Clinical and Molecular Variables Associated With Early Progression to Checkpoint Inhibitors in MSI-High Metastatic Colorectal Cancer: A Retrospective Cohort Study.

BACKGROUND: About one third of patients with deficient mismatch repair/microsatellite instability-high metastatic colorectal cancer (dMMR/MSI-H mCRC) experience primary resistance or early progression on immune checkpoint inhibitors (ICI), while others benefit from exceptionally long-lasting responses. In this single-centre retrospective study, we aimed to identify variables associated with improved overall survival (OS) as well as early disease progression. METHODS: All dMMR/MSI-H mCRC patients treated with ICI between 2014 and 2022 were included. Baseline patient demographics, tumour characteristics as well response and outcome data were recorded. OS was estimated using the Kaplan-Meier method. Uni- and multivariate cox regression analysis was used to identify parameters associated with improved OS. Clinicopathological factors associated with early progression (≤ 12 months after treatment initiation) were assessed using uni- and multivariate logistic regression analysis. RESULTS: About 84 ICI-treated dMMR/MSI-H mCRC patients were included. Progressive disease occurred in 37 (44%) patients, but only in 11 (19%) patients with disease control at 12 months. Median OS was 80 months and improved outcome was associated with a lower neutrophile-to-lymphocyte ratio (NLR) (P = .004) and the presence of immune-related adverse events (irAEs) (P = .015). Early progression was associated with poor performance status (P = .036), a higher blood CRP level (P = .033) and absence of irAEs (P = .002). CONCLUSION: Disease progression in ICI-treated dMMR/MSI-H mCRC rarely occurs in patients experiencing disease control for at least 12 months. Performance status, presence of immune-related adverse events, CRP levels, CEA levels and NLR can be helpful to identify those patients that may benefit from ICI treatment, guiding clinicians in therapeutic decisions.

Therapeutic outcome of diverticular associated colitis - a retrospective single centre experience.

BACKGROUND: Diverticular associated colitis (DAC) has become increasingly appreciated as a form of inflammatory disease, localized mainly in the sigmoid, and defined as chronic inflammation of the interdiverticular mucosa with sparing of rectum, right colon and diverticula themselves. METHODS: A retrospective case identification from January 2005 to December 2016 was performed. Patients with a diagnosis of DAC based on clinical, endoscopic and histological findings were enrolled. We analyzed their characteristics and response to therapy, and performed a review of literature. RESULTS: Out of 377 pathology reports, 37 cases of DAC were identified, with a median age of 73 years and followed during 1-13 years. Six patients (16.22%) were refractory to conservative treatment and required surgery. In three patients (8.11%) evolution to ulcerative colitis (UC) was observed. Patients were divided into four endoscopic patterns, with a more benign course for type A "crescentic fold disease" compared to the other subtypes. Patients with type B "mild to moderate ulcerative colitis-like" were at significantly higher risk of persistent disease activity or relapse (p < 0.01). CONCLUSION: DAC is a multifaceted disease and considered to be a relatively benign condition. However, a subset of patients requires surgery and/or may progress to develop UC.