Cancers

Background: High-risk prostate cancer is often treated with combined androgen deprivation therapy (ADT) and radiotherapy (RT). Blood biomarkers may enable treatments to be tailored to individual patients. Metabolomics, the study of small-molecule alterations in blood, is promising, and lipids are emerging as potential markers of poor prognosis. This study aims to investigate metabolic changes during prostate cancer treatment and their correlation to disease outcome. Methods: This study included 136 blood plasma samples from 35 patients with high-risk prostate cancer treated with RT and ADT, recruited from the Uppsala/Umeå Comprehensive Cancer Consortium (U-CAN) project. Blood samples were collected before, during, and after treatment and analyzed at Metabolon Inc. (Durham, NC, USA). To study differences in metabolic levels during treatment, three different sampling time points were considered: before ADT, in-between ADT and RT, and after RT. Both multivariate (orthogonal projections to latent structures, OPLS) and univariate analyses were performed, where statistical significance in combination with a large fold change was considered indicative of a substantial change. Results: Significant changes in metabolite levels were observed. Many of the significant metabolites for the whole course of treatment were also significant during ADT but not during RT, indicating that changes during ADT dominated the overall treatment. Changes were found to be especially common in steroids and fatty acids. Multivariate analysis revealed significant differences in metabolites between relapsing and non-relapsing patients. Among the significant metabolites were cholesterol and epiandrosterone. Conclusions: Metabolomics can identify biomarkers for prostate cancer treatment response and relapse. Further studies are needed to identify patterns and individual metabolites to personalize treatment strategies for prostate cancer.

Background: The importance of integrating enhanced recovery after surgery protocols in gynecologic oncology has been proven in numerous studies. However, the actual adherence to protocol among institutions remains inconsistent in clinical practice, particularly among those without prior structured implementation. This pragmatic multicenter study provides a preliminary report from the ongoing ERGO (Enhanced Recovery in Gynecologic Oncology) cohort study (ClinicalTrials.gov: NCT06655506) and aims to evaluate adherence to enhanced recovery protocols during the early phases of its adoption as well as identify factors that determine low uptake. Methods: Overall, 300 consecutive patients undergoing gynecologic oncology surgery across five institutions were included in the present study. Adherence to preoperative, intraoperative, and postoperative enhanced recovery elements was documented using standardized forms. Optimal adherence was predetermined as fulfillment of more than 70% of the enhanced recovery components included in the pathway. Multinomial analysis was used to identify predictors of adherence. Results: Overall, 70.3% of patients achieved optimal adherence; however, rates varied across centers (26.9–84.4%), reflecting the limited institutional familiarity with enhanced recovery pathways in most participating centers. The actual volume of cases handled was an important determinant of adherence, with high-volume units consistently demonstrating substantially higher compliance compared with lower-volume hospitals. Routine preoperative items demonstrated high uptake, whereas several intraoperative and early postoperative components showed low and heterogeneous implementation, which might be the result of anesthesiology-driven practices. Higher surgical complexity and poorer performance status independently predicted reduced adherence. Visual mapping confirmed that complex procedures resulted in lower adherence. Conclusions: The significant variability in enhanced recovery protocol adherence that was observed in our study indicates the need to institute structured workflows that help increase team familiarization, particularly in high-complexity cases and centers new to these elements.

Background: Radiotherapy (RT) combined with immune checkpoint inhibitors (ICIs) has shown therapeutic benefits, and the potential for enhanced immune activation has raised concerns about increased immune-related adverse events (irAEs). The immunological implications of mediastinal RT combined with ICI therapy remain unclear. Methods: We conducted an exploratory retrospective review of 58 patients with esophageal oresophagogastric junction cancer who received ICIs between 2021 and 2024. Patients were categorized into RT (+) and RT (-) groups based on whether they underwent mediastinal RT. The incidence and severity of irAEs were compared using chi-square testing. Subgroup analyses included treatment sequence (RT before vs. after ICI), interval between RT and ICI (<90 vs. ≥90 days), and ICI regimen (nivolumab [N], pembrolizumab [P], or nivolumab plus ipilimumab [NI]). Results: irAEs occurred in 28.6% of RT (+) and 39.1% of RT (-) (p = 0.42). Severe irAEs were uncommon in both groups. Treatment sequence and RT-ICI interval did not significantly influence irAE incidence. irAEs were more frequent in the NI group (85.7%) than in N (22.9%) or P (31.2%) (p = 0.01). Mediastinal RT itself did not increase irAE risk. Conclusions: Although RT combined with ICIs has been hypothesized to elevate irAEs through enhanced immune activation, mediastinal RT did not increase irAEs in this cohort. However, given the exploratory and small patient cohort, these findings suggest, with caution, that mediastinal irradiation may attenuate systemic immune activation through lymphocyte depletion, potentially balancing ICI-induced immune responses.