Ovarian endometrioma recurrence after laparoscopic surgery: First assessment of ACSAP predicting score.

PURPOSE: We aimed to develop and validate a predictive score to estimate the post-operative recurrence risk after laparoscopic excision of ovarian endometrioma (OMA). PATIENTS AND METHODS: The prediction score was developed using a training set comprising 431 patients with OMA who underwent laparoscopic surgery at our institution between January 2015 and September 2017. A follow-up period of at least 5 years was required. Clinical data were entered into least absolute shrinkage and selection operator (LASSO) regression to build a scoring system that predicted OMA recurrence. A testing set containing 185 patients from October 2017 to October 2018 was used to assess its performance. RESULTS: Based on LASSO regression, the final score (ACSAP score) included five clinical predictors (0-15 points): Age, cyst size, previous surgery for OMA, revised American Society for Reproductive Medicine stage and post-operative pregnancy. The area under the curve values of the score were 0.741 (0.765) and 0.727 (0.795) for predicting 3-year and 5-year OMA recurrence, respectively, in the training (testing) set. The score stratified patients into three risk groups in both sets, with significant differences in the 5-year recurrence rates (low-risk, 5.3% [0%]; intermediate-risk, 20.2% [16.5%] and high-risk, 48.0% [36.5%]; P < 0.001). Moreover, patients in the intermediate- and high-risk groups exhibited a significant reduction in the 5-year cumulative recurrence following a minimum of 15-month post-operative medical treatment (both P < 0.05). CONCLUSIONS: The ACSAP score may be a concise and useful tool for identifying patients with a higher risk of OMA recurrence after surgery who might receive long-term post-operative medical treatment.

Association of body composition and systemic inflammation for patients with locally advanced cervical cancer following concurrent chemoradiotherapy.

PURPOSE: Systemic inflammation and body composition are associated with survival outcomes of cancer patients. This study aimed to examine the combined prognostic value of systemic inflammatory markers and body composition parameters in patients with locally advanced cervical cancer (LACC). METHODS: Patients who underwent concurrent chemoradiotherapy (CCRT) for LACC at a tertiary referral teaching hospital between January 2010 and January 2018 were enrolled. A predictive model was established based on systemic immune-inflammation index (SII) and computer tomography-derived visceral fat-to-muscle ratio (vFMR). Overall survival (OS) and progression-free survival (PFS) were assessed using the Kaplan-Meier method and Cox regression models. The model performance was assessed using discrimination, calibration, and clinical usefulness. RESULTS: In total, 212 patients were enrolled. The SII and vFMR were closely related, and both independently predicted survival (P < 0.05). A predictive model was established based on the above biomarkers and included three subgroups: high-risk [both high SII (>828) and high vFMR (>1.1)], middle-risk (either high SII or high vFMR), and low-risk (neither high SII nor high vFMR). The 3-year OS (PFS) rates for low-, middle-, and high-risk patients were 90.5% (86.0%), 73.9% (58.4%), and 46.8% (36.1%), respectively (P < 0.05). This model demonstrated satisfactory predictive accuracy (area under the curve values for predicting 3-year OS and PFS were 0.704 and 0.718, respectively), good fit (Hosmer-Lemeshow tests: P > 0.05), and clinical usefulness. CONCLUSION: Systemic inflammatory markers combined with body composition parameters could independently predict the prognosis of patients with LACC, highlighting the utilization of commonly collected indicators in decision-making processes. CLINICAL SIGNIFICANCE: The SII and vFMR, as well as their composite indices, were promising prognostic factors in patients with LACC who received definitive CCRT. Future studies are needed to explore novel therapies to improve the outcomes in high-risk patients.

Proteolysis Targeting Chimeras for the Selective Degradation of Mcl-1/Bcl-2 Derived from Nonselective Target Binding Ligands.

Proteolysis targeting chimera (PROTAC) recruits an E3 ligase to a target protein to induce its ubiquitination and subsequent degradation. We reported success in the development of two PROTACs (C3 and C5) that potently and selectively induce the degradation of Mcl-1 and Bcl-2 (DC50 = 0.7 and 3.0 µM), respectively, by introducing the E3 ligase cereblon-binding ligand pomalidomide to Mcl-1/Bcl-2 dual inhibitors S1-6 and Nap-1 with micromolar-range affinity. C3-induced Mcl-1 ubiquitination translated into much more lethality in Mcl-1-dependent H23 cells than the most potent Mcl-1 occupancy-based inhibitor A-1210477 with nanomolar-range affinity. Moreover, structure-activity relationship analysis and molecular dynamic simulations discovered the structural basis for turning nonselective or promiscuous Bcl-2 family ligands into selective PROTACs. C3 and C5 exhibited reversible depletion in living cells, which provides a new potent toolkit for gain-of-function studies to probe the dynamic roles of Bcl-2 and Mcl-1 in apoptosis networks.