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Background Therapeutic options are limited for advanced, metastatic biliary tract cancer. The pivotal NAPOLI-1 trial demonstrated the superior clinical benefit of nanoliposomal irinotecan (Nal-IRI) in gemcitabine-pretreated patients with metastatic pancreatic ductal adenocarcinoma; however, the antitumor activity of Nal-IRI in biliary tract cancer is unknown. This is the first report describing the efficacy of Nal-IRI in biliary tract cancer. Methods In this multicenter retrospective cohort analysis, we identified patients with metastatic biliary tract adenocarcinoma who were treated with Nal-IRI in combination with 5-fluorouracil and folinic acid following tumor progression under standard therapy at one of the study centers between May 2016 and January 2019. We assessed disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). Results There were 14 patients; the median age at the time of diagnosis and the median age at the initiation of Nal-IRI were 59.3 and 60.0 years, respectively. Nal-IRI in combination with 5-fluorouracil and folinic acid was administered as second-, third-, fourth-, and fifth-line treatment in 6 (43%), 5 (36%), 2 (14%), and 1 (7%) patient with metastatic disease, respectively. The objective DCR with Nal-IRI was 50% (7/14 patients). Six patients (43%) had partial response, and one patient (7%) had stable disease. Progressive disease was observed in seven patients. The median PFS and median OS following Nal-IRI initiation were 10.6 and 24.1 months, respectively. Conclusions This retrospective analysis provides the first evidence that Nal-IRI might exhibit a clinical meaningful antitumor activity in metastatic biliary tract cancer.

Introduction Recent advances in prophylactic anticoagulation and antineoplastic treatment for advanced pancreatic cancer (aPC) warrant an updated reassessment of thromboembolic risk in this population. This multicenter retrospective cohort study aims to comprehensively characterize incidence, risk factors, and outcomes of venous (VTE) and arterial thromboembolism (ATE) in homogenously treated patients with aPC. Methods Four hundred and fifty-five patients with aPC undergoing palliative first-line chemotherapy (Gemcitabine/nab-Paclitaxel (GN) or FOLIRINOX) were included. Primary outcomes were objectively confirmed VTE and/or ATE. Results Over a median follow-up of 26 months, 86 VTE (cumulative incidence: 20.0%; 95% confidence interval [CI]: 16.3–24.0) and 11 ATE events (cumulative incidence: 2.8%; 95% CI: 1.5–4.9) were observed. VTE diagnosis was associated with increased mortality (transition hazard ratio [THR]: 1.59 [95% CI: 1.21–2.09]) and increased risk of cancer progression (THR: 1.47 [95% CI: 1.08–2.01]), while the impact of ATE on mortality was numerically but not statistically significant (THR: 1.85 [95% CI: 0.87–3.94]). The strongest predictor of increased VTE risk was history of cancer-associated VTE (subdistribution hazard ratio [SHR]: 3.29 [95% CI: 2.09–5.18]), while the Khorana score (SHR: 0.78 [0.57–1.06]) failed to predict VTE risk. A history of cerebrovascular disease was associated with markedly increased ATE risk (SHR: 22.05 [95% CI: 6.83–71.22], p Conclusion Patients with aPC undergoing palliative first-line chemotherapy with FOLFIRINOX or GN face a high risk for VTE/ATE and its diagnosis is linked to worse clinical outcomes. VTE-risk prediction models have limited ability to sub-stratify thrombotic events in this high-risk scenario.

Summary Colorectal cancer (CRC) is one of the most frequent cancer entities worldwide and a leading cause of death. The disease is known to develop from potentially curable, premalignant lesions over several years and therefore is suitable for screening procedures and preventive measures. Several trials have demonstrated reduced incidence and mortality in screening cohorts. A multitude of different screening strategies for CRC have been implemented in different parts of the world. While randomized controlled studies directly comparing screening procedures are still ongoing, colonoscopy remains the gold standard for screening and the only procedure that allows to effectively prevent CRC by treating premalignant lesions. However, population-wide participation rates vary greatly but often only reach approximately 25%. Noninvasive screening strategies are indispensable to increase acceptance rates and for resource-limited regions with limited capacity for colonoscopy. Importantly, while incidence of CRC increases with age, lately we have seen a raise in incidence for CRC in the population below 50 years of age, potentially requiring to include younger adults (e.g., 45 years of age) into established screening programs. It remains important to continue to gather data and evidence regarding effectiveness of various screening strategies, preferably in randomized controlled trials. This short review will outline currently established screening procedures and will discuss the pros and cons for each individual approach.

The majority of patients diagnosed with pancreatic cancer have inoperable disease at the time of presentation. For this reason, systemic treatment is the cornerstone of therapy and more options for systemic therapy have now become available than were a decade ago. In this short review, we will give an overview on the systemic therapeutic landscape in 2018 and briefly discuss the challenging topic of neoadjuvant therapy. However, there are a lot of unsolved questions and an urgent need of more clinical trials and new therapies. In conclusion, despite recent advances, there remains much room for improvement in all aspects of treatment for pancreatic cancer.

With a global incidence of 1.8 million cases, colorectal cancer represents one of the most common cancers worldwide. Despite impressive improvements in treatment efficacy through cytotoxic and biological agents, the cancer-related death burden of metastatic colorectal cancer (mCRC) is still high. mCRC is not a genetically homogenous disease and various mutations influence disease development. Up to 12% of mCRC patients harbor mutations of the signal transduction molecule BRAF, the most prominent being BRAFV600E. In mCRC, BRAFV600E mutation is a well-known negative prognostic factor, and is associated with a dismal prognosis. The currently approved treatments for BRAF-mutated mCRC patients are of little impact, and there is no treatment option superior to others. However, the gradual molecular understanding over the last decades of the extracellular signal-regulated kinase/mitogen-activated protein kinase pathway, resulted in the development of new therapeutic strategies targeting the involved molecules. Recently published and ongoing studies administering a combination of different inhibitors (e.g., BRAF, MEK, and EGFR) showed promising results and represent the new standard of care. In this review, we present, both, the molecular and clinical aspects of BRAF-mutated mCRC patients, and provide an update on the current and future treatment approaches that might direct the therapy of mCRC in a new era.

Background Pancreatic cancer (PC) ranks among the deadliest malignancies worldwide. In the MPACT study, first-line nab-paclitaxel plus gemcitabine (nab-P/G) demonstrated activity (median overall survival [OS], 8.7 months) and tolerability in patients with metastatic PC (mPC). However, the clinical evidence of nab-P/G in the elderly (>70 years), who account for the majority of patients with mPC, is limited. This is the first prospective, multicentre, non-interventional study evaluating the tolerability and effectiveness of nab-P/G in younger (≤70 years) versus elderly (>70 years) patients with mPC in the daily clinical routine. Methods Eligible patients with mPC were treated with nab-P/G and observed until disease progression or unacceptable toxicity. The primary objectives were safety and tolerability of nab-P/G, and the secondary objectives were efficacy and real-life dosing. Results A total of 317 patients with mPC (median age, 70 years) were recruited, of which 299, aged ≤70 (n = 162) and >70 (n = 137) years, were eligible for analysis. Baseline characteristics and the safety profile were comparable between the groups. However, fatigue (22.8% versus 13.0%) and decreased appetite (8.8% versus 1.2%) were more frequent in elderly patients. Younger versus elderly patients equally benefited in terms of objective response rate (36% versus 48%), median progression-free survival (5.6 versus 5.5 months; hazard ratio [HR] = 1.03; p = 0.81) and OS (10.6 versus 10.2 months; HR = 0.89; p = 0.4). In addition, the median treatment duration (5 versus 4 cycles), relative dose intensity (70% versus 74%) or reasons for treatment discontinuation were similar. Most patients (56.2% versus 47.4%) benefited from a second-line therapy. Conclusion This prospective real-world analysis confirms the feasibility and tolerability of nab-P/G treatment and reveals OS data similar for younger patients and elderly patients aged >70 years. ClinicalTrials.gov registration NCT02555813. Austrian NIS registry NIS005071.

Background: The pretreatment De Ritis ratio [aspartate transaminase (AST)/alanine transaminase (ALT)] has been shown to be an adverse prognostic marker in various cancer entities. However, its relevance to advanced pancreatic ductal adenocarcinoma (PDAC) has not yet been studied. In the present study we investigated the AST/ALT ratio as a possible predictor of treatment response and disease outcome in patients with advanced PDAC treated with first-line gemcitabine/nab-paclitaxel. Methods: A post hoc analysis of a prospective, multicenter, noninterventional study was performed. A total of 202 patients with advanced PDAC treated with first-line gemcitabine/nab-paclitaxel for whom the AST/ALT ratio was measured were included in this analysis. Results: Median and 1-year progression-free survival estimates were 4.8 months and 5.1%, respectively in patients with an AST/ALT ratio above the 75th percentile of its distribution, and 6.0 months and 18.7%, respectively in patients with an AST/ALT ratio less than or equal to this cutoff, respectively (log-rank p = 0.004). In univariable Cox regression, a doubling of the AST/ALT ratio was associated with a 1.4-fold higher relative risk of progression or death [hazard ratio = 1.38, 95% confidence interval (CI): 1.06–1.80, p = 0.017]. The prognostic association was also found in multivariable analysis adjusting for Eastern Cooperative Oncology Group performance status and lung metastases (hazard ratio per AST/ALT ratio doubling = 1.32, 95% CI: 1.00–1.75, p = 0.047). In treatment response analysis, a doubling of the AST/ALT ratio was associated with a 0.5-fold lower odds of objective response (odds ratio = 0.54, 95% CI: 0.31–0.94, p = 0.020). Conclusions: The pretreatment serum AST/ALT ratio predicts poor disease outcome and response rate in patients with advanced PDAC treated with gemcitabine/nab-paclitaxel and might represent a novel and inexpensive marker for individual risk assessment in the treatment of pancreatic cancer.

Supplemental material, Supplementary_Tablesandfigures_TAM for The AST/ALT (De Ritis) ratio predicts clinical outcome in patients with pancreatic cancer treated with first-line nab-paclitaxel and gemcitabine: post hoc analysis of an Austrian multicenter, noninterventional study by Jakob Michael Riedl, Florian Posch, Gerald Prager, Wolfgang Eisterer, Leopold Oehler, Thamer Sliwa, Klaus Wilthoner, Andreas Petzer, Petra Pichler, Eva Hubmann, Thomas Winder, Sonja Burgstaller, Markus Korger, Johannes Andel, Richard Greil, Martin Pecherstorfer, Kathrin Philipp-Abbrederis, Angela Djanani, Birgit Gruenberger, Friedrich Laengle, Ewald Wöll and Armin Gerger in Therapeutic Advances in Medical Oncology