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Pancreatic ductal adenocarcinoma (PDAC) is characterized by its poor prognosis. The current challenge remains the absence of predictive biomarkers. Cytokines are crucial factors in the pathogenesis and prognosis of PDAC. Furthermore, there is growing interest in differentiating between molecular subtypes of PDAC. The aim of our study is to evaluate the association between the analyzed cytokines and the molecular subtypes of PDAC and to determine their prognostic value. Cytokine levels were measured in 73 patients, and molecular subtypes were analyzed in 34 of these patients. Transforming Growth Factor Beta 2 (TGF-β2) levels were independently associated with the basal-like and null subtypes. In patients with locally advanced and metastatic PDAC, elevated levels of interleukin (IL)-1α, IL-1β, IL-6, IL-8, IL-9, and IL-15 were associated with a higher risk of progression during first-line treatment, and increased levels of IL-1β, IL-6, IL-8, IL-9, and IL-15 were related to increased mortality. Furthermore, a significant association was observed between higher percentiles of IL-6 and IL-8 and shorter progression-free survival (PFS) during first-line treatment, and between higher percentiles of IL-8 and shorter overall survival (OS). In the multivariate analysis, only elevated levels of IL-8 were independently associated with a higher risk of progression during first-line treatment and mortality. In conclusion, the results of our study suggest that cytokine expression varies according to the molecular subtype of PDAC and that cytokines also play a relevant role in patient prognosis. [ABSTRACT FROM AUTHOR]

Aim: To describe the evolution of regorafenib use, since its approval, in patients with previously treated metastatic colorectal cancer (mCRC) in routine clinical practice in Spain. Methods: We extracted patient characteristics, dosing, safety and efficacy data for the Spanish cohorts of the CORRECT and CONSIGN trials, and the real-world CORRELATE study. Results: The Spanish cohorts represented 10.7–13.8% of the global cohorts. Efficacy and safety in the Spanish cohorts reflected findings from the global cohorts, with evidence of a flexible dosing approach being adopted in routine clinical practice. Conclusion: Regorafenib use in patients with mCRC has evolved in the real-world setting, emphasizing the need for further research evaluating dosing patterns that can optimize clinical outcomes in these patients. Clinical trial registration: The CORRECT trial is registered at ClinicalTrials.gov, number NCT01103323; the CONSIGN trial is registered at ClinicalTrials.gov, number NCT01538680; the CORRELATE study is registered at ClinicalTrials.gov, number NCT02042144. Plain Language Summary Bowel cancer (also called colorectal cancer) affects the large bowel, including the colon and rectum. Approximately one in ten patients with advanced bowel cancer that has spread to other areas of the body (metastatic bowel cancer) survive 5 years after diagnosis or the start of treatment. Regorafenib is a treatment for patients with advanced bowel cancer that has continued to spread after receiving other treatments. It can slow down cancer growth, as shown in three international studies (CORRECT, CONSIGN and CORRELATE). In Spain, bowel cancer is the most common type of cancer and the cancer that causes the second most deaths. This study describes how the use of regorafenib in Spain has changed since it was approved in 2012, by looking at the patients from Spain who made up 11–14% of the participants in the three international studies. The CORRECT trial that compared regorafenib with a non-therapeutic placebo and the CONSIGN trial of regorafenib alone showed that treatment with regorafenib prolonged life and was well tolerated in patients with metastatic bowel cancer who had previously received or were not suitable to receive other treatments. The CORRELATE study showed that in the real world (i.e., outside of a controlled clinical trial), patients are sometimes prescribed regorafenib at lower starting doses than the recommended dose, without an apparent overall effect on how well regorafenib works or side effects. In the future, it will be important to continue researching how doctors prescribe regorafenib in daily clinical practice in Spain. Tweetable Abstract This article describes how #Stivarga use in Spain has evolved since its approval for metastatic #colorectalcancer, by analyzing data from Spanish patients enrolled in three international studies (CORRECT, CONSIGN and CORRELATE). In Spain, metastatic colorectal cancer (mCRC) is ranked first among cancers in terms of incidence and second in terms of mortality. An increasing number of patients with mCRC reaching third or further line therapy are able to receive additional treatment, including anti-tumor therapy. The oral multikinase inhibitor regorafenib was first approved in 2012, based on the results of the international, phase III randomized controlled trial CORRECT (NCT01103323). Safety was further evaluated in a larger population in the international, phase IIIb, single-arm trial CONSIGN (NCT01538680). Safety and efficacy were subsequently evaluated in an unselected, real-world population of patients in the international, prospective, observational CORRELATE study. This report presented data for the Spanish cohorts of these three prospective studies, representing 10.7–13.8% of the corresponding global cohorts. Overall, efficacy and safety in the Spanish cohorts reflect the findings from the corresponding global cohorts. Importantly, a proportion of the Spanish cohort of CORRELATE initiated treatment at a dose lower than the approved 160 mg/day, with 9.1% of patients starting at 120 mg/day and 7.7% starting at 80 mg/day. These three studies, separated by time, design and sample size, showed that a flexible dosing approach has been adopted in routine clinical practice since initial regorafenib approval. Regorafenib use in patients with mCRC has evolved in the real-world setting, emphasizing the need for further research evaluating dosing patterns that can optimize clinical outcomes in these patients. [ABSTRACT FROM AUTHOR]

Simple Summary: Colorectal cancer is often associated with MUTYH mutations, but their connection to breast cancer remains unclear. We aimed to assess if MUTYH mutations contribute to breast cancer susceptibility. Analyzing data from 3598 patients, we found MUTYH mutations in 1.6%, with a significant association in colonic polyposis cases. However, our findings did not reveal a substantial association between MUTYH mutations and breast cancer. These insights emphasize the need for cautious interpretation of MUTYH mutations in breast cancer risk assessments. Background: MUTYH has been implicated in hereditary colonic polyposis and colorectal carcinoma. However, there are conflicting data refgarding its relationship to hereditary breast cancer. Therefore, we aimed to assess if MUTYH mutations contribute to breast cancer susceptibility. Methods: We retrospectively reviewed 3598 patients evaluated from June 2018 to June 2023 at the Hereditary Cancer Unit of La Paz University Hospital, focusing on those with detected MUTYH variants. Results: Variants of MUTYH were detected in 56 patients (1.6%, 95%CI: 1.2–2.0). Of the 766 patients with breast cancer, 14 patients were carriers of MUTYH mutations (1.8%, 95%CI: 0.5–3.0). The prevalence of MUTYH mutation was significantly higher in the subpopulation with colonic polyposis (11.3% vs. 1.1%, p < 0.00001, OR = 11.2, 95%CI: 6.2–22.3). However, there was no significant difference in the prevalence within the subpopulation with breast cancer (1.8% vs. 1.5%, p = 0.49, OR = 1.2, 95%CI: 0.7–2.3). Conclusion: In our population, we could not establish a relationship between MUTYH and breast cancer. These findings highlight the necessity for a careful interpretation when assessing the role of MUTYH mutations in breast cancer risk. [ABSTRACT FROM AUTHOR]