Immunotherapy for Cervical Cancer: Are We Ready for Prime Time?

The prognosis of invasive cervical cancer (CC) remains poor, with a treatment approach that has remained the same for several decades. Lately, a better understanding of the interactions between the disease and the host immune system has allowed researchers to focus on the employment of immune therapy in various clinical settings. The most advanced strategy is immune checkpoint inhibitors (ICIs) with numerous phase II and III trials recently concluded with very encouraging results, assessing single agent therapy, combinations with chemotherapy and radiotherapy. Apart from ICIs, several other compounds have gained the spotlight. Tumor Infiltrating Lymphocytes (TILs) due to their highly selective tumoricidal effect and manageable adverse effect profile have received the FDA’s Breakthrough Therapy designation in 2019. The antibody drug conjugate (ADC) Tisotumab-Vedotin has shown activity in metastatic CC relapsed after at least one line of chemotherapy, with a phase III trial currently actively enrolling patients. Moreover, the deeper understanding of the ever-changing immune landscape of CC carcinogenesis has resulted in the development of active therapeutic vaccines. This review highlights the different immunotherapeutic strategies being explored reflects on what role immunotherapy might have in therapeutic algorithms of CC and addresses the role of predictive biomarkers

COVID-19 and Breast Cancer: Analysis of Surgical Management of a Large Referral Center during the 2020-2021 Pandemic Period

Background: Coronavirus disease-19 (COVID-19) has spread worldwide since December 2019 and was officially declared a pandemic in March 2020. Due to the rapid transmission and the high fatality rate, drastic emergency restrictions were issued, with a negative impact on routine clinical activities. In particular, in Italy, many authors have reported a reduction in the number of breast cancer diagnoses and critical problems in the management of patients who accessed the breast units during the dramatic first months of the pandemic. Our study aims to analyze the global impact of COVID-19 in the two years of the pandemic (2020–2021) on the surgical management of breast cancer by comparing them with the previous two years. Methods: In our retrospective study, we analyzed all cases of breast cancer diagnosed and surgically treated at the breast unit of “Città della Salute e della Scienza” in Turin, Italy, making a comparison between the 2018–2019 pre-pandemic period and the 2020–2021 pandemic period. Results: We included in our analysis 1331 breast cancer cases surgically treated from January 2018 to December 2021. A total of 726 patients were treated in the pre-pandemic years and 605 in the pandemic period (−121 cases, 9%). No significant differences were observed regarding diagnosis (screening vs. no screening) and timing between radiological diagnosis and surgery for both in situ and invasive tumors. There were no variations in the breast surgical approach (mastectomy vs. conservative surgery), while a reduction in axillary dissection compared to the sentinel lymph node in the pandemic period was observed (p-value < 0.001). Regarding the biological characteristics of breast cancers, we observed a greater number of grades 2–3 (p-value = 0.007), pT stage 3–4 breast cancer surgically treated without previous neoadjuvant chemotherapy (p-value = 0.03), and a reduction in luminal B tumors (p-value = 0.007). Conclusions: Overall, we report a limited reduction in surgical activity for breast cancer treatment considering the entire pandemic period (2020–2021). These results suggest a prompt resumption of surgical activity similar to the pre-pandemic period

Ovarian Cancer Cells in Ascites Form Aggregates That Display a Hybrid Epithelial-Mesenchymal Phenotype and Allows Survival and Proliferation of Metastasizing Cells

Peritoneal metastases are the leading cause of morbidity and mortality in ovarian cancer. Cancer cells float in peritoneal fluid, named ascites, together with a definitely higher number of non neo-neoplastic cells, as single cells or multicellular aggregates. The aim of this work is to uncover the features that make these aggregates the metastasizing units. Immunofluorescence revealed that aggregates are made almost exclusively of ovarian cancer cells expressing the specific nuclear PAX8 protein. The same cells expressed epithelial and mesenchymal markers, such as EPCAM and αSMA, respectively. Expression of fibronectin further supported a hybrid epithelia-mesenchymal phenotype, that is maintained when aggregates are cultivated and proliferate. Hematopoietic cells as well as macrophages are negligible in the aggregates, while abundant in the ascitic fluid confirming their prominent role in establishing an eco-system necessary for the survival of ovarian cancer cells. Using ovarian cancer cell lines, we show that cells forming 3D structures neo-expressed thoroughly fibronectin and αSMA. Functional assays showed that αSMA and fibronectin are necessary for the compaction and survival of 3D structures. Altogether these data show that metastasizing units display a hybrid phenotype that allows maintenance of the 3D structures and the plasticity necessary for implant and seeding into peritoneal lining

Affected Ovary Relative Volume: A Novel Sonographic Predictor of Ovarian Reserve in Patients with Unilateral Endometrioma-A Pilot Study

Background: The assessment of ovarian reserve in the case of endometrioma is of pivotal importance for planning a tailored management. However, both the antral follicle count (AFC) and the antimüllerian hormone (AMH) dosage are subject to a fair degree of variability in ovarian endometriosis. This study aimed to identify a sonographic parameter of ovarian reserve that could implement current available markers in patients with unilateral endometrioma. Methods: Patients with unilateral endometrioma admitted to our Endometriosis Center between March 2018 and April 2019 were enrolled. Transvaginal ultrasonography for the evaluation of eight sonographic indicators and AMH level determination were performed. The relationship between AMH level and each indicator was assessed. Results: Thirty-four women were included. There was a positive significant correlation between AMH level and the healthy ovary AFC (HO-AFC) (r = 0.36 p = 0.034). A stronger, negative correlation between AMH level and the ratio between the volume of the affected and the healthy ovary (affected ovary relative volume, AORV) (r = -0.47; p = 0.005) was evidenced. AORV had a satisfactory accuracy (AUC 0.73; CI 0.61-0.90; p = 0.0008), and the cut-off value of 5.96 had the best balance of sensitivity/specificity in distinguishing between patients with a good ovarian reserve (AMH ≥ 2 ng/mL) and those at risk of ovarian reserve depletion after excisional surgery. Conclusion: AORV may be a useful tool to assess ovarian reserve in patients with unilateral endometrioma without previous surgery and to guide physicians in clinical management

Low-Grade Uterine Endometrial Stromal Sarcoma: Prognostic Analysis of Clinico-Pathological Characteristics, Surgical Management, and Adjuvant Treatments. Experience From Two Referral Centers

OBJECTIVE: Low-grade uterine endometrial stromal sarcoma (LG-ESS) is a rare tumor characterized by an overall good survival but showing a indolent behavior and a variable risk of recurrence. There is no clear consensus on the optimal management of these tumors and no prognostic or predictive factors have been established. With this study, we evaluated the prognostic relevance of several clinical, surgical, and pathological features in patients affected by LG-ESS to identify risk factors associated with recurrence. METHODS: We retrospectively analyzed 52 LG-ESS cases, treated from January 1st, 1994, to May 31st, 2020, in two referral centers. The relationship between recurrence and clinicopathological characteristics as well as surgical treatment was investigated. Risk of recurrence and disease-free survival (DFS) were estimated by Cox regression and the Kaplan-Meier analysis, respectively. RESULTS: Of 52 patients with LG-ESS, 8 experienced recurrence (15%). The median follow-up was 100 months (SD ± 96, range: 15–336). By univariate analysis, fragmentation/morcellation, tumor size, FIGO stage, higher mitotic count, presence of necrosis, and lymphovascular space invasion (LSVI) resulted associated with a poorer outcome. Conversely, the surgical modality (laparotomic vs laparoscopic and hysterectomy with bilateral salpingo-oophorectomy vs local excision) and pelvic lymphadenectomy were not. Even the different modalities of adjuvant therapy (hormonal therapy, radiotherapy, and chemotherapy) showed no prognostic significance. Tumor fragmentation/morcellation and higher mitotic count resulted independent prognostic variables at multivariate analysis. CONCLUSIONS: This data supports the avoidance of any type of morcellation if LG-ESS is suspected preoperatively. Higher mitotic count and, possibly, tumor size, advanced FIGO stage, necrosis, and LVSI could be exploited to tailor the adjuvant therapy, but these results need to be confirmed in larger prospective studies

Obstetric and neonatal outcomes after SARS-CoV-2 infection in the first trimester of pregnancy: A prospective comparative study

OBJECTIVE(S): This prospective observational cohort study aimed to evaluate whether women with severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection during the first trimester of pregnancy are at higher risk of adverse obstetric and neonatal outcomes compared to negative patients. STUDY DESIGN: Seromolecular testing for SARS‐CoV‐2 was performed at 12, 16, 21 weeks, and at delivery; the cohort was then subdivided into a first‐trimester SARS‐CoV‐2‐positive (case) group and a SARS‐CoV‐2‐negative (control) group. The primary outcome was a composite adverse obstetric outcome, defined as the presence of either abortion, preterm delivery, preterm prelabor rupture of membranes, preeclampsia, intrauterine growth restriction, stillbirth; and a composite measure of adverse neonatal events, including either 1‐ and 5‐min Apgar score ≤ 7, neonatal intensive care unit admission and congenital birth defects. Maternal symptoms and antibody titer were secondarily assessed. RESULTS: A total of 17 of 164 women tested positive for SARS‐CoV‐2 (10.3%) in the first trimester. One SARS‐CoV‐2‐positive patient who gave birth at another hospital was excluded. Composite adverse obstetric outcome was observed in 6.2% (1/16) SARS‐CoV‐2‐positive and 10.5% (11/105) SARS‐CoV‐2‐negative women; composite adverse neonatal outcome in 12.5% (2/16) and 7.6% (8/105), respectively. In the newborns of women who had developed IgG antibodies, the same antibodies were detected in arterial cord blood and the nasopharyngeal swab tested negative for SARS‐CoV‐2. No maternal pneumonia or hospital admission due to coronavirus disease‐19 were recorded. CONCLUSION: Asymptomatic or mildly symptomatic women during the first trimester of pregnancy did not experience significantly more adverse events than SARS‐CoV‐2‐negative women