Refining research on access to gynecologic cancer care: The DIMeS framework.

BACKGROUND: Despite its importance, there is no consensus definition of access to care, and several fundamental philosophical questions about access remain unanswered. Lack of clarity impedes interventional research designed to develop and test methods of correcting barriers to access. To help remedy this problem, we propose a conceptual framework to help guide empirical research about access to gynecologic cancer care. METHODS: Relevant philosophical and empirical literature was reviewed and analyzed to highlight key elements needed to refine research on access to care. RESULTS: The DIMeS framework involves 1) choice and justification of a Definition of access to cancer care that will guide research; 2) Identification of essential gynecologic cancer care services for which access disparities are ethically unacceptable; 3) quantitative MEasurement of specific parameters that affect access to care; and 4) Selection of a target threshold on measured parameters above which access is acceptable. CONCLUSIONS: The DIMeS framework provides clarity and reproducibility for investigators seeking to develop and test interventions to improve cancer health equity. This framework should be considered for use in research on access to gynecologic cancer care.

Underrepresentation of racial and ethnic minority groups in gynecologic oncology: An analysis of over 250 trials.

OBJECTIVE: To describe the participation of racial and ethnic minority groups (REMGs) in gynecologic oncology trials. METHODS: Gynecologic oncology studies registered on ClinicalTrials.gov between 2007 and 2020 were identified. Trials with published results were analyzed based on reporting of race/ethnicity in relation to disease site and trial characteristics. Expected enrollment by race/ethnicity was calculated and compared to actual enrollment, adjusted for 2010 US Census population data. RESULTS: 2146 gynecologic oncology trials were identified. Of published trials (n = 252), 99 (39.3%) reported race/ethnicity data. Recent trials were more likely to report these data (36% from 2007 to 2009; 51% 2013-2015; and 53% from 2016 to 2018, p = 0.01). Of all trials, ovarian cancer trials were least likely to report race/ethnicity data (32.1% vs 39.3%, p = 0.011). Population-adjusted under-enrollment for Blacks was 7-fold in ovarian cancer, Latinx 10-fold for ovarian and 6-fold in uterine cancer trials, Asians 2.5-fold in uterine cancer trials, and American Indian and Alaska Native individuals 6-fold in ovarian trials. Trials for most disease sites have enrolled more REMGs in recent years - REMGs made up 19.6% of trial participants in 2007-2009 compared to 38.1% in 2016-2018 (p < 0.0001). CONCLUSION: Less than half of trials that published results reported race/ethnicity data. Available data reveals that enrollment of REMGs is significantly below expected rates based on national census data. These disparities persisted even after additionally adjusting for population size. Despite improvement in recent years, additional recruitment of REMGs is needed to achieve more representative and equitable participation in gynecologic cancer clinical trials.

Critical decisions: A mixed-methods study of decision-making among diverse gynecologic cancer patients considering therapeutic clinical trial enrollment.

OBJECTIVE: Participation in therapeutic clinical trials does not reflect the diversity of gynecologic cancer patients, limiting access to novel therapeutics and generalizability of results. Reasons for inequities in participation among historically underrepresented populations remain undertheorized, as studies have shown equal willingness to participate among groups. We sought to apply a precarity framework to conceptualize the factors that impact patients' desire to enroll, to improve equity in gynecologic oncology clinical trial participation. METHODS: Gynecologic cancer patients at a single tertiary care facility in the Southwestern United States who discussed participation in therapeutic clinical trial with their oncology provider from 2020 to 2021 were identified. Enrolled participants completed surveys and qualitative interviews regarding treatment experiences and decision-making. Oncology providers completed parallel surveys at the time of their patient's enrollment. Descriptive statistics and thematic coding were used to analyze data. RESULTS: 30 patients were enrolled and participated in surveys and interviews. No differences were found in quantitative data assessing shared decision-making and patient-centered communication between those who enrolled and those who did not. Qualitative data demonstrated that patients who declined trial enrollment expressed concerns regarding uncertainty and loss of control, independence in decision-making, and significant resource challenges and financial toxicity of cancer treatment. CONCLUSIONS: We identified a constellation of factors that contribute to desire to enroll in clinical trials, that we describe using the framework of precarity. Through identification of precarious patients and mitigation of burdens, we anticipate improved enrollment and retention in therapeutic clinical trials among diverse gynecologic oncology patients.

Effect of low uterine segment involvement on prognosis of early stage endometrial cancer.

AIM: Our aim is to investigate the effect of uterine lower segment involvement on prognosis of early-stage endometrial cancer cases diagnosed and treated in our clinic. MATERIALS AND METHODS: The file records of 316 cases reviewed retrospectively.Only stage I (a and b, n=209) cases were investigated, because they were more homogeneous group. RESULTS: The lymphovascular invasion rate was found to be higher in patients with stage Ia and uterine lower segment involvement (p < 0.001). Adjuvant treatment requirement was higher in patients with stage Ia and uterine lower segment involvement (p < 0.001). Among stage Ia cases, the recurrence rate between 1 and 3 years was found to be higher in cases with uterine lower segment involvement (p = 0.001). Among the stage Ib cases, lymphovascular invasion was found to be higher in cases with uterine lower segment involvement (p < 0.001). The recurrence rate between 1 and 3 years was found to be higher in stage Ib compared to Ia (p = 0.01). Uterine lower segment involvement was found to be associated with high lymphovascular invasion rate in all stage I cases (p < 0.001). It was determined that the need for adjuvant treatment was higher in cases with uterine lower segment involvement (p < 0.001). It was determined that the probability of recurrence between 1 and 3 years was higher in cases with uterine lower segment involvement (p = 0.007). CONCLUSION: Uterine lower segment involvement is associated with increased lymphovascular invasion even in the early stages. It is an important risk factor for systemic spread such as lymphovascular invasion, myometrial invasion, and lymph node involvement.

A Retrospective Study of Complications Following Pelvic and Para-Aortic Lymphadenectomy in Gynecologic Oncology.

Background: Lymphadenectomy plays an essential role in the staging protocols for gynecologic cancers, as recommended by International Federation of Gynecology and Obstetrics (FIGO). While its benefits vary, complications may arise during intra-operative, acute post-operative, or long-term periods. Notably, lymphadenectomy-associated systemic morbidity and specific complications such as lymphocele and lymphedema have been reported. Methods: This retrospective study involved 399 patients with cervical, endometrial, and ovarian cancers who underwent pelvic and para-aortic lymphadenectomy. The follow-up period was at least 3 months. Intra-operative complications encompassed adjacent organ injury and significant blood loss, while acute post-operative complications occurred within 29 days. Post-30-day complications included lymphocele and lymphedema. Logistic regression analysis identified predictors for complications. Results: The overall complication rate was 42.4%, with intra-operative, acute post-operative, and long-term rates of 26.1%, 11.0%, and 14.0%, respectively. Predictors for overall complications included laparotomy, positive lymph nodes, and operative time > 240 min. For intra-operative complications, age > 60 years, laparotomy, positive lymph nodes, and operative time > 240 min were significant predictors. Symptomatic lymphocele and lymphedema occurred in 6.0% and 2.0% of patients, respectively, mainly in the long-term period. Conclusion: Although the overall complication rate after gynecologic surgery was found to be almost half of all cases, the rate of severe complications was low. Additionally, the rates of symptomatic lymphocele and lymphedema were low. Lymphadenectomy in gynecologic cancer surgery can be performed safely.

VISTA: A promising target for overcoming immune evasion in gynecologic cancers.

Immune checkpoint blockade (ICB) therapy has revolutionized cancer treatment but has shown limited efficacy in gynecologic cancers. VISTA (V-domain Ig suppressor of T-cell activation), a member of the B7 family, is emerging as another checkpoint that regulates the anti-tumor immune responses within the tumor microenvironment. This paper reviews the structure, expression, and mechanism of action of VISTA. Furthermore, it highlights recent advances in VISTA-blocking therapies and their potential in improving outcomes for patients with gynecologic cancers. By understanding the role of VISTA in mediating the immune evasion of gynecologic tumors, we can develop more effective combinatory treatment strategies that could overcome resistance to current ICB therapies.

Physician perspectives on clinician-to-clinician telemedical consultation for gynecologic cancers: A qualitative study.

Objective: Approximately fifteen million women in the United States live > 50 miles from a gynecologic oncologist. Telemedical technology allows patients' local physicians to consult with subspecialist gynecologic oncologists without burdening patients with unnecessary in-person visits. Although critical to adoption of this technology, physicians' input into implementation of clinician-to-clinician consultation has not been sought. We therefore gathered feedback about experiences with referrals, communication, and openness to telemedical consultation from gynecologic oncologists, gynecologists, and medical oncologists. Methods: We recruited gynecologic oncologists, gynecologists, and medical oncologists from practices serving rural patients to participate in semi-structured interviews. The Consolidated Framework for Implementation Research and the Theoretical Domains Framework guided the interviews. Questions focused on factors influencing adoption and implementation of clinician-to-clinician telemedicine. Interviews were conducted via WebEx, recorded, and transcribed. Two investigators coded interviews using the combined frameworks and identified salient themes. Results: We conducted 11 interviews (6 gynecologic oncologists, 3 gynecologists, 2 medical oncologists) and identified themes encompassing communication burnout, barriers to sharing patient information, need for further logistical information, and potential benefits to patients. Conclusions: Clinician-to-clinician telemedicine may improve access to gynecologic cancer care by decreasing barriers to subspecialty expertise while simultaneously benefiting referring and consultant clinicians through improved identification and workup of patients who may need in-person consultation. To optimize desired outcomes, telemedical consultation must allow for communication of relevant patient information and records and easy integration into clinical workflow. Importantly, clinicians must perceive the consultation as improving patients' access to specialty care.

Maximizing ovarian function and fertility following chemotherapy in premenopausal patients: Is there a role for ovarian suppression?

As more premenopausal patients undergo fertility preserving cancer treatments, there is an increased need for fertility counseling and ovarian sparing strategies. Many patients receive gonadotoxic chemotherapeutic agents which can put them at risk of primary ovarian insufficiency or profoundly diminished ovarian reserve. Traditionally, estradiol and follicle stimulating hormone (FSH) values have been used to evaluate ovarian function but more recently, reproductive endocrinologists have been proponents of anti-mullerian hormone (AMH) as a validated measure of ovarian potential. While the gold standard for fertility preservation remains oocyte cryopreservation, data suggest there may be additional interventions that can mitigate the gonadotoxic effects of chemotherapeutic agents. The main objectives of this focused review were to quantify the risk of primary ovarian failure associated with the most common chemotherapies used in treatment of gynecologic cancers and to evaluate and recommend potential interventions to mitigate toxic effects on ovarian function. Chemotherapeutic agents can cause direct loss of oocytes and primordial follicles as well as stromal and vascular atrophy and the extent is dependent upon mechanism of action and age of the patient. The risk of ovarian failure is the highest with alkylating agents (42.2 %), anthracyclines (<10-34 % in patients under 40 years versus 98 % in patients aged 40-49), taxanes (57.1 %) and platinum agents (50 %). Multiple trials demonstrate that gonadotropin releasing hormone (GnRH) agonists, when administered concurrently with chemotherapy, may have protective effects, with more patients experiencing resumption of a regular menstruation pattern and recovering ovarian function more quickly post-treatment. Premenopausal patients receiving chemotherapy for the treatment of gynecologic cancers should receive adequate counseling on the potential adverse effects on their fertility. Although oocyte cryopreservation remains the gold standard for fertility preservation, there is some evidence to suggest that GNRH agonists could help maintain and preserve ovarian function and should be considered.

Utilization and Impact of a Radiation Nursing Clinic to Address Acute Care Needs for Patients with Gynecologic Cancers.

BACKGROUND: The risk factors for acute care utilization in gynecologic oncology patients are poorly understood. This study aimed to evaluate risk factors for the utilization of our centre's acute care radiation nursing clinic (RNC) by gynecologic oncology patients receiving radiotherapy (RT). METHODS: This was a retrospective cohort study of gynecological cancer patients treated with RT at an academic cancer centre between 1 August 2021 and 31 January 2022. Data on socio-demographics, clinical and treatment characteristics, and RNC visits were collected and summarized by descriptive statistics. The Wilcoxon rank sum test and chi-squared test/Fisher's exact test were used for comparisons of continuous and categorical variables, respectively. RESULTS: RT was delivered to 180 patients, of whom 42 (23%) received concurrent chemoradiation (CCR). Compared to those receiving RT alone, patients receiving CCR had higher rates of RNC utilization (55% vs. 19%, p < 0.001). Within the CCR cohort, patients who presented to the RNC were more likely to be unpartnered (43% vs. 11%, p = 0.04), receive a referral to Psychosocial Oncology (39% vs. 5.3%, p = 0.01), and experience treatment interruptions (52% vs. 16%, p = 0.02). There were no associations between RNC visits and age, disease site, or distance from the cancer centre. CONCLUSIONS: The receipt of CCR and specific psychosocial risk factors were associated with increased RNC utilization. Targeted strategies and early intervention to better meet the supportive care and psychosocial needs of this vulnerable population are needed.

Interplay between LncRNA/miRNA and TGF-ß Signaling in the Tumorigenesis of Gynecological Cancer.

Gynecologic cancers are among the most common malignancies with aggressive features and poor prognosis. Tumorigenesis in gynecologic cancers is a complicated process that is influenced by multiple factors, including genetic mutations that activate various oncogenic signaling pathways, including the TGF-ß pathway. Aberrant activation of TGF-ß signaling is correlated with tumor recurrence and metastasis. It has been shown that non-coding RNAs (ncRNAs) have crucial effects on cancer cell proliferation, migration, and metastasis. Upregulation of various ncRNAs, including long non-coding RNAs (lncRNA) and microRNAs (miRNAs), has been reported in several tumors, like cervical, ovarian, and endometrial cancers, but their cellular mechanisms remain to be investigated. Thus, recognizing the role of ncRNAs in regulating the TGF-ß pathway may provide novel strategies for better treatment of cancer patients. The present study summarizes recent findings on the role of ncRNAs in regulating the TGF-ß signaling involved in tumor progression and metastasis in gynecologic cancers.

Hepatitis B virus infection and the risk of gynecologic cancers: a systematic review and meta-analysis.

OBJECTIVES: The relationship between hepatitis B virus (HBV) infection and gynecologic cancers is controversial. We aimed to evaluate the risk of gynecologic cancers associated with HBV infection using a meta-analysis. METHODS: Two independent reviewers identified publications in the PubMed, Embase and Cochrane Library databases that reported an association between HBV and the risk of gynecologic malignancy from inception to December 31, 2022. The Newcastle-Ottawa Scale (NOS) was used to evaluate the quality of the included articles. Pooled odds ratios (ORs) and 95% corresponding confidence intervals (CIs) were calculated using a fixed effects model or random effects model. RESULTS: We collected data from 7 studies that met the inclusion criteria, including 2 cohort studies and 5 case-control studies. HBV was significantly associated with the risk of cervical cancer in the general population (OR 1.22, 95% CI 1.09-1.38, P = 0.001), although the same trend was not found in endometrial cancer (OR 1.30, 95% CI 0.95-1.77, P = 0.105) and ovarian cancer (OR 1.03, 95% CI 0.79-1.35, P = 0.813). Subgroup analysis showed that HBV infection was positively associated with the risk of cervical cancer (OR 1.27, 95% CI 1.13-1.44, P = 0.000) in case-control studies. Asian women infected with HBV have a significantly increased risk of cervical cancer (OR 1.24, 95% CI 1.10-1.40, P = 0.001) and endometrial cancer (OR 1.46, 95% CI 1.07-1.99, P = 0.018). Hospital-based studies were found to be associated with an increased risk of cervical cancer (OR 1.30, 95% CI 1.14-1.47, P = 0.000) and endometrial cancer (OR 1.61, 95% CI 1.04-2.49, P = 0.032). The results of Begg's and Egger's tests showed no publication bias. CONCLUSIONS: This meta-analysis shows a positive association between HBV infection and cervical cancer. HBV is positively correlated with the risk of cervical cancer and endometrial cancer in Asian women and hospital-based populations. More multicenter prospective studies are required to confirm the findings.

Moving beyond "Better Late than Never": High Symptom Burden and Diminished Functional Status at First Palliative Care Visit for Patients with Gynecological Cancers.

Background: Despite physical and emotional distress in patients with gynecologic malignancies, palliative care (PC) is underutilized. Objectives: We characterize referral practices, symptom burden and functional status at the time of initial PC encounter for patients with gynecologic cancer. Design: Data were extracted from the standardized Quality Data Collection Tool for Palliative Care (QDACT-PC). We describe symptom burden and performance status. Results: At initial specialty PC encounter, patients with gynecologic cancers reported a mean of 3.3 moderate/severe symptoms. Outpatients experienced the most moderate/severe symptoms (mean 3.9) versus inpatient (mean 2.1) or home (mean 1.5). A total of 72.7% of patients had significantly impaired functional status (palliative performance scale [PPS] <70) at initial encounter. Inpatients had a more impaired functional status (mean PPS 48.8) than outpatients (mean PPS 67.0). Conclusions: The symptom burden for gynecologic cancer patients at initial PC encounter is high. Despite better functional status, patients referred in the outpatient setting had the highest symptom burden.

ARID1A in Gynecologic Precancers and Cancers.

The highest frequency of genetic alterations in the tumor suppressor ARID1A occurs in malignancies of the female reproductive tract. The prevalence of ARID1A alterations in gynecologic precancers and cancers is summarized from the literature, and the putative mechanisms of tumor suppressive action examined both in benign/precursor lesions including endometriosis and atypical hyperplasia and in malignancies of the ovary, uterus, cervix and vagina. ARID1A alterations in gynecologic cancers are usually loss-of-function mutations, resulting in diminished or absent protein expression. ARID1A deficiency results in pleiotropic downstream effects related not only to its role in transcriptional regulation as a SWI/SNF complex subunit, but also related to the functions of ARID1A in DNA replication and repair, immune modulation, cell cycle progression, endoplasmic reticulum (ER) stress and oxidative stress. The most promising actionable signaling pathway interactions and therapeutic vulnerabilities of ARID1A mutated cancers are presented with a critical review of the currently available experimental and clinical evidence. The role of ARID1A in response to chemotherapeutic agents, radiation therapy and immunotherapy is also addressed. In summary, the multi-faceted role of ARID1A mutation in precancer and cancer is examined through a clinical lens focused on development of novel preventive and therapeutic interventions for gynecological cancers.

Mutational analysis of selected high-grade malignancies in a premenopausal gynecologic cancer population: a potential for targeted therapies?

Background: In 2017, there will be 107,000 cases of gynecologic cancer diagnosed in the US with an overall survival of around 70%-most occurring in post-menopausal individuals. In this study, we have examined a younger (≤ 40 years of age) subpopulation of these women with high grade/ high stage gynecologic malignancies, attempting to identify unique genetic abnormalities or combinations thereof through tissue block specimens. This information was then analyzed in light of known target therapies to see if genetic analysis in this setting would yield significant therapeutic advantage. Methods: We retrospectively evaluated patients with high grade/high stage gynecologic cancers (≤ 40 years of age), examined the presence and status of 400 oncogenes and tumors suppressor genes from Formalin-fixed, Paraffin-embedded (FFPE) tissue and functionally classified mutations by SIFT and Polyphen. Results: Twenty women were identified and stratified into positive and negative outcomes. No demographic, clinicopathologic or treatment factors were significant between these groups. Of the 400 genes evaluated, twelve mutations were significant between the groups, six with targeted therapies. Mutations associated with negative outcomes within histologies/locations were evaluated: ERBB3 in epithelial (ovarian), ALK/GPR124/KMT2D in neuroendocrine (ovarian/endometrial), ROS1/EGFR, ROS1/ERBB3/KMT2D/NIRK1 and GPR124 in sarcoma. All negative outcomes were void of mutations in APC/ABL2. A predictive model for negative outcomes in our cohort was developed from these data: AKAP9-/MBD1-/APC-/ABL2- with a mutation load of > 20.5. Conclusions: Unique multi-gene and mutational outcome correlations were identified in our cohort. Resulting complex mutational profiles in distinctly aggressive gynecologic cancers suggested potential for novel therapeutic treatment. Future larger scale studies will be needed to correlate the genotypic and phenotypic features identified here (AU)

Functional roles of long noncoding RNA MALAT1 in gynecologic cancers

Gynecologic cancers are reproductive disorders characterized by pelvic pain and infertility. The identification of new predictive markers and therapeutic targets for the treatment of gynecologic cancers is urgently necessary. One of the recent successes in gynecologic cancers research is identifying the role of signaling pathways in the pathogenesis of the disease. Recent experiments showed long noncoding RNAs (lncRNA) can be novel therapeutic approaches for the diagnosis and treatment of gynecologic cancers. LncRNA are transcribed RNA molecules that play pivotal roles in multiple biological processes by regulating the different steps of gene expression. Metastasis‐associated lung adenocarcinoma transcript‐1 (MALAT1) is a well-known lncRNA that plays functional roles in gene expression, RNA processing, and epigenetic regulation. High expression of MALAT1 is closely related to numerous human diseases. It is generally believed that MALAT1 expression is associated with cancer cell growth, autophagy, invasion, and metastasis. MALAT1 by targeting multiple signaling pathways and microRNAs (miRNAs) could contribute to the pathogenesis of gynecologic cancers. In this review, we will summarize functional roles of MALAT1 in the most common gynecologic cancers, including endometrium, breast, ovary, and cervix (AU)

Potential opportunities to reduce cervical cancer by addressing risk factors other than HPV / 부인종양

Cervical cancer is the most common cancer in developing world and 80% of global burden is reported from these nations. Human papillomavirus along with poverty, illiteracy/lower education level and standards, multi-parity, tobacco, malnutrition and poor genital hygiene may act synergistically to cause cervical cancer. Risk factor of cervical cancer may in itself be the reason for non-viability of cervical cancer vaccine program in this part of the world. Interventions to address these risk factors in addition to vaccination of girls before their sexual debut may hold promises of reducing the morbidity and mortality of female genital cancers.

Laparoscopic pelvic and para-aortic lymphadenectomy / 한양의대학술지

Laparoscopic surgery has many benefits over a conventional abdominal approach. These include less blood loss, low morbidity, shorter recovery time, shorter hospital stay, and shorter time interval to adjuvant therapy. With advances of laparoscopic instruments and surgical skills, laparoscopic surgery is becoming a dominant paradigm in the surgical management of gynecologic cancers. Advanced laparoscopic procedures including radical hysterectomy and trachelectomy with pelvic and para-aortic lymphadenectomy are now used in the management of early cervical cancer. For patients with apparent early-stage endometrial and ovarian cancer, laparoscopic complete staging operation including pelvic and para-aortic lymphadenectomy can be applied. Of several laparoscopic surgical procedures, laparoscopic pelvic and para-aortic lymphadenectomy is a cornerstone in the management of gynecological cancers cancers. The evaluation of lymph node status has an important role in diagnosis, treatment, and prognosis of gynecologic cancers because lymphatics are the main pathways of dissemination of gynecologic cancers. Laparoscopic pelvic and para-aortic lymphadenectomy is feasible and safe without increase of perioperative complications and decrease in patient's survival in gynecologic cancers, if it is performed by an experienced laparoscopic oncologic surgeon. During the last 10 years, laparoscopic procedures including pelvic and para-aortic lymphadenectomy in over 600 patients with gynecologic cancers were underwent in our department. We have found that the surgical and oncologic outcomes were similar or even better compared to conventional laparotomic procedures. In conclusion, the gynecologic oncologist should be familiar with lymphatic anatomy and laparoscopic skills to perform pelvic and para-aortic lymphadenectomy, because laparoscopic management of gynecologic cancers will be the choice of surgical treatment in the near future.