Primary malignant ovarian carcinoid; management and outcomes.

OBJECTIVE: To investigate the clinicopathological characteristics and survival of patients with malignant ovarian carcinoid tumor (OC). MATERIALS AND METHODS: The National Cancer Database was accessed and patients diagnosed between 2004 and 2015 with a OC who did not have a personal history of a tumor at another site were selected. Overall survival (OS) was assessed for patients who had ≥1 month of follow-up. OS rates were estimated following generation of Kaplan-Meier curves and compared with the log-rank test. RESULTS: A total of 588 patients with a median age of 51.5 years were identified. The majority were White (71.6%), had unilateral tumors (94.2%) with a median size of 3.8 cm that were confined to the ovary (88%). Patients with early stage disease (n = 431) had excellent OS compared to those with advanced stage (II-IV) disease (n = 51), p < 0.001; 5-yr OS rates were 95.4% and 53.1% respectively. For patients with stage I disease, there was no difference in OS between those who did (n = 211) and did not (n = 175) have hysterectomy, p = 0.92. For patients with advanced stage disease, administration of adjuvant chemotherapy was not associated with better survival, p = 0.093. CONCLUSIONS: OCs are typically small, unilateral tumors confined to the ovary arising in perimenopausal patients. Survival outcomes are excellent for patients with early stage disease and unilateral salpingo-oophorectomy appears to be curative.

Low-grade serous ovarian cancer: State of the science.

In January 2019, a group of basic, translational, and clinical investigators and patient advocates assembled in Miami, Florida, to discuss the current state of the science of low-grade serous carcinoma of the ovary or peritoneum-a rare ovarian cancer subtype that may arise de novo or following a diagnosis of serous borderline tumor. The purpose of the conference was to review current knowledge, discuss ongoing research by established researchers, and frame critical questions or issues for future directions. Following presentations and discussions, the primary objective was to initiate future collaborations, uniform database platforms, laboratory studies, and clinical trials to better understand this disease and to advance clinical care outside the boundaries of single academic institutions. This review summarizes the state of the science in five principal categories: epidemiology and patient outcomes, pathology, translational research, patient care and clinical trials, and patients' perspective.

Outcomes of minimally invasive surgery for patients with endometrial carcinoma involving the cervix.

OBJECTIVE: Most studies evaluating the oncologic safety of minimally invasive surgery for endometrial cancer focus on patients with stage I disease. The aim of this study was to investigate the outcomes of minimally invasive surgery for patients with endometrial carcinoma involving the cervix. METHODS: Patients diagnosed between January 2010 and December 2015, with clinical stage II endometrial carcinoma, who underwent hysterectomy with lymphadenectomy, were drawn from the National Cancer Database. Inclusion criteria were clinical International Federation of Gynecology and Obstetrics (FIGO 2009) stage II, patients who underwent hysterectomy with lymphadenectomy, and known route of surgery (open or minimally invasive). Patients who received radiation therapy prior to surgery, those who had subtotal/supracervical hysterectomy, or unknown type of hysterectomy were excluded. The exposure of interest was performance of minimally invasive surgery either laparoscopic or robotic-assisted. Overall survival (primary endpoint) was assessed for patients diagnosed between January 2010 and December 2014 following generation of Kaplan-Meier curves and compared with the log-rank test. A Cox model was constructed to control for confounders. RESULTS: A total of 2175 patients were identified and 1282 (58.9%) had minimally invasive surgery. Of these, 339 and 943 patients had laparoscopic or robotic-assisted laparoscopic hysterectomy, respectively. Minimally invasive surgery was converted to open surgery in 74 (5.8%) patients. Those undergoing minimally invasive surgery had shorter hospital stay (median 1 vs 3 days, p<0.001), lower unplanned readmission rate (2.7% vs 4.7%, p=0.014), and 90-day mortality (0.8% vs 1.8%, p=0.05). Patients who had open surgery (n=796) had worse overall survival compared with those who had minimally invasive surgery (n=1048, p=0.003); 3-year overall survival rates were 76.8% and 83.6%, respectively. After controlling for patient age, race, type of insurance, presence of co-morbidities, performance of extensive lymphadenectomy, presence of positive lymph nodes, tumor histology, presence of lymphovascular space invasion, tumor size, and administration of radiotherapy, performance of minimally invasive surgery was not associated with worse survival (HR 0.90, 95% CI 0.73 to 1.11). CONCLUSIONS: In this retrospective analysis, minimally invasive surgery in patients with stage II endometrial carcinoma was associated with superior short-term peri-operative outcomes and improved 3-year overall survival.

Is hysterectomy necessary for the treatment of preinvasive stratified mucin producing intraepithelial lesions of the cervix?

OBJECTIVES: Stratified mucin producing intraepithelial lesion (SMILE) is an uncommon premalignant cervical intraepithelial lesion, characterized by histopathologic features resembling those observed in high grade squamous intraepithelial lesions and adenocarcinoma in situ of the cervix. Its hybrid morphology poses a pathologic challenge with no specific management guidelines. The goal of this study was to review the natural history of SMILE and treatment based outcomes. METHODS: A retrospective pathology review of all cases of cervical intraepithelial lesions, with confirmation of all SMILE lesions, at one institution between 2007 and 2019, was performed. Clinical and pathologic characteristics, management options, and patient outcomes were reviewed and analyzed. Inclusion criteria included all patients diagnosed initially with SMILE on biopsy, excisional procedure, or simple hysterectomy. Patients diagnosed with SMILE had to fulfill the following pathologic features: stratified columnar epithelium with nuclear atypia and mucin production throughout the epithelial thickness with increased mitotic activity, and/or apoptotic bodies. Pathologic slides were re-evaluated by a pathologist to confirm the diagnosis and review margin status. RESULTS: 24 patients with SMILE were identified. Mean age at diagnosis was 36.2 years (range 25-53) with 67% (16/24) diagnosed before the age of 40. The majority (54%, 13/24) were nulliparous and 63% (15/24) had a past history of abnormal Pap smears. 92% (22/24) of patients were positive for high risk human papillomavirus, with 13% (n=3) presenting with a normal Pap smear. Diagnosis was made primarily on colposcopy (n=16), cold knife cone/loop electrosurgical excision procedure (n=7), or hysterectomy (n=1). Most patients (71%, 17/24) had a co-existing precancerous lesion at the time of diagnosis and the most common was high grade squamous intraepithelial lesion (53%). Five invasive lesions were also identified at the time of diagnosis of SMILE (2 adenocarcinoma, 3 adenosquamous), 1 of which underwent chemoradiation. Among all patients, 25% (6/24) underwent hysterectomy (4 simple, 2 radical), while 63% (17/24) of patients underwent a fertility sparing excisional procedure; 4% (1/24) were incidentally diagnosed on hysterectomy. 18 patients had negative margins and 2 patients had positive margins. Over a median follow-up of 29 months (range 3-105), all of the fertility sparing patients with negative margins had no recurrence. Among the two patients with positive margins, one had no recurrence on repeat excision and the other underwent repeat excision with persistent SMILE identified, subsequent negative margin, and no recurrence since. DISCUSSION: Our data showed that most patients with SMILE were young, positive for high risk human papillomavirus, nulliparous, and presented with coexisting lesions. Excisional procedures with negative margins may be sufficient fertility sparing treatment in patients with preinvasive SMILE with a low risk of recurrence. There should be consideration of hysterectomy at the completion of childbearing.

Universal endometrial cancer tumor typing: How much has immunohistochemistry, microsatellite instability, and MLH1 methylation improved the diagnosis of Lynch syndrome across the population?

BACKGROUND: Universal tumor testing for defective DNA mismatch repair (MMR) is recommended for all women diagnosed with endometrial cancer to identify those with underlying Lynch syndrome. However, the effectiveness of these screening methods in identifying individuals with Lynch syndrome across the population has not been well studied. The aim of this study was to evaluate outcomes of MMR immunohistochemistry (IHC), mutL homolog 1 (MLH1) methylation, and microsatellite instability (MSI) analysis among patients with endometrial cancer. METHODS: A complete systematic search of online databases (PubMed, EMBASE, MEDLINE, and the Cochrane Library) for 1990-2018 was performed. A DerSimonian-Laird random effects model meta-analysis was used to estimate the weighted prevalence of Lynch syndrome diagnoses. RESULTS: The comprehensive search produced 4400 publications. Twenty-nine peer-reviewed studies met the inclusion criteria. Patients with endometrial cancer (n = 6649) were identified, and 206 (3%) were confirmed to have Lynch syndrome through germline genetic testing after positive universal tumor molecular screening. Among 5917 patients who underwent tumor IHC, 28% had abnormal staining. Among 3140 patients who underwent MSI analysis, 31% had MSI. Among patients with endometrial cancer, the weighted prevalence of Lynch syndrome germline mutations was 15% (95% confidence interval [CI], 11%-18%) with deficient IHC staining and 19% (95% CI, 13%-26%) with a positive MSI analysis. Among 1159 patients who exhibited a loss of MLH1 staining, 143 (13.7%) were found to be MLH1 methylation-negative among those who underwent methylation testing, and 32 demonstrated a germline MLH1 mutation (2.8% of all absent MLH1 staining cases and 22.4% of all MLH1 methylation-negative cases). Forty-three percent of patients with endometrial cancer who were diagnosed with Lynch syndrome via tumor typing would have been missed by family history-based screening alone. CONCLUSIONS: Despite the widespread implementation of universal tumor testing in endometrial cancer, data regarding testing results remain limited. This study provides predictive values that will help practitioners to evaluate abnormal results in the context of Lynch syndrome and aid them in patient counseling.

Impact of hospital surgical volume on complete gross resection (CGR) rates following primary debulking surgery for advanced stage epithelial ovarian carcinoma.

BACKGROUND: To investigate the impact of hospital surgical volume on the rate of complete gross resection for patients with advanced stage epithelial ovarian carcinoma undergoing primary debulking surgery. METHODS: The National Cancer Data Base was used to identify patients undergoing between 2010 and 2014 for an advanced stage (III-IV) epithelial ovarian cancer. For analyses purposes facility surgical volume was divided into tertiles (high, intermediate and low). Patients with bulky stage III disease who underwent primary debulking surgery with known residual disease status were selected for further analysis. RESULTS: A total of 8894 patients with macroscopic peritoneal disease were included. Rates of complete gross resection for patients managed in low, intermediate and high-volume centers were 41.0%, 41.6% and 43.3% respectively (p = 0.20). After controlling for year of diagnosis, age, insurance status, presence of co-morbidities, histology, size of peritoneal implants, stage, and complexity of surgery, patients undergoing primary debulking surgery at low (OR: 0.85, 95% CI: 0.74, 0.97, p = 0.013) and intermediate (OR: 0.90, 95% CI: 0.82, 0.99, p = 0.043) volume centers had a lower likelihood of achieving complete gross resection compared to those managed in high volume centers. CONCLUSIONS: After controlling for multiple potential confounders, patients receiving surgery in high volume centers had a higher likelihood of complete gross resection following primary debulking surgery for advanced-stage epithelial ovarian cancer.

Prognostic significance of residual disease in advanced stage malignant ovarian germ cell tumors.

OBJECTIVE: To investigate the prognostic significance of complete gross resection following cytoreductive surgery for patients with advanced stage malignant ovarian germ cell tumors. METHODS: The National Cancer Data Base was accessed and patients diagnosed with an advanced stage (II-IV) malignant ovarian germ cell tumor who underwent primary cytoreductive surgery between 2011 and 2014 were selected for further analysis. For analysis purposes two groups were formed: patients with complete gross resection and those with macroscopic residual disease. Demographic and clinico-pathological characteristics were compared with the chi-square and Mann-Whitney U test. Univariate survival analysis was performed with the log-rank test after generation of Kaplan-Meier curves, while a Cox proportional hazard model was constructed to evaluate mortality after controlling for confounders. RESULTS: A total of 343 patients who met the inclusion criteria were identified. Residual disease status was available for 276 patients: the rate of complete gross resection was 69.2 %. By univariate analysis there was no difference in overall survival between patients in the complete gross resection and macroscopic residual disease groups, P= 0.26; 3-year overall survival rates: 86.4 % and 82.8 %, respectively. No difference in overall survival was noted following stratification by histology; P = 0.64 and P = 0.24 for dysgerminoma and non-dysgerminoma tumor groups. After controlling for stage IV disease, histology and the administration of chemotherapy, macroscopic residual disease was not associated with a worse mortality (HR: 1.22, 95% CI: 0.61 to 2.46). CONCLUSIONS: Macroscopic residual disease following primary cancer-directed surgery was not associated with a worse prognosis in a cohort of patients with advanced stage malignant ovarian germ cell tumors.

Minimally Invasive Staging of Apparent Stage I Malignant Ovarian Germ Cell Tumors: Prevalence and Outcomes.

STUDY OBJECTIVE: Evaluate the prevalence, trends, and outcomes of minimally invasive surgical (MIS) staging of malignant ovarian germ cell tumors (MOGCTs) apparently confined to the ovary. DESIGN: Retrospective cohort study (Canadian Task Force classification II-2). SETTING: Participating hospitals in the National Cancer Data Base. PATIENTS: Women diagnosed between 2010 and 2014 with a MOGCT apparently confined to the ovary with information on the planned surgical approach. INTERVENTIONS: Staging with MIS or laparotomy. MEASUREMENT AND MAIN RESULTS: A total of 918 patients were identified. MIS was planned for 294 patients (32%): a laparoscopic approach for 237 patients and a robotic-assisted approach for 57 patients. Rate of conversion to laparotomy was 11% (46 cases), 1.7% and 15.6% in the robotic and laparoscopy groups, respectively (p = .003). No difference in the use of MIS was noted based on year of diagnosis (p = .38). By multivariate analysis white race, higher level of education, and smaller tumor size were associated with the receipt of MIS. Patients in the MIS group were less likely to undergo lymph node dissection (39.6% vs 51.3%, p = .001) and omentectomy (18.7% vs 28.5%, p = .002). Hospital stay after surgery was shorter for patients who had MIS (median, 2 vs 3 days; p <.001). Unplanned 30-day readmission rate was also lower in the MIS group (1.4% vs 3.9%, p = .043). No difference in overall survival was noted between the 2 groups (p = .81). CONCLUSION: MIS for apparent early-stage MOGCTs was less comprehensive but associated with a decreased hospital stay and unplanned readmission rate.

Novel Fumarate Hydratase Mutation in Siblings With Early Onset Uterine Leiomyomas and Hereditary Leiomyomatosis and Renal Cell Cancer Syndrome.

Hereditary leiomyomatosis renal cell cancer syndrome is an autosomal dominant disorder characterized by uterine and cutaneous leiomyomas and increased predisposition to renal cell carcinoma, papillary type II. The syndrome is caused by heterozygous mutations to the fumarate hydratase (FH) gene located on chromosome 1. Affected females generally present with early onset, atypical uterine leiomyomas and cutaneous findings, however, delays in diagnosis are very common in patients with isolated uterine findings. We present a case series of 2 sisters in their 20s who presented with isolated uterine leiomyomas and were found to carry a novel mutation for the fumarate hydratase gene. One patient was referred for treatment of infertility and recurrent miscarriages and the other was referred for acute symptomatic anemia due to myomas. Prompt diagnosis of hereditary leiomyomatosis renal cell cancer was made due to a high index of clinical suspicion based on early onset disease and familial clustering as well as characteristic pathologic findings on uterine leiomyoma surgical specimen. Timely diagnosis not only allowed for genetic counseling and renal cancer surveillance, but also for fertility counseling given the increased morbidity associated with uterine leiomyoma due to hereditary leiomyomatosis and renal cell cancer syndrome.

Small Cell Carcinoma of the Ovary: A Rare Tumor With a Poor Prognosis.

OBJECTIVE: The aim of this study was to investigate the demographic and clinicopathological characteristics and prognosis of women diagnosed with small cell carcinoma of the ovary. METHODS: The National Cancer Data Base was accessed, and women diagnosed with small cell carcinoma of the ovary, between 2004 and 2014 were identified. Median and 3- and 5-year overall survival (OS) rates were calculated following generation of Kaplan-Meir curves and compared with the log-rank test. A Cox multivariate model was constructed to identify variables associated with mortality. RESULTS: A total 469 women were identified with a median age of 39 years; 81.7% of tumors were unilateral, whereas median size was 13 cm. Only 20.1% of patients had stage I disease. Women who underwent cancer-directed surgery had a 5-year OS rate of 24.1%. Five-year OS rates were 48.6%, 30.7%, 18%, and 12.3% for those with stages I, II, III, and IV disease, respectively, P < 0.001. Younger age (P = 0.013) and the combination of surgery with chemotherapy (CT) (P < 0.001) were associated with superior OS. By multivariate analysis, earlier disease stage and use of CT, but not patient age or performance of lymphadenectomy, were associated with lower mortality. CONCLUSIONS: Small cell carcinomas of the ovary are unilateral tumors primarily arising in premenopausal women. Multimodal treatment with cancer-directed surgery and CT results in a modest increase of a generally poor survival.

Management and prognosis of ovarian yolk sac tumors; an analysis of the National Cancer Data Base.

OBJECTIVE: To evaluate the clinico-pathological characteristics, management and prognosis of women diagnosed with ovarian yolk sac tumors (OYSTs). METHODS: The U.S National Cancer Data Base was queried for women diagnosed with OYST between 2004 and 2014. Overall survival (OS) was calculated following generation of Kaplan-Meir curves. Univariate analysis was performed with the log-rank test. A Cox model was constructed to determine independent predictors of mortality. RESULTS: A total of 561 women were identified with a median age of 23years. The majority (58.5%) had early stage (I-II), while 29.6% and 11.9% had stage III and IV disease respectively. Five-year OS for women with stage I, II, III and IV disease were 94.8%, 97.1%, 70.9% and 51.6% respectively, p<0.001. Better 5-yr OS was observed for adolescents (94.4%) and young adults (89.3%) compared to older premenopausal (67.6%) and postmenopausal women (30.6%), p<0.001. Omentectomy, hysterectomy and lymph node sampling/dissection (LND) were not associated with better OS. Women who received adjuvant chemotherapy had superior OS compared to those who did not, p=0.016. Early disease stage, younger age and receipt of adjuvant chemotherapy, but not LND were independently associated with better mortality. CONCLUSIONS: Women with OYST commonly present with early stage disease. Administration of adjuvant chemotherapy, early stage and younger age are associated with superior outcomes.

Fertility-preserving surgery for advanced stage ovarian germ cell tumors.

OBJECTIVE: To evaluate the prevalence and safety of uterine preservation among premenopausal women diagnosed with a malignant ovarian germ-cell tumor (MOGCT) of advanced stage (stage II-IV). MATERIALS AND METHODS: The National Cancer Database was accessed and a cohort of women aged <40years, diagnosed with a MOGCT were identified. Those with stage II-IV disease who underwent cancer-directed surgery and received chemotherapy were selected for further analysis. Performance of hysterectomy was assessed from site-specific surgery codes. Overall survival (OS) was determined following generation of Kaplan-Meier curves and compared with the log-rank test. A Cox multivariate model was constructed to control for possible confounders. RESULTS: A total of 526 eligible patients were identified; rate of hysterectomy was 20.2%. Women who had a hysterectomy were older (median age 30.5 vs 20years, p<0.001) and more likely to present with bilateral tumors (12.6% vs 3.8%, p<0.001). No differences were noted based on tumor histology (p=0.67). Rate of uterine preservation was 82.8%, 79.5% and 75% for those with stage II, III and IV disease respectively (p=0.46). There was no difference in OS between women who had hysterectomy and those who did not (p=0.051); five-year OS rates were 87.1% and 94.4% respectively. After controlling for disease stage, tumor histology and patient race, uterine preservation was not associated with a decreased survival (HR: 0.59, 95% CI: 0.28, 1.24, p=0.19). CONCLUSIONS: Uterine preservation was not associated with decreased survival and should be considered in women with advanced stage GCTs interested in future fertility.

Should epithelial ovarian carcinoma metastatic to the inguinal lymph nodes be assigned stage IVB?

OBJECTIVE: According to the revised FIGO staging system women with ovarian carcinoma and inguinal lymph node (LN) metastases, formerly stage III, are now considered stage IVB. In this study we compare their survival to that of women with stage III and stage IV disease. METHODS: Women diagnosed with epithelial ovarian carcinoma were drawn from the Surveillance, Epidemiology, and End Results database (2004-2013). Four groups were formed: group 1 (stage IV due to positive inguinal nodes), group 2 (stage III with positive para-aortic/pelvic nodes), group 3 (stage IV with positive distant nodes) and group 4 (stage IV with distant metastases). Overall (OS) and cancer-specific survival (CSS) rates were evaluated with the Kaplan-Meier method. The log-rank test and Cox-hazard models were employed for univariate and multivariate survival analysis. RESULTS: A total of 11,152 women were identified. Five-year OS for women in group 1 (n=151) was 46.3% compared to 44.9% for those in group 2 (n=4,403) (p=0.4), 32.9% in group 3 (n=642) (p<0.001) and 25.3% in group 4 (n=5,956) (p<0.001). After controlling for age, race and histology, group 1 had improved overall and cancer-specific mortality compared to groups 3 and 4 but not group 2. CONCLUSIONS: Ovarian cancer patients with stage IV ovarian cancer due solely to inguinal nodal metastases have similar survival as those with pelvic/para-aortic nodal involvement and improved survival compared to those harboring distant metastases. Our findings do not support the reclassification of these patients as stage IVB.

Adjuvant radiation therapy in uterine carcinosarcoma: A population-based analysis of patient demographic and clinical characteristics, patterns of care and outcomes.

OBJECTIVE: To examine clinical and demographic characteristics of a population-based cohort of patients with uterine carcinosarcoma (UCS), to assess access to treatment and survival patterns. METHODS: Surveillance, Epidemiology and End Results database was queried for patients diagnosed in 1999-2010 and treated with surgery with or without adjuvant radiation therapy (aRT). The Kaplan-Meier method was used to estimate survival functions, and Cox proportional hazards regression - to analyze the effect of covariates on survival. RESULTS: 2342 patients were eligible. African Americans presented with more advanced AJCC stages than other races (35.4% vs. 29.1%; p<0.01). African Americans vs. others, and women diagnosed in 1999-2004 vs. in 2005-2010, received aRT at a similar rate: 36.5% vs. 39.9% (p=NS), and 39.5% vs. 38.9% (p=NS), respectively. There was a trend towards higher aRT utilization among patients younger than 65 vs. older (41.4% vs. 37.5%; p<0.06). We observed better overall and cause-specific survival in the aRT group: 42 vs. 22 (p<0.0001) and 57 vs. 28months (p<0.0001), respectively. Black race, diagnosis in 1999-2004, advanced stage and age≥65years carried a higher risk of UCS death. CONCLUSIONS: We observed greater survival rate in the aRT group. African Americans were more likely to present with later stage disease and die of UCS than non-African Americans. Age and stage, but not race, influenced receipt of aRT. Patients treated more recently survived longer.

Inhibition of autophagy in peripheral blood mononuclear cells by vaginal fluid from women with a malignant adnexal mass.

Inhibition of autophagy is a characteristic of ovarian cancer. We determined whether inhibition of autophagy by vaginal fluid could provide a non-invasive test for cancer risk stratification in women presenting with an adnexal mass. Vaginal fluid supernatants from 90 women undergoing evaluation for a suspicious adnexal mass were incubated with peripheral blood mononuclear cells (PBMCs) obtained from healthy women under conditions that induce autophagy. Rapamycin, an autophagy inducer, was added to some cultures. After 48 hr the cells were collected, lysed and assayed by ELISA for intracellular p62 concentration. p62 is a cytoplasmic protein that is consumed during autophagy induction. Its concentration is inversely proportional to the extent of autophagy induction. Clinical information including pathological diagnoses was obtained after completion of laboratory studies. Mean p62 levels were 9.4 ng/ml in the 21 women with a subsequent malignant diagnosis, 4.5 ng/ml in the eight women with a borderline tumor diagnosis and 3.6 ng/ml in the 61 women with benign disease (p < 0.0001, malignant vs. others). When rapamycin was added to the vaginal fluid-PBMC co-incubation, p62 levels in samples from women with a malignant diagnosis decreased to 3.3 ng/ml, a level comparable to what was observed with the nonmalignant samples. Vaginal fluid inhibition of autophagy can differentiate between women with malignant and benign adnexal masses.

Reproductive and oncologic outcomes after progestin therapy for endometrial complex atypical hyperplasia or carcinoma.

OBJECTIVES: This study evaluated fertility and oncological outcomes in women with complex atypical hyperplasia (CAH) or nonmyoinvasive grade 1 endometrioid endometrial carcinoma (EM) who desired fertility-sparing therapy. STUDY DESIGN: The retrospective cohort study included women younger than 45 years with CAH or EM who desired fertility-sparing treatment at our institution. Only patients for whom both oncological treatment and pregnancy outcomes were available were included. Statistical analyses were performed using a Fisher exact test, Pearson χ(2) test, and Spearman rank correlation test, as appropriate. RESULTS: Seventy-five patients were identified, and 23 (13 CAH, 10 EM) met the inclusion criteria. All 23 patients had at least 1 prior pregnancy. Treatment was split between oral progesterone only (38.5% CAH, 40% EM), levonorgestrel intrauterine device only (30.8% CAH, 20% EM), and both (30.8% CAH, 40% EM). After a median follow-up of 13 months (range, 3-74 months), 9 patients (46.2% CAH, 30% EM, P = .39) had persistent/progressive disease. Eight patients (30.8% CAH, 40% EM, P = .69) ultimately had a hysterectomy, and 3 of these (13.0%) were found to have persistent/progressive disease. Median time from diagnosis to hysterectomy was 13 months (range, 4-56 months). Fourteen of the 23 patients utilized assisted reproductive techniques (60.9%); 12 underwent IVF and 2 chose a gestation carrier. Seven clinical intrauterine pregnancies (30.4%) resulting in 6 live births (26.1%) were found in the entire cohort. CONCLUSION: Fertility-sparing treatment for CAH and grade 1 endometrial cancer is feasible with progestin therapy and leads to clinically meaningful rates of pregnancy in young women who desire fertility.

Molecular alterations of PIK3CA in uterine carcinosarcoma, clear cell, and serous tumors.

OBJECTIVES: Type II endometrial carcinomas-uterine carcinosarcomas or uterine malignant mesodermal mixed tumors (UMMMTs), clear cell carcinomas (UCCs), and uterine serous carcinomas (USCs)-are aggressive malignancies that present with advanced disease and have high mortality rates. PIK3CA mutations are commonly found in endometrial cancers. The objective of the study was to characterize molecular alterations in the PIK3CA gene in these tumors. METHODS: A total of 84 cases (20 UMMMTs, 18 UCCs, and 46 USCs) were selected from the surgical pathology files of Weill Cornell Medical College and Johns Hopkins Hospital. The diagnoses were confirmed by gynecologic pathologists (L.H.E. and A.Y.). DNA was extracted from paraffin-embedded tissue. Polymerase chain reaction was performed for mutational analysis. All the studies were performed in accordance with approved Institutional Review Board protocols. RESULTS: Mutations in the PIK3CA gene were identified in 3 (15%) of 20 UMMMT, 3 (16.7%) of 18 UCC, and 10 (21.7%) of 46 USC cases. We report novel mutations in PIK3CA in uterine carcinosarcoma. CONCLUSIONS: A significant percentage of UMMMTs, UCCs, and USCs have mutations in PIK3CA. Further investigation is needed to develop targeted therapies for these aggressive uterine cancers.

Physician knowledge of and adherence to the revised breast cancer screening guidelines by the United States Preventive Services Task Force.

OBJECTIVE: We sought to assess knowledge and adherence to the revised US Preventive Services Task Force breast cancer screening guidelines among gynecologic care providers. STUDY DESIGN: This was a cross-sectional descriptive study based on a survey conducted among gynecologic care providers. RESULTS: Forty providers completed the survey (80%). In response to the statement "The current recommended age to initiate breast cancer screening is … .," 48.7% of providers responded in accordance with revised guidelines. For the statement "Women between the age of 50 and 74 years old are recommended to have screening mammography," 46.2% of respondents answered in accordance. In response to the statement "The United States Preventative Services Task Force recommends teaching breast self-examination," 71.8% of providers responded in accordance. A total of 37 respondents (92.5%) stated that they were aware of the revised guidelines, but 17 (42.4%) stated that they were applicable to their patient population. CONCLUSION: Knowledge of the revised guidelines appeared to be relatively low in our provider sample.

Surveillance Only for High-risk FIGO Stage IA/IB Malignant Ovarian Germ Cell Tumors: Results From a National Cancer Database.

OBJECTIVES: Investigate the use and outcomes of a surveillance only strategy for patients with high-risk stage I malignant ovarian germ cell tumors. METHODS: Patients with International Federation of Gynecology and Obstetrics stage IA/IB grade 2 or 3 immature teratoma, yolk sac, or mixed germ cell tumor diagnosed between 2004 and 2014 who had at least 1 month of follow-up were drawn from the National Cancer Database. Overall survival (OS) was evaluated for each histologic subtype using Kaplan-Meier curves, and compared with the log-rank test. RESULTS: A total of 497 patients were identified; 115 (23.1%) with grade 2 immature teratoma, 157 (31.6%) with grade 3 immature teratoma, 101 (20.3%) with yolk sac tumor, 124 (25%) with mixed germ cell tumor. Rate of adjuvant chemotherapy was 68.2% (655 patients), while rate of lymph node biopsy/dissection was 55.2%. A total of 19 (3.8%) deaths were observed at a median of 29.8 months. There was no difference in OS between patients who did and did not receive adjuvant chemotherapy with grade 2 (P=0.35) and grade 3 immature teratoma (P=0.47) or mixed germ cell tumors (P=0.55). Patients with yolk sac tumors those who received chemotherapy had better OS compared with those who did not, P=0.019; 5-year OS rates were 92.7% and 79.6%, respectively. CONCLUSIONS: A surveillance only strategy for patients with stage I malignant ovarian germ cell tumors is associated with excellent survival outcomes for patients with grade 2 or 3 immature teratoma or mixed germ cell tumors.

Paclitaxel plus oxaliplatin for recurrent or metastatic cervical cancer: a New York Cancer Consortium Study.

OBJECTIVE: Survival in women with recurrent or metastatic cervical cancer remains poor. More effective and less toxic regimens are needed. Cisplatin is an effective radiosensitizer, but its single agent activity in recurrent cervical cancer, especially after prior cisplatin exposure, is disappointing, with a response rate of only 13%. Oxaliplatin has preclinical activity in cisplatin-resistant tumors and may have synergic activity when combined with paclitaxel. Our objective is to determine the efficacy and toxicity of paclitaxel and oxaliplatin in patients with recurrent or metastatic cervical cancer. METHODS: Patients with histologic confirmation of primary metastatic or recurrent cervical cancer not amenable to surgical management were eligible. Treatment consisted of paclitaxel 175 mg/m(2) IV and oxaliplatin 130 mg/m(2) IV every 21 days. The primary endpoints were toxicity, recorded every cycle, and response, determined by RECIST criteria and were assessed every 9 weeks, with subsequent confirmation as required. Sample size determinations were made using a Simon's two-stage design with a projected overall response proportion of 13% with cisplatin alone. Survival rates were calculated with Kaplan-Meier methods. RESULTS: Of the 35 patients enrolled, 32 were evaluable. The median age was 56 (27-78); 30 had had prior radiation (23 concomitant with cisplatin). Patients completed a mean of 4.2 cycles (1-11). There were 2 complete and 5 partial responses for a total response rate of 7/32 (22%; 95% CI: 9.3%-40.0%). Eight patients had stable disease for an overall clinical benefit rate of 15/32 (47%; 95% CI: 29.1%-65.3%). The mean time to best response was 13.5 weeks (95% CI: 10.6, 16.4). The mean progression-free survival was 21 weeks (95% CI: 14.7, 27.2) and mean overall survival was 52 weeks (95% CI: 39.4, 64.8). A total of 135 cycles were administered. There were 28 (20.1%) grade 3/4 hematologic toxicities and 46 (34.1%) grade 3/4 non-hematologic toxicities, which were predominantly sensory neuropathy. There were 13 treatment delays, 4 dose reductions, and no treatment-related deaths. CONCLUSIONS: The combination of paclitaxel and oxaliplatin is an effective regimen in patients with recurrent or persistent cervical cancer including a majority previously exposed to cisplatin. Further study and comparison with other platinum-based regimens is warranted.