Blood Transfusion Has An Adverse Impact On The Prognosis of Patients Receiving Chemotherapy For Advanced Colorectal Cancer: Experience From a Single Institution With a Patient Blood Management Program

Purpose: Perioperative blood transfusion in early stage cancer patients had a negative effect on the prognosis of patients, but the prognostic impact of transfusion in advanced cancer patients remains unclear. To minimize transfusion, a institutional patient blood management (PBM) program was launched, and we evaluated the new program has changed practice and impacted on prognosis of advanced cancer patients. Methods: We investigated the medical records of colorectal cancer patients who received chemotherapy from 2015 to 2020. The amount and frequency of transfusion, iron replacement and laboratory findings, and overall survival were compared before and after implementation of PBM. Results: The rate of transfusion in colorectal cancer patients was significantly decreased from 23.5/100 person-quarter in 2015 to 1.2/100 person-quarter in 2020, but iron supplementation therapy was frequently used and the proportion of patients who received transfusion under haemoglobin 7 g/dL significantly increased from 15.9% in 2015 to 55.3% in 2020. Multivariate analysis revealed that transfusion was a significant risk factor affecting the overall survival of patients (HR 2.70, 95% CI: 1.93–3.78, p<0.001). Kaplan–Meier analysis revealed that overall survival was significantly longer in non-transfused patients than in transfused patients (11.0 versus 22.4 months; HR 0.69, 95% CI: 0.56–0.86, p<0.001). Conclusions: This study shows that minimized transfusion through an institutional PBM can positively affect the prognosis of patients who are receiving chemotherapy for advanced colorectal cancer.

Systemic Interleukins’ Profile in Early and Advanced Colorectal Cancer

Tumor microenvironment (TME) is characterized by mutual interactions of the tumor, stromal and immune cells. Early and advanced colorectal tumors differ in structure and present altered serum cytokine levels. Mutual crosstalk among TME infiltrating cells may shift the balance into immune suppressive or pro-inflammatory, antitumor response this way influencing patients’ prognosis. Cancer-related inflammation affects all the body and this way, the systemic level of cytokines could reflect TME processes. Despite numerous studies, it is still not known how systemic cytokines levels change during colorectal cancer (CRC) tumor development. Better understanding tumor microenvironment processes could help in planning therapeutic interventions and more accurate patient prognosis. To contribute to the comprehension of these processes within TME, we reviewed cytokines levels from clinical trials in early and advanced colorectal cancer. Presented data were analyzed in the context of experimental studies and studies analyzing tumor infiltration with immune cells. The review summarizes clinical data of cytokines secreted by tumor microenvironment cells: lymphocytes T helper 1 (Th1), lymphocytes T helper 2 (Th2), lymphocytes T helper 17 (Th17), regulatory T cells (Treg cells), regulatory T cells (Breg cells), M1/M2 macrophages, N1/N2 neutrophils, myeloid-derived suppressor cells (MDSC), dendritic cells (DC), innate lymphoid cells (ILC) natural killer (NK) cells and tumor cells.

Cost-Effectiveness of First-Line Versus Second-Line Pembrolizumab or Chemotherapy in Patients With Microsatellite-Instability-High/Mismatch Repair-Deficient Advanced Colorectal Cancer

Background: Pembrolizumab is a guideline-recommended, both first- and second-line treatment option for microsatellite-instability-high (MSI-H)/mismatch repair-deficient (dMMR)advanced colorectal cancer patients. The aim of the present study is to investigates the health and economic outcomes of three treatment strategies with or without pembrolizumab in MSI-H/dMMR advanced colorectal cancer to define the best treatment strategy from the perspective of the US payer.Methods: A microsimulation model was developed to estimate the cost and effectiveness of three treatment strategies: 1) pembrolizumab used as first-line, 2) pembrolizumab used as second-line and, 3) chemotherapy. Life years (LYs), quality-adjusted LYs (QALYs) and lifetime costs were estimated.Results: The model projected that patients receiving pembrolizumab in the first-line setting gained 5.579 QALYs; this value was 1.501 and 3.941 QALYs more than that for patients receiving pembrolizumab in the second-line setting and chemotherapy, respectively. First-line pembrolizumab strategy dominated second-line pembrolizumab strategy. Compared with chemotherapy, first-line pembrolizumab strategy yielded an incremental cost of $50613.7, which resulted in an ICER of $13441 per QALY.Conclusion: For patients with MSI-H/dMMR advanced colorectal cancer, reserving pembrolizumab for second-line line use is dominated by its first-line use, and first-line use of pembrolizumab is cost-effective compared with chemotherapy.

The implication of BRAF mutation in advanced colorectal cancer

Background Advanced colorectal cancer (CRC) is frequently a lethal disease. Mutations in the BRAF gene is a key driver in CRC pathogenesis and confers a poor prognosis. To date, Irish data on this molecular subtype of CRC is lacking. Aims Our aim was to compare the natural history of Irish patients with BRAF (BRAFMUT) metastatic CRC with a control group of metastatic CRC patients without BRAF mutation (BRAFWT wild- type). Method A retrospective observational analysis of advanced CRC patients with known BRAFMUT was conducted by chart review. BRAFMUT patients were identified from the Cork University Hospital (CUH) histopathology database. Controls with known BRAFWT were randomly selected from the database. Demographic characteristics and clinicopathological data were recorded. Survival was assessed with Kaplan–Meier curve/Cox proportional hazard models. Results Twenty patients with BRAFMUT and 36 with BRAFWT were studied. BRAFMUT were more likely female (75% vs 33%, p = 0.007) and right-sided (65% vs 31.4%, p = 0.033). Median overall survival was lower in BRAFMUT group (17.3 months (95% CI 0–40.8)) compared to patients with BRAFWT (median survival not reached, log rank p = 0.001). On multivariate analysis, BRAFMUT was independently associated with an increased risk of mortality (HR 12.76 (95% CI 3.15–51.7), p < 0.001). Conclusion BRAFMUT advanced colorectal cancer was associated with significantly reduced overall survival in this Irish CRC population. Knowledge of mutation status should now be considered standard of care and should dictate management. Surgeons should be aware of this genetic signature as the natural history of the disease may mitigate against an aggressive surgical strategy. A prospective study should be conducted to further corroborate these findings.