Sex and Regorafenib Toxicity in Refractory Colorectal Cancer: Safety Analysis of the RegARd-C Trial.

Background: Regorafenib is a standard treatment for refractory metastatic colorectal cancer (mCRC). In view of the toxicity burden, significant research efforts have been made to increase the therapeutic ratio of this multikinase inhibitor. Predictive factors for treatment-related adverse events (TRAEs), however, are still lacking.

Fortnightly or fractionated weekly docetaxel-cisplatin-5-FU as first-line treatment in advanced gastric and gastroesophageal junction adenocarcinoma: The randomized phase II DoGE study.

Background: While docetaxel/cisplatin/5-fluorouracil (DCF) outperforms CF in first-line gastric adenocarcinoma, toxicity remains an issue.

Methods: This multicenter phase II trial randomized chemonaïve metastatic gastric adenocarcinoma patients to fractionated weekly DCF (D 40 mg/m , C 35 mg/m², F 1800 mg/m² over 24 h, on days 1 and 8 every 3 weeks, arm (1) or fortnightly DCF (D 50 mg/m , C 50 mg/m², F 2000 mg/m² over 48 h every 2 weeks, arm (2). Prophylactic granulocyte colony-stimulating factor (G-CSF) was not allowed.

Peptide receptor radionuclide therapy controls inappropriate calcitriol secretion in a pancreatic neuro-endocrine tumor: a case report.

Background: Hypercalcemia of malignancy is not uncommon in patients with advanced stage cancer. In rare cases the cause of the hypercalcemia is excessive production of calcitriol, the active form of vitamin D. Although inappropriate tumoral secretion of calcitriol is typically associated with lymphomas and some ovarian germ cell tumors, we present a case of calcitriol overproduction-induced hypercalcemia due to a pancreatic neuroendocrine tumor.

Regorafenib after failure of gemcitabine and platinum-based chemotherapy for locally advanced/metastatic biliary tumors: REACHIN, a randomized, double-blind, phase II trial.

Background: There is a high unmet clinical need for treatments of advanced/metastatic biliary tract cancers after progression on first-line chemotherapy. Regorafenib has demonstrated efficacy in some gastrointestinal tumors that progress on standard therapies.

Patients And Methods: REACHIN was a multicenter, double-blind, placebo-controlled, randomized phase II study designed to evaluate the safety and efficacy of regorafenib in patients with nonresectable/metastatic biliary tract cancer that progressed after gemcitabine/platinum chemotherapy.

Prognostic value of adipose tissue and muscle mass in advanced colorectal cancer: a post hoc analysis of two non-randomized phase II trials.

Background: The prognostic value of body composition in cancer patients has been widely studied during the last decade. The main finding of these studies is that sarcopenia, or skeletal muscle depletion, assessed by CT imaging correlates with a reduced overall survival (OS). By contrast, the prognostic value of fat mass remains ill-defined.

Circulating tumor DNA in early response assessment and monitoring of advanced colorectal cancer treated with a multi-kinase inhibitor.

Predictive biomarkers are eagerly awaited in advanced colorectal cancer (aCRC). Targeted sequencing performed on tumor and baseline plasma samples in 20 patients with aCRC treated with regorafenib identified 89 tumor-specific mutations of which ≥50% are also present in baseline plasma. Droplet digital PCR (ddPCR) assays were optimized to monitor circulating tumor DNA (ctDNA) levels in plasmatic samples collected throughout the treatment course and showed the importance of using the absolute value for ctDNA rather than the mutant/wild type ratio in monitoring the therapy outcome.

Monitoring metabolic response using FDG PET-CT during targeted therapy for metastatic colorectal cancer.

Introduction: The introduction of targeted drugs has had a significant impact on the approach to assessing tumour response. These drugs often induce a rapid cytostatic effect associated with a less pronounced and slower tumoural volume reduction, thereby impairing the correlation between the absence of tumour shrinkage and the patient's unlikelihood of benefit. The aim of the study was to assess the predictive value of early metabolic response (mR) evaluation after one cycle, and its interlesional heterogeneity to a later metabolic and morphological response assessment performed after three cycles in metastatic colorectal cancer (mCRC) patients treated with combined sorafenib and capecitabine.

Long-acting octreotide as secondary prevention of chemotherapy-induced diarrhea: proof of concept.

Background: The aim of this study is to investigate the role of Octreotide LAR in secondary prevention in patients with chemotherapy-induced diarrhea.

Methods: In this study, patients experiencing CID ≥ grade 2 received 30 mg long-acting octreotide as a monthly injection and the next chemotherapy dose was administrated with a 25% dose decrease. If no CID ≥ grade 2 occurred, subsequent chemotherapy doses were increased to the initial 100% values.

Phase II study of necitumumab plus modified FOLFOX6 as first-line treatment in patients with locally advanced or metastatic colorectal cancer.

Background: This single-arm phase II study investigated the EGFR monoclonal antibody necitumumab plus modified FOLFOX6 (mFOLFOX6) in first-line treatment of locally advanced or metastatic colorectal cancer (mCRC).

Methods: Patients received 800-mg intravenous necitumumab (day 1; 2-week cycles), followed by oxaliplatin 85 mg m(-2), folinic acid 400 mg m(-2), and 5-fluorouracil (400 mg m(-2) bolus then 2400 mg m(-2) over 46 h). Radiographic evaluation was performed every 8 weeks until progression.

The Prognostic Significance of Metabolic Response Heterogeneity in Metastatic Colorectal Cancer.

Background: Tumoral heterogeneity is a major determinant of resistance in solid tumors. FDG-PET/CT can identify early during chemotherapy non-responsive lesions within the whole body tumor load. This prospective multicentric proof-of-concept study explores intra-individual metabolic response (mR) heterogeneity as a treatment efficacy biomarker in chemorefractory metastatic colorectal cancer (mCRC).

Panitumumab as a radiosensitizing agent in KRAS wild-type locally advanced rectal cancer.

Our goal was to optimize the radiosensitizing potential of anti-epidermal growth factor receptor (EGFR) monoclonal antibodies, when given concomitantly with preoperative radiotherapy in KRAS wild-type locally advanced rectal cancer (LARC). Based on pre-clinical studies conducted by our group, we designed a phase II trial in which panitumumab (6 mg/kg/q2 weeks) was combined with preoperative radiotherapy (45 Gy in 25 fractions) to treat cT3-4/N + KRAS wild-type LARC. The primary endpoint was complete pathologic response (pCR) (H0 = 5%, H1 = 17%, α = 0.

Adenocarcinoma arising in gastric heterotopic pancreas. Case report and review of the literature.

A sixty years-old patient was admitted with a gastric tumor corresponding to an adenocarcinoma developed in ectopic pancreatic tissue. Hundred cases of gastric heterotopic pancreas are shown in literature. This entity may remain asymptomatic.

Combination of gemcitabine and cetuximab in patients with advanced cholangiocarcinoma: a phase II study of the Belgian Group of Digestive Oncology.

Background: Cholangiocarcinomas are uncommon tumours with a poor prognosis, that frequently present epidermal growth factor receptor overexpression.

Methods: In a multi-centre phase II trial, patients with unresectable cholangiocarcinoma, naïve to chemotherapy, received Cetuximab (400 mg/m(2) at week 1, then 250 mg/m(2)/week) and Gemcitabine (1 g/m(2) on day 1, 8 and 15 every 4 weeks). Primary end point was progression-free survival (PFS) rate at 6 months, using a Simon 2-stage design.

Management of esophageal superficial tumors: non take away approaches.

Development of screening programs in patients with high risk of developing esophageal cancer, as well as recent advances in diagnostic endoscopic techniques, have allowed clinicians to improve early detection of esophageal malignant tumors. Surgical resection, although currently considered as the standard of care for patients with early stage esophageal cancer, is sometimes contra-indicated. In this subset of patients, endoscopic resection techniques including endoscopic mucosal resections (EMR), thermal or non-thermal laser, or cryoablation are amongst the well-recognized modalities safely and efficiently used by gastroenterologists.

Splenic metastasis from gastrointestinal neoplasms: a review.

Spleen metastases from solid tumours are rather exceptional, especially for those located in the digestive tract. Although these lesions are usually associated with multivisceral disease at terminal stage, several cases of isolated lesions have also been described in the literature. Diagnosis of spleen lesions associated with multivisceral disease rarely influences patient's outcome.

Phase I trial to investigate the safety, pharmacokinetics and efficacy of sorafenib combined with docetaxel in patients with advanced refractory solid tumours.

Aim: The safety, pharmacokinetics and efficacy of sorafenib plus docetaxel in patients with advanced refractory cancer were investigated in a phase I, dose-escalation trial.

Methods: Twenty-seven patients in four cohorts received docetaxel on day 1 (cohorts 1 and 4: 75 mg/m2; cohorts 2 and 3: 100 mg/m2) plus sorafenib on days 2-19 (cohorts 1 and 2: 200 mg twice-daily (bid); cohorts 3 and 4: 400 mg bid) in 21-day cycles.

Results: Most common adverse events (AEs) (grade 3-5) included neutropenia (89%), leucopaenia (81%), hand-foot skin reaction (30%) and fatigue (30%).

Acute upper gastrointestinal bleeding in cirrhosis: changes and advances over the past two decades.

Background And Aims: Few studies have compared two or more cohorts of cirrhotic patients admitted for upper gastrointestinal bleeding (UGIB) several decades apart. Our aim was to compare epidemiological, clinical, therapeutic and prognostic characteristics of UGIB (whatever the source) in two cohorts of cirrhotic patients admitted to the emergency room of the same general hospital 2 decades apart.

Methods: One-hundred cases of UGIB in cirrhotic patients consecutively admitted between 1984 and 1990 (cohort A) were compared with 100 similar cases admitted between 2004 and 2009 (cohort B).

Short course chemotherapy followed by concomitant chemoradiotherapy and surgery in locally advanced rectal cancer: a randomized multicentric phase II study.

Background: Induction chemotherapy has been suggested to impact on preoperative chemoradiation efficacy in locally advanced rectal cancer (LARC). To evaluate in LARC patients, the feasibility and efficacy of a short intense course of induction oxaliplatin before preoperative chemoradiotherapy (CRT).

Patients And Methods: Patients with T2-T4/N+ rectal adenocarcinoma were randomly assigned to arm A-preoperative CRT with 5-fluorouracil (5-FU) continuous infusion followed by surgery-or arm B-induction oxaliplatin, folinic acid and 5-FU followed by CRT and surgery.

Latest developments and emerging treatment options in the management of stomach cancer.

Gastric cancer remains a significant health burden worldwide. Most of these malignancies are diagnosed at an advanced stage and are associated with a grim prognosis. Complete removal of macroscopic and microscopic tumor masses along with regional lymphnodes (R0 surgical resection) represents the treatment of choice in localized, nonmetastatic gastric cancer.

Feasibility of percutaneous radiofrequency ablation for pulmonary malignancies in the hands of the surgeon.

Aim: To assess the feasibility of percutaneous pulmonary radiofrequency ablation (RFA) executed by a single surgeon.

Materials And Methods: Between 2007 and 2010, 15 procedures were performed in 11 patients during 13 sessions. Sex, age, pulmonary localisation and tumor diameter are discussed.

Phase III trial comparing protracted intravenous fluorouracil infusion alone or with yttrium-90 resin microspheres radioembolization for liver-limited metastatic colorectal cancer refractory to standard chemotherapy.

Purpose: Liver dissemination is a major cause of mortality among patients with advanced colorectal cancer. Hepatic intra-arterial injection of the beta-emitting isotope yttrium-90 ((90)Y) bound to resin microspheres (radioembolization) delivers therapeutic radiation doses to liver metastases with minimal damage to adjacent tissues.

Patients And Methods: We conducted a prospective, multicenter, randomized phase III trial in patients with unresectable, chemotherapy-refractory liver-limited metastatic CRC (mCRC) comparing arm A (fluorouracil [FU] protracted intravenous infusion 300 mg/m(2) days 1 through 14 every 3 weeks) and arm B (radioembolization plus intravenous FU 225 mg/m(2) days 1 through 14 then 300 mg/m(2) days 1 through 14 every 3 weeks) until hepatic progression.

The potential role of targeted therapies in the management of neuroendocrine tumours.

The management of gastro-entero-pancreatic neuroendocrine tumours is evolving thanks to new TNM-classification, diagnostic and staging procedures and new therapeutic options. Targeting new pathways, mostly angiogenesis, development of novel agents is under way and opens new perspectives in controlling the evolution of these tumours and possibly changing their management. In parallel, new functional imaging techniques and biomolecular markers will be developed to provide adequate tools for the assessment of tumor response according to therapeutic intervention on angiogenesis, proliferation and apoptosis.