Uterine Cancer Research Articles

Navigating the thyroid-gynecologic interplay: a systematic review and meta-analysis thyroid-gynecologic interaction.

Thyroid disorders are considered to be linked to various health issues, including gynecologic cancers. Studying this association is crucial in clinical practice. This approach was applied through searches in Scopus, WOS, PubMed, and Google Scholar. A Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist was followed. The quality assessment was checked. The meta-analyses were performed using R-4.3.2 (COMPANY, CITY, STATE, COUNTRY) and SPSS version 28 (COMPANY, CITY, STATE, COUNTRY). The results demonstrated that 19 studies investigated the association between thyroid disorders and gynecologic cancers in adult females. The studies were categorized into two groups: group 1 examined thyroid status in various gynecologic cancers, while group 2 comprised case-control studies examining gynecologic cancer incidence in females with thyroid disorders compared to control. Among females with gynecologic cancers, 13% (95% confidence interval [CI], 10-17%) had hypothyroidism. When comparing hypothyroidism and hyperthyroidism across studies, the overall percentage for hypothyroidism was 14% (95% CI, 9-22%), while for hyperthyroidism, it was 3% (95% CI, 2-5%). The odds ratio for hypothyroidism in females with uterine cancer was 2.65 (P<0.05). Additionally, hypothyroidism showed a significant risk ratio of 1.3 (P<0.05) for different gynecologic cancers. However, hyperthyroidism was significantly associated with increased ovarian cancer mortality (RR, 2.14; P=0.03); conversely, hypothyroidism showed no significant relationship (RR, 1.35; P=0.26). The findings concluded that hypothyroidism is significantly associated with various gynecologic cancers, suggesting a potential role in its pathogenesis. Conversely, hyperthyroidism is linked to an increased risk of ovarian cancer mortality. Further research is needed to clarify whether hyperthyroidism predisposes females to ovarian cancer.

Study on the expression and prognostic relationship of MYL6B in liver cancer based on bioinformatics.

Primary liver cancer is a prevalent and deadly cancer type. Despite treatment advances, prognosis remains poor, with high recurrence rates. Early detection is crucial but challenging due to the disease's insidious nature. Myosin proteins play significant roles in cancer development, influencing cell migration, invasion, and tumor suppression. MYL6B, a myosin light chain, is involved in various cellular processes and has been associated with poor prognosis in colorectal adenocarcinoma and potential as a biomarker in breast cancer. To investigate the expression of MYL6B in liver hepatocellular carcinoma (LIHC) and its impact on prognosis and potential mechanisms of action using bioinformatics methods. The expression of MYL6B in pan-cancer and normal tissues was analyzed using the gene expression profiling interactive analysis 2 and tumor immune estimation resource databases. The expression level of MYL6B in LIHC tissues and its relationship with prognosis were analyzed, immunohistochemical analysis of MYL6B and its effect on immune cell infiltration, and the protein network were further studied. MYL6B was highly expressed in diffuse large b-cell lymphoma, LIHC, pancreatic adenocarcinoma, skin cutaneous melanoma, thymoma, uterine corpus endometrial carcinoma, uterine carcinosarcoma, and lowly expressed in kidney chromophobe, acute myeloid leukemia, testicular germ cell tumors. The expression level of MYL6B was significantly different between cancer and normal tissues. It had a significant impact on both overall survival and disease-free survival. MYL6B is highly expressed in hepatocellular carcinoma and its expression level increases with cancer progression. High MYL6B expression is associated with poor prognosis in terms of overall survival and recurrence-free survival. The immunohistochemical level of MYL6B is high in hepatocellular carcinoma tissues, and MYL6B has a high level of immune infiltration inflammation. In protein network analysis, MYL6B is correlated with MYL2, MYL6, MYL9, MYLK4, MYLK2, MYL12A, MYL12B, MYH11, MYH9 and MYH10. The expression level of MYL6B in LIHC was significantly higher than in normal liver tissues, and it was correlated with the degree of differentiation survival rate, and immune infiltration. MYL6B is a potential target for LIHC treatment.

Abstract C139: Cancer related excess death and potential life years lost among Black Americans

Abstract Introduction: Cancer represents the second leading cause of death in the United States and disproportionately affects Black Americans. In recent years, cancer-related mortality rates have declined for both Black and White Americans. However, mortality rates and rate ratios alone are insufficient for characterizing the burden of cancer disparities between racial groups. Among the most prevalent cancers in the US, we evaluated trends in excess mortality and years of potential life lost between Black and White Americans. Methods: This was a serial cross-sectional study using US national level data from CDC Wonder between the years 1999-2020. We included White and non-Hispanic Black Americans with a cause of death from breast, prostate, lung, colon, bladder, or uterine cancer. We measured age-adjusted excess death as well as excess years of potential life lost for each cancer site among Black and White Americans, stratified by sex when applicable. Annual mortality rates for each cancer site were sourced from the CDC Cancer Statistic Data Visualization tool. Results: The age adjusted mortality rate for all cancers declined between 1999-2020 for Black (257.2 to 166.8 per 100,000) and White Americans (200.9 to 149.3 per 100,000). Site specific cancer mortality rates declined in Black and White Americans for breast, prostate, lung, colon, and bladder cancer, but increased for uterine cancer. Among the most prevalent cancer sites, there were a total of 115,43 excess deaths with 2,093,327 excess years potential life lost for Black men and 59,134 excess deaths with 1,508,052 excess years potential life lost for Black women over a 22-year period. The trend of annual excess death and years potential life lost has slowly increased for Black men with colon cancer as well as Black women with breast and uterine cancer. Annual excess death and years potential life lost in Black men with prostate cancer decreased until 2013 after which it has slowly increased. Conclusion: Despite declining mortality rates in most cancers in the United States, Black Americans still experience a staggering number of excess deaths and years potential life lost due to cancer. Furthermore, the discordance between declining mortality rates and increasing excess death or years potential life lost in breast, prostate, colon, and uterine cancer highlight that racial disparities in cancer care and outcomes are likely worsening among Black Americans. Action is needed to support interventions and organizations committed to addressing cancer health inequities among Black Americans. Citation Format: Daniel S. Carson, Navya Gunaje, Sarah K. Holt, Nana Frimpong, Jenney R. Lee, Liz Sage, Erika M Wolff, Yaw A. Nyame. Cancer related excess death and potential life years lost among Black Americans [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr C139.

Abstract C144: Poor survival in non-Hispanic Black HR+/HER2- and HR-/HER2+ breast cancer patients at an NCI-Designated Comprehensive Cancer Center

Abstract Introduction: In the US, 1 in 8 women face a breast cancer diagnosis within their lifetime. While this disease is pervasive, it does not affect all groups of women equally. Non-Hispanic Black (NHB) populations tend to have worse survival outcomes than Non-Hispanic White (NHW) and Hispanic (H) populations. Studying this disparity presents challenges, as it is influenced by many social and biological factors, including quality of cancer care. By comparing NHB, NHW, and H breast cancer patients at Moffitt Cancer Center (MCC), we can describe various factors related to disparate outcomes, while attenuating the effect of varying cancer care settings. Methods: Clinical data (collected from 1986-2018) and patient questionnaire data (collected from 2012-2020) were acquired from MCC databases. Patients were divided into NHW, NHB, and H groups based on their race and ethnicity. Family cancer history, hormonal contraception use, and HR/HER2 subtype were selected for analysis due to their relevance to breast cancer risk or prognosis. Descriptive statistics, chi-square tests, ANOVA, and Tukey tests were performed as appropriate. Results: On preliminary analysis, NHW patients most frequently report a history of cancer diagnosis in one or more first-degree relatives. This is found when considering all cancer types (p&amp;lt;0.001) as well as specifically considering breast, ovarian, and uterine cancer (p=0.029). Patients also disclosed their hormonal contraception use, with 38% of NHW patients reporting an age at which they began using hormonal contraception compared to only 22% of both NHB and H patients (p&amp;lt;0.001). Among those who have used hormonal contraception, there was no significant difference in age of use onset, or total years of use. Significant differences in HR+/HER2-(p&amp;lt;0.001) and HR-/HER2- (p&amp;lt;0.001) frequency were seen between groups. NHB women had the lowest frequency of HR+/HER2- cancers (57%), and the highest frequency of HR-/HER2- cancers (27%). HR-/HER2+ NHB patients displayed significantly worse overall survival relative to NHW (p&amp;lt;0.001) and H (p=0.014) patients of the same subtype. HR+/HER2-NHB patients also have significantly worse overall survival relative to NHW (p=0.010) and H (p=0.010) patients of the same subtype. No significant difference in between-group overall survival is found for the HR-/HER2- and HR+/HER2+ patients. Conclusion: The cohorts in this study provide an opportunity to analyze characteristics and outcomes in breast cancer patients at an NCI-Designated Comprehensive Cancer Center. Higher rates of family cancer history in NHW women and higher rates of HR-/HER2- disease in NHB women align with the literature. NHW patients more frequently reported hormonal contraception use, while showing similarities to NHB and H groups in age and length of use. Despite comparable survival in two HR/HER2 subtypes, HR-/HER2+ and HR+/HER2- NHB women have significantly worse survival than NHW and H women. Further analyses of risk/prognostic factors and treatment regimens are needed to better understand this concerning survival finding. Citation Format: Abigail E. Lantz, Jiannong Li, Ryan F. Gebert, Dung-Tsa Chen, Edna R. Gordián, W. Douglas Cress. Poor survival in non-Hispanic Black HR+/HER2- and HR-/HER2+ breast cancer patients at an NCI-Designated Comprehensive Cancer Center [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr C144.

Abstract C083: Meta-analysis reveals differences in somatic alterations by genetic ancestry across common cancers

Abstract Genetic similarity of populations (or genetic ancestry) contributes to cancer driving alterations. We performed a meta-analysis leveraging two real-world cohorts of targeted gene panel sequencing, comprising 275,605 tumor samples, to investigate ancestry-associated somatic alterations across 14 common cancers. We focused on five continental ancestries – European (EUR), African (AFR), East Asian (EAS), South Asian (SAS), and admixed American (AMR). Genetic ancestry was inferred using single nucleotide polymorphism markers from captured regions of gene panel sequencing in each cohort. The combined cohort from Memorial Sloan Kettering – Integrated Mutation Profiling of Actionable Cancer Targets (MSK-IMPACT) and Foundation Medicine (FMI) contains a substantial number (45,131) of non-EUR samples. Within each cohort, we performed multivariate logistic regression to test association of each cancer gene alteration with proportion of genetic ancestry as a continuous variable, controlling for relevant covariates (age, sex, gene panel version, and histological subtypes) for every combination of ancestry and cancer type. Our analysis focused on oncogenic or likely oncogenic alterations spanning mutations, copy number alterations, and structural rearrangements for each gene. We then aggregated the logistic regression results from the two cohorts using a fixed effects model of meta-analysis weighted by cohort sample size. We found 444 significant associations involving 116 unique genes with consistent logistic regression coefficients between cohorts and False Discovery Rate (FDR)-adjusted p-value &amp;lt; 0.1. These genes were involved in cancer-specific and cross-cancer associations. TP53, KRAS, and TERT were the top three recurrent ancestry-associated genes respectively. TERT promoter mutations were depleted in patients of AFR or EAS ancestry, but enriched in EUR ancestry in bladder urothelial carcinoma, glioblastoma, cutaneous melanoma, and hepatocellular carcinoma. Additionally, TP53 mutations were enriched in AFR and EAS ancestry across multiple cancers, consistent with previous reports, but depleted in prostate cancer in both AFR and EAS ancestries. Among the novel cancer-specific associations with FDA-approved targeted therapies, we found that CDK12 mutations in prostate adenocarcinoma were enriched in EAS ancestry while ERBB2 mutations in lung adenocarcinoma were enriched in AMR ancestry. We also found novel potential drug targets/biomarkers associated with AFR ancestry, such as enrichment of BAP1 mutations in head and neck squamous cell carcinoma and depletion of FGFR2 mutations in uterine endometrioid carcinoma. Overall, our work identified ancestry-associated somatic alteration differences of cancer genes in a combined cohort with a large number of non-European samples. This work underscores the value of studying under-represented populations to replicate or reveal new potential targets for precision oncology. Citation Format: Setor Amuzu, Amy Xie, Xuechun Bai, Kelly R. Pekala, David Ma, Tomin Perea-Chamblee, Kanika Aurora, Garrett Frampton, Michael Berger, Nikolaus Schultz, Justin Y. Newberg, Jian Carrot-Zhang. Meta-analysis reveals differences in somatic alterations by genetic ancestry across common cancers [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr C083.

Abstract A081: Comprehensive examination of disparities in cancer incidences by race, gender, and age over 65 years in Alabama's Black belt counties, USA

Abstract In the United States, significant disparities persist in cancer incidence, mortality, and treatment outcomes, particularly among Black populations. Despite advances in medical care, disparities continue to challenge efforts to achieve health equity. Understanding and addressing these complex issues are imperative to ensure that all individuals, regardless of race or ethnicity, have equal access to effective cancer prevention, diagnosis, and treatment. Alabama stands out as the leading state among the top ten in terms of densely populated Black Belt counties in the United States. With 67 counties in total, Alabama is home to 24 designated Black Belt counties. Given this concentration, Alabama becomes a key focus for comprehending cancer disparities. The ongoing research seeks to examine the occurrence of various types of cancer among the predominant racial groups in the United States, focusing particularly on the Black Belt counties of Alabama. Data on cancer occurrences, obtained from the database of National Cancer Institute (NIH) and the Centers for Disease Control and Prevention (CDC), offer insights into cancer incidences among various demographic groups, age categories, and specific types of cancer spanning the last five years (2016-2020). Analysis of the data, focusing on patients aged 65 years and older, was performed using GraphPad Prism 5 software. Graphs were created to visually represent and interpret the data regarding incidences per 100,000 populations. We observe significantly elevated incidences of major cancer types such as prostate, colon, lung, stomach, pancreas, and liver among Black males, and similarly heightened rates of uterus, cervix, stomach, pancreas, and kidney cancers among Black females, when compared to white populations. Notably, within Alabama's Black Belt regions, only a small number of counties have reported incidences of cancer regardless of gender and cancer types, except for prostate cancer in males and breast cancer in females. Moreover, in certain Black Belt counties, rates of colon and lung cancer (in both males and females), as well as prostate cancer in males and breast cancer in females, are exceptionally elevated compared to both the statewide average in Alabama and even the national average in the United States. Generally, females tend to have lower rates of cancer across various types compared to males. In conclusion, factors contributing to these disparities include genetic predispositions, socioeconomic status, healthcare accessibility, systemic biases, and cultural influences. Further investigations, including molecular screening studies, are imperative to corroborate these health disparities and foster community-wide cancer awareness and public health initiatives. Citation Format: Faith Onomeh, Anathbandhu Chaudhuri. Comprehensive examination of disparities in cancer incidences by race, gender, and age over 65 years in Alabama's Black belt counties, USA [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr A081.

Successful outcome achieved with adjuvant chemotherapy with irinotecan plus cisplatin in rectal neuroendocrine carcinoma: a case report

BackgroundRectal neuroendocrine carcinomas (NECs) are rare and associated with poorer prognoses compared to conventional adenocarcinomas. The efficacy of adjuvant chemotherapy for resectable rectal NECs remains uncertain. Herein, we present a case of rectal NEC successfully treated with postoperative chemotherapy using irinotecan plus cisplatin.Case presentationA 48-year-old woman with a history of endometrial cancer presented with an intramural rectal tumour detected on follow-up imaging. Colonoscopy revealed a 30 mm submucosal tumour, and laparoscopic low anterior resection was performed. Histopathological examination showed poorly differentiated atypical cells with solid growth patterns. Metastasis from the uterine cancer was ruled out due to histological differences between the primary uterine tumour and the rectal lesion, as well as the absence of hormone receptor immunohistochemical expression. Further immunohistochemical analysis revealed diffuse CD56 positivity, a high mitotic rate (> 20/10 high power fields) and a Ki-67 labelling index exceeding 70%. Based on these findings, a diagnosis of rectal NEC, T3N0M0, Stage IIB (UICC 8th edition), was established. Given the aggressive nature of the tumour evidenced by a high Ki-67 labelling index, adjuvant chemotherapy comprising six cycles of irinotecan plus cisplatin was administered to mitigate the risk of recurrence. At the 3-year follow-up, the patient was free of disease recurrence.ConclusionThis case highlights the importance of multidisciplinary surgical interventions followed by adjuvant chemotherapy in managing rectal NECs.

A case of grade1 follicular lymphoma diagnosed by laparoscopic lymph node resection: differentiating from late lymph node recurrence of endometrial cancer.

Follicular lymphoma is a common hematologic malignancy; however, it is less common among all malignant diseases and is difficult to suspect in advance due to the lack of specific clinical findings. Here, we report a case in which a late recurrence of corpus cancer was first suspected and finally diagnosed as follicular lymphoma. A 67-year-old female presented to our department with enlarged pelvic lymph nodes. She was diagnosed with breast cancer (HER2-posiotive with lymph node metastasis) and corpus cancer (endometrioid carcinoma grade 2, stage IA) 16years prior, received definitive therapy and was followed up. A positron emission tomography scan was performed, and an accumulation of 18F-fluorodeoxyglucose (FDG) was detected in multiple lymph nodes, including the lymph nodes with no change in size or enlargement. We performed laparoscopic resection of the enlarged and FDG-accumulated lymph nodes and a pathological examination. The patient was diagnosed with follicular lymphoma (FL) grade 1 and is currently under observation at the Department of Hematology. FL can be considered when there is a discrepancy between the change in lymph node size and the degree of FDG accumulation. A pathological examination is useful for accurate diagnosis. Therefore, it is important to consider tissue collection; however, care must be taken to minimize the invasiveness of the procedure for the patient.

Cardiac metastasis in uterine cervical cancer : Asystematic review and case study.

Cardiac metastasis from cervical cancer is rare and only scarcely documented. We aim to present anew case and systematically summarize the available literature. PubMed, Scopus, Web of Science, Central, and ClinicalTrials.gov were systematically searched following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) criteria. Results were screened via title, abstract, and full text. Additionally, the reference lists of all papers chosen for the review were screened. Eighty-one papers were identified, describing 86cases in total. Cardiac metastasis occurred at all stages of cervical cancer and in all age groups. Median time from initial diagnosis to diagnosis of cardiac metastasis was 12months. Patients mainly complained of dyspnea and chest pain, 60.8% had pathologic ECG (electrocardiographic) findings. The cardiac mass was most frequently detected by transthoracic echography. The most common tumor histology was squamous cell carcinoma. Chemotherapy and surgical interventions were the main treatment modalities. Median survival after diagnosis of cardiac metastasis was 3months. This largest review on cardiac metastases from cervical cancer confirmed the heart as avery infrequent site of metastasis. There are < 100 cases described in the literature, with very poor prognosis and undefined clinical management.

Unlocking the Door for Precision Medicine in Rare Conditions: Structural and Functional Consequences of Missense ACVR1 Variants.

Rare diseases and conditions have thus far received relatively less attention in the field of precision/personalized medicine than common chronic diseases. There is a dire need for orphan drug discovery and therapeutics in ways that are informed by the precision/personalized medicine scholarship. Moreover, people with rare conditions, when considered collectively across diseases worldwide, impact many communities. In this overarching context, Activin A Receptor Type 1 (ACVR1) is a transmembrane kinase from the transforming growth factor-β superfamily and plays a critical role in modulating the bone morphogenetic protein signaling. Missense variants of the ACVR1 gene result in modifications in structure and function and, by extension, abnormalities and have been predominantly linked with two rare conditions: fibrodysplasia ossificans progressiva and diffuse intrinsic pontine glioma. We report here an extensive bioinformatic analyses assessing the pool of 50,951 variants and forecast seven highly destabilizing mutations (R206H, G356D, R258S, G328W, G328E, R375P, and R202I) that can significantly alter the structure and function of the native protein. Protein-protein interaction and ConSurf analyses revealed the crucial interactions and localization of highly deleterious mutations in highly conserved domains that may impact the binding and functioning of the protein. cBioPortal, CanSAR Black, and existing literature affirmed the association of these destabilizing mutations with posterior fossa ependymoma, uterine corpus carcinoma, and pediatric brain cancer. The current findings suggest these deleterious nonsynonymous single nucleotide polymorphisms as potential candidates for future functional annotations and validations associated with rare conditions, further aiding the development of precision medicine in rare diseases.

Reliable estrogen-related prognostic signature for uterine corpus endometrial carcinoma

BackgroundUterine corpus endometrial carcinoma (UCEC) is a predominant gynecological malignancy worldwide. Overdosed estrogen exposure has been widely known as a crucial risk factor for UCEC patients. The purpose of this work is to explore crucial estrogen-related genes (ERGs) in UCEC. MethodsUCEC scRNA-seq data, bulk RNA data, and ERGs were obtained from GEO, TCGA, and Molecular Signature Database, respectively. Differential expression analysis and cross analysis determined the candidate genes, and optimal genes in risk score were obtained after univariate Cox regression analysis, LASSO Cox regression analysis, and multivariate Cox regression analysis. The functional information was revealed by GO, KEGG, and GSVA enrichment analyses. CCK8 assay was used to detect the drug sensitivity. ResultsAfter cross analysis of the differentially expressed genes and the 8734 ERGs, 86 differentially expressed ERGs were identified in UCEC, which were significantly enriched in some immune related pathways and microbiota related pathways. Of them, the most optimal 8 ERGs were obtained to build prognostic risk score, including GAL, PHGDH, SLC7A2, HNMT, CLU, AREG, MACC1, and HMGA1. The risk score could reliably predict patient prognosis, and high-risk patients had worse prognosis. Higher HMGA1 gene expression exhibited higher sensitivity to Osimertinib. ConclusionsPredictive risk score based on 8 ERGs exhibited excellent prognostic value in UCEC patients, and high-risk patients had inferior survival. UCEC patients with distinct prognoses showed different tumor immune microenvironment.

Sialylation-associated long non-coding RNA signature predicts the prognosis, tumor microenvironment, and immunotherapy and chemotherapy options in uterine corpus endometrial carcinoma

BackgroundSialylation in uterine corpus endometrial carcinoma (UCEC) differs significantly from apoptotic and ferroptosis pathways. It plays a crucial role in cancer progression and immune response modulation. Exploring how sialylation affects tumor behavior and its link with long non-coding RNAs (lncRNAs) may provide new insights into UCEC prognosis and treatment.MethodsWe obtained RNA transcriptome, clinical, and mutation data of UCEC samples from the TCGA database. Our approach involved developing a risk model based on the co-expression patterns of sialylation genes and lncRNAs. Prognostic lncRNAs were identified through Cox regression and further refined using LASSO analysis. To understand the biological functions and pathways of model-associated differentially expressed genes (MADEGs), we conducted enrichment analyses. We also assessed the immune infiltration status of MADEGs using eight different algorithms, which helped in evaluating the potential for immunotherapy. Additionally, we validated the expression of these lncRNAs in UCEC using cell lines and clinical samples.ResultsWe developed a UCEC risk model using five sialylation-related lncRNAs (AC004884.2, AC026202.2, LINC01579, LINC00942, SLC16A1-AS1). This model, confirmed through Cox analysis and clinical evaluation, effectively predicted patient outcomes. Survival data analysis across entire cohort, as well as within training and test groups, indicated better survival in low-risk UCEC patients. Enrichment analyses linked MADEGs to sialylation functions and cancer pathways. High-risk patients showed increased responsiveness to immune checkpoint inhibitors (ICIs), as indicated by immunological assessments. Subgroup C2 patients showed superior outcomes and a robust response to immunotherapy and chemotherapy. Notably, LINC01579, LINC00942, and SLC16A1-AS1 were significantly overexpressed in UCEC clinical tumor samples as well as in Ishikawa and HEC-1-B cell lines, compared to the normal groups.ConclusionsThis lncRNA signature associated with sialylation could guide prognosis, enhance the understanding of molecular mechanisms, and inform treatment strategies in UCEC. It highlights the potential for the use of ICIs and chemotherapy.

Trends in the incidence and mortality of cervical, ovarian, and corpus uteri cancers in Wales, UK: A joinpoint regression analysis from 2002 to 2021

ObjectivesThe primary objective of this study was to examine the secular trends of cervical, ovarian, and corpus uteri neoplasm in Wales, UK, over the period from 2002 to 2021. We aimed to identify changes in the incidence and mortality rates of these cancers to inform future healthcare policies and cancer prevention programs. MethodsWe sourced incidence data from 2002 to 2019 and mortality data from 2002 to 2021 from the Welsh Cancer Intelligence and Surveillance Unit. The data were analysed using Joinpoint regression to compute the average annual percentage change (AAPC) in age-standardized incidence rates (ASIR) and mortality rates (ASMR) per 100,000 population for each type of cancer. ResultsThe results showed that the ASIR for cervical cancer remained stable between 2002 and 2019 (AAPC = −0.5; 95 %CI = −1.4–0.4). However, the ASMR significantly declined from 4.88 in 2002–3.03 in 2021 (AAPC = −2.3; 95 %CI = −3.4 to −1.1). The ASIR for ovarian cancer significantly decreased from 27.39 in 2002–17.87 in 2019 (AAPC = −2.6; 95 %CI = −3.0 to −2.1), and the ASMR showed a statistically significant decreasing trend from 15.92 in 2002–11.2 in 2021 (AAPC = −1.7; 95 %CI = −2.5 to −0.9). In contrast, the ASIR for corpus uteri neoplasm significantly increased from 22.24 in 2002–30.41 in 2019 (AAPC = 2.2; 95 %CI = 1.2–3.4), and ASMR also showed a statistically significant increasing trend from 3.27 in 2002–6.42 in 2021 (AAPC = 3.8; 95 %CI = 2.3–5.3). ConclusionsThe study concludes that while the incidence and mortality rates for cervical and ovarian cancers in Wales have significantly decreased, corpus uteri neoplasm rates have increased during the study period. These findings underscore the need for continued efforts to improve early detection and treatment strategies, including national screening programs and public health initiatives, to mitigate the burden of these cancers.

Utilizing CT imaging for evaluating late gastrointestinal tract side effects of radiotherapy in uterine cervical cancer: a risk regression analysis

BackgroundRadiotherapy (RT) is effective for cervical cancer but causes late side effects (SE) to nearby organs. These late SE occur more than 3 months after RT and are rated by clinical findings to determine their severity. While imaging studies describe late gastrointestinal (GI) SE, none demonstrate the correlation between the findings and the toxicity grading. In this study, we demonstrated the late GI toxicity prevalence, CT findings, and their correlation.MethodsWe retrospectively studied uterine cervical cancer patients treated with RT between 2015 and 2018. Patient characteristics and treatment(s) were obtained from the hospital’s databases. Late RTOG/EORTC GI SE and CT images were obtained during the follow-up. Post-RT GI changes were reviewed from CT images using pre-defined criteria. Risk ratios (RR) were calculated for CT findings, and multivariable log binomial regression determined adjusted RRs.ResultsThis study included 153 patients, with a median age of 57 years (IQR 49–65). The prevalence of ≥ grade 2 RTOG/EORTC late GI SE was 33 (27.5%). CT findings showed 91 patients (59.48%) with enhanced bowel wall (BW) thickening, 3 (1.96%) with bowel obstruction, 7 (4.58%) with bowel perforation, 6 (3.92%) with fistula, 0 (0%) with bowel ischemia, and 0 (0%) with GI bleeding. Adjusted RRs showed that enhanced BW thickening (RR 9.77, 95% CI 2.64–36.07, p = 0.001), bowel obstruction (RR 5.05, 95% CI 2.30–11.09, p < 0.001), and bowel perforation (RR 3.82, 95% CI 1.96–7.44, p < 0.001) associated with higher late GI toxicity grades.ConclusionsOur study shows CT findings correlate with grade 2–4 late GI toxicity. Future research should validate and refine these findings with different imaging and toxicity grading systems to assess their potential predictive value.

A signal-seeking phase 2 study of Trastuzumab emtansine in tumours harbouring HER2 amplification or mutation

This single-arm phase II non-randomised trial (ACTRN12619001265167) evaluated trastuzumab emtansine in solid cancers with HER2 amplification or mutation detected by comprehensive genomic profiling. The primary objective was objective response (OR), while secondary objectives included the time to progression (TTP) on study to TTP on prior therapy ratio, progression-free survival (PFS) and overall survival (OS). The cohort included 16 tumours with HER2 mutations (group 1) and 16 with HER2 amplification (group 2). After 17 months median follow-up, ORs occurred in 19% of group 1 (1 salivary gland carcinoma (SGC), 2 lung cancers) and 25% of group 2 (3 SGCs, 1 uterine carcinoma). Fourteen of 29 TTP-evaluable patients achieved a TTP ratio ≥1.3, including 10 without an OR. Median PFS and OS were 4.5 (95% CI 2.1–7.0) and 18.2 months (95% CI 8.1-not reached) respectively. Trastuzumab emtansine showed modest ORs and a favourable change in disease trajectory in select HER2-altered solid cancers.

Functional Analysis of RE1 Silencing Transcription Factor as a Putative Tumor Suppressor in Human Endometrial Cancer.

Uterine cancer is the most common gynecologic malignancy in the United States, with endometrioid endometrial adenocarcinoma (EC) being the most common histologic sub-type. Considering the molecular classifications of EC, efforts have been made to identify additional biomarkers that can assist in diagnosis, prognosis, and individualized therapy. We sought to explore the relationship of Repressor Element 1 (RE1) silencing transcription factor (REST), which downregulates neuronal genes in non-neuronal tissue, along with matrix metalloproteinase-24 (MMP24) and EC. We analyzed the expression of REST and MMP24 in 31 cases of endometrial cancer and 16 controls. We then explored the baseline expression of REST and MMP24 in two EC cell lines (Ishikawa and HEC-1-A) compared to a benign cell line (t-HESC) and subsequently evaluated proliferation, migration, and invasion in the setting of loss of REST gene expression. REST and MMP24 expression were significantly lower in human EC samples compared to control samples. REST was highly expressed in EC cell lines, but decreasing REST gene expression increased proliferation (FC: 1.13X, p < 0.0001), migration (1.72X, p < 0.0001), and invasion (FC: 7.77X, p < 0.05) in Ishikawa cells, which are hallmarks of cancer progression and metastasis. These findings elicit a potential role for REST as a putative tumor suppressor in EC.

Rapid Desensitization to Antitumoral Agents. Result from a Retrospective Study, DESARCh

Antitumoral drugs (ADs) can induce drug hypersensitivity reactions (DHRs). Rapid drug desensitization (RDD) protocols represent an important option to mitigate recurrent DHRs thus allowing the safe administration of ADs at therapeutic doses. The aim of this retrospective study was to assess the effectiveness of the RDD protocols performed at our institution. The “DESARCh” study was a retrospective, observational study that included consecutive patients who underwent RDD protocols from January 2011 to December 2022 at IRCCS Ospedale Sacro Cuore Don Calabria in Negrar di Valpolicella, Verona, Italy. The RDD protocol consisted of a 5-step protocol with 5 different concentrations of the drugs at 1:1, 1:10, 1:100, 1:1,000 and 1:10,000 dilution given intravenously over a 1-hour infusion each, with concentrations increasing from the most diluted to the most concentrated form, preceded by a 30-min premedication regimen. A total of 66 RDD protocols were administered to 25 female patients with ovarian (64%; n = 16/25), breast (12%; n = 3/25), endometrium (8%; n = 2/25), cervix (8%; n = 2/25), uterine (4%; n = 1/25) and fallopian tubes (4%; n = 1/25) cancers. A known history of atopy/allergy was reported by 36% (n = 9/25) of patients. Patients received RDD protocols because of DHRs to carboplatin (n = 23/66, 34.85%), paclitaxel (n = 18/66, 27.27%), pegylated liposomal doxorubicin (n = 3/66, 4.55%), and trastuzumab (n = 22/66, 33.33%). DHRs were mild-moderate, severe and life-threatening in 60.72%, 28.57% and 10.71% of cases, respectively. The success rate of RDD protocols, defined as the rate of complete administration of full target dose with no breakthrough reactions, was 81.82% (n = 54/66). Success rate was lower for carboplatin compared to other drugs (65.22% vs 90.7%; P = .017678). The RDD protocol used in our institution was found to be safe, with a meaningful success rate. However, further research is needed to better understand the underlying mechanisms of DHRs and to enhance effectiveness, particularly for patients experiencing DHRs to platinum compounds. This study was approved by the ethics committee of Verona and Rovigo (Italy) with approval number 15476 on 10/03/2023 and it was registered with the Register of Observational Studies of the Italian Medicines Agency (AIFA) (available since 31 January 2023), with ID n. 109, on 28/02/2023 ( https://www.aifa.gov.it/en/registro-studi-osservazionali ).

Utility of Pipet Curet Cytology and Biopsy as a Diagnostic Method for Endometrial Endometrioid Carcinoma

Introduction: We aimed to determine the utility of Pipet Curet cytology (PCC) and Pipet Curet biopsy (PCB) for diagnosing uterine endometrial endometrioid carcinoma (EEC). Methods: We divided 77 patients with EEC into two groups per Federation of Gynecology and Obstetrics (FIGO) grades: G1 (n = 44) and G2/3 (n = 33) and compared the diagnostic sensitivity of PCC, PCB, and PCC and PCB combined, retrospectively. Next, we investigated any diagnostic discordance between PCC-based and PCB-based diagnoses per FIGO grade group. Results: The diagnostic sensitivity of PCC, PCB, and the two modalities combined was significantly higher for G2/3 EECs than for G1 EECs (72.7% vs. 45.5%, p = 0.0209; 84.8% vs. 63.6%, p = 0.0434; and 93.9% vs. 65.9%, p = 0.0046, respectively), likely due to more friable cancer cells in higher grade EEC cases. Among our 77 EEC patients, there were 4 patients (5.19%) with PCC-based concordant but PCB-based discordant results against EEC, in the G2/3 group predominantly. Diagnostic sensitivity of all cases increased from 72.7% (56/77) by PCB alone to 77.9% (60/77) by use of both modalities combined. Conclusion: Cytologic evaluation can reduce the number of false-negative histologic diagnoses. By providing complementary information, the two modalities combined from the Pipet Curet procedure would be valuable as a diagnostic method for EEC.

Assessment of using an Octavius 4D Measuring System for Patient-specific VMAT Quality Assurance in Togo

Purpose and objective: Quality assurance (QA) programs are designed to improve the quality and the safety of radiation treatments, including machine- and patient-specific QA (PSQA). The objective of this study was to evaluate the current state of PSQA practice and identify the area for potential improvement for VMAT delivery. Materials and methods: The Octavius 4D (O4D) system accuracy was evaluated using an O4D homogeneous phantom for different field sizes. The system response to dose linearity, field sizes, and PDD difference tests were performed against the calculated dose of the treatment planning system (TPS) for a 6 MV photon beam. The deviation of the delivered dose was evaluated at the isocenter and different depths. Moreover, pretreatment verification of 40 VMAT plans was performed including prostate cancer (PC), head and neck cancer (HNC), uterine and cervical cancer (UCC), and breast cancer (BC). The PTW VeriSoft software was used to perform the local and global 3D gamma analysis by comparing the reconstructed 3D dose against the calculated dose using criteria 2%/2 mm and 3%/3 mm, 20% of low-dose threshold, and 95% of gamma passing rate (%GP) tolerance level. In the clinical scenario, the sensitivity of the O4D system in detecting VMAT delivery and setup errors has been investigated by measuring the variation of %GP values before and after the simulated errors using one of the VMAT plans related to each treatment site. Results: The O4D system reported good agreement for linearity, field size, and PDD differences with TPS dose being within ± 2% tolerance for a 6 MV photon beam. Output factors were consistent between the ionization chamber and the O4D detector 1500 array down to 4 x 4 cm2 field size with a maximum deviation of less than 1%. The introduction of deliberate errors caused the decrease of %GP values. In most scenarios, the %GP value of simulated errors was detected with 2%/2 mm and ranged between the detection threshold and gamma passing threshold. Conclusion: The results indicate that the O4D system is sensitive to detect delivery and setup errors with restrictive criteria of 2%/2 mm for routine pretreatment verification. Moreover, this system should be used in combination with kV-CBCT to improve dosimetry accuracy and treatment reproducibility.

Uterine Cancer: A Nine-year Review from a Tertiary Hospital in Tamil Nadu

Background: With increasing uterine cancer in developing nations, there is a need for timely determination of the diagnosis, prognosis, and management options to reduce morbidity and mortality. Objective: To analyze the socio-demographic, etio-pathological features and management of uterine cancer and evaluate its correlation with grading/staging in our population. Methods: This retrospective descriptive study analyzed data from 97 histologically proven uterine cancer cases. Age, parity, symptoms, co-morbidities, body mass index (BMI), ultrasound features, histopathology type, stage and grade of the tumor, type of hysterectomy done, complications and mortality were analysed. Statistical analysis was done using ANOVA and chi-square test, and a p-value&lt;0.05 indicated statistical significance. Results: The mean age of diagnosis was 57.91 years, and the mean BMI was 29.32 Kg/m2. Majority of the patients were multiparous (42.27%), and only 10% were nulliparous. The disease was detected at an earlier age in nulliparous and obese women. Diabetes and hypertension were found in 75.25%. Most of the patients were detected with stage I cancer (80.6%). Patients diagnosed with uterine cancer on biopsy were treated with total abdominal hysterectomy with bilateral salpingo-oophorectomy andbilateral pelvic lymph node dissection (55.8%). Over 36% of patients received postop radiotherapy and/or chemotherapy. 21% patients were lost to follow-up and 12.37% died. Also, 24 cases had postoperative complications (wound infection). Conclusion: Uterine cancer is common among obese women with diabetes and hypertension. In nulliparous and the obese, the cancer was detected at an earlier age. Most of our patients had stage 1 disease, and 90% was endometroid cancer. The study highlights the importance of endometrial sampling before hysterectomy in perimenopausal women to avoid suboptimal surgery in patients diagnosed with uterine cancer after a simple hysterectomy.