Objective: The management of stage II endometrial cancer (EC) is challenging due to the wide variation in surgical practice and adjuvant treatment recommendations. We sought to describe the treatment patterns for patients with stage II EC and to evaluate the association between surgical management and adjuvant therapy on survival outcomes in a large cohort of patients with stage II EC. Methods: Using data from the National Cancer Database, we identified 9,690 women with stage II EC. We used logistic regression to identify association of sociodemographic and tumor characteristics with surgery type and receipt of adjuvant therapy. We used Cox proportional hazards regression models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for associations between adjuvant therapy, hysterectomy type, and overall survival. Results: Almost 11% of the cohort underwent radical hysterectomy; however, there was no difference in survival between surgical types even when adjusted for adjuvant therapy (HR=0.94; 95% CI=0.82–1.07). Compared to no adjuvant treatment, radiation only (HR=0.66; 95% CI=0.61–0.73) and combination radiation and chemotherapy (HR=0.53;95% CI=0.45–0.62) were associated with lower risk of death. There was no survival benefit of chemotherapy alone even when separated by histologic subtype (HR range, 0.55–1.46). Conclusions Women with stage II EC do not appear to benefit from routine radical hysterectomy though all patients appear to benefit from receipt of radiation therapy (RT), regardless of modality. Additionally, there may be an added survival benefit with the combination of computed tomography and RT in patients with non-endometrioid, high-risk histologies.

PURPOSE: The selective elimination of cancer stem cells (CSCs) in tumor patients is a crucial goal because CSCs cause drug refractory relapse. To improve the current conventional bispecific immune-engager platform, a 16133 bispecific natural killer (NK) cell engager (BiKE), consisting of scFvs binding FcγRIII (CD16) on NK cells and CD133 on carcinoma cells, was first synthesized and a modified interleukin (IL)-15 crosslinker capable of stimulating NK effector cells was introduced. MATERIALS AND METHODS: DNA shuffling and ligation techniques were used to assemble and synthesize the 1615133 trispecific NK cell engager (TriKE). The construct was tested for its specificity using flow cytometry, cytotoxic determinations using chromium release assays, and lytic degranulation. IL-15–mediated expansion was measured using flow-based proliferation assays. The level of interferon (IFN)-γ release was measured because of its importance in the anti-cancer response. RESULTS: 1615133 TriKE induced NK cell–mediated cytotoxicity and NK expansion far greater than that achieved with BiKE devoid of IL-15. The drug binding and induction of cytotoxic degranulation was CD133+ specific and the anti-cancer activity was improved by integrating the IL-15 cross linker. The NK cell–related cytokine release measured by IFN-γ detection was higher than that of BiKE. NK cytokine release studies showed that although the IFN-γ levels were elevated, they did not approach the levels achieved with IL-12/IL-18, indicating that release was not at the supraphysiologic level. CONCLUSION: 1615133 TriKE enhances the NK cell anti-cancer activity and provides a self-sustaining mechanism via IL-15 signaling. By improving the NK cell performance, the new TriKE represents a highly active drug against drug refractory relapse mediated by CSCs.
Antibody-Dependent Cell Cytotoxicity ; Chromium ; DNA Shuffling ; Flow Cytometry ; Humans ; Interferons ; Interleukin-15 ; Interleukins ; Killer Cells, Natural ; Ligation ; Neoplastic Stem Cells ; Recurrence ; Sensitivity and Specificity