E.J. Diver

Carcinosarcoma of the ovary compared to papillary serous ovarian carcinoma: A SEER analysis

OBJECTIVE The aims of this study are to determine if outcomes of patients with ovarian carcinosarcoma (OCS) differ from women with high grade papillary serous ovarian carcinoma when compared by stage as well as to identify any associated clinico-pathologic factors. METHODS The Surveillance, Epidemiology, and End Results (SEER) Program data for all 18 registries from 1998 to 2009 was reviewed to identify women with OCS and high grade papillary serous carcinoma of the ovary. Demographic and clinical data were compared, and the impact of tumor histology on survival was analyzed using the Kaplan-Meier method. Factors predictive of outcome were compared using the Cox proportional hazard model. RESULTS The final study group consisted of 14,753 women. 1334 (9.04%) had OCS and 13,419 (90.96%) had high grade papillary serous carcinoma of the ovary. Overall, women with OCS had a worse five-year, disease specific survival rate, 28.2% vs. 38.4% (P<0.001). This difference persisted for each FIGO disease stages I-IV, with five year survival consistently worse for women with OCS compared with papillary serous carcinoma. Over the entire study period, after adjusting for histology, age, period of diagnosis, SEER registry, marital status, stage, surgery, radiotherapy, lymph node dissection, and history of secondary malignancy after the diagnosis of ovarian cancer, carcinosarcoma histology was associated with decreased cancer-specific survival. CONCLUSIONS OCS is associated with a poor prognosis compared to high grade papillary serous carcinoma of the ovary. This difference was noted across all FIGO stages.

Modest benefit of total parenteral nutrition and chemotherapy after venting gastrostomy tube placement

OBJECTIVE The aim of the study is to review a single institutions experience with gastrostomy tubes (GTs) performed for malignant bowel obstruction from gynecologic cancers. METHODS Women with gynecologic cancers who underwent venting GT placement from 2000 to 2008 were identified and clinical data were extracted. Logistic regression and spearman correlational coefficients were used to determine relationships between variables. Survival analysis was performed using the Kaplan-Meier method and a Cox proportional hazard model. RESULTS We identified 115 women who underwent GT placement, the majority of whom were diagnosed with ovarian cancer (84%). Median time from cancer diagnosis to GT placement was 2.2 years. Median survival following GT placement was 5.6 weeks. A majority (56%) developed GT complications requiring GT revision. While burden of disease as assessed on CT scan by the validated peritoneal cancer index (PCI) was not associated with survival, low CA-125 within one week of GT placement was associated with improved survival (p<0.01). TPN was administered in 36% of women, was associated with concurrent chemotherapy (p<0.001) and a 5 week survival benefit (p<0.01). Chemotherapy after GT was administered in 40% of women and was associated with a 10 week survival benefit (p<0.001). Age-adjusted multivariate analysis identified chemotherapy as the only independent variable associated with survival. CONCLUSIONS Women with malignant bowel obstructions from gynecologic cancers requiring palliative GT placement had a guarded prognosis measured in weeks. Gastrostomy tubes near the end of life had a high rate of complications requiring medical intervention. Chemotherapy after GT was associated with TPN administration, and both were associated with a modest extension in survival.

Uterine leiomyosarcoma: an updated series.

Objective The aim of this study was to analyze and compare the clinicopathologic characteristics, treatment, and survival in patients with uterine leiomyosarcoma (ULMS) during the last 10 years in 3 referral academic centers. Methods All patients with ULMS who underwent treatment at the participating institutions between January 1, 2000, and December 31, 2010, were identified from the tumor registry database. In each case, the diagnosis was confirmed by a dedicated gynecologic pathologist following postsurgery pathology review. The Kaplan-Meier method was used to generate overall survival (OS) data. Factors predictive of outcome were compared using the log-rank test and Cox regression analysis. Results Analysis of 167 women with ULMS with adequate follow-up was performed. One hundred twenty-eight patients (77%) were initially managed at the participating institutions, and 39 (23%) were referred after initial management at a different institution. Ninety-two (55%) had stage I disease, 7 (4%) had stage II, 18 (11%) stage III, and 50 (30%) had stage IV disease. The median OS for women with stage I was 75 months, for stage II 66 months, stage III 34 months, and stage IV 20 months (P < 0.001). For patients with early stage (I and II), race, lower grade, smaller tumor size (<11 cm), low number of mitosis (<25/10 high-power field [HPF]), lymphovascular space invasion, and presence of necrosis were identified as variables with prognostic influence on survival in the univariate analysis. A Cox proportional hazards model identified size 11 cm or greater (hazard ratio, 5.9; P < 0.001) and mitotic count of 25/10 HPF or greater (hazard ratio, 2.3; P = 0.05) as independent predictors of OS. For patients with late stage (stage III and IV), race, stage III versus IV, lower grade, smaller tumor size (<11 cm), and low number of mitosis (<25/10 HPF) were all associated with significantly improved OS. A Cox proportional hazards model identified mitotic count of 25/10 HPF or greater (P = 0.01) as independent predictor of OS. Conclusions In early stage, size of the tumor and number of mitosis were associated to survival. In contrast to late stage, only mitotic count was associated to survival.

Adherence to evidence-based guidelines for preoperative testing in women undergoing gynecologic surgery.

OBJECTIVE: To examine adherence to evidence-based recommendations for preoperative testing and health care costs associated with excessive testing. METHODS: An institutional review of women who underwent gynecologic surgery between 2005 and 2007 was performed. Data on the type of surgery, age, comorbidities, and perioperative testing was extracted. We noted the preoperative performance of chest X-ray, electrocardiogram, metabolic panel, complete blood count, coagulation studies, liver function tests, and urinalysis. Each test was classified as being guideline-based (appropriate) or non–guideline-based (inappropriate) as described by the National Institute of Clinical Excellence perioperative guidelines. RESULTS: A total of 1,402 patients were identified. Ninety-five percent of patients underwent all of the guideline-recommended preoperative testing. Ninety percent of women underwent at least one nonindicated preoperative test. None of the 749 urinalyses, 407 liver function tests, or 1,046 coagulation studies performed was appropriate. Ninety-nine percent of the 427 chest X-rays ordered were inappropriate. Only 17% of metabolic panels, 36% of electrocardiograms, and 29% of complete blood counts were in accordance with evidence-based guidelines. Inappropriate perioperative tests led to a direct cost of more than

The Therapeutic Challenge of Targeting HER2 in Endometrial Cancer

418,000. Of the inappropriate tests ordered, abnormalities were noted frequently but rarely changed management. CONCLUSION: Adherence to evidence-based recommendations for preoperative testing is poor. Inappropriate preoperative tests represent a major health care expenditure. LEVEL OF EVIDENCE: III

Trends in the treatment of uterine leiomyosarcoma in the Medicare population.

UNLABELLED Endometrial cancer is the most common gynecologic cancer in the United States, diagnosed in more than 50,000 women annually. While the majority of women present with low-grade tumors that are cured with surgery and adjuvant radiotherapy, a significant subset of women experience recurrence and do not survive their disease. A disproportionate number of the more than 8,000 annual deaths attributed to endometrial cancer are due to high-grade uterine cancers, highlighting the need for new therapies that target molecular alterations specific to this subset of tumors. Numerous correlative scientific investigations have demonstrated that the HER2 (ERBB2) gene is amplified in 17%-33% of carcinosarcoma, uterine serous carcinoma, and a subset of high-grade endometrioid endometrial tumors. In breast cancer, this potent signature has directed women to anti-HER2-targeted therapies such as trastuzumab and lapatinib. In contrast to breast cancer, therapy with trastuzumab alone revealed no responses in women with recurrent HER2 overexpressing endometrial cancer, suggesting that these tumors may possess acquired or innate trastuzumab resistance mechanisms. This review explores the literature surrounding HER2 expression in endometrial cancer, focusing on trastuzumab and other anti-HER2 therapy and resistance mechanisms characterized in breast cancer but germane to endometrial tumors. Understanding resistance pathways will suggest combination therapies that target both HER2 and key oncogenic escape pathways in endometrial cancer. IMPLICATIONS FOR PRACTICE This review summarizes the role of HER2 in endometrial cancer, with a focus on uterine serous carcinoma. The limitations to date of anti-HER2 therapy in this disease site are examined, and mechanisms of drug resistance are outlined based on the experience in breast cancer. Potential opportunities to overcome inherent resistance to anti-HER2 therapy in endometrial cancer are detailed, offering opportunities for further clinical study with the goal to improve outcomes in this challenging disease.

Changing trends in lymphadenectomy for endometrioid adenocarcinoma of the endometrium

Objective Uterine leiomyosarcoma (LMS) is a relatively rare malignancy that is associated with a poor prognosis. The rarity of LMS has led to a lack of consensus regarding appropriate treatment. The goal of this study was to identify the role that chemotherapy and radiotherapy have played in the treatment of uterine LMS in the United States as well as the effectiveness of adjuvant treatment. Materials/Methods We used the SEER (Surveillance, Epidemiology, and End Results)-Medicare database to gather information on uterine LMS patients older than the age of 66 years diagnosed between 1992 and 2009. Basic demographic and clinical characteristics were collected. A logistic regression model analysis was performed to determine predictors of treatment. Cox proportional hazards models were used to identify clinical parameters and treatment strategies associated with survival differences. Results Our final study group included 230 patients. We found that the rate of use of chemotherapy and radiotherapy in the treatment of patients with uterine LMS increased over the period investigated. However, we identified no significant survival advantage associated with either mode of therapy. The strongest predictor of survival was stage at diagnosis. The logistic regression model analysis revealed that age at diagnosis, treatment year, stage, and underlying health status were all independent predictors of chemotherapy. Age at diagnosis was also a predictor of radiation therapy. Conclusions The increasing rates of chemotherapy and radiotherapy use in this population seem to be unfounded given the lack of survival benefit. Further investigation into alternative treatment regimens is merited. The prognostic significance of stage at diagnosis indicates the importance of improving early detection of uterine LMS.

Patterns of care, associations and outcomes of chemotherapy for uterine serous carcinoma: analysis of the National Cancer Database.

OBJECTIVE: To describe trends in the use of lymphadenectomy for endometrioid adenocarcinoma of the endometrium between 1998 and 2012. METHODS: A time-trend analysis was conducted using a population-based cancer registry covering 28% of the population of the United States. To quantify differences over the study period time, the frequency of lymphadenectomy and nodal metastasis among women who underwent surgical treatment of endometrioid endometrial adenocarcinoma was compared among consecutive 3- to 4-year periods. Biannual frequency of lymphadenectomy was modeled with Joinpoint regression to identify when potential changes in trends occurred and calculate annual percentage change. RESULTS: A total of 74,365 women who underwent surgery between 1998 and 2012 were analyzed. Frequency of lymphadenectomy increased by 4.2% annually (95% confidence interval [CI] 3.7–4.6) from 1998 to 2007, after which the frequency declined by 1.6% per year (95% CI 0.9–2.2). Between 1998–2000 and 2007–2009, the frequency of lymphadenectomy rose from 48.7% to 65.5% (risk difference 16.8%, 95% CI 15.4–18.1), the proportion of women found to have nodal metastasis increased by 1.1% (95% CI 0.4–1.7), and the frequency of negative lymphadenectomy increased by 15.7% (95% CI 14.3–17.1). The decline in frequency of lymphadenectomy after 2007 was associated a 3.1% (95% CI 2.1–4.1) decline in the rate of negative lymphadenectomy, but no change in the proportion of women found to have nodal metastasis (P=.17). CONCLUSION: The frequency of lymphadenectomy in the surgical treatment of endometrioid endometrial cancer increased by 4.2% annually from 1998 to 2007 and decreased by 1.6% annually from 2007 to 2012. LEVEL OF EVIDENCE: II

The Role of Lymphadenectomy Versus Sentinel Lymph Node Biopsy in Early-stage Endometrial Cancer: A Review of the Literature.

OBJECTIVE Evaluate rates of chemotherapy and radiotherapy delivery in the treatment of uterine serous carcinoma, and compare clinical outcomes of treated and untreated patients. METHODS The National Cancer Database was queried to identify patients diagnosed with uterine serous carcinoma between 2003 and 2011. The impact of chemotherapy on survival was analyzed using the Kaplan-Meier method. Factors predictive of outcome were compared using the Cox proportional hazards model. RESULTS A total of 13,752 patients met the study eligibility criteria. Stage I, II, III, and IV disease accounted for 4355 (31.7%), 1023 (7.4%), 3484 (25.3%), and 2451 (17.8%) of the study population, respectively. 2439 (17.7%) women had unknown stage. Chemotherapy was administered in 4290 (35.4%) patients, radiotherapy to 1673 (12.2%), adjuvant chemo-radiation to 2915 (21.2%), and 4874 (35.4%) of women did not receive adjuvant therapy during the study period. Utilization of chemotherapy became more frequent over time. Over the entire study period, after adjusting for age, period of diagnosis, race, facility location, facility type, insurance provider, socioeconomic status, comorbidity index, lymph node dissection, treatment modality, and stage, there was an association between treatment modality and survival, with the lowest hazard ratio in patients that received chemo-radiation. After adjusting for the same factors in women with stages I and II, chemo-radiation was associated with improved survival compared to patients that received no treatment. Radiotherapy or chemotherapy alone was not associated with improved survival. CONCLUSION Utilization of chemotherapy is increased in this population over the study period from 2003-2012 and more importantly that survival, particularly in advanced stage patients, is improving.

Racial disparities in survival in malignant germ cell tumors of the ovary

Objective:The objective of this study is to review existing data regarding the feasibility, diagnostic performance, and oncologic outcomes of sentinel lymph node biopsy (SLNB) versus lymphadenectomy (LND) in endometrial cancer. Materials and Methods:A PubMed search identified studies on different staging strategies in endometrial cancer, including routine LND, predictive models of selective nodal dissection, and SLNB. Results:There is ongoing controversy over the risk-benefit ratio of LND in assessing nodal involvement in presumed early-stage endometrial cancer. Current experience with sentinel node biopsy suggests high detection rates and low false-negative rates across most series, as well as the increased detection of occult metastatic disease overlooked by conventional pathology. Although data on the long-term oncologic outcomes of sentinel node biopsy in this setting are limited, short-term follow-up shows no immediate impairment of disease-free survival or overall survival rates when compared with LND. Conclusions:SLNB holds promise as a less-morbid and more accurate alternative to LND for determining nodal spread in early-stage endometrial cancer. Further studies are necessary to understand how lymph node status will guide postoperative management and impact survival of women with nodal metastases.