CCL3 predicts exceptional response to TGFβ inhibition in basal-like pancreatic cancer enriched in LIF-producing macrophages.

The TGFβ receptor inhibitor galunisertib showed promising efficacy in patients with pancreatic ductal adenocarcinoma (PDAC) in the phase 2 H9H-MC-JBAJ study. Identifying biomarkers for this treatment remains essential. Baseline plasma levels of chemokine CCL3 were integrated with clinical outcomes in PDAC patients treated with galunisertib plus gemcitabine (n = 104) or placebo plus gemcitabine (n = 52).

Complete pathological response to pembrolizumab in pretreated pancreatic acinar cell carcinoma.

Background: Therapeutic approach used for pancreatic ductal adenocarcinoma is usually translated also for the rarer acinar counterpart, which shows a different mutational landscape nevertheless. While dMMR/MSI-H status is rare in the ductal histotype, it appears to be more prevalent in pancreatic acinar cell carcinoma (PACC).

Case Presentation: We report the case of a patient with locally advanced MSI-H PACC in whom the treatment with the anti-PD-1 pembrolizumab, administered as third line, made possible surgical resection, achieving even an exceptional pathological complete response.

Integration of liposomal irinotecan in the first-line treatment of metastatic pancreatic cancer: try to do not think about the white bear.

The approval of novel therapeutic agents remains widely reliant on evidence derived from large phase III randomized controlled trials. Liposomal irinotecan (ONIVYDE) stands out as the only drug that has demonstrated improved survival both as a first-line therapy in combination with oxaliplatin and 5-fluorouracil/leucovorin (5FU/LV) (NALIRIFOX) compared to the standard gemcitabine plus nab-paclitaxel in the NAPOLI3 trial, and as a second-line treatment in combination with 5FU/LV compared to the standard 5FU/LV in the NAPOLI1 trial. However, just as the white bear of the Dostoevsky's paradox, the judgment of these results is invariably distracted by the intrusive thought of how different they might be if compared to similar regimens containing standard-free irinotecan as FOLFIRINOX or FOLFIRI, respectively.

Perioperative NALIRIFOX in patients with resectable pancreatic ductal adenocarcinoma: The open-label, multicenter, phase II nITRO trial.

Background: Upfront surgery followed by postoperative treatment is a commonly adopted treatment for resectable pancreatic ductal adenocarcinoma (rPDAC). However, the risk of positive surgical margins, the poor recovery that often impairs postoperative treatments, and the risk of recurrence might limit the outcome of this strategy. This study evaluated the safety and the activity of liposomal irinotecan 50 mg/m + 5-fluorouracil 2400 mg/m + leucovorin 400 mg/m + oxaliplatin 60 mg/m (NALIRIFOX) in the perioperative treatment of patients with rPDAC.

YAP Activation Is Associated with a Worse Prognosis of Poorly Cohesive Gastric Cancer.

Poorly cohesive (PC) gastric cancer (GC) is extremely aggressive in progression, and there is an urgent need to identify the molecular pathways involved. We hypothesized the essential role of the RhoA-YAP axis in these mechanisms. The present observational multicenter retrospective study included 133 patients with PC GC treated at two dedicated European surgical centers between 2004 and 2014.

Autotaxin Secretion Is a Stromal Mechanism of Adaptive Resistance to TGFβ Inhibition in Pancreatic Ductal Adenocarcinoma.

Unlabelled: The TGFβ receptor inhibitor galunisertib demonstrated efficacy in patients with pancreatic ductal adenocarcinoma (PDAC) in the randomized phase II H9H-MC-JBAJ study, which compared galunisertib plus the chemotherapeutic agent gemcitabine with gemcitabine alone. However, additional stromal paracrine signals might confer adaptive resistance that limits the efficacy of this therapeutic strategy. Here, we found that autotaxin, a secreted enzyme that promotes inflammation and fibrosis by generating lysophosphatidic acid (LPA), mediates adaptive resistance to TGFβ receptor inhibition.

The role of nanoliposomal irinotecan plus fluorouracil/leucovorin in the continuum of care of patients with metastatic pancreatic ductal adenocarcinoma.

Background: The NAPOLI-I trial showed better outcome of nanoliposomal irinotecan (nal-IRI) plus 5-fluorouracil/leucovorin (5-FU/LV) compared to 5-FU/LV in patients with advanced pancreatic ductal adenocarcinoma cancer (advPDAC) progressed to gemcitabine-based therapy. This study aims to explore the real-world efficacy and safety of 5-FU/LV-nal-IRI.

Methods: This is a retrospective multicenter analysis including advPDAC patients receiving 5-FU/LV-nal-IRI after failure of gemcitabine-based therapy.

Second-Line Chemotherapy in Elderly Patients with Advanced Biliary Tract Cancer: A Multicenter Real-World Study.

Objectives: The ABC-06 and the NIFTY trials recently established the role of second-line chemotherapy (2L) in patients with advanced biliary tract cancer (BTC). Our real-world study aimed to explore 2L in BTC patients aged ≥ 70 years old and to compare their outcomes with younger subjects. Methods: Institutional registries across three academic medical centers were retrospectively reviewed.

Multicentre match-paired analysis of advanced biliary cancer long-term survivors: The BILONG study.

Background: Advanced biliary cancers (ABC) are aggressive malignancies with a median overall survival (mOS) <12 months when treated with first-line chemotherapy. Nevertheless, a subset of patients experiencing longer survival has been described in the updated analysis of ABC-02 trial. We aimed to provide a real-world description of ABC long-term survivors (LS), identifying which factors impact on survival.

Predictive Biomarkers for a Personalized Approach in Resectable Pancreatic Cancer.

The mainstay treatment for patients with immediate resectable pancreatic cancer remains upfront surgery, which represents the only potentially curative strategy. Nevertheless, the majority of patients surgically resected for pancreatic cancer experiences disease relapse, even when a combination adjuvant therapy is offered. Therefore, aiming at improving disease free survival and overall survival of these patients, there is an increasing interest in evaluating the activity and efficacy of neoadjuvant and perioperative treatments.

Development and Multicentre Validation of the Modena Score to Predict Survival in Advanced Biliary Cancers Undergoing Second-Line Chemotherapy.

Background: The role of second-line chemotherapy in advanced biliary cancers (ABCs) has only recently been established in phase III randomized trial and the optimal selection of patients most likely to benefit from it remains challenging.

Methods: A cohort of 98 ABC treated second-line chemotherapy was used as a developmental dataset to identify covariates independently associated with overall survival (OS). Kaplan-Meier analysis was used to investigate the association between variables and OS and those retaining statistically significance were combined in a multiplexed score.

Third-line chemotherapy in advanced biliary cancers (ABC): pattern of care, treatment outcome and prognostic factors from a multicenter study.

Objectives: Here, we aim at describing the pattern of care, survival outcome and prognostic factors of ABC patients (pts) receiving third-line chemotherapy.

Methods: Institutional registries across three academic medical centers were retrospectively reviewed. Kaplan-Meier estimators were used to calculate survival, the log-rank test to make comparisons, and the Cox proportional hazard models to assess the progostic impact of variables.

Resectable and Borderline Resectable Pancreatic Ductal Adenocarcinoma: Role of the Radiologist and Oncologist in the Era of Precision Medicine.

The incidence and mortality of pancreatic ductal adenocarcinoma are growing over time. The management of patients with pancreatic ductal adenocarcinoma involves a multidisciplinary team, ideally involving experts from surgery, diagnostic imaging, interventional endoscopy, medical oncology, radiation oncology, pathology, geriatric medicine, and palliative care. An adequate staging of pancreatic ductal adenocarcinoma and re-assessment of the tumor after neoadjuvant therapy allows the multidisciplinary team to choose the most appropriate treatment for the patient.

Role of next-generation genomic sequencing in targeted agents repositioning for pancreaticoduodenal cancer patients.

Background: Pancreaticoduodenal cancer (PDC) is a group of malignant tumors arising in the ampullary region, which lack approved targeted therapies for their treatment.

Methods: This retrospective, observational study is based on Secondary Data Use (SDU) previously collected during a multicenter collaboration, which were subsequently entered into a predefined database and analyzed. FoundationOne CDx or Liquid, a next-generation DNA sequencing (NGS) service, was used to identify genomic alterations of patients who failed standard treatments.

Pyrene-Based "Turn-Off" Probe with Broad Detection Range for Cu , Pb and Hg Ions.

Detection of metals in different environments with high selectivity and specificity is one of the prerequisites of the fight against environmental pollution with these elements. Pyrenes are well suited for the fluorescence sensing in different media. The applied sensing principle typically relies on the formation of intra- and intermolecular excimers, which is however limiting the sensitivity range due to masking of e.

Targeting KRAS: The Elephant in the Room of Epithelial Cancers.

Mutations of the proto-oncogene KRAS are the most frequent gain-of-function alterations found in cancer. KRAS is mutated in about 30% of all human tumors, but it could reach more than 90% in certain cancer types such as pancreatic adenocarcinoma. Although historically considered to be undruggable, a particular KRAS mutation, the G12C variant, has recently emerged as an actionable alteration especially in non-small cell lung cancer (NSCLC).

Safety and activity of the TGFβ receptor I kinase inhibitor galunisertib plus the anti-PD-L1 antibody durvalumab in metastatic pancreatic cancer.

Background: We assessed the safety, efficacy, and pharmacokinetics of the transforming growth factor beta (TGFβ) receptor inhibitor galunisertib co-administered with the anti-programmed death-ligand 1 (PD-L1) antibody durvalumab in recurrent/refractory metastatic pancreatic cancer previously treated with ≤2 systemic regimens.

Methods: This was a two-part, single-arm, multinational, phase Ib study. In a dose-finding phase, escalating oral doses of galunisertib were co-administered on days 1-14 with fixed-dose intravenous durvalumab 1500 mg on day 1 every 4 weeks (Q4W), followed by an expansion cohort phase.

A phase II study of liposomal irinotecan with 5-fluorouracil, leucovorin and oxaliplatin in patients with resectable pancreatic cancer: the nITRO trial.

Background: Up-front surgery followed by postoperative chemotherapy remains the standard paradigm for the treatment of patients with resectable pancreatic cancer. However, the risk for positive surgical margins, the poor recovery after surgery that often impairs postoperative treatment, and the common metastatic relapse limit the overall clinical outcomes achieved with this strategy. Polychemotherapeutic combinations are valid options for postoperative treatment in patients with good performance status.