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Clinical Management and Prognosis of Gynecological Cancer

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A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Clinical Research of Cancer".

Deadline for manuscript submissions: 30 July 2024 | Viewed by 6049

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Prof. Dr. Linus T. Chuang

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Guest Editor

Obstetrics and Gynecology, Danbury Hospital, Nuvance Health, Larner College of Medicine at the University of Vermont, Danbury, CT, USA
Interests: gynecologic oncology; reproductive tract; pregnancy; childbirth

Special Issue Information

Dear Colleagues,

Over the last decade, advances have been made in tumor profiling in gynecologic cancers through DNA sequencing. This is seen in various gynecologic cancers, including ovarian, uterine and cervical malignancies. Biomarker-based therapy progress varies among these tumor types, but improvements in either progression-free or overall survival outcomes have been made. In ovarian cancer, molecular signatures differ between traditionally used histologic classifications. The finding of defective homologous recombination in 50% of high-grade serous carcinomas has led to treatment with PARP inhibitors. Conversely, 80% of low-grade serous carcinomas has activated MAPK kinase pathways, with a smaller cohort being estrogen and progesterone receptor-positive. MEK inhibitors and hormonal agents are effective in these patients. A rapidly increasing number of women have been diagnosed with uterine cancer in the past two decades. Finding effective treatments for women with advanced and recurrent endometrial cancer is urgent. The TCGA molecular subtypes of endometrial cancer identify tumors in four categories. The finding of an ultra-mutated DNA polymerase epsilon (POLE) tumor in high-grade histology can help de-escalate the treatment strategy. In contrast, a high copy number (p53 mutation) would draw attention to the consideration of system therapy. In this Special Issue, translational and clinical research or reviews are invited, as this provides a direction for future research in gynecologic cancers.

Prof. Dr. Linus T. Chuang
Guest Editor

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Published Papers (6 papers)

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Research

16 pages, 657 KiB

Open AccessArticle

LUNA EMG as a Marker of Adherence to Prehabilitation Programs and Its Effect on Postoperative Outcomes among Patients Undergoing Cytoreductive Surgery for Ovarian Cancer and Suspected Ovarian Tumors

by Marcin Adam Zębalski, Krzysztof Parysek, Aleksandra Krzywon and Krzysztof Nowosielski

Cancers 2024, 16(14), 2493; https://doi.org/10.3390/cancers16142493 - 9 Jul 2024

Viewed by 284

Abstract

Background: Prehabilitation is a novel strategy in preoperative management. The aim of this study was to investigate the effect of prehabilitation programs on peri- and postoperative outcomes and to verify if LUNA EMG has the capacity to monitor compliance with prehabilitation programs. Methods: A total of seventy patients with suspected ovarian cancer were recruited between April 2021 and September 2022 and were divided into a prehabilitation group (36 patients) or a control group (34 patients). A LUNA EMG device was utilized to monitor muscle strength and tension. Results: Within the prehabilitation group, we observed a significant increase in the 6-Minute Walk Test distance by 17 m (median, IQR: 0–42.5, p < 0.001) and a significant increase in muscle strength measured with LUNA EMG. In comparison to the control group, the prehabilitation group showed fewer complications according to the Clavien–Dindo classification (47.2% vs. 20.6%, p = 0.02) and shorter postoperative hospital stays (median 5.0 days [IQR: 4.0–6.2] vs. 7.0 days [IQR: 6.0–10.0], p < 0.001). Conclusion: Prehabilitation has a positive effect on physical capacity and muscle strength and is associated with a reduction in the number of complications after surgery. LUNA EMG can be a useful tool for monitoring patients’ adherence to prehabilitation programs. Full article

(This article belongs to the Special Issue Clinical Management and Prognosis of Gynecological Cancer)

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11 pages, 650 KiB

Open AccessArticle

Prognostic Role of CA-125 Elimination Rate Constant (KELIM) in Patients with Advanced Epithelial Ovarian Cancer Who Received PARP Inhibitors

by Ji Hyun Kim, Eun Taeg Kim, Se Ik Kim, Eun Young Park, Min Young Park, Sang-Yoon Park and Myong Cheol Lim

Cancers 2024, 16(13), 2339; https://doi.org/10.3390/cancers16132339 - 26 Jun 2024

Viewed by 848

Abstract

Background: This multicenter retrospective study aimed to investigate the prognostic value of the CA-125 elimination rate constant K (KELIM) in EOC patients who received platinum-based chemotherapy followed by PARP inhibitors, in either upfront or interval treatment settings. Methods: Between July 2019 and November 2022, we identified stage III–IV EOC patients who underwent primary or interval cytoreductive surgery and received olaparib or niraparib. Individual KELIM values were assessed based on validated kinetics and classified into favorable and unfavorable cohorts. Results: In a study of 252 patients undergoing frontline maintenance therapy with olaparib or niraparib, favorable KELIM (≥1) scores were associated with a higher PFS benefit in the primary cytoreductive surgery (PCS) cohort (hazard ratio (HR) for disease progression or death 3.51, 95% confidence interval (CI); 1.37–8.97, p = 0.009). Additionally, within the interval cytoreductive surgery (ICS) cohort, a favorable KELIM score (≥1) significantly increased the likelihood of achieving complete resection following cytoreductive surgery, with 59.4% in the favorable KELIM group compared to 37.8% in those with unfavorable KELIM. Conclusions: A favorable KELIM score was associated with improved PFS in patients with advanced EOC undergoing PCS. Furthermore, in the ICS cohort, a favorable KELIM score increased the probability of complete cytoreduction. Full article

(This article belongs to the Special Issue Clinical Management and Prognosis of Gynecological Cancer)

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23 pages, 3256 KiB

Open AccessArticle

Combined Treatment of Uterine Leiomyosarcoma with Gamma Secretase Inhibitor MK-0752 and Chemotherapeutic Agents Decreases Cellular Invasion and Increases Apoptosis

by Yasmin Abedin, Alexander Fife, Cherie-Ann Samuels, Rasheena Wright, Trystn Murphy, Xusheng Zhang, Emily Alpert, Emma Cheung, Qingshi Zhao, Mark H. Einstein and Nataki C. Douglas

Cancers 2024, 16(12), 2184; https://doi.org/10.3390/cancers16122184 - 10 Jun 2024

Viewed by 519

Abstract

Due to limited effective therapeutics for uterine leiomyosarcoma (uLMS), the impact of the gamma secretase inhibitor (GSI) MK-0752 with common chemotherapeutics was explored in uLMS. MTT assays were performed on two human uLMS cell lines, SK-UT-1B and SK-LMS-1, using MK-0752, docetaxel, doxorubicin, and gemcitabine, individually and in combination, to determine cell viability after treatment. Synergistic combinations were used in transwell invasion assays, cell cycle flow cytometry, proliferation assays, and RNA sequencing. In SK-UT-1B, MK-0752 was synergistic with doxorubicin and gemcitabine plus docetaxel. In SK-LMS-1, MK-0752 was synergistic with all individual agents and with the combination of gemcitabine plus docetaxel. MK-0752, gemcitabine, and docetaxel decreased invasion in SK-UT-1B 2.1-fold* and in SK-LMS-1 1.7-fold*. In SK-LMS-1, invasion decreased 1.2-fold* after treatment with MK-0752 and docetaxel and 2.2-fold* after treatment with MK-0752 and doxorubicin. Cell cycle analysis demonstrated increases in the apoptotic sub-G1 population with MK-0752 alone in SK-UT-1B (1.4-fold*) and SK-LMS-1 (2.7-fold**), along with increases with all combinations in both cell lines. The combination treatments had limited effects on proliferation, while MK-0752 alone decreased proliferation in SK-LMS-1 (0.63-fold**). Both MK-0752 alone and in combination altered gene expression and KEGG pathways. In conclusion, the combinations of MK-0752 with either doxorubicin, docetaxel, or gemcitabine plus docetaxel are potential novel therapeutic approaches for uLMS. (* p < 0.05, ** p < 0.01). Full article

(This article belongs to the Special Issue Clinical Management and Prognosis of Gynecological Cancer)

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11 pages, 1134 KiB

Open AccessArticle

The Prognostic Value of the Systemic Immune-Inflammation Index (SII) and Red Cell Distribution Width (RDW) in Patients with Cervical Cancer Treated Using Radiotherapy

by Emilia Staniewska, Karolina Grudzien, Magdalena Stankiewicz, Katarzyna Raczek-Zwierzycka, Justyna Rembak-Szynkiewicz, Zuzanna Nowicka, Rafal Tarnawski and Marcin Miszczyk

Cancers 2024, 16(8), 1542; https://doi.org/10.3390/cancers16081542 - 18 Apr 2024

Viewed by 900

Abstract

Introduction: There is growing interest in the prognostic value of routinely performed pre-treatment blood test indices, such as the RDW or SII, with the latter combining the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR). These indices were shown to be prognostic for survival in some malignancies. The purpose of this study was to evaluate the association between pre-treatment RDW and SII, and OS in patients treated with radiotherapy for primary localised cervical cancer. Material and Methods: This retrospective analysis included patients treated with definitive CRT between 2011 and 2017 for histopathologically confirmed FIGO 2018 stage IB2-IVA cervical cancer. Statistical analysis was performed using the Kaplan–Meier method, two-sided log-rank tests, and Cox proportional hazards models, with the AIC serving as a prediction error estimator. Results: The study group included 249 patients with a median age of 57.2 years and a median follow-up of 75.8 months. The majority were diagnosed with squamous cell carcinoma (237; 95.2%) and had FIGO stage III (211; 84.7%). Approximately half of the patients (116; 46.4%) had regional lymph node metastases. Patients with a low RDW (≤13.4%) and low SII (≤986.01) had a significantly longer OS (p = 0.001 and p = 0.002). The RDW remained as an independent prognostic factor in the multivariable model (high vs. low; HR = 2.04; 95% CI: 1.32–3.16; p = 0.001). Including RDW in the model decreased the Akaike Information Criterion from 1028.25 to 1018.15. Conclusions: The RDW is a cheap and widely available index that is simultaneously an independent prognostic factor for survival and could be used to improve pre-treatment prognosis assessments in patients with cervical cancer undergoing CRT. Available data encourage assessing the RDW as a prognostic factor in prospective trials to aid the identification of candidates for treatment escalation. Full article

(This article belongs to the Special Issue Clinical Management and Prognosis of Gynecological Cancer)

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13 pages, 1864 KiB

Open AccessArticle

Exploring the Potential Role of Upper Abdominal Peritonectomy in Advanced Ovarian Cancer Cytoreductive Surgery Using Explainable Artificial Intelligence

by Alexandros Laios, Evangelos Kalampokis, Marios Evangelos Mamalis, Amudha Thangavelu, Richard Hutson, Tim Broadhead, David Nugent and Diederick De Jong

Cancers 2023, 15(22), 5386; https://doi.org/10.3390/cancers15225386 - 13 Nov 2023

Viewed by 1764

Abstract

The Surgical Complexity Score (SCS) has been widely used to describe the surgical effort during advanced stage epithelial ovarian cancer (EOC) cytoreduction. Referring to a variety of multi-visceral resections, it best combines the numbers with the complexity of the sub-procedures. Nevertheless, not all potential surgical procedures are described by this score. Lately, the European Society for Gynaecological Oncology (ESGO) has established standard outcome quality indicators pertinent to achieving complete cytoreduction (CC0). There is a need to define what weight all these surgical sub-procedures comprising CC0 would be given. Prospectively collected data from 560 surgically cytoreduced advanced stage EOC patients were analysed at a UK tertiary referral centre.We adapted the structured ESGO ovarian cancer report template. We employed the eXtreme Gradient Boosting (XGBoost) algorithm to model a long list of surgical sub-procedures. We applied the Shapley Additive explanations (SHAP) framework to provide global (cohort) explainability. We used Cox regression for survival analysis and constructed Kaplan-Meier curves. The XGBoost model predicted CC0 with an acceptable accuracy (area under curve [AUC] = 0.70; 95% confidence interval [CI] = 0.63–0.76). Visual quantification of the feature importance for the prediction of CC0 identified upper abdominal peritonectomy (UAP) as the most important feature, followed by regional lymphadenectomies. The UAP best correlated with bladder peritonectomy and diaphragmatic stripping (Pearson’s correlations > 0.5). Clear inflection points were shown by pelvic and para-aortic lymph node dissection and ileocecal resection/right hemicolectomy, which increased the probability for CC0. When UAP was solely added to a composite model comprising of engineered features, it substantially enhanced its predictive value (AUC = 0.80, CI = 0.75–0.84). The UAP was predictive of poorer progression-free survival (HR = 1.76, CI 1.14–2.70, P: 0.01) but not overall survival (HR = 1.06, CI 0.56–1.99, P: 0.86). The SCS did not have significant survival impact. Machine Learning allows for operational feature selection by weighting the relative importance of those surgical sub-procedures that appear to be more predictive of CC0. Our study identifies UAP as the most important procedural predictor of CC0 in surgically cytoreduced advanced-stage EOC women. The classification model presented here can potentially be trained with a larger number of samples to generate a robust digital surgical reference in high output tertiary centres. The upper abdominal quadrants should be thoroughly inspected to ensure that CC0 is achievable. Full article

(This article belongs to the Special Issue Clinical Management and Prognosis of Gynecological Cancer)

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12 pages, 1172 KiB

Open AccessArticle

Risk Factors and Prognosis of Stroke in Gynecologic Cancer Patients

by Ji Young Kwon, Kena Park, Jeong Min Song, Seung Yeon Pyeon, Seon Hwa Lee, Young Shin Chung and Jong-Min Lee

Cancers 2023, 15(19), 4895; https://doi.org/10.3390/cancers15194895 - 9 Oct 2023

Cited by 1 | Viewed by 1165

Abstract

Increased life expectancy and cancer prevalence rates expose patients to a higher risk of developing other comorbidities such as stroke. This study aimed to evaluate the risk factors for and prognosis of stroke in patients with gynecological cancers. A single-center retrospective cohort study was conducted on patients with cervical, endometrial, and epithelial ovarian cancers. Patients were classified into three groups based on the period of stroke onset: at least one year before cancer diagnosis, within one year before cancer diagnosis to six months after the last treatment date, and six months after the last treatment date. Among the 644 patients, stroke occurred in 54 (8.4%). In univariate analysis, stroke was significantly associated with overall survival. In contrast, in multivariate analysis, stroke was significantly associated with age and hypertension, but not with overall survival. Age, pulmonary thromboembolism/deep vein thrombosis, histological grade, and tumor stage were significantly associated with overall survival. Therefore, it is important to establish an appropriate examination and treatment plan for patients with gynecologic cancers using a multidisciplinary approach that incorporates the patient’s age, medical condition, and tumor characteristics rather than excessively considering the adverse effects of stroke on cancer prognosis. Full article

(This article belongs to the Special Issue Clinical Management and Prognosis of Gynecological Cancer)

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