The Initial Journey of Patients with Metastatic Pancreatic Cancer (PaCTO Project): A Nationwide Survey among Portuguese Specialist Physicians.

Introduction: We aimed to characterize the initial healthcare journey of metastatic pancreatic ductal adenocarcinoma (mPDAC) patients in Portugal, including healthcare provision and factors affecting therapeutic decisions, namely BRCA mutations testing. Methods: This is a descriptive cross-sectional, web-based survey using a convenience sampling approach. Portuguese oncologists and pathologists that routinely work with mPDAC patients from the different geographical regions and settings were invited to participate in the study via email (December 2020). Descriptive statistical analyses were performed, with categorical variables reported as absolute and relative frequencies, and continuous variables with non-normal distribution as median and interquartile range (IQR) (Stata v.15.0). Results: Seventy physicians participated in the study (43 oncologists, 27 pathologists). According to the responses, a median of 28 patients per center (IQR 12-70) was diagnosed with PDAC in the previous year; 22 of them referring (IQR 8-70) to mPDAC. The pointed median time from patients' first hospital admission until disease diagnosis/staging is between 2 and 4 weeks. Endoscopic ultrasound with fine-needle biopsy is available in most hospitals (86%). Around 50% of physicians request BRCA testing; the assessment of additional biomarkers besides BRCA is requested by 40% of professionals. Half of them stated that BRCA testing should be requested earlier-upon histological diagnosis, especially because the median time for results is of 4.0 weeks (IQR 4-8). PARP inhibitors such as olaparib, when available, would be the therapy of choice for most oncologists (71%) if no disease' progression occurs after 4 months. Treatments' selection is usually grounded on clinical criteria (e.g., performance status, liver function). Around 45% of patients use FOLFIRINOX/mFOLFIRINOX as the first-line therapy. Gemcitabine + nab-paclitaxel is used by 35% of patients as the second-line therapy. Conclusions: Physicians in Portugal support the increasing role of patient-tailored treatments in mPDAC, whose selection should be grounded on tumoral subtyping and molecular profiling. Further efforts to develop multidisciplinary teams, standardized clinical practice, and optimize the implementation of new target therapies are needed.

Introdução: Este estudo teve como objetivo caracterizar o percurso inicial dos doentes com adenocarcinoma ductal pancreático metastático (ACDPm) em Portugal, incluindo a prestação de cuidados de saúde e determinação de fatores que afetam as decisões terapêuticas, nomeadamente o teste de mutações BRCA. Métodos: Trata-se de um estudo descritivo transversal (web-based) usando uma abordagem de amostragem por conveniência. Médicos oncologistas e anatomopatologistas portugueses dedicados ao ACDPm e de diferentes regiões geográficas e instituições foram convidados a participar do estudo por email (Dez-2020). Foram realizadas análises estatísticas descritivas, com variáveis categóricas relatadas como frequências absolutas e relativas, e variáveis contínuas com distribuição não-normal como mediana e intervalo interquartil (IIQ) (Stata v.15.0). Resultados: Setenta médicos participaram do estudo (43 oncologistas, 27 patologistas). De acordo com as respostas, uma mediana de 28 doentes por centro (IIQ 12­70) foi diagnosticada com ACDP no ano anterior; 22 deles (IIQ 8­70) referentes a ACDPm. O tempo médio desde a primeira admissão hospitalar dos doentes até o diagnóstico/estadiamento da doença foi entre 2­4 semanas. A ultrassonografia endoscópica com biópsia por agulha fina é realizada pela maioria dos hospitais (86%). Aproximadamente 50% dos médicos referem solicitar o teste BRCA; a avaliação de biomarcadores adicionais além do BRCA é solicitada por 40% dos profissionais. Metade dos médicos assume que o teste BRCA deveria ser solicitado mais precocemente ­ durante o diagnóstico histológico, principalmente porque o tempo médio para obtenção do resultado é de 4,0 semanas (IIQ 4­8). Os inibidores PARP, como o olaparibe, quando disponíveis, seriam a terapia de escolha para a maioria dos oncologistas (71%) caso não haja progressão da doença após quatro meses. A seleção dos tratamentos é usualmente baseada em critérios clínicos (por exemplo, performance status, função hepática). Em cerca de 45% dos doentes é utilizado FOLFIRINOX/mFOLFIRINOX como terapia de primeira linha. Um esquema com Gemcitabina + nab-paclitaxel é usado em 35% dos doentes como terapia de segunda linha. Conclusões: Os médicos em Portugal apoiam o papel crescente do tratamento individualizado no ACDPm, cuja seleção deve ser baseada na subtipagem tumoral e no perfil molecular. São necessários mais esforços para capacitar as equipas multidisciplinares, desenvolver práticas clínicas padronizadas e otimizar a implementação de novas terapias-alvo.

Treatment optimization of locally advanced and metastatic pancreatic cancer (Review).

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignant tumor types, being the sixth leading cause of mortality worldwide and the fourth in Europe. Globally, it has a mortality/incidence ratio of 98%, and the 5­year survival rate in Europe is only 3%. Although risk factors, such as obesity, diabetes mellitus, smoking, alcohol consumption and genetic factors, have been identified, the causes of PDAC remain elusive. Additionally, the only curative treatment for PDAC is surgery with negative margins. However, upon diagnosis, ~30% of the patients already present with locally advanced disease. In these cases, a multidisciplinary approach is required to improve disease­related symptoms and prolong patient survival. In the present article, a comprehensive review of PDAC epidemiology, physiology and treatment is provided. Moreover, guidelines on patient treatment are suggested. Among the different available therapeutic options for the treatment of advanced PDAC, results are modest, most likely due to the complexity of the disease, and so the prognostic remains poor. Molecular approaches based on multi­omics research are promising and will contribute to groundbreaking personalized medicine. Thus, economic investment that promotes research of pancreatic cancer will be critical to the development of more efficient diagnostic and treatment strategies.