Short-term effects of the COVID-19 pandemic on cancer screening, diagnosis and treatment procedures in Brazil: a descriptive study, 2019-2020. / Efeitos de curto prazo da pandemia de COVID-19 na realização de procedimentos de rastreamento, investigação diagnóstica e tratamento do câncer no Brasil: estudo descritivo, 2019-2020.

OBJECTIVE: To analyze the short-term effects of the COVID-19 pandemic on cancer screening, diagnosis and treatment in Brazil. METHODS: This was a descriptive study using data from the Outpatient and Hospital Information Systems, and the Cancer Information System. Monthly percentage variation of cancer screening, diagnosis and treatment procedures in 2019 and 2020 was calculated, as well as waiting time for cervical and breast cancer tests. RESULTS: In 2020 cytopathology tests fell by 3,767,686 (-44.6%), screening mammograms fell by 1,624,056 (-42.6%), biopsies fell by 257,697 (-35.3%), cancer surgery fell by 25,172 (-15.7%), and radiotherapy procedures fell by 552 (-0.7%), compared to 2019. Time intervals for performing cervical and breast cancer screening exams were little affected. CONCLUSION: Cancer control actions were impacted by the pandemic, making it necessary to devise strategies to mitigate the effects of possible delays in diagnosis and treatment.

Covid-19 in Brazil in 2020: impact on deaths from cancer and cardiovascular diseases.

OBJECTIVE: To analyze the impact of the covid-19 pandemic on mortality from cancer and cardiovascular diseases (CVD) as underlying cause and comorbidity in Brazil and Brazilian regions in 2020. METHODS: We used the 2019 and 2020 databases of the Mortality Information System (SIM) to analyze deaths occurring between March and December of each year that had cancer or CVD as the underlying cause or comorbidity. Deaths from covid-19 in 2020 were also analyzed. To estimate the Standardized Mortality Ratio (SMR) and the excess of deaths, 2019 data were considered as standard. RESULTS: Between March and December 2020, there were 181,377 deaths from cancer and 291,375 deaths from cardiovascular diseases in Brazil, indicating reduction rates of 9.7% and 8.8%, respectively, compared to the same period of the previous year. The pattern was maintained in the five Brazilian regions, with lower variation for cancer (-8.4% in the South to -10.9% in the Midwest). For CVD, the variation was greater, from -2.2% in the North to -10.5 in the Southeast and South. In the same period of 2020, these diseases were classified as comorbidities in 18,133 deaths from cancer and 188,204 deaths from cardiovascular diseases, indicating a proportional excess compared to data from 2019, of 82.1% and 77.9%, respectively. This excess was most significant in the Northern Region, with a ratio of 2.5 between observed and expected deaths for the two conditions studied. CONCLUSIONS: Excess deaths from cancer and CVD as comorbidities in 2020 may indicate that covid-19 had an important impact among patients with these conditions.

General anaesthesia versus other types of anaesthesia in patients undergoing surgery for treatment of cutaneous melanoma: a systematic review and meta-analysis.

General and local anaesthetics alter tumour behaviour in experimental models. Objectives: To investigate the relationship between general anaesthesia and recurrence or survival in patients who received surgery for malignant melanoma. A meta-analysis was performed based on a comprehensive literature search. Controlled and observational studies of patients undergoing surgery for melanoma under general anaesthesia, compared with other types of anaesthesia, were included. The primary outcomes were overall survival and disease-free survival. The secondary outcomes included cancer-specific survival, cost analysis, and adverse events. Risk of bias was assessed. Individual study information was summarized. The meta-analysis was performed using a random-effects model. The GRADE approach was used to summarise the certainty of evidence. Eight studies were included (n = 5,832). The use of general anaesthesia was not associated with any statistical difference in overall survival (p = 0.087; 1 NRS; n= 104; very low certainty of evidence) or disease-free survival (HR: 1.266; 95% CI: 0.904-1.773; p = 0.169; 1 NRS; n = 281; very low certainty of evidence). However, general anaesthesia was associated with worse melanoma-specific survival (HR: 1.46; 95% CI: 1.22-1.68: p < 0.00001; 3 NRS; n = 4654; low certainty of evidence). Three studies reported increased intraoperative costs associated with the use of general anaesthesia (3 NRT; n = 513; very low certainty of evidence). No study adequately reported other primary or secondary outcomes. General anaesthesia may reduce melanoma-specific survival in patients undergoing surgery for treatment of cutaneous melanoma. We are uncertain whether general anaesthesia impacts the other reported outcomes.

Breast Cancer Quality of Life and Health-state Utility at a Brazilian Reference Public Cancer Center.

Objectives: To evaluate health-related-quality-of-life and derive health-state-utility (HSU) from breast cancer patients, before and after routine therapy at a Brazilian reference public cancer center.Methods: In a prospective cohort study, a consecutive sample of outpatients newly diagnosed with breast cancer was submitted to two interviews (baseline, 6-month) to complete EQ-5D-3L/VAS and EORTC-QLQ-C30/BR23 questionnaires. Demographic and clinical information was reviewed from medical records.Results: For 196 patients, EQ-5D domains of pain/discomfort and anxiety/depression were mainly affected, but partially improved overtime, while mobility/usual activities/self-care worsened after therapy. EORTC-QLQ-C30/BR23 scales mostly affected were emotional functioning, insomnia, pain, sexual enjoyment and future self-health perspective at baseline, while financial difficulties, insomnia, fatigue and therapy side-effects at follow-up. Overtime mean scores were 71.4 (95%CI68.5-74.4) and 76.1 (95%CI73.3-78.8) for EQ-5D-VAS, and 0.712 (95%CI0.686-0.737) and 0.732 (95%CI0.707-0.757) for HSU. HSU was 0.689 (95%CI0.648-0.730) in stages III-IV, and 0.692 (95%CI0.652-0.731) under two/three chemotherapy regimens.Conclusion: In a context of impairments in emotional functioning, sexual enjoyment, symptoms burden, and poor future self-health perspective, breast cancer produced a mean HSU of 0.712. After routine care, there was a small improvement in quality of life, with lower HSU particularly in advanced disease and multiple chemotherapy regimens.

Custo-utilidade de terapias-alvo comparadas à dacarbazina para o tratamento de primeira linha do melanoma avançado não-cirúrgico e metastático no Sistema Único de Saúde do Brazil.

OBJECTIVE: To estimate the incremental cost-utility ratio (ICUR) of isolated and combined targeted therapy regimens compared to dacarbazine for first-line treatment of advanced and metastatic melanoma with BRAF V600 mutation. METHODS: A Markov model with three health states (no progression, progression and death), monthly duration cycle and 10-year time horizon was constructed to compare targeted therapy regimens (vemurafenib, dabrafenib, vemurafenib/cobimetinib and dabrafenib/trametinib) with dacarbazine chemotherapy under the Brazilian public health perspective. One-way and probabilistic sensitivity analyses were performed. RESULTS: Mean cost was R$5662.50 ($1490.13) for dacarbazine, R$175 937.18 (46 299.26) for vemurafenib, R$167 461.70 ($44 068.87) for dabrafenib, R$425 901 ($112 079.21) for vemurafenib/cobimetinib and R$411 799.81 ($108 368.37) for dabrafenib/trametinib, whereas QALY was 0.91 for dacarbazine, 1.08 for vemurafenib, 1.12 for dabrafenib, 1.64 for vemurafenib/cobimetinib and 1.56 for dabrafenib/trametinib. The ICUR was estimated from R$572 165.76 ($150 569.94) to R$1 012 524.56 ($266 453.83) per patient, and the most impactful parameters were risk of progression and death, and treatment cost. CONCLUSION: The incorporation of targeted therapies in the Brazilian public health system would produce an additional expenditure of at least 19 times the national GDP per capita to increase in one year the quality-adjusted survival of each patient with advanced/metastatic BRAF-mutant melanoma.

Target therapy versus dacarbazine in first-line treatment of advanced non-surgical and metastatic melanoma: budget impact analysis from the perspective of the Brazilian National Health System, 2018-2020. / Terapia-alvo versus dacarbazina no tratamento de primeira linha do melanoma avançado não cirúrgico e metastático: análise de impacto orçamentário na perspectiva do Sistema Único de Saúde, 2018-2020.

OBJECTIVE: to estimate the incremental budget impact of target therapy for first-line treatment of advanced non-surgical and metastatic melanoma compared to dacarbazine treatment. METHODS: budget impact analysis, from the Brazilian National Health System (SUS) perspective; based on demographic data and incidence estimates, the population over a three-year time horizon (2018-2020) was delimited and the direct medical costs were estimated; the reference scenario was treatment with dacarbazine, and the alternative scenarios were target therapy with vemurafenib, dabrafenib, vemurafenib + cobimetinib and dabrafenib + trametinib; uncertainty assessment was conducted through scenario analysis. RESULTS: the incremental budget impact ranged from R$ 451,867,881.00 to R$ 768,860,968.00, representing 0.70 to 1.53% of total SUS annual outpatient drugs expenditure; in best and worst scenario, results ranged from R$ 289,160,835.00 to R$ 1,107,081,926.00. CONCLUSION: the use of target therapy compared to dacarbazine implies an excessive impact on the budget, this bring unfovorable to its possible incorporation.

Patient Preferences for Breast Cancer Treatment Interventions: A Systematic Review of Discrete Choice Experiments.

INTRODUCTION: Understanding how patients value different characteristics of an intervention and make trade-offs in a therapy choice context with potential benefit and possible harm may result in decisions for which a better reflected value is delivered. This systematic review summarizes patient preferences for breast cancer treatments elicited by discrete choice experiments (DCE). METHODOLOGY: The electronic databases MEDLINE (PubMed), Scopus, PsycINFO, CINAHL, LILACS, and Web of Science were last searched on May 9, 2019 without restrictions regarding language and time of publication. Original studies reporting patient preferences related to breast cancer treatment (surgery, radiotherapy, endocrine therapy, chemotherapy or palliative care) elicited by DCE were eligible. A narrative synthesis of the relative importance and trade-offs of the treatment attributes of each study was reported. RESULTS: Five studies conducted in Japan, Thailand, USA and the Netherlands with 146-298 participants evaluated preferences regarding chemotherapy regimens for advanced/metastatic disease, and breast reconstruction after mastectomy. The attributes with major relative effects on preferences were greater survival, better aesthetic result of the surgery, and lower side effects and complication rates. Patients would trade a better aesthetic result to minimize complication rates, and, in advanced disease, the willingness to pay was greater for gains in survival and to avoid some severe adverse events. CONCLUSION: Despite the relative lack of evidence in this specific context, our review shows that breast cancer patients naturally value greater benefit and, in scenarios of advanced and metastatic disease, are willing to face risks of some side effects for gains in survival.

Impact of general anaesthesia in overall and disease-free survival compared to other types of anaesthesia in patients undergoing surgery for cutaneous melanoma: a systematic review and meta-analysis protocol.

INTRODUCTION: Cutaneous melanoma is an aggressive type of skin cancer. Anaesthetic agents may have an impact on the immune response, postoperative neurohumoral response and tumour progression. This systematic review aims to evaluate the impact of general anaesthesia on overall and disease-free survival compared with other types anaesthesia in patients undergoing surgery for cutaneous melanoma. METHODS AND ANALYSIS: The review will analyse data from controlled and observational studies of patients undergoing surgery for melanoma under general anaesthesia compared with other types of anaesthesia. The primary outcomes are overall survival and disease-free survival. The secondary outcomes are health-related quality of life, time to tumour progression, distant disease-free survival, time to treatment failure, cancer-specific survival, biochemical recurrence, return of intended oncological therapy, days alive and out of the hospital at 90 days, cost analysis and adverse events. A comprehensive literature search will be performed using the MEDLINE, EMBASE, Cochrane CENTRAL, Web of Science, LILACS and IBECS databases. Grey literature will also be searched. Risk of methodological bias will be assessed using The Cochrane Collaboration's revised tool for assessing risk of bias in randomised trials (RoB 2.0) and the Newcastle-Ottawa scale. Two reviewers will independently assess the eligibility of studies and risk of bias; a third author will solve discrepancies. One author will perform data extraction and the other will check the process and data. Qualitative analysis will be carried out using all included studies. A meta-analysis using a random-effects model for pooled risk estimates will be carried out for the two main outcomes and for selected secondary outcomes if they conform to previously stated criteria. The GRADE approach will be used to summarise the quality of evidence. ETHICS AND DISSEMINATION: Ethics approval is not required as we analyse data from previously reported studies. PROSPERO REGISTRATION NUMBER: CRD42018114918.

Guidelines for HPV-DNA Testing for Cervical Cancer Screening in Brazil.

Evidence-based clinical guidelines ensure best practice protocols are available in health care. There is a widespread use of human papillomavirus deoxyribonucleic acid (HPV-DNA) tests in Brazil, regardless of the lack of official guidelines. On behalf of the Brazilian Association for the Lower Genital Tract Pathology and Colposcopy (ABPTGIC, in the Portuguese acronym), a team of reviewers searched for published evidence and developed a set of recommendations for the use of HPV-DNA tests in cervical cancer screening in Brazil. The product of this process was debated and consensus was sought by the participants. One concern of the authors was the inclusion of these tests in the assessment of women with cytologic atypia and women treated for cervical intraepithelial neoplasia (CIN). Testing for HPV is recommended in an organized screening scenario to identify women with precursor lesions or asymptomatic cervical cancer older than 30 years of age, and it can be performed every 5 years. It also has value after the cytology showing atypical squamous cells of undetermined significance (ASC-US) or low-grade squamous intraepithelial lesions (LSILs) as a triage test for colposcopy, in the investigation of other cytological alterations when no abnormal findings are observed at colposcopy, seeking to exclude disease, or, further, after treatment of high-grade cervical intraepithelial neoplasia, to rule out residual disease.

O uso de diretrizes clínicas baseadas em evidências visa assegurar as melhores práticas na área de cuidado à saúde. O uso de testes de ácido desoxirribonucleico de papilomavírus humano (DNA-HPV) vem crescendo e se disseminando sem que existam recomendações de uso no cenário brasileiro. Em nome da Associação Brasileira de Patologia do Trato Genital Inferior e Colposcopia (ABPTGIC), grupos de revisores pesquisaram evidências e formularam recomendações para o uso dos testes de DNA-HPV no rastreamento do câncer do colo do útero, no seguimento de mulheres com atipias citológicas, e após tratamento de neoplasia intraepitelial cervical (NIC). O produto desse processo foi debatido e foi buscado consenso entre participantes. Os testes de DNA-HPV são recomendados num cenário de rastreamento organizado para identificação de mulheres portadoras de lesões precursoras ou câncer assintomático com mais de 30 anos e podem ser realizados a cada 5 anos. Também têm valor após a citologia mostrando células escamosas atípicas de significado indeterminado (ASC-US) ou lesão intraepitelial escamosa de baixo grau (LSIL) como teste de triagem para colposcopia, na investigação de outras alterações citológicas quando não são observados achados anormais à colposcopia, buscando excluir doença, ou, ainda, no seguimento após tratamento das neoplasias intraepiteliais de alto grau, para exclusão de doença residual.

Efeitos de curto prazo da pandemia de COVID-19 na realização de procedimentos de rastreamento, investigação diagnóstica e tratamento do câncer no Brasil: estudo descritivo, 2019-2020 / Efectos a corto plazo de la pandemia COVID-19 en la realización de procedimientos de rastreo, investigación diagnóstica y tratamiento del cáncer en Brasil: estudio descriptivo, 2019-2020 / Short-term effects of the COVID-19 pandemic on cancer screening, diagnosis and treatment procedures in Brazil: a descriptive study, 2019-2020

Objetivo: Analisar efeitos de curto prazo da pandemia de COVID-19 no rastreamento, investigação diagnóstica e tratamento de câncer no Brasil. Métodos: Estudo descritivo, utilizando-se dados do Sistema de Informações Ambulatoriais e do Sistema de Informações Hospitalares, e Sistema de Informação do Câncer. Calculou-se a variação percentual mensal de procedimentos de rastreamento, diagnóstico e tratamento de câncer, em 2019 e 2020, além do tempo esperado para realização dos exames relacionados aos cânceres do colo do útero e de mama. Resultados: Em 2020, houve redução de 3.767.686 (-44,6%) exames citopatológicos, 1.624.056 (-42,6%) mamografias, 257.697 (-35,3%) biópsias, 25.172 cirurgias oncológicas (-15,7%) e 552 (-0,7%) procedimentos de radioterapia, comparando-se a 2019. Os intervalos de tempo para realização de exames de rastreamento de câncer do colo uterino e mama foram pouco afetados. Conclusão: Ações de controle do câncer foram afetadas pela pandemia, sendo necessárias estratégias para mitigar efeitos dos atrasos no diagnóstico e tratamento.

Objetivo: Analizar los efectos a corto plazo de la pandemia por COVID-19 en rastreo, diagnóstico y tratamiento de cáncer en Brasil. Métodos: Estudio descriptivo utilizando datos del Sistemas de Información Ambulatoria y Hospitalaria del SUS y Sistema de Información del Cáncer. Se calculó la variación porcentual mensual en procedimientos de rastreo, diagnóstico y tratamiento de cáncer para 2019 y 2020, y el tiempo para realizar exámenes de cánceres de cérvix y mama. Resultados: En 2020 hubo reducción de 3.767.686 (-44,6%) en exámenes citopatológicos, 1.624.056 (-42,6%) en mamografías, 257.697 (-35,3%) en biopsias, 25.172 (-15,7%) en cirugías oncológicas y 552 (-0,7%) en radioterapia en comparación con 2019. Tiempos de los exámenes de rastreo para los cánceres de cérvix y de mama se vieron poco afectados. Conclusión: Acciones de control del cáncer se vieron impactadas por la pandemia, por lo que fue necesario diseñar estrategias para mitigar los efectos de posibles retrasos en diagnóstico y tratamiento.

Objective: To analyze the short-term effects of the COVID-19 pandemic on cancer screening, diagnosis and treatment in Brazil. Methods: This was a descriptive study using data from the Outpatient and Hospital Information Systems, and the Cancer Information System. Monthly percentage variation of cancer screening, diagnosis and treatment procedures in 2019 and 2020 was calculated, as well as waiting time for cervical and breast cancer tests. Results: In 2020 cytopathology tests fell by 3,767,686 (-44.6%), screening mammograms fell by 1,624,056 (-42.6%), biopsies fell by 257,697 (-35.3%), cancer surgery fell by 25,172 (-15.7%), and radiotherapy procedures fell by 552 (-0.7%), compared to 2019. Time intervals for performing cervical and breast cancer screening exams were little affected. Conclusion: Cancer control actions were impacted by the pandemic, making it necessary to devise strategies to mitigate the effects of possible delays in diagnosis and treatment.

Covid-19 in Brazil in 2020: impact on deaths from cancer and cardiovascular diseases / Covid-19 no Brasil em 2020: impacto nas mortes por câncer e doenças cardiovasculares

ABSTRACT OBJECTIVE To analyze the impact of the covid-19 pandemic on mortality from cancer and cardiovascular diseases (CVD) as underlying cause and comorbidity in Brazil and Brazilian regions in 2020. METHODS We used the 2019 and 2020 databases of the Mortality Information System (SIM) to analyze deaths occurring between March and December of each year that had cancer or CVD as the underlying cause or comorbidity. Deaths from covid-19 in 2020 were also analyzed. To estimate the Standardized Mortality Ratio (SMR) and the excess of deaths, 2019 data were considered as standard. RESULTS Between March and December 2020, there were 181,377 deaths from cancer and 291,375 deaths from cardiovascular diseases in Brazil, indicating reduction rates of 9.7% and 8.8%, respectively, compared to the same period of the previous year. The pattern was maintained in the five Brazilian regions, with lower variation for cancer (-8.4% in the South to -10.9% in the Midwest). For CVD, the variation was greater, from -2.2% in the North to -10.5 in the Southeast and South. In the same period of 2020, these diseases were classified as comorbidities in 18,133 deaths from cancer and 188,204 deaths from cardiovascular diseases, indicating a proportional excess compared to data from 2019, of 82.1% and 77.9%, respectively. This excess was most significant in the Northern Region, with a ratio of 2.5 between observed and expected deaths for the two conditions studied. CONCLUSIONS Excess deaths from cancer and CVD as comorbidities in 2020 may indicate that covid-19 had an important impact among patients with these conditions.

RESUMO OBJETIVO Analisar o impacto da pandemia de covid-19 sobre a mortalidade por câncer e por doenças cardiovasculares (DCV) como causa básica e comorbidade no Brasil e em suas regiões em 2020. MÉTODOS Foram utilizadas as bases de dados de 2019 e 2020 do Sistema de Informações de Mortalidade (SIM), analisando os óbitos ocorridos entre março e dezembro de cada ano que tiveram o câncer e as DCV como causa básica ou como comorbidade. Também foram analisados os óbitos por covid-19 em 2020. Para o cálculo da Razão de Mortalidade Padronizada (RMP) e estimativa do excesso de mortes, os dados de 2019 foram considerados como padrão. RESULTADOS Entre março e dezembro de 2020 ocorreram no Brasil 181.377 mortes por câncer e 291.375 mortes por doenças cardiovasculares, indicando redução de 9,7% e de 8,8%, respectivamente, em relação ao mesmo período do ano anterior. O padrão foi mantido nas cinco regiões brasileiras, com menor variação para o câncer (-8,4% na Região Sul a -10,9% na Região Centro-Oeste). Para as DCV houve uma maior variação, de -2,2% na Região Norte até -10,5 nas regiões Sudeste e Sul. No mesmo período de 2020, essas enfermidades foram classificadas como comorbidade em 18.133 óbitos por câncer e 188.204 óbitos por doenças cardiovasculares, indicando um excesso proporcional, se comparado aos dados de 2019, de 82,1% e 77,9%, respectivamente. Esse excesso foi mais expressivo na Região Norte, com razão de 2,5 entre mortes observadas e esperadas, para as duas condições estudadas. CONCLUSÕES O excesso de óbitos por câncer e DCV como comorbidade em 2020 pode indicar que a covid-19 teve um importante impacto entre pacientes portadores dessas condições.

Terapia-alvo versus dacarbazina no tratamento de primeira linha do melanoma avançado não cirúrgico e metastático: análise de impacto orçamentário na perspectiva do Sistema Único de Saúde, 2018-2020 / Terapia dirigida versus dacarbazina en el tratamiento de primera línea del melanoma avanzado no quirúrgico y metastásico: análisis de impacto presupuestario en la perspectiva del Sistema Nacional de Salud de Brasil, 2018-2020 / Target therapy versus dacarbazine in first-line treatment of advanced non-surgical and metastatic melanoma: budget impact analysis from the perspective of the Brazilian National Health System, 2018-2020

Objetivo: estimar o impacto orçamentário incremental da terapia-alvo para tratamento de primeira linha do melanoma avançado não cirúrgico e metastático, em comparação à dacarbazina. Métodos: análise de impacto orçamentário na perspectiva do Sistema Único de Saúde (SUS) do Brasil; a partir de dados demográficos e estimativas da incidência, foi delimitada a população no horizonte temporal de três anos (2018-2020) e estimados os custos diretos médicos; foi considerado cenário de referência o tratamento com dacarbazina, e como cenários alternativos a terapia-alvo com vemurafenibe, dabrafenibe, vemurafenibe + cobimetinibe e dabrafenibe + trametinibe; a avaliação das incertezas foi conduzida mediante análise por cenários. Resultados: o impacto orçamentário incremental variou de R$ 451.867.881,00 a R$ 768.860.968,00, representando 0,70 a 1,53% dos gastos anuais totais com medicamentos ambulatoriais no SUS; no melhor e no pior cenário, os resultados variaram de R$ 289.160.835,00 a R$ 1.107.081.926,00. Conclusão: a terapia-alvo, comparada à dacarbazina, implica impacto excessivo no orçamento, desfavorecendo eventual incorporação.

Objetivo: estimar el impacto presupuestario incremental de la terapia dirigida para tratamiento de primera línea del melanoma avanzado no quirúrgico y metastásico comparado con la dacarbazina. Métodos: análisis de impacto presupuestario, en la perspectiva del Sistema Único de Salud (SUS) de Brasil; a partir de datos demográficos y estimaciones de incidencia se delimitó la población en un horizonte temporal de tres años (2018-2020) y se estimaron los costos directos médicos. El escenario de referencia fue el tratamiento con dacarbazina y los escenarios alternativos la terapia dirigida con vemurafenib, dabrafenib, vemurafenib + cobimetinib y dabrafenib + trametinib; la evaluación de incertidumbre se llevó a cabo mediante análisis por escenarios. Resultados: el impacto presupuestario incremental varió de R$ 451.867.881,00 a R$ 768.860.968,00, representando 0,70 a 1,53% de gastos anuales totales con medicamentos de ambulatorios en el SUS; en el mejor y el peor escenario los resultados variaron de R$ 289.160.835,00 a R$ 1.107.081.926,00. Conclusión: el uso de terapia dirigida comparado a la dacarbazina implica en impacto excesivo en el presupuesto, desfavoreciendo una eventual incorporación.

Objective: to estimate the incremental budget impact of target therapy for first-line treatment of advanced non-surgical and metastatic melanoma compared to dacarbazine treatment. Methods: budget impact analysis, from the Brazilian National Health System (SUS) perspective; based on demographic data and incidence estimates, the population over a three-year time horizon (2018-2020) was delimited and the direct medical costs were estimated; the reference scenario was treatment with dacarbazine, and the alternative scenarios were target therapy with vemurafenib, dabrafenib, vemurafenib + cobimetinib and dabrafenib + trametinib; uncertainty assessment was conducted through scenario analysis. Results: the incremental budget impact ranged from R$ 451,867,881.00 to R$ 768,860,968.00, representing 0.70 to 1.53% of total SUS annual outpatient drugs expenditure; in best and worst scenario, results ranged from R$ 289,160,835.00 to R$ 1,107,081,926.00. Conclusion: the use of target therapy compared to dacarbazine implies an excessive impact on the budget, this bring unfovorable to its possible incorporation.

Guidelines for HPV-DNA testing for cervical cancer screening in Brazil / Recomendações para o uso de testes de DNA-HPV no rastreamento do câncer do colo útero no Brasil

Abstract Evidence-based clinical guidelines ensure best practice protocols are available in health care. There is a widespread use of human papillomavirus deoxyribonucleic acid (HPVDNA) tests in Brazil, regardless of the lack of official guidelines. On behalf of the Brazilian Association for the Lower Genital Tract Pathology and Colposcopy (ABPTGIC, in the Portuguese acronym), a team of reviewers searched for published evidence and developed a set of recommendations for the use of HPV-DNA tests in cervical cancer screening in Brazil. The product of this process was debated and consensus was sought by the participants. One concern of the authors was the inclusion of these tests in the assessment of women with cytologic atypia and women treated for cervical intraepithelial neoplasia (CIN). Testing for HPV is recommended in an organized screening scenario to identify women with precursor lesions or asymptomatic cervical cancer older than 30 years of age, and it can be performed every 5 years. It also has value after the cytology showing atypical squamous cells of undetermined significance (ASC-US) or low-grade squamous intraepithelial lesions (LSILs) as a triage test for colposcopy, in the investigation of other cytological alterations when no abnormal findings are observed at colposcopy, seeking to exclude disease, or, further, after treatment of high-grade cervical intraepithelial neoplasia, to rule out residual disease.

Resumo O uso de diretrizes clínicas baseadas em evidências visa assegurar as melhores práticas na área de cuidado à saúde. O uso de testes de ácido desoxirribonucleico de papilomavírus humano (DNA-HPV) vem crescendo e se disseminando sem que existam recomendações de uso no cenário brasileiro.Emnomeda Associação Brasileira de Patologia doTrato Genital Inferior e Colposcopia (ABPTGIC), grupos de revisores pesquisaram evidências e formularamrecomendações para o uso dos testes de DNA-HPV no rastreamento do câncer do colo do útero, no seguimento de mulheres com atipias citológicas, e após tratamento de neoplasia intraepitelial cervical (NIC). O produto desse processo foi debatido e foi buscado consenso entre participantes. Os testes de DNA-HPV são recomendados num cenário de rastreamento organizado para identificação de mulheres portadoras de lesões precursoras ou câncer assintomático com mais de 30 anos e podem ser realizados a cada 5 anos. Também têm valor após a citologia mostrando células escamosas atípicas de significado indeterminado (ASC-US) ou lesão intraepitelial escamosa de baixo grau (LSIL) como teste de triagempara colposcopia, na investigação de outras alterações citológicas quando não são observados achados anormais à colposcopia, buscando excluir doença, ou, ainda, no seguimento após tratamento das neoplasias intraepiteliais de alto grau, para exclusão de doença residual.

Colposcopic triage methods for detecting cervical intraepithelial neoplasia grade 3 after cytopathological diagnosis of low-grade squamous intraepithelial lesion: a systematic review on diagnostic tests.

CONTEXT AND OBJECTIVE: The age-stratified performance of the oncogenic HPV-DNA (human papillomavirus deoxyribonucleic acid) test for triage of low-grade squamous intraepithelial lesions (LSIL) requires investigation. The objective of this study was to evaluate and compare the age-stratified performance (cutoff point: 35 years) of oncogenic HPV-DNA testing and repeated cytological tests, for detecting cervical intraepithelial neoplasia grade 3 (CIN3), in order to triage for LSIL. DESIGN AND SETTING: Systematic review. Studies were identified in nine electronic databases and in the reference lists of the articles retrieved. METHODS: The eligibility criteria consisted of initial cytological findings of LSIL; subsequent oncogenic HPV-DNA testing and repeated cytological tests; and CIN3 detection. The Quality Assessment of Diagnostic Accuracy Studies (QUADAS) guidelines were used for quality assessment. Qualitative information synthesis was performed. RESULTS: Out of 7,776 studies, 284 were identified as pertinent and three fulfilled the eligibility criteria. The CIN3 prevalence ranged from 6% to 12%. The HPV-DNA positivity rate ranged from 64% to 83%; sensitivity for CIN3 detection ranged from 95.2% to 100%; and specificity was available in two studies (27% and 52%). The sensitivity of repeated cytological tests, in relation to the threshold for atypical squamous cells of undetermined significance (ASCUS), was available in two studies (33% and 90.8%); and specificity was available in one study (53%). CONCLUSIONS: Currently, there is no scientific evidence available that would prove that colposcopic triage using oncogenic HPV-DNA testing to detect CIN3 performs better than repeated cytological tests, among women with LSIL aged 35 years and over.

Risk of persistent high-grade squamous intraepithelial lesion after electrosurgical excisional treatment with positive margins: a meta-analysis.

CONTEXT AND OBJECTIVE: Even if precursor lesions of cervical cancer are properly treated, there is a risk of persistence or recurrence. The aim here was to quantify the risks of persistence of high-grade intraepithelial squamous lesions, one and two years after cervical electrosurgical excisional treatment with positive margins. DESIGN AND SETTING: Systematic review of the literature and meta-analysis at Instituto Fernandes Figueira. METHODS: This meta-analysis was on studies published between January 1989 and July 2009 that were identified in Medline, Scopus, Embase, Cochrane, SciELO, Lilacs, Adolec, Medcarib, Paho, Wholis, Popline, ISI Web of Science and Sigle. Articles were selected if they were cohort studies on electrosurgical excisional treatment of high-grade squamous intraepithelial lesions with a minimum follow-up of one year, a histopathological outcome of persistence of these lesions and a small risk of bias. RESULTS: The search identified 7,066 articles and another 21 in the reference lists of these papers. After applying the selection and exclusion criteria, only four articles were found to have extractable data. The risk of persistence of high-grade intraepithelial lesions after one year was 11.36 times greater (95% confidence interval, CI: 5.529-23.379, P < 0.0001) in patients with positive margins and after two years, was four times greater (95% CI: 0.996-16.164), although without statistical significance. CONCLUSION: This meta-analysis confirms the importance of positive margins as an indicator of incomplete treatment after the first year of follow-up and highlights the need for appropriately chosen electrosurgical techniques based on disease location and extent, with close surveillance of these patients.

Colposcopic triage methods for detecting cervical intraepithelial neoplasia grade 3 after cytopathological diagnosis of low-grade squamous intraepithelial lesion: a systematic review on diagnostic tests / Métodos de triagem colposcópica para detecção de neoplasia intraepitelial cervical grau 3 após diagnóstico citopatológico de lesão intraepitelial escamosa de baixo grau: uma revisão sistemática de testes diagnósticos

CONTEXT AND OBJECTIVE: The age-stratified performance of the oncogenic HPV-DNA (human papillomavirus deoxyribonucleic acid) test for triage of low-grade squamous intraepithelial lesions (LSIL) requires investigation. The objective of this study was to evaluate and compare the age-stratified performance (cutoff point: 35 years) of oncogenic HPV-DNA testing and repeated cytological tests, for detecting cervical intraepithelial neoplasia grade 3 (CIN3), in order to triage for LSIL. DESIGN AND SETTING: Systematic review. Studies were identified in nine electronic databases and in the reference lists of the articles retrieved. METHODS: The eligibility criteria consisted of initial cytological findings of LSIL; subsequent oncogenic HPV-DNA testing and repeated cytological tests; and CIN3 detection. The Quality Assessment of Diagnostic Accuracy Studies (QUADAS) guidelines were used for quality assessment. Qualitative information synthesis was performed. RESULTS: Out of 7,776 studies, 284 were identified as pertinent and three fulfilled the eligibility criteria. The CIN3 prevalence ranged from 6 percent to 12 percent. The HPV-DNA positivity rate ranged from 64 percent to 83 percent; sensitivity for CIN3 detection ranged from 95.2 percent to 100 percent; and specificity was available in two studies (27 percent and 52 percent). The sensitivity of repeated cytological tests, in relation to the threshold for atypical squamous cells of undetermined significance (ASCUS), was available in two studies (33 percent and 90.8 percent); and specificity was available in one study (53 percent). CONCLUSIONS: Currently, there is no scientific evidence available that would prove that colposcopic triage using oncogenic HPV-DNA testing to detect CIN3 performs better than repeated cytological tests, among women with LSIL aged 35 years and over.

CONTEXTO E OBJETIVO: O desempenho do teste de DNA-HPV (ácido desoxirribonucleico-papilomavírus humano) oncogênico estratificado por idade para triagem de lesão intraepitelial escamosa de baixo grau (LSIL) demanda investigação. O objetivo do estudo foi avaliar e comparar o desempenho, para detecção de neoplasia intraepitelial cervical (NIC3), do teste de DNA-HPV oncogênico e da citologia de repetição estratificados por idade (ponto de corte 35 anos), para triagem de LSIL. TIPO DE ESTUDO E LOCAL: Revisão sistemática da literatura. Foram identificados estudos em nove bases de dados eletrônicas e listas de referências dos artigos recuperados. MÉTODOS: Critérios de elegibilidade: citologia inicial LSIL, realização do teste de DNA-HPV oncogênico e da citologia de repetição e detecção de NIC3. A diretriz QUADAS (Quality Assessment of Diagnostic Accuracy Studies) foi utilizada para avaliação da qualidade. As informações foram sintetizadas qualitativamente. RESULTADOS: Dentre 7.776 estudos, 284 eram pertinentes ao tema e três atenderam aos critérios de elegibilidade. A prevalência de NIC3 apresentou variação entre 6 por cento e 12 por cento. A taxa de positividade do teste de DNA-HPV apresentou variação entre 64 por cento e 83 por cento; a sensibilidade para NIC3 apresentou variação entre 95,2 por cento e 100 por cento; a especificidade estava disponível em dois estudos (27 por cento e 52 por cento). A sensibilidade da citologia de repetição (ponto de corte ASCUS - células escamosas atípicas de significado indeterminado) estava disponível em dois estudos (33 por cento e 90,8 por cento); a especificidade estava disponível em um estudo (53 por cento). CONCLUSÕES: Não existem, atualmente, evidências científicas disponíveis para comprovar que, em mulheres com 35 anos ou mais e citologia LSIL, a triagem colposcópica com teste de DNA-HPV oncogênico apresenta melhor desempenho para detecção de NIC3 do que a repetição citológica.

Risk of persistent high-grade squamous intraepithelial lesion after electrosurgical excisional treatment with positive margins: a meta-analysis / Risco de persistência da lesão intraepitelial escamosa de alto grau após tratamento excisional eletrocirúrgico com margens comprometidas: uma metanálise

CONTEXT AND OBJECTIVE: Even if precursor lesions of cervical cancer are properly treated, there is a risk of persistence or recurrence. The aim here was to quantify the risks of persistence of high-grade intraepithelial squamous lesions, one and two years after cervical electrosurgical excisional treatment with positive margins. DESIGN AND SETTING: Systematic review of the literature and meta-analysis at Instituto Fernandes Figueira. METHODS: This meta-analysis was on studies published between January 1989 and July 2009 that were identified in Medline, Scopus, Embase, Cochrane, SciELO, Lilacs, Adolec, Medcarib, Paho, Wholis, Popline, ISI Web of Science and Sigle. Articles were selected if they were cohort studies on electrosurgical excisional treatment of high-grade squamous intraepithelial lesions with a minimum follow-up of one year, a histopathological outcome of persistence of these lesions and a small risk of bias. RESULTS: The search identified 7,066 articles and another 21 in the reference lists of these papers. After applying the selection and exclusion criteria, only four articles were found to have extractable data. The risk of persistence of high-grade intraepithelial lesions after one year was 11.36 times greater (95% confidence interval, CI: 5.529-23.379, P < 0.0001) in patients with positive margins and after two years, was four times greater (95% CI: 0.996-16.164), although without statistical significance. CONCLUSION: This meta-analysis confirms the importance of positive margins as an indicator of incomplete treatment after the first year of follow-up and highlights the need for appropriately chosen electrosurgical techniques based on disease location and extent, with close surveillance of these patients.

CONTEXTO E OBJETIVO: As lesões precursoras do câncer de colo uterino, mesmo se tratadas adequadamente, têm risco de persistirem ou recidivarem. O objetivo foi quantificar o risco de persistência da lesão intraepitelial escamosa de alto grau (HSIL) em um e dois anos após tratamento excisional eletrocirúrgico do colo uterino com margens comprometidas. TIPO DE ESTUDO E LOCAL: Revisão sistemática da literatura e metanálise no Instituto Fernandes Figueira. METÓDO: Metanálise de estudos publicados entre janeiro de 1989 e julho de 2009 identificados em Medline, Scopus, Embase, Cochrane, SciELO, Lilacs, Adolec, Medcarib, Paho, Wholis, Popline, Isis Web of Science e Sigle. Os artigos eram selecionados se fossem estudos tipo coorte sobre tratamento excisional eletrocirúrgico de HSIL com acompanhamento mínimo de um ano e tivessem como desfecho histopatológico a persistência de HSIL com pequeno risco de viés. RESULTADOS: Foram identificados 7.066 artigos e mais 21 nas listas de referências desses artigos. Após aplicação de critérios de seleção e de exclusão, somente quatro artigos ofereciam dados passíveis de extração. O risco de persistência da HSIL em um ano foi 11.36 vezes maior nas pacientes com margens comprometidas (intervalo de confiança, IC 95%: 5.529-23.379; P < 0,0001) e, em dois anos, chegou a quatro vezes, embora sem significância estatística (IC 95% 0.996-16.164). CONCLUSÃO: Esta metanálise confirma a importância de margem comprometida como indicador de tratamento incompleto no primeiro ano e ressalta a necessidade de uma adequada escolha da técnica eletrocirúrgica em função da localização e extensão da doença e um acompanhamento adequado dessas pacientes.

Avaliação da qualidade dos laboratórios de citopatologia do colo do útero no Brasil / Quality evaluation of cervical cytopathology laboratories in Brazil

Introdução: O exame citopatológico é a estratégia mais adotada no mundo para o rastreamento do câncer do colo do útero e a única que teve impacto comprovado na redução da incidência e da mortalidade por essa doença.Garantir a qualidade desse Procedimento é uma prioridade para a efetividade do Programa de Controle do Câncer do Colo do Útero no Brasil. Objetivo: Apresentar o perfil dos laboratórios de citopatologia cervicouterina no ano de 2010 para todos os Estados brasileiros e o Distrito Federal, analisando alguns indicadores de Monitoramento Interno da Qualidade (MIQ). Método: As informações contidas no Sistema de Informação do Câncer do Colo do Útero (SISCOLO ) referentes a 2010, por Unidade da Federação, foram utilizadas para o cálculo dos indicadores de qualidade estudados. Resultados: O Brasil possui um grande quantitativo de prestadores de serviço de citopatologiaconcentrados em faixas de positividades abaixo de 2,0%. Parte dos casos positivos registrados no sistema não traziam conclusão diagnóstica devido aos elevados percentuais de atipias de significado indeterminado em células escamosas. Outra evidência constatada foi a baixa capacidade da rede laboratorial para a identificação de lesões intraepiteliais de alto grau. Conclusão: Os resultados apontam para o risco de não identificação dos casos sugestivos de alteração celular e alertam para a possibilidade de emissão de laudos falsos-negativos. É importante implementar programas de controle de qualidade do exame citopatológico. O estudo serve de auxílio aos gestores na organização da rede de laboratórios