Defining the learning curve for successful staging with sentinel lymph node biopsy for endometrial cancer among surgeons at an academic institution.

BACKGROUND: Sentinel lymph node (SLN) biopsy is increasingly used in endometrial cancer staging; however, success of the technique is variable, and the learning curve needs to be better understood. Success is defined as identification of a SLN specimen containing nodal tissue in bilateral hemi-pelvises. OBJECTIVE: To assess the learning curve of surgeons at an academic institution in performing successful SLN mapping and biopsy during robotic staging for endometrial cancer. METHODS: After institutional review board approval, patients who underwent staging with robotic SLN mapping using indocyanine green at a single academic program between July 2012 and December 2017 were identified. Demographic, pathologic, and surgical data were retrospectively collected from the medical records. Descriptive and comparative statistics were performed. Surgeon rates of successful bilateral SLN mapping and removal of lymphoid-containing SLN specimens were compared. A logistic model was used to analyze the probability of successful SLN mapping and removal of lymph node-containing tissue with increasing number of procedures performed. RESULTS: Three hundred and seventeen patients met the eligibility criteria. Most had early-stage, low-grade endometrial cancer. A total of 194 (61%) patients had successful bilateral mapping. Among seven surgeons, a plateau in rates of successful bilateral mapping was achieved after 40 cases. No linear correlation was seen between the number of surgeries performed and the rate of removal of lymph node-containing tissue among surgeons. Each additional 10 procedures performed was associated with a 5% and an 11% increase in the odds of successful SLN mapping and removal of lymph node-containing tissue, respectively. DISCUSSION: The successful removal of lymph node-containing specimens appears to be a surgeon-specific phenomenon. The plateau of the learning curve for successful bilateral mapping seems to be reached at around 40 cases. These first 40 cases offer a time for auditing of individual rates of SLN mapping and removal to identify surgeons who may benefit from procedure-specific remediation.

ONC206 has anti-tumorigenic effects in human ovarian cancer cells and in a transgenic mouse model of high-grade serous ovarian cancer.

ONC206, a dopamine receptor D2 (DRD2) antagonist and imipridone, is a chemically modified derivative of ONC201. Recently, ONC206 and other imipridones were identified as activators of the mitochondrial protease ClpP, inducing downstream pathways that allow them to selectively target cancer cells. Clinical trials showed that ONC201, the first in class imipridone, was well tolerated and exhibited tumor regression in some solid tumors. Our goal was to evaluate the effect of ONC206 on cell proliferation and tumor growth in ovarian cancer cell lines and in a transgenic mouse model of high grade serous ovarian cancer (KpB model). ONC206 was more potent than ONC201 in inhibiting cell proliferation, as evidenced by a 10-fold decrease in IC50 for the SKOV3 and OVCAR5 cell lines. This was accompanied by the results that ONC206 significantly inhibited cellular proliferation, induced cell cycle G1 arrest and apoptosis, caused cellular stress, and inhibited adhesion and invasion in vitro. Treatment of obese and non-obese KpB mice with ONC206 elevated Bip and ClpP expression and reduced KI67, BCL-XL and DRD2 expression in the ovarian tumors. Our findings demonstrate that ONC206 has anti-tumorigenic effects in ovarian cancer as previously demonstrated by ONC201 but appears to be as well tolerated and more potent. Thus, ONC206 deserves further evaluation in clinical trials.

Physical Activity: Impact on Survival in Gynecologic Cancer.

IMPORTANCE: Physical activity has many important health benefits. There is also growing evidence that physical activity plays a role in the prevention and prognosis of multiple cancers, including gynecologic malignancies. Despite the many benefits of physical activity, the number of individuals meeting physical activity recommendations remains low. OBJECTIVE: To examine the role that physical activity plays in the prevention, treatment, and prognosis of gynecologic malignancies and to review the feasibility of physical activity interventions among gynecologic cancer survivors. EVIDENCE ACQUISITION: A PubMed search was performed using relevant terms to identify journal articles related to the proposed subject. The websites of multiple national and international organizations were also used to obtain up-to-date guidelines and recommendations. RESULTS: Physical activity appears to decrease the risk of ovarian, endometrial, and cervical cancer, with the strongest evidence of this association seen in endometrial cancer. Although the literature is scarce, participation in physical activity is feasible during active treatment for gynecologic cancers and may decrease symptom burden and increase chemotherapy completion rates. Gynecologic cancer survivors are motivated to increase physical activity, and lifestyle intervention programs are feasible and well received among this population. CONCLUSIONS AND RELEVANCE: Health care providers caring for women with gynecologic malignancies must counsel patients regarding the importance of physical activity. This should include a discussion of the health benefits and, specifically, the cancer-related benefits. A personalized approach to physical activity intervention is essential.