Uterine Corpus Cancer Research Articles

Burden of cancers in six female organs in China and worldwide.

Cancers in female organs remain a substantial burden in China and worldwide. GLOBOCAN 2022has recently updated the estimates of cancer burden. This study aims to depict the profiles of disease burden and to compare the age-specific rates of cancers in female organs in China with those in other countries. The latest estimates of incidence and mortality of cancers in female organs from various regions and countries were extracted from the GLOBOCAN 2022database. We compared the proportion of total cases or deaths for cancers affecting six female organs and other tumor types in China and globally. Correlation analysis was conducted to evaluate the relationship between age-standardized incidence rate (ASIR) or age-standardized mortality rate (ASMR) and the Human Development Index (HDI). Additionally, age-specific rate curves were plotted for ten exemplary countries with different income levels. Globally, there are varying burdens of female organ cancers, with higher incidence rates in Northern America and elevated rates of cervical cancer in Africa. Female organ cancers in China remain a significant burden due to their large proportion of the six tumors. A positive correlation between socioeconomic development and the incidence of breast, uterine corpus, ovarian, and vulvar cancers was noted, whereas a negative association between the HDI tiers and mortality rates was found for cervical and vaginal cancers. In 2022, Chinese women aged 50-54years are experiencing high incidence rates of breast, cervix uteri, corpus uteri, and ovarian cancers. Cancers in female organs continue to be a significant health concern for women in China and worldwide. It is crucial to implement comprehensive prevention strategies tailored to address the increasing trend among younger individuals and reduce regional disparities.

Differences in cancer rates among adults born between 1920 and 1990 in the USA: an analysis of population-based cancer registry data

Trends in cancer incidence in recent birth cohorts largely reflect changes in exposures during early life and foreshadow the future disease burden. Herein, we examined cancer incidence and mortality trends, by birth cohort, for 34 types of cancer in the USA. In this analysis, we obtained incidence data for 34 types of cancer and mortality data for 25 types of cancer for individuals aged 25-84 years for the period Jan 1, 2000, to Dec 31, 2019 from the North American Association of Central Cancer Registries and the US National Center for Health Statistics, respectively. We calculated birth cohort-specific incidence rate ratios (IRRs) and mortality rate ratios (MRRs), adjusted for age and period effects, by nominal birth cohort, separated by 5 year intervals, from 1920 to 1990. We extracted data for 23 654 000 patients diagnosed with 34 types of cancer and 7 348 137 deaths from 25 cancers for the period Jan 1, 2000, to Dec 31, 2019. We found that IRRs increased with each successive birth cohort born since approximately 1920 for eight of 34 cancers (pcohort<0·050). Notably, the incidence rate was approximately two-to-three times higher in the 1990 birth cohort than in the 1955 birth cohort for small intestine (IRR 3·56 [95% CI 2·96-4·27]), kidney and renal pelvis (2·92 [2·50-3·42]), and pancreatic (2·61 [2·22-3·07]) cancers in both male and female individuals; and for liver and intrahepatic bile duct cancer in female individuals (2·05 [1·23-3·44]). Additionally, the IRRs increased in younger cohorts, after a decline in older birth cohorts, for nine of the remaining cancers (pcohort<0·050): oestrogen-receptor-positive breast cancer, uterine corpus cancer, colorectal cancer, non-cardia gastric cancer, gallbladder and other biliary cancer, ovarian cancer, testicular cancer, anal cancer in male individuals, and Kaposi sarcoma in male individuals. Across cancer types, the incidence rate in the 1990 birth cohort ranged from 12% (IRR1990 vs 1975 1·12 [95% CI 1·03-1·21] for ovarian cancer) to 169% (IRR1990 vs 1930 2·69 [2·34-3·08] for uterine corpus cancer) higher than the rate in the birth cohort with the lowest incidence rate. The MRRs increased in successively younger birth cohorts alongside IRRs for liver and intrahepatic bile duct cancer in female individuals, uterine corpus, gallbladder and other biliary, testicular, and colorectal cancers, while MRRs declined or stabilised in younger birth cohorts for most cancers types. 17 of 34 cancers had an increasing incidence in younger birth cohorts, including nine that previously had declining incidence in older birth cohorts. These findings add to growing evidence of increased cancer risk in younger generations, highlighting the need to identify and tackle underlying risk factors. American Cancer Society.

Trends of endometrial cancer incidence in Sri Lanka from 2011 to 2020: An analysis of annual national cancer incidence data reports.

The incidence of endometrial cancer in low-income countries is rising at a rapid rate. This could be due to changes in risk factors and socio-economic transitions occurring in developing countries. The main aim of this study was to assess the changes in endometrial cancer incidence in Sri Lanka. Incidence data for uterine corpus cancer and endometrial cancer between 2011 and 2020 were extracted from the National Cancer Register of Sri Lanka. This included the crude rate, age standardised incidence rate, and age-specific incidence. Joinpoint trend analysis software was used to analyse the temporal pattern of incidence. The estimated annual percentage change of incidence (EAPC) was calculated. A total of 8332 patients with uterine corpus cancer were reported with the highest incidence in the 60-70-year-old age group. The EAPC of uterine corpus cancer was 9.26%, while it was 8.26% for endometrial cancer. The highest rise of age-specific incidence was observed in the 70 years plus age group (EAPC 13.3968%, 95% confidence interval (CI): 9.6916-17.1994). There is a clear rise in endometrial and uterine cancer incidence in Sri Lanka. While part of this could be due to better reporting of new cases, a true increase in incidence should have occurred due to different rates of EAPC among age categories. Studies to evaluate the factors leading to the rising incidence of endometrial cancer are recommended.

Abstract B021: Early onset uterine corpus cancer incidence rates and 5-year relative survival by histologic subtype and race/ethnicity among women aged 20-49 years

Abstract Purpose: Uterine cancer, including early onset cases, is increasing among all women, particularly in minority populations. Despite nearly 25% of cancers occurring in younger women, changes in tumor characteristics (e.g., histology) by race/ethnicity remain poorly understood. We examined incidence rates and 5-year relative survival of uterine cancer among women aged 20-49, overall and by race/ethnicity and histology. Methods: We used the Surveillance, Epidemiology, and End Results Program (SEER 22) Research Plus Data, representing 47.9% of the total U.S. population. We included women aged 20-49 years with microscopically confirmed malignant uterine cancer (diagnosed 2000-2019) to calculate age-adjusted incidence and age-standardized 5-year relative survival (2000-2018) overall and by race/ethnicity and histology. Time trends were described across two time periods: 2000-2009 and 2010-2019. All analyses were conducted using SEER*Stat; incidence rates were presented for per 100,000 population. Results: We included 57,128 cases (55% Non-Hispanic [NH]-White, 9% NH-Black, 10% NH-Asian/Pacific Islander [PI], and 25% Hispanic). From the period of 2000-2009 to 2010-2019, the proportion of cases that were 20-29 and 30-39 increased by 1% and 4%, respectively. Overall, incidence increased over time for all women (8.7 in 2000-2009 to. 10.4 in 2010-2019), and increases were observed for both endometrioid and non-endometrioid subtypes. In the most recent period, rates were highest for endometrioid subtypes (8.4), followed by sarcomas (1.0), and non-endometrioid subtypes (0.7). Rates for endometrioid and non-endometrioid cancers were highest in Hispanics (9.9 and 0.8) and NH-Asian/Pacific Islanders (9.7 and 0.8), respectively and lowest in NH-Blacks (5.5 and 0.6). Rates of sarcomas were highest in NH-Blacks (1.5). 5-year relative survival remained relatively unchanged over time in most racial/ethnic groups, except NH-Blacks experienced slight improvement (57% to 60%). In terms of histology, survival increased for endometrioid (87% to 89%) and non-endometrioid cases (54% to 58%) and decreased for sarcomas (46% to 42%). Conclusions: Early onset uterine cancer is rising in all women, and for both endometrioid and non-endometrioid subtypes. Of interest is the differences in the rates by histology when compared the full U.S. population: Among women aged &amp;lt;50 years, rates of uterine sarcomas were higher compared to non-endometrioid subtypes. These findings are concerning given that sarcomas are associated with poor prognosis and were the only cases to show decreased 5-year survival in our analysis. While rates of non-endometrioid subtypes are known to be higher among NH-Black women in the U.S., we did not observe a striking racial difference among early onset cases. In fact, NH-Black women had the lowest rates of endometrioid and non-endometrioid subtypes, but highest rates of sarcomas compared to others. Next step for this analysis is hysterectomy correction, which, while expected to be relatively lower among women aged&amp;lt;50 years, is known to vary by race/ethnicity. Citation Format: Akemi T. Wijayabahu, Megan A. Clarke. Early onset uterine corpus cancer incidence rates and 5-year relative survival by histologic subtype and race/ethnicity among women aged 20-49 years [abstract]. In: Proceedings of the AACR Special Conference on Endometrial Cancer: Transforming Care through Science; 2023 Nov 16-18; Boston, Massachusetts. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(5_Suppl):Abstract nr B021.

Gene Expression Analysis for Uterine Cervix and Corpus Cancer Characterization.

The analysis of gene expression quantification data is a powerful and widely used approach in cancer research. This work provides new insights into the transcriptomic changes that occur in healthy uterine tissue compared to those in cancerous tissues and explores the differences associated with uterine cancer localizations and histological subtypes. To achieve this, RNA-Seq data from the TCGA database were preprocessed and analyzed using the KnowSeq package. Firstly, a kNN model was applied to classify uterine cervix cancer, uterine corpus cancer, and healthy uterine samples. Through variable selection, a three-gene signature was identified (VWCE, CLDN15, ADCYAP1R1), achieving consistent 100% test accuracy across 20 repetitions of a 5-fold cross-validation. A supplementary similar analysis using miRNA-Seq data from the same samples identified an optimal two-gene miRNA-coding signature potentially regulating the three-gene signature previously mentioned, which attained optimal classification performance with an 82% F1-macro score. Subsequently, a kNN model was implemented for the classification of cervical cancer samples into their two main histological subtypes (adenocarcinoma and squamous cell carcinoma). A uni-gene signature (ICA1L) was identified, achieving 100% test accuracy through 20 repetitions of a 5-fold cross-validation and externally validated through the CGCI program. Finally, an examination of six cervical adenosquamous carcinoma (mixed) samples revealed a pattern where the gene expression value in the mixed class aligned closer to the histological subtype with lower expression, prompting a reconsideration of the diagnosis for these mixed samples. In summary, this study provides valuable insights into the molecular mechanisms of uterine cervix and corpus cancers. The newly identified gene signatures demonstrate robust predictive capabilities, guiding future research in cancer diagnosis and treatment methodologies.

Trends in gynecologic cancer in Japan: incidence from 1980 to 2019 and mortality from 1981 to 2021.

In Japan, comprehensive cancer statistics data have been collected through national cancer registries, but these data are rarely summarized and reported in research articles. Here, we compiled the national registry data on malignant tumors originating from gynecologic organs (ovary, corpus uteri, cervix uteri) in Japan. The number of new patients in 2019 was 13,380, 17,880, and 10,879, respectively, and the number of deaths in 2021 was 5081, 2741, and 2894, respectively. Compared with 40years ago, the incidence of ovarian cancer has tripled, the incidence of uterine corpus cancer (mainly endometrial cancer) has increased eightfold, the mortality rate of uterine corpus cancer has tripled, and the incidence of cervical intraepithelial cancer has increased ninefold in data standardized by the world population. Compared with the United States, the incidence rate of ovarian cancer has overtaken and the mortality rate of uterine corpus cancer is the same, while both the incidence and mortality rates of cervical cancer are higher in Japan. The incidence of gynecologic cancer is increasing significantly in Japan.

Trends in gynaecologic cancer mortality and the impact of the COVID-19 pandemic in the United States

ObjectivesOur aim was to assess the trend in gynaecologic cancer (GC) mortality in the period from 2010 to 2022 in the United States, with focus on the impact of the pandemic on increased deaths.MethodsGC mortality data were extracted from the Center for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research (CDC WONDER) platform. We analysed mortality trends and evaluated observed vs. predicted mortality for the period from 2020 to 2022 with joinpoint regression and prediction modelling analyses.ResultsA total of 334,382 deaths among adults aged 25 years and older with gynaecologic cancer were documented from 2010 to 2022. The overall age-standardised mortality rate (ASMR, per 100,000 persons) for ovarian cancer-related death decreased gradually from 7.189 in 2010 to 5.517 in 2019, yielding an APC (annual percentage change) of -2.8%. However, the decrease in ovarian cancer-related mortality slowed down by more than 4-fold during the pandemic. Cervical cancer -related mortality decreased slightly prior to the pandemic and increased during the pandemic with an APC of 0.6%, resulting in excess mortality of 4.92%, 9.73% and 2.03% in 2020, 2021 and 2022, respectively. For uterine corpus cancer, the ASMR increased from 1.905 in 2010 to 2.787 in 2019, and increased sharply to 3.079 in 2021 and 3.211 in 2022. The ASMR rose steadily between 2013 and 2022, yielding an APC of 6.9%.ConclusionsOverall, we found that GC-related mortality increased during the COVID-19 pandemic, and this increase was not specific to age, race, or ethnicity.

Hypothyroidism and hyperthyroidism related to gynecologic cancers: a nationwide population-based cohort study

The purpose of this study was to assess the risks of hyperthyroidism and hypothyroidism related to gynecological cancers. Population-based retrospective cohort study. We conducted a cohort study using the Taiwan National Health Insurance Research Database to explore hyperthyroidism and hypothyroidism associated with site-specific gynecologic cancers in women from January 1, 2000 to December 31, 2018. The examined gynecologic cancers included endometrial (EC), uterine corpus cancer (UC), and ovarian cancer (OC). The incidence and hazard ratios were quantified using Cox proportional hazards models. The incidence of developing gynecological (Gyn) cancers in the hyperthyroid and hypothyroid women was 0.29 and 0.44 per 1000 person-years, which was 0.86 fold lower and 1.13 fold higher than that in the comparison cohort (p < 0.001). Compared with patients aged 20–40 years, patients in older age groups had a lower and higher risk of developing Gyn cancers (for hyperthyroid, 40–65 years: adjusted hazard ratio (aHR) = 0.82; > 65 years: aHR = 0.94; for hypothyroid, adjusted hazard ratio (aHR) = 1.26; > 65 years: aHR = 1.38). Compared with the non-hypothyroid women and non-hyperthyroid women beyond 6 years of follow-up, hypothyroid and hyperthyroid women showed decreased risk of Gyn cancers. Medication treatment for hyperthyroid and hypothyroid disease did not showed significant association in subgroup analyses (aHR = 0.99 and 0.80, respectively). Our results show that women with hyperthyroidism have a significantly reduced risk of gynecological cancers, whereas women with hypothyroidism have a slightly increased risk of gynecological cancers suggesting an association between thyroid function level and risk of gynecological cancers.

Deciphering the Causal Relationship between Sodium-glucose Cotransporter 2 Inhibition and Cancer Risks: A Comprehensive Mendelian Randomization Study.

Background: Controversy persists regarding the effects of sodium-glucose cotransporter 2 (SGLT2) inhibitors on cancer. The underlying causal relationship remains unclear. Method: A two-sample Mendelian randomization (MR) strategy was employed to investigate the causal associations between SGLT2 inhibitors and 26 site-specific malignancies. Instrumental variants strongly associated with SLC5A2 gene expression and glycated hemoglobin A1c levels were identified as the genetic proxy for SGLT2 inhibition. Cancer-related outcome datasets sourced from the OpenGWAS project were separated into discovery and replication datasets. The meta-analysis was conducted to determine the final causality. Results: Genetically proxied SGLT2 inhibition showed a significant association with bronchial and lung cancer (beta: -0.028 [-0.041, -0.015], P < 0.001), bladder cancer (beta: 0.018 [0.008, 0.027], P < 0.001), prostate cancer (beta: 1.168 [0.594, 1.742], P < 0.001), cervical cancer (beta: -0.019 [-0.031, -0.008], P = 0.001), corpus uterine cancer (beta: 0.015 [0.006, 0.025], P = 0.001) and non-melanoma skin cancer (beta: -0.080 [-0.116, -0.044], P < 0.001) in the discovery cohort. The suggestive causal effect of SGLT2 inhibition on the increased risk of cervical cancer (beta: 3.241 [0.855, 5.627], P = 0.008) and lymphoid leukemia (beta: 4.126 [0.383, 7.868], P = 0.031) was found in the replication cohort. The combined causality of the following types of cancer was observed to remain significant after meta-analysis: bronchial and lung cancer, bladder cancer, prostate cancer, corpus uterine cancer, and non-melanoma skin cancer (all P ≤ 0.001). Conclusion: For the first time we discovered that the SGLT2 inhibition may exert protection on bronchial and lung cancer and non-melanoma skin cancer from a genetic perspective. However, suggestive higher cancer risks of bladder, prostate, and corpus uteri were also noted, which warrants real-world data validation in the future.

Cancer statistics, 2024.

Each year, the American Cancer Society estimates the numbers of new cancer cases and deaths in the United States and compiles the most recent data on population-based cancer occurrence and outcomes using incidence data collected by central cancer registries (through 2020) and mortality data collected by the National Center for Health Statistics (through 2021). In 2024, 2,001,140 new cancer cases and 611,720 cancer deaths are projected to occur in the United States. Cancer mortality continued to decline through 2021, averting over 4 million deaths since 1991 because of reductions in smoking, earlier detection for some cancers, and improved treatment options in both the adjuvant and metastatic settings. However, these gains are threatened by increasing incidence for 6 of the top 10 cancers. Incidence rates increased during 2015-2019 by 0.6%-1% annually for breast, pancreas, and uterine corpus cancers and by 2%-3% annually for prostate, liver (female), kidney, and human papillomavirus-associated oral cancers and for melanoma. Incidence rates also increased by 1%-2% annually for cervical (ages 30-44 years) and colorectal cancers (ages <55 years) in young adults. Colorectal cancer was the fourth-leading cause of cancer death in both men and women younger than 50years in the late-1990s but is now first in men and second in women. Progress is also hampered by wide persistent cancer disparities; compared to White people, mortality rates are two-fold higher for prostate, stomach and uterine corpus cancers in Black people and for liver, stomach, and kidney cancers in Native American people. Continued national progress will require increased investment in cancer prevention and access to equitable treatment, especially among American Indian and Alaska Native and Black individuals.

Rationale for early rehabilitation of patients with uterine corpus cancer

To study the dynamics of hemorheologic changes and the frequency of early complications of laparoscopic radical hysterectomy in patients with uterine corpus cancer depending on conducting rehabilitation activities in the early postoperative period. The number of patients with uterine corpus cancer equal 49 (mean age 54.8±2.2 years), divided into 2 comparable groups, was examined: experimental group - 23 patients, who received local magnetotherapy since the first day after surgery for 5-6 days, and control group - 26 patients without physiotherapy. Comparative group included 24 healthy women. The basic rheological parameters, namely blood viscosity at high and low shear rate, hematocrit, erythrocytes' aggregation and deformability, erythrocytes and platelets electrophoretic mobility, were evaluated in all patients initially, on the 1st and 5th days after surgery and in comparison group. There were changes in the rheological properties of the blood before surgery in patients of both groups: increase of blood viscosity, enhancement of aggregation activity of its formed elements, decrease of erythrocytes' deformability properties. The laparoscopic radical hysterectomy was accompanied by the exacerbation of these disorders. The early magnetotherapy in patients reduced hemorheological abnormalities up to the preoperative parameters (p<0.05) for 5 days, as well as reduced the incidence of early postoperative complications by 2.4 times compared to the control group. The application of local low-frequency low-intensity magnetotherapy since the first postoperative day allows to reduce the level of postoperative hemorheological abnormalities up to the level of preoperative parameters, as well as the frequency of early postoperative complications.

Practice guidelines for management of uterine corpus cancer in Korea: a Korean Society of Gynecologic Oncology consensus statement.

The Korean Society of Gynecologic Oncology (KSGO) had been making an effort to standardize and enhance the quality of domestic uterine corpus cancer treatment by developing updated clinical practice guidelines in 2021. The KSGO revised the guidelines based on a literature search using 4 key elements: Population, Intervention, Comparison, and Outcome framework. These elements include the evaluation of the efficacy and safety of immune checkpoint inhibitor treatment in recurrent/advanced endometrial cancer patients who have failed platinum-based chemotherapy, as well as the effect of combined treatment with trastuzumab in patients with HER2/neu-positive endometrial cancer. Additionally, the guideline assessed the efficacy and safety of omitting lymph node dissection in low-risk endometrial cancer patients, investigated the effect of sentinel lymph node mapping in early-stage endometrial cancer surgery, addressed the outcome of chemoradiation therapy as a postoperative treatment in patients with advanced (stage III-IVA) endometrial cancer, and explored the impact of initial treatment with immune checkpoint inhibitors on survival in patients with advanced or recurrent endometrial cancer patients.

Опухолевое поражение нижнего сегмента матки как потенциальный фактор неблагоприятного прогноза эндометриоидного рака тела матки I стадии для эскалации лечения в виде адъювантной лучевой терапии. Обзор литературы

The aim of research is to analyze available scientific data for the study of the relationship between carcinoma of the lower uterine segment and traditional prognostic factors for the stage 1 uterine corpus cancer, and to assess its prognostic significance related to the treatment outcomes and the feasibility of adjuvant radiotherapy in cases with the disease poor prognosis. Search for the data of concern in electronic databases with the use of keywords and analysis of Russian and English translated data published between 1987 and 2024. The tumor in the lower segment occurs in 3-27.8% of endometrial cancer of the uterus body and, due to the anatomical features of the structure, blood supply, and lymphatic drainage, can be considered as a potential prognostic factor. According to limited studies data, a tumor lesion in the lower segment has not been associated with other clinical and morphological prognostic factors, and it does not affect the relapse-free survival in patients. Other researchers demonstrate the relationship between a lesion in the lower segment and the myometrium deep invasion, lymphovascular space invasion, and metastatic involvement of lymph nodes, however, they have not found any they have not impacted on treatment outcomes. However, a wide range of studies has demonstrated that the lower segment lesions are independent and poor prognostic factors. The factors significantly correlate with traditional prognostic factors and reduce both overall and recurrence-free survival. Therefore, it may be justified to consider postoperative radiotherapy for patients with a low or intermediate risk of disease progression, despite the absence of evidence of lymph node involvement. Analysis of the found research data has revealed the potential for further research into the impact of tumors in the lower segment of the uterus on patients with stage I endometrioid cancer. This could help identify new prognostic factors and determine whether adjuvant radiation therapy is appropriate for this group of patients.

Diagnostic role and prognostic impact of positron emission tomography/computed tomography in patients treated for uterine corpus cancer

Introduction/Objective. The goal of our research was to evaluate diagnostic and prognostic role of positron emission tomography/computed tomography (PET-CT) in patients previously treated for uterine cancer and compare it to conventional imaging methods (CIM). Methods. We analyzed 37 patients examined on PET-CT for follow-up or suspicion of uterine cancer recurrence, and who were previously treated with surgery and/or chemoradiotherapy. All patients underwent CT or magnetic resonance imaging prior to PET-CT, and were followed-up for at least one year. Results. PET-CT showed sensitivity, specificity and diagnostic accuracy in uterine cancer relapse detection of 96.3%, 70%, and 89.2%, while those values for CIM were 92.6%, 40%, and 78.4 %, respectively. Correlation of PET-CT and CIM findings was 78% (29/37). In 13 out of 25 true positive patients on CIM, PET-CT found greater number of active sites missed by conventional imaging. Positive findings on PET-CT were associated with shorter progression free survival (p = 0.023, logrank test). Conclusion. PET-CT constitutes an important diagnostic method in management of recurrent cancer of uterine corpus, demonstrating high sensitivity and accuracy. In comparison to CIM, PET-CT can discover larger number of active tumor sites, and also shows better specificity. PET-CT positive patients have worse prognosis with shorter progression free survival.

Cesium-131 Low-Dose Rate Interstitial Brachytherapy as a Salvage Re-Irradiation Technique in Treating Cervical and Uterine Cancer Pelvic Recurrence with Prior History of Pelvic Radiation

Pelvic recurrence among cervical and uterine cancer patients with prior history of pelvic radiation is a poor prognostic factor and remains challenging. The standard of care is pelvic exenteration, which is a highly morbid surgical procedure. The purpose of this study is to report local control rate and toxicity profile of Cesium-131 low-dose rate interstitial brachytherapy (LDR) as a salvage re-irradiation technique in managing pelvic relapse. We reviewed procedures and outcomes from patients with previously irradiated uterine corpus or cervix neoplasms, who subsequently relapsed and then underwent cesium-131 LDR implants between January 2016 and December 2022. Patient demographics, treatment planning variables, and disease response were reviewed. Acute toxicities, late toxicities, and local control rate were compiled for this study. A total of 12 eligible patients (6 cervical and 6 uterine cancer) with 16 cesium-131 LDR implants were included in this study. The majority (75%) of pelvic relapses occurred at the exocervix (cervix-intact) or vaginal cuff (post-hysterectomy). Median time from disease relapse to cesium implant was 32 days. The average area of implementation was 9 cm2 and average number of seeds implanted was 16. The mean prescription dose was 50 Gy. Six patients also received high-dose rate vaginal intracavitary brachytherapy in addition to cesium-131 LDR. Median follow up was 12 months. 81% of cesium implants achieved complete response at first post-treatment follow-up, while the remaining 19% demonstrated partial response. The 6-months local control rate was 79%. After cesium implant, 25% patients had local recurrence and 33% with distal metastasis. The most reported acute toxicities included vaginal mucositis (63%), dysuria (50%) and pain (19%). All patients had various degrees of vaginal stenosis and strictures long-term. Only 1 (8%) out of 12 patients, with 4 repeated cesium-131 LDR implants, developed a rectovaginal fistula and chronic pain. Cesium-131 LDR interstitial brachytherapy is a safe and feasible salvage re-irradiation technique in treating pelvic relapse among uterine corpus or cervix cancer patients with prior history of pelvic radiation. Local control rate at 6-months was acceptable with minimum toxicity. Long-term follow up is warranted to validate the efficacy of cesium-131 LDR. We conclude that cesium-131 LDR interstitial brachytherapy is a promising alternative to pelvic exenteration in selective patient population. Future prospective study is warranted.

Are HPV-negative lesions concerned for the introduction of primary HPV testing for cervical cancer screening in Japan?

In Japan, primary human papilloma virus (HPV) testing has not been introduced for cervical cancer screening due to concerns that HPV-negative lesions may be missed and a lack of Japanese data. The purpose of this study was to evaluate the validity of primary HPV testing in Japan by analyzing cervical intraepithelial neoplasia 2 (CIN2) or more/high-risk HPV- (CIN2+/hrHPV-) cases in cervical cancer screening. Data from 35 525 cervical cancer screenings with HPV testing and cervical cytology from 2011 to 2019 in Saga City, Japan, were reviewed. The cases with low-grade squamous intraepithelial lesion (LSIL+)/hrHPV- were analyzed in detail. The results of the 35 525 examinees were as follows: 31 123 were negative for intraepithelial lesion or malignancy (NILM)/hrHPV-, 2612 were NILM/hrHPV+, 262 were atypical squamous cells of undetermined significance (ASC-US)/hrHPV-, 213 were ASC-US/hrHPV+, 291 were LSIL+/hrHPV-, and 1024 were LSIL+/hrHPV+. Of the 256 LSIL+/hrHPV- examinees for whom histology was available, CIN2+ were CIN2 9.4% (24/256), CIN3 3.9% (10/256), cervical adenocarcinoma 0.4% (1/256), uterine corpus cancer 1.2% (3/256), and uterine sarcoma 0.4% (1/256). Overall, the rate of LSIL+/hrHPV- was 0.82% (291/35.525), 0.1% (36/35525) of which were cervical lesions with CIN2+. Only one cervical adenocarcinoma was detected, but gastric-type adenocarcinoma was not included. HPV-negative CIN2+ or cervical adenocarcinoma is not a concern for the introduction of primary HPV screening in Japan. Primary HPV testing in cervical cancer screening is considered a feasible method that can be used in Japan, although an algorithm suitable for Japan and a national-level management system need to be established.

Racial and ethnic disparities in survival among persons with subsequent primary cancer.

12093 Background: Racial and ethnic disparities in survival after first primary cancer diagnoses have been well documented. Yet comprehensive data for disparities after subsequent primary cancer (SPC) are lacking despite the growing burden of SPCs. Methods: This study included 230,370 persons diagnosed with one of the 13 common SPCs at ages≥20 years during 2000-2013 in 18 Surveillance, Epidemiology, and End Results registries. Cause-specific proportional hazards models were used to estimate HR (hazard ratio), overall and stratified by SPC types, comparing the risk of cancer or cardiovascular death in Hispanic, non-Hispanic Asian or Pacific Islander (API), or non-Hispanic Black (Black) persons to that in non-Hispanic White (White) persons. HRs were adjusted for sex, first primary cancer type and stage, age and year of SPC diagnosis (base model); and additionally household income, urbanicity, SPC stage, subtype, and treatment receipt (surgery, radiotherapy, chemotherapy) (final model). Results: During 54 months of median follow-up, 109,757 cancer deaths and 18,283 cardiovascular deaths occurred among persons with SPCs. Overall, HRs for cancer death were higher among Black (HR = 1.21, 95% CI = 1.18-1.23) and Hispanic (HR = 1.10, 95% CI = 1.07-1.13) persons compared with White persons, but lower among API persons (HR = 0.93, 95% CI = 0.90-0.96) in the base model. When stratified by SPC types, the increased HRs were evident for 10 of 13 cancers among Black persons with the greatest HR among those with uterine corpus cancer (HR = 1.87, 95%CI = 1.63-2.15) and for 7 of 13 cancers among Hispanic persons with the highest HR among those with melanoma (HR = 1.46, 95%CI = 1.21-1.76). For cardiovascular death, compared with White persons, the overall HR was higher among Black (HR = 1.42, 95% CI = 1.35-1.49) persons but lower among API (HR = 0.75, 95%CI = 0.69-0.81) and Hispanic (HR = 0.90, 95% CI = 0.84-0.96) persons. The risk of cardiovascular death was higher for 11 of 13 cancers among Black persons with the greatest HR among those with pancreatic (HR = 1.80, 95%CI = 1.17-2.75), thyroid (HR = 1.70, 95%CI = 1.12-2.57), and kidney (HR = 1.63, 95%CI = 1.38-1.93) cancers. Additional adjustments in the final model reduced the elevated HRs substantially especially for cancer death among Black or Hispanic persons, although the associations remained statistically significant for most cancers. Conclusions: Among persons with SPCs, Black persons had a higher risk of death from both cancer and cardiovascular disease, whereas Hispanic persons had a higher risk of death from cancer. Adjusting for differences in potentially modifiable factors attenuated the associations substantially, highlighting opportunities for interventions toward health equities among cancer survivors.

Pathogenesis of endometrium-related diseases based on genomic alterations in normal uterine endometrium.

The human endometrium is a dynamically remodeling tissue that undergoes more than 400 cycles of regeneration, differentiation, shedding, and rapid healing during a woman's reproductive years. The endometrium is also the origin of various gynecologic diseases, such as endometriosis, adenomyosis, and uterine corpus cancer. Cancer-associated gene mutations are detected in endometriosis, adenomyosis, and normal endometrium. Some reports have demonstrated that the accumulation of genomic alterations is a critical carcinogenic mechanism in the progression from normal endometrium to ovarian clear cell carcinoma via endometriosis. In this review, we discuss the clinical importance of genomic alterations in the normal endometrium, contributing to the elucidation of the pathogenesis of endometrium-related diseases.

Clinical trial assessing the safety of edoxaban with concomitant chemotherapy in patients with gynecological cancer-associated thrombosis (EGCAT study)

BackgroundGynecological cancer is one of the highest risk factors for cancer-associated thrombosis (CAT). Although low-molecular-weight heparin (LMWH) is recommended as an anticoagulant for treating CAT, recent studies have shown that direct oral anticoagulants (DOACs) are an acceptable alternative. Patients with cancer require a series of chemotherapies concomitantly with DOAC administration; however, the extent to which these drugs influence DOAC blood concentrations is unknown. In this study, we measured the plasma concentration of edoxaban during chemotherapy for gynecological cancers to determine its safety.MethodsPatients histologically diagnosed with ovarian or uterine corpus cancer and CAT were recruited after primary surgery and before the initiation of postoperative adjuvant chemotherapy, including paclitaxel. Patients were administered edoxaban (30 or 60 mg) orally for CAT. The plasma concentrations of edoxaban and active factor Xa were determined and their percentage change before and after chemotherapy was calculated. Additionally, blood coagulation tests were analyzed.ResultsSixteen patients with gynecological cancer (12 with ovarian cancer and 4 with uterine corpus cancer) were enrolled. Among these, 15 samples were collected one day after chemotherapy initiation. During chemotherapy, the trough concentration of edoxaban changed from 17.6 ± 10.6 to 20.0 ± 15.6 ng/ml, and the mean percentage change in edoxaban concentration was 14.5%. Therefore, the trough concentrations of edoxaban, which represent excretion capacity, were not significantly increased by chemotherapy with paclitaxel. The area under the plasma edoxaban concentration–time curve and the active factor Xa concentration were also unaffected.ConclusionPatients with CAT and ovarian or uterine corpus cancer administered edoxaban orally showed no significant increase in the trough concentration of edoxaban while undergoing chemotherapy. This suggests the safety of edoxaban use during the treatment of gynecological cancers.Trial registrationEGCAT study; Japan Registry of Clinical Trials, jRCTs051190024.

Risk of second primary cancer among women in the Kaiser Permanente Breast Cancer Survivors Cohort

BackgroundBreast cancer survivors are living longer due to early detection and advances in treatment and are at increased risk for second primary cancers. Comprehensive evaluation of second cancer risk among patients treated in recent decades is lacking.MethodsWe identified 16,004 females diagnosed with a first primary stage I-III breast cancer between 1990 and 2016 (followed through 2017) and survived ≥ 1 year at Kaiser Permanente (KP) Colorado, Northwest, and Washington. Second cancer was defined as an invasive primary cancer diagnosed ≥ 12 months after the first primary breast cancer. Second cancer risk was evaluated for all cancers (excluding ipsilateral breast cancer) using standardized incidence ratios (SIRs), and a competing risk approach for cumulative incidence and hazard ratios (HRs) adjusted for KP center, treatment, age, and year of first cancer diagnosis.ResultsOver a median follow-up of 6.2 years, 1,562 women developed second cancer. Breast cancer survivors had a 70% higher risk of any cancer (95%CI = 1.62–1.79) and 45% higher risk of non-breast cancer (95%CI = 1.37–1.54) compared with the general population. SIRs were highest for malignancies of the peritoneum (SIR = 3.44, 95%CI = 1.65–6.33), soft tissue (SIR = 3.32, 95%CI = 2.51–4.30), contralateral breast (SIR = 3.10, 95%CI = 2.82–3.40), and acute myeloid leukemia (SIR = 2.11, 95%CI = 1.18–3.48)/myelodysplastic syndrome (SIR = 3.25, 95%CI = 1.89–5.20). Women also had elevated risks for oral, colon, pancreas, lung, and uterine corpus cancer, melanoma, and non-Hodgkin lymphoma (SIR range = 1.31–1.97). Radiotherapy was associated with increased risk for all second cancers (HR = 1.13, 95%CI = 1.01–1.25) and soft tissue sarcoma (HR = 2.36, 95%CI = 1.17–4.78), chemotherapy with decreased risk for all second cancers (HR = 0.87, 95%CI = 0.78–0.98) and increased myelodysplastic syndrome risk (HR = 3.01, 95%CI = 1.01–8.94), and endocrine therapy with lower contralateral breast cancer risk (HR = 0.48, 95%CI = 0.38–0.60). Approximately 1 in 9 women who survived ≥ 1 year developed second cancer, 1 in 13 developed second non-breast cancer, and 1 in 30 developed contralateral breast cancer by 10 years. Trends in cumulative incidence declined for contralateral breast cancer but not for second non-breast cancers.ConclusionsElevated risks of second cancer among breast cancer survivors treated in recent decades suggests that heightened surveillance is warranted and continued efforts to reduce second cancers are needed.