Efficacy and safety of tivozanib in recurrent, platinum-resistant ovarian, fallopian tube or primary peritoneal cancer, an NCCN phase II trial.

OBJECTIVE: Tivozanib is a potent selective pan-vascular endothelial growth factor receptor tyrosine kinase inhibitor with a long half-life. This study assessed its activity in patients with recurrent, platinum-resistant ovarian, fallopian tube or primary peritoneal cancer (OC). METHODS: This open-label phase II study used a Simon's two-stage design. Eligible patients had recurrent, platinum-resistant OC and measurable or detectable disease. There was no limit on the number of prior regimens. Treatment consisted of tivozanib 1.5 mg orally once daily for 21 days in a 28-day cycle. The primary endpoint was objective response rate (ORR). Secondary endpoints were progression-free survival (PFS), overall survival (OS), and toxicity assessment. RESULTS: Thirty-one patients were enrolled, and 30 were treated. The median age was 59.5 years, and median number of prior regimens was 4 (range 1-9). Twenty-four patients were evaluable for response, and four (16.7%) achieved a partial response (PR; ORR = 16.7%). An additional fourteen (58.3%) patients had stable disease (SD). The clinical benefit rate (PR + SD) was 75.0%, and the median duration of objective response was 5.7 months. For all patients on trial, the median PFS was 4.1 months (95% confidence interval (CI): 1.7-5.8) and OS 8.6 months (95% CI: 5.4-12.5). There were no treatment-related deaths. Serious adverse events occurred in 13.3% of patients and included small intestinal perforation or obstruction and stroke. Grade 3-4 adverse events occurred in 60% of patients, including hypertension (26.7%) and fatigue (10%). CONCLUSIONS: Tivozanib is effective in patients with recurrent OC, with moderate toxicity and no treatment-related deaths, supporting its further development.

Gestational Trophoblastic Neoplasia, Version 2.2019, NCCN Clinical Practice Guidelines in Oncology.

Gestational trophoblastic neoplasia (GTN), a subset of gestational trophoblastic disease (GTD), occurs when tumors develop in the cells that would normally form the placenta during pregnancy. The NCCN Guidelines for Gestational Trophoblastic Neoplasia provides treatment recommendations for various types of GTD including hydatidiform mole, persistent post-molar GTN, low-risk GTN, high-risk GTN, and intermediate trophoblastic tumor.

Cervical Cancer, Version 3.2019, NCCN Clinical Practice Guidelines in Oncology.

Cervical cancer is a malignant epithelial tumor that forms in the uterine cervix. Most cases of cervical cancer are preventable through human papilloma virus (HPV) vaccination, routine screening, and treatment of precancerous lesions. However, due to inadequate screening protocols in many regions of the world, cervical cancer remains the fourth-most common cancer in women globally. The complete NCCN Guidelines for Cervical Cancer provide recommendations for the diagnosis, evaluation, and treatment of cervical cancer. This manuscript discusses guiding principles for the workup, staging, and treatment of early stage and locally advanced cervical cancer, as well as evidence for these recommendations. For recommendations regarding treatment of recurrent or metastatic disease, please see the full guidelines on NCCN.org.

Uterine Neoplasms, Version 1.2018, NCCN Clinical Practice Guidelines in Oncology.

Endometrial carcinoma is a malignant epithelial tumor that forms in the inner lining, or endometrium, of the uterus. Endometrial carcinoma is the most common gynecologic malignancy. Approximately two-thirds of endometrial carcinoma cases are diagnosed with disease confined to the uterus. The complete NCCN Guidelines for Uterine Neoplasms provide recommendations for the diagnosis, evaluation, and treatment of endometrial cancer and uterine sarcoma. This manuscript discusses guiding principles for the diagnosis, staging, and treatment of early-stage endometrial carcinoma as well as evidence for these recommendations.

Surgery and Platinum/Etoposide-Based Chemotherapy for the Treatment of Epithelioid Trophoblastic Tumor.

OBJECTIVE: Epithelioid trophoblastic tumor (ETT) is a rare variant of gestational trophoblastic neoplasia that develops from chorionic-type intermediate trophoblast, simulates carcinoma, presents years after a pregnancy event, is associated with low or normal human chorionic gonadotropin levels, and is relatively resistant to chemotherapy. Our aim was to identify the role of surgery in combination with platinum/etoposide-based chemotherapy in the management of both localized and metastatic ETT. METHODS: A retrospective review was performed of women with ETT treated at a gestational trophoblastic disease center from 2010 to 2016. RESULTS: Five patients were identified who had complete records. Mean age was 38.0 years. Three women presented with abnormal uterine bleeding, 2 women presented with respiratory complaints, and 1 woman was asymptomatic. Two women had no identifiable antecedent pregnancy, 2 women had spontaneous abortions, and 1 woman had a normal term delivery before diagnosis. Four (80%) of 5 women had metastatic pulmonary disease. All 5 women underwent hysterectomy, and 3 women had resection of metastatic pulmonary disease. The 4 women with metastatic disease were also treated with chemotherapy. All 5 women are currently without evidence of disease. CONCLUSIONS: Surgery, including hysterectomy and resection of metastatic disease, is an important component in the treatment of women with ETT. Adjuvant chemotherapy with a platinum/etoposide-containing regimen should be used in women with metastatic disease. All 5 women with ETT in this series were cured using this approach, including the 4 who had metastatic disease.

Synuclein-γ in uterine serous carcinoma impacts survival: An NRG Oncology/Gynecologic Oncology Group study.

BACKGROUND: Synuclein-γ (SNCG) is highly expressed in advanced solid tumors, including uterine serous carcinoma (USC). The objective of the current study was to determine whether SNCG protein was associated with survival and clinical covariates using the largest existing collection of USCs from the Gynecologic Oncology Group (GOG-8023). METHODS: High-density tissue microarrays (TMAs) of tumor tissues from 313 patients with USC were stained by immunohistochemistry for SNCG, p53, p16, FOLR1, pERK, pAKT, ER, PR, and HER2/neu. Associations of SNCG and other tumor markers with overall and progression-free survival were assessed using log-rank tests and Cox proportional-hazards models, which also were adjusted for age, race, and stage. RESULTS: The overall survival at 5 years was 46% for women with high SNCG expression and 62% for those with low SNCG expression (log-rank P = .021; hazard ratio [HR], 1.31; 95% confidence interval [CI], 0.91-1.9 in adjusted Cox model). The progression-free survival rate at 5 years was worse for women who had high SNCG expression, at 40%, compared with 56% for those who had low SNCG expression (log-rank P = .0081; HR, 1.36; 95% CI, 0.96-1.92 in adjusted Cox model). High levels of both p53 and p16 were significantly associated with worse overall survival (p53: HR, 4.20 [95% CI, 1.54-11.45]; p16: HR, 1.95 [95% CI, 1.01-3.75]) and progression-free survival (p53: HR, 2.16 [95% CI, 1.09-4.27]; p16: HR, 1.53 [95% CI, 0.87-2.69]) compared with low levels. CONCLUSIONS: This largest collection of USCs to date demonstrates that SNCG was associated with poor survival in univariate analyses. SNCG does not predict survival outcome independent of p53 and p16 in models that jointly consider multiple markers. Cancer 2017;123:1144-1155. © 2016 American Cancer Society.

Vulvar Cancer, Version 1.2017, NCCN Clinical Practice Guidelines in Oncology.

Vulvar cancer is a rare gynecologic malignancy. Ninety percent of vulvar cancers are predominantly squamous cell carcinomas (SCCs), which can arise through human papilloma virus (HPV)-dependent and HPV-independent pathways. The NCCN Vulvar Cancer panel is an interdisciplinary group of representatives from NCCN Member Institutions consisting of specialists in gynecological oncology, medical oncology, radiation oncology, and pathology. The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Vulvar Cancer provide an evidence- and consensus-based approach for the management of patients with vulvar SCC. This manuscript discusses the recommendations outlined in the NCCN Guidelines for diagnosis, staging, treatment, and follow-up.

Receipt of vaginal brachytherapy is associated with improved survival in women with stage I endometrioid adenocarcinoma of the uterus: A National Cancer Data Base study.

BACKGROUND: Randomized controlled trials have consistently shown that the use of postoperative radiotherapy (RT) for stage I endometrial cancer leads to a reduction in the incidence of pelvic recurrences without a corresponding reduction in overall mortality. It was hypothesized that a reduction in mortality associated with the receipt of RT could be identified in a large data set with greater statistical power. METHODS: Women with surgically staged IA or IB endometrial adenocarcinoma who were treated with total hysterectomy between 2003 and 2011 were identified in the National Cancer Data Base. Chi-square tests and multivariate logistic regression were performed to analyze factors associated with the treatment type. A survival analysis was performed with log-rank testing, Cox proportional hazards regression, and Kaplan-Meier estimates. RESULTS: A total of 44,309 eligible women were identified (33,380 at stage IA and 10,929 at stage IB): 88.4% of the women with stage IA tumors and 51.6% of the women with stage IB tumors received no RT. Older age, comorbid disease, a higher histologic grade, and a larger tumor size were independently associated with an increase in mortality. The receipt of vaginal brachytherapy (VB) was independently associated with a reduction in mortality for both stage IA disease (hazard ratio [HR], 0.81; 95% confidence interval [CI], 0.67-0.97) and stage IB disease (HR, 0.62; 95% CI, 0.51-0.74). CONCLUSIONS: Analyses of this large database support the utility of postoperative VB for many women with stage I endometrial cancer. Unfortunately, RT appears to be underused in this population. Greater adherence to consensus guidelines may lead to improved outcomes. Cancer 2016;122:3724-31. © 2016 American Cancer Society.

Characterization of the Influence of Semen-Derived Enhancer of Virus Infection on the Interaction of HIV-1 with Female Reproductive Tract Tissues.

UNLABELLED: The majority of human immunodeficiency virus type 1 (HIV-1) transmission events occur in women when semen harboring infectious virus is deposited onto the mucosal barriers of the vaginal, ectocervical, and endocervical epithelia. Seminal factors such as semen-derived enhancer of virus infection (SEVI) fibrils were previously shown to greatly enhance the infectivity of HIV-1 in cell culture systems. However, when SEVI is intravaginally applied to living animals, there is no effect on vaginal transmission. To define how SEVI might function in the context of sexual transmission, we applied HIV-1 and SEVI to intact human and rhesus macaque reproductive tract tissues to determine how it influences virus interactions with these barriers. We show that SEVI binds HIV-1 and sequesters most virions to the luminal surface of the stratified squamous epithelium, significantly reducing the number of virions that penetrated the tissue. In the simple columnar epithelium, SEVI was no longer fibrillar in structure and was detached from virions but allowed significantly deeper epithelial virus penetration. These observations reveal that the action of SEVI in intact tissues is very different in the anatomical context of sexual transmission and begin to explain the lack of stimulation of infection observed in the highly relevant mucosal transmission model. IMPORTANCE: The most common mode of HIV-1 transmission in women occurs via genital exposure to the semen of HIV-infected men. A productive infection requires the virus to penetrate female reproductive tract epithelial barriers to infect underlying target cells. Certain factors identified within semen, termed semen-derived enhancers of virus infection (SEVI), have been shown to significantly enhance HIV-1 infectivity in cell culture. However, when applied to the genital tracts of living female macaques, SEVI did not enhance virus transmission. Here we show that SEVI functions very differently in the context of intact mucosal tissues. SEVI decreases HIV-1 penetration of squamous epithelial barriers in humans and macaques. At the mucus-coated columnar epithelial barrier, the HIV-1/SEVI interaction is disrupted. These observations suggest that SEVI may not play a significant stimulatory role in the efficiency of male-to-female sexual transmission of HIV.

Postmolar choriocarcinoma: An independent risk factor for chemotherapy resistance in low-risk gestational trophoblastic neoplasia.

OBJECTIVE: To evaluate the effect of a clinicopathologic diagnosis of choriocarcinoma (CCA) on clinical characteristics, extent of disease, and response to chemotherapy in low-risk gestational trophoblastic neoplasia (GTN). METHODS: We reviewed the records of 678 patients with low-risk GTN (FIGO stage I and stages IIIII, score<7) treated from 1962 to 2009. Patient and disease characteristics, treatment course, as well as clinical response and survival were analyzed retrospectively. Patients with a clinicopathologic diagnosis of CCA were compared to those with a clinical diagnosis of postmolar GTN. RESULTS: Of 678 women with low-risk GTN, 129 (19.0%) had a clinicopathologic diagnosis of CCA. Patients with CCA had higher parity (median 1 vs. 0, p=0.003), more pretreatment human chorionic gonadotropin (hCG) levels at >100,000mIU/mL (12.7% vs. 5.9%, p=0.009), longer duration of disease (19.6 vs. 9.9weeks, p<0.001), and higher FIGO scores (median 2 vs. 1, p<0.001) compared with those with other histology; however, patients with CCA and postmolar GTN presented with similar stage of disease (stage I, 83.1% vs 88.2%, p=0.126). Although there was no difference in survival between groups, increased resistance to first-line methotrexate chemotherapy was significantly associated with a diagnosis of postmolar CCA (OR 2.67, p=0.007)), pretreatment hCG level at >10,000mIU/mL (OR 2.62, p=0.002), and higher FIGO score (3-4: OR 2.02, p=0.027; 5-6: OR 5.56, p<0.001) on multivariate analysis. CONCLUSIONS: Clinicopathologic diagnosis of postmolar CCA in patients with low-risk GTN is associated with higher pretreatment hCG levels, higher FIGO scores, and increased resistance to first-line single-agent methotrexate chemotherapy.

Pulmonary Resection in the Management of High-Risk Gestational Trophoblastic Neoplasia.

OBJECTIVE: The aim of this study was to evaluate the role of pulmonary resection in the management of high-risk gestational trophoblastic neoplasia (GTN). METHODS: Patients who underwent pulmonary resection as part of their treatment for chemotherapy-resistant high-risk GTN from 1986 and 2014 were retrospectively analyzed. All patients had received 1 or more multiagent chemotherapy regimens preoperatively. Patient and disease characteristics were evaluated with respect to outcome. RESULTS: Fifteen (26%) of 58 patients treated for high-risk GTN underwent pulmonary resection with curative intent. Mean age of patients was 29 years (range, 19-37 years). International Federation of Gynecology and Obstetrics stage was III in 12 and IV in 3. International Federation of Gynecology and Obstetrics scores ranged from 5 to 20 (mean, 10). Antecedent pregnancy was nonmolar in 11 patients (73%). Adjuvant surgical procedures other than pulmonary resection were performed in 8 patients (53%). Preoperative chemotherapy regimens ranged from 1 to 10 (median, 4) and courses numbered from 2 to 32 (median, 14). Preoperative human chorionic gonadotropin (hCG) levels ranged from 2 to 2786 mIU/mL (median, 177 mIU/mL). Pulmonary wedge resections or lobectomies were performed via video-assisted thoracoscopic surgery (11) or thoracotomy (4). Two patients underwent pulmonary resections on 2 separate occasions. No patient had complications as a result of these procedures. Eleven patients (73%) were cured. In these 11 patients, hCG levels decreased to less than 2 mIU/mL within 6 to 52 days (mean, 22 days) postoperatively. CONCLUSIONS: Pulmonary resection of chemotherapy-resistant GTN was an important component of treatment in 26% of high-risk patients, 73% of whom were cured. Ideal candidates have disease isolated to the lungs and low hCG levels.

Follow-Up After Molar Pregnancy Evacuation: Feasibility of Using Semi-Quantitative Urine Pregnancy Tests.

OBJECTIVE: To evaluate human chorionic gonadotropin (hCG) trends after evacuation of complete hydatidiform moles to determine if urinary semiquantitative pregnancy tests (SQPTs) could replace blood draws. while still detecting early postmolar gestational trophoblastic neoplasia. STUDY DESIGN: A retrospective review of complete hydatidiform moles at a safety-net hospital from 2003-2013 was performed. hCG curves were used to extrapolate expected SQPT results over timefor a resolving hydatidiform mole. RESULTS: Of 61 complete moles, 37 had an uncomplicated hCG decline and at least 4 serum hCG results. All of those patients had hCG < 10,000 mIU/mL within 15 days, < 2,000 within 64 days, < 500 within 70 days (92.2% within 1 month), < 100 within 89 days (90% within 2 months), and < 25 within 152 days (95.2% within 3 months). After reaching levels < 25, hCG rose only in cases of new pregnancies. CONCLUSION: Based on this retrospective analysis, SQPT monitoring could have avoided 90% of blood draws while still flagging all patients with subsequent postmolar GTN within 45 days by limiting blood draws to (1) patients with SQPT levels of > 10,000, > 500, and >100 mIU/mL at 15, 30, and 45 days, respectively, (2) hCG > 25 after 60 days, or (3) increasing SQPT levels.

Fatal gestational trophoblastic neoplasia: An analysis of treatment failures at the Brewer Trophoblastic Disease Center from 1979-2012 compared to 1962-1978.

OBJECTIVE: To determine clinical factors that contributed to death from gestational trophoblastic neoplasia (GTN) at the Brewer Trophoblastic Disease Center from 1979-2012 compared to 1962-1978. METHODS: Nineteen women who died of GTN from 1979-2012 were retrospectively identified and compared to 45 women previously reported on who died of GTN from 1962-1978. Clinical factors analyzed included demographics, pretreatment human chorionic gonadotropin (hCG) level, duration of disease, antecedent pregnancy, number and sites of metastases, FIGO stage and score, treatment, and cause of death. RESULTS: Death from GTN occurred in 19 (4%) of 483 patients treated from 1979-2012 compared to 45 (11%) of 396 patients treated from 1962-1978 (P<0.001). Pretreatment hCG level >100,000 mIU/mL, time from pregnancy event to treatment >4 months, nonmolar antecedent pregnancy and use of surgery to control metastatic disease were similar between the two treatment eras. Patients in the recent series were more likely to have presented with FIGO IV disease or brain metastasis, been initially treated with multiagent chemotherapy, and received treatment before referral to our center compared to the earlier series. The most common causes of death from 1979-2012 and 1962-1978 were hemorrhage from one or more metastatic sites (11% vs. 42%), respiratory failure (37% vs. 31%), and multiorgan failure due to widespread chemoresistant disease (42% vs. 8%), respectively. CONCLUSIONS: Our overall survival rate in patients with gestational trophoblastic neoplasia improved from 89% in 1962-1978 to 96% in 1979-2012. More patients treated between 1979-2012 died from widespread chemoresistant disease rather than hemorrhagic complications.

Cervical Cancer, Version 2.2015.

The NCCN Guidelines for Cervical Cancer provide interdisciplinary recommendations for treating cervical cancer. These NCCN Guidelines Insights summarize the NCCN Cervical Cancer Panel's discussion and major guideline updates from 2014 and 2015. The recommended systemic therapy options for recurrent and metastatic cervical cancer were amended upon panel review of new survival data and the FDA's approval of bevacizumab for treating late-stage cervical cancer. This article outlines relevant data and provides insight into panel decisions regarding various combination regimens. Additionally, a new section was added to provide additional guidance on key principles of evaluation and surgical staging in cervical cancer. This article highlights 2 areas of active investigation and debate from this new section: sentinel lymph node mapping and fertility-sparing treatment approaches.

Uterine Sarcoma, Version 1.2016: Featured Updates to the NCCN Guidelines.

The NCCN Guidelines for Uterine Neoplasms provide interdisciplinary recommendations for treating endometrial carcinoma and uterine sarcomas. These NCCN Guidelines Insights summarize the NCCN Uterine Neoplasms Panel's 2016 discussions and major guideline updates for treating uterine sarcomas. During this most recent update, the panel updated the mesenchymal tumor classification to correspond with recent updates to the WHO tumor classification system. Additionally, the panel revised its systemic therapy recommendations to reflect new data and collective clinical experience. These NCCN Guidelines Insights elaborate on the rationale behind these recent changes.

A Comparison of Survival and Recurrence Outcomes in Patients With Endometrial Cancer Undergoing Robotic Versus Open Surgery.

OBJECTIVE: To compare recurrence and survival outcomes in women who underwent either robotic or open surgical procedures to treat endometrial cancer. DESIGN: A retrospective chart review (Canadian Tack Force classification II-2). SETTING: A single academic institution. PATIENTS: A total of 936 patients who underwent surgical staging for endometrial cancer between 2001 and 2013. INTERVENTION: Through retrospective chart review, data were collected on patient characteristics, surgical procedures, intraoperative and postoperative complications, histopathology, adjuvant therapies, and recurrence and survival outcomes. Estimated 3-year progression-free survival and 5-year overall survival were calculated using Kaplan-Meier curves. MAIN RESULTS: Of the 936 patients who underwent endometrial cancer surgery, 350 had robotic-assisted surgery and 586 had laparotomy. Both groups were comparable in terms of age, race, body mass index, and comorbid conditions. The laparotomy group had significantly more patients with grade 2-3 tumors, nonendometrioid histology, and stage III-IV disease. In a multivariate analysis, operative type was not an independent prognostic factor for intraoperative complications, but robotic surgery was associated with decreased postoperative complications and readmission rate. Median duration of follow-up was 30 months in the robotic cohort and 42 months in the laparotomy cohort. Estimated 3-year progression-free survival was 90.87% for the robotic group and 78.30% for the laparotomy group, and estimated 5-year overall survival was 89.14%for the robotic group and 79.47% for the laparotomy group. In a multivariate analysis, including stage, grade, histology, operative type, and adjuvant therapy, operative type was not an independent prognostic factor for recurrence or overall survival. CONCLUSION: Compared with laparotomy, robotic staging for endometrial cancer is associated with less postoperative morbidity without compromising short-term recurrence rates or survival outcomes.

Management of adenocarcinoma in situ of the uterine cervix: a comparison of loop electrosurgical excision procedure and cold knife conization.

OBJECTIVE: This study aimed to compare loop electrosurgical excision procedure (LEEP) with cold knife conization (CKC) as therapeutic management procedures for women with adenocarcinoma in situ (ACIS) of the cervix. METHODS: We conducted a retrospective chart review of all patients who underwent a conization procedure with a preoperative or postoperative diagnosis of ACIS of the cervix from 1997 to 2011. Data gathered included demographics, risk factors, pretreatment Pap test and colposcopic biopsy results, conization pathology including presence of invasive cancer and margin status, subsequent need for reconization or hysterectomy, and follow-up. Outcome measures, such as diagnosis of invasive cancer, margin status, and recurrence of ACIS or development of invasive cancer, were compared between LEEP and CKC. RESULTS: Of 115 conization procedures performed, 61 were LEEP (31 diagnostic and 30 therapeutic) and 54 were CKC (6 diagnostic and 48 therapeutic). Patients who underwent CKC were more often nulliparous, on oral contraceptive pills, and smoking cigarettes than patients who underwent LEEP. For the 78 patients who underwent conization procedures with therapeutic intent, there were no differences in the rates of positive margins (20% vs 17%), invasive cancer (3.3% vs 4.2%), recurrence of ACIS (6.7% vs 8.3%), or subsequent development of invasive adenocarcinoma (0 vs 2.0%) between LEEP and CKC, respectively. CONCLUSIONS: In our study, LEEP was as good as CKC for the treatment of ACIS of the cervix, achieving the same rates of negative margins, diagnosis of invasive cancer, and recurrence of ACIS or invasive cancer. The benefits of LEEP versus CKC include the ability to perform the procedure in an outpatient clinic under local anesthesia with less morbidity. Patients treated for ACIS of the cervix by a conization procedure need careful, regular follow-up given the risk of recurrent ACIS or invasive cancer.

Defining the interaction of HIV-1 with the mucosal barriers of the female reproductive tract.

Worldwide, HIV-1 infects millions of people annually, the majority of whom are women. To establish infection in the female reproductive tract (FRT), HIV-1 in male ejaculate must overcome numerous innate and adaptive immune factors, traverse the genital epithelium, and establish infection in underlying CD4(+) target cells. How the virus achieves this remains poorly defined. By utilizing a new technique, we define how HIV-1 interacts with different tissues of the FRT using human cervical explants and in vivo exposure in the rhesus macaque vaginal transmission model. Despite previous claims of the squamous epithelium being an efficient barrier to virus entry, we reveal that HIV-1 can penetrate both intact columnar and squamous epithelial barriers to depths where the virus can encounter potential target cells. In the squamous epithelium, we identify virus entry occurring through diffusive percolation, penetrating areas where cell junctions are absent. In the columnar epithelium, we illustrate that virus does not transverse barriers as well as previously thought due to mucus impediment. We also show a statistically significant correlation between the viral load of inocula and the ability of HIV-1 to pervade the squamous barrier. Overall, our results suggest a diffusive percolation mechanism for the initial events of HIV-1 entry. With these data, we also mathematically extrapolate the number of HIV-1 particles that penetrate the mucosa per coital act, providing a biological description of the mechanism for HIV-1 transmission during the acute and chronic stages of infection.

Uterine neoplasms, version 1.2014.

Adenocarcinoma of the endometrium (also known as endometrial cancer or more broadly as uterine cancer or carcinoma of the uterine corpus) is the most common malignancy of the female genital tract in the United States. An estimated 49,560 new uterine cancer cases will occur in 2013, with 8190 deaths resulting from the disease. Uterine sarcomas (stromal/mesenchymal tumors) are uncommon malignancies, accounting for approximately 3% of all uterine cancers. The NCCN Guidelines for Uterine Neoplasms describe malignant epithelial carcinomas and uterine sarcomas; each of these major categories contains specific histologic groups that require different management. This excerpt of these guidelines focuses on early-stage disease.

Venous thromboembolism in advanced ovarian cancer patients undergoing frontline adjuvant chemotherapy.

OBJECTIVE: The aim of this study was to define the incidence and prognostic significance of venous thromboembolism (VTE) in patients with advanced, epithelial ovarian cancer undergoing frontline adjuvant chemotherapy after an extended period (28 days) of postoperative prophylaxis. METHODS: A retrospective analysis of patients with advanced, epithelial ovarian cancer who underwent surgery and chemotherapy at a single institution from January 2008 through December 2011 was performed. Exclusion criteria were history of VTE, VTE during the postoperative period, clear cell histology, use of anticoagulation for a different indication, and lack of compliance with 28 days of postoperative prophylaxis with a low-molecular-weight heparin. Baseline patient demographics and oncologic outcomes were analyzed. Clinically symptomatic VTE was identified and confirmed with imaging studies. Otherwise, VTE was identified on imaging studies done to assess disease status at the conclusion of adjuvant chemotherapy. RESULTS: One hundred twenty-eight patients met criteria for inclusion. Sixteen patients had a reported VTE during the time they were on frontline chemotherapy (12.5%). Nine patients (7%) had a pulmonary embolus, and 8 (6.3%) had a deep vein thrombus. The mean BMI in the group that developed VTE was 28, and in the group without VTE, it was 26.5 (P = 0.23). Three (23%) of the 16 patients who developed VTE had undergone a suboptimal cytoreduction compared with 12 (11%) of the 112 in the group with no VTE (P = 0.4). Six (37%) of the 16 patients who developed VTE during chemotherapy underwent a bowel resection and/or splenectomy during their cytoreductive surgery compared with 18 (16%) of the 112 patients who did not develop VTE (P = 0.079). Eight of the patients in the VTE group had indwelling venous catheters during chemotherapy (50%) compared with 39 (35%) in the group with no VTE (P = 0.27). In the group that developed VTE, there was a trend toward increased preoperative CA-125, higher rates of bowel resection and/or splenectomy during surgery, decreased use of aspirin, and inferior survival. On multivariate analysis, patients who developed VTE had significantly longer postoperative hospital stays (7 vs 5 days [P = 0.009]) and lower rates of complete response (P = 0.01). CONCLUSIONS: A 12.5% risk for VTE merits consideration of prophylaxis during chemotherapy in this cohort. A randomized, controlled trial is needed to clarify whether the benefits of long-term prophylaxis outweigh the risks and costs of such therapy.