Perioperative Chemotherapy Including Bevacizumab in Potentially Curable Metastatic Colorectal Cancer: Long-Term Follow-Up of the ASSO-LM1 Trial.

In 2007, the ASSO-LM1 trial, a multicenter prospective study, was initiated to investigate the resectability (R0) rate following preoperative combination therapy with XELOX and bevacizumab in patients with potentially resectable colorectal liver metastases. Six cycles of systemic therapy were administered preoperatively, although the sixth cycle did not include bevacizumab, resulting in 5 weeks between the last bevacizumab dose and surgery. Treatment with bevacizumab plus XELOX was restarted for another six cycles postoperatively.

Pan-European survey on current treatment strategies in patients with upfront resectable colorectal liver metastases.

Background: There is a lack of consensus on the definition of upfront resectability and use of perioperative systemic therapy for colorectal liver metastases (CRLM). This survey aimed to summarize the current treatment strategies for upfront resectable CRLM throughout Europe.

Methods: A survey was sent to all members of the European-African Hepato-Pancreato-Biliary Association to gain insight into the current views on resectability and the use of systemic therapy for upfront resectable CRLM.

Systemic treatment of patients with locally advanced or metastatic cholangiocarcinoma - an Austrian expert consensus statement.

Locally advanced or metastatic cholangiocarcinoma is an aggressive carcinoma with a dismal prognosis. For the first-line treatment of locally advanced or metastatic cholangiocarcinoma, cisplatin/gemcitabine has been the standard of care for more than 10 years. Its combination with the immune checkpoint inhibitor durvalumab resulted in an efficiency improvement in the phase III setting.

Multisocietal European consensus on the terminology, diagnosis, and management of patients with synchronous colorectal cancer and liver metastases: an E-AHPBA consensus in partnership with ESSO, ESCP, ESGAR, and CIRSE.

Background: Contemporary management of patients with synchronous colorectal cancer and liver metastases is complex. The aim of this project was to provide a practical framework for care of patients with synchronous colorectal cancer and liver metastases, with a focus on terminology, diagnosis, and management.

Methods: This project was a multiorganizational, multidisciplinary consensus.

Comparison of nab-paclitaxel plus gemcitabine in elderly versus younger patients with metastatic pancreatic cancer: Analysis of a multicentre, prospective, non-interventional study.

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).

The AST/ALT (De Ritis) ratio predicts clinical outcome in patients with pancreatic cancer treated with first-line nab-paclitaxel and gemcitabine: analysis of an Austrian multicenter, noninterventional study.

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.

Oxaliplatin/Irinotecan/Bevacizumab Followed by Docetaxel/Bevacizumab in Inoperable Locally Advanced or Metastatic Gastric Cancer Patients - AGMT_GASTRIC-3.

Background/aim: Although high response rates using the doublet-chemotherapy of oxaliplatin and irinotecan as well as its combination with cetuximab in advanced gastric cancer were shown in previous trials, time to progression was short, suggesting acquired chemotherapy resistance.

Patients And Methods: Sequential chemotherapy (oxaliplatin and irinotecan followed by docetaxel) combined with bevacizumab was investigated in the GASTRIC-3 trial. Patients achieving at least stable disease were continued on maintenance bevacizumab.

The VEGF rise in blood of bevacizumab patients is not based on tumor escape but a host-blockade of VEGF clearance.

Vascular endothelial growth factor (VEGF) has become a major target in cancer treatment as it promotes tumor angiogenesis. Therapy with anti-VEGF antibody bevacizumab reportedly induces high levels of circulating VEGF which may potentially contribute to resistance. Based on animal or computational models, mechanisms of VEGF induction by bevacizumab have been proposed but not verified in the clinical setting.

Chemotherapy of colorectal liver metastases induces a rapid rise in intermediate blood monocytes which predicts treatment response.

We have previously reported that intermediate monocytes (CD14(++)/CD16(+)) were increased in colorectal cancer (CRC) patients, while the subset of pro-angiogenic TIE2-expressing monocytes (TEMs) was not significantly elevated. This study was designed to evaluate changes in frequency and function of intermediate monocytes and TEMs during chemotherapy and anti-angiogenic cancer treatment and their relation to treatment response. Monocyte populations were determined by flow cytometry in 60 metastasized CRC (mCRC) patients who received neoadjuvant chemotherapy with or without bevacizumab.

Treatment sequence of synchronously (liver) metastasized colon cancer.

No standards for staging, systemic therapy or the timing of an operation are defined for patients newly diagnosed with synchronous metastases and a primary in the colon. An expert group of radiologists, medical, radiation and surgical oncologists therefore came together to discuss staging and treatment sequence for these patients and came up with a recommendation based on current evidence of potential therapeutic options. The discussion was organized to debate recommendations centred on 5 topics and therefore the position paper is built upon these titles and their subtitles.

Deficiency in thrombopoietin induction after liver surgery is associated with postoperative liver dysfunction.

Background And Aims: Thrombopoietin (TPO) has been implicated in the process of liver regeneration and was found to correlate with hepatic function in patients with liver disease. With this investigation we aimed to determine if perioperative TPO levels were associated with postoperative outcome in patients undergoing liver resection.

Methods: Perioperative TPO was analyzed prior to liver resection as well as on the first and fifth postoperative day in 46 colorectal cancer patients with liver metastasis (mCRC) as well as 23 hepatocellular carcinoma patients (HCC).

Monocytes with angiogenic potential are selectively induced by liver resection and accumulate near the site of liver regeneration.

Background: Monocytes reportedly contribute to liver regeneration. Three subsets have been identified to date: classical, intermediate, non-classical monocytes. The intermediate population and a subtype expressing TIE2 (TEMs) were suggested to promote angiogenesis.

CEA change after neoadjuvant chemotherapy including bevacizumab and clinical outcome in patients undergoing liver resection for colorectal liver metastases.

Background: Liver resection after neoadjuvant chemotherapy offers the chance of cure and long-term survival in patients with resectable colorectal liver metastases (CLM). Currently, there are no established biomarkers that could help identify patients with low risk of recurrence who may benefit most from liver resection in curative intent. To address this issue, the value of carcinoembryonic antigen (CEA) change after neoadjuvant chemotherapy was investigated to predict clinical outcome in this study.

Clinical pharmacokinetics of capecitabine and its metabolites in combination with the monoclonal antibody bevacizumab.

Aim: Capecitabine, designed as a pro-drug to the cytotoxic agent 5-fluorouracil, is widely used in the management of colorectal cancer. This study was designed to investigate whether co-administration of the monoclonal antibody bevacizumab (BVZ) shows potential to modulate the plasma disposition of capecitabine (CCB) and its metabolites.

Patients And Methods: Nine patients treated with CCB and BVZ for advanced colorectal cancer entered this pharmacokinetic study.

Evidence for serotonin as a relevant inducer of liver regeneration after liver resection in humans.

Unlabelled: Liver regeneration (LR) involves a complex interplay of growth factors and antagonists. In this context, platelet-derived serotonin (5-HT) has been identified as a critical inducer of LR in mice. Clinical evidence for a role of 5-HT in LR in humans is lacking.

Cetuximab, gemcitabine, and oxaliplatin in patients with unresectable advanced or metastatic biliary tract cancer: a phase 2 study.

Background: Patients with biliary tract cancer have a poor prognosis, and, until recently, no standard palliative chemotherapy has been defined. We aimed to investigate the efficacy and safety of cetuximab in combination with gemcitabine and oxaliplatin (GEMOX) for first-line treatment of biliary tract cancer.

Methods: From Oct 1, 2006, to July 26, 2008, patients with unresectable locally advanced or metastatic biliary tract cancer were sequentially enrolled and treated at one centre in Austria.

Sinusoidal obstruction syndrome impairs long-term outcome of colorectal liver metastases treated with resection after neoadjuvant chemotherapy.

Background: Chemotherapy-induced liver injury is a considerable problem in patients undergoing surgery for colorectal liver metastases, since an increase in postoperative morbidity and mortality has been observed. We investigated whether liver damage had further implications on long-term outcome in these patients.

Materials And Methods: Liver specimens from 196 patients resected for colorectal liver metastases were evaluated for chemotherapy-associated hepatic damage in the nontumorous liver.

Pharmacokinetics of irinotecan in combination with biweekly cetuximab in patients with advanced colorectal cancer.

Background: The effect of biweekly cetuximab (CTX) on the pharmacokinetics of CPT-11 and its metabolites was evaluated in this prospective, paired, crossover study.

Patients And Methods: Patients with epidermal growth factor receptor-positive advanced colorectal cancer received infusions of CPT-11 (180 mg/m(2); FOLFIRI schedule) every second week. CTX (500 mg/m(2) for 120 min) was infused on day 2, followed by biweekly infusions (500 mg/m(2) for 120 min).

Liver resection remains a safe procedure after neoadjuvant chemotherapy including bevacizumab: a case-controlled study.

Objective: This study was conducted to analyze if the combination of Bevacizumab with standard chemotherapy increases postoperative morbidity and mortality after resection of colorectal liver metastases as compared with resection after chemotherapy alone. Parameters contributing to an increased morbidity were evaluated.

Summary Background Data: Most patients referred for colorectal liver metastases are treated with neoadjuvant chemotherapy before hepatic surgery.

Bevacizumab improves pathological response of colorectal cancer liver metastases treated with XELOX/FOLFOX.

Background: Histological response of colorectal cancer liver metastases to chemotherapy may be graded based on the extent of tumor regression. The knowledge about the effect of bevacizumab, if given in addition to fluoropyrimidines and oxaliplatin, on tumor regression and its consequences on clinical outcome is limited.

Materials And Methods: Resected liver metastases from patients of 2 prospective nonrandomized trials (fluoropyrimidines and oxaliplatin +/- bevacizumab) were analyzed retrospectively.

Surgery after neoadjuvant chemotherapy for colorectal liver metastases is safe and feasible in elderly patients.

Background: Surgery for colorectal liver metastases is part of the endeavor to cure metastatic colorectal cancer (mCRC). Neoadjuvant chemotherapy increases progression free survival in resectable patients. The safety and feasibility of this concept has not been investigated in elderly patients.