Gastrointestinal cancer (GI) is a major health problem. Patients with gastric, pancreatic, colorectal, bile duct and gall bladder cancer often have advanced disease at the time of diagnosis and are generally difficult to cure, resulting in a dismal prognosis for most patients. Inflammation plays an important role in the development and growth of cancer, which has led to a growing interest in the pro-inflammatory cytokine interleukin 6 (IL-6).The aim of the present review was to evaluate the clinical use of IL-6 as a biomarker or therapeutic target in patients with GI cancer. We did a systematic review of studies (1993–2018), to assess the clinical use of IL-6 as a diagnostic, prognostic or predictive tumor biomarker or as a potential therapeutic target.This review includes 48 studies and 5316 patients. Circulating IL-6 levels appear to be an independent prognostic biomarker in patients with GI cancer, with high IL-6 levels associated with short overall survival (OS). The results for colorectal cancer were too ambiguous to give conclusive results. IL-6 seemed to be a marker for some of the clinical characteristics of GI cancer, and may have a role in the diagnostic workup in general practice. No published studies have examined the use of IL-6 as a therapeutic target in pancreatic, gastric, bile duct or colorectal cancer.In conclusion, high circulating IL-6 was associated with short OS in most studies in GI cancer patients. Whether inhibition of IL-6 would decrease GI cancer symptoms and increase quality of life is unknown.

The chronic lymphocytic leukemia comorbidity index (CLL-CI) is an efficient, CLL-specific tool derived from the Cumulative Illness Rating Scale. The CLL-CI is based on the assessment of the organ systems found to be most strongly associated with event-free survival in CLL: vascular, upper gastrointestinal, and endocrine, at the time of initiation of CLL therapy. The CLL-CI categorizes patients into low, intermediate, and high risk groups. In the present study, we have employed the CLL-CI in a population-based cohort comprising 4 975 patients with CLL. We demonstrate that CLL-CI retains prognostic significance in this large cohort and is associated with overall survival and event-free survival from time of first therapy. Furthermore, CLL-CI associates with overall survival, event-free survival, and time to first treatment from diagnosis independently of the CLL International Prognostic Index. These findings support the use of the CLL-CI both in research and in clinical practice.

I N TRODUC TIONModern treatment options for chronic lymphocytic leukaemia (CLL) are ample, with first-line treatment options including chemotherapy [fludarabine, cyclophosphamide and rituximab (FCR), bendamustine and rituximab (BR), chlorambucil with or without a CD20 antibody (CD20Clb/Clb) and targeted therapies such as bcl-2 inhibitors (venetoclax), BTK inhibitors (ibrutinib/acalabrutinib) and PI3Kδ inhibitors (idelalisib)]. [1][2][3][4][5] Treatment choice depends on age, fitness and prognostic factors, including genetic alterations such as deletion(17p) (del[17p]) or TP53 mutations (TP53 aberrations) and immunoglobulin heavy-chain variable (IGHV) mutational status. 6,7 While long progression-free survival (PFS) is common after first-line treatment, many patients will eventually require second-line treatment therapy. 8 Previous Danish guidelines recommended targeted treatment in second-line treatment settings for patients with IGHV-U, del(17p)/TP53 aberration or progression within three years only. 9,10 According to current Danish 9 and European Society of Medical Oncology (ESMO) guidelines, 10 second-line treatment may consists of either venetoclax and rituximab

Age‐related comorbid conditions are exceedingly common in patients with chronic lymphocytic leukemia (CLL). As the prevalence of type 2 diabetes (T2D) is predicted to double during the next two decades, a better understanding of the interplay between CLL and T2D is of increasing importance. In this study, analyses were performed in parallel in two separate cohorts, based on Danish national registers and the Mayo Clinic CLL Resource. The primary outcomes were overall survival (OS) from time of CLL diagnosis, OS from time of treatment, and time to first treatment (TTFT), studied using Cox proportional hazard regression analysis and Fine‐Gray regression analysis. In the Danish CLL cohort, the prevalence of T2D was 11%, in the Mayo CLL cohort, it was 12%. Patients with CLL and T2D had shorter OS both from time of diagnosis and from first‐line treatment for were less likely to receive treatment for CLL compared with patients with CLL and without T2D. The increased mortality was largely driven by an increased risk of death due to infections, especially in the Danish cohort. The findings of this study emphasize a substantial subgroup of CLL patients with co‐occurring T2D with an inferior prognosis and a possible unmet treatment need requiring additional interventions and further research.

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