1,720,977 research outputs found
Trabectedin and lurbinectedin: Mechanisms of action, clinical impact, and future perspectives in uterine and soft tissue sarcoma, ovarian carcinoma, and endometrial carcinoma
No full textThe ecteinascidins trabectedin and lurbinectedin are very interesting antineoplastic agents, with a favorable toxicity profile and peculiar mechanisms of action. These drugs form adducts in the minor groove of DNA, which produce single-strand breaks (SSBs) and double-strand breaks (DSBs) and trigger a series of events resulting in cell cycle arrest and apoptosis. Moreover, the ecteinascidins interact with the tumor microenvironment, reduce the number of tumor-associated macrophages, and inhibit the secretion of cytokines and chemokines. Trabectedin has been approved by the Federal Drug Administration (FDA) for patients with unresectable or metastatic liposarcoma or leiomyosarcoma who received a prior anthracycline-based regimen. Moreover, trabectedin in combination with pegylated liposomal doxorubicin (PLD) has been approved in the European Union for the treatment of platinum-sensitive recurrent ovarian cancer. Lurbinectedin has been approved by the FDA for patients with metastatic small cell lung cancer with disease progression on or after platinum-based chemotherapy. The review assesses in vitro and in vivo experimental studies on the antineoplastic effects of both ecteinascidins as well as the clinical trials on the activity of trabectedin in uterine sarcoma and ovarian carcinoma and of lurbinectedin in ovarian carcinoma and endometrial carcinoma
Reproductive outcomes after hydatiform mole and gestational trophoblastic neoplasia
No full textGestational trophoblastic disease includes complete hydatidiform mole (CHM) or partial hydatidiform mole (PHM) and gestational trophoblastic neoplasia (GTN). Given the very high-curability rate of trophoblastic disease, the risk of further molar pregnancy after CHM or PHM as well as the risk of second primary tumors and fertility compromise after chemotherapy for GTN represent major concerns. The incidence of subsequent molar pregnancy ranges from 0.7 to 2.6% after one CHM or PHM, and is approximately 10% after two previous CHMs. Among patients who have received chemotherapy, there is an increased risk of myeloid leukemia which is mainly related to the cumulative dose of etoposide. Resumption of normal menses occurs in approximately 95% of women treated with chemotherapy, but menopause occurs 3 years earlier compared with those non-treated with chemotherapy. Term live birth rates higher than 70% without increased risk of congenital abnormalities have been reported in these women, and pregnancy outcomes are comparable to those of general population, except a slightly increased risk of stillbirth. Fertility-sparing treatment for placental site trophoblastic tumor is a therapeutic option reserved to highly selected, young women who do not present markedly enlarged uterus or diffuse multifocal disease within the uterus
Hyperthermic Intraperitoneal Chemotherapy in the Management of Primary Epithelial Ovarian Cancer: A Debated Issue for Gynecologic Oncologists
No full textHyperthermic intraperitoneal chemotherapy (HIPEC) has been widely investigated in patients with peritoneal carcinomatosis, including those with epithelial ovarian cancer (EOC), with conflicting results. The hyperthermia enhances drug tissue penetration, synergizes with several cytotoxic drugs including cisplatin, degrades BRCA2, suppresses homologous recombination, and elicits an anticancer immune response. A meta-analysis of retrospective studies including both patients with primary advanced EOC and those with recurrent platinum-sensitive EOC failed to detect a benefit in terms of progression-free survival (PFS) or overall survival (OS) from the addition of HIPEC after surgery. The aim of the present review was to analyze the recent randomized clinical trials designed to assess the value of HIPEC in the management of patients with primary advanced EOC. Although not free from criticism and bias, the available data from two phase III trials seem to suggest that the addition of HIPEC to interval debulking surgery after neoadjuvant chemotherapy significantly improves PFS and OS. Conversely, HIPEC does not appear to offer any advantage after primary debulking surgery. Several phase III trials are currently ongoing on these issues and the use of HIPEC is still a matter of debate in the scientific community. Additional translational research is strongly warranted to detect biological variables able to identify a subset of patients who may have a major benefit from this therapeutic approach. In particular, the clinical outcome of patients who undergo HIPEC should be correlated with BRCA status and homologous recombination repair status
Screening for Ovarian Cancer in the General Population: State of Art and Perspectives of Clinical Research
No full textBackground/Aim: Screening for ovarian cancer in the general population is a challenging issue. The aim of this review was to analyze both the studies based on serum CA125 assay and ultrasound (US) and the novel perspectives of clinical and biological research on this issue. Materials and Methods: The trials on the combination of serum CA125 and vaginal/ pelvic US as well as the investigations on microRNA (miRNA)s, circulating tumor DNA and tumor protein 53 (TP53) variants in DNA purified from Pap smears have been critically analyzed. Results: Two large randomized trials failed to detect a reduction in ovarian cancer-related deaths in women who underwent serum CA125-and US-based screening compared to those who had no screening. The United Kingdom Collaborative Trial of Ovarian Cancer Screening reported a 39.2% higher incidence of stage I-II and 10.2% lower incidence of stage III-IV disease in women who underwent annual multimodal screening with serum CA125 and vaginal US compared to women who had no screening, but this stage shifting did not translate into a survival benefit. A longitudinal, multiple biomarker algorithm-based strategy might improve ovarian cancer detection compared with serial CA125 alone. The use of serum tumor-associated autoantibodies, circulating tumor DNA and microRNA is still investigational. The identification of TP53 clonal variants in DNA purified from Pap smears can detect early steps of serous ovarian carcinogenesis. Conclusion: The availability of sensitive next-generation sequencing-based approaches for TP53 assessment in PAP smears may allow the reliability of this genetic marker for early detection of ovarian cancer to be verified
Is Perineural Invasion a Novel Prognostic Factor Useful to Tailor Adjuvant Treatment in Patients Treated With Primary Surgery for Cervical and Vulvar Carcinoma?
No full textPerineural invasion (PNI) is detected in 7.0-35.1% of cervical carcinomas. This histological finding correlates with cervical invasion, lymph-vascular space invasion (LVSI), tumor size, positive resection margins, parametrial invasion, node metastases and advanced stage. Some authors have reported that PNI has no prognostic relevance, others have found that PNI is related to disease-free survival or overall survival (OS) at univariate analysis, and others have observed that it is an independent poor prognostic factor for OS. The evaluation of PNI status should be included in the decision-making process for planning adjuvant treatment. PNI has been found in 7.6-52.4% of vulvar carcinomas. This feature, which is strongly associated with depth of invasion, LVSI, tumor size, advanced stage and nodal involvement, is an independent prognostic variable for the risk of recurrence and death in most series. PNI should be evaluated routinely in histopathology reports of vulvar carcinoma and could help clinicians to tailor adjuvant treatment
Correlation between CA125 levels after sixth cycle of chemotherapy and clinical outcome in advanced ovarian carcinoma
No full textAim: To correlate CA125 levels after platinum- and paclitaxel-based chemotherapy with progression-free survival (PFS) and overall survival (OS) in advanced ovarian carcinoma following primary cytoreduction. Materials and Methods: The study was conducted on 247 patients. Results: By log-rank test, PFS and OS were related to performance status (PS) (p=0.04 and p=0.00002), residual disease (p=0.00002 and p=0.001), ascites (p=0.00001 and p=0.0003) and post-chemotherapy CA125 using 10.8 U/ml as cut-off (p=0.0001 and p=0.01). PFS was related to post-chemotherapy CA125 assay (cut-off values of 7.1 U/ml (p=0.02), 18.5 U/ml (p<0.000001) and 35.0 U/ml (p=0.0001)). OS was related to FIGO stage (p=0.02). On multivariate analysis, residual disease, ascites and post-chemotherapy CA125 with any selected cut-off were independent prognostic variables for PFS, whereas residual disease, PS and post-chemotherapy CA125 (10.8 U/ml as cut-off) were independent prognostic variables for OS. Conclusion: Post-operative CA125 using 10.8 U/ml as cut-off was an independent prognostic variable for both PFS and OS. © 2015, International Institute of Anticancer Research. All rights reserved
Dose-dense paclitaxel-and carboplatin-based neoadjuvant chemotherapy followed by surgery or concurrent chemoradiotherapy in cervical cancer: A preliminary analysis
No full textAim: To assess preliminary results with dosedense neoadjuvant chemotherapy (NACT) prior to surgery or concurrent chemo-radiotherapy (CCRT) in cervical cancer. Patients and Methods: Thirty patients received weekly paclitaxel (80 mg/m2) plus carboplatin (AUC2) for 6 cycles followed by radical hysterectomy in 16 (stage Ib2-IIb), conisation in one (stage Ib1), and CCRT in 13 (stage Ib2-IIb). Median follow-up of survivors was 12 months (range= 3-22). Results: Among the surgically treated patients, clinical overall response rate (RR) was 82.3%, optimal pathological RR was 17.6%, and suboptimal pathological RR with intracervical residual disease was 41.2%. Only one patient relapsed. Among the CCRT treated patients, partial RR after NACT was 76.9% and complete RR after CCRT was 58.3%. However, 42.8% of complete responders recurred. Toxicity was acceptable. Conclusion: Dose-dense NACT seems to achieve promising RRs with manageable toxicity in cervical cancer. Investigation on larger series with longer follow-up is warranted
Endometrial stromal tumors of the uterus: Epidemiology, pathological and biological features, treatment options and clinical outcomes
No full textEndometrial stromal tumors (EST) are uterine mesenchymal tumors, which histologically resemble endometrial stroma of the functioning endometrium. The majority of EST are malignant tumors classified as low-grade endometrial stromal sarcoma (LG-ESS), high-grade endometrial stromal sarcoma (HG-ESS), and undifferentiated uterine sarcoma (UUS).Overall, ESTs are rare malignancies, with an annual incidence of approximately 0.30 per 100'000 women, mainly affecting peri-or postmenopausal women. The most common genetic alteration identified in LG-ESS is the JAZF1-SUZ12 rearrangement, while t(10;17) (q23,p13) translocation and BCOR gene abnormalities characterize two major subtypes of HG-ESS. The absence of specific genetic abnormalities is the actual hallmark of UUS. Unlike HG-ESSs, LG-ESSs usually express estrogen and progesterone receptors.Total hysterectomy without morcellation and bilateral salpingo-oophorectomy (BSO) is the first-line treatment of early-stage LG-ESS. Ovarian preservation, fertility-sparing treatment, and adjuvant hormonal therapy +/- radiotherapy may be an option in selected cases. In advanced or recurrent LG-ESS, surgical cytoreduction followed by hormonal treatment, or vice versa, are acceptable treatments. The standard treatment for apparently early-stage HG-ESS and UUS is total hysterectomy without morcellation with BSO. Ovarian preservation and adjuvant chemotherapy +/- radiotherapy may be an option. In advanced or recurrent HG-ESS, surgical cytoreduction and neoadjuvant or adjuvant chemotherapy can be considered. Alternative treatments, including biological agents and immunotherapy, are under investigation.LG-ESSs are indolent tumorwith a 5-year overall survival (OS) of 80-100% and present as stage I-II at diagnosis in two third of patients. HG-ESSs carry a poor prognosis, with amedian OS ranging from 11 to 24 months, and 70% of patients are in stage III-IV at presentation. UUS median OS ranges from 12 to 23 months and, at diagnosis, 70% of patients are in stage III-IV. The aimof this reviewis to assess the clinical, pathological, and biological features and the therapeutic options for malignant ESTs. (c) 2023 Elsevier Inc. All rights reserved
Prognostic factors and clinical outcome of patients with recurrent early-stage epithelial ovarian cancer : An italian multicenter retrospective study
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