Trusted authorities can change minds and shift norms during conflict.

The reintegration of former members of violent extremist groups is a pressing policy challenge. Governments and policymakers often have to change minds among reticent populations and shift perceived community norms in order to pave the way for peaceful reintegration. How can they do so on a mass scale? Previous research shows that messages from trusted authorities can be effective in creating attitude change and shifting perceptions of social norms. In this study, we test whether messages from religious leaders-trusted authorities in many communities worldwide-can change minds and shift norms around an issue related to conflict resolution: the reintegration of former members of violent extremist groups. Our study takes place in Maiduguri, Nigeria, the birthplace of the violent extremist group Boko Haram. Participants were randomly assigned to listen to either a placebo radio message or to a treatment message from a religious leader emphasizing the importance of forgiveness, announcing the leader's forgiveness of repentant fighters, and calling on followers to forgive. Participants were then asked about their attitudes, intended behaviors, and perceptions of social norms surrounding the reintegration of an ex-Boko Haram fighter. The religious leader message significantly increased support for reintegration and willingness to interact with the ex-fighter in social, political, and economic life (8 to 10 percentage points). It also shifted people's beliefs that others in their community were more supportive of reintegration (6 to 10 percentage points). Our findings suggest that trusted authorities such as religious leaders can be effective messengers for promoting peace.

Identifying the need to refine the potential patient risk factors for niraparib-induced thrombocytopenia.

OBJECTIVE: Niraparib is a poly (ADP-ribose) polymerase inhibitor (PARP) approved for use in maintenance therapy for ovarian cancer that is associated with the unpredictable grade 3/4 thrombocytopenia. This study was conducted to refine patient dosing recommendations for niraparib based upon clinical practice observations of grade 3/4 thrombocytopenia. METHODS AND MATERIALS: Six patient cases were reviewed to identify similarities in patient factors. An in vitro study was conducted using healthy volunteer blood spiked with Niraparib concentrations ranging from 0 ng/mL to 5000 ng/mL. Manual platelet counts were evaluated at different time intervals for each concentration and compared to untreated controls. Data was then analyzed based on percent change in platelet count versus untreated control for each concentration/time point. RESULTS: In three patients with body weight > 80 kg and platelet count >200 × 109/L, decreased creatinine clearance (CrCl) <60 mL/min was identified as potential signal. An additional three patients with weights below 77 kg and/or baseline platelet counts <150 × 109/L were re-evaluated, and it was observed that all had decreased CrCl of <60 mL/min. Albumin <3.5 g/dL was also observed in some patients with thrombocytopenia. The in vitro study, observed a direct concentration-dependent relationship between niraparib and thrombocytopenia. CONCLUSION: The data suggests that renal insufficiency and hypoalbuminemia may be associated with the development of niraparib-induced thrombocytopenia. Moreover, the preliminary in vitro studies also demonstrated a concentration-dependent relationship between niraparib and direct toxicity to platelets.

Accuracy of Intraoperative Frozen Section Diagnosis of Borderline Ovarian Tumors by Hospital Type.

STUDY OBJECTIVE: To compare the accuracy of frozen section diagnosis of borderline ovarian tumors among 3 distinct types of hospital-academic hospital with gynecologic pathologists, academic hospital with nongynecologic pathologists, and community hospital with nongynecologic pathologists-and to determine if surgical staging alters patient care or outcomes for women with a frozen section diagnosis of borderline ovarian tumor. DESIGN: Retrospective study (Canadian Task Force classification II-1). SETTING: Tertiary care, academic, and community hospitals. PATIENTS: Women with an intraoperative frozen section diagnosis of borderline ovarian tumor at 1 of 3 types of hospital from April 1998 through June 2016. INTERVENTIONS: Comparison of final pathology with intraoperative frozen section diagnosis. MEASUREMENTS AND MAIN RESULTS: Two hundred twelve women met the inclusion criteria. The frozen section diagnosis of borderline ovarian tumor correlated with the final pathologic diagnosis in 192 of 212 cases (90.6%), and the rate of correlation did not differ among the 3 hospital types (p = .82). Seven tumors (3.3%) were downgraded to benign on final pathologic analysis and 13 (6.1%) upgraded to invasive carcinoma. The 3 hospital types did not differ with respect to the proportion of tumors upgraded to invasive carcinoma (p = .62). Mucinous (odds ratio, 7.1; 95% confidence interval, 2.1-23.7; p = .002) and endometrioid borderline ovarian tumors (odds ratio, 32.4; 95% confidence interval, 1.8-595.5; p = .02) were more likely than serous ovarian tumors to be upgraded to carcinoma. Only 88 patients (41.5%) underwent lymphadenectomy, and only 1 (1.1%) had invasive carcinoma in a lymph node. CONCLUSIONS: A frozen section diagnosis of borderline ovarian tumor correlates with the final pathologic diagnosis in a variety of hospital types.

Managing Variant Interpretation Discrepancies in Hereditary Cancer: Clinical Practice, Concerns, and Desired Resources.

Variant interpretation is a complex process, and classification may vary between sources. This study aimed to determine the practice of cancer genetic counselors regarding discrepancies in variant interpretation and to identify concerns when counseling these discrepancies. An electronic survey was sent to genetic counselors in the NSGC Cancer Special Interest Group. The vast majority of counselors (93%) had seen a variant interpretation discrepancy in practice. A large majority (96%) of respondents indicated that they conducted their own research on reported variants. Most respondents cited variant databases as the most common resource utilized in researching variants. Approximately 33% of counselors spent 45 min or more of extra time researching a discrepancy compared to researching a variant with a single classification. When asked how they approached counseling sessions involving variant interpretation discrepancies, the free responses emphasized that counselors considered family history, clinical information, and psychosocial concerns, showing that genetic counselors tailored the session to each individual. Discrepancies in variant interpretation are an ongoing concern for clinical cancer genetic counselors, as demonstrated by the fact that counselors desired further resources to aid in addressing these discrepancies, including a centralized database (89%), guidelines from a major organization (88%), continuing education about the issue (74%), and functional studies (58%). Additionally, most respondents reported that the ideal database would be owned by a non-profit organization (59%) and obtain information directly from laboratories (91%). This investigation was the first to address these discrepancies from a clinical point of view. The study demonstrates that discrepancies in variant interpretation are a concern for clinical cancer genetic counselors and outlines the need for additional support.

Effectiveness of cyanoacrylate microbial sealant in the reduction of surgical site infection in gynecologic oncology procedures: A phase III single institution prospective randomized trial.

OBJECTIVES: Surgery is a cornerstone for patients with gynecologic malignancies. Surgical site infections (SSI) remain a source of post-operative morbidity. Consequences range from escalated costs, delay in adjuvant therapy, and increased morbidity. Our primary objective was to evaluate the effectiveness of a cyanoacrylate microbial sealant (CMS) to reduce post-operative SSI following laparotomy for suspected gynecologic malignancy. METHODS: Patients were randomized using a 1:1 allocation to receive either standard skin preparation or standard preparation with CMS and stratified by BMI. Patients were followed for 6weeks for SSI. Demographic data was collected through the EMR. Associations between SSI, use of CMS, and clinicopathologic factors were explored using descriptive statistics, chi-square and multivariate analysis. RESULTS: 300 patients underwent randomization. Median age of the cohort was 58. Arms were matched and there was no difference in rate of medical comorbidities. Mean BMI was 38.8kg/m2 in patients randomized to BMI≥30 and 26.3kg/m2 randomized to BMI<30. Surgical characteristics for the entire cohort: 66% malignancy, 91% clean-contaminated, 21% bowel surgery, 25% transfusion. Seventy-six (25%) patients developed a SSI: 43 patients (28%) treated with CMS, compared to 33 (21%) patients treated without CMS (p=0.18). Multivariate model demonstrated that BMI≥30 (p<0.005), surgery for malignancy (p=0.010), transfusion in the OR (p<0.001), and closure with staples (p=0.0005) were associated with post-operative SSI. CONCLUSIONS: Patients presenting to a gynecologic oncologist for surgery frequently present with multiple risk factors for SSI and laparotomy is complicated by surgical-site complications in up to 30% of cases. The addition of CMS alone does not appear to reduce risk of overall SSI. Additional risk-reducing strategies including use of antimicrobial agents and optimization of modifiable risk factors prior to surgery should be explored as pathways for reducing this significant post-operative morbidity.

Chemotherapy Response Rates Among Patients With Endometrial Cancer Who Have Elevated Serum Platelets.

OBJECTIVE: This retrospective study evaluates the influence of serum platelet count on chemotherapy response rates among women with endometrial cancer. METHODS: From 3 separate cancer centers, a total of 318 patients with endometrial cancer who received postoperative chemotherapy between June 1999 and October 2009 were retrospectively identified. Endometrioid, serous, clear cell, and carcinosarcoma histologies were included. Patients were classified as having an elevated platelet count if their serum platelet count was greater than 400 × 109/L at the time of initial diagnosis. Primary outcome was chemotherapy response, classified as either complete or partial/refractory. Secondary outcomes were disease-free and disease-specific survival. χ² Test and Student t test were performed as appropriate. Kaplan-Meier curves and Cox proportional hazards models were used to assess serum platelet effect on survival. RESULTS: There were 125 deaths, 76 recurrences, and 48 disease progressions. Of the total group, 53 (16.7%) were categorized as having an elevated platelet count. An elevated platelet count was associated with a lower chemotherapy response rate in univariate analysis (hazard ratio [HR], 2.8; 95% 95% confidence interval [CI], 1.46-5.38; P < 0.01). Multivariate analysis showed elevated platelets to be independently associated with decreased disease-free survival (HR, 2.24; 95% CI, 1.26-3.98; P < 0.01) but not disease-specific survival (HR, 1.03; 95% CI, 0.56-1.88, P = 0.93). CONCLUSIONS: Patients with endometrial cancer who have an elevated serum platelet count greater than 400 × 109/L may have lower chemotherapy response rates and are at increased risk for recurrence when compared with patients with a count within the reference range.

Referrals to phase I clinical trials in a gynecologic oncology unit.

OBJECTIVES: Previous reviews of phase I clinical trials report limited response rates. Development of novel biologic agents and trials designs have increased these rates. A contemporary appraisal of phase I clinical trials in gynecologic malignancies could help validate these findings. METHODS: Retrospectively reviewed records for 410 patients with gynecologic malignancies treated in a phase I unit, January 1999 to October 2012. Patient characteristics and treatment outcomes were abstracted and analyzed. RESULTS: Patients enrolled in 43 different phase I trials, 17 phase Ia, 17 phase Ib dose escalation and 9 dose expansion. 9 trials (21%) investigated unique cytotoxic delivery methods, 15 (35%) conventional cytotoxic plus novel agents and 19 (44%) novel agents alone. For patients treated in the first-line setting, 90 (74.4%) achieved CR, 20 (16.5%) PR, 9 (7.4%) SD and 2 (1.7%) PD, yielding an overall response rate of 90.9%. In patients treated for recurrent disease, 2 (1.6%) achieved CR, 11 (8.9%) PR, 57 (46.0%) SD and 54 (43.5%) PD, yielding a response rate of 11% and an overall clinical benefit rate of 57%. Response rate for molecular targeted therapies was 11.5% with an overall clinical benefit rate of 46.2%. Patients with prior anti-angiogenic exposure had comparable median PFS to those who had not been previously exposed (3.5 vs. 4.0 months, p = 0.29). CONCLUSIONS: Results support referral of gynecologic cancer patients for phase I clinical trials. Patients with advanced, heavily pretreated disease fare at least as well as they do on phase II trials and a proportion of them can attain an objective response or stabilization of their disease.

Phase II trial of vaginal cuff brachytherapy followed by chemotherapy in early stage endometrial cancer patients with high-intermediate risk factors.

OBJECTIVE: To determine the progression free survival (PFS), toxicity, and patterns of failure for early stage, high-intermediate risk (H-IR) patients in a phase II trial with adjuvant vaginal cuff brachytherapy (VCB) and three cycles of carboplatin and paclitaxel. METHODS: Surgically staged patients with stage I-IIb endometrial cancer with H-IR factors were treated with VCB (2100cGy) followed by three cycles of carboplatin (AUC 6) and paclitaxel (175 mg/m(2)). The primary endpoint was PFS at 2 years, with toxicity and sites of failure as secondary endpoints. Toxicity was assessed by patient report (CTCAE v. 3) as well as by delays or dose modifications in treatment. RESULTS: All patients completed VCB and 19/23 (83%) completed both VCB and 3 cycles of chemotherapy. Mean time to complete VCB was 14.5 days with minimal acute toxicity noted. At 6 months, all toxicity related to VCB had resolved. In total 60 cycles of chemotherapy were given, with one dose reduction (1.6%) for grade 2 neuropathy and seven delays (11.6%) in treatment due to hematologic toxicity. At a median follow-up of 44.5 months, 91% of patients remained progression free at 2 years. Four patients experienced a recurrence; they recurred both locally and distant. CONCLUSIONS: Adjuvant therapy with VCB and chemotherapy is well tolerated in a population of patients with H-IR endometrial carcinoma and provides 2 year PFS of 91%. A randomized trial is currently underway to assess whether combined VCB and chemotherapy reduces the rate of recurrence compared to external beam radiation therapy (EBRT) in this patient population.

Outcomes of cervical cancer and positive para-aortic lymph nodes in the modern era of chemoradiation.

OBJECTIVE: Patients with cervical cancer with positive para-aortic lymph nodes have a poor prognosis. Our primary aim was to describe outcomes among this subgroup in the era of modern chemoradiation. METHODS: Patients with histologically confirmed cervical cancer metastatic to their para-aortic lymph nodes diagnosed between 1998 and 2011 and treated with curative intent were included in this analysis. Surgicopathologic, demographic, and outcome data were collected. Descriptive and survival statistics were generated to evaluate overall survival (OS) and progression-free survival (PFS) and to compare outcomes by treatment. P values were generated using both Wilcoxon and log-rank methods and listed respectively. RESULTS: The median PFS was 19 months. The median OS was 23.4 months. The median PFS for radiation only was 14 months and for chemoradiation was 20 months (P = 0.27 and 0.60, respectively). There was no difference in median OS for the radiation-only group versus chemoradiation. The median OS stratified by stage was 32 months (stage I), 21 months (stage II), 19.4 months (stage III), and 19.8 months (stage IV; P = 0.17 and 0.22). CONCLUSIONS: Our study shows a median OS of 23 months, which is less than what was documented in the literature. Despite the use of modern chemoradiation therapy, most of the cohort died within 3 years. The low OS presented in our study highlights the limitations of the current treatment regimens and the need for identification of for more effective therapy.

A contemporary analysis of epidemiology and management of vaginal intraepithelial neoplasia.

OBJECTIVE: The purpose of this study was to review a large cohort of patients with vaginal intraepithelial neoplasia (VAIN) and to analyze the epidemiology and outcomes with various treatment modalities. STUDY DESIGN: A retrospective chart review was performed that encompassed patients who were treated for VAIN at a single center from 1990-2007. Demographics, disease characteristics, referring cytology, and histologic information were recorded. Primary outcome was recurrence or progression to carcinoma. Statistical analyses were performed with statistical software. RESULTS: One hundred sixty-three women were included in the study: median age, 50 years (range, 21-84 years); white, 87%; current or previous smokers, 35%. At the time of diagnosis, 23% of the women had VAIN1; 37% of the women had VAIN2, and 35% of the women had VAIN3. Referral Papanicolaou smear results of high-grade squamous intraepithelial lesion or atypical glandular cells revealed VAIN2 or VAIN3 in 89% of cases (P = .0019) vs 53% of cases with low-grade squamous intraepithelial lesion. The median follow-up period was 18 months (range, 1-194 months). VAIN1 was observed in 70% of cases; 71% of patients who were treated for VAIN1 had recurrence or progression. VAIN2 was treated in 77% of patients; 53% of those who were treated had recurrence or progression. VAIN3 was treated in 94% of cases; 31% of them had recurrence or progression. Risk of recurrence was not correlated to VAIN type (P = .3). Six carcinomas were discovered in patients with VAIN2 and VAIN3. Median time to progression was 17 months for VAIN1, 11 months for VAIN2, and 11 months for VAIN3 (P = .036). CONCLUSION: Despite the subtype, VAIN often recurs but does so more quickly with higher grade dysplasia.

Distance traveled for treatment of cervical cancer: who travels the farthest, and does it impact outcome?

OBJECTIVE: To evaluate the impact of distance from residence to treatment center on disease characteristics and recurrence of cervical cancer. MATERIALS AND METHODS: A single-institution retrospective chart review of patients treated for cervical cancer during 2006-2011 was performed. Demographic, socioeconomic, and clinicopathologic characteristics were recorded. Distance traveled from home to treatment facility was calculated and categorized. Recurrence and follow-up data were extracted; progression-free survival and overall survival were calculated. SAS version 9.2 was used for statistical analysis. RESULTS: Two hundred nineteen patients met the study criteria; 75% were Caucasian. Forty-nine percent used tobacco. Twenty-five percent had stage III/IV disease. Insurance type was 46% private, 25% Medicaid, 20% Medicare, and 9% uninsured. Distance between residence and hospital was less than 15 miles (29%), 15 to 30 miles (21%), 30 to 50 miles (17%), and more than 50 miles (33%). Median follow-up period was 23 months (range, 1-65). Caucasians were more likely to travel more than 30 miles to a treatment center (P = 0.018) Non-Caucasians were less likely to have private insurance (P = 0.0005) and more likely to recur (P = 0.0045). Recurrence was highest (50%) in African Americans. Travel of more than 30 miles was not associated with age, stage, histology, tobacco abuse, employment, clinical trial enrollment, primary chemoradiation for stage IB disease, or delayed radiation. Travel of more than 30 miles was associated with government insurance (P = 0.029) and a trend toward unemployment (P = 0.059). Four-year progression-free survival (53% vs 52%; P = 0.992) and overall survival (57% vs 62%; P = 0.73) were similar between less than or more than 30-mile travel. CONCLUSIONS: Fifty percent of the patients reside more than 30 miles from treating hospital. Despite farther travel, stage of disease, clinical trial enrollment, treatment type, radiation completion, and recurrence rates were similar among patients with cervical cancer. Non-Caucasians are less likely to travel more than 30 miles.

Vaginal cancer: the experience from 2 large academic centers during a 15-year period.

OBJECTIVE: Limited data regarding the natural history, management, and prognosis of vaginal cancer exist owing to the relative disease rarity. MATERIALS AND METHODS: A retrospective chart review was performed at 2 institutions to identify women receiving treatment for vaginal cancer between 1990 and 2004. Demographics, risk factors, histology, International Federation of Gynecology and Obstetrics stage, treatment, and treatment-related complications were recorded. Statistical Analysis Software (SAS) version 9.2 was used. RESULTS: A total of 110 patients were identified in the 2 university databases. Median age was 63 years (range = 36-93 years), and 84% were white; 73% had squamous cell carcinoma, 40% were ever users of tobacco, and 64% had no abnormal Pap smear results. Of the patients, 83% had early-stage (I or II) disease. Treatment varied by stage with increasing use of radiation with advancing stage. Recurrence was 24%, 32%, and 53% for stage I, II, and III/IV disease, respectively. After a median follow-up of 21 months, progression-free survival was 59, 35, and 23 months for stage I, II, and III/IV disease, respectively. Overall survival was 106, 58, and 34 months for stage I, II, and III/IV disease, respectively. Age greater than 60 years (p = .0339; hazard ratio [HR] = 2.162), advanced stage (p = .0004; HR = 2.475), and tobacco use (p = .0004; HR = 1.02) were negatively associated with survival. Thirty percent developed a significant complication (fistula, stricture, cystitis, or proctitis), and 21% developed a vesicovaginal and/or rectovaginal fistula. There was no association of fistula development with age, stage, tobacco use, histological finding, or treatment history (including radiation therapy). CONCLUSIONS: Age, stage, and tobacco abuse seem to be negatively associated with survival in vaginal cancer. However, no risk factors were associated with fistula development.

Wound complications after gynecologic cancer surgery.

OBJECTIVE: To explore clinical correlates of wound complications in high-risk women undergoing abdominal gynecologic surgery in a tertiary referral center. METHODS: Retrospective analysis of patient demographics, pre-operative and intra-operative information, and outcomes was performed in a cohort of patients who underwent abdominal surgery for suspected gynecologic malignancy between 1/2005 and 6/2008. The primary outcome was wound complication within 6 weeks of surgery. Univariate and multivariate logistic regression analyses were employed. A nomogram predicting post-operative wound complications was created and validated by receiver operating characteristic (ROC) curve analysis and 10-fold cross-validation. RESULTS: Median age of 373 women analyzed was 57years (range 25-88), median body mass index (BMI) 32.3kg/m(2) (range 14.0-70.7). A total of 150 patients (40%) had prior abdominal surgery; 40 (11%) had a pre-operative serum albumin <3.5g/dl; and 78 (21%) had pulmonary disease. Wound complications occurred in 125 patients (34%). In multivariate analysis wound complications were correlated with BMI of 30-39.9kg/m(2) (OR=5.62, 95% CI 2.08-15.19, p<0.0001) and BMI≥40kg/m(2) (OR=10.27, 95% CI 3.66-28.88, p<0.0001), prior abdominal surgery (OR 3.28, 95%CI1.89-5.70, p<0.0001), serum albumin≤3.5g/dl (OR 4.24, 95%CI 1.87-9.61, p=0.0005), pulmonary disease (OR 2.22, 95%CI 1.09-4.51, p=0.03), lysis of adhesions (OR 3.57, 95%CI 1.04-12.26, p=0.04), and length of surgery (OR 2.42, 95%CI 1.35-4.35, p=0.003). Risk for wound complication was lower with pelvic drain placement (OR 0.26, 95%CI 0.11-0.64, p=0.003). CONCLUSIONS: Wound complications are common in gynecologic oncology. Further studies should explore whether risk factor modification decreases complications.

Clinical and pathologic features of vulvar intraepithelial neoplasia in premenopausal and postmenopausal women.

OBJECTIVE: To explore the clinical and pathologic differences between vulvar intraepithelial neoplasia (VIN) in premenopausal and postmenopausal women cared for in a tertiary referral center. METHODS: Between January 1997 and June 2008, 145 women received care at our institution for VIN and VIN-associated squamous cell carcinoma (SCC). All patients' demographic characteristics and recurrence histories were recorded throughout the study period and were retrieved retrospectively. Menopausal status was self-reported at the time of initial diagnosis. χ, odds ratio, and logistic regression analyses were used. RESULTS: The median age was 50 years (range = 19-91 y) with 77% (111/145) of patients white, 20% (29/145) African American, and 3% (5/145) other ethnicity. Sixty percent of patients diagnosed with VIN were current smokers, 18% (26/145) were immunocompromised (positive for human immunodeficiency virus/transplant/steroids), and 30% (44/145) had concomitant or previous lower genital tract dysplasia. Vulvar intraepithelial neoplasia or VIN-related cancer recurred in 57 (39%) of 145 patients; of these, 40 (71%) had recurrence of VIN and 18 (29%) had recurrence of cancer. Fifty-one percent (74/145) of patients were menopausal at initial VIN diagnosis. Among women with VIN, the odds of initially presenting with a VIN-related SCC was 3.2 times greater in postmenopausal than in premenopausal women (confidence interval = 1.5-7.1, p < .01), and postmenopausal women were more likely to present with stage II to IV SCC (p = .021). Recurrence risk of SCC, but not VIN, was associated with menopause status (p < .05). CONCLUSIONS: Among women with VIN, the risk of SCC is higher in postmenopausal than in premenopausal women both initially and at recurrence. Excisional therapies to identify occult invasion are especially important for postmenopausal women with VIN.

Polymorphisms in MMP9 and SIPA1 are associated with increased risk of nodal metastases in early-stage cervical cancer.

OBJECTIVE: Heritable polymorphisms modulate metastatic efficiency in Cancer Single nucleotide polymorphisms (SNPs) in MMP9 (rs17576) and SIPA1 (rs746429, rs931127) have been associated with nodal metastases in multiple cancers. We investigated the association of these SNPs with nodal metastases in early-stage cervical cancer. METHODS: Consecutive patients with stage IB cervical cancer who underwent a pelvic lymph node (LN) dissection were included. Cases (>1 positive LN, n=101) were compared with controls (negative LN pathology, n=273). Genotyping was performed on genomic DNA in the 3 SNPs using a TaqMan assay and correlated with clinical variables. RESULTS: The G allele at SIPA1 rs931127 was associated with an increased risk of nodal disease (OR 1.9, P=0.03) and approached significance at SIPA 1 rs746429 (OR 2.2, P=0.09) and MMP9 rs17576 (OR 1.5, 0.08). In patients with stage Ib1 lesions (n=304), the G allele at both SIPA1 SNPs was associated with LN metastases (rs746429 OR 10.1, P=0.01; rs931127 OR 2.4, P=0.01). In patients with no lymph vascular space invasion, SIPA1 SNPs were again associated with LN metastases, and all patients with nodal disease had at least one G allele at SIPA1 rs746429. CONCLUSIONS: In this case-control study, SNPs in SIPA1 varied statistically in cervical cancer patients with and without nodal metastases and in MMP9 after controlling for stage and lymphvascular space invasion. Further work is needed to characterize inherited polymorphisms that provide a permissive background for the metastatic cascade.

Chemoradiation in locally advanced cervical carcinoma: an analysis of cisplatin dosing and other clinical prognostic factors.

OBJECTIVES: The aim of this study was to evaluate the effect of number of chemotherapy cycles and other clinical and pathologic factors on progression-free (PFS) and overall survival (OS) in patients with newly diagnosed cervical cancer. METHODS: We identified 118 patients with locally advanced cervical cancer (stages IB2-IVA) treated with combination weekly cisplatin (40 mg/m(2)) and radiation therapy (RT) between 2003 and 2007. Kaplan-Meier and Cox proportional hazard models were utilized to evaluate PFS and OS for associations with number of chemotherapy cycles and other factors. RESULTS: The majority of patients had stage IB2 or II disease (70%), squamous histology (91%), and size <6 cm (65%). Median RT duration was 50 days and 95% received brachytherapy. Thirty percent of patients completed <6 cycles of chemotherapy, and estimated PFS and OS were 63% and 75%, respectively. In multivariate analyses, the number of chemotherapy cycles was independently predictive of PFS and OS. Patients who received <6 cycles of cisplatin had a worse PFS (HR 2.65; 95% CI 1.35-5.17; p=0.0045) and OS (HR 4.47; 95% CI 1.83-10.9; p=0.001). Advanced stage, longer time to RT completion, and absence of brachytherapy were also associated with decreased OS and PFS (p<0.05). Similar results were found when analysis was conducted using a breakpoint of at least five but not less than five chemotherapy cycles. Higher grade was associated with decreased PFS (p=0.03) but not OS. Age, race, BMI, tumor size, smoking, histology, and IMRT were not statistically significant for OS or PFS. CONCLUSIONS: Aggressive supportive care to minimize missed chemotherapy treatments may improve survival after chemoradiation.

The Management of Women's Health Care by Internists With a Focus on the Utility of Ultrasound.

Adult women require routine care for the acute and chronic health problems found in both sexes, and they require specialized care for women's health problems, including disease prevention, disease screening, and disease management. Internists should direct primary care and participate in specialized care and to the extent possible follow guidelines published by various professional organizations. They should understand the use of ultrasound in breast cancer screening, the management of pregnancy, and other gynecologic problems, including vaginal bleeding, pelvic pain, and investigation for pelvic malignancy. Finally, all management decisions need discussions on the potential benefit or harm in each step of a woman's care with an emphasis on personal preferences.

The value of perioperative imaging in patients with uterine sarcomas.

OBJECTIVE: To explore the yield and impact of perioperative imaging on management among patients undergoing surgical resection and treatment of uterine sarcomas. METHODS: A retrospective chart review was done for women with histologically confirmed uterine sarcomas treated at Barnes Jewish Hospital/Washington University from 2001 to 2007. Descriptive statistics, Cox multivariate models, and Kaplan-Meier plots were used to evaluate associations and survival. RESULTS: A total of 92 patients were identified and 55 (60%) were diagnosed with stage III-IV disease. Perioperative imaging was obtained in 84 (91%) cases, including chest X-ray in 66 (72%), computerized tomography (CT) of the abdomen and pelvis in 59 (64%), chest CT in 33 (36%), positron emission tomography (PET) in 8 (9%), and CT of the head, pelvic magnetic resonance imaging (MRI), or bone scan in a total of 2 (2.2%). Imaging identified abnormalities concerning for metastases in 30 (32%) studies. Thirty-four recurrences have been documented, and 21 (62%) of these treatment failures were extrapelvic. Multivariate analysis of this series noted that tomographic evidence of extrauterine disease predicted recurrence (p=0.028) and incomplete surgical resection (p=0.003, HR 6.0 95% CI 1.9-19.9) predicted disease-free survival. Imaging contributed to change in surgical and post-surgical treatment decisions in 8 (9%) patients. CONCLUSION: Pretreatment imaging studies change management in a minority of patients with newly diagnosed uterine sarcomas.

Clinical and biological significance of vascular endothelial growth factor in endometrial cancer.

PURPOSE: Vascular endothelial growth factor (VEGF) is critical for angiogenesis and tumor progression; however, its role in endometrial cancer is not fully known. Therefore, we examined the clinical and therapeutic significance of VEGF in endometrial carcinoma using patient samples and an endometrioid orthotopic mouse model. EXPERIMENTAL DESIGN: Following Institutional Review Board approval, VEGF expression and microvessel density (MVD) counts were evaluated using immunohistochemistry in 111 invasive endometrioid endometrial cancers by two independent investigators. Results were correlated with clinicopathologic characteristics. For the animal model, Ishikawa or Hec-1A cancer cell lines were injected directly into the uterine horn. Therapy experiments with bevacizumab alone or in combination with docetaxel were done and samples were analyzed for markers of angiogenesis and proliferation. RESULTS: Of 111 endometrial cancers, high expression of VEGF was seen in 56% of tumors. There was a strong correlation between VEGF expression and MVD (P < 0.001). On multivariate analysis, stage (P = 0.04), grade (P = 0.003), VEGF levels (P = 0.03), and MVD (P = 0.037) were independent predictors of shorter disease-specific survival. In the murine model, whereas docetaxel and bevacizumab alone resulted in 61% to 77% tumor growth inhibition over controls, combination therapy had the greatest efficacy (85-97% inhibition over controls; P < 0.01) in both models. In treated tumors, combination therapy significantly reduced MVD counts (50-70% reduction over controls; P < 0.01) and percent proliferation (39% reduction over controls; P < 0.001). CONCLUSIONS: Increased levels of VEGF and angiogenic markers are associated with poor outcome in endometrioid endometrial cancer patients. Using a novel orthotopic model of endometrioid endometrial cancer, we showed that combination of antivascular therapy with docetaxel is highly efficacious and should be considered for future clinical trials.

Cost-Effectiveness of Niraparib and Olaparib as Maintenance Therapy for Patients with Platinum-Sensitive Recurrent Ovarian Cancer.

BACKGROUND: The recent approval of olaparib and niraparib as maintenance therapy can significantly affect the management of ovarian cancer. Clinical benefits, however, come with trade-offs in adverse events and costs. OBJECTIVE: To evaluate the cost-effectiveness of new ovarian cancer poly-ADP ribose polymerase (PARP) inhibitor therapies, olaparib and niraparib, as maintenance therapy for patients with platinum-sensitive recurrent ovarian cancer. METHODS: A decision tree model was constructed to evaluate the costs and effectiveness of olaparib and niraparib compared with placebo from a U.S. health care sector perspective. Costs included drug costs and costs of disease monitoring and management of adverse events throughout the treatment course. Costs were estimated from RED BOOK, Medicare reimbursement rates, and the literature and reported in 2017 U.S. dollars. Clinical effectiveness was measured in progression-free survival (PFS) life-years based on clinical trial results (NCT00753545, NCT01874353, and NCT01847274). The incremental cost-effectiveness ratio (ICER) was computed by dividing the incremental cost by the incremental effectiveness. RESULTS: At base case, niraparib was the more effective treatment option with slightly higher PFS, followed by olaparib. The ICERs for niraparib and olaparib compared with common baseline placebo were $235K and $287K per PFS life-year, respectively, with olaparib extended-dominated by niraparib. Both drugs were associated with lower ICERs in patients with a gBRCA mutation than in patients without a gBRCA mutation. One-way sensitivity analysis suggested that drug prices and PFS could affect ICERs significantly, but the ICERs remained above $100K per PFS life-year within the plausible ranges of all parameters. Probabilistic sensitivity analysis suggested that niraparib was associated with higher net benefits compared with placebo only when willingness-to-pay (WTP) values were above $210K per PFS life-year thresholds. CONCLUSIONS: PARP inhibitors niraparib and olaparib will extend PFS in platinum-sensitive recurrent ovarian cancer patients but are also associated with high drug acquisition costs. The base case ICERs were around or above $250K per PFS life-year in this model. No formal cost-effectiveness WTP threshold for health technology assessment exists in the United States. At a reference WTP of $100K per PFS life-year, the PARP inhibitors may not be cost-effective options. DISCLOSURES: This study was unfunded. The authors have nothing to disclose.