IL-2-free tumor-infiltrating lymphocyte therapy with PD-1 blockade demonstrates potent efficacy in advanced gynecologic cancer.

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.

Small-cell neuroendocrine carcinoma of the female genital tract: A comprehensive overview.

Small-cell neuroendocrine carcinomas (SCNECs) of the female genital tract are rare and aggressive tumors that are characterized by a high rate of recurrence and poor prognosis. They can arise from various sites within the female genital tract, including the cervix, endometrium, ovary, fallopian tube, vagina, and vulva. They are composed of cells with neuroendocrine features, such as the ability to produce and secrete hormones and peptides, and a high mitotic rate. Immunohistochemical staining for neuroendocrine markers, such as chromogranin A, synaptophysin, and CD56, can aid in the diagnosis of these tumors. This article provides an overview of the epidemiology, etiology, and risk factors associated with these tumors, as well as their clinical presentation, cellular characteristics, diagnosis, and finally the current treatment options for SCNECs, including surgery, chemotherapy, and radiation therapy, alone or in combination.

Patient Location and Disparities in Access to Fertility Preservation for Women With Gynecologic or Breast Cancer.

OBJECTIVE: To assess the effect of geographic factors on fertility-sparing treatment or assisted reproductive technology (ART) utilization among women with gynecologic or breast cancers. METHODS: We conducted a cohort study of reproductive-aged patients (18-45 years) with early-stage cervical, endometrial, or ovarian cancer or stage I-III breast cancer diagnosed between January 2000 and December 2015 using linked data from the California Cancer Registry, the California Office of Statewide Health Planning and Development, and the Society for Assisted Reproductive Technology. Generalized linear mixed models were used to evaluate associations between distance from fertility and gynecologic oncology clinics, as well as California Healthy Places Index score (a Census-level composite community health score), and ART or fertility-sparing treatment receipt. RESULTS: We identified 7,612 women with gynecologic cancer and 35,992 women with breast cancer. Among all patients, 257 (0.6%) underwent ART. Among patients with gynecologic cancer, 1,676 (22.0%) underwent fertility-sparing treatment. Stratified by quartiles, residents who lived at increasing distances from gynecologic oncology or fertility clinics had decreased odds of undergoing fertility-sparing treatment (gynecologic oncology clinics: Q2, odds ratio [OR] 0.76, 95% CI, 0.63-0.93, P =.007; Q4, OR 0.72, 95% CI, 0.56-0.94, P =.016) (fertility clinics: Q3, OR 0.79, 95% CI, 0.65-0.97, P =.025; Q4, OR 0.67, 95% CI, 0.52-0.88, P =.004), whereas this relationship was not observed among women who resided within other quartiles (gynecologic oncology clinics: Q3, OR 0.81 95% CI, 0.65-1.01, P =.07; fertility clinics: Q2, OR 0.87 95% CI, 0.73-1.05, P =.15). Individuals who lived in communities with the highest (51 st -100 th percentile) California Healthy Places Index scores had greater odds of undergoing fertility-sparing treatment (OR 1.29, 95% CI, 1.06-1.57, P =.01; OR 1.66, 95% CI, 1.35-2.04, P =.001, respectively). The relationship between California Healthy Places Index scores and ART was even more pronounced (Q2 OR 1.9, 95% CI, 0.99-3.64, P =.05; Q3 OR 2.86, 95% CI, 1.54-5.33, P <.001; Q4 OR 3.41, 95% CI, 1.83-6.35, P <.001). CONCLUSION: Geographic disparities affect fertility-sparing treatment and ART rates among women with gynecologic or breast cancer. By acknowledging geographic factors, health care systems can ensure equitable access to fertility-preservation services.

Potential role of immune cell therapy in gynecological cancer and future promises: a comprehensive review.

Gynecological malignancies are most leading causes of death among women worldwide. The high prevalence of gynecologic malignancies remains significant, necessitating to turn the novel treatment approach like immunotherapy, wherein cancer cells are killed by the invasion of immune system. In recent year, immunotherapy has mostly an advanced treatment approach to repressing the tumor cells survival, proliferation, and invasion via the activation of immune systems. Moreover, various types of immune cells including T-cells, B-cells, and dendritic cells are associated with the immunotherapeutic strategy in cancer treatment. Although the significant role of T-cells against cancer is well established, while B-cells and dendritic cells also play an important role against different gynecological cancer by regulating the immune system. This review focuses on that arena and highlight the role of immune cells in the treatment of gynaecological cancer. Various immune cell-based anticancer therapies such as T-cell therapies, Adoptive Cellular transfer, B-cell therapies as well as approaches to Dendritic Cell therapies have been discussed in detail. Furthermore, the clinical settings and future avenues regarding immunotherapy on gynecological cancer have also been reviewed and illuminated in the recent study.

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.

Circulating Tumor DNA (ctDNA) and Its Role in Gynecologic Malignancies.

OPINION STATEMENT: Circulating tumor DNA (ctDNA) refers to small fragments of DNA released into the bloodstream by cancer cells. It is obtained through "liquid biopsy;" which most commonly refers to plasma or blood samples, but can be obtained from a number of bodily fluids including ascitic fluid, saliva, and even urine and stool. ctDNA is detected via polymerase chain reaction (PCR) or next-generation sequencing (NGS). The DNA from these samples is analyzed for the detection of point mutations, copy-number alterations, gene fusion, and DNA methylation. These results have the potential for use in cancer diagnosis, determining prognosis, targeting gene-specific therapies, and monitoring for/predicting disease recurrence and response to treatment. ctDNA offers an alternative to tissue biopsy; it is less invasive and can be monitored serially over time without multiple procedures. Moreover it may have the ability to detect disease recurrence or predict behavior in a way that solid tissue biopsies, tumor marker surveillance, and imaging cannot. Recent explosion in interest in ctDNA shows promising developments for widespread adoption of these techniques in cancer care. However, the use of ctDNA in diagnosis and treatment of gynecologic malignancies is currently limited, compared to adoption in other solid-organ tumors such as breast and colorectal cancers. Compared to other cancer types, there appear to be fewer comprehensive studies and clinical validations specifically focusing on the use of ctDNA in gynecologic cancers. More research is needed in this area to advance the potential for use of ctDNA in ovarian, endometrial, and cervical cancers before this can be routinely adopted to improve care for patients with gynecologic malignancies.

Familial and Social Implications of Breast and Gynaecological cancer in Kerala, India.

BACKGROUND: Due to the paucity of reliable data to determine the components of family-based comprehensive care for cancer in India, we explored the familial implications of gynaecological and breast cancer diagnosis and treatment through a mixed-method study. METHODS: The mixed method study included 130 women aged above 18 with a confirmed diagnosis of gynaecological or breast cancer recruited from three selected tertiary hospitals in Kerala, India. Information on quality of life (36-Item Short Form Survey (SF-36)), psychological distress (distress thermometer), and the familial, interpersonal, social, and community impacts of cancer (semi-structured interview guide) were elicited. Linear regression was used to identify the factors associated with distress and the factors were explored further using thematic analysis. RESULTS: Patients included in the study (n = 130; mean age 57.5 years) had moderate or mild (66.9%) to severe (25.4%) distress. Concerns about work (93%), difficulty in; home care and housing (82%), care for dependents (65%), unempathetic family (87.6%), isolation (70%), and body image (65%) were major reasons for their distress. Physiological, social, and family-related stressors among the respondents included challenges in physical functioning, intense physical symptoms like fatigue, loss of appetite and sleep, role restrictions, alterations in family responsibilities, functional dependency, inadequate family support, challenges in social and interpersonal interactions, and an unsupportive work environment. CONCLUSION: Cancer is a health crisis that involves psychological, social, and economic distress, compelling professionals to design multifaceted individualized care packages rather than only concentrating on medical management to alleviate their distress.

System-level recommendations for improved wellness for gynecologic oncologists: A Society of Gynecologic Oncology Review.

Burnout and its negative sequelae are a persistent problem in gynecologic oncology, threatening the health of our physician workforce. Individual-level interventions such as stress management training, physical activity, and sleep hygiene only partially address this widespread, systemic crisis rooted in the extended work hours and stressful situations associated with gynecologic oncology practice. There is an urgent need for systematic, institution-level changes to allow gynecologic oncologists to continue the crucial work of caring for people with gynecologic cancer. We present recommendations for institution-level changes which are grounded in the framework presented by the National Plan for Health Workforce Well-Being by the National Academy of Medicine. These are aimed at facilitating gynecologic oncologists' well-being and reduction of burnout. Recommendations include efforts to create a more positive and inclusive work environment, decrease administrative barriers, promote mental health, optimize electronic medical record use, and support a diverse workforce. Implementation and regular evaluation of these interventions, with specific attention to at-risk groups, is an important next step.

Delayed publication of clinical trials in gynecologic oncology.

OBJECTIVES: Delays in clinical trial publication can hinder timely implementation of evidence-based practices. We sought to determine publication rates and time to publication for clinical trials addressing gynecologic malignancies. METHODS: All clinical trials addressing gynecologic cancers in the ClinicalTrials.gov registry with a primary completion date between 1/1/2018 and 1/1/2020 were identified. The primary outcome was publication rate. All included studies had been completed for at least 3 years. Secondary outcomes were time to publication and associations between publication rate and sponsor, cancer type, and the number and location of primary study sites. RESULTS: Of the 290 trials included, 161 (55.5%) had a peer-reviewed publication for the primary outcome within at least 3 years after completion. Of these, 123 had positive results (76.4%) and 38 were negative (23.6%). The average duration from primary completion to manuscript publication was 23.6 months (SD 13.9; median 21.4, IQR 15.1-32.4). Only 73 had results posted on the ClinicalTrials.gov registry (25.2%). Studies with positive findings had a significantly faster time to publication than those with negative results (22.0 mo vs 29.0 mo, p = 0.009). There was no significant difference between publication rate and funding source, cancer type, or location and number of primary sites. CONCLUSIONS: Timely publication of clinical trials addressing gynecologic cancers remains an issue. Studies with positive findings were published faster than those with negative results, but the average publication time was still almost 2 years from trial completion. Further efforts should be made to identify and address barriers to clinical trial publication.

Imaging the post-treatment pelvis with gynecologic cancers.

Gynecological malignancies, such as ovarian cancers, cervical cancers, and endometrial cancers, have a significant global impact. Women with gynecologic malignancies may receive a single or a combination of treatments, including surgery, chemotherapy, and radiation-based therapies. Radiologists utilize various diagnostic imaging modalities to provide the surgeon with relevant information about the diagnosis, prognosis, optimal surgical strategy, and prospective post-treatment imaging. Computerized Tomography (CT) and magnetic resonance imaging (MRI) may be used initially to evaluate and detect post-treatment complications. Although CT is primarily used for staging, MRI is commonly used for a more accurate evaluation of a tumor's size and detection of local invasion. Complications such as hematoma, abscess, inclusion cyst, seroma, tumor thrombosis, anorectovaginal fistula, and gossypiboma may occur after the three primary treatments, and systems such as the genitourinary, gastrointestinal, neurological, and musculoskeletal may be affected. In order to distinguish between early-onset and late-onset complications following gynecological treatment, radiological findings of the most common post-treatment complications will be presented in this review.

Gynecological Cancers and Microbiota Dynamics: Insights into Pathogenesis and Therapy.

In recent years, the relationship between the microbiota and various aspects of health has become a focal point of scientific investigation. Although the most studied microbiota concern the gastrointestinal tract, recently, the interest has also been extended to other body districts. Female genital tract dysbiosis and its possible impact on pathologies such as endometriosis, polycystic ovary syndrome (PCOS), pelvic inflammatory disease (PID), and gynecological cancers have been unveiled. The incursion of pathogenic microbes alters the ecological equilibrium of the vagina, triggering inflammation and compromising immune defense, potentially fostering an environment conducive to cancer development. The most common types of gynecological cancer include cervical, endometrial, and ovarian cancer, which occur in women of any age but especially in postmenopausal women. Several studies highlighted that a low presence of lactobacilli at the vaginal level, and consequently, in related areas (such as the endometrium and ovary), correlates with a higher risk of gynecological pathology and likely contributes to increased incidence and worse prognosis of gynecological cancers. The complex interplay between microbial communities and the development, progression, and treatment of gynecologic malignancies is a burgeoning field not yet fully understood. The intricate crosstalk between the gut microbiota and systemic inflammation introduces a new dimension to our understanding of gynecologic cancers. The objective of this review is to focus attention on the association between vaginal microbiota and gynecological malignancies and provide detailed knowledge for future diagnostic and therapeutic strategies.