Facilitated referral pathway for genetic testing at the time of ovarian cancer diagnosis: uptake of genetic counseling and testing and impact on patient-reported stress, anxiety and depression.

BACKGROUND: Timely genetic testing at ovarian cancer diagnosis is essential as results impact front line treatment decisions. Our objective was to determine rates of genetic counseling and testing with an expedited genetics referral pathway wherein women with newly-diagnosed ovarian cancer are contacted by a genetics navigator to facilitate genetic counseling. METHODS: Patients were referred for genetic counseling by their gynecologic oncologist, contacted by a genetics navigator and offered appointments for genetic counseling. Patients completed quality of life (QoL) surveys immediately pre- and post-genetic assessment and 6 months later. The primary outcome was feasibility of this pathway defined by presentation for genetic counseling. RESULTS: From 2015 to 2018, 100 patients were enrolled. Seventy-eight had genetic counseling and 73 testing. Median time from diagnosis to genetic counseling was 34 days (range 10-189). Among patients who underwent testing, 12 (16%) had pathogenic germline mutations (BRCA1-7, BRCA2-4, MSH2-1). Sixty-five patients completed QoL assessments demonstrating stress and anxiety at time of testing, however, scores improved at 6 months. Despite the pathway leveling financial and logistical barriers, patients receiving care at a public hospital were less likely to present for genetic counseling compared to private hospital patients (56% versus 84%, P = 0.021). CONCLUSIONS: Facilitated referral to genetic counselors at time of ovarian cancer diagnosis is effective, resulting in high uptake of genetic counseling and testing, and does not demonstrate a long term psychologic toll. Concern about causing additional emotional distress should not deter clinicians from early genetics referral as genetic testing can yield important prognostic and therapeutic information.

Neoadjuvant chemotherapy in patients with advanced endometrial cancer.

OBJECTIVES: Neoadjuvant chemotherapy (NACT) followed by interval debulking surgery (IDS) is a treatment strategy for ovarian cancer patients with unresectable disease or poor performance status (PS). This strategy has been used in the treatment of advanced endometrial cancer and a survival benefit has been shown in patients who are subsequently able to undergo interval cytoreduction. This study sought to review our single institution experience with NACT for advanced endometrial cancer. METHODS: We conducted a retrospective review of all patients who received NACT for advanced endometrial cancer at two institutions in New York City between 2002 and 2016. RESULTS: We identified 39 patients (median age 61, range 35-89). The histologic subtype distribution was: serous (44%), endometrioid (28%), carcinosarcoma (10%), clear cell (8%), mixed (8%), neuroendocrine (3%). Contraindications to primary surgery included: unresectable disease (72%), poor PS (15%), unresectable disease and poor PS (13%). Twenty-three patients (59%) did not undergo IDS due to: progression of disease (70%), medical ineligibility (4%), unresectable disease (17%), lost to follow-up (4%), death (4%). Sixteen patients (41%) underwent IDS, 81% had an optimal cytoreduction. Disease status at NACT completion was: partial response (56%), stable disease (3%) and progression of disease (41%). There were no complete responses. Patients who responded to NACT had a significantly longer overall survival than those who did not (15 vs. 5 months. P = 0.015). IDS was also associated with an improvement in overall survival versus no surgery (16 vs. 6 months, P = 0.04). CONCLUSIONS: Unlike ovarian cancer, less than half of the patients undergoing NACT for endometrial cancer underwent IDS, none had a complete response, and 41% had disease progression during NACT. However, endometrial cancer patients who underwent IDS had a high rate of optimal cytoreduction. Both response to NACT and IDS were associated with improved survival.

Timing is everything: intraperitoneal chemotherapy after primary or interval debulking surgery for advanced ovarian cancer.

PURPOSE: To evaluate the outcomes of intraperitoneal chemotherapy (IP) compared with those of intravenous chemotherapy (IV) in patients with advanced ovarian cancer after neoadjuvant chemotherapy (NACT) and interval debulking surgery (IDS) or primary debulking surgery (PDS). METHODS: Patients with advanced epithelial ovarian carcinoma treated with PDS or NACT and IDS from 2006 to 2015 were identified. Comparative statistics were used to evaluate covariates, and survival rates were calculated using the Kaplan-Meier method and compared with log-rank tests. RESULTS: Sixty-six patients received NACT followed by IDS with residual disease of ≤ 1 cm; 42 of these patients (63.6%) received IP therapy; and 24 patients (36.3%) had IV therapy only after IDS. The median progression-free survival (PFS) was 16.0 months in the IP group and 13.5 months in the IV group (p = 0.13). The estimated median overall survival (OS) was 64.0 months with IP and 50.0 months with IV (p = 0.44). During the same study period, 149 patients underwent optimal PDS after which 93 patients (62.4%) received IP and 56 patients (37.6%) were given IV chemotherapy. Patients after IP demonstrated improved survival outcomes when compared to patients after IV therapy. The median PFS was 28.0 months after IP and 16.5 months after IV (p = 0.0006), and the median OS was not reached for IP and 50.0 months after IV (p < 0.0001). CONCLUSIONS: Although IP chemotherapy after PDS is associated with improved survival, IP therapy after NACT and IDS, despite high rates of completion, may not have the same degree of survival advantage over IV therapy.

Laparoscopy decreases the disparity in postoperative complications between black and white women after hysterectomy for endometrial cancer.

OBJECTIVES: Black race has been associated with increased 30-day morbidity and mortality following surgery for endometrial cancer. Black women are also less likely to undergo laparoscopy when compared to white women. With the development of improved laparoscopic techniques and equipment, including the robotic platform, we sought to evaluate whether there has been a change in surgical approach for black women, and in turn, improvement in perioperative outcomes. METHODS: Using the American College of Surgeons' National Surgical Quality Improvement Project's database, patients who underwent hysterectomy for endometrial cancer from 2010 to 2015 were identified. Comparative analyses stratified by race and hysterectomy approach were performed to assess the relationship between race and perioperative outcomes. RESULTS: A total of 17,692 patients were identified: of these, 13,720 (77.5%) were white and 1553 (8.8%) were black. Black women were less likely to undergo laparoscopic hysterectomy compared to white women (49.3% vs 71.3%, p<0.0001). Rates of laparoscopy in both races increased over the 6-year period; however these consistently remained lower in black women each year. Black women had higher 30-day postoperative complication rates compared to white women (22.5% vs 13.6%, p<0.0001). When laparoscopic hysterectomies were isolated, there was no difference in postoperative complication rates between black and white women (9.2% vs 7.5%, p=0.1). CONCLUSIONS: Overall black women incur more postoperative complications compared to white women undergoing hysterectomy for endometrial cancer. However, laparoscopy may mitigate this disparity. Efforts should be made to maximize the utilization of minimally invasive surgery for the surgical management of endometrial cancer.

Endometrial cancer surveillance adherence reduces utilization and subsequent costs.

OBJECTIVES: In June 2011, the SGO recommended that physical exam and symptoms be the primary surveillance methods in patients with endometrial cancer. We sought to evaluate adherence to these guidelines by comparing the use of CT scans, paps and serum CA125 ordered for endometrial cancer surveillance before and after publication of these guidelines. METHODS: A retrospective review was performed for all patients undergoing surveillance for endometrial cancer at a single institution between June 2009 and June 2013. We assessed the number of patients without symptoms or abnormal physical exam findings who underwent surveillance CT scans, paps and/or CA125 during the 2years pre- and 2years post-SGO guidelines. RESULTS: 92 patients (n=48 pre-6/2011, n=44 post-6/2011) were identified. Mean patient age was 58years. No significant difference in age, ethnicity, body mass index, or disease grade or stage was noted. There was a significant decline in surveillance CT scans (n=13, 27% vs. n=4, 9%, p=0.03), CA125 (n=14, 29% vs. 5, 11%, p=0.035) and paps (n=34, 71% vs. n=8 vs. 18%, p<0.001). There was no significant difference in disease status at the last follow-up. Institutional cost of surveillance also declined ($14,102.46 2years pre-guidelines, $3,054.99 2years post-guidelines). CONCLUSIONS: In a single urban academic public hospital, after only 2years, clinical adherence to the 2011 SGO endometrial cancer surveillance guidelines resulted in a significant decline in the use of CT scans, CA125 and paps. This reduction does not appear to affect patient outcomes and led to an appreciable decrease in surveillance costs.

Multigene panels in Ashkenazi Jewish patients yield high rates of actionable mutations in multiple non-BRCA cancer-associated genes.

OBJECTIVE: To evaluate the results of multigene panel testing among Ashkenazi Jewish compared with non-Ashkenazi Jewish patients. METHODS: We reviewed the medical records for all patients who underwent multigene panel testing and targeted BRCA1/2 testing at a single institution between 6/2013-1/2015. Clinical actionability for identified pathogenic mutations was characterized based on the National Comprehensive Cancer Network (NCCN) guidelines and consensus statements and expert opinion for genes not addressed by these guidelines. RESULTS: Four hundred and fifty-four patients underwent multigene panel screening, including 138 Ashkenazi Jewish patients. The median patient age was fifty-two years. Three hundred and fifty-four patients (78%) had a personal history of cancer. Two hundred and fifty-one patients had breast cancer, 49, ovarian cancer, 26, uterine cancer and 20, colorectal cancer. We identified 62 mutations in 56 patients and 291 variants of uncertain significance in 196 patients. Among the 56 patients with mutations, 51 (91%) had actionable mutations. Twenty mutations were identified by multigene panels among Ashkenazi Jewish patients, 18 of which were in genes other than BRCA1/2. A review of targeted BRCA1/2 testing performed over the same study period included 103 patients and identified six mutations in BRCA1/2, all of which occurred in Ashkenazi Jewish patients. Among all Ashkenazi Jewish patients undergoing genetic testing, 25/183 (14%) had a mutation, 24/25 of which were actionable (96%) and 17/25 patients (68%) had mutations in non BRCA1/2 genes. CONCLUSIONS: With the rapid acceptance of multigene panels there is a pressing need to understand how this testing will affect patient management. While traditionally many Ashkenazi Jewish patients have undergone targeted BRCA1/2 testing, our data suggest consideration of multigene panels in this population as the majority of the results are clinically actionable and often in genes other than BRCA1/2.

The safety of same-day discharge after laparoscopic hysterectomy for endometrial cancer.

OBJECTIVE: To determine factors influencing discharge patterns after laparoscopic hysterectomy for endometrial cancer and to evaluate the safety of same-day discharge during the 30-day postoperative period. METHODS: Using the American College of Surgeons' National Surgical Quality Improvement Project's database, patients who underwent hysterectomy for endometrial cancer from 2010 to 2014 were identified and categorized by their hospital length of stay. Statistical analyses were performed to assess the relationship between hospital stay and demographics, medical comorbidities, intraoperative surgical factors and postoperative outcomes. RESULTS: A total of 9020 patients had laparoscopic hysterectomies for endometrial cancer and of these, 729 patients (8.1%) were successfully discharged on the day of surgery. These patients were younger and had lower body mass indexes and fewer medical comorbidities than patients who were admitted after their procedure. The same-day discharge group underwent surgical procedures of less complexity than the hospital admission group based on shorter operative times and fewer relative value units (RVUs). There was a lower rate of surgical site infections in the same-day discharge group, and no difference in rates of other postoperative complications including hospital readmissions and reoperations. CONCLUSIONS: Rates of laparoscopic hysterectomy for endometrial cancer are gradually increasing but the rates of same-day discharge have increased at a much slower rate. Same-day discharge has been successful despite differences in preoperative demographics, medical comorbidities and intraoperative surgical complexity. Overall postoperative complication rates were equivalent despite length of hospital stay, demonstrating the safety and feasibility of same-day discharge after laparoscopic hysterectomy for endometrial cancer.

Dual mTORC1/2 Inhibition as a Novel Strategy for the Resensitization and Treatment of Platinum-Resistant Ovarian Cancer.

There is considerable interest in the clinical development of inhibitors of mTOR complexes mTORC1 and 2. Because mTORC1 and its downstream mRNA translation effectors may protect against genotoxic DNA damage, we investigated the inhibition of mTORC1 and mTORC1/2 in the ability to reverse platinum resistance in tissue culture and in animal tumor models of serous ovarian cancer. Cell survival, tumor growth, PI3K-AKT-mTOR pathway signaling, DNA damage and repair response (DDR) gene expression, and translational control were all investigated. We show that platinum-resistant OVCAR-3 ovarian cancer cells are resensitized to low levels of carboplatin in culture by mTOR inhibition, demonstrating reduced survival after treatment with either mTORC1 inhibitor everolimus or mTORC1/2 inhibitor PP242. Platinum resistance is shown to be associated with activating phosphorylation of AKT and CHK1, inactivating phosphorylation of 4E-BP1, the negative regulator of eIF4E, which promotes increased cap-dependent mRNA translation and increased levels of CHK1 and BRCA1 proteins. Animals with platinum-resistant OVCAR-3 tumors treated with carboplatin plus mTORC1/2 inhibition had significantly longer median survival and strikingly reduced metastasis compared with animals treated with carboplatin plus everolimus, which inhibits only mTORC1. Reduced tumor growth, metastasis, and increased survival by mTORC1/2 inhibition with carboplatin treatment was associated with reduced AKT-activating phosphorylation and increased 4E-BP1 hypophosphorylation (activation). We conclude that mTORC1/2 inhibition is superior to mTORC1 inhibition in reversing platinum resistance in tumors and strongly impairs AKT activation, DNA repair responses, and translation, promoting improved survival in the background of platinum resistance. Mol Cancer Ther; 15(7); 1557-67. ©2016 AACR.

Preoperative experience for public hospital patients with gynecologic cancer: Do structural barriers widen the gap?

BACKGROUND: Widespread disparities in care have been documented in women with gynecologic cancer in the United States. This study was designed to determine whether structural barriers to optimal care were present during the preoperative period for patients with gynecologic cancer. METHODS: A retrospective review was conducted for patients undergoing surgery for a gynecologic malignancy at a public hospital or a private hospital staffed by the same team of gynecologic oncologists between July 1, 2013 and July 1, 2014. RESULTS: Two hundred fifty-seven cases were included for analysis (public hospital, 69; private hospital, 188). Patients treated at the private hospital were older (58 vs 52 years; P = .004) and had similar medical comorbidities (median Charlson comorbidity index at both hospitals, 6) but required fewer hospital visits in preparation for surgery (2 vs 4; P < .001). Public hospital patients had a longer wait time from the diagnosis of disease to surgery (63 vs 34 days; P < .001). According to a multiple linear regression model, the public hospital setting was associated with a longer interval from diagnosis to surgery with adjustments for the insurance status, age at diagnosis, cancer stage, and number of preoperative hospital visits (P < .001). CONCLUSIONS: Patients at the public hospital were subject to a greater number of preoperative visits and had to wait longer for surgery than patients at the private hospital. Attempts to reduce health care disparities should focus on improving efficiency in health care delivery systems once contact has been established.

Appropriate Recommendations for Surgical Debulking in Stage IV Ovarian Cancer.

OPINION STATEMENT: Epithelial ovarian cancer continues to be the leading cause of death due to gynecologic malignancy, and it is the fifth leading cause of cancer death in women in the USA and seventh worldwide. In most women with ovarian cancer, the disease is diagnosed at an advanced stage and primary cytoreductive surgery is considered standard of care. Traditionally, the gynecologic oncology literature supports the dictum that aggressive radical debulking to reduce intra-abdominal tumor burden to minimal or less than 1 cm of disease has significant impact on overall survival. However, the European Organization for Research and Treatment of Cancer (EORTC) trial found that survival after neoadjuvant followed by interval debulking surgery was similar to survival with the standard approach of primary surgery followed by chemotherapy. Many gynecologic oncologists have now adopted neoadjuvant chemotherapy for the treatment of stage IV ovarian cancer given the complex nature of this disease. Currently, there are conflicting results in the literature with regards to neoadjuvant chemotherapy versus primary debulking for stage IV ovarian cancer. While there is evidence that neoadjuvant treatment is not inferior to primary debulking, the literature also supports that maximizing debulking efforts with radical surgery can provide a survival benefit in patients with stage IV ovarian carcinoma.

Use of a Flexible Inflatable Multi-Channel Applicator for Vaginal Brachytherapy in the Management of Gynecologic Cancer.

INTRODUCTION: Evaluate use of novel multi-channel applicator (MC) Capri™ to improve vaginal disease coverage achievable by single-channel applicator (SC) and comparable to Syed plan simulation. MATERIALS AND METHODS: Twenty-eight plans were evaluated from four patients with primary or recurrent gynecologic cancer in the vagina. Each received whole pelvis radiation, followed by three weekly treatments using HDR brachytherapy with a 13-channel MC. Upper vagina was treated to 5 mm depth to 1500 cGy/3 fractions with a simultaneous integrated boost totaling 2100 cGy/3 fractions to tumor. Modeling of SC and Syed plans was performed using MC scans for each patient. Dosimetry for MC and SC plans was evaluated for PTV700 cGy coverage, maximum dose to 2 cm(3) to bladder, rectum, as well as mucosal surface points. Dosimetry for Syed plans was calculated for PTV700 cGy coverage. Patients were followed for treatment response and toxicity. RESULTS: Dosimetric analysis between MC and SC plans demonstrated increased tumor coverage (PTV700 cGy), with decreased rectal, bladder, and contralateral vaginal mucosa dose in favor of MC. These differences were significant (p < 0.05). Comparison of MC and Syed plans demonstrated increased tumor coverage in favor of Syed plans which were not significant (p = 0.71). Patients treated with MC had no cancer recurrence or ≥grade 3 toxicity. CONCLUSION: Use of MC was efficacious and safe, providing superior coverage of tumor volumes ≤1 cm depth compared to SC and comparable to Syed implant. MC avoids excess dose to surrounding organs compared to SC, and potentially less morbidity than Syed implants. For tumors extending ≤1 cm depth, use of MC represents an alternative to an interstitial implant.

Cross-Sectional Study of the Impact of a Natural Disaster on the Delivery of Gynecologic Oncology Care.

OBJECTIVE: We aimed to compare access to gynecologic oncology care at a private and a city hospital, both of which closed for a period of time because of Hurricane Sandy. METHODS: This was a cross-sectional study of gynecologic oncology chemotherapy, radiotherapy, and surgical patients from October 29, 2012 (the eve of the storm), to February 7, 2013 (the reopening of the city hospital). New referrals during this time were excluded. Delays in chemotherapy, radiotherapy, and surgery were compared. RESULTS: Analysis included 113 patients: 59 private patients (52.2%) and 54 city patients (47.8%). Of the private patients, 33/59 received chemotherapy (55.9%), 1/59 received radiotherapy (1.7%), and 28/59 had planned surgery (47.5%). Of the city patients, 40/54 received chemotherapy (74.1%), 7/54 received radiotherapy (12.3%), and 18/54 had planned surgery (33.3%). The mean delay in chemotherapy was 7.6 days at the private hospital and 21.7 days at the city hospital (P=0.0004). The mean delay in scheduled surgery was 14.2 days at the private hospital and 22.7 days at the city hospital (P=0.3979). The mean delay in radiotherapy was 0.0 days at the private hospital and 25.0 days at the city hospital (P=0.0046). Loss to follow-up rates were 3/59 of the private patients (5.1%) and 3/54 of the city patients (5.6%). CONCLUSIONS: Gynecologic oncology care was maintained during a natural disaster despite temporary closure and relocation of services. Disparity in care was in access to chemotherapy.

Surveillance epidemiology and end results analysis demonstrates improvement in overall survival for cervical cancer patients treated in the era of concurrent chemoradiotherapy.

BACKGROUND: In February 1999, the National Cancer Institute (NCI) issued a clinical alert based on five randomized trials that reported better overall survival (OS) with concurrent chemoradiotherapy (CCRT) than with surgery or radiation alone for locoregional cervical cancer. This study analyzes data from the surveillance epidemiology and end results (SEER) program to evaluate the improvement in survival in the era of CCRT. METHODS: The SEER database was queried for FIGO stages IB2-IVA cervical cancer patients treated with radiotherapy between 1995 and 2002. Patients diagnosed between 1999 and 2002 (CCRT era) were assumed to have received CCRT more frequently than patients diagnosed between 1995 and 1998 (RT era). Cases were stratified by period of diagnosis, age, and SEER region. OS and cause specific survival (CSS) were compared between the two time periods with chi-square log-rank tests. Multivariable Cox models were also used to compare OS and CSS between the two time periods, with adjustment for stratification variables and other covariates. RESULTS: The study included 3517 patients. Unadjusted OS and CSS were significantly improved in 1999-2002 compared with 1995-1998 (OS: p < 0.001, hazard ratio (HR): 0.81; CSS: p < 0.001, HR: 0.79). Significant improvements in OS and CSS were retained after adjustment for multiple variables (multivariable OS HR 0.78; CSS HR 0.76). CONCLUSION: Cervical cancer patients treated with radiotherapy after 1999 had improved OS and CSS compared with patients treated before 1999, likely reflecting increased usage of CCRT. This study adds to the population-level evidence supporting the adoption of CCRT as the standard of care for locoregional cervical cancer.

A prospective comparison of postoperative pain and quality of life in robotic assisted vs conventional laparoscopic gynecologic surgery.

OBJECTIVE: We sought to compare robotic vs laparoscopic surgery in regards to patient reported postoperative pain and quality of life. STUDY DESIGN: This was a prospective study of patients who presented for treatment of a new gynecologic disease requiring minimally invasive surgical intervention. All subjects were asked to take the validated Brief Pain Inventory-Short Form at 3 time points to assess pain and its effect on quality of life. Statistical analyses were performed using Pearson x(2) and Student's t test. RESULTS: One hundred eleven were included in the analysis of which 56 patients underwent robotic assisted surgery and 55 patients underwent laparoscopic surgery. There was no difference in postoperative pain between conventional laparoscopy and robotic assisted surgery for gynecologic procedures. There was a statistically significant difference found at the delayed postoperative period when evaluating interference of sleep, favoring laparoscopy (ROB 2.0 vs LSC 1.0; P = .03). There were no differences found between the robotic and laparoscopic groups of patients receiving narcotics (56 vs 53, P = .24, respectively), route of administration of narcotics (47 vs 45, P > .99, respectively), or administration of nonsteroidal antiinflammatory medications (27 vs 21, P = .33, respectively). CONCLUSION: Our results demonstrate no difference in postoperative pain between conventional laparoscopy and robotic assisted surgery for gynecologic procedures. Furthermore, pain did not appear to interfere consistently with any daily activity of living. Interference of sleep needs to be further evaluated after controlling for bilateral salpingo-oophorectomy.

Is renal thrombotic angiopathy an emerging problem in the treatment of ovarian cancer recurrences?

BACKGROUND AND OBJECTIVE: Ovarian cancer is usually diagnosed at an advanced stage, with most patients undergoing surgery followed by platinum- and taxane-based chemotherapy. After initial clinical remission, the majority recur, leading to additional treatments, including not only platinums and taxanes but also pegylated liposomal doxorubicin (PLD), gemcitabine, topotecan, and, more recently, bevacizumab, which may extend survival times. PLD, in particular, has been extensively studied by our group, with encouraging therapeutic results. We, however, observed instances of chronic kidney disease (CKD) developing among patients who received long-term treatment for recurrent ovarian cancer. To document the frequency and contributing factors to the emergence of CKD, we initiated a retrospective review at two institutions. PATIENTS AND METHODS: Fifty-six consecutive patients with recurrent ovarian cancer receiving treatment at New York University Cancer Institute were reviewed for the presence of renal disease in 1997-2010. At Shaare Zedek Medical Center, 73 consecutive patients with ovarian cancer were reviewed in 2002-2010. Patients were diagnosed with CKD if they had an estimated GFR <60 mL/minute per 1.73 m2 for >3 months and were staged according to the National Kidney Foundation guidelines. RESULTS: Thirteen patients (23%) developed stage ≥3 CKD. Three patients had renal biopsies performed that showed thrombotic microangiopathy. CONCLUSIONS: CKD is emerging as a potential long-term consequence of current chemotherapy for recurrent ovarian cancer.

Surgical options for recurrent uterine sarcomas.

Leiomyosarcoma, the most frequent pure uterine sarcoma, is an aggressive tumor with a tendency toward early relapse. Survival for patients with recurrent disease is poor. In contrast, endometrial stromal sarcoma, the second most common uterine sarcoma, is a more indolent malignancy with a tendency toward recurrence after a long latency period. The relative infrequency of both diseases makes the study and standardization of treatment for recurrent disease challenging. Treatment of recurrence with cytotoxic chemotherapy, radiation therapy, or hormone therapy produces modest to poor response rates. Surgical resection is one treatment modality offering the potential for cure and perhaps a more durable response than is seen with medical management. Although initial studies focused on pulmonary metastasectomy in recurrent soft tissue sarcoma, an increasingly large body of data specifically evaluating outcomes after both thoracic and extrathoracic metastasectomy in patients with recurrent uterine sarcoma is now available. Though no prospective trials have been conducted, retrospective comparisons of chemotherapy or radiation therapy with surgery for recurrent uterine sarcoma suggest improvement in disease-specific survival for the surgery group. Clearly defined factors are associated with better prognosis after surgical resection of recurrence, including a prolonged disease-free interval and complete resection of disease. In properly selected women, surgery and even repeated metastasectomy for recurrent disease may improve survival and should be considered.

Targeting the mTOR/4E-BP pathway in endometrial cancer.

Endometrial cancer is the most common gynecologic malignancy. Although it is highly treatable in the early stages of disease, therapies for advanced and recurrent disease are rarely curative. A molecular and genetic understanding of endometrial cancer involves the mTOR signaling pathway, an emerging target for treatment of type I disease (the most common presentation). Endometrial cancers show a significant reliance on the mTOR pathway for survival, and studies to date have revealed a clinical advantage in targeting this pathway. Less well developed in the study of endometrial cancer is an understanding of mTOR signaling to its major downstream effector, translational control. Given the poor rate of success for treatment of late-stage endometrial cancer, increasing attention is being directed to the development of new therapeutic approaches, including targeting the mTOR pathway. Here, we discuss the potential benefit of targeting mTOR combined with existing chemotherapies by monitoring its impact on translational regulatory pathways and key translation targets in endometrial cancer. We also highlight laboratory and clinical research findings that will provide new avenues for future research and clinical development.