Stefano Cosma

Oncolytic Viruses in Ovarian Cancer: Where Do We Stand? A Narrative Review

Ovarian cancer (OC) remains the most lethal gynecologic malignancy with limited effective treatment options. Oncolytic viruses (OVs) have emerged as a promising therapeutic approach for cancer treatment, capable of selectively infecting and lysing cancer cells while stimulating anti-tumor immune responses. Preclinical studies have demonstrated significant tumor regression and prolonged survival in OC models using various OVs, such as herpes simplex. Early-phase clinical trials have shown a favorable safety profile, though the impact on patient survival has been modest. Current research focuses on combining OVs with other treatments like immune checkpoint inhibitors to enhance their efficacy. We provide a comprehensive overview of the current understanding and future directions for utilizing OVs in the management of OC.

Targeting TOP2A in Ovarian Cancer: Biological and Clinical Implications

The enzyme topoisomerase II alpha (TOP2A) plays a critical role in DNA replication and cell proliferation, making it a promising target for cancer therapy. In epithelial ovarian cancer (EOC), TOP2A overexpression is associated with poor prognosis and resistance to conventional treatments. This review explores the biological functions of TOP2A in EOC and discusses its potential as a therapeutic target. We highlight studies on the mechanisms through which TOP2A contributes to tumor progression and recurrence. Additionally, we evaluate the clinical implications of targeting TOP2A, including the use of TOP2A inhibitors and their combination with novel drugs. We provide a comprehensive overview of the current understanding and future directions for targeting TOP2A in the management of EOC.

Link between isolated para-aortic lymph node metastasis and intrauterine cancer site in early stage endometrial cancer

Missing occult para-aortic lymph node metastasis is one of the primary concerns of sentinel lymph node biopsy in endometrial cancer. Our study aimed to evaluate the relationship between intrauterine cancer site and isolated para-aortic lymph node metastasis to tailor treatment and reduce the false negative rate of the sentinel lymph node procedure. A retrospective, multicenter, case control study was performed in four international centers. All patients with positive lymph nodes who had complete surgical staging with pelvic and para-aortic lymphadenectomy, between January 2013 and December 2023, were included. Detailed descriptions of the cancer location within the uterine cavity on the cranio-caudal plane and the myometrial wall involvement on the cranio-caudal and ventro-dorsal planes were collected, as were clinical data and cancer histological features. Patients with isolated para-aortic lymph node metastasis were allocated to group 1; patients with pelvic lymph node metastasis and those with both pelvic and para-aortic lymph node metastasis were allocated to group 2. The groups were compared according to the variables collected. 200 preoperative early stage endometrial cancer patients with postoperative International Federation of Gynecology and Obstetrics 2009/2023 stage IIIC1/IIIC2 were included in our study: 42 patients (21%) with isolated para-aortic lymph node metastasis were allocated to group 1 and the remaining patients to group 2. The two groups had comparable clinical and pathological characteristics (p>0.05): mean age was 66.5±10.3 (group 1) and 63.5±11.9 (group 2); endometrioid histotype was the predominant one for both groups (50%); most patients had myometrial infiltration >50% (80.9% and 79.7%), grade 3 (61.9% and 63.9%), and lymph vascular space invasion (78.5% and 82.2%). Cancers involving the fundal uterine cavity, the fundal myometrial wall, or the anterior myometrial wall were 3.11 (1.04-9.27), 3.03 (1.12-8.21), and 2.12 (0.77-5.80) times more likely to metastasize only to para-aortic lymph nodes compared with cancers located in other uterine sites. In this study, the intrauterine location of the cancer determined the site of lymph node metastasis. When the tumor involved the fundus (cavity or wall) and infiltrated exclusively the anterior wall, the baseline risk of spreading only into the para-aortic area increased significantly in selected patients at risk of nodal disease.

Biomarkers of Central Nervous System Involvement from Epithelial Ovarian Cancer

Epithelial ovarian cancer (EOC) is the leading cause of death among women affected by gynaecological malignancies. Most patients show advanced disease at diagnosis (FIGO stage III-IV) and, despite the introduction of new therapeutic options, most women experience relapses. In most cases, recurrence is abdominal-pelvic; however, EOC can occasionally metastasize to distant organs, including the central nervous system. The incidence of brain metastases (BMs) from EOC is low, but it has grown over time; currently, there are no follow-up strategies available. In the last decade, a few biomarkers able to predict the risk of developing BMs from OC or as potential therapeutic targets have been investigated by several authors; to date, none have entered clinical practice. The purpose of this review is to offer a summary on the role of the most relevant predictors of central nervous system (CNS) involvement (hormone receptors; BRCA; MRD1; PD-1/PD-L1) and to highlight possible therapeutic strategies for the management of metastatic brain disease in EOC

Is There a Place for Immune Checkpoint Inhibitors in Vulvar Neoplasms? A State of the Art Review

Vulvar cancer (VC) is a rare neoplasm, usually arising in postmenopausal women, although human papilloma virus (HPV)-associated VC usually develop in younger women. Incidences of VCs are rising in many countries. Surgery is the cornerstone of early-stage VC management, whereas therapies for advanced VC are multimodal and not standardized, combining chemotherapy and radiotherapy to avoid exenterative surgery. Randomized controlled trials (RCTs) are scarce due to the rarity of the disease and prognosis has not improved. Hence, new therapies are needed to improve the outcomes of these patients. In recent years, improved knowledge regarding the crosstalk between neoplastic and tumor cells has allowed researchers to develop a novel therapeutic approach exploiting these molecular interactions. Both the innate and adaptive immune systems play a key role in anti-tumor immunesurveillance. Immune checkpoint inhibitors (ICIs) have demonstrated efficacy in multiple tumor types, improving survival rates and disease outcomes. In some gynecologic cancers (e.g., cervical cancer), many studies are showing promising results and a growing interest is emerging about the potential use of ICIs in VC. The aim of this manuscript is to summarize the latest developments in the field of VC immunoncology, to present the role of state-of-the-art ICIs in VC management and to discuss new potential immunotherapeutic approaches.