Antibody-Drug Conjugates and Their Potential in the Treatment of Patients with Biliary Tract Cancer.

Biliary tract cancers (BTCs) are aggressive in nature, often presenting asymptomatically until they are diagnosed at an advanced stage. Surgical resection or liver transplantation are potential curative options. However, a large proportion of patients present with incurable locally advanced or metastatic disease and most of these patients are only eligible for palliative chemotherapy or best supportive care.

Relevant Study: Patient and Clinician Perspectives on Clinically-Meaningful Outcomes in Advanced Pancreatic Cancer.

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer with a poor prognosis and significant symptom burden. This prospective observational study aimed to evaluate expectations and priorities of patients with advanced PDAC and their clinicians through a study survey and two quality of life (QoL) questionnaires (QLQ-C30 and PAN26) at three time-points: baseline (T1), before (T2) and after (T3) their 1st on-treatment CT scan. Over a 1-year period, 106 patients were approached, 71 patients and 12 clinicians were recruited.

The Management and Outcomes of Patients with Extra-Pulmonary Neuroendocrine Neoplasms and Brain Metastases.

Background: Brain metastases (BMs) in patients with extra-pulmonary neuroendocrine neoplasms (EP-NENs) are rare, and limited clinical information is available. The aim of this study was to detail the clinicopathological features, management and outcomes in patients with EP-NENs who developed BMs.

Methods: A retrospective single-centre analysis of consecutive patients with EP-NENs (August 2004-February 2020) was conducted.

Molecular Profiling of Well-Differentiated Neuroendocrine Tumours: The Role of ctDNA in Real-World Practice.

: The role of tumour genomic profiling in the clinical management of well-differentiated neuroendocrine tumours (WdNETs) is unclear. Circulating tumour DNA (ctDNA) may be a useful surrogate for tumour tissue when the latter is insufficient for analysis. : Patients diagnosed with WdNETs underwent ctDNA genomic profiling (FoundationLiquid); non-WdNETs (paraganglioma, goblet cell or poorly-differentiated neuroendocrine carcinoma) were used for comparison.

Expanding Therapeutic Opportunities for Extrapulmonary Neuroendocrine Carcinoma.

Poorly differentiated neuroendocrine carcinomas (PD-NEC) are rare cancers garnering interest as they become more commonly encountered in the clinic. This is due to improved diagnostic methods and the increasingly observed phenomenon of "NE lineage plasticity," whereby nonneuroendocrine (non-NE) epithelial cancers transition to aggressive NE phenotypes after targeted treatment. Effective treatment options for patients with PD-NEC are challenging for several reasons.

Is the Morphological Subtype of Extra-Pulmonary Neuroendocrine Carcinoma Clinically Relevant?

Extra-pulmonary neuroendocrine carcinomas (EP-NECs) are lethal cancers with limited treatment options. Identification of contributing factors to the observed heterogeneity of clinical outcomes within the EP-NEC family is warranted, to enable identification of effective treatments. A multicentre retrospective study investigated potential differences in "real-world" treatment/survival outcomes between small-cell (SC) versus (vs.

Fibrolamellar carcinoma: Challenging the challenge.

Fibrolamellar carcinoma (FLC) is a rare and poorly understood malignancy, which seems to be more prevalent in young patients compared with conventional hepatocellular carcinoma (HCC). Performing prospective clinical trials recruiting patients diagnosed with FLC has proven challenging with scarce data available guiding clinical management. The use of a number of chemotherapy compounds in these patients, including cisplatin, epirubicin, 5-fluorouracil (5-FU) and recombinant interferon α-2B (IFN-α-2B), has been reported in the literature, mainly in the form of case reports.

Second-line treatment in patients with advanced extra-pulmonary poorly differentiated neuroendocrine carcinoma: a systematic review and meta-analysis.

Background: There is no standard second-line treatment for patients with advanced extra-pulmonary poorly differentiated neuroendocrine carcinoma (EP-PD-NEC). This study explored data evaluating second-line treatment in these patients.

Methods: A search of MEDLINE and EMBASE identified studies reporting survival and/or response data for patients with EP-PD-NEC receiving second-line therapy.

Current Translational and Clinical Challenges in Advanced Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is a frequent and increasing cause of cancerrelated deaths worldwide. Reversing this trend is complicated by the varied aetiological factors leading to liver cirrhosis resulting in molecular genetic and clinical heterogeneity, combined with frequent presentation at advanced stage. Large-scale genomic studies have identified alterations in key signalling pathways for HCC development and progression, but these findings have not yet directly influenced patient management in the clinical setting.

Clinical and Translational Research Challenges in Biliary Tract Cancers.

Background: Biliary Tract Cancers (BTC) are rare malignancies with a poor prognosis. There are many challenges encountered in treating these patients in daily practice as well as in clinical, translational and basic research.

Objective: This review summarises the most relevant challenges in clinical and translational research in BTCs and suggests potential solutions towards an improvement in quality of life and outcomes of patients diagnosed with such malignancies.

Mixed Neuroendocrine Non-Neuroendocrine Neoplasms: A Systematic Review of a Controversial and Underestimated Diagnosis.

Mixed neuroendocrine non-neuroendocrine neoplasms (MiNENs) represent a rare diagnosis of the gastro-entero-pancreatic tract. Evidence from the current literature regarding their epidemiology, biology, and management is of variable quality and conflicting. Based on available data, the MiNEN has an aggressive biological behaviour, mostly driven by its (often high-grade) neuroendocrine component, and a dismal prognosis.

Retrospective study on mixed neuroendocrine non-neuroendocrine neoplasms from five European centres.

Background: Mixed neuroendocrine non-neuroendocrine neoplasm (MiNEN) is a rare diagnosis, mainly encountered in the gastro-entero-pancreatic tract. There is limited knowledge of its epidemiology, prognosis and biology, and the best management for affected patients is still to be defined.

Aim: To investigate clinical-pathological characteristics, treatment modalities and survival outcomes of a retrospective cohort of patients with a diagnosis of MiNEN.

Follow-Up Recommendations after Curative Resection of Well-Differentiated Neuroendocrine Tumours: Review of Current Evidence and Clinical Practice.

The incidence of neuroendocrine neoplasms (NENs) is increasing, especially for patients with early stages and grade 1 tumours. Current evidence also shows increased prevalence, probably reflecting earlier stage diagnosis and improvement of treatment options. Definition of adequate postsurgical follow-up for NENs is a current challenge.

Carboplatin in Combination with Oral or Intravenous Etoposide for Extra-Pulmonary, Poorly-Differentiated Neuroendocrine Carcinomas.

Background: Carboplatin-etoposide (CarboEtop) is a 1st-line option for patients with advanced extra-pulmonary (EP), poorly-differentiated (PD) neuroendocrine carcinoma (NEC). Different schedules are used in clinical practice and randomised evidence is lacking.

Objectives: To provide real-life outcomes of carboplatin combined with oral or intravenous (IV) etoposide (Etop) in advanced EP-PD-NEC, from 2 specialist centres.

Sorafenib as first-line therapy in patients with advanced Child-Pugh B hepatocellular carcinoma-a meta-analysis.

Background: Sorafenib has demonstrated survival benefit in first-line treatment of advanced hepatocellular carcinoma (HCC); utility of sorafenib in patients with advanced HCC and Child-Pugh B (CP-B) liver function remains a subject of debate.

Methods: A systematic review identified studies using first-line sorafenib in patients with advanced HCC and CP-A/B liver function. Meta-regression analysis comprising linear regression was conducted to explore the association between the baseline factors and overall survival (OS).

MicroRNAs as Mediators of Resistance Mechanisms to Small-Molecule Tyrosine Kinase Inhibitors in Solid Tumours.

Receptor tyrosine kinases (RTKs) are widely expressed transmembrane proteins that act as receptors for growth factors and other extracellular signalling molecules. Upon ligand binding, RTKs activate intracellular signalling cascades, and as such are involved in a broad variety of cellular functions including differentiation, proliferation, migration, invasion, angiogenesis, and survival under physiological as well as pathological conditions. Aberrant RTK activation can lead to benign proliferative conditions as well as to various forms of cancer.

Somatostatin analogue-induced pancreatic exocrine insufficiency in patients with neuroendocrine tumors: results of a prospective observational study.

Background: Patients with advanced well-differentiated neuroendocrine tumours (Wd-NETs) are commonly treated with somatostatin analogues (SSAs). Some patients may develop SSA-related side effects such as pancreatic exocrine insufficiency (PEI).

Methods: In this prospective, observational study, the frequency of SSA-induced PEI in 50 sequential patients with advanced Wd-NETs treated with SSAs was investigated.

A circulating T2 cytokines profile predicts survival in patients with resectable pancreatic adenocarcinoma.

Surgery is the only potentially curative option for patients with pancreatic ductal adenocarcinoma (PDAC), but metastatic relapse remains common. We hypothesized that the expression levels of inflammatory cytokines could predict recurrence of PDAC, thus allowing to select patients who most likely could benefit from surgical resection. We prospectively collected plasma at diagnosis from 287 patients with pancreatic resectable neoplasms.

Targeting the Epidermal Growth Factor Receptor in Addition to Chemotherapy in Patients with Advanced Pancreatic Cancer: A Systematic Review and Meta-Analysis.

Overexpression of epidermal growth factor receptors (EGFR) occurs in >90% of pancreatic ductal adenocarcinomas (PDACs) and is associated with a poorer prognosis. A systematic review of electronic databases identified studies exploring the addition of EGFR-targeted treatment to chemotherapy in patients with locally advanced (LA)/metastatic PDAC. Efficacy, safety and tolerability of EGFR-targeted therapy were explored using meta-analysis of randomised controlled trials (RCTs).

Molecular analysis of a male breast cancer patient with prolonged stable disease under mTOR/PI3K inhibitors BEZ235/everolimus.

The mTORC1 inhibitor everolimus (Afinitor/RAD001) has been approved for multiple cancer indications, including ER(+)/HER2(-) metastatic breast cancer. However, the combination of everolimus with the dual PI3K/mTOR inhibitor BEZ235 was shown to be more efficacious than either everolimus or BEZ235 alone in preclinical models. Herein, we describe a male breast cancer (MBC) patient who was diagnosed with hormone receptor-positive (HR(+))/HER2(-) stage IIIA invasive ductal carcinoma and sequentially treated with chemoradiotherapy and hormonal therapy.

Current Strategies to Overcome Resistance to ALK-Inhibitor Agents.

The rearrangements of the anaplastic lymphoma kinase (ALK) gene are key drivers in the carcinogenesis of a portion of anaplastic large cell lymphomas (ALCL) and non-small cell lung cancers (NSCLC). Crizotinib, an orally available small molecule, has been the first ALK inhibitor to demonstrate a significant clinical activity in patients with ALK-positive tumors and, thus, to achieve the US food and drug administration approval for the treatment of advanced NSCLC harboring ALK-rearrangements. However, despite initially dramatic and quite durable responses in most cases, acquired resistance to crizotinib arises unavoidably often within the first year of treatment.