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Pragmatic gynecologic cancer clinical trials: statements and roadmap from the Gynecologic Cancer InterGroup Chicago Brainstorming Meeting.

Randomized controlled trials remain fundamental to evidence generation in oncology but are increasingly complex, costly, and often misaligned with real-world practice. Traditional explanatory trials, designed under ideal, controlled conditions, frequently enroll highly selected populations, limiting generalizability and underrepresenting key groups such as older adults, patients with comorbidities, and those from low- and middle-income countries. Pragmatic clinical trials offer an alternative by evaluating interventions under routine care conditions, with broader eligibility, simplified procedures, and patient-centered outcomes. To address these challenges, the Gynecologic Cancer InterGroup convened an international brainstorming meeting in May 2025 with multi-disciplinary experts, patients, and advocates to define priorities and develop a roadmap for pragmatic trials in gynecologic oncology. Key discussions emphasized embedding trial design within routine care, aligning eligibility criteria and procedures with standard practice, minimizing non-essential data collection, and prioritizing outcomes meaningful to patients, including quality of life. Innovative designs such as registry-based randomized trials, trials-within-cohorts, and cluster randomization were highlighted as feasible approaches to improve efficiency while preserving internal validity. Integration of patient-reported outcomes and real-world data was considered achievable when carefully streamlined. Major challenges identified included regulatory heterogeneity, consent complexity, data interoperability, and funding limitations, particularly in multi-national settings. Proposed solutions include simplified consent models, centralized ethics processes, hybrid funding strategies, and the responsible use of artificial intelligence to enhance patient identification, recruitment, and potential development of synthetic control arms. Patient engagement was recognized as essential to ensure relevance, feasibility, and equity. Incorporation of patient-reported outcomes was discussed as key to informing acceptance and tolerability. In summary, pragmatic trials within Gynecologic Cancer InterGroup represent a critical pathway to generate efficient, inclusive, and practice-changing evidence in gynecologic cancers across diverse health care settings.

Humans

Interdisciplinary support of the gynecologic cancer patient.

The gynecologic cancer patient has unique needs and problems that require a specialized approach not available through traditional and established hospital services. Discussed here are the innovations made at one urban hospital to meet this patient's needs. Central to the program is an interdisciplinary committee that routinely reviews and plans health care services for the individual.

Female

Survey on the current status of novel cancer drug therapies for gynecological cancers in Japan: a nationwide survey by the Japan Society of Obstetrics and Gynecology (JSOG).

OBJECTIVE: To characterize real-world implementation of novel therapies in gynecological oncology in Japan and identify actionable gaps through a nationwide survey. METHODS: A cross-sectional questionnaire was distributed to Japan Society of Obstetrics and Gynecology-affiliated institutions. The items covered institution characteristics; use of poly (ADP-ribose) polymerase (PARP) inhibitors, immune checkpoint inhibitors (ICIs), kinase inhibitors, and antibody-based agents; local adverse event (AE) manuals; availability of expert panels and immune-related adverse event (irAE) teams; and perceptions of educational sufficiency. RESULTS: Valid responses were obtained from 245 institutions, spanning universities, cancer centers, and general hospitals. Most institutions reported the routine use of PARP inhibitors, ICIs, kinase inhibitors, and antibody drugs. However, only 40.4% of institutions had an in-hospital irAE management team, 57.1% had an AE/irAE manual, and 31.0% and 12.2% considered prior educational opportunities sufficient for physicians and nurses/other medical staff, respectively. High-volume institutions and academic centers were significantly more likely to have medical oncology support, expert-panel access, irAE teams, manuals, and higher self-rated evidence-based management capacity. The majority favored e-learning and society-led case conferences, and 76.3% supported the development of drug therapy subspecialties in gynecologic oncology. CONCLUSION: Innovative drug modalities are widely implemented across Japanese gynecological oncology services. However, critical gaps persist in multidisciplinary irAE management, standardized manuals, and practical education. Coordinated society-led programs to expand irAE teams, streamline companion diagnostics, disseminate ready-to-use algorithms, and provide credential-targeted training may enhance safety, equity, and evidence-concordant care nationwide.

Immune Checkpoint Inhibitors

Intraarterial pelvic infusion chemotherapy in advanced gynecologic cancer.

Fourteen patients with advanced localized gynecologic cancer were treated with 44 courses of intraarterial pelvic infusion chemotherapy. All patients received methotrexate with folinic acid rescue; 9 patients also received vincristine. Tumor regression was observed in 3 of 14 patients (21.4%). In 5 patients there were major complications related to 28 intraarterial catheter placements. Two patients developed leukopenia following chemotherapy. The value of intraarterial infusion chemotherapy in gynecologic cancer is limited. Its use in gynecologic oncology is discussed.

Adult

Mental changes in women with gynecologic cancer.

In 47 women with gynecologic cancer a questionnaire method was used for investigation mental changes in these patients. Alteration of value orientation, self-image, sexuality, attitude to cancer, etc., were analyzed in the group of the followed patients.

Adult

Regional chemotherapy--a comparison of pelvic perfusion and intra-arterial infusion in patients with advanced gynecologic cancer.

Forty-patients with advanced gynecologic cancer were treated with two different regional chemotherapeutic techniques. They were divided into two comparable groups. Twenty were treated by isolated regional perfusion and 20 were treated by intra-arterial infusion. The simple technique of intra-arterial infusion had a much lower mortality rate and gave equally satisfactory results when compared with the more complicated "closed" pelvic perfusion method. This comparative study suggests that the further use of isolated pelvic perfusion should await improvements in techniques and the development of more rapidly acting drugs. Further efforts in the area of infusion should be directed toward the development of more rapidly acting drugs, the development of better tumor-cytotoxic drug sensitivity tests, better use of the newer knowledge of cellular kinetics, and improved techniques for accuracy in the placement of arterial infusion catheters. While it is felt that regional chemotherapy has a place in management, it is not being proposed as a substitute for surgery or radiotherapy in the patient who will benefit from orthodox treatment.

Adult

Sexual rehabilitation of gynecologic cancer patients.

The gynecologic oncologist's obligation encompasses more than cure or successful palliation of pelvic malignancy. The sexual rehabilitation of such patients is vital and must be done sensitively lest one's own concepts of "adequate sexuality" be imposed. Instruction in coital technics and alternative modes of sexual expression can be provided simply and effectively.

Counseling

Association between gynecological cancers and female infertility: insights from bidirectional Mendelian randomization analysis.

PURPOSE: In recent years, research interest in the potential link between female infertility (FI) and gynecological cancer (GC), including ovarian cancer (OC), endometrial cancer (EC), cervical cancer (CC), and breast cancer (BC), has grown, yet findings remain inconclusive. This study aims to explore the causal relationship between FI and GC using bidirectional two-sample Mendelian randomization (MR) analyses, thereby informing future strategies for FI and GC prevention. METHODS: We utilized SNPs identified from genome-wide association studies (GWAS) on FI and GC. The inverse variance weighted (IVW) method served as the primary approach to assess the causal association between FI and GC. Additionally, five other MR methods-Weighted median, Weighted mode, MR-Egger, Simple mode, and Robust-Adjusted Profile Score-were employed to enhance result robustness and credibility. RESULTS: In the forward MR analysis, our IVW results indicated no significant association between FI and GC (FI-BC: OR = 0.95, 95% CI: 0.83-1.09, P = 0.47, P-FDR = 0.775; FI-OC: OR = 1.01, 95% CI: 0.84-1.24, P = 0.789, P-FDR = 0.896; FI-CC: OR = 0.80, 95% CI: 0.61-1.06, P = 0.118, P-FDR = 0.775; FI-EC: OR = 1.07, 95% CI: 0.88-1.30, P = 0.490, P-FDR = 0.775).In the reverse MR analysis, we found a marginal association between BC and FI. However, after adjusting for multiple testing using the FDR method, no significant causal relationship was found between BC and FI, suggesting a marginal association (OR = 1.054, 95% CI: 1.001-1.108, P = 0.043, P-FDR = 0.331). For other cancers, no significant causal relationships were observed between OC, CC and EC with FI(OC-FI: OR = 1.043, 95% CI: 0.999-1.087, P = 0.051, P-FDR = 0.331;CC-FI: OR = 0.992, 95% CI: 0.956-1.028, P = 0.654, P-FDR = 0.836; EC-FI: OR = 1.006, 95% CI: 0.956-1.055, P = 0.809, P-FDR = 0.885). CONCLUSIONS: Our study found no significant causal relationship between FI and GC. However, a potential marginal association between BC and FI was observed. These findings underscore the need for further research to confirm this association and emphasize the importance of reproductive protection for young breast cancer patients to preserve fertility.

Humans

Advances in chemotherapy for gynecologic cancer.

Considerable progress is being made in the chemotherapy of some gynecologic cancers. A random study comparing postoperative irradiation therapy with chemotherapy shows the two to be equally effective. Chemotherapy has the advantages of added safety and of being much less expensive for the patient. Postoperative chemotherapeutic treatment with VAC of patients with embryonal carcinoma of the ovary can prevent recurrence of this frequently fatal tumor. In some patients with advanced embryonal carcinoma of the ovary, chemotherapy with VAC may produce permanent remissions. Combined irradiation and chemotherapy and vincristine and actinomycin-D may be curative for some patients with advanced sarcomas in the pelvis or abdomen. This treatment combination is associated with severe complications; however, some are preventable.

Adolescent

[Clinical experience with the chemotherapy of gynecologic cancer].

The report is given about the experiences with chemotherapy of gynecological cancer. The best results were achieved with the long time prolonged therapy of the ovarian cancer. Very good results were registered by the stages III. and IV. of cervix uteri cancer and by all recurrencies of the stages I. and II. of cervical carcinoma. By all cases of advanced corpus uteri cancer and its recurrencies was used systematically chemotherapy.

Acrylates

Evaluation of B-mode ultrasound as a means of improving radium dosimetry in the treatment of gynecologic cancer.

The radiation dose to the base of the bladder and anterior rectal wall during radium applications for gynecologic cancer is a function of the distances between the source and the bladder and rectum. Precise measurement of these distances depends on a number of factors and cannot be obtained with current radiographic localization techniques. B-mode ultrasound is useful as a means of supplementing available information. While it is not necessarily more accurate than standard radiographs, it offers a three-dimensional appreciation of pelvic anatomy and does appear to be more accurate than transverse axial tomography.

Female

Hormones and gynecologic cancer.

Available basic information about the regulation of rates of production, blood levels, intracellular metabolism, and action of steroid hormones and prolactin is reviewed and related to high-risk factors and therapeutic procedures applicable to gynecologic cancer.

Androgens

Combined modality therapy of gynecologic cancer.

In the treatment of gynecologic malignancies, various combinations of surgery, drugs, and radiation therapy are used with increasing frequency. An examination is made of data dealing with combined modalities in the treatment of tumors of the cervix, endometrium, and ovary. Although the efficacy of such treatments has not been established, they are increasingly popular. Newer studies now being conducted, together with newer drugs employed in combination with radiation therapy and surgery, can result in the benefits which to date have not been realized.

Adenocarcinoma

Tumor-associated antigens in gynecologic cancer.

If the study of tumor immunology is to have a profound impact on clinical medicine, certain hypotheses must be proven to be valid. First and foremost, it must be demonstrated that malignant tissue possesses antigenic substances (probably protein moieties) that are unique to that particular malignant process. In addition, these antigenic substances must be very similar in histologically similar tumors. Second, the host defense mechanisms must be capable of reacting to these tumor-associated antigens. The reaction is, of course, necessary in order to develop both diagnostic and therapeutic routes of application. The reaction of the immunologic system to these tumor-associated antigens could be monitored as an early serodiagnostic tool for subclinical cancer, and the cytotoxic reaction holds great promise as an immunotherapeutic tool. The essence of tumor immunologic research can thus be stated in the form of the following questions: 1. Do histologically similar cancers from identical primary sites share common tumor-associated antigens? 2. Does the immunologic system react to these antigens? 3. Can this reaction be assayed on one hand for serodiagnosis and augmented on the other for immunotherapy? Specific antigens have been found in animal tumors and have been divided into two classes: the viral induced tumors, which share common antigens when caused by the same viral agent, and carcinogen-induced tumors, which appear to have unique antigenic determinants for each tumor. In recent years a great many human tumors have been found to have tumor-associated antigens; these include colonic carcinoma, neuroblastoma, melanoma, soft tissue and osteogenic sarcoma, bladder carcinoma and Burkitt's lymphoma. This report includes evidence for the existence of such antigens in adenocarcinoma of the ovary and squamous cell carcinoma of the cervix. The laboratory evidence that has been presented would suggest that there are both a cell-mediated response and humoral response to the antigenic determinants of these two gynecologic cancers. It would appear that the mediated (lymphocyte) effect is considerably more cytotoxic and definitive than the humoral factors measured. In addition, the allogenic experiments would suggest strongly that indeed (at least with regard to these two cancers) histologically similar cancers from the same organ share common antigenic determinants. The identification and isolation of these tumor-associated antigens appears complex. The complexity is increased when one studies patients afflicted with these cancers for plasma carcinoembryonic antigens. This antigen, which was thought to be specific for adenocarcinoma of the colon, is found in the blood of a significant number of patients with adenocarcinoma of the ovary and squamous cell carcinoma of the cervix.

Adenocarcinoma

Some surgical aspects of gynecologic cancer.

The most important developments in gynecologic oncology in recent years have been the advent of supervoltage irradiation that allows the delivery of better and safer therapy; the diligent search for new cancerostatic drugs and hormones and their clinical application, singly and in combination; and studies suggesting the possibility of immunotherapy. Conversely, few noteworthy developments have emerged in the operative management of gynecologic malignancy, even though refinements of surgical technique, improved preoperative and postoperative care, and better control of infectious problems gradually have decreased the operative morbidity and mortality rates and have improved the survival rates significantly. Surgery continues to be the dominant therapy. Irradiation, chemotherapy, and hormones are therapeutic adjuvants in the management of ovarian, endometrial, cervical, vulvar, and other genital malignancies. As a result of earlier diagnosis, with the greatly diminished incidence of far-advanced carcinoma of the cervix, primary surgery is having a larger role in the management of the early stages of this lesion. Aggressive surgical removal of advanced, dissemenated ovarian carcinoma is worthwhile; diminishing the volume of the lesion significantly improves the response of residual tumor to adjuvant therapy.

Adenocarcinoma

CRISPR/Cas in gynecologic cancers: A review of experimental and therapeutic applications.

Gynecological malignancies-including cervical, ovarian, and endometrial cancers-remain a major global health challenge, contributing significantly to cancer-related morbidity and mortality among women. Despite advances in conventional treatments such as surgery, chemotherapy, radiotherapy, and immunotherapy, issues such as drug resistance, tumor recurrence, and limited efficacy in advanced-stage disease necessitate novel therapeutic strategies. The emergence of CRISPR/Cas-based genome editing has revolutionized cancer research by enabling precise, efficient, and programmable modifications of specific genomic loci. In gynecologic oncology, CRISPR/Cas systems have been employed to dissect oncogenic mechanisms, identify therapeutic targets, and develop innovative treatment modalities. In cervical cancer, CRISPR-mediated targeting of HPV E6 and E7 oncogenes has shown potential in restoring tumor suppressor pathways and enhancing chemosensitivity. In ovarian cancer, gene editing has been used to modulate chemoresistance, tumor angiogenesis, and metastasis through the knockout of key regulators such as DNMT1, EGFL6, and BRCA1/2. Similarly, in endometrial cancer, CRISPR tools have elucidated mechanisms of hormonal resistance and facilitated the development of in vivo models via somatic gene editing. This review highlights recent advances in the application of CRISPR/Cas technology to gynecologic malignancies, discussing its potential as both a therapeutic and research platform while acknowledging current limitations and translational hurdles.

Humans

[Specificity in the management of gynecological cancers in French overseas departments].

The five overseas departments and regions (DROMs) are Guadeloupe, French Guiana, Reunion, Martinique and Mayotte. In the DROMs, certain areas show significantly higher incidence rates for certain cancers, particularly gynaecological cancers; overall, the 5-year net standardised survival rates are lower than those observed in mainland France. Here, we present an overview of the management of gynaecological cancers in each DROM.

Humans

Laparoscopy in the evaluation of gynecologic cancer.

Laparoscopy was used to evaluate 60 patients with a variety of known or suspected gynecologic neoplasms. Diagnostic laparoscopy was performed on 18 patients to confirm benign or malignant pelvic masses or to confirm peritoneal carcinomatosis. Ten of these 18 patients (56%) were found to have unresectable carcinomatosis or benign disease which did not require further surgery. Staging laparoscopy was performed on 13 patients of which 3 had clinically unsuspected intraperitoneal spread of their disease. Surveillance laparoscopy was performed on 29 patients to determine the remission, regression, or progression of their disease following treatment; 8 (27%) had progressive or unresectable persistent disease. Despite the fact that the study comprised a high-risk group of previously operated on or irradiated patients, there was only one major complication. There was, however, a 10% incidence of laparoscopic failure from inadequate visualization. Twenty-one of the study patients (35%) were spared a laparotomy by the use of laparoscopy. The findings of this investigation help to identify those gynecologic oncology patients who should benefit most from the use of laparoscopy as an adjunct to the diagnosis, staging, or surveillance of intraabdominal malignant tumors.

Abdominal Neoplasms