stable. We observed an increase in the incidence of in situ cervical cancer and a decrease in invasive incidence rates during the study period, and we noted that the cervical cancer mortality significantly declined during the study period.

Prevalence of high risk HPV DNA in esophagus is high in Brazil but not related to esophageal squamous cell carcinoma.

BACKGROUNDS: The first publication that associated Human Papillomavirus (HPV) infection and esophageal cancer was published in 1982. However, data are still contradictory and require further investigation. The aim of this study was to identify high risk HPV DNA in esophageal tissue of patients with and without esophageal squamous cell carcinoma (ESCC) and correlate HPV presence with classical risk factors. METHODS: Invited patients signed the informed consent form, and interviews were conducted in order to obtain information about sociodemographic and lifestyle behavior. During endoscopy, esophageal biopsies were collected from case and controls. Multiplex polymerase chain reaction genotyping was conducted on endoscopic biopsies to identify HPV types and HPV-16 was further evaluated by specific PCR real time. RESULTS: Among 87 cases, 12 (13.8%) had tumors harboring high risk HPV DNA and among 87 controls, 12 (13.8%) had high risk HPV DNA (OR:1.025 [CI:0.405:2.592]). Variables regarding consumption of alcohol and use of tobacco continued to characterize risk factors even after adjustments by presence or absence of high risk HPV. CONCLUSION: HPV was demonstrated to be frequently and similarly associated to normal and malignant esophageal tissues, but not as an independent risk factor to esophageal cancer. IMPACT: To contribute to the Brazilian population data on this subject, which is still contradictory.

HPV infection and p53 and p16 expression in esophageal cancer: are they prognostic factors?

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is a highly lethal malignant tumor. Currently, Human papillomavirus (HPV) is suggested as a potential risk factor for esophageal cancer (EC) in addition to the classic risk factors, alcohol and tobacco, but this hypothesis still remains contradictory. We sought to investigate wether HPV and well-known biomarkers (p16 and p53) and patient-related factors that may have impact on survival of ESCC. METHODS: We conducted a prospective cohort study. By using multiplex PCR, we determined the prevalence of high risk HPV in ESCC, and evaluated the immunohistochemical expression of p16 and p53, molecular markers related to esophageal carcinogenesis in order to verify the potential influence of these variables in patients's survival. Survival rates were estimated using Kaplan-Meier methods. A multivariate confirmatory model was performed using Cox proportional hazards regression. RESULTS: Twelve (13.8%) of 87 patients were HPV-DNA positive. Positive reactions of p16 and p53 were 10.7% and 68.6%, respectively. Kaplan-Meier analysis indicated that men (p = 0.025) had poor specific-cancer survival and a shorter progression-free survival (p = 0.050) as compared to women; III or IV clinical stage (p < 0.019) had poor specific-cancer survival and a shorter progression-free survival (p < 0.001) compared to I and II clinical stage; not submitted to surgery (<0.001) and not submitted to chemoradiotherapy (p = 0.039) had a poor specific-cancer survival, as well. The multivariate analysis showed that HPV, p16 and p53 status are not predictive parameters of progression-free and specific-cancer survival. CONCLUSION: HPV infection and p53 and p16 expression are not prognostic factors in ESCC.

The Relation of HPV Infection and Expression of p53 and p16 Proteins in Esophageal Squamous Cells Carcinoma.

GOAL: To investigate the HPV prevalence and characterize the expression of potential molecular surrogate markers of HPV infection in esophageal squamous cell carcinoma. MATERIALS AND METHODS: The prevalence of HPV in individuals with and without esophageal cancer (EC) was determined by using multiplex PCR; p16 and p53 protein levels were assessed by immunohistochemistry (IHC). RESULTS: High-risk HPV (hr-HPV) was found in the same frequency (13.8%) in esophageal squamous cell carcinoma (ESCC) and in healthy individuals. The p53 expression was positive in 67.5% of tumor tissue, 20.0% of adjacent non-tumoral tissue and 1.8% of normal esophageal tissue. p16 was positive in 11.6% of esophageal cancer cases and 4.7% of adjacent non-tumoral tissue. p16 was undetectable among control group samples. p53 and p16 levels were not significantly associated with the HPV status. CONCLUSIONS: These results suggest that hr-HPV types are not associated with the development of ESCC and that p53 and p16 protein expression have no relationship with HPV infection in normal or cancerous esophagus.

Risk Factors for Arm Lymphedema in a Cohort of Breast Cancer Patients Followed up for 10 Years.

BACKGROUND: The etiology of lymphedema is multifactorial, and definition criteria of lymphedema, its limitation, and follow-up must be considered in studies related to risk factors. The aim of this study is to evaluate risk factors related to arm lymphedema in a cohort study with a long follow-up. PATIENTS AND METHODS: The study was performed in 622 breast cancer patients. The main endpoint reported was the presence of clinical lymphedema reported in medical records. Univariate and multivariate regression analyses were performed to identify factors related to lymphedema. RESULTS: 66.4% of the patients were submitted to mastectomy, 88.4% to level III axillary lymphadenectomy, 34.9% to radiotherapy in the supraclavicular fossa, and 4.3% to axillary radiotherapy. The mean follow-up was 96.7 months. 45 patients (7.2%) developed lymphedema, of which 82.2% had developed lymphedema at 60 months. Univariate regression analysis showed that supraclavicular radiotherapy, adjuvant/palliative chemotherapy, ≥ 15 lymph nodes dissected, and axillary surgery increase the lymphedema rate by 1.87, 2.28, 2.03, and 6.17, respectively. Adjusted multivariate regression analysis showed that the combination of axillary dissection and number of lymph nodes dissected was the main factor related to lymphedema (p = 0.017). CONCLUSION: In the pre-sentinel era, axillary dissection and the number of lymph nodes resected are related to 10-year lymphedema.

Retrospective analysis of breast cancer prognosis among young and older women in a Brazilian cohort of 738 patients, 1985-2002.

Invasive breast cancer (BC) is infrequent among women aged ≤40 years, however, the disease outlook in these younger patients is generally worse than among older women. The present study aimed to compare socio-demographic, clinical and pathological characteristics, and their association with long-term survival, between two random cohorts of young (≤40 years) and older (50-69 years) Brazilian patients with BC. The cohort comprised of 738 randomly selected women who were diagnosed with BC at Barretos Cancer Hospital, Pio XII Foundation (Barretos, Brazil) between January 1985 and December 2002; the patients included young women (n=376) and older women (n=362). The current analysis suggested that BC in young women is associated with numerous pathological features of aggressiveness. Second cancer and bilateral BC were independent predictors of a poor outcome in the younger group. Furthermore, C-erB-2 was positively correlated with poor outcome in the older group, whereas estrogen receptor status and TNM stage were associated with disease prognosis in both groups. The overall survival rates of the two age groups were similar except when analyzed according the treatment period (1997-2002). Although patients aged ≤40 years harbored tumors with more aggressive clinicopathological characteristics, these characteristics were not independent predictors of overall survival. The present study indicates that medical advances associated with prevention of breast cancer may improve screening programs, which may therefore increase early diagnosis and subsequently lower mortality rates.

Ki-67 and CD100 immunohistochemical expression is associated with local recurrence and poor prognosis in soft tissue sarcomas, respectively.

Soft tissue sarcomas (STSs) are a heterogeneous group of mesenchymal tumors of >50 subtypes. However, STSs represent <1% of types of cancer. Despite this low frequency, the disease is aggressive and treatment, when possible, is based on traditional chemotherapies. A number of cases of resistance to adjuvant therapies have been reported. Metastases are commonly identified in STS patients during diagnosis and the development of effective clinical parameters is crucial for correct management of the disease. The use of biological markers in cancer is a useful tool to determine patient prognosis. Ki-67 is a protein marker for proliferation of somatic cells and is widely used in prognostic studies of various types of tumor, including STSs. Cluster of differentiation 100 (CD100) is a member of the semaphorin family. The family was initially described as axon guidance molecules important for angiogenesis, organogenesis, apoptosis and neoplasia. CD100 was previously utilized as a prognostic factor in tumors and also in STSs. In the present study, protein expression of Ki-67 and CD100 was analyzed by immunohistochemistry in samples of STS patients of the Barretos Cancer Hospital (Barretos, Brazil) to establish prognostic criteria of the disease. Results demonstrate a correlation between CD100 expression and poor prognosis, consistent with a previous study. Moreover, the expression of Ki-67 was identified to correlate with presence of local or locoregional recurrence. To the best of our knowledge, no large casuistic study has revealed this correlation between Ki-67 and local recurrence in STSs. The use of Ki-67 and CD100 as markers in clinical pathological analysis may be suitable as a prognostic criterion in disease progression.

[The evaluation of an instrument for pediatric oncology patient classification]. / Avaliação de um instrumento para classificação de pacientes pediátricos oncológicos.

The objectives of this study were to assess the interrater reproducibility of the instrument to classify pediatric patients with cancer; verify the adequacy of the patient classification instrument for pediatric patients with cancer; and make a proposal for changing the instrument, thus allowing for the necessary adjustments for pediatric oncology patients. A total of 34 pediatric inpatients of a Cancer Hospital were evaluated by the teams of physicians, nurses and nursing technicians. The Kappa coefficient was used to rate the agreement between the scores, which revealed a moderate to high value in the objective classifications, and a low value in the subjective. In conclusion, the instrument is reliable and reproducible, however, it is suggested that to classify pediatric oncology patients, some items should be complemented in order to reach an outcome that is more compatible with the reality of this specific population.