Emerging Role of MicroRNAs in the Therapeutic Response in Cervical Cancer: A Systematic Review

Cervical cancer is a common female cancer, with nearly 600,000 cases and more than 300,000 deaths worldwide every year. From a clinical point of view, surgery plays a key role in early cancer management, whereas advanced stages are treated with chemotherapy and/or radiation as adjuvant therapies. Nevertheless, predicting the degree of cancer response to chemotherapy or radiation therapy at diagnosis in order to personalize the clinical approach represents the biggest challenge in locally advanced cancers. The feasibility of such predictive models has been repeatedly assessed using histopathological factors, imaging and nuclear methods, tissue and fluid scans, however with poor results. In this context, the identification of novel potential biomarkers remains an unmet clinical need, and microRNAs (miRNAs) represent an interesting opportunity. With this in mind, the aim of this systematic review was to map the current literature on tumor and circulating miRNAs identified as significantly associated with the therapeutic response in cervical cancer; finally, a perspective point of view sheds light on the challenges ahead in this tumor

miRNA levels are associated with body mass index in endometrial cancer and may have implications for therapy

Endometrial cancer (EC) is the most prevalent gynecological cancer in high-income countries. Its incidence is skyrocketing due to the increase in risk factors such as obesity, which represents a true pandemic. This study aimed to evaluate microRNA (miRNA) expression in obesity-related EC to identify potential associations between this specific cancer type and obesity. miRNA levels were analyzed in 84 EC patients stratified based on body mass index (BMI; >= 30 or <30) and nine noncancer women with obesity. The data were further tested in The Cancer Genome Atlas (TCGA) cohort, including 384 EC patients, 235 with BMI >= 30 and 149 with BMI <30. Prediction of miRNA targets and analysis of their expression were also performed to identify the potential epigenetic networks involved in obesity modulation. In the EC cohort, BMI >= 30 was significantly associated with 11 deregulated miRNAs. The topmost deregulated miRNAs were first analyzed in 84 EC samples by single miRNA assay and then tested in the TCGA dataset. This independent validation provided further confirmation about the significant difference of three miRNAs (miR-199a-5p, miR-449a, miR-449b-5p) in normal-weight EC patients versus EC patients with obesity, resulting significantly higher expressed in the latter. Moreover, the three miRNAs were significantly correlated with grade, histological type, and overall survival. Analysis of their target genes revealed that these miRNAs may regulate obesity-related pathways. In conclusion, we identified specific miRNAs associated with BMI that are potentially involved in modulating obesity-related pathways and that may provide novel implications for the clinical management of obese EC patients

Electrochemotherapy in Vulvar Cancer and Cisplatin Combined with Electroporation. Systematic Review and In Vitro Studies

Electrochemotherapy (ECT) is an emerging treatment for solid tumors and an attractive research field due to its clinical results. This therapy represents an alternative local treatment to the standard ones and is based on the tumor-directed delivery of non-ablative electrical pulses to maximize the action of specific cytotoxic drugs such as cisplatin (CSP) and bleomycin (BLM) and to promote cancer cell death. Nowadays, ECT is mainly recommended as palliative treatment. However, it can be applied to a wide range of superficial cancers, having an impact in preventing or delaying tumor progression and therefore in improving quality of life. In addition, during the natural history of the tumor, early ECT may improve patient outcomes. Our group has extensive clinical and research experience on ECT in vulvar tumors in the palliative setting, with 70% overall response rate. So far, in most studies, ECT was based on BLM. However, the potential of CSP in this setting seems interesting due to some theoretical advantages. The purpose of this report is to: (i) compare the efficacy of CSP and BLM-based ECT through a systematic literature review; (ii) report the results of our studies on CSP-resistant squamous cell tumors cell lines and the possibility to overcome chemoresistance using ECT; (iii) discuss the future ECT role in gynecological tumors and in particular in vulvar carcinoma

SARS-CoV-2 vaccination modelling for safe surgery to save lives : data from an international prospective cohort study

Background: Preoperative SARS-CoV-2 vaccination could support safer elective surgery. Vaccine numbers are limited so this study aimed to inform their prioritization by modelling. Methods: The primary outcome was the number needed to vaccinate (NNV) to prevent one COVID-19-related death in 1 year. NNVs were based on postoperative SARS-CoV-2 rates and mortality in an international cohort study (surgical patients), and community SARS-CoV-2 incidence and case fatality data (general population). NNV estimates were stratified by age (18-49, 50-69, 70 or more years) and type of surgery. Best- and worst-case scenarios were used to describe uncertainty. Results: NNVs were more favourable in surgical patients than the general population. The most favourable NNVs were in patients aged 70 years or more needing cancer surgery (351; best case 196, worst case 816) or non-cancer surgery (733; best case 407, worst case 1664). Both exceeded the NNV in the general population (1840; best case 1196, worst case 3066). NNVs for surgical patients remained favourable at a range of SARS-CoV-2 incidence rates in sensitivity analysis modelling. Globally, prioritizing preoperative vaccination of patients needing elective surgery ahead of the general population could prevent an additional 58 687 (best case 115 007, worst case 20 177) COVID-19-related deaths in 1 year. Conclusion: As global roll out of SARS-CoV-2 vaccination proceeds, patients needing elective surgery should be prioritized ahead of the general population.Peer reviewe

Post-operative residual disease and number of cycles of neoadjuvant chemotherapy in advanced epithelial ovarian carcinoma

BackgroundThe optimal number of neoadjuvant chemotherapy cycles in patients with advanced ovarian cancer is still disputed. ObjectiveTo evaluate the impact of the number of neoadjuvant chemotherapy cycles and role of optimal cytoreduction on the prognosis of patients with advanced ovarian cancer. MethodsClinical and pathological details were examined. Patients were evaluated combining the number of cycles of neoadjuvant chemotherapy-namely, 'interval debulking surgery' after up to four neoadjuvant chemotherapy cycles, and 'delayed debulking surgery' after more than four cycles of therapy. ResultsA total of 286 patients were included in the study. Complete cytoreduction with no residual peritoneal disease (CC0) was achieved in 74 (74%) patients with interval debulking surgery and 124 (66.7%) patients with delayed interval debulking. Of those with residual disease, there were 26/88 (29.5%) patients in the interval debulking surgery group and 62/88 (70.5%) patients in the delayed debulking surgery group. Comparison of patients with delayed debulking-CC0 and interval debulking-CC0 showed no difference in progression-free survival (p=0.3) or overall survival (p=0.4), while significantly worse outcomes were observed in patients with interval debulking-CC1 (p=0.02 and p=0.04, respectively). Specifically, patients with interval debulking-CC1 had an approximately 67% increased risk of disease progression (p=0.04; HR=2.01 (95% CI 1.04 to 4.18)) and a 69% higher risk of death than patients with delayed debulking-CC0 (p=0.03; HR=2.34 (95% CI 1.11 to 4.67)). ConclusionIncreasing the number of neoadjuvant chemotherapy cycles does not worsen patient outcomes if complete resection is achieved. Nevertheless, additional prospective trials are necessary to establish the optimum number of neoadjuvant chemotherapy cycles

Quality of Life with Vulvar Carcinoma Treated with Palliative Electrochemotherapy: The ELECHTRA (ELEctroCHemoTherapy vulvaR cAncer) Study

The ELECHTRA (ELEctroChemoTherapy vulvaR cAncer) project was conceived to collect data on palliative electrochemotherapy (ECT) in vulvar cancer (VC) assessing patients’ outcomes (response and survival) and impact on quality of life (QoL). After reporting outcome data in 2019, here, we present the results on QoL. A multicenter prospective observational study was conducted on patients with VC refractory or not amenable to standard therapies undergoing palliative ECT as per clinical practice. The following questionnaires were administered before and after ECT (two and four months later, early and late follow-up): visual analog pain scale (VAS), EuroQol 5-Dimension 5-Level (EQ-5D-L5) and Functional Assessment of Cancer Therapy—Vulva cancer (FACT—V). Analyses were conducted on both the whole study population and by subgroups (clinical response after ECT and site, number and size of lesions). Questionnaires from 55 patients were evaluated. Compared to the baseline (6.1 ± 2.1), the VAS was significantly reduced at early (4.3 ± 2.5) and late follow-up (4.6 ± 2.8) (p < 0.0001). The FACT—V score improved significantly at early (9.6 ± 4.0) (p < 0.0001) and late follow-up (8.9 ± 4.1) (p < 0.0054) as compared to the baseline (7.1 ± 3.6). No EQ-5D-5L statistically significant changes were observed. Subgroup analyses showed worse QoL in patients with stable or progressive disease, posterior site and multiple or larger than 3 cm nodules. This is the first study reporting improved QoL in VC patients after palliative ECT. Based on these results, ECT in VC should be considered an effective option based on the favorable outcomes both in terms of response and QoL

Uterine Preservation Treatments in Sarcomas: Oncological Problems and Reproductive Results: A Systematic Review

Uterine sarcomas are rare cancers, sometimes diagnosed in women of childbearing age. Hysterectomy is the standard treatment in early stages. The option of lesion removal to save fertility is described in the literature, but it is still considered experimental. The objective of this systematic review is to report on the available evidence on the reproductive and oncological outcomes of fertility-sparing treatment in women with uterine sarcomas. PubMed, Scopus and Cochrane Central Register of Controlled Trials were searched between 1 January 2011 and 21 June 2021 for publications in English about women with uterine sarcoma treated with a fertility-sparing intervention. Thirty-seven studies were included for a total of 210 patients: 63 low-grade endometrial stromal sarcomas, 35 embryonal rhabdomyosarcomas of the cervix, 19 adenosarcomas, 7 leiomyosarcomas and 2 uterine tumors resembling an ovarian sex cord. Conservative treatment ensured pregnancy in 32% of cases. In terms of oncological outcomes, relapse was related to histology and the worst prognosis was reported for leiomyosarcoma, followed by low-grade endometrial stromal sarcoma, which relapsed in 71% and 54% of cases, respectively. The highest death rate was associated with leiomyosarcoma (57.1%). This study demonstrated that fertility-sparing treatments may be employed in selected cases of early stage uterine sarcoma

Classification Systems of Endometrial Cancer: A Comparative Study about Old and New

Endometrial cancer is the most common gynecological malignancy of the female reproductive organs. Historically it was divided into type I and type II, until 2013 when the Cancer Genome Atlas molecular classification was proposed. Here, we applied the different classification types on our endometrial cancer patient cohort in order to identify the most predictive one. We enrolled 117 endometrial cancer patients available for the study and collected the following parameters: age, body mass index, stage, menopause, Lynch syndrome status, parity, hypertension, type of localization of the lesion at hysteroscopy, type of surgery and complications, and presence of metachronous or synchronous tumors. The tumors were classified according to the European Society for Medical Oncology, Proactive Molecular Risk Classifier for Endometrial Cancer, Post-Operative Radiation Therapy in Endometrial Carcinoma, and Cancer Genome Atlas classification schemes. Our data confirmed that European Society for Medical Oncology risk was the strongest predictor of prognosis in our cohort. The parameters correlated with poor prognosis were the histotype, FIGO stage, and grade. Our study cohort shows that risk stratification should be based on the integration of histologic, clinical, and molecular parameters

Electrochemotherapy in Vulvar Cancer and Cisplatin Combined with Electroporation. Systematic Review and In Vitro Studies

Electrochemotherapy (ECT) is an emerging treatment for solid tumors and an attractive research field due to its clinical results. This therapy represents an alternative local treatment to the standard ones and is based on the tumor-directed delivery of non-ablative electrical pulses to maximize the action of specific cytotoxic drugs such as cisplatin (CSP) and bleomycin (BLM) and to promote cancer cell death. Nowadays, ECT is mainly recommended as palliative treatment. However, it can be applied to a wide range of superficial cancers, having an impact in preventing or delaying tumor progression and therefore in improving quality of life. In addition, during the natural history of the tumor, early ECT may improve patient outcomes. Our group has extensive clinical and research experience on ECT in vulvar tumors in the palliative setting, with 70% overall response rate. So far, in most studies, ECT was based on BLM. However, the potential of CSP in this setting seems interesting due to some theoretical advantages. The purpose of this report is to: (i) compare the efficacy of CSP and BLM-based ECT through a systematic literature review; (ii) report the results of our studies on CSP-resistant squamous cell tumors cell lines and the possibility to overcome chemoresistance using ECT; (iii) discuss the future ECT role in gynecological tumors and in particular in vulvar carcinoma