Predictive factors for resection and survival in type A borderline resectable pancreatic ductal adenocarcinoma patients after neoadjuvant therapy: A retrospective cohort study

Introduction:Pancreatic cancer is the seventh leading cause of cancer-related death worldwide, and surgical resection with radical intent remains the only potentially curative treatment option today. However, borderline resectable pancreatic ductal adenocarcinomas (BR-PDAC) stand in the gray area between the resectable and unresectable disease since they are technically resectable but have a high probability of incomplete exeresis. Neoadjuvant treatment (NAT) plays an important role in ensuring resection success.Different survival prognostic factors for BR-PDAC have been well described, but evidence on the predictive factors associated with resection after NAT is scarce. This study aims to study if CA 19-9 plasmatic levels and the tumor anatomical relationship with neighboring vascular structures are prognostic factors for resection and survival (both Overall Survival and Progression-Free Survival) in patients with type A BR-PDAC. Methods:This will be a retrospective cohort study using data from type A BR-PDAC patients who received NAT in the Bellvitge University Hospital. The observation period is from January 2010 until December 2019; patients must have a minimum 12-month follow-up. Patients will be classified according to the MD Anderson Cancer Center criteria for BR-PDAC. Discussion:Patients with BR-PDAC have a high risk for a margin-positive resection. Serum Carbohydrate Antigen 19-9 plasmatic levels and vascular involvement stand out as disease-related prognostic factors.This study will provide valuable information on the prognostic factors associated with resection. We will exclude locally advanced tumors and expect this approach to provide more realistic resection rates without selecting those patients that undergo surgical exploration. However, focusing on an anatomical definition may limit the results' generalizability

Tumor-Associated Microbiome: Where Do We Stand?

Dysbiosis; Gut microbiome; TumorDisbiosis; Microbioma intestinal; TumorDisbiosi; Microbioma intestinal; TumorThe study of the human microbiome in oncology is a growing and rapidly evolving field. In the past few years, there has been an exponential increase in the number of studies investigating associations of microbiome and cancer, from oncogenesis and cancer progression to resistance or sensitivity to specific anticancer therapies. The gut microbiome is now known to play a significant role in antitumor immune responses and in predicting the efficacy of immune-checkpoint inhibitors in cancer patients. Beyond the gut, the tumor-associated microbiome-microbe communities located either in the tumor or within its body compartment-seems to interact with the local microenvironment and the tumor immune contexture, ultimately impacting cancer progression and treatment outcome. However, pre-clinical research focusing on causality and mechanistic pathways as well as proof-of-concept studies are still needed to fully understand the potential clinical utility of microbiome in cancer patients. Moreover, there is a need for the standardization of methodology and the implementation of quality control across microbiome studies to allow for a better interpretation and greater comparability of the results reported between them. This review summarizes the accumulating evidence in the field and discusses the current and upcoming challenges of microbiome studies

Quality of life of patients with metastatic pancreatic adenocarcinoma initiating first-line chemotherapy in routine practice

Background: Despite advances in surgery, radiotherapy, and chemotherapy, pancreatic adenocarcinoma often progresses rapidly and causes death. The physical decline of these patients is expected to impact their quality of life (QoL). Therefore, in addition to objective measures of effectiveness, the evaluation of health-related QoL should be considered a matter of major concern when assessing therapy outcomes. Methods: Observational, prospective, multicenter study including patients with metastatic pancreatic adenocarcinoma who started first-line chemotherapy in 12 Spanish centers. Treatment and clinical characteristics were recorded at baseline. Patients' health-related quality of life, ECOG, and Karnofsky index were measured at baseline, at Days 15 and 30, and every four weeks up to 6months of chemotherapy. Health-related quality of life was measured using the EORTC-QLQ-C30 and EQ-5D questionnaires. Other endpoints included overall survival and progression-free survival. Results: The study sample included 116 patients (median age of 65years). Mean (SD) scores for the QLQ-C30 global health status scale showed a significant increasing trend throughout the treatment (p=0.005). Patients with either a Karnofsky index of 70-80 or ECOG 2 showed greater improvement in the QLQ-C30 global health status score than the corresponding groups with better performance status (p 50 at baseline had significantly greater overall survival and progression-free survival (p=0.005 and p=0.021, respectively). No significant associations were observed regarding the EQ-5D score. Conclusions: Most metastatic pancreatic adenocarcinoma patients receiving first-line chemotherapy showed an increase in health-related quality of life scores throughout the treatment. Patients with lower performance status and health-related quality of life at baseline tended to greater improvement. The EORTC QLQ-C30 scale allowed us to measure the health-related quality of life of metastatic pancreatic adenocarcinoma patients receiving first-line chemotherapy

Tumor-Associated Microbiome: Where Do We Stand?

The study of the human microbiome in oncology is a growing and rapidly evolving field. In the past few years, there has been an exponential increase in the number of studies investigating associations of microbiome and cancer, from oncogenesis and cancer progression to resistance or sensitivity to specific anticancer therapies. The gut microbiome is now known to play a significant role in antitumor immune responses and in predicting the efficacy of immune-checkpoint inhibitors in cancer patients. Beyond the gut, the tumor-associated microbiome-microbe communities located either in the tumor or within its body compartment-seems to interact with the local microenvironment and the tumor immune contexture, ultimately impacting cancer progression and treatment outcome. However, pre-clinical research focusing on causality and mechanistic pathways as well as proof-of-concept studies are still needed to fully understand the potential clinical utility of microbiome in cancer patients. Moreover, there is a need for the standardization of methodology and the implementation of quality control across microbiome studies to allow for a better interpretation and greater comparability of the results reported between them. This review summarizes the accumulating evidence in the field and discusses the current and upcoming challenges of microbiome studies

Endoscopic biliary drainage in unresectable biliary obstruction: the role of endoscopic ultrasound-guidance in a cohort study

Background and study aims: the use of endoscopic ultrasound-guided biliary drainage (EUS-BD) has increased in cases of failed endoscopic retrograde cholangiopancreatography (ERCP) and there are some concerns. The main aim of the study was to determine the role of EUS-BD in a palliative case cohort. The secondary aim was to compare the efficacy, safety and survival of EUS-BD and ERCP procedures. Patients and methods: this was an observational study at a single tertiary institution, with a consecutive inclusion from January 2015 to December 2016. The inclusion criteria were unresectable tumors of the biliopancreatic region with an indication of BD. Statistical comparison analysis was performed between the ERCP and EUS-BD groups. The incidence between groups was compared using the Chi-square and Fisher exact tests. The log rank test was used to compare the risk of death. Results: fifty-two cases with an indication of palliative BD were included in the study. Transpapillary drainage via ERCP was possible in 44 procedures and EUS-BD was required in eight cases; 15.4% of the cohort and seven using lumen apposing metal stent (LAMS). The technical and clinical success of global endoscopic BD was 100% and 88.5% (ERCP: 84.6% and 78.9%; EUS-BD: 100% and 62.5%, respectively). Pancreatitis was the most frequent adverse event (AE) in the ERCP group (9.62%) and bleeding in the EUS-BD (25%). There were fatal AEs in ERCP (1.9%) and EUS-BD (25%) cases. Patient survival was higher with ERCP transpapillary stents compared to EUS-guided stents, which was statistically significant (p = 0.007). Conclusions: the requirement of EUS-BD in palliative biliopancreatic pathology is not marginal. EUS-BD is associated with a lower survival rate and a higher rate of fatal AE, which argues against its use as a first choice procedure

Antiangiogenic effect of gemcitabine following metronomic administration in a pancreas cancer model

Gemcitabine shows a marked antitumor effect as a result of its cytotoxic action toward proliferative cells. In this article, we aim to investigate the potential antitumor and antiangiogenic effect of gemcitabine following a metronomic schedule that involves the regular administration of cytotoxic drugs at doses lower than standard treatment. In vitro results showed that human endothelial cells are more sensitive to gemcitabine (IC50 3 nmol/L) than pancreatic tumor cells (IC50 20 nmol/L). For in vivo studies, we used an orthotopic implantation model of human pancreatic carcinoma in nude mice. Gemcitabine was administered i.p. following a low-dose schedule (1 mg/kg/d for a month) and compared with the conventional schedule (100 mg/kg days 0, 3, 6, and 9 postimplantation). Metronomic treatment effect on established tumor was equivalent to standard administration. The measure of CD31 endothelial marked area allowed us to show an in vivo antiangiogenic effect of this drug that was further enhanced by using metronomic administration. This effect correlated with an induction of thrombospondin-1, a natural inhibitor of angiogenesis. Our results allow us to hypothesize that, in addition to a direct antiproliferative or cytotoxic antiendothelial cell effect, a secondary effect involving thrombospondin-1 induction might provide an explanation for the specificity of the effects of metronomic gemcitabine treatment

A randomized phase II study of capecitabine-based chemoradiation with or without bevacizumab in resectable locally advanced rectal cancer: clinical and biological features

Background: perioperatory chemoradiotherapy (CRT) improves local control and survival in patients with locally advanced rectal cancer (LARC). The objective of the current study was to evaluate the addition of bevacizumab (BEV) to preoperative capecitabine (CAP)-based CRT in LARC, and to explore biomarkers for downstaging. Methods: patients (pts) were randomized to receive 5 weeks of radiotherapy 45 Gy/25 fractions with concurrent CAP 825 mg/m2 twice daily 5 days per week and BEV 5 mg/kg once every 2 weeks (3 doses) (arm A), or the same schedule without BEV (arm B). The primary end point was pathologic complete response (ypCR: ypT0N0). Results: ninety pts were included in arm A (44) or arm B (46). Grade 3-4 treatment-related toxicity rates were 16% and 13%, respectively. All patients but one (arm A) proceeded to surgery. The ypCR rate was 16% in arm A and 11% in arm B (p =0.54). Fifty-nine percent vs 39% of pts achieved T-downstaging (arm A vs arm B; p =0.04). Serial samples for biomarker analyses were obtained for 50 out of 90 randomized pts (arm A/B: 22/28). Plasma angiopoietin-2 (Ang-2) levels decreased in arm A and increased in arm B (p <0.05 at all time points). Decrease in Ang-2 levels from baseline to day 57 was significantly associated with tumor downstaging (p =0.02). Conclusions: the addition of BEV to CAP-based preoperative CRT has shown to be feasible in LARC. The association between decreasing Ang-2 levels and tumor downstaging should be further validated in customized studies

Multicenter study of lumen-apposing metal stents with or without pigtail in endoscopic ultrasound-guided biliary drainage for malignant obstruction - BAMPI TRIAL: an open-label, randomized controlled trial protocol

Background It is unclear whether the insertion of an axis-orienting double-pigtail plastic stent (DPS) through biliary lumen-apposing meal stent (LAMS) in EUS-guided choledochoduodenostomy (CDS) improves the stent patency. The aim of this study is to determine whether this technical variant offers a clinical benefit in EUS-guided biliary drainage (BD) for the management of distal malignant biliary obstruction. Methods/design This is a multicenter open-label, randomized controlled trial with two parallel groups. Eighty-four patients with malignant biliary obstruction will undergo EUS-BD (CDS type) using LAMS in 7 tertiary hospitals in Spain and will be randomized to the LAMS and LAMS plus DPS groups. The primary endpoint is the rate of recurrent biliary obstruction, as a stent dysfunction parameter, detected during follow-up. Secondary endpoints: technical and clinical success (reduction in bilirubin > 50% within 14 days of stent placement), safety, and others (number of reinterventions, time to biliary obstruction, prognostic factors, survival rate). Discussion The BAMPI trial has been designed to determine whether the addition of a coaxial axis-orienting DPS through LAMS is superior to LAMS alone to prevent stent dysfunction

ICO-ICS Praxis para el tratamiento médico y con irradiación del adenocarcinoma del páncreas

Tractament mèdic; Tractament amb irradiació; Adenocarcinoma; Pàncrees; CàncerTratamiento médico; Tratamiento con irradiación; Adenocarcinoma; Páncreas; CáncerMedical treatment; Irradiation treatment; Adenocarcinoma; Pancreas; CancerEl càncer de pàncrees se situa com la tercera causa més freqüent de càncer en la forma d'adenocarcinoma ductal pancreàtic. És un dels càncers més agressius i amb un percentatge més baix de curació. Els objectius d'aquesta guia són: -Desenvolupar, difondre, implementar i avaluar resultats de la ICO-ICSPraxi de càncer de pàncrees. -Disminuir la variabilitat terapèutica entre els pacients tractats als diferents centres d'aquesta institució. -Implementar els resultats de la terapèutica en els pacients amb adenocarcinoma de pàncrees tractats d'acord amb les recomanacions d'aquesta guia