Search Results (253)

Introduction: The increasing costs of cancer care have raised the need for economic evaluations that integrate treatment efficacy and resource utilization. This study aimed to assess the economic value of Lutetium-177 (¹⁷⁷Lu)–prostate-specific membrane antigen (PSMA)-617 in patients with PSMA-positive metastatic castration-resistant prostate cancer (mCRPC) from an Italian healthcare perspective. Patients and Methods: A cost-effectiveness analysis was performed using clinical efficacy data from randomized controlled trials (RCTs) evaluating ¹⁷⁷Lu-PSMA-617. Two scenarios were considered. Scenario 1 evaluated ¹⁷⁷Lu-PSMA-617 plus standard care (SC) versus SC alone using pivotal phase III trial data. Scenario 2 compared ¹⁷⁷Lu-PSMA-617 with chemotherapy and androgen receptor pathway inhibitors (ARPIs) using phase II and III RCTs. Drug costs were based on Italian ex-factory prices. In addition, an exploratory three-state Markov cost–utility model including progression-free survival (PFS), progressive disease, and death was developed using data from the VISION trial. Results: In Scenario 1, 730 patients were analyzed. The ESMO-MCBS grade was 3, and the incremental cost per month of PFS gained with ¹⁷⁷Lu-PSMA-617 versus SC was €20,906. In Scenario 2, 651 patients were included. The monthly cost per PFS gained with ¹⁷⁷Lu-PSMA-617 was €19,017 versus enzalutamide and €20,565 versus abiraterone. In the exploratory cost–utility model, estimated QALYs were 1.02 with ¹⁷⁷Lu-PSMA-617 and 0.64 with SC, corresponding to an incremental gain of 0.38 QALYs. At an incremental cost of approximately €32,000 per patient, the resulting model-based ICER was approximately €85,000/QALY. Conclusions:¹⁷⁷Lu-PSMA-617 provides meaningful clinical benefit in appropriately selected patients with PSMA-positive mCRPC, but this benefit is associated with substantial incremental treatment costs. The exploratory model-based ICER was sensitive to treatment duration and other model assumptions. These findings support careful assessment of the clinical value and economic sustainability of ¹⁷⁷Lu-PSMA-617 in the Italian healthcare setting. Further studies incorporating real-world resource utilization, treatment-related costs, post-progression therapies, and prospectively collected quality-of-life data are warranted. Full article

Background/Objectives: Vacuum-assisted breast biopsy (VABB) is widely used for the diagnosis of nonpalpable breast cancer but is not considered definitive treatment because microscopic residual disease may persist within or around the biopsy cavity. The ARTHE phase I trial evaluated a cavity-targeted radionuclide strategy based on same-session sequential intralesional administration of avidin followed by [⁹⁰Y]Y-DOTA-biotin after VABB. Methods: Eighteen women with nonpalpable breast cancer measuring ≤15 mm and a skin-to-cavity distance ≥ 13 mm were treated in three sequential activity-escalation cohorts. The primary objective was to assess acute local and systemic safety, including dose-limiting toxicity. The protocol-specified co-primary objective was to evaluate preliminary antitumor activity, assessed as breast-only pathologic complete response (pCR) at surgery. Given the phase I single-arm design, pCR was analyzed descriptively. The protocol-specified secondary objective was patient-specific dosimetry. Additional exploratory assessments included post-injection biodistribution and integration with subsequent breast-conserving surgery. Results: No dose-limiting toxicities, grade ≥ 3 adverse events, clinically relevant hematologic toxicity, treatment discontinuations, hospitalizations, or treatment-related surgical delays were observed. Local toxicity was limited to grade 1 injection-site pain and/or erythema. Post-injection imaging consistently demonstrated focal intralesional localization without clinically relevant extra-lesional uptake. All patients underwent breast-conserving surgery 4–7 weeks after treatment. No residual tumor cellularity (RTC), from either invasive or in situ carcinoma, was identified in the breast surgical specimen in 5/18 patients (27.8%). However, because diagnostic VABB may have removed part or all of the malignant lesion, the absence of residual carcinoma at surgery cannot be attributed specifically to the radionuclide treatment. Conclusions: The intralesional avidin-mediated local trapping strategy using [⁹⁰Y]Y-DOTA-biotin after VABB was feasible, showed favorable acute and short-term tolerability, was associated with early focal localization on post-injection imaging, and was compatible with standard breast-conserving surgery. Controlled studies are warranted to determine the therapeutic contribution of this post-biopsy cavity-targeted strategy, optimize administered activity, and refine patient selection. Full article

Chronic non-communicable conditions—type 1 and type 2 diabetes mellitus (T1DM, T2DM), metabolic obesity syndrome (MOS), polycystic ovary syndrome (PCOS), colorectal and extra-intestinal cancers, and systemic autoimmune disease—share a prolonged asymptomatic phase during which conventional screening is invasive, insensitive, or resource-intensive. This review synthesizes the 2021–2026 literature on fecal microbiome-based artificial intelligence (AI) diagnostics across these conditions, extracting reported discrimination, validation strategy, microbial and short-chain fatty acid (SCFA) biomarkers, and cross-cohort reproducibility. Across the primary classifier studies tabulated here, reported areas under the curve (AUCs) span 0.76–0.99 under internal validation but 0.69–0.91 under external or cross-population validation; in the four studies reporting both, the median AUC falls from 0.875 to 0.810. Verified external-validation values include 0.82 for colorectal cancer, 0.79 for T2DM and 0.792 for discrimination of systemic lupus erythematosus from rheumatoid arthritis and controls. Clinical readiness turns on this internal-to-external gap more than on the headline AUC. We propose a multimodal deep learning architecture coupled with explainable AI; no component has been implemented or evaluated on data, and it is presented as a design proposal. Fecal-microbiome-based multimodal AI is technically feasible but clinically unvalidated, pending prospective, harmonized cross-cohort trials. Full article

Background: A Phase I trial to study the efficacy and safety of MR-guided FUS-MB (focused ultrasound–microbubble) treatment combined with radiotherapy (RT) using a fully electronically MRI-guided steerable focused ultrasound system was performed. The investigation here carried out an exploratory quantitative analysis of images for the first ten participants who were treated with MRgFUS-MB therapy, identifying texture-based MRI features that changed significantly after treatment and indicating probable treatment-related changes in tumour morphology. Methods and Findings: Ten patients with stage I-IV breast cancer (Age: 64 ± 10.8) underwent 2 FUS-MB therapies throughout their radiation treatments, as deemed appropriate by a multidisciplinary team. MRI scans were performed prior to treatment and at 1- and 3-month follow-up. The tumours were segmented, and 2D and 3D features, including shape, first-order and texture features, were extracted for original and wavelet-filtered T1-weighted fat-saturated MR images. The overall significance of radiomic features in association with morphological changes in the target tumour over 1-month and 3-month follow-up in comparison to the first treatment day was investigated. Results: The five most significant features (p < 0.05) were selected using a sample-related t-test, out of which most features were wavelet-filtered first-order features. First-order wavelet-filtered robust mean absolute deviation (RMAD) emerged as the most consistent significant feature for both 2D and 3D features with sampled grid spacings of 0.5 mm and 1 mm. The volume of the tumour demonstrated a decline for 80% of patients over 3 months, as measured by the 3D mesh volume of the tumour ROI. There was a significant decline in tumour size and image heterogeneity, indicating plausible changes in the tumour microenvironment possibly related to the treatment. Conclusions: Previous preclinical studies and clinical evaluations have demonstrated the efficacy of MR-guided FUS-MB therapy. MRI image-based features from the T1-weighted MR scans over various follow-up times provide potential evidence of changes in tumour tissue heterogeneity that might be treatment-related. MRgFUS MB therapy can possibly evolve as a mode of radiotherapy enhancement in the future, which warrants further controlled validation. The availability of adequate data in the future might possibly lead to the identification of image biomarkers related to treatment response, thus providing better clinical evaluations. Full article

Background: This study aimed to evaluate the association between the uptake on F-18 florastamin PET/CT, which targets the prostate-specific membrane antigen (PSMA), and the histopathological grade of the primary tumor in newly diagnosed prostate cancer patients. Methods: As a subset analysis of a phase III multicenter trial of florastamin PET/CT in East Asian men, the data from a single institution of pathologically confirmed prostate cancer cases were reviewed. The maximum standardized uptake value (SUVmax) was measured from the primary tumor on florastamin PET/CT images of 110 participants. The International Society of Urological Pathology (ISUP) grade group obtained from surgery or biopsy was classified into three risk groups: low (ISUP 1), intermediate (ISUP 2–3), or high (ISUP 4–5). Correlation was tested between the SUVmax of the prostate cancer and the ISUP-based risk. The PSA level and Prostate Imaging Reporting and Data System (PIRADS) score from MRI were also assessed for association with the SUVmax and ISUP-based risk. Results: The SUVmax of the primary tumor and the PSA level showed significant positive correlation with the ISUP-based risk (ρ = 0.541, p < 0.001; ρ = 0.328, p = 0.001, respectively). The tumor SUVmax increased with higher PIRADS scores (ρ = 0.516, p < 0.001). Conclusions: The SUVmax of the primary tumor on florastamin PET/CT was associated with the ISUP-based risk in East Asian men with prostate cancer, suggesting that it could be an imaging biomarker of tumor aggressiveness. Full article

Background: Former and current smokers in lung cancer screening remain at elevated risk for lung cancer despite smoking cessation. We and others have shown that curcumin (CUR) exhibits anti-inflammatory and antiproliferative effects but is limited by poor bioavailability. However, since CUR is lipophilic, co-administration with ω-3 FAs represents a mechanistically rational strategy to enhance delivery and target complementary pathways, including signal transducer and activator of transcription 3 (STAT3) and the transcription factor NF-κB (NF-κB) signaling for lung cancer chemoprevention. Methods: We conducted a randomized, single-blind, placebo-controlled Phase II pilot study evaluating CUR combined with ω-3 FAs in high-risk former and current smokers with CT-detected pulmonary nodules. Participants received intervention agents with active-dose groups (low dose = 3; high dose = 9) or a placebo (n = 7) for 6 months. Primary endpoints included radiologic changes in nodule size, number, and density. Secondary endpoints included safety, adherence to the study agent and exploratory biomarker analyses. Correlation analyses of imaging-derived metrics were performed to assess relationships among LDCT parameters. Results: Nineteen participants were enrolled (intervention, n = 12; placebo, n = 7). Eighteen (11 intervention, 7 placebo) subjects completed post-intervention imaging. One subject was unable to complete follow-up and study-related procedures. Data from the treatment arms were pooled for analysis and comparison with the placebo arm. No statistically significant between-group differences were observed in primary imaging endpoints. The intervention was well tolerated, with predominantly grade 1 adverse events. Exploratory analyses demonstrated consistent positive correlations among established imaging biomarkers, with clustering of size-based metrics (mean diameter, volume, sum of longest diameters) and density-based parameters. Multidimensional scaling supported this structure, indicating internal coherence among imaging-derived endpoints. Conclusions: Although no statistically significant treatment effect on the image biomarkers was observed, this pilot study demonstrates feasibility challenges and identifies coherent imaging biomarkers that may serve as intermediate endpoints in early-phase chemoprevention trials. These results support further investigation of strategies utilizing agent combinations with enhanced bioavailability and safety and refinement of trial design in high-risk lung cancer patient populations. Full article

T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibitory motif (ITIM) domains (TIGIT) emerged as one of the most promising next-generation immune checkpoint targets following the success of programmed cell death protein 1 (PD-1), programmed death-ligand 1 (PD-L1), and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) blockade. TIGIT suppresses antitumor immunity through interaction with cluster of differentiation 155 (CD155), inhibition of CD226-mediated co-stimulation, and promotion of immunosuppressive regulatory T-cell (Treg) activity within the tumor microenvironment (TME). Strong preclinical evidence demonstrated that TIGIT blockade, particularly in combination with PD-1/PD-L1 inhibition, restored T-cell and natural killer (NK) cell function and produced durable antitumor responses in multiple tumor models, leading to rapid clinical development. Despite this compelling biological rationale, most late-stage clinical programs failed to reproduce early success. Although the phase II CITYSCAPE trial showed encouraging activity in PD-L1-high non-small cell lung cancer (NSCLC), subsequent phase III trials, including SKYSCRAPER-01, SKYSCRAPER-02, SKYSCRAPER-03, SKYSCRAPER-14, AdvanTIG-302, KEYVIBE, and STAR-221, failed to improve survival outcomes or meet primary endpoints. The notable exception was SKYSCRAPER-08 in esophageal squamous cell carcinoma, suggesting that TIGIT blockade may be effective only in selected biological contexts. This review critically examines the molecular biology of the TIGIT–CD155–CD226 axis, its role in immune regulation and tumor immune evasion, and the preclinical and clinical evidence supporting TIGIT-targeted therapy. Particular emphasis is placed on understanding the causes of clinical failure, including CD226 loss during T-cell exhaustion, checkpoint network redundancy, Fc-engineering uncertainty, immunosuppressive TMEs, inadequate biomarker-guided patient selection, and tumor-type-specific dependence on the TIGIT pathway. We also present original bioinformatics analyses demonstrating that broader checkpoint network signatures outperform TIGIT expression alone for patient stratification. Finally, we evaluate emerging solutions including biomarker-guided precision immunotherapy, Fc-optimized antibodies, bispecific checkpoint inhibitors, TIGIT-engineered chimeric antigen receptor T-cell (CAR-T) cells, radiotherapy combinations, and multi-checkpoint blockade. Collectively, current evidence suggests that the future of TIGIT-directed therapy lies not in universal checkpoint inhibition but in biologically informed, precision-guided immunotherapy strategies. Full article

Glioblastoma remains the most lethal primary malignancy of the central nervous system, and the modest gains achieved with maximal surgery, radiotherapy and temozolomide have not been matched by the immune checkpoint inhibitors and antigen-specific vaccines that reshaped the treatment of many extracranial cancers. The recurrent disappointment of these approaches has been attributed less to a single molecular lesion than to a confluence of obstacles: profound intratumoural heterogeneity, a densely immunosuppressive and myeloid-rich microenvironment, sequestration and exhaustion of conventional T cells, and the practical difficulty of delivering effectors across the blood–brain barrier. Against this background, γδ T cells have attracted interest as an unconventional effector population that recognises transformed cells through stress-associated and metabolic cues rather than peptide–major histocompatibility complex (MHC) complexes, that kills in an MHC-unrestricted manner, and that can be expanded from healthy donors for allogeneic, off-the-shelf use with little expectation of graft-versus-host disease. This narrative review examines, with a deliberately critical lens, the biological rationale and the experimental evidence for γδ T cell-based immunotherapy of glioblastoma. We summarise the developmental biology and functional subsets of human γδ T cells, the natural killer group 2 member D (NKG2D)-, DNAX accessory molecule 1 (DNAM-1)- and T-cell-receptor-dependent mechanisms through which they engage glioblastoma cells and glioma stem-like cells, and the in vitro and animal-model studies that underpin the field, taking care not to overstate efficacy that has so far been demonstrated only in preclinical or early-phase settings. We then weigh the principal opportunities—locoregional and repeated dosing, combination with chemoradiotherapy, checkpoint blockade and antibody-based redirection—against barriers that include limited persistence, uncertain intratumoural trafficking, donor and manufacturing variability, and the unsettled requirements of potency testing and trial design. We give particular weight to what becomes of γδ T cells inside a hostile tumour—the exhaustion-like dysfunction that follows chronic stimulation, the oxygen and glucose dependence of their effector programme, the interleukin-17-polarising signals generated by activated microglia and by genotoxic therapy, and the confounding effect of corticosteroids—together with the engineering and pharmacological strategies proposed to counter them. The first peer-reviewed phase 1 report of intracranially delivered, drug-resistant γδ T cells has now appeared and documents tolerability in a small, single-arm cohort without establishing survival benefit. Throughout, γδ T cells are presented as a biologically plausible but still investigational strategy whose clinical value will be determined by adequately powered trials rather than by mechanistic appeal alone. Full article

High-resolution micro-ultrasound (microUS) is a 29 MHz imaging modality that allows visualisation of prostatic ductal architecture at 70 µm resolution, enabling real-time recognition of architectural disruption associated with clinically significant prostate cancer (csPCa). This review summarises the current evidence for microUS in the diagnosis and management of prostate cancer, with emphasis on developments since the pivotal OPTIMUM phase-3 randomised controlled trial. OPTIMUM provided level 1 evidence for microUS-guided biopsy as non-inferior to MRI-guided biopsy for csPCa detection. We examine the PRI-MUS risk identification protocol, the pre- and post-OPTIMUM evidence base, biopsy targeting and core number, inter-observer reliability and the learning curve, and emerging applications in active surveillance, restaging biopsy, local staging and tumour characterisation, and post-treatment surveillance for local recurrence. We also review the growing body of work on artificial intelligence-enhanced microUS, alongside workflow, cost, and environmental considerations. Whilst inter-reader variability and the learning curve remain barriers, microUS offers comparable sensitivity to multiparametric MRI with practical advantages in cost, accessibility, and workflow. In our view, microUS warrants acceptance as a primary imaging modality for the work-up of suspected prostate cancer. Full article

Background: Radiation therapy with or without systemic treatment for lung cancer can cause adverse reactions, e.g., fatigue. Affected patients may experience a decrease in physical activity and, as a consequence, be unable to receive the complete assigned treatment. Physical exercise may be helpful. A benefit of exercise regarding completion of systemic treatment and quality of life was previously suggested. Irradiated patients may benefit as well. A smartphone-based app reminding patients to make a minimum number of steps might positively influence physical activity. The prototype of an app called “Step Reminder” was recently finalized. The randomized APPAREL trial (NCT07627022) evaluates whether this app can improve physical activity during irradiation for lung cancer. Methods: The primary endpoint of this phase 2 trial focuses on the within-patient change regarding the mean number of daily steps (week 5 minus week 1). Secondary objectives include satisfaction with the application and its impact on the perception of digital health technology. Patients are randomized 1:1 to be treated with a standard approach (conventionally fractionated irradiation with or without systemic treatment) supported by the “Step Reminder” app (Arm A) or standard treatment without the app (Arm B). The app provides reminders several times per day to walk a pre-defined number of steps. To make sure that the required 28 patients are included in the primary analysis population (full analysis set), 32 patients have to be randomized. Results: At this stage, results are not available. Conclusions: It is expected that the app will have a positive effect on the patients’ physical activity (number of steps). Full article

Background/Objectives: Lutetium (¹⁷⁷Lu) TLX591 (¹⁷⁷Lu-TLX591) is a radio antibody–drug conjugate (rADC) that utilizes a novel monoclonal antibody-based approach for treatment of patients with prostate-specific membrane antigen (PSMA)-expressing metastatic castration-resistant prostate cancer (mCRPC). ProstACT SELECT (NCT04786847) was a multicenter, single-arm, open-label Phase 1 trial evaluating patient selection for ¹⁷⁷Lu-TLX591 therapy using ⁶⁸Ga-PSMA-11 PSMA positron emission tomography (PET) in a heterogenous sample of patients with mCRPC. Primary and key secondary objectives were to evaluate safety and tolerability, biodistribution, and organ radiation dosimetry of ¹⁷⁷Lu-TLX591 in combination with the best standard of care (SOC) for patients with PSMA-expressing mCRPC who progressed despite prior treatment with an androgen receptor pathway inhibitor. Methods: Thirty patients received ¹⁷⁷Lu-TLX591 intravenously in combination with investigator-determined SOC. Cohort 1 (n = 5) received an imaging dose of ¹⁷⁷Lu-TLX591 (1 GBq [27 mCi]), followed 14 days later by one therapeutic dose (2.8 GBq [76 mCi]). Cohort 2 received two therapeutic doses of ¹⁷⁷Lu-TLX591, 14 days apart. Baseline ⁶⁸Ga-PSMA-11 PET was performed to confirm eligibility and was qualitatively compared with serial ¹⁷⁷Lu-TLX591 single-photon emission computed tomography (SPECT)/CT, which was performed at five timepoints following the first ¹⁷⁷Lu-TLX591 administration and also used to evaluate organ radiation dosimetry. Safety assessments included monitoring for treatment-emergent adverse events and collection of laboratory samples at specified timepoints used for biomarker analyses. Results: Tumor targeting observed on ¹⁷⁷Lu-TLX591 SPECT/CT imaging was qualitatively consistent with uptake observed on ⁶⁸Ga-PSMA-11 PET imaging. No new safety signals were observed. Radiation exposure was within safety limits, with the highest absorbed dose to liver (clearance organ; 2.44 ± 0.56 Gy/GBq) and with lower exposure to salivary glands (0.07 ± 0.03 Gy/GBq) and kidneys (0.64 ± 0.17 Gy/GBq). Activity was retained in tumor lesions through to the final protocol-specified imaging timepoint (312 h) following administration. Conclusions: In this Phase 1, single-arm study, ⁶⁸Ga-PSMA-11 PET supported patient selection for ¹⁷⁷Lu-TLX591 therapy. In a heterogenous population representative of a real-world setting, ¹⁷⁷Lu-TLX591 therapy in combination with SOC demonstrated a manageable and predictable safety profile, durable retention, and low salivary gland radiation exposure. Further evaluation in larger, randomized studies is warranted. Full article

Background/Objectives: The PRO-CTCAE Average Composite Score (ACS), calculated as the mean of PRO-CTCAE composite scores, summarizes overall symptom and side effect burden. This study evaluated the test–retest reliability, responsiveness to change, known-groups validity, and sensitivity to group differences in the ACS. Methods: Analyses used the original PRO-CTCAE validation dataset, including lung (n = 174), breast (n = 222), and head and neck (n = 139) cancer cohorts, and data from the COMET-2 randomized phase III trial comparing cabozantinib (n = 53) and mitoxantrone–prednisone (n = 54) in men with previously treated prostate cancer. Test–retest reliability was assessed using intraclass correlation coefficients (ICCs) from two-way mixed-effects models for agreement. Responsiveness was evaluated by relating ACS change scores (Visit 1 minus follow-up Visit 2) to patient-reported global ratings of change (GRC; worsened, unchanged, or improved) using standardized response means (SRMs) and Jonckheere–Terpstra trend tests. Known-groups validity was examined by comparing mean ACS values between ECOG performance status groups (0–1 vs. 2–4). Sensitivity to treatment group differences was assessed using model-based area-under-the-curve (AUC) comparisons of longitudinal ACS trajectories. Results: Test–retest reliability was acceptable, with ICCs among GRC-defined stable patients of 0.80 (95% CI: 0.70–0.87) in lung cancer, 0.84 (95% CI: 0.77–0.89) in breast cancer, and 0.77 (95% CI: 0.63–0.86) in head and neck cancer; ICCs based on assessments completed one day apart ranged from 0.88 to 0.90. The ACS demonstrated responsiveness, with SRMs of 0.30/0.15/−0.37 (lung), 0.29/0.14/−0.40 (breast), and −0.01/−0.20/−0.56 (head/neck) for improved/no-change/worsened groups, respectively, and significant monotonic trends across GRC categories (all p < 0.01). Known-groups validity was supported by conceptually expected differences in ACS values across distinct levels of self-reported patient-reported physical functioning and ECOG performance status categories. Mean ACS values were lower among patients with good versus limited physical functioning (0.71 vs. 1.23 in lung cancer, 0.52 vs. 1.19 in breast cancer, and 0.69 vs. 1.29 in head and neck cancer) and among patients with ECOG PS 0–1 versus 2–4 (0.93 vs. 1.31, 0.74 vs. 1.22, and 0.90 vs. 1.06, respectively). In COMET-2, higher symptom burden was detected in the cabozantinib arm compared with the mitoxantrone–prednisone arm (AUC difference = 1.5, 95% CI: 0.2–2.8, p = 0.02). Conclusions: The ACS demonstrated acceptable test–retest reliability, responsiveness, and known-groups validity across multiple cancer populations. These findings support its use as a complementary summary measure of overall symptomatic adverse event burden alongside individual symptom-level analyses. Full article

Background: C-reactive protein (CRP) is a well-established marker of systemic inflammation, while Growth Differentiation Factor-15 (GDF-15) has emerged as a potential biomarker of cellular stress. Their relative perioperative dynamics remain incompletely defined. This prospective observational study aimed to explicitly characterize and compare the longitudinal dynamics of CRP and GDF-15 in patients undergoing elective knee arthroplasty. Characterizing these biomarkers in a controlled acute surgical model provides clinical relevance by mapping systemic acute-phase inflammation against cellular stress pathways, which may offer a baseline reference for evaluating chronic tissue-wasting states. Methods: This prospective observational study included 47 patients undergoing elective knee arthroplasty. After excluding nine patients with elevated baseline CRP (>10 mg/L), serial measurements of CRP and GDF-15 were analysed daily in 38 patients from pre-operation to postoperative Days 1–3. Results: CRP rose sharply after surgery, peaking on Day 3 (median: 206.0 mg/L vs. baseline: 3.0 mg/L), representing a maximal increase exceeding 6100%. GDF-15 levels also increased progressively, peaking on Day 3 (median: 1682.5 pg/mL vs. baseline: 968.8 pg/mL), which represented a statistically significant but more modest rise of 33%. CRP and GDF-15 were significantly correlated on postoperative day 1 (rs = 0.53, p = 0.001) but not days 2 and 3. Baseline GDF-15, but not CRP, was significantly associated with oral hypoglycaemic agent use and vitamin B12 supplementation. Compared to values reported in recent randomized trials of ghrelin, anti-GDF-15, and anti-IL-6 therapies, GDF-15 levels in this surgical cohort remained lower, while CRP approached levels observed in such studies. Conclusions: CRP and GDF-15 rise in parallel following surgical injury; however, GDF-15 shows a considerably lower sensitivity to the inflammatory response. These findings suggest a complementary role of GDF-15 alongside CRP in profiling the perioperative stress response. While its relatively modest acute elevation limits its utility as a primary marker of acute inflammation, this surgical stress model serves as a reference that may help contextualize biomarker profiles in chronic inflammatory or wasting conditions, such as cancer cachexia, rather than serving as a direct tool for cachexia management. Full article

Background: Messenger RNA (mRNA) vaccines have emerged as a versatile platform beyond SARS-CoV-2, with expanding applications in infectious diseases and oncology. However, comprehensive evidence synthesis of non-SARS-CoV-2 mRNA vaccines remains limited. Methods: This systematic review followed PRISMA 2020 guidelines and was registered in PROSPERO (CRD420261323500). MEDLINE, Embase, Web of Science, Scopus, ClinicalTrials.gov, and WHO ICTRP were systematically searched for studies published between 1 January 2000 and 28 February 2026. Eligible studies included phase I–III clinical trials and in vivo preclinical studies evaluating non-SARS-CoV-2 mRNA vaccines. Two reviewers independently screened studies, extracted data, and assessed risk of bias using RoB 2, ROBINS-I, and SYRCLE tools. Findings were synthesized narratively because of substantial heterogeneity. Results: A total of 40 studies met the eligibility criteria and were included in the review, comprising 20 clinical studies and 20 preclinical studies. Advanced clinical programs targeted influenza and respiratory syncytial virus (RSV), with phase III trials displaying seroconversion rates above 70% with good safety profiles. Preliminary phase I studies for HIV, cytomegalovirus, rabies, and personalized cancer mRNA vaccines showed promising humoral and cellular immune responses. Preclinical studies showed strong antibody and T-cell responses against malaria, tuberculosis, Group B Streptococcus, and Zika virus. Most adverse events were mild to moderate, while serious vaccine-related adverse events were uncommon. Conclusions: Non-SARS-CoV-2 mRNA vaccines demonstrate substantial translational potential across infectious disease and oncology applications. Although the vaccine candidates have demonstrated promising immunogenicity and safety, most are in the early stages of development. This highlights the need for large trials, long-term safety follow-up and better global representation. Full article

Epithelial ovarian cancer (EOC) remains one of the most lethal gynecologic malignancies, largely owing to advanced-stage presentation, high rates of relapse, and the eventual emergence of therapeutic resistance. Despite the transformative success of immune checkpoint inhibitors (ICIs) across multiple solid tumors, their clinical impact in ovarian cancer has been comparatively modest. This literature review provides a comprehensive synthesis of recent advances in ICI strategies for ovarian cancer (OC), with particular emphasis on phase II and III clinical trials evaluating programmed cell death protein 1 (PD-1), programmed death-ligand 1 (PD-L1), cytotoxic T-lymphocyte–associated protein 4 (CTLA-4), and T cell immunoglobulin and mucin-domain-containing-3 (TIM-3)-directed therapies. Accumulating evidence indicates that PD-1/PD-L1 monotherapy yields limited clinical activity in unselected OC populations, with low objective response rates and minimal survival benefit. Dual checkpoint blockade with PD-1 and CTLA-4 inhibitors demonstrates enhanced antitumor activity, particularly in clear cell ovarian carcinoma (CCOC), albeit at the expense of increased immune-related toxicity. Large randomized trials incorporating ICI into first-line chemotherapy or maintenance settings have largely failed to improve outcomes in biomarker-unselected cohorts. Available evidence demonstrates that combinatorial approaches integrating ICI with anti-angiogenic agents, PARP inhibitors, or neoadjuvant chemotherapy provide modest benefit in selected molecular and histologic subgroups. Early-phase investigations of TIM-3–targeting strategies further expand the immunotherapeutic landscape, although clinical efficacy remains preliminary. Current evidence underscores that OC is not uniformly responsive to immunotherapy and that rational combination strategies, biomarker-driven patient selection, and improved understanding of tumor immune microenvironment heterogeneity are essential to unlocking the full therapeutic potential of ICI in this disease. Full article