Torres, Diogo

INTRODUCTION: Obesity is associated with endometrial cancer (EC); however, most patients are unaware of this association and the long-term consequences of their elevated body mass index (BMI). Our objectives were to increase both patient awareness of this association and referral rates to our weight loss clinic using quality improvement (QI) methodology. METHODS: A multidisciplinary team used QI methods to create a multi-pronged toolkit to improve obesity education in patients < 80 years old with a BMI ≥30 mg/kg2 and diagnosis of grade 1-2, stage I EC. Gynecologic oncology and bariatric surgery providers, endocrinologists, nutritionists, and psychologists collaboratively implemented the toolkit comprised of provider communication workshops, patient education resources, and dictation templates. A historic cohort from (July through December 2015) was compared to a post-intervention cohort (July through December 2017). Clinical characteristics, documented conversations, and referrals to the weight loss clinic were abstracted. Data for the two cohorts were compared using Chi-squared test, Fisher exact test, and Student t-test. RESULTS: The historic cohort had 54 patients and the post-intervention cohort had 53 patients. Clinical characteristics were balanced between groups. Conversations about obesity increased from 11.1% (6/54) to 79.2% (42/53) after toolkit implementation (P<.001). Referral rates to the weight loss clinic also increased from 3.7% (2/54) to 25.9% (14/53) (P<.005). No clinical characteristics, including age, BMI, or pre-operative diagnosis, were associated with documented conversations or referrals (P=1.0). CONCLUSION: A multidisciplinary quality improvement project can be used to increase discussion about obesity and referral to a weight loss clinic in patients with low-risk EC.

Abstract Malignant ascites is one of the most common causes of morbidity in end stage ovarian cancer patients with negative impact on quality of life. Novel non-invasive palliative therapeutic options are lacking for such patients. The zinc metalloprotease, pregnancy-associated plasma protein-A (PAPP-A), plays a key role in the insulin-like growth factor (IGF) pathway, promoting ovarian cancer cellular transformation, growth and invasiveness. Furthermore, patient primary malignant ascites is known to contain high levels of PAPP-A by ELISA. Preliminary data shows that inhibition of PAPP-A through a neutralizing monoclonal PAPP-A antibody (mAb-PA) inhibits the accumulation and promote the regression of ascites in an ovarian cancer patient-derived xenograft (PDX) models. In the current study, we investigated whether mAb-PA can promote ascites regression in an additional ovarian PDX model with measurable ascites. Patient derived ascites xenograft (PDAX) models were defined as SCID mice that developed ascites after intraperitoneal heterotransplantation of patient solid tumor collected at the time of primary cytoreduction. Ascites from these models (n=51) was screened for human PAPP-A protein by ELISA and models were divided into two groups by the relative concentration of PAPPA-A: high (n=18) and low (n=33). PAPP-A High PDAX model PH438 was re-established intraperitoneal in 20 SCID mice by ascites injection (0.1 ml per mouse). When ascites area reached a threshold of &gt;0.60 cm2 by ultrasound, mice were treated with 60mg/Kg of mAb-PA (n=10) or IgG2a control (n=10) on day one and three. On day four, a second ultrasound measurement was obtained and the mice were euthanized. Ascites burden was measured at necropsy. Personnel involved with the acquisition of ultrasounds measurements, subsequent ascites harvests, and post hoc analyses were blinded to the treatments. The ratio of mean ascites (mAb-PA/IgG2a in grams) collected at necropsy was 2.04/2.51, indicating that the mAb-PA arm had less ascites compared to control. These data were consistent with pre- and post-treatment ultrasound measurements of ascites burden; a statistically significant (p=0.0283 by paired t test) reduction of ascites burden of 52.3% was observed, compared to the starting baseline, indicating that mAb-PA treatment causes ascites regression. Ascites weight at necropsy was compared to the area of greatest fluid echogenicity by ultrasound and the Pearson correlation R value achieved was of 0.859 (p&lt;0.0001). These PDAX data implicate PAPP-A attenuation as a potential strategy to treat malignant ascites in OC. Additional PDAX models are under examination to confirm these findings and support the translational development of PAPP-A as a new therapeutic target for women with refractory ascites. Citation Format: Valentina Zanfagnin, Laurie K. Bale, Marc A. Becker, Xiaonan Hou, Diogo Torres, Cheryl A. Conover, Saravut J. Weroha. Regression of malignant ascites via PAPP-A inhibition in ovarian cancer patient-derived xenograft model [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4817. doi:10.1158/1538-7445.AM2017-4817