Search Results (514)

Background: Members of the tumor necrosis factor receptor superfamily (TNFRSF), including 4-1BB (CD137) and OX-40 (CD134), play central roles in regulating cytotoxic lymphocyte activation and anti-tumor immunity. In addition to their membrane-bound forms, soluble receptor isoforms may modulate signaling by influencing ligand availability and receptor engagement. However, the peripheral regulation of soluble and membrane 4-1BB and OX-40 in cervical cancer remains incompletely defined. Methods: Plasma concentrations of soluble 4-1BB (s4-1BB) and soluble OX-40 (sOX-40) were quantified by ELISA in 20 treatment-naïve cervical cancer (CC) patients and 20 healthy controls (HCs). Membrane expression (m4-1BB and mOX-40) on circulating T cells and NK cells was evaluated by flow cytometry. Correlation and stage-stratified analyses were performed. Results: Plasma levels of s4-1BB and sOX-40 were significantly elevated in CC patients compared with HCs. Membrane 4-1BB expression was increased on both T cells and NK cells, while OX-40 expression was selectively elevated in NK cells, with no difference observed in T cells. A moderate positive correlation was identified between s4-1BB and T-cell membrane 4-1BB expression. Notably, membrane 4-1BB expression decreased in advanced-stage disease, whereas soluble concentrations remained unchanged. Conclusions: These findings demonstrate differential regulation of soluble and membrane 4-1BB and OX-40 in the peripheral compartment in cervical cancer, highlighting distinct regulatory layers within the TNFRSF axis. Full article

Background/Objectives: Magnetic resonance imaging (MRI)-based image-guided adaptive brachytherapy (IGABT) is the preferred standard for cervical cancer, but access remains limited in many settings. Computed tomography (CT)-based IGABT provides a practical alternative. We evaluated clinical outcomes and prognostic factors following its routine implementation. Methods: This retrospective cohort study included patients with International Federation of Gynecology and Obstetrics (FIGO) 2018 stage I–IVA cervical carcinoma treated with definitive radiotherapy incorporating CT-based IGABT from January 2019 to December 2021. Patients received pelvic external beam radiotherapy (45–50.4 Gy in 23–28 fractions), with or without concurrent platinum-based chemotherapy, followed by four high-dose-rate brachytherapy fractions. Local control and overall survival were estimated using Kaplan–Meier analysis, and prognostic factors were evaluated using Cox regression. Results: Among 237 patients, 56.9% had FIGO stage III–IV disease, and hybrid intracavitary/interstitial brachytherapy was used in 30.2% of fractions. The mean high-risk clinical target volume D90 (HR-CTV D90) was 85.4 ± 2.7 Gy EQD₂. Median follow-up was 59.9 months for local control and 71.1 months for overall survival. The 5-year local control and overall survival rates were 84.4% (95% CI, 79.1–88.5%) and 62.9% (95% CI, 56.3–68.8%), respectively. Squamous histology was independently associated with improved local control and overall survival. HR-CTV D90 ≥ 85 Gy EQD₂ was associated with improved local control, whereas ≥4 chemotherapy cycles and overall treatment time ≤ 56 days were associated with improved overall survival. Conclusions: Routine CT-based IGABT achieved clinically meaningful outcomes despite the high proportion of advanced-stage disease. Achieving HR-CTV D90 ≥ 85 Gy EQD₂, delivering ≥4 chemotherapy cycles, and completing treatment within 56 days were associated with improved outcomes. Full article

Objectives: The endometrium and cervix share a common Müllerian origin and may exhibit overlapping biological responses to oncogenic stimuli. However, the clinical significance of preoperative cervical cytology in patients with endometrial cancer remains unclear. This study aimed to investigate the association between preoperative cervical smear cytology and clinicopathologic characteristics, with particular emphasis on advanced FIGO stage (III–IV) as the primary outcome. Methods: This retrospective cohort study included 154 patients who underwent primary surgery for histologically confirmed endometrial cancer. Preoperative cervical smear cytology was classified according to the Bethesda System into four categories: normal, low-grade, high-grade, and malignant. For subgroup analyses, low-grade, high-grade, and malignant cytology results were combined and compared with normal cytology. FIGO stage was analyzed both as individual stages (IA–IV) and as early-stage (I–II) versus advanced-stage (III–IV) disease, where appropriate. Continuous variables were summarized as mean ± standard deviation or median (interquartile range), while categorical variables were expressed as n (%). Group comparisons were performed using the Pearson chi-square test or Fisher’s exact test, as appropriate, and a two-sided p value < 0.05 was considered statistically significant. Results: A total of 154 patients with endometrial cancer were included in the analysis. Preoperative cervical smear cytology was normal in 140 patients (90.9%), low-grade in 6 (3.9%), high-grade in 3 (1.9%), and malignant in 5 (3.2%). Comparison across cytology categories demonstrated a significant association between smear cytology and FIGO stage (p < 0.001), with high-grade and malignant cytology occurring more frequently in patients with advanced-stage disease. Vaginal cuff involvement was also significantly associated with smear cytology (p = 0.001), whereas no significant associations were observed for myometrial invasion, lymphovascular space invasion, cervical stromal involvement, tubo-ovarian involvement, omental involvement, or lymph node metastasis. Subgroup analysis comparing normal and abnormal cytology yielded similar findings, confirming significant associations with FIGO stage (p < 0.001) and vaginal cuff involvement (p = 0.002). In a multivariable model additionally including cervical cytology, LVSI and deep myometrial invasion were independent predictors of advanced stage (AUC = 0.888), whereas cytology was not statistically significant after adjustment (OR 4.51, p = 0.076) and showed poor standalone diagnostic performance (AUC = 0.564, sensitivity 19.4%, specificity 93.5%). All patients with vaginal cuff involvement had advanced-stage disease (Fisher’s exact p < 0.001). The cytology–FIGO stage association was not significant in postmenopausal (p = 0.065) or endometrioid-only (p = 1.00) subgroup analyses. Conclusions: Abnormal preoperative cervical smear cytology was significantly associated with advanced FIGO stage and vaginal cuff involvement in patients with endometrial cancer. These findings suggest that cervical cytological abnormalities may reflect overall disease extent rather than individual histopathological risk factors. Given the retrospective design and the limited number of patients with abnormal cytology, these findings should be interpreted cautiously and validated in larger prospective studies. However, cytology was not an independent predictor of advanced stage after multivariable adjustment and performed poorly as a standalone diagnostic marker, suggesting it should not be used alone to assess disease extent. Full article

Background: Tumor hypoxia is a major determinant of radioresistance, limiting oxygen-mediated fixation of radiation-induced DNA damage and promoting metabolic adaptation, tumor aggressiveness, and treatment failure. Nitroimidazole derivatives and related hypoxia-targeting compounds have been investigated as radiosensitizers because of their oxygen-mimetic properties and selective activation under low-oxygen conditions. Methods: A structured narrative review was conducted to evaluate recent evidence on hypoxia-targeting strategies and nitroimidazole-based radiosensitizers combined with radiotherapy. PubMed and Scopus were searched in March 2026 using terms related to radiotherapy and nitroimidazoles. Studies published within the last five years were included if they investigated hypoxia-targeting compounds, radiosensitization strategies, or dose–response relationships relevant to radiotherapy. Preclinical, computational, and clinical studies were considered. Results: Sixteen studies were included, comprising preclinical, computational, and clinical investigations. Most studies were preclinical and evaluated in vitro cell lines, murine tumor models, or xenografts across multiple tumor types, including head and neck cancer, glioblastoma, breast cancer, colorectal cancer, cervical cancer, renal carcinoma, pancreatic cancer, and ovarian-related models. Nitroimidazole-based and related hypoxia-targeting strategies generally enhanced radiation response under hypoxic conditions, with sensitizer enhancement ratio values ranging from approximately 1.09 to 1.65. In vivo studies reported reductions in tumor growth or tumor volume when radiosensitizers were combined with radiotherapy. Clinical evidence, mainly in head and neck squamous cell carcinoma, showed variable effects on locoregional outcomes. Conclusions: Current evidence supports the biological relevance of hypoxia-targeting strategies for improving radiotherapy response. Nitroimidazole-based compounds show consistent radiosensitizing effects in preclinical models, but clinical translation remains heterogeneous. Future studies should integrate hypoxia imaging, standardized endpoints, advanced drug delivery systems, and clinically relevant radiotherapy models to better define their role in modern radiation oncology. Full article

Reactive Oxygen Species Modulator 1 (ROMO1) and CD47 have both been implicated in cervical carcinogenesis, but their relationship within the same tumor has not been investigated. We retrospectively analyzed immunohistochemical H-scores for ROMO1 and CD47 in 221 invasive cervical carcinomas, including 205 tumors with evaluable expression of both markers, and examined their associations with clinicopathological characteristics. ROMO1 and CD47 expression did not correlate at the individual-tumor level (Spearman ρ = −0.08, p = 0.25; κ = −0.10). CD47 expression decreased significantly with increasing local tumor extent (ρ = −0.21, p = 0.002) and FIGO stage (p = 0.006), while ROMO1 showed a weaker, non-significant trend in the same direction. The ROMO1-high/CD47-high phenotype was observed in 15.7% of early-stage tumors but was absent in locally advanced (pT2–pT4) tumors (χ² p = 0.001). These findings suggest that ROMO1 and CD47 are not directly co-regulated in cervical cancer, despite showing similar changes with local tumor progression. Their parallel expression patterns may therefore reflect separate responses to common factors involved in cervical carcinogenesis rather than a direct relationship between the two proteins. Further functional studies are needed to clarify the mechanisms underlying these findings. Full article

Background/Objectives: Cervical cancer (CC) is currently one of the leading causes of cancer-related mortality worldwide. Patients with advanced, recurrent, or metastatic CC, for whom treatment options are limited, are particularly at risk. Tisotumab vedotin (TV) is a first-in-class antibody–drug conjugate targeting tissue factor (TF), representing a promising therapeutic breakthrough. This systematic review aims to comprehensively evaluate the clinical efficacy, safety profile, and therapeutic potential of TV, both as monotherapy and in combination regimens, in patients with advanced cervical cancer. Methods: A systematic literature search was conducted in the PubMed, Scopus, and Embase databases, as well as on the ClinicalTrials.gov website, for prospective clinical trials (Phases I–III) in accordance with the PRISMA 2020 guidelines. The search focused on original articles and studies published between 2019 and 2026. Four key clinical trial programmes (innovaTV 201, 204, 205, and 301), involving 548 patients, were selected. Quality assessment was performed using the Cochrane RoB 2.0 tool and the NIH tool for assessing the quality of “before-and-after” studies. Results: Objective response rates (ORR) with TV ranged from 17.8% in monotherapy to 65.8% in combination regimens, confirming its efficacy in treatment. In randomised Phase III trials, the use of TV improved overall survival compared to standard chemotherapy. Adverse effects characteristic of TV are primarily ophthalmic complications, peripheral neuropathy, and hemorrhagic events. These were managed through pre-established prophylactic and monitoring protocols. Combination therapies increased therapeutic efficacy but also raised the incidence of grade ≥ 3 adverse events occurring during treatment. Conclusions: TV offers new hope by changing the treatment algorithm for cervical cancer. As a targeted therapy, it provides an effective alternative to conventional chemotherapy in previously treated patients. It also has the potential for use in first-line multi-drug treatment regimens. Strict adherence to safety protocols is essential to minimise toxicity and ensure treatment continuity. Full article

Background/Objectives: Angiogenesis plays a central role in the progression of cervical intraepithelial neoplasia (CIN) to cervical cancer (CC). Transvaginal Doppler ultrasonography (TVDUSG) offers a non-invasive means of assessing hemodynamic changes associated with neoplastic transformation. This study aimed to evaluate the diagnostic performance of uterine artery (UA) Doppler parameters across the full cervical disease spectrum and their associations with adverse prognostic features and clinicopathological features in CC. Methods: This prospective observational cohort study enrolled 170 patients who were divided into four groups: controls, CIN 1, CIN 2–3, and CC. All underwent TVDUSG prior to treatment. Pulsatility index (PI), resistance index (RI), peak systolic velocity (PS), end-diastolic velocity (ED), PS/ED ratio, ED/PS ratio, and time-averaged maximum velocity were recorded. ROC curve analysis was performed to assess diagnostic performance. Results: PI and RI increased progressively from controls to CC, while ED declined across groups (all p < 0.001). In patients with CC, PI correlated with tumor volume and was elevated in those with advanced-stage, parametrial and lymph node involvement (all p < 0.001). ROC analysis revealed strong diagnostic performance for PI in distinguishing CC from controls (AUC = 0.861, sensitivity 80.0%, specificity 80.4%); however, PI showed limited ability to distinguish cervical cancer specifically from high-grade CIN (AUC = 0.593). Conclusions: UA Doppler parameters, particularly PI, are associated with cervical neoplastic severity and adverse prognostic features in CC. TVDUSG may serve as a practical, non-invasive adjunct in the preoperative evaluation of cervical neoplasia, especially where advanced imaging is unavailable. Full article

Endometrial and cervical cancers can recur from subclinical disease not evident on routine surveillance. This narrative review critically evaluates liquid biopsy for minimal residual disease (MRD) assessment and recurrence monitoring. Post-treatment human papillomavirus (HPV) circulating tumor DNA (ctDNA) in cervical cancer has the strongest disease-specific prospective evidence of clinical validity; persistent detection is strongly associated with recurrence, but moderate sensitivity and false-negative results do not support treatment de-escalation on negativity alone. With regard to endometrial cancer, perioperative ctDNA has prognostic support from an 11-study, 1298-patient meta-analysis and additional cohorts, although assay heterogeneity and limited independent replication constrain clinical readiness. Postoperative positivity generally shows stronger associations than preoperative detection. Cervicovaginal and urine DNA-methylation studies provide preliminary evidence for detecting established recurrence, especially local recurrence, but not prospective molecular lead time or clinical utility. Digital PCR, disease-specific fixed panels, tumor-informed assays, and error-corrected sequencing serve distinct settings; broad pan-cancer plasma profiling remains mainly an advanced-disease tool. Circulating tumor cells, extracellular vesicles, microRNAs, tumor-educated platelets, and fragmentomics remain exploratory. Liquid biopsy should remain an investigational adjunct until prospective trials show that acting on molecular findings improves outcomes. Full article

Background: Emergency services in urban areas are overcrowded due to a rise in mild-to-moderate acuity consultations, and physician-led home visits are less common. In response, a home-based urgent care model in an urban setting (Docadom) was developed. Consultation requests via a dedicated mobile application or phone call are triaged by a trained emergency nurse. Physicians travel to the patient via an electric cargo bike that has storage for medical equipment. During home visits, physicians perform testing/diagnosis and advanced procedures (e.g., intravenous medication delivery) and prescribe treatment (if needed). This descriptive analysis reports activities during the first 12 months of Docadom. Methods: Data from all patients seen during the first 12 months of Docadom activity (1 May 2023–30 April 2024) were analysed. Outcomes analysed included: age, sex, diagnosis, and whether the patient was referred to the hospital. Patient satisfaction (from 1 [worst] to 5 [best]) is also reported. Each outcome was analysed in two subgroups based on patient age (<75 or ≥75 years) because the Swiss health insurance system distinguishes between these two age groups, using Wilcoxon or chi-square tests as appropriate. Results: A total of 1736 patients requested a consultation (66% female; median age 70 years [interquartile range 36, 84]; 43% aged ≥75 years). The five most frequent clinical presentations were: ear, nose and throat infection, epistaxis and bronchitis (25.7%); soft tissue trauma (7.8%); acute cervical or lower back pain syndrome (5.6%); gastroenteritis and dehydration (5.0%); and cancer and general decline in the elderly (4.6%). Only 4.7% of the patients were referred to the hospital. The mean satisfaction score was 4.97 (response rate: 207/422 patients [49%] who requested a consultation via the app). Conclusions: These data highlight the feasibility and acceptability of a home-based urgent care model in an urban setting. The service effectively addressed a wide range of acute conditions, especially in elderly patients. The low hospital referral rate and high patient satisfaction are encouraging, but as a single-arm descriptive analysis without post-consultation outcome data or a comparator group, this study cannot establish clinical safety or an effect on emergency department use; these questions require a future comparative study. Full article

Oncogenic viruses contribute to approximately 20% of human cancers globally, with their impact falling disproportionately on populations in Sub-Saharan Africa. In this region, cervical cancer, hepatocellular carcinoma, endemic Burkitt lymphoma, and Kaposi sarcoma represent major causes of cancer-related morbidity and mortality, driven by persistent infection with human papillomavirus (HPV), hepatitis B and C viruses (HBV/HCV), Epstein–Barr virus (EBV), Kaposi sarcoma-associated herpesvirus (KSHV), and human T-lymphotropic virus-1 (HTLV-1). This review synthesizes current insights into the immunological mechanisms that underpin viral carcinogenesis in Africa, emphasizing how defective viral clearance, chronic immune activation, and immune evasion arise from the convergence of region-specific co-infections, host genetic diversity, and environmental exposures. We examine the mechanistic roles of HIV-associated CD4⁺ T cell depletion, malaria-induced perturbation of antiviral T cell immunity, helminth-driven T helper 2 polarization, and tuberculosis-associated inflammatory signaling in promoting viral persistence and malignant transformation. In addition, the influence of the extensive diversity of African human leukocyte antigens (HLA) and cytokine gene polymorphisms on antiviral immune responses and cancer susceptibility was discussed. We also assessed how virus-associated tumors establish profoundly immunosuppressive microenvironments characterized by impaired antigen presentation and the dominance of immune checkpoint pathways. Finally, we examined how gaps in vaccination, screening, and diagnostic capacity intersect with immunological vulnerability across Africa, contributing to the burden of infection-associated cancers. These challenges position Africa as a critical setting for developing targeted, genotype-inclusive public health interventions and reducing global cancer disparities through advances in immunoprevention and immunotherapy. Full article

Malondialdehyde (MDA) is one of the main end-products of lipid peroxidation (LPO) and represents a widely investigated marker of oxidative stress (OS) and oxidative tissue damage. Beyond its role as a measurable byproduct of polyunsaturated fatty acid peroxidation, MDA can interact with proteins and nucleic acids, generating adducts that may contribute to mutagenic, genotoxic, and cytotoxic events involved in carcinogenesis and tumor progression. This narrative review summarizes current evidence on the role of MDA in cancers, including breast, lung, head and neck, colorectal, cervical, and cutaneous tumors. Across these cancer types, increased circulating or tissue MDA levels have frequently been associated with enhanced LPO, impaired antioxidant defenses, tumor burden, advanced disease stage, aggressive histopathological features, treatment-related oxidative injury, and, in selected studies, poorer clinical outcomes. MDA-derived DNA adducts may further reflect oxidative DNA damage and provide mechanistic insight into the relationship between chronic redox imbalance, inflammation, and malignant transformation. However, MDA remains a non-specific biomarker influenced by age, smoking, diet, metabolic disorders, systemic inflammation, comorbidities, treatment exposure, and analytical methodology. Current evidence therefore supports MDA as a biologically relevant indicator of oxidative damage rather than a validated stand-alone diagnostic, prognostic, or therapeutic biomarker. Larger prospective studies using standardized and specific analytical methods are needed to clarify its clinical utility and to integrate MDA within broader redox biomarker panels. Full article

Background/Objectives: Image-guided adaptive brachytherapy is a core component of definitive treatment for locally advanced cervical cancer (LACC). However, implantation remains challenging in bulky, asymmetric, or anatomically complex tumors, where standard applicator geometry or purely straight interstitial trajectories may be insufficient for individualized target coverage. This study evaluated the real-world implementation of a patient-specific 3D-printed template-guided adaptive brachytherapy workflow for complex LACC. Methods: We retrospectively reviewed 120 consecutive patients with FIGO 2018 stage IB3–IVA cervical cancer treated with definitive chemoradiotherapy followed by high-dose-rate image-guided brachytherapy between March 2023 and March 2025. All patients were treated using a patient-specific 3D-printed template-guided hybrid intracavitary/interstitial workflow integrating CT/MRI-based target assessment, individualized catheter trajectory planning, template fabrication, implantation verification, and adaptive treatment planning. Straight-channel or curved-channel guidance was selected according to residual tumor geometry and pelvic anatomy, with flexible plastic interstitial catheters used for curved or anatomically constrained trajectories. Procedural deliverability, dosimetry, toxicity, early clinical outcomes, and exploratory dose–outcome patterns were analyzed. Results: The median HR-CTV volume was 55.9 cm³, and the median HR-CTV D90 was 92.9 Gy EQD2. Median organ-at-risk D2cc values remained within contemporary institutional and guideline-consistent constraints. A total of 555 template-guided HDR brachytherapy fractions were delivered. The median applicator-and-catheter placement time was 4.21 min per fraction, with a median of 7.25 implanted channels. Minor and major insertion-related bleeding occurred in 10.8% and 1.7% of patients, respectively. At a median follow-up of 20.1 months, estimated 3-year overall survival, progression-free survival, local recurrence-free survival, regional recurrence-free survival, and distant metastasis-free survival were 77.9%, 76.8%, 94.3%, 98.0%, and 86.2%, respectively. Late grade ≥ 3 gastrointestinal and genitourinary toxicities occurred in 2.5% and 1.7% of patients, respectively, with no grade 4–5 events. Exploratory dose–outcome analyses suggested hypothesis-generating dose–outcome patterns, but these findings were not intended to define or validate a clinical dose threshold. Conclusions: This real-world implementation study supports the feasibility of patient-specific 3D-printed template-guided adaptive brachytherapy for complex LACC. By translating CT/MRI-based individualized trajectory planning into template-guided intracavitary/interstitial catheter placement, this workflow achieved guideline-consistent target coverage, acceptable organ-at-risk doses, efficient procedural delivery, and low severe toxicity within the available follow-up. Dose–outcome findings remain exploratory and require validation in more mature cohorts. Full article

Immune checkpoint inhibitors and antibody–drug conjugates have rapidly expanded treatment options for gynecologic malignancies, although the magnitude of benefit varies substantially across tumor types and biomarker-defined populations. This narrative review summarizes the biologic rationale, predictive biomarkers, pivotal clinical trials, regulatory approvals, guideline-supported strategies, and emerging directions for immune checkpoint blockade and antibody–drug conjugates in endometrial, cervical, and ovarian cancers. In endometrial cancer, molecular classification and mismatch repair status have transformed treatment selection, with PD-1 or PD-L1 blockade now integrated into first-line chemoimmunotherapy and recurrent disease management. HER2-directed and TROP-2-directed antibody–drug conjugates are also emerging as biomarker-directed strategies. In cervical cancer, human papillomavirus-driven tumor biology, PD-L1 expression, and tissue factor expression support the use of checkpoint inhibitors, antibody–drug conjugates, and therapeutic vaccine approaches across locally advanced and recurrent or metastatic settings. In ovarian cancer, single-agent checkpoint blockade has shown limited activity in unselected populations, but recent advances include biomarker-selected chemoimmunotherapy in platinum-resistant disease and clinically meaningful activity of folate receptor alpha-directed and HER2-directed antibody–drug conjugates. Across gynecologic cancers, key challenges include refining predictive biomarkers, optimizing sequencing after prior immunotherapy exposure, managing overlapping toxicities, and designing trials that enrich for biologically responsive subgroups. Future progress will depend on integrating molecular classification, immune contexture, ADC target expression, and patient-specific clinical factors into treatment selection. Full article

Background/Objectives: Thymidylate synthase (TYMS) represents an important therapeutic target. Methods: In this study, TYMS expression was analyzed by immunohistochemistry on a tissue microarray containing 17,371 samples from 136 different tumor types. Results: TYMS staining was seen in 42.9% of 15,361 analyzable tumors, with weak staining in 35.4%, moderate in 5.7%, and strong in 1.8%. TYMS occurred in at least one case of 127 categories, of which 71 showed TYMS staining in at least 50% of cases, and 56 included at least one case with strong positivity. TYMS positivity occurred most commonly in lymphomas (81.3–96.5%), sarcomas and sarcomatoid carcinomas (33.3–100%), malignant melanoma (70.5–90.7%), cervical adenocarcinoma (78.3%), and squamous cell carcinomas of various sites (57.1–77.9%). High TYMS expression was linked to advanced pT (p = 0.0097), high grade (p < 0.0001), ER negativity (p < 0.0001), and PR negativity (p = 0.0002) in invasive breast cancer of no special type; high grade (p < 0.0050), high UICC stage (p = 0.0060), and nodal metastasis (p = 0.0120) in clear cell renal cell carcinoma (RCC); high grade (p < 0.05) and nodal metastasis (p = 0.0045) in papillary RCC; high Gleason grade (p < 0.0001) and advanced pT stage (p = 0.0149) in prostatic adenocarcinoma; high pT (p < 0.0001), nodal metastasis (p = 0.005), lymphatic (p = 0.0064) and venous invasion (p = 0.0005), left side location (p < 0.0001), and microsatellite instability (p < 0.0001) in colorectal adenocarcinoma; and high grade (p < 0.0001) in squamous cell carcinomas of different sites. Conclusions: TYMS is often overexpressed across different cancer entities and shows associations with several adverse histopathological parameters commonly used to describe tumor phenotypes. Full article

Objective: Squamous cell carcinoma antigen (SCC-A) is a widely used biomarker for squamous cell cervical carcinoma and pretreatment elevation is associated with poor prognosis. Normalization during chemoradiation correlates with PET-CT response and survival. This study assessed the prognostic value of SCC-A normalization for biopsy-proven pathological response and survival outcomes. Materials and Methods: This retrospective single-center cohort study included patients with locally advanced or node-positive squamous cell cervical cancer treated with definitive chemoradiation at the Medical University Innsbruck between 2008 and 2023. Eligible patients had baseline SCC-A ≥ 2 ng/mL and at least two additional measurements within 42 days of treatment. SCC-A normalization was evaluated at predefined weekly time points. Associations with biopsy-assessed residual disease, PFS, and OS were assessed. Results: Of 186 screened patients, 83 met the inclusion criteria. Within 42 days, 70% achieved SCC-A normalization, with a median time of 21 days (IQR 19–32). Among predefined time points, normalization by day 28 was associated with reduced odds of residual disease (OR 0.14; 95% CI 0.04–0.44) and improved PFS (HR 0.28; 95% CI 0.12–0.63) and OS (HR 0.37; 95% CI 0.14–0.96), remaining independently significant after multivariate adjustments. Conclusions: SCC-A normalization during chemoradiation is a non-invasive independent biomarker of treatment response. Normalization within 28 days identifies patients at low risk of residual disease, progression, and death, supporting its use for early risk stratification and response monitoring for potential treatment adaptations. Full article