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Novel and Personalized Treatment Concepts in Gynecologic Cancer

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A special issue of Journal of Personalized Medicine (ISSN 2075-4426). This special issue belongs to the section "Mechanisms of Diseases".

Deadline for manuscript submissions: 30 April 2024 | Viewed by 13297

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Dr. Stephan Polterauer

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Department of Obstetrics and Gynecology, Comprehensive Cancer Center-Gynecologic Cancer Unit, Medical University of Vienna, 1090 Vienna, Austria
Interests: gynecologic oncology; tumor biology of ovarian cancer; medical treatment for cervical cancer precursor lesions
Special Issues, Collections and Topics in MDPI journals

Dr. Christoph Grimm

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Division of General Gynaecology and Gynaecological Oncology, Vienna General Hospital, Medical University of Vienna, 1090 Vienna, Austria
Interests: gynecologic oncology; tumor biology of ovarian cancer; medical treatment for cervical cancer precursor lesions
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The field of gynecologic oncology has evolved greatly within the last years. The introduction of molecular analysis has changed the way we classify endometrial and epithelial ovarian cancers. Moreover, surgical treatment concepts have developed due to the introduction of the sentinel lymph node technique, allowing us to spare patients from unnecessary morbidities. Finally, predictive biomarkers such as BRCA mutations, homologous recombination deficiency, and microsatellite instability have revolutionized the treatment of a variety of gynecologic malignancies.

In the precision medicine era, the further understanding of cancer genomics and the identification of predictive biomarkers are essential to achieve better health outcomes for women with gynecologic cancer.

In this Special Issue, we aim to cover highly innovative findings and concepts within the field of gynecologic oncology, ranging from diagnostics to therapeutic approaches, that could improve the way we diagnose, classify, and/or treat gynecologic malignancies. A special focus will be precision medicine using molecular approaches and targeted treatments including Immunotherapy.

Dr. Stephan Polterauer
Dr. Christoph Grimm
Guest Editors

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Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

precision medicine
molecular therapy
targeted therapy
immunotherapy
ovarian cancer
endometrial cancer
vulvar cancer
cervical cancer
homologous recombination
DNA damage repair
biomarkers
imaging
individualized treatment

Published Papers (9 papers)

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Research

12 pages, 661 KiB

Open AccessArticle

Prognostic Value of Lymph Node Ratio in Patients with Uterine Carcinosarcoma

by Rasiah Bharathan, Stephan Polterauer, Martha C. Lopez-Sanclemente, Hanna Trukhan, Andrei Pletnev, Angel G. Heredia, Maria M. Gil, Irina Bakinovskaya, Alena Dalamanava, Margarita Romeo, Dzmitry Rovski, Laura Baquedano, Luis Chiva, Richard Schwameis, Ignacio Zapardiel and on behalf of SARCUT Study Group

J. Pers. Med. 2024, 14(2), 155; https://doi.org/10.3390/jpm14020155 - 30 Jan 2024

Viewed by 719

Abstract

Uterine carcinosarcoma is a rare high-grade endometrial cancer. Controversy has surrounded a number of aspects in the diagnosis and management of this unique clinicopathological entity, including the efficacy of adjuvant therapy, which has been questioned. An unusual surgico-pathological parameter with prognostic significance in a number of tumour sites is the lymph node ratio (LNR). The availability of data in this respect has been scarce in the literature. The primary aim of this collaborative study was to evaluate the prognostic value of LNR in patients with uterine carcinosarcoma. LNR is a recognized lymph node metric used to stratify prognosis in a variety of malignancies. In this European multinational retrospective study, 93 women with uterine carcinosarcoma were included in the final analysis. We used t-tests and ANOVA for comparison between quantitative variables between the groups, and chi-square tests for qualitative variables. A multivariate analysis using Cox regression analysis was performed to determine potential prognostic factors, including the LNR. Patients were grouped with respect to LNR in terms of 0%, 20% > 0% and >20%. The analysis revealed LNR to be a significant predictor of progression-free survival (HR 1.69, CI (1.12–2.55), p = 0.012) and overall survival (HR 1.71, CI (1.07–2.7), p = 0.024). However, LNR did not remain a significant prognostic factor on multivariate analysis. Due to limitations of the retrospective study, a prospective large multinational study, which takes into effect the most recent changes to clinical practice, is warranted to elucidate the value of the pathophysiological metrics of the lymphatic system associated with prognosis. Full article

(This article belongs to the Special Issue Novel and Personalized Treatment Concepts in Gynecologic Cancer)

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12 pages, 2044 KiB

Open AccessArticle

Immunohistochemical Profiling of PD-1, PD-L1, CD8, MSI, and p53 and Prognostic Implications in Advanced Serous Ovarian Carcinoma: A Retrospective Study

by Ana Paula Dergham, Caroline Busatta Vaz de Paula, Seigo Nagashima, Márcia Olandoski, Lucia de Noronha and Vanessa Santos Sotomaior

J. Pers. Med. 2023, 13(7), 1045; https://doi.org/10.3390/jpm13071045 - 26 Jun 2023

Viewed by 893

Abstract

Advanced high-grade serous ovarian carcinoma is a serious malignant neoplasm with a late diagnosis and high mortality rate. Even when treated with standard therapy, such as surgery followed by carboplatin and paclitaxel chemotherapy, the prognosis remains unfavorable. Immunotherapy is a treatment alternative that requires further study. Therefore, we aimed to evaluate the expression of PD-1, PD-L1, CD8, MSI (MLH1, MSH2, MSH6, and PMS2), and p53 in the paraffin samples of high-grade serous ovarian carcinoma. A retrospective study of 28 southern Brazilian patients with advanced serous ovarian carcinoma (EC III or IV) was conducted between 2009 and 2020. The expression of these proteins was evaluated using immunohistochemistry, and the results were correlated with the patients’ clinicopathological data. At diagnosis, the mean age was 61 years, and the most common clinical stage (60%) was EC III. Among the cases, 84.6% exhibited p53 overexpression, 14.8% had MSI, 92.0% were sensitive to platinum, and more than 50.0% relapsed after treatment. Patients with MSI had a lower CD8/PD-1 ratio and more relapses (p = 0.03). In conclusion, analysis of immunotherapeutic markers in paraffin-embedded advanced serous ovarian carcinoma samples is feasible and may assist in prognosis. Full article

(This article belongs to the Special Issue Novel and Personalized Treatment Concepts in Gynecologic Cancer)

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12 pages, 2242 KiB

Open AccessArticle

Sentinel Lymph Node Impact on the Quality of Life of Patients with Endometrial Cancer

by Virginia García-Pineda, Alicia Hernández, Sonia Garrido-Mallach, Elena Rodríguez-González, María Alonso-Espías, Myriam Gracia, Rocío Arnedo and Ignacio Zapardiel

J. Pers. Med. 2023, 13(5), 847; https://doi.org/10.3390/jpm13050847 - 17 May 2023

Viewed by 1020

Abstract

Objective: Given the improvement in the surgical treatment of endometrial cancer with the inclusion of sentinel lymph node biopsy (SLNB), our aim was to evaluate the impact of this minimally invasive and tailored nodal assessment on patients’ quality of life (QoL). Methods: This was a cross-sectional study conducted in a single-centre, tertiary-level hospital. Patients diagnosed with preoperative early-stage endometrial cancer, who underwent primary surgical treatment between August 2015 and November 2021, were included. The enrolled patients were divided into two cohorts according to the nodal staging performed: the first group underwent only SLNB (SLNB group); the second group underwent pelvic and/or para-aortic lymphadenectomy (LND group). We evaluated the overall QoL using the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life core 30-item questionnaire (EORTC QLQ-C30) and a sexual health questionnaire (EORTC SHQ-C20). The scores were compared between the groups. Results: Ninety patients were enrolled in the study: 61 (67.8%) in the SLNB group and 29 (32.2%) in the LND group. In the LND group, 24 (82.7%) patients underwent pelvic and para-aortic LND, while 5 (17.3%) patients underwent pelvic LND. The assessment of the functional scales showed better results for the SLNB group than for the LND group, with a significantly lower impact on physical status (8.2% vs. 25%, respectively; p = 0.031). In terms of the symptom scales, the SLNB group reported a significantly lower negative impact on sleep quality (4.9% vs. 27.6%, respectively; p < 0.01), pain (1.6% vs. 13.8%, respectively; p = 0.019), and dyspnoea (0% vs. 10.3%, respectively; p = 0.011) than the LND group. The SLNB group had better results for all analysed items regarding sexual QoL. Conclusions: The implementation of a surgical technique with SLNB improved patients’ overall QoL by increasing their well-being in the functional and symptom spheres. Full article

(This article belongs to the Special Issue Novel and Personalized Treatment Concepts in Gynecologic Cancer)

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21 pages, 7072 KiB

Open AccessArticle

Comprehensive Analysis of Purine-Metabolism-Related Gene Signature for Predicting Ovarian Cancer Prognosis, Immune Landscape, and Potential Treatment Options

by Jingchun Liu, Xiaoyi Zhang, Haoyu Wang, Xiaohu Zuo and Li Hong

J. Pers. Med. 2023, 13(5), 776; https://doi.org/10.3390/jpm13050776 - 29 Apr 2023

Cited by 2 | Viewed by 1596

Abstract

Purine metabolism is an important branch of metabolic reprogramming and has received increasing attention in cancer research. Ovarian cancer is an extremely dangerous gynecologic malignancy for which there are no adequate tools to predict prognostic risk. Here, we identified a prognostic signature consisting of nine genes related to purine metabolism, including ACSM1, CACNA1C, EPHA4, TPM3, PDIA4, JUNB, EXOSC4, TRPM2, and CXCL9. The risk groups defined by the signature are able to distinguish the prognostic risk and the immune landscape of patients. In particular, the risk scores offer promising personalized drug options. By combining risk scores with clinical characteristics, we have created a more detailed composite nomogram that allows for a more complete and individualized prediction of prognosis. In addition, we demonstrated metabolic differences between platinum-resistant and platinum-sensitive ovarian cancer cells. In summary, we have performed the first comprehensive analysis of genes related to purine metabolism in ovarian cancer patients and created a feasible prognostic signature that will aid in risk prediction and support personalized medicine. Full article

(This article belongs to the Special Issue Novel and Personalized Treatment Concepts in Gynecologic Cancer)

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11 pages, 2287 KiB

Open AccessArticle

Personalized Sentinel Node Mapping in Endometrial Cancer by the Indocyanine Green Implementation as Single Tracer: A Case Control Study

by Ignacio Cristóbal Quevedo, Ignacio Cristóbal García, Myriam Gracia, Virginia Garcia-Pineda, Maria Alonso-Espias, Jaime Siegrist, Maria Dolores Diestro, Alicia Hernández and Ignacio Zapardiel

J. Pers. Med. 2023, 13(2), 170; https://doi.org/10.3390/jpm13020170 - 18 Jan 2023

Cited by 1 | Viewed by 1476

Abstract

The main objective was to analyze the rate of bilateral sentinel lymph node (SLN) detection in endometrial cancer using indocyanine green (ICG) as a unique tracer compared to Technetium99 + ICG. As secondary objectives, we analyzed the drainage pattern and factors that might affect the oncological outcomes. A case-control ambispective study was carried out on consecutive patients at our center. Data on the SLN biopsy with ICG collected prospectively were compared to retrospective data on the use of a double-tracer technique including Technetium99 + ICG. In total, 194 patients were enrolled and assigned to both groups, in which the group with both tracers (controls) included 107 (54.9%) patients and the ICG-alone group (cases) included 87 (45.1%) patients. The rate of bilateral drainage was significantly higher in the ICG group (98.9% vs. 89.7%; p = 0.013). The median number of nodes retrieved was higher in the control group (three vs. two nodes; p < 0.01). We did not find survival differences associated with the tracer used (p = 0.85). We showed significant differences in terms of disease-free survival regarding the SLN location (p < 0.01), and obturator fossa retrieved nodes showed better prognosis compared to external iliac. The use of ICG as a single tracer for SLN detection in endometrial cancer patients seemed to obtain higher rates of bilateral detection with similar oncological outcomes. Full article

(This article belongs to the Special Issue Novel and Personalized Treatment Concepts in Gynecologic Cancer)

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14 pages, 2439 KiB

Open AccessArticle

Tumor Suppressive Role of the PRELP Gene in Ovarian Clear Cell Carcinoma

by Ai Dozen, Kanto Shozu, Norio Shinkai, Noriko Ikawa, Rina Aoyama, Hidenori Machino, Ken Asada, Hiroshi Yoshida, Tomoyasu Kato, Ryuji Hamamoto, Syuzo Kaneko and Masaaki Komatsu

J. Pers. Med. 2022, 12(12), 1999; https://doi.org/10.3390/jpm12121999 - 02 Dec 2022

Cited by 4 | Viewed by 1668

Abstract

Ovarian clear cell carcinoma (OCCC) has a poor prognosis, and its therapeutic strategy has not been established. PRELP is a leucine-rich repeat protein in the extracellular matrix of connective tissues. Although PRELP anchors the basement membrane to the connective tissue and is absent in most epithelial cancers, much remains unknown regarding its function as a regulator of ligand-mediated signaling pathways. Here, we obtained sets of differentially expressed genes by PRELP expression using OCCC cell lines. We found that more than 1000 genes were significantly altered by PRELP expression, particularly affecting the expression of a group of genes involved in the PI3K-AKT signaling pathway. Furthermore, we revealed the loss of active histone marks on the loci of the PRELP gene in patients with OCCC and how its forced expression inhibited cell proliferation. These findings suggest that PRELP is not only a molecule anchored in connective tissues but is also a signaling molecule acting in a tumor-suppressive manner. It can serve as the basis for early detection and novel therapeutic approaches for OCCC toward precision medicine. Full article

(This article belongs to the Special Issue Novel and Personalized Treatment Concepts in Gynecologic Cancer)

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10 pages, 1079 KiB

Open AccessArticle

The Prognostic Value of the Fibrinogen-Albumin-Ratio Index (FARI) in Patients with Advanced Vulvar Cancer

by Arina Onoprienko, Gerda Hofstetter, Tim Dorittke, Christine Bekos, Christoph Grimm, Mariella Polterauer, Thomas Bartl and Stephan Polterauer

J. Pers. Med. 2022, 12(11), 1882; https://doi.org/10.3390/jpm12111882 - 10 Nov 2022

Cited by 1 | Viewed by 1127

Abstract

The present study aims to evaluate the pretherapeutic Fibrinogen-Albumin-Ratio Index (FARI), as currently reliable biomarkers to predict therapy response and prognosis of patients with advanced vulvar cancer are missing. Data of 124 consecutive patients, who underwent primary resection for vulvar cancer ≥ pT1b, were retrospectively analyzed. Associations between the FARI and disease recurrence were assessed fitting receiver operating characteristics (ROC) and binary logistic regression models; univariate and multivariable Cox regression models for disease-specific survival (DSS) and progression-free survival (PFS) were performed. A pretherapeutic low FARI cut at its median (<9.67) is significantly associated with younger age (65.5 vs. 74.0 years) and higher risk of recurrence (52.4% vs. 26.2%). The ROC analysis calculates the area under the curve (AUC) of the FARI for a PFS < 6 months of 0.700 and for a DSS < 12 months of 0.706, outperforming fibrinogen and albumin alone. The FARI remained independently predictive for PFS (HR 0.84, 95% CI [0.99–1.03], p = 0.009) and DSS (HR 0.82, 95% CI [0.70–0.99], p = 0.019), also in multivariable survival analysis. Despite the FARI’s promising predictive and prognostic value, however, further elucidation of its precise mode of action is warranted before clinical application as it appears to rely only on subtle changes of fibrinogen levels. Full article

(This article belongs to the Special Issue Novel and Personalized Treatment Concepts in Gynecologic Cancer)

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17 pages, 29715 KiB

Open AccessArticle

A Promising Approach for Primary Cytoreductive Surgery for Advanced Ovarian Cancer: Survival Outcomes and Step-by-Step Description of Total Retroperitoneal en-Bloc Resection of Multivisceral-Peritoneal Packet (TROMP)

by Mustafa Zelal Muallem, Luisa Kluge, Ahmad Sayasneh, Jalid Sehouli, Dario Zocholl, Jumana Muallem and Andrea Miranda

J. Pers. Med. 2022, 12(6), 899; https://doi.org/10.3390/jpm12060899 - 29 May 2022

Cited by 1 | Viewed by 2013

Abstract

(1) Background: A complete tumor resection during primary cytoreductive surgery has been reported to be the most important and perhaps the only independent prognostic factor in advanced ovarian cancers. The goal of complete cytoreduction needs to be weighed against the potential morbidities and long-term survival outcomes. (2) Methods: in this retrospective analysis of a prospectively obtained database, 208 consecutive patients with advanced ovarian cancer who underwent a conventional primary cytoreductive surgery (150 patients) or TROMP technique (58 patients) were included. Progression-free and overall survival rates were calculated using Kaplan–Meier analysis as well as the 95% confidence interval of the hazard ratio between treatment groups. (3) Results: After a median follow-up phase of more than 3 years (range 1–72 months), there are no statistically significant differences between both groups in progression-free and overall survival rates. Albeit, the TROMP group included statistically significant more advanced-stage cases compared to the conventional surgery group. (4) Conclusions: the TROMP technique is a promising tool for successful primary cytoreductive surgery in a selected group of patients with high tumor burdens in order to achieve optimal surgical results and survival outcomes without introducing any additional risks or complications. Full article

(This article belongs to the Special Issue Novel and Personalized Treatment Concepts in Gynecologic Cancer)

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9 pages, 1518 KiB

Open AccessArticle

Prostate-Specific Membrane Antigen (PSMA) Expression in Tumor-Associated Neovasculature Is an Independent Prognostic Marker in Patients with Ovarian Cancer

by Gerda Hofstetter, Christina Grech, Dietmar Pils, Johannes Pammer, Barbara Neudert, Nina Pötsch, Pascal Baltzer, Tatjana Traub-Weidinger, Veronika Seebacher and Stefanie Aust

J. Pers. Med. 2022, 12(4), 551; https://doi.org/10.3390/jpm12040551 - 31 Mar 2022

Cited by 4 | Viewed by 1858

Abstract

Prostate-specific membrane antigen (PSMA) is present in the tumor-associated neovasculature of many cancer types. Current data in ovarian cancer are limited and controversial; thus, the aim of this study was to investigate PSMA expression in a larger and homogenous patient cohort. This might lead to further studies investigating the use of imaging and therapeutic modalities targeting PSMA. Eighty patients with advanced stage high-grade serous ovarian cancers were included. Using immunohistochemistry, PSMA and CD31, a marker for endothelial cells, were examined in whole tissue sections. Percentage and intensity of PSMA expression were determined in the neovasculature. Expression levels were correlated with clinicopathological parameters and survival. Low (≤10%), medium (20–80%), and high (≥90%) PSMA expression was found in 14, 46, and 20 ovarian cancer samples, respectively. PSMA expression was confined to tumor-associated neovasculature and significantly correlated with progression-free (HR 2.24, 95% CI 1.32–3.82, p = 0.003) and overall survival (HR 2.73, 95% CI 1.41–5.29, p = 0.003) in multivariate models, considering age, FIGO stage, and residual disease. This is the first study showing a clinical relevance for PSMA in patients with ovarian cancer. PSMA was detected in the vast majority of cancer samples and showed an impact on survival. Full article

(This article belongs to the Special Issue Novel and Personalized Treatment Concepts in Gynecologic Cancer)

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