Luca Bertero

Primary ovarian leiomyosarcoma: results from an analysis by the French Sarcoma Group (Ovarian SArcoma MAnagement – OSAMA Study)

Primary ovarian leiomyosarcomas are exceptionally rare, constituting less than 1% of ovarian tumors, and they typically have a poor prognosis. The available data on the management of these tumors are sparse, with limited publications mainly comprising small retrospective series that include multiple histologic types. The aim is to evaluate the clinical, surgical, pathologic characteristics and clinical outcome of patient affected by primary ovarian leiomyosarcomas. Using the national database (NetSarc), we conducted a retrospective study of the outcomes of primary ovarian leiomyosarcomas at 18 French Sarcoma Group centers. Patients with any International Federation of Gynecology and Obstetrics stage of primary ovarian leiomyosarcoma at first diagnosis and available follow-up were included. A total of 39 patients with primary ovarian leiomyosarcomas were included: 35 had localized disease and 4 had metastatic disease. The median tumor size was 134 mm. Radical and wide surgery was performed on 21 (62%) and 13 patients (38%), respectively. Tumor grade 3, presence of necrosis, mitoses ≥20 high-power field, and high Ki-67 expression >30% were reported in 17 of 34 (50%), 29 of 34 (85%), 17 of 34 (50%), and 17 of 27 patients (63%), respectively. Positive estrogen receptor expression was reported in 14 of 27 patients (52%), whereas progesterone receptor expression was observed in 10 of 27 patients (37%). Adjuvant chemotherapy was administered in 12 of 34 patients (35%), whereas pelvic adjuvant radiotherapy in 8 of 34 (23%). Of the early-stage primary ovarian leiomyosarcomas, 9 had isolated pelvic recurrence, whereas 18 had parenchymal distant metastases. A total of 15 patients (44%) died of disease. In early-stage primary ovarian leiomyosarcomas, high mitotic counts and progesterone receptor negativity were variables associated with worse survival. Surgery is the cornerstone of treatment for early-stage primary ovarian leiomyosarcoma, whereas the role of adjuvant treatment remains unclear. Some pathologic features were associated with poorer survival. Owing to the rarity of ovarian leiomyosarcomas, referring patients to expert sarcoma centers is highly recommended.

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.

Comedo-like growth pattern in invasive early-stage cervical cancer: A new feature related to parametrial involvement

The standard surgical treatment for early-stage cervical cancer includes hysterectomy and bilateral oophorectomy along the removal of parametrial tissue to achieve surgical radicality. However, in recent years, the role of simple hysterectomy for cervical cancer with favorable prognostic characteristics has been re-evaluated. One of the challenges in early-stage cervical cancer is identifying predictive factors for neoplastic parametrial infiltration and lymph node metastases that cannot be detected during the preoperative assessment. We hypothesized that histological tumor growth patterns may be associated with these features and could thus be useful for the management of apparent early-stage cervical cancer. We identified 3 different histological patterns: the comedo-like, the infiltrative, and the expansive. We analyzed a series of clinic-pathological characteristics to determine the association of eachpatternwith aggressive features. Furthermore, we estimated odd ratios (ORs) in univariate and multivariate analyses for parametrial infiltration and lymph node metastasis. We found that comedo-like pattern is associated to advanced FIGO stages, larger tumor size, lymphovascular space invasion, deeper invasion depth, parametrium involvement, and lymph node metastases. By univariate analysis, comedo-like pattern was statistically associated with both parametrial involvement (OR: 19.3, CI 5.47-68.6, p-value = < 0.001) and lymph node metastases (OR: 4.98, CI 1.71-14.5, p-value = 0.003). By multivariate analysis, the association between comedo-like pattern and parametrial involvement was confirmed (OR: 8.76, CI 2.34-32.75, p-value = 0.01). The specific growth pattern of cervical cancer, assessed in a conization specimen before hysterectomy, can be useful to tailor surgical radicality.

Differentiated vulvar intraepithelial neoplasia long‐term follow up and prognostic factors: An analysis of a large historical cohort

AbstractIntroductionDifferentiated vulvar intraepithelial neoplasia (dVIN) is a high‐risk preinvasive vulvar lesion and precursor of human papillomavirus‐independent vulvar squamous cell carcinoma (VSCC). Due to its rarity, literature data on its malignant potential are scant. The aim of the study is to assess the risk of developing VSCC in patients surgically treated for dVIN not associated with VSCC (solitary dVIN) and the risk of VSCC recurrence in patients treated for dVIN associated with VSCC (dVIN‐VSCC) at first diagnosis.Material and methodsA historical cohort study was performed in a northern Italy referral center for vulvar neoplasms. All consecutive women surgically treated for histologically confirmed dVIN from 1994 to 2021 were collected. Primary outcome was cancer risk or recurrent cancer risk, secondary outcomes were risk factors associated with VSCC development or recurrence. Kaplan–Meier method and log‐rank test were used to estimate cancer risk or recurrent cancer risk differences and uni‐ and multivariate Cox regression analyses to identify risk factors associated with VSCC development in solitary dVIN and recurrence of dVIN‐VSCC.ResultsSeventy‐six patients with dVIN at preoperative biopsy were included: at excisional specimens 44 were solitary dVIN and 32 were dVIN‐VSCC. The absolute risk of VSCC development after solitary dVIN treatment was 43.2% with median time to to VSCC diagnosis of 25.4 months (range 3.5–128.0 months). VSCC recurrence absolute risk in treated dVIN‐VSCC patients was 31.3% with median time to VSCC recurrence of 52.9 months (range 6.5–94.8 months). At uni‐ and multivariate regression analyses, only compliant topical ultrapotent corticosteroid treatment after solitary dVIN excision showed an ability to prevent VSCC development. No protective effect by corticosteroid treatment was shown for VSCC recurrence in dVIN‐VSCC patients. Smoking was associated with higher cancer recurrence risk in dVIN‐VSCC patients on both uni‐ and multivariate regression analyses.ConclusionsPatients with dVIN have a high risk of developing both primary and recurring VSCC. Early recognition, long‐term follow up, and compliant ultrapotent topical corticosteroid treatment are recommended.

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.