RESUMO
The high recurrence rate and the low overall survival in ovarian cancer suggest that a more specific therapeutic approach in addition to conventional treatment is required. Translational and clinical research is investigating new molecular targets in order to find an alternative way to affect tumor growth and to minimize the overlap of toxicity of antiblastic agents. Given its implication in many cellular activities including regulation of cell growth, motility, survival, proliferation, protein synthesis, autophagy, transcription, as well as angiogenesis, PI3K/AKT/mTOR is one of the most investigated intracellular signaling pathways. A dis-regulation of this pathway has been shown in several tumors, including ovarian cancer. In this setting, mTor proteins represent a potential target for inhibitors, which could ultimately play a pivotal role in counteracting cellular proliferation. Recently, mTor inhibitors have been approved in the treatment of pancreatic neuroendocrine tumors, mantle cell lymphoma and renal cancer. Clinical trials have assessed the safety of these drugs in ovarian cancer patients. Ongoing phase I and II studies are evaluating the oncologic outcome of mTor inhibitor treatment and its effect in combination with conventional chemotherapy and target agents.
RESUMO
PURPOSE: The aim of this study was to determine whether a pre-intraoperative prognostic classification of endometrial cancer (EC) patients may accurately predict prognosis. METHODS: Prognostic factors achievable before and during surgery (histotype, grade, myoinvasion, cervical spread, abdominal spread) were utilized to classify patients in low-risk (endometrial adenocarcinoma, grade 1-2, myoinvasion <50%, no evidence of abdominal spread), and in intermediate/high risk (serous papillary and clear cell, grade 3, myoinvasion >50%, cervical invasion, abdominal spread). Risk classification obtained pre-intraoperatively was compared with the classification obtained from definitive surgical-pathological assessment in 130 consecutive patients with EC treated with surgery. RESULTS: Pre-intraoperative risk assessment correctly identified risk classification in 125 (96%) patients; sensitivity, specificity, PPV and NPV were 98%, 94%, 94%, and 98%, respectively. Median follow-up was 38 months (range 6-93), and 14 (10%) patients relapsed (median time 14 months, range 3-60). Relative risk of relapse was higher in intermediate/high-risk patients with both classifications (pre-intraoperative RR 3.37, CI 0.99-11.5; surgical-pathological RR 4.56, CI 1.2-17.3). As regards survival 11 patients have died, 6 due to endometrial cancer and 5 due to intercurrent disease. Five-years DFS according to pre-intraoperative assessment was 89% and 71% for low-risk and intermediate high-risk patients (p = 0.028), respectively; according to definitive assessment was 91% and 70% for low-risk and intermediate/high-risk patients (p = 0.009), respectively. CONCLUSION: This classification, giving an accurate risk and prognostic estimate with parameters routinely utilized in clinical practice, may help the surgeon when undertaking the decision to perform limited or extended surgical staging according to tumor and patient characteristics.