A real-world analysis on the efficacy and tolerability of liposomal irinotecan plus 5-fluorouracil and folinic acid in metastatic pancreatic ductal adenocarcinoma in Belgium.

Background: Currently, nanoliposomal irinotecan (nal-IRI) + 5-fluorouracil/folinic acid (5-FU/LV) is the only approved second-line treatment for patients suffering from metastatic pancreatic ductal adenocarcinoma (mPDAC). However, also other chemotherapeutic regimens are used in this setting and due to the lack of clear real-world data on the efficacy of the different regimens, there is no consensus on the optimal treatment sequence for mPDAC patients. Objectives: To provide information on the safe and efficacious use of nal-IRI + 5-FU/LV in clinical practice in Belgium, which is needed for healthcare professionals to estimate the risk-benefit ratio of the intervention. Methods: Medical data of adult patients with mPDAC who were treated with nal-IRI + 5-FU/LV in one of the participating Belgian hospitals were retrospectively collected. Kaplan-Meier analysis was performed to obtain survival curves to estimate the median overall survival (OS) and progression-free survival (PFS). All other results were presented descriptively. Results: A total of 56 patients [median age at diagnosis: 69 years (range 43 years), 57.1% male] were included. Patients received a median of 5 (range 49 cycles) nal-IRI + 5-FU/LV cycles, extended over 10 weeks (range 130.8 weeks). The median start dose for nal-IRI was 70 mg/m² (range 49.24 mg/m²) and chemotherapy dose reduction and delay occurred in, respectively, 42.8% and 37.5% of the patients. The median OS was 6.8 months (95% CI: 5.6-8.4 months) with a 6-month survival rate of 57.4% and a 1-year survival rate of 27.8% in the overall study population. The median OS for patients treated with nal-IRI as second-line therapy or as later-line treatment was, respectively, 6.8 months (95% CI: 5.9-7.0 months) and 5.6 months (95% CI: 4.2-no upper limit). In the overall study population, a median PFS of 3.1 months (95% CI: 2.4-4.6 months) and a disease control rate of 48.3%, comprising 30.4% stable disease, 16.1% partial and 1.8% complete response, was observed. The median PFS for patients treated with nal-IRI as second-line therapy was 3.9 months (95% CI: 2.8-4.8 months) while this was 2.4 months (95% CI: 1.9-9.1 months) for those that received nal-IRI in a later-line treatment. In terms of safety, gastrointestinal problems occurred most (64.3% of the patients) and from all reported treatment emergent adverse events, 39.2% were grade 3 or 4. Conclusion: Nal-IRI + 5-FU/LV is a valuable, effective, and safe sequential treatment option following gemcitabine-based therapy in patients with mPDAC. Trial details: Retrospective study on the efficacy and tolerability of liposomal irinotecan (NALIRI); ClinicalTrials.gov Identifier: NCT0509506 (https://clinicaltrials.gov/ct2/show/NCT05095064?term=naliri&draw=2&rank=2).

Ramucirumab: the long and winding road toward being an option for mCRC treatment.

INTRODUCTION: Colorectal cancer (CRC) is one of the main causes of cancer-related morbidity and mortality worldwide. Mortality is most often attributable to metastatic disease. Despite the progress achieved so far, life expectancy continues to be limited in most patients. Ramucirumab, a most recent antiangiogenic drug, is vying in the race to metastatic CRC (mCRC) treatment since its approval by the Food and Drug Administration (FDA), based on the results of the RAISE study. AREAS COVERED: This article reviews the role of ramucirumab in mCRC, including clinical indication, safety issues, and future perspectives. EXPERT OPINION: The use of Ramucirumab in clinical practice is still limited, probably due to economic burden and the lack of specific biomarkers. Future efforts will be addressed to improve our knowledge in the use of this drug and better guide us in patients' care.

The operative risk and natural history after the diagnosis of ileal penetrating Crohn's disease.

BACKGROUND AND PURPOSE: Crohn's disease (CD) is marked by transmural inflammation of the bowel wall leading to stricturing and/or penetrating complications in the majority of patients. The natural history and operative risk after the diagnosis of an ileal penetrating complication is understudied. The aim was to study the disease course and need for surgery in patients diagnosed with a penetrating ileal CD complication and to assess the risk factors associated with worse postoperative outcome. PATIENTS AND METHODS: In this cohort study, all cross-sectional imaging exams (computed tomography and/or magnetic resonance imaging) performed between 2006 and 2014 in patients with CD in a tertiary referral centre were reviewed for the presence of ileal penetrating complications (defined as abscesses, phlegmones and/or fistula). Demographic, clinical, biochemical, radiological and endoscopic factors were assessed retrospectively in these patients as well as the need for surgery (intestinal resection and/or strictureplasties) and postoperative complications. RESULTS: In total, 1803 cross-sectional imaging exams in 957 CD patients were performed during the study period. In 113 patients, penetrating ileal CD complications were identified. The majority of these patients were referred for surgery (86%) (median time to surgery 1 month, interquartile range: 1-4.9 months). In multivariate analysis, only the presence of abscesses was associated with subsequent surgery (P=0.034; hazard ratio=1.65; 95% confidence interval: 1.04-2.61). Severe postoperative complications (Dindo-Clavien>II) were present in 13% of the patients. Albumin less than 32 g/l was associated with a five-fold increase in severe complications (P=0.039; hazard ratio=4.9; 95% confidence interval: 1-22). Up to 35% of the patients needed no further medical treatment during the first 5 years postoperatively. CONCLUSION: In this cohort, the majority of patients with penetrating ileal CD underwent surgery. The presence of an abscess showed a significant association with the need for surgery. There was an acceptable postoperative complication rate. Patients with low albumin had an unfavourable postoperative course. The long-term outcome after surgery was favourable.

Risk Stratification for Surgery in Stricturing Ileal Crohn's Disease: The BACARDI Risk Model.

BACKGROUND AND AIM: Transmural inflammation in Crohn's disease [CD] leads to stricturing or penetrating complications. Factors impacting on the need and timing of surgery in ileal stricturing CD [IS-CD] are understudied. Our aim was to identify risk factors in IS-CD associated with the need for surgery over time. METHODS: All cross-sectional imaging [XSI] performed for CD between 2006 and 2015 in a tertiary referral centre was analysed. The electronic charts of patients with IS-CD were reviewed for demographic, clinical, biochemical, imaging, genetic, and endoscopic factors. An independent cohort was used for validation. RESULTS: A total of 1803 XSI were performed in 957 patients with CD. IS-CD was diagnosed in 235 patients, and 161 of these [69%] needed surgery. Prestenotic dilation (hazard ratio [HR] 2.05, 95% confidence interval [CI] 1.22-3.45, p = 0.007], C-reactive protein at diagnosis of IS-CD > 11 mg/L [HR 1.53, 95% CI 1.05-2.24, p = 0.026], Montreal B3 phenotype [HR 1.58, 95% CI 1.06-2.36, p = 0.023], previous/current anti-tumour necrosis factor [TNF] exposure [HR 1.44, 95% CI 1.00-2.06, p = 0.048], and presence of at least one NOD2 rs2066844 risk allele [HR 1.51, 95% CI 1.02-2.23, p = 0.038] significantly impacted on the need for surgery in multivariate analysis. The risk stratification model [BACARDI] yielded a surgery-free survival after 5 years of 77%, 38%,19%, and 0% for the low, medium, high, and all risk groups, respectively. Based on an independent cohort of 27 patients, the results were validated and demonstrated adequate performance. CONCLUSIONS: This risk model can facilitate therapeutic decisions in IS-CD and suggest the correct time for surgery in daily clinical practice.

Tuberculosis infection following anti-TNF therapy in inflammatory bowel disease, despite negative screening.

We present two patients with inflammatory bowel disease who, despite negative tuberculosis screening, developed a de novo tuberculosis infection after the start of anti tumor necrosis factor alpha treatment. We discuss current screening methods and their limitations, the approach after positive screening and the timing to resume anti-TNFα treatment after TB infection. We shortly mention the immune reconstitution inflammatory syndrome (IRIS), described in a few cases after the stop of anti-TNFalpha while treating the tuberculosis infection. We conclude with some remaining questions concerning tuberculosis in IBD patients.