Epidemiology, Management, and Survival Outcomes of Germ Cell Cancer in Southern Portugal: A Population-Based Study (2008-2012).

INTRODUCTION: Building on previous suboptimal survival results, we aimed to perform a study of the epidemiological status, management, and outcomes of germ cell tumors (GCT) in the Portuguese population. MATERIALS AND METHODS: Retrospective populational study of GCT cases diagnosed between 2008 and 2012 in southern Portugal. Joinpoint regression was used to compute average annual percentage change (AAPC) in incidence rate. ESMO/EAU guidelines served as references to evaluate compliance. Association between compliance with guidelines and hospital GCT case load was performed by generalized estimating equation. Survival was calculated by Kaplan-Meier and prognostic factors by Cox models. RESULTS: The study included 401 GCT male cases. The AAPC was 5.4% (IC 95% 3.3-7.4, P < .001) from 1999 (an earlier cohort published) to 2012. The median time to diagnosis was 63 days (Q25 = 33 days; Q75 = 114 days; IQR = 81 days). For stage II/III the median time to start chemotherapy was 34 days (Q25 = 22 days; Q75 = 56 days; IQR = 22 days). In 86% cases there was noncompliance with guidelines for the orchiectomy report, 6% for staging, 38% for tumor markers evaluation, 20% for treatment and 25% for chemotherapy dose intensity. The 5-year overall survival was 93.8% (95% CI, 91.3%-96.4%). Hospitals that managed ≤ 3 GCT cases/ year had higher odds for noncompliance with guidelines of blood markers, treatment and dose intensity. None of GCT healthcare access and management factors studied were associated with prognosis. CONCLUSIONS: The burden of GCT is rising in Portugal. Although survival has improved, efforts must be made to nationally enhance training and expertise in GCT and support region adapted models of centralization of care.

Effectiveness of palbociclib with aromatase inhibitors for the treatment of advanced breast cancer in an exposure retrospective cohort study: implications for clinical practice.

BACKGROUND: New drugs for locally advanced or metastatic breast cancer have led to clinical benefits, aside with increasing costs to healthcare systems. The current financing model for health technology assessment (HTA) privileges real-world data. As part of the ongoing HTA, this study aimed to evaluate the effectiveness of palbociclib with aromatase inhibitors (AI) and compare it with the efficacy reported in PALOMA-2. METHODS: A population-based retrospective exposure cohort study was conducted including all patients initiating treatment in Portugal with palbociclib under early access use and registered in the National Oncology Registry. The primary outcome was progression free survival (PFS). Secondary outcomes considered included time to palbociclib failure (TPF), overall survival (OS), time to next treatment (TTNT), and proportion of patients discontinuing treatment due to  adverse events (AEs). The Kaplan-Meier method was used and median, 1- and 2-year survival rates were computed, with two-sided 95% confidence intervals (95%CI). STrengthening the Reporting of OBservational studies in Epidemiology (STROBE) guidelines for reporting observational studies were used. RESULTS: There were 131 patients included. Median follow-up was 28.3 months (IQR: 22.7-35.2) and median duration of treatment was 17.5 months (IQR: 7.8-29.1). Median PFS was 19.5 months (95%CI 14.2-24.2), corresponding to a 1-year PFS rate of 67.9% (95%CI 59.2-75.2) and a 2-year PFS rate of 42.0% (95%CI 33.5-50.3). Sensitivity analysis showed median PFS would increase slightly when excluding those not initiating treatment with the recommended dose, raising to 19.8 months (95%CI 14.4-28.9). By considering only patients meeting PALOMA-2 criteria, we could observe a major difference in treatment outcomes, with a mean PFS of 28.8 months (95%CI 19.4-36.0). TPF was 19.8 months (95%CI 14.2-24.9). Median OS was not reached. Median TTNT was 22.5 months (95%CI 18.0-29.8). A total of 14 patients discontinued palbociclib because of AEs (10.7%). CONCLUSIONS: Data suggest palbociclib with AI to have an effectiveness of 28.8 months, when used in patients with overlapping characteristics to those used in PALOMA-2. However, when used outside of these eligibility criteria, namely in patients with less favorable prognosis (e.g., presence of visceral disease), the benefits are inferior, even though still favorable.

Should Colorectal Cancer Screening in Portugal Start at the Age of 45 Years? A Cost-Utility Analysis.

BACKGROUND AND OBJECTIVE: Colorectal cancer (CRC) is one of the most common cancers in Europe. Recently, new data from the USA and Europe revealed an increase in the incidence of CRC in individuals aged <55 years and a reduction in those aged >65 years. Mortality rate was stable in patients aged <55 years and decreased after the age of 55 years. Based on the USA data, the American Cancer Society (ACS) published a qualified recommendation advocating the start of CRC screening at the age of 45 years. We aimed to evaluate if the changes in the CRC incidence/mortality observed in the USA and the rest of Europe also occur in Portugal, and then perform a cost-utility analysis of CRC screening that starts at 45 years of age. METHODS: We evaluated the incidence of CRC by age group using data from the National Cancer Registry, and the mortality rate according to the National Statistics Institute in the periods 1993-2010 and 2003-2016. A cost-utility analysis was performed with a decision tree from a societal perspective comparing biennial fecal immunochemical test (FIT) or a single colonoscopy screening versus nonscreening at the age of 45 years in Portugal. RESULTS: In Portugal, in 1993-2010, there was an increase in CRC incidence of 17% (from 25 to 30/100,000), 35% (from 39 to 54/100,000), and 71% (from 52 to 97/100,000) in patients aged 45-49 years, 50-54 years, and 55-59 years, respectively. The mortality rate of patients aged 45-54 years remained stable between 2003 and 2016 (12/100,000) as a counterpoint to a moderate decrease in those aged 55-64 years (from 38 to 35/100,000) and a sharp reduction in those aged 65-75 years (from 93 to 75/100,000). Screening for CRC at the age of 45 years has no cost utility with the current incidence. FIT screening provided an ICUR of EUR 84,304/quality-adjusted life years (QALY) while colonoscopy provided an ICUR of EUR 3,112,244/QALY. On one-way sensitivity analysis, FIT screening would only have cost utility at the present cost of colonoscopy under sedation (EUR 150) and acceptance rates if the incidence rate rises above 47.5/100,000; colonoscopy at this age would have no cost utility despite changes in costs and/or incidence rates. CONCLUSION: In Portugal, the incidence of CRC in patients aged 45-55 years has been increasing with a stable mortality rate, in contrast to the decrease in mortality in the age groups covered by the current CRC screening program. However, at present, CRC screening in Portugal at the age of 45 years has no cost utility and will only have this if the incidence rate rises above 47.5/100,000 (vs. the actual incidence of 30/100,000).

INTRODUÇÃO E OBJETIVOS: O cancro colorretal (CCR) é uma das neoplasias mais comuns na Europa. Recentemente, temos observado um aumento da incidencia de cancro colorretal (CCR) em individuos <50 anos (não abrangidos pelos programas de rastreio), tanto na europa como nos Estados Unidos da América (EUA). Simultaneamente, a taxa de mortalidade (TM) permaneceu estável em doentes <55 anos e diminuiu >55 anos. Baseado nestes dados, a American Cancer Society (ACS) publicou uma recomendação qualificada advogando o inicio do rastreio aos 45 anos. Avaliar se as alterações na incidência/mortalidade de CCR observadas nos EUA/Europa também ocorrem em Portugal e realizar uma análise de custo-utilidade do início do rastreio de CCR aos 45 anos. MÉTODOS: Avaliamos a incidencia de CCR por faixa etária usando dados do Registro Oncológico Nacional (1993­2010) e TM de acordo com o Instituto Nacional de Estatística (2003­2016). A análise de custo-utilidade foi realizada com uma árvore de decisão sob uma perspetiva social, comparando o teste imunoquímico fecal bienal (FIT) com a realização de uma colonoscopia total aos 45 anos. RESULTADOS: Em Portugal (1993­2010) observou-se um aumento na incidencia de CRC de 17% (25/100.000 vs. 30/100.000), 35% (39/100.000 vs. 54/100.000) e 71% (52/100.000 vs. 97/100.000) em doentes com 45­49 anos, 50­54 anos e 55­59 anos, respetivamente. A TM de indivíduos com 45­54 anos permaneceu estável (12/100.000) ao contrário da diminuição moderada em indivíduos com 55­64 (38/100.000 vs. 35/100.000) e uma acentuada redudo em 65­75 (93/100.000 vs. 75/100.000). O rastreio de CCR aos 45 anos não teve custo-utilidade na presente incidencia (FIT/colonoscopia total). O rastreio com FIT forneceu um RCEI de € 84.304/QALY, enquanto a colonoscopia forneceu um RCEI de € 3.112.244/OALY. Em análise de sensibilidade unilateral, o rastreio com FIT apresentaria custo-utilidade com o custo atual da colonoscopia sob sedação (€ 150) e taxas de aceitado apenas se a incidencia subir acima de 47,5/100.000; o rastreio com colonoscopia nesta idade nunca teria custo-utilidade, apesar das mudanças nos custos e/ou taxas de incidencia. CONCLUSÃO: Em Portugal, a incidencia de CCR em doentes com idades entre 45­55 anos tem aumentado (TM estável). Este cenário é semelhante ao descrito nos EUA/restante europa. No entanto, o inicio do rastreio do CCR aos 45 anos em Portugal apenas terá custo-utilidade se incidencia for >47.5/100.000 (vs. 30/100.000).

The Portuguese Version of the European Deprivation Index: An Instrument to Study Health Inequalities.

INTRODUCTION: Tackling socioeconomic health inequalities is a big public health challenge and ecological deprivation indexes are essential instruments to monitor and understand them. In Portugal, no standard ecological deprivation index exists, contrasting with other countries. We aimed to describe the construction of the Portuguese version of a transnational deprivation index, European Deprivation Index. MATERIAL AND METHODS: The European Deprivation Index was developed under the Townsend theorization of deprivation. Using data from the European Union - Statistics on Income and Living Conditions Survey, we obtained an indicator of individual deprivation. This indicator became the gold-standard variable, based on what we selected the variables at aggregate level (census) to be included in the European Deprivation Index, a total of eight. The European Deprivation Index was produced for the smallest area unit possible (n = 16 094, mean/area = 643 inhabitants) and resulted from the weighted sum of the previous variables. It was then classified into quintiles. RESULTS: The first quintile (least deprived) comprised 20.9% national population and the fifth quintile (most deprived) 18.0%. The European Deprivation Index showed a clear geographic pattern - most deprived areas concentrated in the South and in the inner North and Centre of the country, and the least deprived areas in the coastal areas of North and Centre and in the Algarve. DISCUSSION: The development of the European Deprivation Index was grounded on a solid theoretical framework, individual and aggregate variables, and on a longitudinal Europe-wide survey allowing its replication over the time and in any European country. CONCLUSION: Hopefully, the European Deprivation Index will start being employed by those interested in better understand health inequalities not only in Portugal but across Europe.

Development of a cross-cultural deprivation index in five European countries.

BACKGROUND: Despite a concerted policy effort in Europe, social inequalities in health are a persistent problem. Developing a standardised measure of socioeconomic level across Europe will improve the understanding of the underlying mechanisms and causes of inequalities. This will facilitate developing, implementing and assessing new and more effective policies, and will improve the comparability and reproducibility of health inequality studies among countries. This paper presents the extension of the European Deprivation Index (EDI), a standardised measure first developed in France, to four other European countries-Italy, Portugal, Spain and England, using available 2001 and 1999 national census data. METHODS AND RESULTS: The method previously tested and validated to construct the French EDI was used: first, an individual indicator for relative deprivation was constructed, defined by the minimal number of unmet fundamental needs associated with both objective (income) poverty and subjective poverty. Second, variables available at both individual (European survey) and aggregate (census) levels were identified. Third, an ecological deprivation index was constructed by selecting the set of weighted variables from the second step that best correlated with the individual deprivation indicator. CONCLUSIONS: For each country, the EDI is a weighted combination of aggregated variables from the national census that are most highly correlated with a country-specific individual deprivation indicator. This tool will improve both the historical and international comparability of studies, our understanding of the mechanisms underlying social inequalities in health and implementation of intervention to tackle social inequalities in health.

Breast cancer patients survival and associated factors: reported outcomes from the Southern Cancer Registry in Portugal.

OBJECTIVES: Although the breast cancer incidence in Portugal is lower than the European average, it is the most frequent cancer in women. Overall, mortality rates are heterogeneous throughout Portugal. Implicated factors may include demographic and socioeconomic aspects, tumor biological characteristics, and access to medical care. The aim of this study is to detect survival differences in female breast cancer and identify the main associated factors. MATERIAL AND METHODS: We have conducted a population-based, retrospective cohort study with follow-up. Incident breast cancer cases diagnosed in 2005 of residents in the southern region of Portugal were included. Data was collected from the Southern Portugal Cancer Registry (ROR-Sul) database and completed with clinical chart information. RESULTS: A total of 1 354 patients were included in this study. Observed geographical variations were as follows: for age distribution, with an aging population in Alentejo; for tumor sub-types, there was a higher incidence of HER2-positive tumors in the Algarve and a higher incidence of HER2-negative tumors in Região Autónoma da Madeira. Reported estimated 5-year overall survival was 80%, with significant association with tumor stage, hormone receptor and HER2 status. No survival differences were identified among women from distinct geographical regions. DISCUSSION: Although we found differences in age and tumor sub-type distribution between geographical regions, our study does not support the existence of discrepancies in breast cancer survival between these regions. Tumor biological characteristics seem to be the main associated factor with breast cancer survival in our population. CONCLUSIONS: Our study confirms the association between patient survival and tumor stage, hormone receptor and HER2 status. However, no differences in patient survival were observed among different regions of residence.

Objectivos: A incidência do cancro da mama em Portugal é inferior à média europeia, sendo, ainda assim, a neoplasia mais frequente na mulher. As taxas de mortalidade por cancro de mama apresentam uma distribuição heterogénea nas diferentes regiões de Portugal. São múltiplos os factores que podem influenciar esta distribuição, incluindo aspectos demográficos e socioeconómicos, características biológicas tumorais, e o acesso aos cuidados de saúde. O objectivo deste estudo é detectar diferenças na sobrevivência do cancro de mama feminino e os principais factores associados. Material e Métodos: Estudo de coorte, de base populacional e orientação retrospectiva, com follow-up. Foram incluídos casos de cancro de mama diagnosticados em 2005 e residentes na região sul de Portugal, tendo os dados sido recolhidos a partir da base de dados do Registo Oncológico Regional Sul (ROR-Sul) e complementados com dados dos processos clínicos. Resultados: Foram incluídos neste estudo 1 354 doentes. Observaram-se as seguintes variações geográficas: na distribuição etária, com uma população envelhecida no Alentejo; na distribuição de sub-tipos tumorais, com uma maior incidência de tumores HER2- positivo no Algarve e maior incidência de tumores HER2-negativo na Região Autónoma da Madeira. A sobrevivência global estimada aos 5 anos foi de 80%, com uma associação significativa com o estadio, receptores hormonais e status HER2. Não foram identificadas diferenças na sobrevivência entre mulheres residentes em regiões geográficas distintas. Discussão: Apesar das diferenças observadas na distribuição etária e de sub-tipos tumorais entre regiões geográficas, os nossos resultados não suportam a existência de discrepâncias na sobrevivência do cancro de mama entre estas regiões. As características biológicas tumorais parecem ser os principais factores associados à sobrevivência do cancro de mama feminino na nossa população. Conclusões: O nosso estudo confirma a associação entre a sobrevivência e o estadio, receptores hormonais e status HER2. No entanto, não foram observadas diferenças na sobrevivência entre diferentes regiões geográficas de residência.