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.

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.

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.

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.

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.

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.

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.

TIGIT: A potential immunotherapy target for gynecological cancers.

Gynecological cancer represents a significant global health challenge, and conventional treatment modalities have demonstrated limited efficacy. However, recent investigations into immune checkpoint pathways have unveiled promising opportunities for enhancing the prognosis of patients with cancer. Among these pathways, TIGIT has surfaced as a compelling candidate owing to its capacity to augment the immune function of NK and T cells through blockade, thereby yielding improved anti-tumor effects and prolonged patient survival. Global clinical trials exploring TIGIT blockade therapy have yielded promising preliminary findings. Nevertheless, further research is imperative to comprehensively grasp the potential of TIGIT-based immunotherapy in optimizing therapeutic outcomes for gynecological cancers. This review primarily delineates the regulatory network and immunosuppressive mechanism of TIGIT, expounds upon its expression and therapeutic potential in three major gynecological cancers, and synthesizes the clinical trials of TIGIT-based cancer immunotherapy. Such insights aim to furnish novel perspectives and serve as reference points for subsequent research and clinical application targeting TIGIT in gynecological cancers.

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.

Nuclear Medicine and Molecular Imaging Applications in Gynecologic Malignancies: A Comprehensive Review.

Gynecologic malignancies, consisting of endometrial, cervical, ovarian, vulvar, and vaginal cancers, pose significant diagnostic and management challenges due to their complex anatomic location and potential for rapid progression. These tumors cause substantial morbidity and mortality, often because of their delayed diagnosis and treatment. An estimated 19% of newly diagnosed cancers among women are gynecologic in origin. In recent years, there has been growing evidence supporting the integration of nuclear medicine imaging modalities in the diagnostic work-up and management of gynecologic cancers. The sensitivity of fluorine-18 fluorodeoxyglucose positron emission tomography (18F-FDG PET) combined with the anatomical specificity of computed tomography (CT) and magnetic resonance imaging (MRI) allows for the hybrid evaluation of metabolic activity and structural abnormalities that has become an indispensable tool in oncologic imaging. Lymphoscintigraphy, using technetium 99m (99mTc) based radiotracers along with single photon emission computed tomography/ computed tomography (SPECT/CT), holds a vital role in the identification of sentinel lymph nodes to minimize the surgical morbidity from extensive lymph node dissections. While not yet standard for gynecologic malignancies, promising therapeutic nuclear medicine agents serve as specialized treatment options for patients with advanced or recurrent disease. This article aims to provide a comprehensive review on the nuclear medicine applications in gynecologic malignancies through the following objectives: 1) To describe the role of nuclear medicine in the initial staging, lymph node mapping, response assessment, and recurrence/surveillance imaging of common gynecologic cancers, 2) To review the limitations of 18F-FDG PET/CT and promising applications of 18F-FDG PET/MRI in gynecologic malignancy, 3) To underscore the promising theragnostic applications of nuclear medicine, 4) To highlight the current role of nuclear medicine imaging in gynecologic cancers as per the National Comprehensive Cancer Network (NCCN), European Society of Surgical Oncology (ESGO), and European Society of Medical Oncology (ESMO) guidelines.

Pelvic Floor Therapy and Initial Interventions for Pelvic Floor Dysfunction in Gynecologic Malignancies.

PURPOSE OF REVIEW: This review provides evidence-based updates for the first-line management approaches for pelvic floor disorders in patients with gynecologic malignancies, as well as important provider considerations when referring for pelvic floor physical therapy. RECENT FINDINGS: Currently, there is strong evidence to recommend pelvic floor muscle training as initial treatment for urinary incontinence and for pelvic organ prolapse; some evidence to recommend a more targeted pelvic floor muscle training program for fecal incontinence; and mostly expertise-based evidence to recommend vaginal gels or estrogen to aid with dyspareunia causing sexual dysfunction. More research is greatly needed to understand the role of overactive pelvic floor muscles in survivors with chronic pelvic pain and the treatment of post-radiation pelvic complications such as vaginal stenosis and cystitis. While pelvic floor disorders are common concerns in gynecologic cancer survivors, there are evidence-based initial noninvasive treatment approaches that can provide relief for many individuals.

Counselling and management of women with genetic predisposition to gynaecological cancers.

OBJECTIVE: To review the literature with reference to counselling and management of women with genetic predisposition to gynaecological cancers. METHODS: Histochemical analysis, ultrasound, blood investigations, genetic testing, screening and risk-reducing surgery (RRS) are important tools for the management of gynaecological cancers and mortality reduction. Counselling can assist in timely management of gynaecological cancers. Systematic reviews, review articles, observational studies and clinical trials on PubMed, published in the English language, were included in this review. RESULTS: The management of women with genetic predisposition to gynaecological cancers through screening tests and RRS has led to a significant decrease in the risk of malignancy through RRS in cases with BRCA1 and BRCA2 gene mutations. RRS and screening have also been found to reduce the mortality rate and increase the survival rate in women with BRCA1 and BRCA2 gene mutations. The efficacy of endometrial cancer surveillance in women with Lynch syndrome is still unproven. RRS has not been reported to be effective in women with Cowden syndrome. The risk of ovarian malignancies in individuals with germline mutations remains minimal in the general population in comparison with genetic mutations. CONCLUSION: Genetic testing and RRS should be implemented in addition to genetic counselling for proper management and mortality reduction of women predisposed to gynaecological cancers.

Systematic Review of the Literature on Multiple Co-occurring Symptoms in Patients Receiving Treatment for Gynecologic Cancers.

OBJECTIVE: Patients with gynecologic cancers experience a very high symptom burden that has a negative impact on their quality of life. This systematic review aims to identify the common co-occurring symptoms, the prevalence of common symptoms, common instruments used to measure symptoms, associated risk factors, and the symptom burden in patients with gynecologic cancers. DATA SOURCES: A search of four databases (ie, PubMed, Embase, Web of Science, and CINAHL) was done from January 1, 2012, through September 5, 2022. A qualitative synthesis of the extant literature was performed using Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines (PRISMA 2020). CONCLUSION: A total of 118 studies met the prespecified inclusion criteria. Ninety-six symptoms were assessed across these studies. The top six symptoms and their grand mean prevalence rates were lack of energy (64.4%), fatigue (62.1%), abdominal pain (53.3%), depression (52.6%), concentration dysfunction (52.0%), and drowsiness (51.9%). Numerous methodologic challenges were evident across studies. Future research needs to develop a disease-specific symptom assessment measure, evaluate for risk factors associated with a higher symptom burden, and determine the impact of multiple symptoms on patient outcomes. IMPLICATION FOR NURSING PRACTICE: The results are relevant for oncology clinicians to assess patients with gynecologic cancers for the presence of common symptoms and risk factors for higher symptom burden in the patients and to offer effective management interventions.