Effect of oral versus intrauterine progestins on weight in women undergoing fertility preserving therapy for complex atypical hyperplasia or endometrial cancer.

OBJECTIVE: The objective of this analysis was to evaluate weight changes associated with oral progestin therapies versus the levonorgestrel-containing intrauterine device (LNG-IUD) in women undergoing fertility-preserving therapy for complex atypical hyperplasia (CAH) and endometrial cancer (EMC). METHODS: All patients diagnosed with CAH or EMC managed with fertility-preserving progestin therapy at two institutions from 1998 to 2012 were identified. Those with serial weight measurements before, during and after therapy were included. Patients were categorized according to the type of progestin therapy administered. The rate of weight change over time of patients treated with oral versus intrauterine progestins was compared using the Mann Whitney U test. RESULTS: Sixty patients with EMC (35) or CAH (25) were treated during the study period, with 12 patients receiving multiple regimens. These included megestrol acetate (MA, n=42), LNG-IUD (n=22), and other oral progestins (n=11). The median age at diagnosis was 32 and median pre-progestin body mass index (BMI) was 40.4kg/m(2). The median therapy duration was 11.7months [range: 2.3-118.5]. Median weight change during therapy was greater with MA versus LNG-IUD (+2.95 vs. +0.05kg, P=0.03). Patients with a BMI<35 gained more weight during therapy versus patients with BMI≥35 (+2.30 vs. -0.70kg/month, P=0.04); however, in patients with BMI≥35, MA was still associated with more weight gain than LNG-IUD (+2.2 vs.-5.40kg, P=0.05). CONCLUSION: Oral progestin therapy for conservative treatment of young EMC/CAH survivors is associated with increased weight gain, especially when megestrol acetate is utilized. Utilization of LNG-IUD may result in less weight gain.

Lymphopenia and its association with survival in patients with locally advanced cervical cancer.

OBJECTIVE: To evaluate the association between lymphopenia and survival in women with cervical cancer treated with primary chemoradiation. METHODS: A single institution, retrospective analysis of patients with stage IB2-IVA cervical cancer who received upfront chemoradiation from 1998 to 2013 was performed. Complete blood counts from pre-treatment to 36 months post-treatment were analyzed. Lymphopenia and known prognostic factors were evaluated for an association with progression-free (PFS) and overall survival (OS). RESULTS: Seventy-one patients met study criteria for whom 47 (66%) had a documented total lymphocyte count (TLC) two months after initiating chemoradiation. FIGO stage distribution was 6% Stage I, 46% Stage II, 45% Stage III and 3% Stage IV. Pre-treatment TLC was abnormal (<1000 cells/mm3) in 15% of patients. The mean reduction in TLC was 70% two months after initiating chemoradiation. Severe post-treatment lymphopenia (TLC <500 cells/mm3) was observed in 53% of patients; they experienced inferior median OS (21.2 vs. 45.0 months, P=0.03) and similar 25th percentile PFS (6.3 vs. 7.7 months, P=0.06) compared to patients without severe lymphopenia. Multivariate analysis demonstrated pre-treatment TLC ≥1000 cells/mm3 and post-treatment TLC >500 cells/mm3 had a 77% (HR: 0.23; 95% CI 0.05-1.03; P=0.053) and 58% decrease in hazards of death (HR: 0.42; 95%CI 0.12-1.46; P=0.17) respectively. CONCLUSION: More than half of cervical cancer patients treated with chemoradiation experienced severe and prolonged lymphopenia. Although statistical significance was not reached, the findings suggest that pre- and post-treatment lymphopenia may be associated with decreased survival. Further research is warranted, given that lymphopenia could be a reversible prognostic factor.

Low-grade serous carcinoma: molecular features and contemporary treatment strategies.

Epithelial ovarian carcinoma consists of several subtypes, including high-grade and low-grade serous carcinoma. In the recent past, women with all subtypes of epithelial ovarian carcinoma have been treated similarly and are included in the same clinical trials. However, a distinction has emerged between the type I, low-grade tumors and the type 2, higher-grade epithelial malignancies. Low-grade serous carcinoma exhibits different molecular and clinical features from the other epithelial subtypes, as well as some degree of chemotherapy resistance. This review summarizes the genetic, molecular and clinical characteristics of low-grade serous disease and provides an appraisal of the management strategies.