Leiomyosarcoma: Current Clinical Management and Future Horizons.

Leiomyosarcomas are soft tissue tumors that are derived from smooth muscle mainly in the pelvis and retroperitoneum. Percutaneous biopsy is paramount to confirm diagnosis. Imaging is necessary to complete clinical staging. Multimodal treatment should be directed by expert sarcoma multidisciplinary teams that see a critical volume of these rare tumors. Surgery is the mainstay of curative intent treatment; however due to its high metastatic progression, there may be a benefit for neoadjuvant systemic treatment. Adjuvant systemic treatment has no proven disease-free survival, and its main role is in the palliative setting to potentially prolong overall survival.

Use of Expansion Cohorts in Phase I Trials and Probability of Success in Phase II for 381 Anticancer Drugs.

Purpose: Evaluate the association between the use of phase I expansion cohorts (ECs) and drug performance in phase II as well as time to approval by the FDA.Experimental Design: We performed a systematic search of MEDLINE for single-agent dose-finding adult oncology phase I trials published in 2006 to 2011 and subsequent phase II trials. Successful phase II trials were those that met their primary endpoints. Dates of approval were obtained from the Drugs@FDA website in April 2014. A logistic regression model was used to determine the associations between variables and success in phase II.Results: We identified 533 phase I trials evaluating 381 drugs; 112 drugs had at least one phase I trial with an expansion cohort. Phase I trials with expansion cohorts of two to 20 patients were associated with a higher rate of successful phase II trials than those with no expansion cohort [48% vs. 27%; OR, 2.1; 95% confidence interval (CI), 1.1-4.0; P = 0.037]. Phase II success rates were the same for expansion cohort with two to 20 and more than 20 patients (48% vs. 52%). Other positive associations were disease-specific trials (OR, 1.7; 95% CI, 1.0-2.9; P = 0.037), industry sponsorship (OR, 2.9; 95% CI, 1.5-5.7; P = 0.0024), and response rate of 6% to 20% (OR, 2.89; 95% CI, 1.6-5.2; P = 0.0007). Drugs tested in phase I trials with expansion cohorts had a higher rate of 5-year approval (19% vs. 5%; HR, 4.4; 95% CI, 2.2-8.8; P < 0.001).Conclusions: The use of expansion cohorts in phase I trials was associated with success of subsequent phase II trials. However, confounders may play a role in this association. Clin Cancer Res; 23(15); 4020-6. ©2017 AACR.

Prognostic and predictive value of CA-125 in the primary treatment of epithelial ovarian cancer: potentials and pitfalls.

The serum cancer antigen 125 (CA-125) remains a reliable biomarker in the therapeutic management of epithelial ovarian cancer (EOC). Monitoring the efficacy of cytotoxic chemotherapy (CT) and the early detection of relapse during the follow up of patients in remission represent the two most common clinical situations where the CA-125 has been successfully applied. There are however other scenarios along the course of the disease where the CA-125 can potentially aid in the decision-making process. Preoperative levels of CA-125 can help in selecting a subset of patients where an optimal cytoreduction may not be easily achieved. Perioperative variations in the CA- 125 levels after primary surgery and, more importantly, the nadir value of the CA-125 after primary chemotherapy, are associated with patient outcome. This review focuses on the clinical relevance of dynamic changes in CA-125 levels during the primary treatment of EOC and its potential influence both in the patient management and in the design of clinical trials in the adjuvant setting.