Amy K. Brown

A novel multiple marker bioassay utilizing HE4 and CA125 for the prediction of ovarian cancer in patients with a pelvic mass

INTRODUCTION Patients diagnosed with epithelial ovarian cancer (EOC) have improved outcomes when cared for at centers experienced in the management of EOC. The objective of this trial was to validate a predictive model to assess the risk for EOC in women with a pelvic mass. METHODS Women diagnosed with a pelvic mass and scheduled to have surgery were enrolled on a multicenter prospective study. Preoperative serum levels of HE4 and CA125 were measured. Separate logistic regression algorithms for premenopausal and postmenopausal women were utilized to categorize patients into low and high risk groups for EOC. RESULTS Twelve sites enrolled 531 evaluable patients with 352 benign tumors, 129 EOC, 22 LMP tumors, 6 non EOC and 22 non ovarian cancers. The postmenopausal group contained 150 benign cases of which 112 were classified as low risk giving a specificity of 75.0% (95% CI 66.9-81.4), and 111 EOC and 6 LMP tumors of which 108 were classified as high risk giving a sensitivity of 92.3% (95% CI=85.9-96.4). The premenopausal group had 202 benign cases of which 151 were classified as low risk providing a specificity of 74.8% (95% CI=68.2-80.6), and 18 EOC and 16 LMP tumors of which 26 were classified as high risk, providing a sensitivity of 76.5% (95% CI=58.8-89.3). CONCLUSION An algorithm utilizing HE4 and CA125 successfully classified patients into high and low risk groups with 93.8% of EOC correctly classified as high risk. This model can be used to effectively triage patients to centers of excellence.

Comparison of a novel multiple marker assay vs the Risk of Malignancy Index for the prediction of epithelial ovarian cancer in patients with a pelvic mass.

OBJECTIVE We sought to compare the Risk of Malignancy Index (RMI) to the Risk of Ovarian Malignancy Algorithm (ROMA) to predict epithelial ovarian cancer (EOC) in women with a pelvic mass. STUDY DESIGN In all, 457 women with imaging results from ultrasound, computed tomography, magnetic resonance imaging, and serum HE4 and CA125 determined prior to surgery for pelvic mass were evaluable. RMI values were determined using CA125, imaging score, and menopausal status. ROMA values were determined using HE4, CA125, and menopausal status. RESULTS At a set specificity of 75%, ROMA had a sensitivity of 94.3% and RMI had a sensitivity of 84.6% for distinguishing benign status from EOC (P = .0029). In patients with stage I and II disease, ROMA achieved a sensitivity of 85.3% compared with 64.7% for RMI (P < .0001). CONCLUSION The dual marker algorithm utilizing HE4 and CA125 to calculate a ROMA value achieves a significantly higher sensitivity for identifying women with EOC than does RMI.

Utility of a novel serum tumor biomarker HE4 in patients with endometrioid adenocarcinoma of the uterus

OBJECTIVE Tumor markers with increased sensitivity and specificity for endometrial cancer are needed to help monitor response to therapy and to detect recurrent disease. Currently, the tumor maker CA125 is utilized in this role with limited value. The objectives of this study were to examine the levels of several novel tumor markers HE4, SMRP, CA72.4 and CA125 as potential markers in patients diagnosed with endometrioid adenocarcinoma of the uterus. METHODS Pre-operative serum samples from surgically staged patients with endometrioid adenocarcinoma of the uterus were analyzed for levels of HE4, SMRP, CA72-4 and CA125. Control samples were obtained from healthy postmenopausal women. Logistic regression models and receiver operating characteristic (ROC) curves were constructed for each tumor marker and for all combinations, with cross-validation analyses to obtain average sensitivities at set specificities of 90%, 95%, and 98%. RESULTS Serum samples from 156 healthy subjects and 171 patients with endometrial cancer (122 stage I, 17 stage II, 26 stage III, and 6 stage IV) were analyzed. At a 95% specificity, the sensitivities for differentiating between healthy subjects and all stages of cancer were 45.5% for HE4 and 24.6% for CA125. For stage I disease, HE4 yielded a 17.1% improvement in sensitivity compared with CA125. CONCLUSION HE4 is elevated in all stages of endometrial can100cer and is more sensitive in early-stage endometrial cancer compared to CA125. Further investigation of HE4 as a marker for early detection of recurrent endometrial cancer and monitoring response to therapy is warranted.

Isolated sentinel lymph node dissection with conservative management in patients with squamous cell carcinoma of the vulva: A prospective trial

OBJECTIVES Sentinel lymph node (SLN) dissections have a high sensitivity and negative predictive value for the detection of metastatic disease. The objective of this study was to examine the inguinal recurrence rate along with complication rates for patients undergoing inguinal SLN dissection alone for vulvar carcinoma. METHODS An IRB approved prospective study enrolled patients with biopsy proven squamous cell carcinoma of the vulva. Peritumoral injection of Tc-99 sulfur colloid and methylene blue dye was used to identify SLNs intraoperatively. Patients with SLNs negative for metastatic disease were followed clinically. Patients with metastasis detected in a SLN subsequently underwent a full groin node dissection followed by standard treatment protocols. RESULTS Thirty-six patients were enrolled onto study with 35 undergoing a SLN dissection. All SNL dissections were successful with a mean of 2 SLN obtained per groin. There were 24 patients with stage I disease, 8 stage II, 3 stage III and 1 stage IV. A total of 56 SLN dissections were performed with 4 patients found to have inguinal metastasis by SLN dissection. There were 31 patients with a total of 46 SLN dissections found to be negative for metastatic disease. The median follow-up has been 29 months (range 8 to 51) with 2 groin recurrences for a groin recurrence rate of 4.3% and a recurrence rate per patient of 6.4%. There have been no reports of groin breakdown, extremity cellulitis or lymphedema. CONCLUSIONS The recurrence rate for patients undergoing inguinal sentinel node dissection alone is low. These patients did not experience any complications as seen with complete groin node dissections. Sentinel lymph node dissection should be considered as an option for evaluation of inguinal nodes for metastatic disease.

Utility of tumor marker HE4 to predict depth of myometrial invasion in endometrioid adenocarcinoma of the uterus.

Objective: The purpose of this pilot study was to determine whether the biomarker human epididymis protein 4 (HE4) correlates with depth of myometrial invasion, histologic grade, lymph vascular space invasion, positive cytologic washings, and nodal metastases in patients with endometrioid adenocarcinoma of the uterus. Methods: This was a prospective, observational study in women with biopsy-proven endometrioid adenocarcinoma. Concentrations of HE4 were assessed before surgery, and all surgical specimens were reviewed by dedicated gynecologic pathologists. Results: Included were a total of 96 women with endometrioid adenocarcinomas of the uterus, most (77%) with stage I disease. Levels of serum HE4 greater than 70 pM displayed a sensitivity of 94% and a negative predictive value of 97% in identifying stage IA (<50% myometrial invasion) versus stage IB (≥50% myometrial invasion) tumors and a sensitivity of 82% and negative predictive value of 82% versus all more advanced tumors. Conclusions: Human epididymis protein 4 may be a useful marker preoperatively in the clinical decision process for determining the need for lymph node dissection in women with endometrioid endometrial cancer.

A change in the balance between personal and professional life among female gynecologic oncologists

Background: Female representation in gynecologic oncology has increased over the last two decades. Our objective was to compare work-life balance issues faced by female gynecologic oncologists between 1998 and 2015. Material/Methods: We conducted a cross-sectional survey of physician members of the Society of Gynecologic Oncology. A survey sent to female gynecologic oncologists in 1998 was expanded, piloted with 10 volunteers, and administered in electronic format (DatStat Illume) in February 2015. There were 75 fixed response questions regarding 4 domains: demographics, mentoring issues, work-life balance, and caregiving responsibilities. We compared 2015 responses to the 1998 aggregate survey data. Data were analyzed using Stata 10 (Statacorp, College Station TX) with Chi-square/Fisher’s exact tests using aggregate data functions. Results: 172 of 643 female gynecologic oncologists (26.7% response rate) completed the 2015 survey. The historical comparison group included 82 females (56.2% response rate). While more women in 2015 versus 1998 reported starting a family during residency or fellowship (57.7% vs. 36.0%, p<0.009), 42% still waited until after training. More than half (55.9%) of respondents in 2015 said the timing of becoming a parent led to some or a great deal of relationship stress compared to only 20% in 1998 (p<0.0001). The majority of divorces were in fellowship for both groups with 8 (50.0%) in 2015 compared to 5 (45.5%) in 1998 (p=0.8). In 2015, 5 (83.4%) women divorced after fellowship and felt their career had a moderate to great influence on their divorce. Conclusions: Despite changes in work-life balance and caregiving responsibilities in female gynecologic oncologists between 1998 and 2015, challenges still exist today. Correspondence to: Ashley R Stuckey, Women and Infants Hospital, 101 Dudley St, Providence, RI 02905, USA, Tel: (401) 453-7520; Fax: (401) 453-7529; E-mail: astuckey@wihri.org

Current Mentorship Practices in Gynecologic Oncology [20P]

INTRODUCTION: Our objective was to describe mentoring practices among gynecologic oncologists. METHODS: We conducted a cross-sectional survey of gynecologic oncology physician members of the Society of Gynecologic Oncology. A survey sent to female gynecologic oncologists in 1998 was expanded, piloted, and administered electronically (DataStat Illume). Our 2015 instrument contained 75 fixed response questions in 4 domains: Demographics; Mentoring issues; Work-life Balance; Caregiving Responsibilities. Data was analyzed using Chi-square/Fishers exact test (Stata 10). RESULTS: We had a 22% response rate (268 of 1246), comprised of 64% women and 36% men. Fifty percent were between the ages of 30–40. 54% were in academic practice and 21% in fellowship. The majority (50%) reported currently having a mentor. Most (54%) had a male mentor, but 25% had both a male and female mentor. 41% of women had only a male mentor, while only 8% of men had only a female mentor. Most classified their mentor as academic (86%), but 29% reported a personal mentor. More women than men felt that it was somewhat important, important or very important that a mentor be the same gender (68.6% vs 41.7%, P<.001). Whether it was important that a mentor have children also differed between genders (37.5% of men vs 64.5% of women, P<.001). Formal mentoring programs were uncommon (28%). The majority (58%) also served as mentors themselves. CONCLUSION: The majority of gynecologic oncologists both receive and provide mentorship, despite few formal programs. Women placed greater value on having a mentor of the same gender and with children.

The prognostic significance of lower uterine segment involvement in surgically staged endometrial cancer patients with negative nodes

OBJECTIVES Endometrial cancer is the most common female genital malignancy in the United States. Stage is the most important prognostic factor. Other factors include grade, lymph-vascular space invasion (LVI), and myometrial invasion. Tumor location in the lower uterine segment (LUS) may also be important. LUS involvement correlates with nodal involvement, and nodal involvement is an important prognostic indicator. This study investigates the importance of LUS involvement in patients with pathologically negative nodes. METHODS This was an IRB approved retrospective study. Data were collected for patients diagnosed with endometrial cancer from June 1999 to September 2004. Patients who underwent nodal evaluation with no evidence of nodal disease were eligible for analysis. The primary endpoint was progression-free survival. Secondary endpoints included recurrence rate and overall survival. Analysis was performed with the JMP5.1 statistical program. RESULTS 285 patients were identified. 85 were excluded because they received postoperative care elsewhere. 3 charts were missing, and 15 pathology reports did not mention LUS. 147 of the remaining 182 subjects had negative nodes and formed the study population. 57% of these subjects had LUS involvement. Follow-up was similar for those with and without LUS involvement at 74 vs. 73 months respectively. PFS was similar at 70 and 63 months in those with and without LUS involvement (p=0.2). Recurrence correlated with LUS involvement on univariate analysis, however, not on multivariate analysis. CONCLUSIONS In endometrial cancer patients with negative nodes, disease within the lower uterine segment does not imply a worse prognosis. The previously described implications of LUS involvement are likely due to the strong association of LUS disease with lymph node spread.

The effect of protocol inclusion on the outcomes of ovarian cancer patients receiving first-line chemotherapy

5070 Background: Clinical trials are the gold standard for evidence based medicine however only 2% of cancer patients enroll in clinical trials. Recent data has shown improved outcomes with protocol treatment in a variety of cancers. We investigated the outcomes of patients receiving first-line chemotherapy for ovarian cancer on or off protocol. Methods: Subjects were identified from a database of protocol subjects and from the tumor registry. Controls must have been eligible for entry into protocol. The primary end-point was progression free survival (PFS) in months. Secondary end-points were cycle delays or hospital admissions during treatment and overall survival (OS). Kaplan-Meier survival analysis was performed. Continuous variables were compared with t-tests, and categorical variables with Chi-square or Fisher’s exact. Results: There was no difference in PFS between the two groups. (21 months for patient treated on protocol compared to 23 for patients treat off protocol) Subset analysis revealed imp...