A pilot study of chlorambucil in pre-treated metastatic pancreatic adenocarcinoma patients bearing germline BRCA or other DNA damage repair system variants.

Backgorund: Pancreatic adenocarcinoma remains a malignancy with a grim prognosis and scarce personalized treatment options. Pathogenic variants of DNA damage repair (DDR) genes are emerging as molecular targets, as they confer a higher sensitivity to DNA-damaging agents. This study aimed at assessing the activity of chlorambucil as salvage therapy in metastatic pancreatic cancer patients bearing a germline pathogenetic variant or variant of uncertain significance on a DDR-related gene.

Exploring external validity of chemotherapy for pancreatic ductal adenocarcinoma in real life.

Introduction: Cisplatin, nab-paclitaxel, capecitabine, and gemcitabine (PAXG) regimen activity was assessed in a single institution phase II trial (PACT-19) on pancreatic ductal adenocarcinoma (PDAC). The PACT-31 study explored the external validity of PACT-19 results.

Materials And Methods: Patients aged ≥18 and ≤75 years with KPS ≥70, and PDAC diagnosis receiving PAXG in the participating institutions were eligible and categorized as follows: A) PACT-19; B) PACT-31-HSR; C) PACT-31-non-HSR.

Isolated lung metastases from pancreatic ductal adenocarcinoma (PDAC): Diagnostic and therapeutic challenges of a different disease.

Pancreatic ductal adenocarcinoma (PDAC) has a dismal prognosis, mostly due to the high rate of distant dissemination. However, growing evidence shows that isolated lung recurrence or metastases (ILM) from PDAC are not only less common, but also correlated with a better prognosis. Lung-only recurrence after surgery occurs later in time and is associated with more favorable prognostic characteristics of the primary tumor.

Hypofractionated radiotherapy concomitant to capecitabine after induction chemotherapy for advanced pancreatic adenocarcinoma.

Background And Purpose: To assess feasibility, toxicity and outcome of moderately hypofractionated radiotherapy concomitant to capecitabine after induction chemotherapy for advanced pancreatic cancer.

Materials And Methods: Patients with advanced pancreatic cancer without distant progression after induction chemotherapy (CHT) were considered. Radiochemotherapy (RCT) consisted of 44.

Clinical outcomes and response to chemotherapy in a cohort of pancreatic cancer patients with germline variants of unknown significance (VUS) in BRCA1 and BRCA2 genes.

Purpose: The clinical outcome and the efficacy of chemotherapy in pancreatic cancer patients with BRCA1/2 Variants of Unknown Significance (VUS) is unknown. We explored the effects of chemotherapy with or without Platinum in non metastatic and metastatic pancreatic cancer patients with BRCA1/2 VUS.

Methods: A retrospective analysis of non-metastatic or metastatic pancreatic cancer patients with gBRCA1/2 VUS treated in 13 Italian centers between November 2015 and December 2020 was performed.

Cyclophosphamide maintenance to extend combination chemotherapy-free interval in metastatic pancreatic ductal adenocarcinoma.

Background: Administering chemotherapy until progression to metastatic pancreatic ductal adenocarcinoma (PDAC) patients lacks of supporting evidence and causes cumulative toxicity. We explored the role of cyclophosphamide as maintenance therapy.

Methods: PDAC germline BRCA1-2 wild-type patients who were progression-free after ≥6 months of any regimen and line of chemotherapy and received maintenance cyclophosphamide (mCTX) (50 mg/day), were included in the analysis.

Second-line therapy in pancreatic ductal adenocarcinoma (PDAC) patients with germline BRCA1-2 pathogenic variants (gBRCA1-2pv).

Background: Pancreatic ductal adenocarcinoma (PDAC) harbouring germline BRCA1-2 pathogenic variants (gBRCA1-2pv) is a distinct nosological entity. Information on second-line therapy (2LT) outcome in this setting is lacking.

Methods: Data of gBRCA1-2pv metastatic PDAC patients treated with chemotherapy were collected.

Epidemiology and geographic distribution of BRCA1-2 and DNA Damage response genes pathogenic variants in pancreatic ductal adenocarcinoma patients.

Incidence of pancreatic ductal adenocarcinoma (PDAC) is increasing over the last years, while patients prognosis remains grim. Recently germline BRCA1 and 2 pathogenic variants (gBRCA1-2) have emerged as risk factors for PDAC development, as well as new predictors of response to specific therapeutic interventions. However, data on gBRCA1-2 incidence in PDAC are currently sparse and limited to selected categories of patients, as for positive cancer history cases, for patients affected only by early or late stages of disease and mainly from the North-American population, thus generating incomplete information about the gBRCA1/2 epidemiology.

Pancreatic Enzyme Replacement Therapy in Patients Undergoing First-Line Gemcitabine Plus -paclitaxel for Advanced Pancreatic Adenocarcinoma.

Background: The clinical consequences of pancreatic exocrine insufficiency and its treatment in advanced pancreatic ductal adenocarcinoma (PDAC) are poorly investigated. This retrospective study aims at investigating the pancreatic enzyme replacement therapy (PERT) use and its impact on survival and maldigestion-related symptoms in advanced PDAC patients undergoing chemotherapy.

Methods: A retrospective analysis was conducted on advanced PDAC patients, treated with first-line gemcitabine plus -paclitaxel at two academic institutions (March 2015-October 2018).

Treatment opportunities and future perspectives for pancreatic cancer patients with germline BRCA1-2 pathogenic variants.

Personalized treatments and predictive biomarkers of pancreatic cancer (PDAC) are still lacking. Recently germline mutations in BRCA 1 and 2 genes, leading to homologous repair deficiency, have emerged as new targets for more specific and effective therapies, exploiting the increased susceptibility to platinum salts and PARP inhibitors. In addition to BRCA, pathogenic variants in PALB2 and in other genes involved in the DNA damage response pathway (DDR) represent potential targets, as well as their respective somatic alterations.

Exploring chemotherapy holiday and drugs re-challenge in advanced pancreatic cancer patients.

Purpose: We aimed to explore the role of drugs re-challenge at the disease progression after a chemotherapy-free interval for pancreatic adenocarcinoma (PDAC) patients.

Methods: We retrospectively analyzed the outcome of re-treatments at the progression in two cohorts of advanced PDAC patients who had disease control (DC) and a treatment holiday ≥ 3 months after upfront chemotherapy.

Results: Between 2015 and 2019, 66 advanced PDAC patients (cohort A) had DC with nab-paclitaxel-based chemotherapy (i.

Multidrug regimens for treatment of older patients with metastatic pancreatic cancer.

Background And Aims: Older patients with metastatic pancreatic adenocarcinoma (MPDAC) are under-represented in clinical trials.

Methods: Our single-center, retrospective study enrolled MPDAC patients ≥ 70 treated with chemotherapy RESULTS: 105 patients were divided in groups based on the received treatments: 44 gemcitabine or capecitabine monotherapy (A), 34 nabpaclitaxel-gemcitabine (B) 27 4-drugs combinations (gemcitabine, cisplatin, capecitabine plus either nab-paclitaxel or epirubicin or docetaxel) (C). Group A: median age was 78 (70-87) and Karnofsky performance status (KPS) ≥80 was found in 84% of patients; Group B: median age 77 (71-84) and KPS ≥ 80 in 88% of patients; Group C: median age 73 (70-78) and KPS ≥ 80 in 93% of patients.

Time to CA19-9 nadir: a clue for defining optimal treatment duration in patients with resectable pancreatic ductal adenocarcinoma.

Background: Defining optimal treatment duration in patients with resectable pancreatic ductal adenocarcinoma (PDAC) receiving primary chemotherapy is an unmet need. The role of time to CA19-9 nadir and of nadir magnitude was explored in this study.

Patients And Methods: The databases of our institution's prospective trials were queried to speculate on the time to maximum chemotherapy response.

Chemotherapy in elderly patients with pancreatic cancer: Efficacy, feasibility and future perspectives.

By 2030 70% of newly diagnosed pancreatic ductal adenocarcinoma (PDAC) will occur in older adults. Elderly patients, defined by the World Health Organization (WHO) as people older than 65 years, represent a heterogeneous group with different biological and functional characteristics that need personalized anticancer treatments. Since older patients are under-represented in randomized phase III trials, their management is mostly extrapolated from studies performed in younger patients, without robust evidence-based recommendations.

Nab-paclitaxel plus gemcitabine with or without capecitabine and cisplatin in metastatic pancreatic adenocarcinoma (PACT-19): a randomised phase 2 trial.

Background: Current treatment for metastatic pancreatic ductal adenocarcinoma includes combination chemotherapy, such as FOLFIRINOX or nab-paclitaxel plus gemcitabine. We investigated the activity of a novel four-drug regimen, consisting of cisplatin, nab-paclitaxel, capecitabine, and gemcitabine, compared with nab-paclitaxel plus gemcitabine, in the PACT-19 trial.

Methods: This single-centre, randomised, open-label, phase 2 trial was done in San Raffaele Hospital in Italy.

A randomised phase 2 trial of nab-paclitaxel plus gemcitabine with or without capecitabine and cisplatin in locally advanced or borderline resectable pancreatic adenocarcinoma.

Background: The current trial assessed whether the addition of cisplatin and capecitabine to the nab-paclitaxel-gemcitabine backbone is feasible and active against borderline and locally advanced pancreatic adenocarcinoma (PDAC).

Method: Fifty-four chemo-naive patients, aged between 18 and 75 years, with a pathological diagnosis of locally advanced or borderline resectable PDAC were randomised to receive either nab-paclitaxel, gemcitabine, cisplatin and oral capecitabine (PAXG; arm A; N = 26) or nab-paclitaxel followed by gemcitabine (AG; arm B; N = 28). The primary end-point was the tumour resection rate.

Risk Stratification Model for Resected Squamous-Cell Lung Cancer Patients According to Clinical and Pathological Factors.

Introduction: The aim of this analysis (AIRC-MFAG project no. 14282) was to define a risk classification for resected squamous-cell lung cancer based on the combination of clinicopathological predictors to provide a practical tool to evaluate patients' prognosis.

Methods: Clinicopathological data were retrospectively correlated to disease-free/cancer-specific/overall survival (DFS/CSS/OS) using a Cox model.

An overview of angiogenesis inhibitors in Phase II studies for non-small-cell lung cancer.

Introduction: Angiogenesis plays a major role in the development and progression of solid tumors, including lung cancer. Although some anti-angiogenic agents have demonstrated a statistically significant advantage in terms of primary outcome in clinical trials, the reliable clinical benefit obtained with these drugs is still questionable and often quantitatively limited. To better clarify this complex scenario and definitively establish the concrete benefits of anti-angiogenic strategies in lung cancer, several clinical trials have been conducted with others currently ongoing.

Molecular heterogeneity assessment by next-generation sequencing and response to gefitinib of EGFR mutant advanced lung adenocarcinoma.

Cancer molecular heterogeneity might explain the variable response of EGFR mutant lung adenocarcinomas to tyrosine kinase inhibitors (TKIs). We assessed the mutational status of 22 cancer genes by next-generation sequencing (NGS) in poor, intermediate or good responders to first-line gefitinib. Clinical outcome was correlated with Additional Coexisting Mutations (ACMs) and the EGFR Proportion of Mutated Alleles (PMA).

Immune checkpoint inhibitors for non-small-cell lung cancer: does that represent a 'new frontier'?

Advances in the interpretation and understanding of cancer behaviour, particularly of its ability to evade the host immunosurveillance, deregulating the balance between inhibitory and stimulatory factors, led to the development of an innovative category of immunotherapeutic agents, currently under investigation. Although the disappointing data deriving from the employment of vaccines in non-small cell lung cancer (NSCLC), more promising results have been obtained in the early phase trials with immune checkpoint inhibitors, such as cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4), programmed cell death protein-1 (PD-1) and programmed death-ligand 1 (PD-L1) inhibitors. This review delineates the main features of the available immunotherapeutic agents, focusing the discussion on immune checkpoint inhibitors, those that have already demonstrated a relevant clinical activity (such as Ipilimumab and Nivolumab) and those molecules still in early development phase.

ALK/EML4 fusion gene may be found in pure squamous carcinoma of the lung.

Introduction: The report of cases of lung squamous cell cancers harboring anaplastic lymphoma kinase (ALK) gene rearrangements raises the question whether this histologic subtype should be also evaluated for such molecular predictive test.

Methods: A consecutive series of 40 lung pure squamous cell carcinomas were analyzed for ALK gene status by fluorescence in situ hybridization. Squamous differentiation was validated using an immunohistochemical panel including n-p63 (p40), cytokeratin (CK) 5/6, sex-determining region Y (SRY)-Box2 (SOX2), thyroid transcription factor 1, CK7, and Napsin-A.