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Clinical evidence suggests that high‐intensity focused ultrasound (HIFU) is emerging as an increasingly viable non‐invasive treatment for various gynecological diseases, demonstrating both high safety and effectiveness. Nevertheless, HIFU presents challenges in terms of energy dissipation and prolonged treatment time during the therapeutic process. In this study, liposomes containing ammonium bicarbonate (NH4HCO3) and paclitaxel (PTX), a first‐line chemotherapy drug, are utilized to enhance HIFU imaging and therapy. During HIFU treatment, the NH4HCO3 and PTX‐loaded liposomes (PTN@Lip) can release CO2 and NH3 in the tumor's acidic environment. These not only improve HIFU imaging but also regulate the tumor's acidic environment, thereby enhancing the uptake of PTX by tumor cells. Notably, the implementation of PTN@Lip and HIFU activates the immune system, leading to tumor inhibition or even elimination ultimately. This approach has the potential to address existing clinical treatment challenges and lay the groundwork for new directions in the treatment of gynecological tumors. [ABSTRACT FROM AUTHOR]

Gynecologic malignant tumors are among the leading diseases threatening women’s lives and health, with the highest morbidity and mortality rates among all female diseases. These tumors originate from female reproductive organs and are typically classified based on the affected site. Ovarian cancer (OC), endometrial cancer (EC) and cervical cancer (CCA) are the most common types. Currently, gynecologic malignant tumors are primarily treated with a combination of surgery, chemotherapy and radiotherapy, where drugs play a critical role in the treatment process. However, the actual clinical effectiveness is often influenced by various factors, such as adverse reactions due to drug toxicity and the drug resistance and insensitivity observed in some patients, which limit improvements in patient survival rates. Recent studies have shown that the same type of tumor exhibits significant biological characteristics and drug response heterogeneity among different individuals, which is a key factor contributing to the varied clinical outcomes when using the same drug treatment for the same type of gynecologic malignant tumor. To achieve individualized and precise treatment for gynecologic malignant tumors, there is an urgent need to develop in vitro models that closely resemble human tumors for clinical research. Drug screening is a technique used to identify and evaluate compounds with pharmacological activity and potential therapeutic effects, providing doctors with scientific guidance on drug use, thereby avoiding blind drug testing and reducing patients' therapeutic pain and economic burden by assessing the effects of different drugs under specific conditions. Organoid models have been extensively studied as an innovative drug screening tool and personalized medicine for treating gynecologic malignancies. Organoids are tissue-like structures with a specific spatial arrangement formed in vitro through three-dimensional cell culture, capable of highly simulating the structure and function of tissues in vivo and displaying histological and genotypic characteristics very similar to human organs. This approach has largely overcome the limitations of traditional tumor models, such as patient-derived cancer cell models and patient-derived tumor xenograft models, becoming an essential research tool in oncology. It provides a more physiologically relevant experimental platform for drug screening studies of gynecologic malignancies. This paper compared the advantages and disadvantages of several preclinical cancer models, reviewed the development process of organoids, and described the establishment of gynecologic oncology organoids and their application in drug screening for ovarian, endometrial, and cervical cancers. Additionally, we discussed the current limitations of organoid technology in its application and envisioned its future development, aiming to provide insights for future medical research, particularly in new drug discovery and personalized medicine.

The most common type of alopecia in women is female androgenetic alopecia (FAGA), characterized by progressive hair loss in a patterned distribution. Many oral therapies, including spironolactone (an aldosterone antagonist), androgen receptor blockers (e.g., flutamide/bicalutamide), 5-alpha-reductase inhibitors (e.g., finasteride/dutasteride), and oral contraceptives, target the mechanism of androgen conversion and binding to its respective receptor and therefore could be administered for the treatment of FAGA. Despite significant advances in the oral treatment of FAGA, its management in patients with a history of gynecological malignancies, the most common cancers in women worldwide, may still be a concern. In this review, we focus on the safety of antiandrogens for the treatment of FAGA patients. For this purpose, a targeted literature review was conducted on PubMed, utilizing the relevant search terms. To sum up, spironolactone seems to be safe for the systemic treatment of FAGA, even in high-risk populations. However, a general uncertainty remains regarding the safety of other medications in patients with a history of gynecologic malignancies, and further studies are needed to evaluate their long-term safety in patients with FAGA and risk factors to establish an optimal risk assessment and treatment selection protocol. [ABSTRACT FROM AUTHOR]

Abstract Background Tumor-infiltrating lymphocyte (TIL) therapy has been restricted by intensive lymphodepletion and high-dose intravenous interleukin-2 (IL-2) administration. To address these limitations, we conducted preclinical and clinical studies to evaluate the safety, antitumor activity, and pharmacokinetics of an innovative modified regimen in patients with advanced gynecologic cancer. Methods Patient-derived xenografts (PDX) were established from a local recurrent cervical cancer patient. TILs were expanded ex vivo from minced tumors without feeder cells in the modified TIL therapy regimen. Patients underwent low-dose cyclophosphamide lymphodepletion followed by TIL infusion without intravenous IL-2. The primary endpoint was safety; the secondary endpoints included objective response rate, duration of response, and T cell persistence. Results In matched patient-derived xenografts (PDX) models, homologous TILs efficiently reduced tumor size (p

Background: Tumor-infiltrating lymphocyte (TIL) therapy has been restricted by intensive lymphodepletion and high-dose intravenous interleukin-2 (IL-2) administration. To address these limitations, we conducted preclinical and clinical studies to evaluate the safety, antitumor activity, and pharmacokinetics of an innovative modified regimen in patients with advanced gynecologic cancer. Methods: Patient-derived xenografts (PDX) were established from a local recurrent cervical cancer patient. TILs were expanded ex vivo from minced tumors without feeder cells in the modified TIL therapy regimen. Patients underwent low-dose cyclophosphamide lymphodepletion followed by TIL infusion without intravenous IL-2. The primary endpoint was safety; the secondary endpoints included objective response rate, duration of response, and T cell persistence. Results: In matched patient-derived xenografts (PDX) models, homologous TILs efficiently reduced tumor size (p < 0.0001) and underwent IL-2 absence in vivo. In the clinical section, all enrolled patients received TIL infusion using a modified TIL therapy regimen successfully with a manageable safety profile. Five (36%, 95% CI 16.3–61.2) out of 14 evaluable patients experienced objective responses, and three complete responses were ongoing at 19.5, 15.4, and 5.2 months, respectively. Responders had longer overall survival (OS) than non-responders (p = 0.036). Infused TILs showed continuous proliferation and long-term persistence in all patients and showed greater proliferation in responders which was indicated by the Morisita overlap index (MOI) of TCR clonotypes between infused TILs and peripheral T cells on day 14 (p = 0.004) and day 30 (p = 0.004). Higher alteration of the CD8+/CD4+ ratio on day 14 indicated a longer OS (p = 0.010). Conclusions: Our modified TIL therapy regimen demonstrated manageable safety, and TILs could survive and proliferate without IL-2 intravenous administration, showing potent efficacy in patients with advanced gynecologic cancer. Trial registration: NCT04766320, Jan 04, 2021. [ABSTRACT FROM AUTHOR]

Background: Evidence from observational studies suggested a connection between immune cells and gynecologic malignancies. To investigate potential causative associations between immunophenotype traits and gynecologic malignancies, we used a two-sample Mendelian randomization analysis. Methods: The genetic instrumental variables of 731 immunophenotypes of peripheral blood were obtained by the GWAS database; the GWAS data of common gynecologic cancers were obtained from FinnGen study. The main statistic method was the inverse-variance weighted method. We also used the weighted mode, weighted median, and MR Egger for evaluations. The MR Steiger directionality test was further used to ascertain the reverse causal relationship between immune cells and gynecologic cancers. Results: We identified 50 highly probable immunophenotypes and 65 possible ones associated with gynecologic malignancies. The majority of the B cell panel was protective factors in cervical cancer. However, there was a correlation found in the B cells panel with a probable factor associated with an elevated risk of endometrial cancer. Immunophenotypes in the monocyte panel were linked to a lower probability of ovarian cancer and vulvar cancer. All of the gynecologic cancers in our study had no statistically significant impact on immune cells, according to reverse MR analysis. Conclusion: Our study firstly emphasized the genetically predicted causality between immune cells and gynecologic malignancies. This knowledge will be critical to formulating the measures to prevent malignancies in female at risk in future clinical practice. [ABSTRACT FROM AUTHOR]

The fibroblast activating protein (FAP) is expressed by some fibroblasts found in healthy tissues. However, FAP is overexpressed in more than 90% of epithelial tumors, including breast and gynecological tumors. As a result, the FAP ligand could be used as a target for diagnosis and treatment purposes. Positron emission tomography/computed tomography (PET/CT) is a hybrid imaging technique commonly used to locate and assess the tumor's molecular and metabolic functions. PET imaging involves the injection of a radiotracer that tends to accumulate more in metabolically active lesions such as cancer. Several radiotracers have been developed to target FAP in PET/CT imaging, such as the fibroblast-activation protein inhibitor (FAPI). These tracers bind to FAP with high specificity and affinity, allowing for the non-invasive detection and quantification of FAP expression in tumors. In this review, we discussed the applications of FAPI PET/CT in the diagnosis and treatment of breast and the most common gynecologic malignancies. Radiolabeled FAPI can improve the detection, staging, and assessment of treatment response in breast and the most common gynecologic malignancies, but the problem with normal hormone-responsive organs remains insurmountable. Compared to the diagnostic applications of FAPI, further research is needed for future therapeutic applications. [ABSTRACT FROM AUTHOR]

Objective: Living in a food desert is a known negative health risk, with recent literature finding an associated higher mortality in patients with cancers. Gynecologic cancers have not specifically been studied. We aimed to describe patients with gynecologic cancers who live in a food desert and determine if there is an association between living in a food desert and gynecologic cancer mortality. Methods: The 2013–2019 California Cancer Registry (CCR) was used to identify patients with endometrial, ovarian, or cervical cancers. Patient residential census tract was linked to food desert census tracts identified by the 2015 United States Department of Agriculture Food Access Research Atlas. Comorbidity data were obtained from the California Office of Statewide Health Planning and Development database (OSHPD). Treatment, diagnosis, and survival outcomes were obtained from the CCR’s variables and compared by food desert status. Five-year disease-specific survival was analyzed by applying Cox proportional hazards analysis. Results: 40,340 gynecologic cancer cases were identified. 60.1 % had endometrial cancer, 23.2 % had ovarian cancer, and 15.9 % had cervical cancer. The average age of the cohort was 59.4 years, 48.0 % was non-Hispanic White, 50.3 % was privately insured, and 6.8 % of lived in a food desert. Living in a food desert was associated with higher disease-specific mortality for patients with gynecologic cancers (endometrial cancer HR 1.43p

Minimally Invasive Surgery (MIS) represents a safe and feasible option for the surgical treatment of gynecologic malignancies, offering benefits, including reduced blood loss, lower complications, and faster recovery, without compromising oncological outcomes in selected patients. MIS is widely accepted in early-stage gynecologic malignancies, including endometrial cancer, cervical tumors measuring 2 cm or less, and early-stage ovarian cancer, considering the risk of surgical spillage. Despite its advantages, MIS does not rule out the possibility of adverse events such as postoperative infections. This retrospective study on 260 patients undergoing laparoscopic surgery at Parma University Hospital for gynecologic malignancies explores the incidence and risk factors of postoperative infectious complications. The Clavien-Dindo classification was used to rank postoperative surgical complications occurring 30 days after surgery and Enhanced Recovery After Surgery (ERAS) recommendations put into practice. In our population, 15 (5.8%) patients developed infectious complications, predominantly urinary tract infections (9, 3.5%). Longer surgical procedures were independently associated with higher postoperative infection risk (p = 0.045). Furthermore, C1 radical hysterectomy correlated significantly with infectious complications (p = 0.001, OR 3.977, 95% CI 1.370–11.544). In conclusion, compared to prior research, our study reported a lower rate of infectious complications occurrence and highlights the importance of adopting infection prevention measures. [ABSTRACT FROM AUTHOR]

Simple Summary: Radiotherapy (RT) is often part of the curative intent treatment in gynecologic oncology. In cervical and uterine cancers, RT is typically delivered daily over five weeks. Recently, advances in technology have allowed for higher doses of RT to be given per fraction with an overall shorter treatment time. This treatment course, called hypofractionated RT, has become the standard of care in other pelvic sites such as the prostate and rectum and is being investigated in gynecologic malignancies. In addition, hypofractionation offers a potential solution in low-resource settings where there is insufficient access to radiotherapy as with the challenges faced during the COVID-19 pandemic worldwide. This review summarizes the rationale and application for hypofractionation, the available literature and ongoing clinical trials in the gynecologic space. Radiotherapy (RT) has a fundamental role in the treatment of gynecologic malignancies, including cervical and uterine cancers. Hypofractionated RT has gained popularity in many cancer sites, boosted by technological advances in treatment delivery and image verification. Hypofractionated RT uptake was intensified during the COVID-19 pandemic and has the potential to improve universal access to radiotherapy worldwide, especially in low-resource settings. This review summarizes the rationale, the current challenges and investigation efforts, together with the recent developments associated with hypofractionated RT in gynecologic malignancies. A comprehensive search was undertaken using multiple databases and ongoing trial registries. In the definitive radiotherapy setting for cervical cancers, there are several ongoing clinical trials from Canada, Mexico, Iran, the Philippines and Thailand investigating the role of a moderate hypofractionated external beam RT regimen in the low-risk locally advanced population. Likewise, there are ongoing ultra and moderate hypofractionated RT trials in the uterine cancer setting. One Canadian prospective trial of stereotactic hypofractionated adjuvant RT for uterine cancer patients suggested a good tolerance to this treatment strategy in the acute setting, with a follow-up trial currently randomizing patients between conventional fractionation and the hypofractionated dose regimen delivered in the former trial. Although not yet ready for prime-time use, hypofractionated RT could be a potential solution to several challenges that limit access to and the utilization of radiotherapy for gynecologic cancer patients worldwide. [ABSTRACT FROM AUTHOR]

Opinion Statement: Antibody-drug conjugates (ADCs) are a novel class of targeted cancer therapies with the ability to selectively deliver a cytotoxic drug to a tumor cell using a monoclonal antibody linked to a cytotoxic payload. The technology of ADCs allows for tumor-specificity, improved efficacy, and decreased toxicity compared to standard chemotherapy. Common toxicities associated with ADC use include ocular, pulmonary, hematologic, and neurologic toxicities. Several ADCs have been approved by the United States Food and Drug Administration (FDA) for the management of patients with recurrent or metastatic gynecologic cancers, a population with poor outcomes and limited effective treatment options. The first FDA-approved ADC for recurrent or metastatic cervical cancer was tisotumab vedotin, a tissue factor-targeting agent, after demonstrating response in the innovaTV 204 trial. Mirvetuximab soravtansine targets folate receptor alpha and is approved for use in patients with folate receptor alpha-positive, platinum-resistant, epithelial ovarian cancer based on results from the SORAYA trial. While there are no FDA-approved ADCs for the treatment of uterine cancer, trastuzumab deruxtecan, an anti-human epidermal growth factor receptor 2 (HER2) agent, is actively being investigated. In this review, we will describe the structure and mechanism of action of ADCs, discuss their toxicity profiles, review ADCs both approved and under investigation for the management of gynecologic cancers, and discuss mechanisms of ADC resistance. [ABSTRACT FROM AUTHOR]

Simple Summary: Recent studies have shown a negative association between prior antibiotic use and response rate to immune checkpoint inhibitors (ICIs) in solid tumors, including gynecologic cancers. In this study, use of antibiotics for >14 days prior to ICI treatment was associated with reduced survival. Restricted use and adequate duration and spectrum of antibiotics should be considered when treating patients with recurrent gynecologic cancer. The various response rates to ICI could be attributed to gut dysbiosis. A study of gut microbiota may address the ICI response in the future. Purpose: Antibiotic use preceding immune checkpoint inhibitor (ICI) treatment has been associated with a decreased efficacy of ICI in solid tumors. In this study, we evaluated the effect of antibiotic use before ICI therapy on oncological outcomes. Methods: We examined patients with recurrent gynecologic malignancies at two academic institutions. The clinical data, including antibiotic use within 60 days of ICI initiation, type of antibiotics, reasons for antibiotic use, body mass index, tumor site, chemotherapy-free interval, prior history of radiotherapy, disease control rate (DCR), and overall survival (OS), were assessed. Results: Of 215 patients, 22.9% (n = 47) received antibiotics before ICI treatment. The most common cancer was ovarian (52.1%, n = 112), followed by cervical (24.7%, n = 53) and endometrial (16.7%, n = 36). When we divided the cohort based on antibiotic use before ICIs, there were no significant differences in the DCR and baseline characteristics between the two groups. On multivariate analyses, the variables associated with poor OS were previous use of antibiotics for a cumulative duration of >14 days (HR 2.286, 95% CI 1.210–4.318; p = 0.011); Eastern Cooperative Oncology Group 2 or 3 (HR 4.677, 95% CI 2.497–8.762; p < 0.001); and chemotherapy-free interval of <6 months (HR 2.007, 95% CI 1.055–3.819; p = 0.034). Conclusion: Prior use of antibiotics for a cumulative duration of >14 days was associated with reduced survival in recurrent gynecologic malignancies. [ABSTRACT FROM AUTHOR]

Objective: Immune checkpoint inhibitors are rapidly being used in solid and hematologic malignancies, including gynecologic cancers. The high mortality and relapsing rates of advanced gynecologic malignancies remain a challenging issue. This study aimed to identify the predicting factors associated with survival prognosis and disease control in patients with refractory/relapsing (R/R) gynecologic malignancies receiving anti PD-1 therapy. Materials and methods: We retrospectively reviewed the medical records of 49 patients diagnosed with R/R gynecologic malignancies between July 2012 and June 2019 in Chang Gung Memorial Hospital, Taiwan. Among the 49 patients, 6 were excluded due to incomplete medical records or not receiving anti PD-1 therapy. The remaining 43 patients were further divided into responsive and non-responsive groups according to disease control for predicting prognostic factor analysis. Results: For the 43 cases, the median age at diagnosis and disease follow-up length were 54 years and 29 months, respectively. Among them, 23 (53%) were categorized into the responsive group, and the remaining 20 (47%) were categorized into the non-responsive group. The mortality rates were 17% and 25% in the responsive and non-responsive groups, respectively. The responsive group had significantly higher absolute lymphocyte count (ALC), higher absolute neutrophil count (ANC) and low platelet to lymphocyte ratio (PLR) than the non-responsive group. A superior long-term survival trend was also observed in the responsive group, but the difference was not statistically significant. Conclusions: This study reinforced the hypothesis that high ALC, high ANC and low PLR are associated with superior disease control in patients with R/R gynecologic malignancies receiving anti PD-1 therapy.

Objective: Positron emission tomography with 2-deoxy-2-[fluorine-18] fluoro- D-glucose integrated with computed tomography (18F-FDG PET/CT) or magnetic resonance imaging (18F-FDG PET/MRI) has emerged as a promising tool for managing various types of cancer. This review study was conducted to investigate the role of 18F- FDG PET/CT and FDG PET/MRI in the management of gynecological malignancies. Search strategy: We searched for relevant articles in the three databases PubMed/MEDLINE, Scopus, and Web of Science. Selection criteria: All studies reporting data on the FDG PET/CT and FDG PET MRI in the management of gynecological cancer, performed anywhere in the world and published exclusively in the English language, were included in the present study. Data collection and analysis: We used the EndNote software (EndNote X8.1, Thomson Reuters) to list the studies and screen them on the basis of the inclusion criteria. Data, including first author, publication year, sample size, clinical application, imaging type, and main result, were extracted and tabulated in Excel. The sensitivity, specificity, and diagnostic accuracy of the modalities were extracted and summarized. Main results: After screening 988 records, 166 studies published between 2004 and 2022 were included, covering various methodologies. Studies were divided into the following five categories: the role of FDG PET/CT and FDG-PET/MRI in the management of: (a) endometrial cancer (n = 30); (b) ovarian cancer (n = 60); (c) cervical cancer (n = 50); (d) vulvar and vagina cancers (n = 12); and (e) gynecological cancers (n = 14). Conclusions: FDG PET/CT and FDG PET/MRI have demonstrated potential as non-invasive imaging tools for enhancing the management of gynecological malignancies. Nevertheless, certain associated challenges warrant attention. [ABSTRACT FROM AUTHOR]

Brachytherapy irradiation carries risks of both bleeding and venous thromboembolism (VTE). No screening or management recommendations for VTE in this setting have been developed. Our study aims to understand the incidence of VTE, compile published anticoagulation guidelines, and call for future guidelines to address thromboprophylaxis in this population. A retrospective, single institution study of patients undergoing brachytherapy irradiation between 2012 and 2022 was undertaken. We analyzed 2 cohorts: 87 patients undergoing brachytherapy with an inpatient admission, and 66 patients assessed for risk of VTE or bleeding after discharge from an inpatient admission for brachytherapy. Caprini risk scores were calculated for each patient, and statistical analyses were performed. Eighty-seven patients were included, and 25% had a VTE diagnosis. Forty-seven (54%) of patients included underwent brachytherapy as definitive treatment of cervical cancer, and 16 (18%) received brachytherapy irradiation to treat recurrent endometrial cancer. In the cohort of 66 patients assessed for risk of VTE or bleeding after brachytherapy discharge, 23 (34.8%) were discharged with thromboprophylaxis, and 43 (65.2%) were discharged without thromboprophylaxis. None of the patients discharged on thromboprophylaxis were diagnosed with a VTE within 90 days of discharge after brachytherapy, whereas 3 of 43 (7%) discharged without thromboprophylaxis were diagnosed with a VTE, OR and 95% CI: 0.25 (0.01–5.29), p = 0.37. Of the 23 patients discharged on thromboprophylaxis, 1 was readmitted for bleeding OR and 95% CI: 5.8 (0.22–155.18), p = 0.29. The median Caprini score was 11. VTE is a common occurrence in patients undergoing brachytherapy. Patients undergoing brachytherapy irradiation who require inpatient admission represent a unique population, and specialty organizations should develop consensus recommendations to address these clinical challenges. [ABSTRACT FROM AUTHOR]

Endometrial cancer (EC) is a gynecological neoplasm that is increasing in occurrence and mortality rates. Although endometrial cancer in the early stages shows a relatively favorable prognosis, there is an increase in cancer-related mortality rates in the advanced or recurrent endometrial carcinoma population and patients in the metastatic setting. This discrepancy has presented an opportunity for research and development of target therapies in this population. After obtaining promising results with hematologic cancers, chimeric antigen receptor (CAR)-T cell immunotherapy is gaining acceptance as a treatment for solid neoplasms. This treatment platform allows T cells to express tumor-specific CARs on the cell surface, which are administered to the patient to treat neoplastic cells. Given that CAR-T cell therapy has shown potential and clinical benefit compared to other T cell treatment platforms, additional research is required to overcome physiological limitations such as CAR-T cell depletion, immunosuppressive tumor microenvironment, and the lack of specific target molecules. Different approaches and development are ongoing to overcome these complications. This review examines CAR-T cell therapy’s current use for endometrial carcinomas. We also discuss the significant adverse effects and limitations of this immunotherapeutic approach. Finally, we consolidate signal-seeking early-phase clinical trials and advancements that have shown promising results, leading to the approval of new immunotherapeutic agents for the disease.

Many current radiotherapy patient education materials are not patient-centered. An interprofessional team developed Communicating the Gynecologic Brachytherapy Experience (CoGBE), a graphic narrative discussion guide for cylinder, intracavitary, and interstitial high-dose-rate (HDR) gynecologic brachytherapy. This study assesses perceived clinical benefits, usability, and anxiety-reduction of CoGBE. An electronic survey was sent to members of the American Brachytherapy Society. Participants were assigned to assess one of the three modality-specific CoGBE versions using a modified Systems Usability Scale (SUS), modified state-trait anxiety index (mSTAI), and Likert-type questions. Free response data was analyzed using modified grounded theory. Median modified SUS score was 76.3 (interquartile range [IQR], 71.3−82.5) and there were no significant differences between guide types. Median mSTAI was 40 (IQR, 40−43.3) for all guides collectively. The cylinder guide had a significantly higher median mSTAI than the intracavitary and interstitial guides (41.6 vs. 40.0 and 40.0; p = 0.04) suggesting the cylinder guide may have less impact on reducing anxiety. Most respondents reported that CoGBE was helpful (72%), would improve patient understanding (77%) and consultation memorability (82%), and was at least moderately likely to be incorporated into their practice (80%). Qualitative analysis themes included personalization and relatability (positive); generalizability (negative); illustrations (both). Clinicians rate CoGBE as usable with potential to reduce patient anxiety, especially with more invasive treatment modalities including intracavitary or interstitial high-dose-rate. CoGBE has the potential to improve patient-clinician communication for a wider range of patients due to its accessible, adaptable, and patient-centered design. [ABSTRACT FROM AUTHOR]

Simple Summary: Common gynecologic malignancies include ovarian, cervical, and endometrial cancer. Endometriosis is characterized by distant metastasis and is associated with gynecologic tumors. Most gynecologic malignancies are diagnosed in the middle and late stages of cancer, which complicates treatment; therefore, early diagnosis and therapy are beneficial to patient prognosis. Small extracellular vesicles (sEVs) have rich content, stable existence, and low antigenicity, which can be used for early diagnosis and precision treatment. However, current sEVs detection methods are difficult to popularize, and the contents of sEVs are complex and thus unsuitable to meet the requirements of clinical detection. This highlights the need to find more accurate and targeted molecules with diagnostic value. Our review aims to summarize the extraction and identification of sEVs and their application in the early detection and targeted therapy of gynecologic malignancies in recent years. Small extracellular vesicles (sEVs) are the key mediators of intercellular communication. They have the potential for clinical use as diagnostic or therapeutic biomarkers and have been explored as vectors for drug delivery. Identification of reliable and noninvasive biomarkers, such as sEVs, is important for early diagnosis and precise treatment of gynecologic diseases to improve patient prognosis. Previous reviews have summarized routine sEVs isolation and identification methods; however, novel and unconventional methods have not been comprehensively described. This review summarizes a convenient method of isolating sEVs from body fluids and liquid biopsy-related sEV markers for early, minimally invasive diagnosis of gynecologic diseases. In addition, the characteristics of sEVs as drug carriers and in precision treatment and drug resistance are introduced, providing a strong foundation for identifying novel and potential therapeutic targets for sEV therapy. We propose potential directions for further research on the applications of sEVs in the diagnosis and treatment of gynecologic diseases. [ABSTRACT FROM AUTHOR]

N6-methyladenosine (m6A) methylation is the most prevalent mRNA modification in eukaryotes, and it is defined as the methylation of nitrogen atoms on the six adenine (A) bases of RNA in the presence of methyltransferases. Methyltransferase-like 3 (Mettl3), one of the components of m6A methyltransferase, plays a decisive catalytic role in m6A methylation. Recent studies have confirmed that m6A is associated with a wide spectrum of biological processes and it significantly affects disease progression and prognosis of patients with gynecologic tumors, in which the role of Mettl3 cannot be ignored. Mettl3 is involved in numerous pathophysiological functions, such as embryonic development, fat accumulation, and tumor progression. Moreover, Mettl3 may serve as a potential target for treating gynecologic malignancies, thus, it may benefit the patients and prolong survival. However, there is a need to further study the role and mechanism of Mettl3 in gynecologic malignancies. This paper reviews the recent progression on Mettl3 in gynecologic malignancies, hoping to provide a reference for further research. [ABSTRACT FROM AUTHOR]

Gynecologic cancers, especially ovarian cancer, are associated with a high incidence of venous thromboembolism (VTE). Recent data have shown the risk of VTE development is not only limited to the postoperative period; there also appears to be an increased risk during neoadjuvant chemotherapy (NACT) administration, prompting the need for better risk stratification in this setting. We sought to assess the risk of VTE development in patients with ovarian cancer undergoing NACT. We performed a PubMed literature review using the following medical terms: advanced ovarian cancer, advanced peritoneal cancer, advanced fallopian tube cancer, thrombosis, thromboembolic events, and neoadjuvant chemotherapy. Eligible studies included patients with advanced ovarian, fallopian tube, or peritoneal cancer who underwent NACT and had VTE. VTE was defined as either a deep venous thrombosis or a pulmonary embolism. Seven relevant studies were identified; all 7 were published between 2017 and 2021. Across these studies, we identified 1427 patients who underwent NACT and either had VTE at presentation or developed VTE during their treatment course. Of these patients, 1171 underwent NACT and were at risk for VTE development and were included in our pooled analysis. Of these patients, 144 (12.3%) developed VTE. VTE prophylaxis may be considered in patients with ovarian cancer undergoing NACT. • Venous thromboembolism (VTE) during neoadjuvant chemotherapy (NACT) can worsen morbidity and delay surgery. • The incidence of VTE during NACT administration in patients with ovarian cancer is not negligible. • Further scoring methods should be established to stratify high-risk patients with ovarian cancer. [ABSTRACT FROM AUTHOR]

Abstract Purpose During the severe acute respiratory syndrome coronavirus 2 pandemic, several patient groups are at particular risk. Mortality is higher among cancer patients and may be increased further by thromboembolic events, which are more common in coronavirus 2019 patients according to recent publications. We discuss the association of gynecologic malignancies, Severe acute respiratory syndrome coronavirus 2, and thromboembolism by reporting a case study and summarizing available literature. Case report A 71-year-old Caucasian patient with ovarian cancer receiving first-line chemotherapy was diagnosed with deep vein thrombosis and pulmonary embolism. Routine screening revealed infection with severe acute respiratory syndrome coronavirus 2 in absence of specific symptoms. After uneventful recovery, oncologic treatment could be continued a few weeks later. Methods We performed a systematic review of the literature on PubMed following Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines. The search included articles ahead of print, published between 1 December 2019 and 1 June 2020. Cross-searches were conducted on all relevant articles. Results We identified five articles meeting the defined criteria, including two retrospective studies, a review, a position paper, as well as a letter to the editor. Conclusion Cancer patients infected with severe acute respiratory syndrome coronavirus 2 have a relatively poor outcome, which may partially be due to a higher rate of thromboembolic events. Thromboprophylaxis is recommended, and scoring systems are helpful in early detection. In cancer patients with severe acute respiratory syndrome coronavirus 2, individual risk for thromboembolic events should be taken into account when considering interruption versus continuation of antitumoral therapy. However, further data and studies are required.

Objective: Positron emission tomography with 2-deoxy-2-[fluorine-18] fluoro- D-glucose integrated with computed tomography (18F-FDG PET/CT) or magnetic resonance imaging (18F-FDG PET/MRI) has emerged as a promising tool for managing various types of cancer. This review study was conducted to investigate the role of 18F- FDG PET/CT and FDG PET/MRI in the management of gynecological malignancies. Search strategy: We searched for relevant articles in the three databases PubMed/MEDLINE, Scopus, and Web of Science. Selection criteria: All studies reporting data on the FDG PET/CT and FDG PET MRI in the management of gynecological cancer, performed anywhere in the world and published exclusively in the English language, were included in the present study. Data collection and analysis: We used the EndNote software (EndNote X8.1, Thomson Reuters) to list the studies and screen them on the basis of the inclusion criteria. Data, including first author, publication year, sample size, clinical application, imaging type, and main result, were extracted and tabulated in Excel. The sensitivity, specificity, and diagnostic accuracy of the modalities were extracted and summarized. Main results: After screening 988 records, 166 studies published between 2004 and 2022 were included, covering various methodologies. Studies were divided into the following five categories: the role of FDG PET/CT and FDG-PET/MRI in the management of: (a) endometrial cancer (n = 30); (b) ovarian cancer (n = 60); (c) cervical cancer (n = 50); (d) vulvar and vagina cancers (n = 12); and (e) gynecological cancers (n = 14). Conclusions: FDG PET/CT and FDG PET/MRI have demonstrated potential as non-invasive imaging tools for enhancing the management of gynecological malignancies. Nevertheless, certain associated challenges warrant attention.

Cervical cancer (CC) is the fourth leading cause of death in women worldwide and despite the introduction of screening programs about 30% of patients presents advanced disease at diagnosis and 30-50% of them relapse in the first 5-years after treatment. According to FIGO staging system 2018, stage IB3-IVA are classified as locally advanced cervical cancer (LACC); its correct therapeutic choice remains still controversial and includes neoadjuvant chemoradiotherapy, external beam radiotherapy, brachytherapy, hysterectomy or a combination of these modalities. In this review we focus on the most appropriated therapeutic options for LACC and imaging protocols used for its correct follow-up. We explore the imaging findings after radiotherapy and surgery and discuss the role of imaging in evaluating the response rate to treatment, selecting patients for salvage surgery and evaluating recurrence of disease. We also introduce and evaluate the advances of the emerging imaging techniques mainly represented by spectroscopy, PET-MRI, and radiomics which have improved diagnostic accuracy and are approaching to future direction. [ABSTRACT FROM AUTHOR]

Simple Summary: Gynecological malignancies are among the most common cancers with significant morbidity and mortality worldwide. Management and overall patient survival is reliant upon early detection, accurate staging and early detection of any recurrence. This article provides a comprehensive review of the recent advances in imaging of gynecologic malignancies with emphasis on cervical, endometrial, and ovarian neoplasms. Gynecologic malignancies are among the most common cancers in women worldwide and account for significant morbidity and mortality. Management and consequently overall patient survival is reliant upon early detection, accurate staging and early detection of any recurrence. Ultrasound, Computed Tomography (CT), Magnetic resonance imaging (MRI) and Positron Emission Tomography-Computed Tomography (PET-CT) play an essential role in the detection, characterization, staging and restaging of the most common gynecologic malignancies, namely the cervical, endometrial and ovarian malignancies. Recent advances in imaging including functional MRI, hybrid imaging with Positron Emission Tomography (PET/MRI) contribute even more to lesion specification and overall role of imaging in gynecologic malignancies. Radiomics is a neoteric approach which aspires to enhance decision support by extracting quantitative information from radiological imaging. [ABSTRACT FROM AUTHOR]

We report the feasibility, experience, and early outcomes of the combined intracavitary and interstitial dedicated applicator using the Kelowna GYN template (Varian, Palo Alto, CA). The Kelowna GYN template is CT compatible and used for the treatment of gynecologic cancers. In cases with patients that have an intact uterus, a modified applicator system using the Kelowna GYN template and a 3D printed adapter piece allows for compatibility with an intrautaerine tandem. We reviewed the treatment course of 23 patients comprising of 86 fractions of HDR treatment. Median D90 for cervical tumors (n = 7) was 82.4 Gy (range 77.7–92.6); for postoperative cervical tumors (n = 2) was 73.9 Gy (range 72.0–5.8); for vaginal tumors (n = 4) was 85.8 Gy (range 79.8–88.1); for recurrent endometrial (n = 10) was 86.9 Gy (range 74.8–103.2). Median EQD2 D2cc for bladder was 72.4 Gy (range 47.7–99.4), for rectum was 61.2 Gy (range 52.4–80.6), and for sigmoid colon of 50.5 Gy (44.3–66.9). At a median follow-up of 12 months, 2 patients had a local recurrence. Two patients had distant recurrence: one with carcinomatosis at 6 months, and one with pulmonary metastases at 3 months. No patients had late grade three toxicities. Our single institutional experience supports the use of the Kelowna template as a robust system as a combined IC-IS applicator resulting in versatile and reproducible implants for a variety of gynecologic malignancies. [ABSTRACT FROM AUTHOR]

There is a clinical need to develop anatomic phantoms for simulation-based learning in gynecological brachytherapy. Here, we provide a step-by-step approach to build a life-sized gynecological training phantom based on magnetic resonance imaging (MRI) of an individual patient. Our hypothesis is that this phantom can generate convincing ultrasound (US) images that are similar to patient scans. Organs-at-risk were manually segmented using patient scans (MRI). The gynecological phantom was constructed using positive molds from 3D printing and polyvinyl chloride (PVC) plastisol. Tissue texture/acoustic properties were simulated using different plastic softener/hardener ratios and microbead densities. Nine readers (residents) were asked to evaluate 10 cases (1 ultrasound image per case) and categorize each as a "patient" or "phantom" image. To evaluate whether the phantom and patient images were equivalent, we used a multireader, multicase equivalence study design with two composite null hypotheses with proportion (p r) at H 01 : p r ≤ 0.35 and H 02 : p r ≥ 0.65. Readers were also asked to review US videos and identify the insertion of an interstitial needle into the pelvic phantom. Computed Tomography (CT) and magnetic resonance (MR) images of the phantom were acquired for a feasibility study. Readers correctly classified "patient" and "phantom" scans at p r = 53.3% ± 6.2% (p values 0.013 for H 01 and 0.054 for H 02 , df = 5.96). Readers reviewed US videos and identified the interstitial needle 100% of the time in transabdominal view, and 78% in transrectal view. The phantom was CT and MR safe. We have outlined a manufacturing process to create a life-sized, gynecological phantom that is compatible with multi-modality imaging and can be used to simulate clinical scenarios in image-guided brachytherapy procedures. [ABSTRACT FROM AUTHOR]

Objective: Myocardial edema is an early manifestation of chemotherapy- related myocardial injury. In this study, we used cardiac magnetic resonance (CMR) T2 mapping to assess myocardial edema and its changes during chemotherapy for gynecologic malignancies. Methods: We enrolled 73 patients receiving chemotherapy for gynecologic malignancies, whose the latest cycle was within one month before the beginning of this study, and 41 healthy volunteers. All participants underwent CMR imaging. Of the 73 patients, 35 completed CMR follow-up after a median interval of 6 (3.3 to 9.6) months. The CMR sequences included cardiac cine, T2 mapping, and late gadolinium enhancement. Results: Myocardial T2 was elevated in patients who were treated with chemotherapy compared with healthy volunteers [41ms (40ms to 43ms) vs. 41ms (39ms to 41ms), P = 0.030]. During follow-up, myocardial T2 rose further [40ms (39ms to 42ms) vs. 42.70 ± 2.92ms, P < 0.001]. Multivariate analysis showed that the number of chemotherapy cycles was associated with myocardial T2 elevation (b = 0.204, P = 0.029). After adjustment for other confounders, myocardial T2 elevation was independently associated with a decrease in left ventricular mass (b = -0.186; P = 0.024). Conclusion: In patients with gynecologic malignancies, myocardial edema developed with chemotherapy cycles increase, and was associated with left ventricular mass decrease. T2 mapping allows the assessment of myocardial edema and monitoring of its change during chemotherapy. [ABSTRACT FROM AUTHOR]

N6‐methyladenosine (m6A) modification is one of the most abundant modifications in eukaryotic mRNA, regulated by m6A methyltransferase and demethylase. m6A modified RNA is specifically recognized and bound by m6A recognition proteins, which mediate splicing, maturation, exonucleation, degradation, and translation. In gynecologic malignancies, m6A RNA modification‐related molecules are expressed aberrantly, significantly altering the posttranscriptional methylation level of the target genes and their stability. The m6A modification also regulates related metabolic pathways, thereby controlling tumor development. This review analyzes the composition and mode of action of m6A modification‐related proteins and their biological functions in the malignant progression of gynecologic malignancies, which provide new ideas for the early clinical diagnosis and targeted therapy of gynecologic malignancies. [ABSTRACT FROM AUTHOR]

Cervical cancer (CC) is the fourth leading cause of death in women worldwide and despite the introduction of screening programs about 30% of patients presents advanced disease at diagnosis and 30-50% of them relapse in the first 5-years after treatment. According to FIGO staging system 2018, stage IB3-IVA are classified as locally advanced cervical cancer (LACC); its correct therapeutic choice remains still controversial and includes neoadjuvant chemo-radiotherapy, external beam radiotherapy, brachytherapy, hysterectomy or a combination of these modalities. In this review we focus on the most appropriated therapeutic options for LACC and imaging protocols used for its correct follow-up. We explore the imaging findings after radiotherapy and surgery and discuss the role of imaging in evaluating the response rate to treatment, selecting patients for salvage surgery and evaluating recurrence of disease. We also introduce and evaluate the advances of the emerging imaging techniques mainly represented by spectroscopy, PET-MRI, and radiomics which have improved diagnostic accuracy and are approaching to future direction.

Background: To assess the efficacy and safety of recombinant human adenovirus type 5 (H101) in patients with persistent, recurrent, or metastatic gynecologic malignancies. Methods: The study retrospectively enrolled patients with persistent/recurrent/metastatic gynecologic malignancies who received H101-containing treatment at The First Affiliated Hospital of Xi'an Jiaotong University from September 1, 2019 to September 30, 2021. H101 was injected intratumorally into target lesions and dosage was calculated based on tumor diameter once a day for five consecutive days. The primary endpoint was local control (LC) rate. Secondary endpoints included objective response rate (ORR), duration of response (DOR) and progression-free survival (PFS). Safety was the exploratory endpoint. Depending on prior treatment, patients received H101 either as monotherapy or as a combination therapy. Results: Totally, 29 patients were enrolled in the study. Median follow-up was 6.3 months (range: 3.2-27.9) from data analysis cut-off on December 31, 2021. The LC rate at 3 months was 44.8%, while ORR was 72.4%. Median DOR and PFS rates were not determined. The DOR rate, PFS rate at 6 and 12 months were 88.1%, 74.6% and 70.5%, 62.2%, respectively. Responses were observed in all four cancer types. Most treatment-related adverse events (90.5%) were grade 1 or 2, with the most common being fever (70%). Clinically significant adverse events were uncommon (7.9% in grade 3 and 1.6% in grade 4). No treatment-related deaths occurred. Conclusion: Our study showed that H101 (either monotherapy or combination therapy) has promising efficacy and favorable safety in patients with persistent, recurrent, metastatic gynecologic malignancies. [ABSTRACT FROM AUTHOR]

Introduction: In 2019-20, the American College of Radiology (ACR) introduced Ovarian-Adnexal Reporting and Data System Magnetic Resonance Imaging (O-RADS MRII). Application of the O-RADS MRI in routine clinical practice can increase lesion characterization accuracy, promote better interdisciplinary communication, and help in personalized patient management of adnexal masses. Aim: To assess the diagnostic performance of the ACR O-RADS MRI scoring system for the predicting malignancy in adnexal mass in routine clinical radiology practice by using histology/imaging findings during a minimum 4 month follow-up as the reference standard. Materials and Methods: In this single-tertiary center prospective cohort study done in Jorhat Medical College, Assam, 42 patients with 46 adnexal masses who underwent MRI between April 2020 and June 2021 were assessed. The ACR O-RADS MR scores were assigned using the MRI protocol with a dynamic study. Sensitivity, specificity, positive and negative predictive values along with the area under the Receiver Operating Characteristic (ROC) curve were calculated (cut-off score =4 was considered malignancy,). Histopathologic diagnosis or >4 months followup imaging findings was the reference standard used. Logistic regression analysis of MRI parameters used in identifying malignant masses was assessed. Statistical analysis was done using 95% confidence intervals (CIs). The p-values <0.05 was considered statistically significant. Results: The mean age of subjects in the study was 35.9 (range 10-75 years), and 84.8% of adnexal masses (39) were premenopausal. Malignancy was more common in postmenopausal patients (57.1%). Of 46 lesions, 13 (33.3%) were malignant. The ACR O-RADS-MR scoring system, using a dynamic MRI protocol, showed 92.3% sensitivity and 87.8%specificity in malignancy prediction. The area under the ROC curve for predicting malignancy was 0.962. The positive and negative predictive values were 75% and 89.1%, respectively. Conclusion: In a teaching hospital in assam, the O-RADS MRI scoring system, based on a dynamic MRI protocol demonstrated good sensitivity, specificity and area under the Receiver Operator Characteristic (ROC) curve in identifying malignant adnexal masses. The ACR O-RADS MRI system enables standardized MRI reporting with uniform lexicon and interpretation guide on adnexal masses. This will help to improve communication between radiologists and referring physician and in patient management, particularly in indeterminate masses on ultrasound. [ABSTRACT FROM AUTHOR]

The incidence of human cancers attributable to infectious agents has been estimated to be 15%. Hepatitis B virus (HBV) infects hepatocytes causing hepatocellular carcinoma. It can also infect extrahepatic cells and cause chronic inflammation, which is associated with a variety of extrahepatic cancers. Female reproductive organs communicate with the external environment through vagina. Viral nucleic acid can be detected in the vaginal secretions and ovarian tissues of HBV carriers. Epidemiological studies suggested HBV infection may be a risk factor for gynecologic malignancies, and related to poor prognosis of patients. Cervical cancer, endometrial cancer and ovarian cancer are most common gynecologic malignancies. This paper reviews the recent studies on the association between HBV infection and gynecologic malignancies, and analyzes the potential mechanism of HBV infection in the occurrence and development of cancer and prospects the future research direction. [ABSTRACT FROM AUTHOR]

Purpose: During the severe acute respiratory syndrome coronavirus 2 pandemic, several patient groups are at particular risk. Mortality is higher among cancer patients and may be increased further by thromboembolic events, which are more common in coronavirus 2019 patients according to recent publications. We discuss the association of gynecologic malignancies, Severe acute respiratory syndrome coronavirus 2, and thromboembolism by reporting a case study and summarizing available literature.Case Report: A 71-year-old Caucasian patient with ovarian cancer receiving first-line chemotherapy was diagnosed with deep vein thrombosis and pulmonary embolism. Routine screening revealed infection with severe acute respiratory syndrome coronavirus 2 in absence of specific symptoms. After uneventful recovery, oncologic treatment could be continued a few weeks later.Methods: We performed a systematic review of the literature on PubMed following Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines. The search included articles ahead of print, published between 1 December 2019 and 1 June 2020. Cross-searches were conducted on all relevant articles.Results: We identified five articles meeting the defined criteria, including two retrospective studies, a review, a position paper, as well as a letter to the editor.Conclusion: Cancer patients infected with severe acute respiratory syndrome coronavirus 2 have a relatively poor outcome, which may partially be due to a higher rate of thromboembolic events. Thromboprophylaxis is recommended, and scoring systems are helpful in early detection. In cancer patients with severe acute respiratory syndrome coronavirus 2, individual risk for thromboembolic events should be taken into account when considering interruption versus continuation of antitumoral therapy. However, further data and studies are required. [ABSTRACT FROM AUTHOR]

BackgroundTo assess the efficacy and safety of recombinant human adenovirus type 5 (H101) in patients with persistent, recurrent, or metastatic gynecologic malignancies.MethodsThe study retrospectively enrolled patients with persistent/recurrent/metastatic gynecologic malignancies who received H101-containing treatment at The First Affiliated Hospital of Xi’an Jiaotong University from September 1, 2019 to September 30, 2021. H101 was injected intratumorally into target lesions and dosage was calculated based on tumor diameter once a day for five consecutive days. The primary endpoint was local control (LC) rate. Secondary endpoints included objective response rate (ORR), duration of response (DOR) and progression-free survival (PFS). Safety was the exploratory endpoint. Depending on prior treatment, patients received H101 either as monotherapy or as a combination therapy.ResultsTotally, 29 patients were enrolled in the study. Median follow-up was 6.3 months (range: 3.2-27.9) from data analysis cut-off on December 31, 2021. The LC rate at 3 months was 44.8%, while ORR was 72.4%. Median DOR and PFS rates were not determined. The DOR rate, PFS rate at 6 and 12 months were 88.1%, 74.6% and 70.5%, 62.2%, respectively. Responses were observed in all four cancer types. Most treatment-related adverse events (90.5%) were grade 1 or 2, with the most common being fever (70%). Clinically significant adverse events were uncommon (7.9% in grade 3 and 1.6% in grade 4). No treatment-related deaths occurred.ConclusionOur study showed that H101 (either monotherapy or combination therapy) has promising efficacy and favorable safety in patients with persistent, recurrent, metastatic gynecologic malignancies.

BackgroundDespite the growing number of patients with both coronary artery disease and gynecological cancer, there are no nationally representative studies of mortality and cost effectiveness for percutaneous coronary interventions (PCI) and this cancer type.MethodsBackward propagation neural network machine learning supported and propensity score adjusted multivariable regression was conducted for the above outcomes in this case-control study of the 2016 National Inpatient Sample (NIS), the United States' largest all-payer hospitalized dataset. Regression models were fully adjusted for age, race, income, geographic region, cancer metastases, mortality risk, and the likelihood of undergoing PCI (and also with length of stay [LOS] for cost). Analyses were also adjusted for the complex survey design to produce nationally representative estimates. Centers for Disease Control and Prevention (CDC)-based cost effectiveness ratio (CER) analysis was performed.ResultsOf the 30,195,722 hospitalized patients meeting criteria, 1.27% had gynecological cancer of whom 0.02% underwent PCI including 0.04% with metastases. In propensity score adjusted regression among all patients, the interaction of PCI and gynecological cancer (vs. not having PCI) significantly reduced mortality (OR 0.53, 95%CI 0.36–0.77; p = 0.001) while increasing LOS (Beta 1.16 days, 95%CI 0.57–1.75; p < 0.001) and total cost (Beta $31,035.46, 95%CI 26758.86–35312.06; p < 0.001). Among gynecological cancer patients, mortality was significantly reduced by PCI (OR 0.58, 95%CI 0.39–0.85; p = 0.006) and being in East North Central, West North Central, South Atlantic, and Mountain regions (all p < 0.03) compared to New England. PCI reduced mortality but not significantly for metastatic patients (OR 0.74, 95%CI 0.32–1.71; p = 0.481). Eighteen extra gynecological cancer patients' lives were saved with PCI for a net national cost of $3.18 billion and a CER of $176.50 million per averted death.ConclusionThis large propensity score analysis suggests that PCI may cost inefficiently reduce mortality for gynecological cancer patients, amid income and geographic disparities in outcomes.

Background and PurposeHigh-dose-rate interstitial brachytherapy (HDR-ISBT) is recommended to obtain a better local tumor control for uterine cancer patients in specific situations such as bulky lesions, an extension to the lateral parametrium, or tumors with irregular shapes. Our group uses real-time transrectal ultrasonography (TRUS) to guide freehand interstitial needle insertion. Occasionally, target tumors locate deeper beyond the rectum and cannot be visualized by TRUS. CT can guide needles to deeply located tumors, but in such cases, repeated image obtainment is required to achieve ideal needle localization. In this report, we present nine cases of patients who underwent HDR-ISBT for deeply situated tumors guided by a combination of transrectal and transabdominal ultrasonography (TR/TA-US).Material and MethodsNine uterine cancer patients whose tumors were located deeper than the reach of TRUS and underwent HDR-ISBT guided by TR/TA-US were presented. All nine cases had no distal organ metastasis and underwent external beam radiation therapy (EBRT) to the pelvic region for 45–50.4 Gy in 25–28 fractions followed by boost HDR-ISBT for deeply situated tumors guided by TR/TA-US.ResultsThere were seven cervical cancer and two endometrial cancer patients: six with extensive uterine corpus invasion, one cervical cancer with massive pelvic lymph node metastasis, one cervical cancer with postoperative pelvic recurrence, and one with left ovarian direct tumor invasion. The median follow-up period was 15 months (range 3–28 months). The average clinical target volume at the time of first HDR-ISBT was 131 ml (range 44–335 ml). The linear distance from the vaginal entrance to the deepest part of the tumor at first time brachytherapy of nine cases was 14.0 (9.0–17.0) cm. HDR-ISBT dose fractionation was 24–30 Gy in four or five fractions. Seven out of nine cases had no local recurrence in the follow-up period. One had local in-field recurrence 25 months after HDR-ISBT. Another case with carcinosarcoma could not obtain local control and underwent salvage hysterectomy for a residual uterine tumor 11 months after HDR-ISBT. Four cases had extra-field recurrence in lymph nodes or distant organs.ConclusionsIn brachytherapy for gynecologic malignancies, deeply situated tumors located out of reach of TRUS may obtain favorable local control by HDR-ISBT guided with TR/TA-US.

Background and Purpose: High-dose-rate interstitial brachytherapy (HDR-ISBT) is recommended to obtain a better local tumor control for uterine cancer patients in specific situations such as bulky lesions, an extension to the lateral parametrium, or tumors with irregular shapes. Our group uses real-time transrectal ultrasonography (TRUS) to guide freehand interstitial needle insertion. Occasionally, target tumors locate deeper beyond the rectum and cannot be visualized by TRUS. CT can guide needles to deeply located tumors, but in such cases, repeated image obtainment is required to achieve ideal needle localization. In this report, we present nine cases of patients who underwent HDR-ISBT for deeply situated tumors guided by a combination of transrectal and transabdominal ultrasonography (TR/TA-US). Material and Methods: Nine uterine cancer patients whose tumors were located deeper than the reach of TRUS and underwent HDR-ISBT guided by TR/TA-US were presented. All nine cases had no distal organ metastasis and underwent external beam radiation therapy (EBRT) to the pelvic region for 45–50.4 Gy in 25–28 fractions followed by boost HDR-ISBT for deeply situated tumors guided by TR/TA-US. Results: There were seven cervical cancer and two endometrial cancer patients: six with extensive uterine corpus invasion, one cervical cancer with massive pelvic lymph node metastasis, one cervical cancer with postoperative pelvic recurrence, and one with left ovarian direct tumor invasion. The median follow-up period was 15 months (range 3–28 months). The average clinical target volume at the time of first HDR-ISBT was 131 ml (range 44–335 ml). The linear distance from the vaginal entrance to the deepest part of the tumor at first time brachytherapy of nine cases was 14.0 (9.0–17.0) cm. HDR-ISBT dose fractionation was 24–30 Gy in four or five fractions. Seven out of nine cases had no local recurrence in the follow-up period. One had local in-field recurrence 25 months after HDR-ISBT. Another case with carcinosarcoma could not obtain local control and underwent salvage hysterectomy for a residual uterine tumor 11 months after HDR-ISBT. Four cases had extra-field recurrence in lymph nodes or distant organs. Conclusions: In brachytherapy for gynecologic malignancies, deeply situated tumors located out of reach of TRUS may obtain favorable local control by HDR-ISBT guided with TR/TA-US. [ABSTRACT FROM AUTHOR]

Standardized simulation training geared towards interstitial brachytherapy (IS BT) for gynecologic malignancies is lacking in radiation oncology resident education. We developed and implemented a curriculum for IS BT training with (1) lecture on equipment, workflow, and guidelines, (2) hands-on ultrasound-guided IS BT workshop, and (3) treatment planning workshop. The cost in materials of each phantom was approximately $66. After a lecture, two alternating workshops were performed. The first session consisted of a hands-on ultrasound-guided IS BT workshop with one resident imaging the phantom with a transabdominal ultrasound probe and the other resident implanting the phantom with needles. A second session consisted of a hands-on treatment planning workshop using BrachyVision and an l -Q spreadsheet with the following objectives: coverage goal, meeting D2cc constraints, and minimizing V200. The primary outcome was improvement in knowledge assessed with Likert-style questions and objective knowledge-based questions (KBQs). Four of the seven medical residents that participated in this curriculum had prior IS BT experience. Residents reported significantly improved knowledge regarding gynecologic IS BT equipment and procedure, evaluating gynecologic anatomy using ultrasound, CT simulation, contouring, and plan review (overall median pre-session subjective score 2 (1) −( 3) versus post-session score 4 (3) −( 4 , p < 0.01). Residents demonstrated improvement in answering KBQs correctly from 44% correct at baseline to 88% after completion of the curriculum (p < 0.01). All residents "Agree" and "Strongly Agree" the session was an effective learning experience. Residents participating in phantom training with an ultrasound curriculum and a treatment planning session is effective for improving knowledge and skills in IS BT for radiation oncology residents. [ABSTRACT FROM AUTHOR]