• Immunohistochemical profiling of PD-L1 expression in neuroendocrine carcinoma of the uterine cervix.
    2 weeks ago
    Neuroendocrine carcinoma (NEC) of the uterine cervix is a rare and aggressive malignancy for which disease-specific treatment strategies remain limited. Although immune checkpoint inhibitors (ICIs) have demonstrated activity in several cancers, PD-L1 expression in cervical NEC remains insufficiently characterized. This study descriptively evaluated PD-L1 expression patterns in cervical NEC using the PD-L1 IHC 22C3 pharmDx assay.

    Six surgically resected cervical NEC specimens from Taiwanese women treated between 2010 and 2024 were retrospectively analyzed. PD-L1 expression was assessed using the PD-L1 IHC 22C3 pharmDx assay. TPS, CPS, and IC scores were evaluated descriptively; TC was also recorded but was numerically identical to TPS in all cases and is therefore reported jointly as TPS/TC. Thresholds of TPS/TC ≥1%, CPS ≥1, and IC ≥5% were used solely for exploratory analyses and were not interpreted as validated clinical cutoffs for cervical NEC.

    Tumor-cell PD-L1 expression was uncommon, with TPS/TC ≥1% observed in one case (16.7%). CPS ≥1 and IC ≥5% were each observed in three of six cases (50%). PD-L1 staining was more frequently observed in tumor-infiltrating immune cells than in tumor cells. One case demonstrated dual-compartment staining, with CPS 25, TPS/TC 3%, and IC 30%.

    In this small cohort, PD-L1 expression was heterogeneous. Tumor-cell positivity by TPS/TC was uncommon and largely limited to a single case, whereas PD-L1 staining was more frequently observed in immune cells. CPS and IC provided complementary descriptive information on PD-L1 distribution; however, their biological relevance and predictive value remain unvalidated in cervical NEC. Larger studies integrating molecular profiling, functional immune characterization, and clinical outcome data are needed to determine the potential clinical utility of PD-L1 assessment in this rare malignancy.
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  • Serological Evaluation of Anti- FSH Antibody and Anti- LH antibody In Iraqi Women with Polycystic Ovarian Syndrome.
    2 weeks ago
    Polycystic ovarian syndrome (PCOS) is a hormonal, metabolic disorder in women of reproductive age. It can be induced by genetic, immunological, and environmental determinants. The main pathophysiology of PCOS, is hyperandrogenism, which can lead to acne, hirsutism, menstrual irregularities, as well as infertility. However, PCOS is also associated with chronic low-grade inflammation. There was little study on the autoimmunity, like anti-FSH and anti-LH antibodies, of PCOS, so the current study was designed to test the effectiveness of these antibodies on the occurrence of PCOS.

    This study aimed to compare the serum levels of anti-gonadotropin antibodies (anti-FSH, and anti-LH antibodies) between women with PCOS and healthy controls; and to evaluate their association with BMI status.

    A total of 65 patients with PCOS, and 56 healthy women (controls) were recruited. Their ages were 18-45 years. Body mass index (BMI) was computed as, (weight) divided by (height squared, (kg/m 2). Blood samples were obtained from both patients and controls during the early follicular phase (day 2-3 of the menstrual cycle) using convenience sampling from the Medical City Hospital in Baghdad and private infertility clinics. PCOS was diagnosed according to the Rotterdam criteria (2003). This study was conducted between November 2024 and January 2025. The levels of anti-FSH and anti-LH antibodies were measured by ELISA.

    The results revealed a non-significant increase in anti-FSH antibody in patients (36.22±6.73) ng/ml, compared to controls (34.99±9.78 ng/ml), and a highly significant decrease in anti-LH antibody in patients (45.29±3.04 ng/ml), as compared to controls (69.16±10.90 ng/ml), (p<0.05). The fertility hormone, FSH showed a non-significant increase in unhealthy women (8.12±0.74 mIU/ml), in contrast to healthy women (7.35±0.62 mIU/ml) (p>0.05). While the LH hormone results was, in patients with PCOS (7.61±0.73 mIU/ml), as opposed to the control group, which was (5.62±0.56 mIU/ml), the (p>0.05). Finally, the LH/FSH ratio showed a non-significant increase in both patients (1.161±0.37) and controls (0.7819±0.22) (p>0.05). There was a non-significant correlation between BMI and anti-LH or anti-FSH antibodies (p >0.05).

    Women with PCOS exhibit a significant decrease in anti-LH antibody levels along with variations in LH levels and LH/FSH ratio compared to healthy controls.
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  • Stratifying Cardiovascular Risk in Patients With HCC Receiving Atezolizumab/Bevacizumab: A Comparison of ESC and CARDIOSOR Scores.
    2 weeks ago
    The management of comorbidities has become increasingly relevant in unresectable hepatocellular carcinoma (uHCC) as immunotherapy prolongs survival. Atezolizumab plus bevacizumab (AB) is a standard first-line option, but bevacizumab carries a risk of cardiovascular toxicities. Data on cardiovascular risk stratification in patients with cirrhosis remain limited. Identifying patients at increased cardiovascular risk is therefore clinically important, particularly given the availability of bevacizumab-free alternatives.

    We retrospectively analysed prospectively collected data from the multicenter Italian ARTE database, including patients with uHCC treated with first-line AB between June 2022 and July 2025. Traditional major adverse cardiovascular events (tMACE) were defined as acute coronary syndromes, heart failure, cerebrovascular events, or peripheral ischemia, while an extended composite (eMACE) additionally included venous thromboembolism and immune-related myocarditis. Cardiovascular risk was stratified using the European Society of Cardiology (ESC) Cardio-Oncology classification and the CARDIOSOR score. Competing-risk analyses were performed considering treatment discontinuation as a competing event.

    This study included 538 patients (median age 69.8 years). During follow-up, 20 patients (3.7%) experienced tMACE, and 30 (5.6%) experienced eMACE. Patients assigned to the very high-risk category by ESC criteria and those with a high-risk CARDIOSOR score had a significantly increased risk of tMACE and eMACE. Both scores demonstrated a moderate ability to stratify cardiovascular risk (Harrell's c-index 0.68 for ESC and 0.59 for CARDIOSOR).

    Cardiovascular adverse events were uncommon overall, but their incidence was not negligible in patients in high-risk subgroups. Risk scores may help identify vulnerable subgroups and support patient-tailored treatment strategies, including consideration of bevacizumab-free regimens in selected cases.

    Multicenter ARTE database (NCT06806579).
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  • Assessment of Selected Immunophenotypic Markers in Childhood Non-Hodgkin's Lymphomas in Ghana: A Possible Tool for Effective Stratification of Patients and Assessment of Survival Outcomes.
    2 weeks ago
    Non-Hodgkin lymphomas (NHL) represent a heterogeneous group of malignancies with varying molecular and immunophenotypic characteristics. In Ghana, NHL is the third most common childhood cancer, highlighting the need for precise diagnostic approaches to improve survival rates. The identification of immunophenotypic biomarkers expressed by both healthy and neoplastic cells of the immune systems has been shown to provide information on the diagnostic and prognostic characterization of tumors leading to personalized treatment of NHL. We evaluated the immunophenotypic profiles of pediatric NHL and their correlation with survival outcomes.

    This study aimed to evaluate the immunophenotypic characteristics of three subtypes of non-Hodgkin lymphoma (NHL) and their associated survival outcomes among children diagnosed at Komfo Anokye Teaching Hospital, Kumasi.

    In this retrospective study, 38 NHL patients were recruited from the Komfo Anokye Teaching Hospital from 2018 to 2022. Clinico-pathological characteristics and treatment outcome were obtained in patients' folders. Formalin fixed paraffin embedded tissues were histologically examined and immunohistochemistry performed using monoclonal antibodies targeting CD3, CD25 and BCL-2. The Kaplan-Meier method was used to obtain survival curves and compared by the log-rank test. Statistical analysis was performed using SPSS (version 26.0) and XLSTAT.

    Females accounted for 55.3% of cases, with most patients being under 10 years. Within the first-year post-diagnosis, 30.6% of children died, and 27.8% abandoned treatment. BCL-2 was the most frequently expressed marker (55.3%), with co-expression observed across all lymphoma types and age groups. Survival analysis was performed on 21/38 participants with complete follow-up data. The median survival time was 22 months (95% CI: 3.96-40.11), with survival rates declining from 76% at 10 months to 20% at 40 months. Factors significantly associated with poor survival included BCL-2 expression (poorer survival) and extranodal spread (p < 0.05).

    The survival rate for NHL patients in Ghana is very low. BCL-2 was the most expressed marker, significantly influencing survival outcomes. The extent of tumor spread also influenced survival outcomes. Identifying prognostic factors for early diagnosis and treatment is essential to improving survival outcomes for NHL patients in this setting.
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  • Lifestyle Behaviors and Physical Health in Canadian Childhood, Adolescent, and Young Adult Cancer Survivors.
    2 weeks ago
    With this study, we aimed to investigate the longitudinal relationships between lifestyle behaviors and physical health in childhood, adolescent, or young adult (CAYA) cancer survivors attending the Long-Term Survivor's Clinic (LTSC) in Calgary, Canada.

    Survivors attended the LTSC once or twice a year and completed a questionnaire at each visit. Among survivors of any cancer diagnosis who were aged ≥ 11 years at the time of assessment, physical health was captured using two outcomes: the number of self-reported physical health problems and the number of physical health-related medications used. Self-reported lifestyle behaviors, including physical activity, alcohol, tobacco, and cannabis use, and sleep quality were scored as healthy (1) or unhealthy (0), and combined into a sum score ranging from 0 to 5. Multivariable, generalized linear mixed models (GLMM) were estimated to assess the association between lifestyle behaviors (sum score and individual behaviors) and physical health outcomes, irrespective of time. To address our second research question, cross-lagged GLMMs, incorporating a time component, were estimated to assess directionality between lifestyle sum score and the number of physical health problems.

    In total, 766 responses from 312 CAYA cancer survivors (median age at follow-up 23.8 years; 49% male; 37% diagnosed with leukemia) were included. A healthier lifestyle sum score and sufficient physical activity were associated with fewer physical health problems (estimate -0.15, SE 0.06, p-value 0.02 and estimate -0.23, SE 0.11, p-value 0.04, respectively). No significant associations were found between lifestyle and the number of medications used. Lifestyle behaviors at an earlier time did not predict better physical health at a later time and vice versa.

    Findings confirm an association between a healthy lifestyle and fewer physical health problems. Additional studies are warranted to further elucidate directional pathways between a survivor's lifestyle and physical health.
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  • Next-Generation Sequencing-Based Molecular Profiling and Management of Advanced Solid Tumors: A Real-World Experience in a Community-Based Academic Cancer Center.
    2 weeks ago
    Advances in molecular and cell biology have led to a paradigm shift in cancer management. We implemented next-generation sequencing (NGS) at our community-based academic cancer center over a decade ago. We sought to optimize the use of genomics and understand its impact in identifying actionable genomic alterations to determine therapy options in patients with advanced solid tumors for whom standard therapies had been exhausted.

    Through a prospective non-randomized trial, patients with advanced solid tumors who had exhausted standard therapies and who did not qualify for routine guideline-concordant NGS at the time of the study (the study excluded at least Stage 1B lung and Stage IV colorectal cancers) underwent in-house NGS on tumor specimens to identify actionable alterations, and pharmacogenomic testing. Our in-house-developed/integrated bioinformatics pipeline (Flype) was used for structured reporting and served as a molecular knowledgebase. Patients were presented at a multidisciplinary molecular tumor board.

    251 patients underwent somatic tissue NGS. 173 patients (68.9%) had alterations targetable with FDA-approved or currently investigational drugs. 75 patients (29.9%) had alteration(s) qualifying them for FDA-approved drug(s) for their tumor type. An additional 61 patients (24.3%) had alterations qualifying them for "off-label" use of FDA-approved drugs. 40 patients (15.9%) qualified for tumor-agnostic therapies. Of the 224 patients (89.2%) who had RNA analysis, eight (3.6%) had targetable fusions. Of the 33 patients (19.1%) who received NGS-guided targeted therapies, 19 (57.6%) were on treatment for longer than three months. 255 patients underwent pharmacogenomics testing, with over 40% having an alteration in typical response to opioids or antidepressants.

    In this real-world study, 54.2% of patients with advanced solid tumors were identified as candidates for FDA-approved therapies (on- or off-label), supporting the utility of in-house NGS in providing genomics-guided care for patients.
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  • Introducing a novel prediction index for treatment quality of gamma knife and stereotactic-based radiotherapy: Nabaa Efficiency Index ( η Nabaa ).
    2 weeks ago
    An accurate assessment of the radiotherapy plans requires an accurate dose to the target and efficient confinement of the doses. However, present indices do not completely cover these aspects in a single framework.

    To develop a unified, dimensionless metric that integrates geometric conformity and dosimetric efficiency for evaluating stereotactic and fractionated radiotherapy plans aims to reduce QA workload by providing a rapid, quantitative estimate of plan acceptability, allowing early prediction of treatment plan performance.

    In this study, the Nabaa Efficiency Index η N a b a a is introduced and defined as the product of the Conformity Index (CI) and a Dose-Efficiency Ratio (DER), evaluated at 50% and 90% isodose levels ( η 50 % N a b a a , η 90 % N a b a a ). We analyzed theoretical behavior against normalized dose-volume ratios and compared η N a b a a with established indices of conformity, homogeneity, and the Paddick efficiency index ( η 50 % P a d d i c k ) . Clinical validation used 100 plans (50 Gamma Knife, 50 VMAT-SRS). Statistics included ANOVA, correlations, ROC/AUC, and decision-curve analysis.

    η 50 % N a b a a and η 90 % N a b a a were monotonic, bounded, and dimensionless. η 50 % N a b a a distinguished gradient/halo efficiency between stereotactic and linac plans (p < 0.001). η 90 % N a b a a most strongly reflected prescription-dose conformity (pooled AUC = 0.94) and outperformed the Paddick Efficiency Index ( η 50 % P a d d i c k ) in discrimination and interpretability.

    η N a b a a unifies geometric and dosimetric assessment across modalities. Its simplicity, physical interpretability, and software-ready formulation support integration into automated QA and treatment-planning pipelines.
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  • Evaluation of registration accuracy using short-arc cone-beam computed tomography for image-guided radiotherapy in breast cancer.
    2 weeks ago
    Image-guided radiotherapy (IGRT) using cone-beam computed tomography (CBCT) enables highly accurate imaging registration; however, increased radiation exposure remains a concern. Recently, short-arc CBCT (SA-CBCT), which reduces projection data and reconstructs images, has become available. Although previous studies have shown that image quality deteriorates when projection data are reduced, no study has directly evaluated the clinical usefulness of SA-CBCT or its effect on registration accuracy.

    We verified the registration accuracy of SA-CBCT in breast tangential irradiation using an anthropomorphic phantom and clinical data, and examined its clinical feasibility compared with the commonly used 200° scan.

    An anthropomorphic phantom was placed on the treatment bed, and CT and CBCT images acquired during treatment planning were aligned. Bed movement was measured for both conventional CBCT and SA-CBCT images. The difference between the two measurements was quantified as N, defined as the norm of the vector difference between CBCT and SA-CBCT registration shifts, to evaluate registration accuracy. The acquisition angle was varied to assess the effects of central and total angles. In the clinical study, registration data from 30 consecutive patients who underwent whole-breast irradiation were analyzed. Data were reconstructed by changing the acquisition angle from 200° to 120°, and N was calculated as in the phantom experiment.

    In the phantom experiment, N was within 0.15 mm (3-axis) and 0.55 mm (6-axis) when the acquisition angle was reduced to 120°. In clinical data, the average N was 0.64 mm in 3-axis registration (84.7% within 1 mm) and 0.85 mm in 6-axis registration (71.3% within 1 mm). Even with a 120° acquisition angle, the body contour and chest wall edges were sufficiently preserved.

    SA-CBCT maintained adequate registration accuracy in breast tangential irradiation. These findings suggest its clinical applicability with appropriate acquisition angle settings.
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  • Incidence, Clinical Characteristics, Management, and Outcomes of Hematologic Immune-Related Adverse Events Associated With Immune Checkpoint Inhibitors: A Single-Center Japanese Retrospective Cohort Study.
    2 weeks ago
    Immune-related adverse events (irAEs) are complications associated with immune checkpoint inhibitors (ICIs). Hematologic irAEs (heme-irAEs) are rare but potentially serious and may interfere with cancer treatment. However, their clinical characteristics remain insufficiently described.

    We conducted a single-center retrospective study using the National Cancer Center Hospital East medical database from April 1, 2014, to March 31, 2024. Potential heme-irAE cases were identified using diagnostic name searches, bone marrow examination records, and positive DAT results and were followed by chart review to exclude alternative etiologies, such as chemotherapy-related myelosuppression, marrow involvement, infection, and hematologic malignancy.

    Of the 3371 patients treated with ICI-containing regimens, 40 patients developed heme-irAEs, indicating an observed incidence of 1.2%. The most common heme-irAE reported was immune thrombocytopenia, and 85.0% of these events were Grade 3 or higher. The median time from ICI initiation to heme-irAE onset was 12 weeks. For all affected patients included in the regimen-specific onset-time comparison, the median time to heme-irAE onset appeared shorter with dual ICI therapy without chemotherapy than with ICI monotherapy, although this descriptive comparison was based on a small number of cases. ICI-containing regimens were interrupted or discontinued in most patients, and systemic corticosteroids were administered to 25 patients, 18 of whom achieved hematologic improvement. Cancer treatment was resumed or continued for 20 patients, with no recurrent heme-irAEs observed during the follow-up period. In an exploratory landmark analysis, hematologic response was associated with longer survival after heme-irAE onset.

    Heme-irAEs were rare but frequently severe in this Japanese single-center cohort. Their occurrence was associated with prolonged interruption of cancer treatment, underscoring the importance of early recognition, careful diagnostic evaluation, and multidisciplinary management of heme-irAEs. Our findings regarding dual ICI therapy, survival, and subsequent ICI therapy after heme-irAE onset should be interpreted as exploratory.
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  • Age-Dependent Patterns of Cisplatin-Induced Ototoxicity in Head and Neck Cancer: A Longitudinal Audiologic Analysis.
    2 weeks ago
    Cisplatin (CDDP) is a key chemotherapeutic agent used to treat head and neck cancer. Improved survival rates have increased concerns about CDDP-induced ototoxicity, as this toxicity significantly impacts survivors' quality of life. However, the dose-dependent and age-related patterns of CDDP-induced ototoxicity remain incompletely defined. Therefore, in this study, we aimed to characterize CDDP-induced ototoxicity by tracking longitudinal hearing data and evaluating the associated factors.

    We retrospectively analyzed a cohort of 316 patients with head and neck cancer who received CDDP-based chemotherapy at a tertiary cancer center between January 2009 and June 2023. Hearing function was longitudinally assessed using pure-tone audiometry (PTA) and distortion product otoacoustic emissions (DPOAE) across the cumulative CDDP dose. Multivariate logistic regression analyses were performed to identify the factors associated with ototoxicity, including the cumulative dose, age, radiotherapy, and the primary tumor site.

    At baseline, older patients exhibited substantially impaired high-frequency hearing compared with younger patients. Across all age groups, hearing deteriorated in a dose-dependent manner following CDDP exposure. However, despite smaller apparent longitudinal threshold shifts, older patients developed clinically relevant PTA-defined ototoxicity at lower cumulative CDDP doses than younger patients, reflecting limited auditory reserve. Contrastingly, larger threshold shifts observed in younger patients reflected greater measurable dynamic range from preserved baseline hearing rather than an increased vulnerability. DPOAE changes were attenuated in older patients, suggesting that DPOAE had reduced sensitivity for detecting CDDP-induced ototoxicity in the presence of pre-existing cochlear damage.

    CDDP-induced ototoxicity shows distinct age-dependent patterns, with older patients experiencing clinically significant hearing impairment at lower cumulative doses despite smaller longitudinal changes. These findings highlight the need for age-adapted monitoring strategies and cumulative dose-conscious treatment planning to preserve auditory function in cancer survivors.
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