RESUMO
PURPOSE: Laparoscopic pancreatoduodenectomy (LPD) has emerged as an alternative to open technique in treating periampullary tumors. However, the safety and efficacy of LPD compared to open pancreatoduodenectomy (OPD) remain unclear. Thus, we conducted an updated meta-analysis to evaluate the efficacy and safety of LPD versus OPD in patients with periampullary tumors, with a particular focus on the pancreatic ductal adenocarcinoma patient subgroup. METHODS: According to PRISMA guidelines, we searched PubMed, Embase, and Cochrane Library in December 2023 for randomized controlled trials (RCTs) that directly compare LPD versus OPD in patients with periampullary tumors. Endpoints and sensitive analysis were conducted for short-term endpoints. All statistical analysis was performed using R software version 4.3.1 with a random-effects model. RESULTS: Five RCTs yielding 1018 patients with periampullary tumors were included, of whom 511 (50.2%) were randomized to the LPD group. Total follow-up time was 90 days. LPD was associated with a longer operation time (MD 66.75; 95% CI 26.59 to 106.92; p = 0.001; I2 = 87%; Fig. 1A), lower intraoperative blood loss (MD - 124.05; 95% CI - 178.56 to - 69.53; p < 0.001; I2 = 86%; Fig. 1B), and shorter length of stay (MD - 1.37; 95% IC - 2.31 to - 0.43; p = 0.004; I2 = 14%; Fig. 1C) as compared with OPD. In terms of 90-day mortality rates and number of lymph nodes yield, no significant differences were found between both groups. CONCLUSION: Our meta-analysis of RCTs suggests that LPD is an effective and safe alternative for patients with periampullary tumors, with lower intraoperative blood loss and shorter length of stay.
Assuntos
Carcinoma Ductal Pancreático , Laparoscopia , Neoplasias Pancreáticas , Pancreaticoduodenectomia , Humanos , Ampola Hepatopancreática/cirurgia , Ampola Hepatopancreática/patologia , Carcinoma Ductal Pancreático/cirurgia , Carcinoma Ductal Pancreático/patologia , Carcinoma Ductal Pancreático/mortalidade , Laparoscopia/efeitos adversos , Laparoscopia/métodos , Tempo de Internação/estatística & dados numéricos , Duração da Cirurgia , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/cirurgia , Pancreaticoduodenectomia/métodos , Pancreaticoduodenectomia/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
INTRODUCTION: Pancreatic adenocarcinoma is an extremely aggressive neoplasm, with many challenges to be overcome in order to achieve a truly effective treatment. It is characterized by a mostly immunosuppressed environment, with dysfunctional immune cells and active immunoinhibitory pathways that favor tumor evasion and progression. Thus, the study and understanding of the tumor microenvironment and the various cells subtypes and their functional capacities are essential to achieve more effective treatments, especially with the use of new immunotherapeutics. METHODS: Seventy cases of pancreatic adenocarcinoma divided into two groups 43 with resectable disease and 27 with unresectable disease were analyzed using immunohistochemical methods regarding the expression of programmed cell death ligand 1 (PD-L1), programmed cell death ligand 2 (PD-L2), and human leukocyte antigen G (HLA-G) molecules as well as the populations of CD4+ and CD8+ T lymphocytes, regulatory T cells (Tregs), and M2 macrophages (MM2). Several statistical tests, including multivariate analyses, were performed to examine how those immune cells and immunoinhibitory molecules impact the evolution and prognosis of pancreatic adenocarcinoma. RESULTS: CD8+ T lymphocytes and M2 macrophages predominated in the group operated on, and PD-L2 expression predominated in the unresectable group. PD-L2 was associated with T stage, lymph node metastasis, and clinical staging, while in survival analysis, PD-L2 and HLA-G were associated with a shorter survival. In the inoperable cases, Tregs cells, MM2, PD-L1, PD-L2, and HLA-G were positively correlated. CONCLUSIONS: PD-L2 and HLA-G expression correlated with worse survival in the cases studied. Tumor microenvironment was characterized by a tolerant and immunosuppressed pattern, mainly in unresectable lesions, where a broad positive influence was observed between immunoinhibitory cells and immune checkpoint proteins expressed by tumor cells.
Assuntos
Adenocarcinoma , Antígeno B7-H1 , Antígenos HLA-G , Neoplasias Pancreáticas , Microambiente Tumoral , Humanos , Neoplasias Pancreáticas/imunologia , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/mortalidade , Masculino , Feminino , Adenocarcinoma/imunologia , Adenocarcinoma/patologia , Pessoa de Meia-Idade , Idoso , Microambiente Tumoral/imunologia , Antígeno B7-H1/metabolismo , Antígenos HLA-G/metabolismo , Proteína 2 Ligante de Morte Celular Programada 1/metabolismo , Prognóstico , Linfócitos T CD8-Positivos/imunologia , Adulto , Linfócitos T Reguladores/imunologia , Idoso de 80 Anos ou mais , Macrófagos/imunologia , Macrófagos/metabolismo , Macrófagos/patologiaRESUMO
BACKGROUND: Limited data exist on the prognostic significance of the chronology of VTE in patients with PDAC. METHODS: Medical data and survival characteristics of patients treated for PDAC from 2019 to 2021 were retrospectively reviewed. Early VTE was defined as occurring within the three months of PDAC diagnosis. RESULTS: 197 patients were included, 54 (27.4%) developed a VTE. Early appearance of VTE was associated with worse prognosis: median overall survival (mOS) VTE < 3 months 8.5 months (HR 1.65, 95% CI 1.11-2.46; p = 0.014), mOS VTE > 3 months 12.8 months (HR 0.78, 95% CI 0.39-1.54; p = 0.5) and mOS patients without VTE 11.4 months (95% CI 10.1-15.4). There was no significant association between the patient's VTE risk according to the Khorana risk score (KRS) (chi2 test p-value = 0.9). CONCLUSION: Early VTE is a prognostic factor in PDAC, which may identify a more aggressive subtype.
Assuntos
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Tromboembolia Venosa , Humanos , Tromboembolia Venosa/etiologia , Tromboembolia Venosa/mortalidade , Feminino , Masculino , Carcinoma Ductal Pancreático/mortalidade , Carcinoma Ductal Pancreático/complicações , Carcinoma Ductal Pancreático/patologia , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/complicações , Neoplasias Pancreáticas/patologia , Estudos Retrospectivos , Pessoa de Meia-Idade , Idoso , Prognóstico , Fatores de Tempo , Taxa de Sobrevida , Fatores de Risco , Idoso de 80 Anos ou maisRESUMO
INTRODUCTION: Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy about 50% of PDAC are metastatic at presentation. In this study, we evaluated PDAC demographics, annual trend analysis, racial disparities, survival rate, and the role of different treatment modalities in localized and metastatic disease. METHODS: A total of 144,824 cases of PDAC were obtained from the SEER database from 2000 to 2018. RESULTS: The median age was 69 years, with a slightly higher incidence in males (52%) and 80% of all cases were white. Among cases with available data, 43% were grade III tumors and 57% were metastatic. The most common site of metastasis was the liver (15.7%). The annual incidence has increased steadily from 2000 to 2018. The overall observed (OS) 5-year survival rate was 4.4% (95% CI 4.3-4.6%), and 5 years cause-specific survival (CSS) was 5% (95% CI 5.1-5.4%). The 5-year survival with multimodal therapy (chemotherapy, surgery, and radiation) was 22% (95% CI 20.5-22.8%). 5-year CSS for the blacks was lower at 4.7% (95% CI 4.2-5.1%) compared to the whites at 5.3% (95% CI 5.1-5.4%). Multivariate analysis found male gender and black race associated with worse prognosis. Kaplan-Meier survival analysis found multimodal therapy to have the best outcomes in all three stages. CONCLUSION: PDAC is an aggressive malignancy with male gender and black race are associated with a poor prognosis. Surgery with chemoradiation was associated with the best overall survival. With steadily increasing rates of PDAC, improved treatment modalities are paramount to improving survival in these patients.
Assuntos
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Programa de SEER , Humanos , Masculino , Carcinoma Ductal Pancreático/terapia , Carcinoma Ductal Pancreático/patologia , Carcinoma Ductal Pancreático/mortalidade , Carcinoma Ductal Pancreático/etnologia , Carcinoma Ductal Pancreático/epidemiologia , Feminino , Idoso , Neoplasias Pancreáticas/terapia , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/etnologia , Estados Unidos/epidemiologia , Pessoa de Meia-Idade , Taxa de Sobrevida , População Branca/estatística & dados numéricos , Terapia Combinada , Idoso de 80 Anos ou mais , Incidência , Adulto , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/etnologia , Negro ou Afro-Americano/estatística & dados numéricos , Disparidades em Assistência à SaúdeRESUMO
Introdução: O câncer de pâncreas é um tumor de alta letalidade, é o décimo segundo tipo mais comum e a sétima causa de morte, em ambos os sexos, no mundo. Estima-se que o câncer de pâncreas terá um aumento contínuo de incidência e mortalidade nos próximos 20 anos e isso causará um enorme ônus econômico para as populações em todo o mundo. Para o monitoramento e vigilância epidemiológica em câncer, pode-se apoiar em dados secundários como no Sistema de Informação em Mortalidade e dos registros de câncer (de base populacional e hospitalares) e estimativas a partir destes dados; por essa razão, investigou-se a epidemiologia do câncer de pâncreas na América Latina e no Brasil. Métodos: A tese compreende três manuscritos: (i) tendências de incidência, mortalidade e anos de vida ajustados por incapacidade (DALYs), bem como a fração de mortes por câncer de pâncreas atribuíveis a fatores de risco comportamentais e metabólicos em países da América Latina e Caribe (LAC) entre 1990 e 2019 (Global Burden Disease, 2019); (ii) mortalidade por câncer de pâncreas no Brasil e unidades da federação entre 1979 e 2019, dados do Sistema de Informação em Mortalidade (SIM); (iii) comparabilidade, validade, completude e pontualidade para cinco tumores gastrointestinais, câncer de esôfago, estômago, colorretal, fígado e pâncreas, em Registros de Câncer de Base Populacional (RCBPs) brasileiros. Resultados: Observou-se um aumento na incidência, mortalidade e DALYs para o câncer de pâncreas em ambos os sexos na maioria dos países da América Latina e Caribe; as maiores taxas de incidência e mortalidade foram observadas no Uruguai e as menores no Haiti. Redução na fração de mortes atribuíveis ao tabagismo entre 1990 e 2019, para ambos os sexos nos países da LAC; entretanto, aumento dentre os fatores metabólicos. No Brasil, entre 1979 e 2019, foram notificados um total de 209.425 óbitos por câncer de pâncreas, com tendência de aumento de 1,5% ao ano em homens e 1,9% em mulheres. Houve tendência de aumento da mortalidade na maioria dos estados brasileiros, com maiores tendências nas regiões Norte e Nordeste, e correlação positiva entre o índice de desenvolvimento humano e a tendência de aumento da mortalidade por câncer de pâncreas. Dentre os dezesseis RCBPs brasileiros estudados, todos atenderam aos critérios de comparabilidade, porém metade apresentou índices abaixo do esperado para validade e completude para tumores de fígado e pâncreas. Para pontualidade, os dezesseis registros apresentaram mais de 48 meses de atraso na divulgação dos dados em relação ao ano calendário de 2023. Considerações finais: O câncer de pâncreas representa um desafio para a saúde pública nos países da América Latina e no Brasil, diante do desafio na redução da incidência e da mortalidade, assim como na vigilância epidemiológica em câncer através dos RCBPs brasileiros que necessitam de suporte para continuidade do monitoramento da incidência do câncer.
Introduction: Pancreatic cancer is a tumor of high lethality, is the twelfth most common type and the seventh cause of death, in both sexes, in the world. It is estimated that pancreatic cancer will have a continuous increase in incidence and mortality over the next 20 years and this will cause a huge economic burden for populations around the world. For epidemiological monitoring and surveillance in cancer, it is possible to use on secondary data such as the Mortality Information System and cancer registries (population-based and hospital) and estimates from these data, for this reason the epidemiology of pancreatic cancer in Latin America and Brazil was investigated. Methods: The thesis comprises three manuscripts: (i) trends in incidence, mortality and disability-adjusted life years (DALYs) as well as the fraction of pancreatic cancer deaths attributable to behavioral and metabolic risk factors in Latin American and Caribbean (LAC) countries between 1990 and 2019 (Global Burden Disease, GBD 2019); (ii) mortality from pancreatic cancer in Brazil and federal units between 1979 and 2019, data from the Mortality Information System (SIM); (iii) comparability, validity, completeness and timeless for five gastrointestinal tumors, esophageal, stomach, colorectal, liver and pancreatic cancers, in the Brazilian Population-Based Cancer Registries (PBCRs). Results: An increase in the incidence, mortality and DALYs of pancreatic cancer was observed in most countries in Latin America and the Caribbean, the highest incidence and mortality rates were observed in Uruguay and the lowest in Haiti. The fraction of pancreatic cancer deaths attributable to smoking reduced between 1990 and 2019 for both sexes in LAC countries, however, it increased for metabolic risk factors. In Brazil, between 1979 and 2019, a total of 209,425 deaths from pancreatic cancer were reported, with a trend of increase of 1.5% per year in men and 1.9% in women. There was an increase in mortality in most Brazilian states, higher in the North and Northeast regions with a positive correlation between the improvement of the human development index and the trend of increased mortality from pancreatic cancer. Among the sixteen Brazilian PBCRs studied, all agreement the criteria of comparability, but half have lower than expected indices for validity and completeness for liver and pancreatic tumors, and as for timeless the sixteen records are more than 48 months late in the release of data in relation to the calendar year 2023. Conclusions: Pancreatic cancer represents a challenge for public health in LAC and Brazil, given the challenge in reducing incidence and mortality, as well as in epidemiological surveillance in cancer through Brazilian PBCRs to ensure the activity and stability for continued monitoring of cancer incidence.
Assuntos
Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/epidemiologia , Registros de Doenças , Carga Global da DoençaRESUMO
OBJECTIVE: To build a prognostic score for patients with primary chemotherapy undergoing surgery for pancreatic cancer based on pathological parameters and preoperative Carbohydrate antigen 19-9 (CA19-9) levels. BACKGROUND: Prognostic stratification after primary chemotherapy for pancreatic cancer is challenging and prediction models, such as the AJCC staging system, lack validation in the setting of preoperative chemotherapy. METHODS: Patients with primary chemotherapy resected at the Massachusetts General Hospital between 2007 and 2017 were analyzed. Tumor characteristics independently associated with overall survival were identified and weighted by Cox-proportional regression. The pancreatic neoadjuvant Massachusetts-score (PANAMA-score) was computed from these variables and its performance assessed by Harrel concordance index and area under the receiving characteristics curves analysis. Comparisons were made with the AJCC staging system and external validation was performed in an independent cohort with primary chemotherapy from Heidelberg, Germany. RESULTS: A total of 216 patients constituted the training cohort. The multivariate analysis demonstrated tumor size, number of positive lymph-nodes, R-status, and high CA19-9 to be independently associated with overall survival. Kaplan-Meier analysis according to low, intermediate, and high PANAMA-score showed good discriminatory power of the new metrics (P < 0.001). The median overall survival for the three risk-groups was 45, 27, and 12 months, respectively. External validation in 258 patients confirmed the prognostic ability of the score and demonstrated better accuracy compared with the AJCC staging system. CONCLUSION: The proposed PANAMA-score, based on independent predictors of postresection survival, including pathologic variables and CA19-9, not only provides better discrimination compared to the AJCC staging system, but also identifies patients at high-risk for early death.
Assuntos
Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/cirurgia , Idoso , Antígeno CA-19-9/sangue , Terapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/mortalidade , Período Pré-Operatório , Prognóstico , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
BACKGROUND: To investigate the role of adjuvant radiotherapy in patients with pancreatic cancer. METHODS AND PATIENTS: The patients with pancreatic cancer from 18 registered institutions in the Surveillance Epidemiology and End Results (SEER) database were retrospectively analyzed. The characteristics of patients who would benefit from adjuvant radiotherapy were screened, as well as whether neoadjuvant or adjuvant radiotherapy conferred to a better clinical outcome. Propensity score matching was used to control for confounding features. RESULTS: Thirty thousand two hundred and forty-nine patients were included in this study (21,295 vs 8954 in surgery and adjuvant radiotherapy group); 1150 patients were matched in two groups. The median survivals in the surgery (S) group and adjuvant radiotherapy (S + R) group were 24 and 21 months, respectively. The 1-, 3-, and 5-year overall survival (OS) rates in the S group and S + R group were 68%, 40%, 31%, and 75%, 30%, 20%, respectively (p < 0.001), and the median OS was 22 and 25 months in S and S + R group after PSM, the former 1-, 2-, 3-, and 5-year OS were 73%, 45%, 30%, and 19%, and the later were 81%, 52%, 37%, and 24% (p = 0.0015), respectively; stratified analysis showed patients whose carcinoma located at pancreatic head with II stage infiltrating duct carcinoma (22 vs 25, p = 0.0276), T4 adenocarcinoma (28 vs 33, p = 0.0022), N1 stage adenocarcinoma (20 vs 23, p = 0.0203), and patients with infiltrating duct carcinoma received regional resection (23 vs 25, p = 0.028) and number of resected lymph node were ≥ 4 (22 vs 25, p = 0.009) had better OS after additional radiotherapy than surgery alone. Patients with pancreatic body/tail carcinoma III stage adenocarcinoma (13 vs, p = 0.0503) and T4 adenocarcinoma (14 vs, p = 0.0869) had survival advantage within 24 months for additional radiotherapy. However, patients with T2 stage adenocarcinoma located in pancreatic body/tail had better OS in surgery group than that in R + S group. CONCLUSIONS: Additional radiotherapy may contribute to improved prognosis for patients with pancreatic head II stage infiltrating duct carcinoma, III stage adenocarcinoma, T4 stage carcinoma, N1 stage adenocarcinoma, regional resection, or number of lymphadenectomy ≥ 4 in infiltrating duct carcinoma. A specific subgroup of patients with specific stage and histological type pancreatic cancer should be considered for additional radiotherapy.
Assuntos
Adenocarcinoma/radioterapia , Neoplasias Pancreáticas/radioterapia , Radioterapia Adjuvante , Adenocarcinoma/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Bases de Dados Factuais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/mortalidade , Estudos Retrospectivos , Programa de SEER , Taxa de Sobrevida , Adulto JovemRESUMO
BACKGROUND: Vein resection pancreatoduodenectomy (VRPD) may be performed in selected pancreatic cancer patients. However, the main risks and benefits related to VRPD remain controversial. OBJECTIVE: This review aimed to evaluate the risks and survival benefits that the VRPD may add when compared with standard pancreatoduodenectomy (PD). METHODS: A systematic review and meta-analysis of studies comparing VRPD and PD were performed. RESULTS: VRPD was associated with a higher risk for postoperative mortality (risk difference: -0.01; 95% confidence interval [CI] -0.02 to -0.00) and complications (risk difference: -0.05; 95% CI -0.09 to -0.01) than PD. The length of hospital stay was not different between the groups (mean difference [MD]: -0.65; 95% CI -2.11 to 0.81). In the VRPD, the operating time was 69 minutes higher on average (MD: -69.09; 95% CI -88.4 to -49.78), with a higher blood loss rate (MD: -314.04; 95% CI -423.86 to -195.22). In the overall survival evaluation, the hazard ratio for mortality during follow-up on the group of VRPD was higher compared to the PD group (hazard ratio: 1.13; 95% CI 1.03-1.23). CONCLUSION: VRPD is associated with a higher risk of short-term complications and mortality and a lower probability of survival than PD. Knowing the risks and potential benefits of surgery can help clinicians to properly manage pancreatic cancer patients with venous invasion. The decision for surgery with major venous resection should be shared with the patients after they are informed of the risks and prognosis.
Assuntos
Carcinoma Ductal Pancreático/cirurgia , Neoplasias Pancreáticas/cirurgia , Pancreaticoduodenectomia/métodos , Idoso , Perda Sanguínea Cirúrgica/estatística & dados numéricos , Carcinoma Ductal Pancreático/mortalidade , Feminino , Humanos , Tempo de Internação/estatística & dados numéricos , Masculino , Veias Mesentéricas/cirurgia , Pessoa de Meia-Idade , Duração da Cirurgia , Neoplasias Pancreáticas/mortalidade , Pancreaticoduodenectomia/efeitos adversos , Pancreaticoduodenectomia/mortalidade , Veia Porta/cirurgiaRESUMO
OBJECTIVES: Former studies found that circRNAs play an important part in the occurrence of a variety of malignant biological characteristics that are critical for cancer progression. It has been shown that circ_03955 is highly expressed and implicated with quantities of biological processes in solid tumor. However, whether circ_03955 regulates the tumorigenesis and Warburg effect of pancreatic cancer (PC) remains largely unknown. MATERIALS AND METHODS: The level of circ_03955 in PC tissues and cell lines was determined by real-time qPCR (RT-qPCR). Loss-of-function and gain-of-function assays were employed to investigate the biological role of circ_03955 in cell proliferation, apoptosis, and glycolysis. RT-qPCR, western blotting, bioinformatics analysis, luciferase reporter assay, and in vivo tumorigenicity assay were employed to determine the underlying mechanisms. RESULTS: In this study, it was investigated that circ_03955 was up-regulated in PC clinical samples as well as PC cell lines and associated with poor clinical outcomes of PC patients. Functional assays revealed that circ_03955 exerts a certain stimulative effect on the growth of PC cells in vitro and in vivo. Circ_03955 also inhibited apoptosis and promotes Warburg effect in PC cells. Mechanistically, bioinformatics analysis indicated that circ_03955 acts as a sponge for microRNA (miR)-3662, and hypoxia-inducible factor 1É (HIF-1É) was one of the transcriptional targets of miR-3662. Importantly, genetic promoting of HIF-1É or downregulation of miR-3662 largely compromised circ_03955 depletion mediated tumor-inhibiting effects. CONCLUSIONS: Taken together, circ_03955 functions as a tumor promoter through miR-3662/HIF-1α axis, which might provide a novel sight for PC treatment.
Assuntos
Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , MicroRNAs/metabolismo , Neoplasias Pancreáticas/metabolismo , RNA Circular/metabolismo , Efeito Warburg em Oncologia , Apoptose/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Regulação para Baixo , Glicólise/genética , Humanos , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/patologia , Prognóstico , Regulação para CimaRESUMO
BACKGROUND: Second-line (2L) treatments for advanced pancreatic ductal adenocarcinoma (PDAC) achieve a modest benefit at the expense of potential toxicity. In the absence of predictive factors of response, the identification of prognostic factors could help in the therapeutic decisions-making. The purpose of this study was to assess the prognostic factors associated with shorter survival in patients with advanced PDAC who received 2L treatment. METHODS: We conducted a single institution retrospective study, which included all patients with advanced PDAC who received 2L treatment between September 2006 and February 2020 at La Paz University Hospital, Madrid (Spain). Significant variables in the logistic regression model were used to create a prognostic score. RESULTS: We included 108 patients. The median overall survival (OS) was 5.10 months (95%CI 4.02-6.17). In the multivariate analysis, time to progression (TTP) shorter than 4 months after first-line treatment (OR 4.53 [95%CI 1.28-16.00] p = 0.01), neutrophil-to-lymphocyte ratio (NLR) greater than 3 at the beginning of 2L (OR 9.07 [95%CI 1.82-45.16] p = 0.01) and CA-19.9 level higher than the upper limit of normal at the beginning of 2L (OR 7.83 [95%CI 1.30-49.97] p = 0.02) were independently associated with OS shorter than 3 months. The prognostic score classified patients into three prognostic groups (good, intermediate and poor) with significant differences in OS (p < 0.001). CONCLUSIONS: TTP shorter than 4 months after first-line treatment, NLR greater than 3 and CA-19.9 level higher than the upper limit of normal at the beginning of 2L were associated with shorter overall survival. We developed a prognostic score that classifies patients with advanced PDAC into three prognostic groups after progression to the first-line. This score could help in the decision-making for 2L treatment.