Doubling down on the future of gynecologic oncology: The SGO future of the profession summit report.

The original vision of the field of gynecologic oncology was to establish a multidisciplinary approach to the management of patients with gynecologic cancers. Fifty years later, scientific advances have markedly changed the overall practice of gynecologic oncology, but the profession continues to struggle to define its value-financial and otherwise. These issues were examined in full at the Society of Gynecologic Oncology (SGO) Future of the Profession Summit and the purpose of this document is to summarize the discussion, share the group's perceived strengths, weaknesses, opportunities, and threats (SWOT) for gynecologic oncologists, further educate members and others within the patient care team about the unique role of gynecologic oncologists, and plan future steps in the short- and long- term to preserve the subspecialty's critical mission of providing comprehensive, longitudinal care for people with gynecologic cancers.

A pilot study of lower extremity lymphedema, lower extremity function, and quality of life in women after minimally invasive endometrial cancer staging surgery.

OBJECTIVE: The primary aim of this study was to pilot the use of an objective measurement technique to prospectively evaluate the incidence of lower extremity lymphedema (LEL) after minimally invasive staging surgery for endometrial cancer. Secondary objectives included observation of changes in lower extremity function and quality of life in this patient population. METHODS: A prospective evaluation of LEL was performed in 97 women who underwent minimally invasive staging surgery for endometrial cancer using comparative circumferential volume measurements. Postoperative changes in lower extremity function and global quality of life were also assessed using patient-reported outcome measures. RESULTS: Ninety-seven patients were included for lymphedema analysis. The rate of LEL was 25% at 4-6 weeks, 19% at 6-9 months, and 27% at 12-18 months postoperatively. The presence of LEL was associated with a significant worsening from baseline Lower Extremity Functional Scale (LEFS) scores at 4-6 weeks (-27.0% vs -3.7%, p = 0.02) and 6-9 months (-13.0% vs 0%, p = 0.01). LEL was not associated with a change in patient-reported global quality of life. CONCLUSIONS: Up to one in four women experience lymphedema following surgical staging for endometrial cancer, and its presence is associated with diminished lower extremity function. Larger, prospective trials using the objective methodology piloted in this study should better clarify risk factors and long-term outcomes of this morbidity.

Constitutively active ESR1 mutations in gynecologic malignancies and clinical response to estrogen-receptor directed therapies.

OBJECTIVE: Endocrine therapy is often considered as a treatment for hormone-responsive gynecologic malignancies. In breast cancer, activating mutations in the estrogen receptor (mutESR1) contribute to therapeutic resistance to endocrine therapy, especially aromatase inhibitors (AIs). The purpose of this study was to evaluate the frequency and clinical relevance of ESR1 genomic alterations in gynecologic malignancies. METHODS: DNA from FFPE tumor tissue obtained during routine clinical care for 9645 gynecologic malignancies (ovary, fallopian tube, uterus, cervix, vagina, vulvar, and placenta) was analyzed for all classes of genomic alterations (base substitutions (muts), insertions, deletions, rearrangements, and amplifications) in ESR1 by hybrid capture next generation sequencing. A subset of alterations was characterized in laboratory-based transcription assays for response to endocrine therapies. RESULTS: A total of 295 ESR1 genomic alterations were identified in 285 (3.0%) cases. mutESR1 were present in 86 (0.9%) cases and were more common in uterine compared to other cancers (2.0% vs <1%, respectively p < 0.001). mutESR1 were enriched in carcinomas with endometrioid versus serous histology (4.4% vs 0.2% respectively, p < 0.0001 in uterine and 3.5% vs 0.3% respectively, p = 0.0004 in ovarian carcinomas). In three of four patients with serial sampling, mutESR1 emerged under the selective pressure of AI therapy. Despite decreased potency of estrogen receptor (ER) antagonists in transcriptional assays, clinical benefit was observed following treatment with selective ER-targeted therapy, in one case lasting >48 months. CONCLUSIONS: While the prevalence of ESR1 mutations in gynecologic malignancies is low, there are significant clinical implications useful in guiding therapeutic approaches for these cancers.

Reduction in opioid use and postoperative pain scores after elective laparotomy with implementation of enhanced recovery after surgery protocol on a gynecologic oncology service.

OBJECTIVE: Enhanced Recovery After Surgery (ERAS) protocols are designed to mitigate the physiologic stress response created by surgery, to decrease the time to resumption of daily activities, and to improve overall recovery. This study aims to investigate postoperative recovery outcomes following gynecologic surgery before and after implementation of an ERAS protocol. METHODS: A retrospective chart review was performed of patients undergoing elective laparotomy at a major academic center following implementation of an ERAS protocol (11/4/2014-7/27/2016) with comparison to a historical cohort (6/23/2013-9/30/2014). The primary outcome was length of hospital stay. Secondary outcomes included surgical variables, time to recovery of baseline function, opioid usage, pain scores, and complication rates. Statistical analyses were performed using Wilcoxon rank sum, Fisher's exact, and chi squared tests. RESULTS: One hundred and thirty-three women on the ERAS protocol who underwent elective laparotomy were compared with 121 historical controls. There was no difference in length of stay between cohorts (median 4 days; P = 0.71). ERAS participants had lower intraoperative (45 vs 75 oral morphine equivalents; P < 0.0001) and postoperative (45 vs 154 oral morphine equivalents; P < 0.0001) opioid use. ERAS patients reported lower maximum pain scores in the post-anesthesia care unit (three vs six; P < 0.0001) and on postoperative day 1 (four vs six; P = 0.002). There was no statistically significant difference in complication or readmission rates. CONCLUSIONS: ERAS protocol implementation was associated with decreased intraoperative and postoperative opioid use and improved pain scores without significant changes in length of stay or complication rates.

DNA methylation of imprinted gene control regions in the regression of low-grade cervical lesions.

The role of host epigenetic mechanisms in the natural history of low-grade cervical intraepithelial neoplasia (CIN1) is not well characterized. We explored differential methylation of imprinted gene regulatory regions as predictors of the risk of CIN1 regression. A total of 164 patients with CIN1 were recruited from 10 Duke University clinics for the CIN Cohort Study. Participants had colposcopies at enrollment and up to five follow-up visits over 3 years. DNA was extracted from exfoliated cervical cells for methylation quantitation at CpG (cytosine-phosphate-guanine) sites and human papillomavirus (HPV) genotyping. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated using Cox regression to quantify the effect of methylation on CIN1 regression over two consecutive visits, compared to non-regression (persistent CIN1; progression to CIN2+; or CIN1 regression at a single time-point), adjusting for age, race, high-risk HPV (hrHPV), parity, oral contraceptive and smoking status. Median participant age was 26.6 years (range: 21.0-64.4 years), 39% were African-American, and 11% were current smokers. Most participants were hrHPV-positive at enrollment (80.5%). Over one-third of cases regressed (n = 53, 35.1%). Median time-to-regression was 12.6 months (range: 4.5-24.0 months). Probability of CIN1 regression was negatively correlated with methylation at IGF2AS CpG 5 (HR = 0.41; 95% CI = 0.23-0.77) and PEG10 DMR (HR = 0.80; 95% CI = 0.65-0.98). Altered methylation of imprinted IGF2AS and PEG10 DMRs may play a role in the natural history of CIN1. If confirmed in larger studies, further research on imprinted gene DMR methylation is warranted to determine its efficacy as a biomarker for cervical cancer screening.

Prospective Evaluation of Lymph Node Processing at Staging Surgery for High-grade Endometrial Cancer.

To determine whether the processing of additional adipose tissue collected during lymph node (LN) dissection results in the identification of additional LNs during endometrial cancer (EC) staging and to determine if the division of LNs into nodal basin-specific specimens has an effect on the number of LNs identified during EC staging. A prospective randomized controlled trial was performed on women with high-grade EC undergoing surgical staging. Subjects were randomized to collection of LNs into nodal basin-specific containers on the randomized side versus simple labeling on the nonrandomized side. The total number of LNs and total number of LNs with metastases on the randomized versus the nonrandomized side were compared. The remaining adipose tissue from each LN specimen was submitted for histologic examination. We analyzed the number of LNs with and without metastases identified from additional adipose tissue. Of 120 consented subjects, 56 had sufficient data for analysis. The additional adipose tissue contained 7.5 additional LNs per patient on average (range: 0-26). In 2/54 total cases (3.7%) and 2/5 cases with nodal metastases (40%), the additional adipose contained LNs with metastases. In both cases, metastases were also detected in grossly identified LN candidates. The mean number of LNs identified was not significantly different based on method of collection (P=0.22). The mean number of LNs containing metastases per side was not significantly different (P=0.58). Processing of adipose tissue does increase the total number of LNs identified, however, it does not influence EC stage. No difference in LN counts was noted with basin-specific collection.

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.

Robotic surgical training: Where are we?

BACKGROUND AND OBJECTIVE: Over the past 10years, robotic surgery has revolutionized the advancement of MIS in gynecologic oncology. As the use of robotic surgery has increased, so has the interest in the surgical training of gynecologic oncology fellows. The purpose of this review is to summarize the state of robotic surgical education in Gynecologic Oncology. METHODS: Several electronic databases were searched to identify studies that discussed robotic surgical education in gynecologic oncology. Particular attention was given to articles that discussed educational curriculum. The various curriculums were compared and summarized. RESULTS: The first reports of robotic surgery curriculums in gynecologic oncology emerged in 2008. Prior to that the early adapters had to rely on less structured curriculums that essentially used live animal models and cadaveric dissections on the robot to simulate live surgery. More recent surgical curriculums are more structured and include the same basic components: didactics and a graduated hands-on experience. There is also an accredited robotic educational curriculum, the Fundamentals of Robotic Surgery (FRS), which combine an on-line curriculum with dry lab and operating room components that can be scored using a validated assessment tool. CONCLUSIONS: Robotic surgical education has come a long way in the decade that the robotic platform has been available in the U.S. Although there is still no standardized curriculum, most fellowship training programs in gynecologic oncology have fairly consistent training. Simulation training is another tool that can help a surgeon achieve proficiency quicker.

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.

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.

Postoperative Pain Scores and Narcotic Use in Robotic-assisted Versus Laparoscopic Hysterectomy for Endometrial Cancer Staging.

STUDY OBJECTIVE: To retrospectively evaluate perioperative pain and analgesic and antiemetic use in patients who underwent surgical staging for endometrial cancer using traditional versus robotic-assisted laparoscopy. DESIGN: We identified women in a single institution who underwent minimally hysterectomy for endometrial cancer from 2008 to 2012. Patient characteristics and perioperative outcomes, including analgesic and antiemetic use and pain scores, were analyzed. After univariate analysis, a multivariate linear regression model was generated to determine factors associated with narcotic use in the post anesthesia care unit (PACU) (Canadian Task Force Classification II-3). SETTING: A single academic institution in the United States from 2008 to 2012. PATIENTS: Women undergoing total laparoscopic hysterectomy or robotic-assisted laparoscopic hysterectomy for endometrial cancer. INTERVENTIONS: Laparoscopic or robotic-assisted laparoscopic hysterectomy. MEASUREMENTS AND MAIN RESULTS: Three hundred thirty-five women were included (213 laparoscopy and 122 robotic-assisted laparoscopy). There was no difference in pain scores at 0 to 6 and 6 to 12 hours after surgery; at 12 to 24 hours, robotic-assisted surgery was associated with higher median pain scores (5/10 vs 4/10, p = .012). Robotic-assisted surgery was associated with a longer anesthesia time (289 vs 255 minutes, p < .001), similar antiemetic use (p = .40), and lower narcotic use in the postanesthesia care unit (PACU) (1.3 mg vs 2.5 mg morphine equivalents, p = .003). There was no difference in narcotic use on the postoperative floor (p = .46). In multivariate analysis controlling for age, menopausal status, anesthesia duration, and local anesthetic use, hysterectomy type was not a significant predictor of PACU narcotic use (p = .86). CONCLUSIONS: In a retrospective analysis, a robotic-assisted approach to endometrial cancer was not associated with reduced PACU narcotic or antiemetic use compared with the traditional laparoscopic approach. Twenty-four-hour narcotic and antiemetic use was also not different between the 2 approaches.

Vaginal cuff thermal injury by mode of colpotomy at total laparoscopic hysterectomy: a randomized clinical trial.

STUDY OBJECTIVE: To evaluate if the use of Valleylab mode ("V mode") (Covidien, Mansfield, MA) electrothermal energy for colpotomy during total laparoscopic hysterectomy (LH) results in a smaller margin of thermal injury to the upper vagina compared with traditional cut/coagulate (cut/coag) electrothermal energy. DESIGN: Prospective randomized clinical trial (Canadian Task Force classification I). SETTING: University medical center. PATIENTS: A total of 101 subjects who underwent LH between June 2010 and August 2012. INTERVENTIONS: Subjects were randomized to colpotomy by V mode electrothermal energy or cut/coag electrothermal energy. MEASUREMENTS AND MAIN RESULTS: The primary end point was the median depth of thermal injury measured in millimeters. The secondary end points included the proportion of subjects who developed granulation tissue, induration, infection, or dehiscence at the vaginal cuff at 4 weeks, 3 months, or 6 months postoperatively. There was no significant difference in the median depth of thermal injury in the cut/coag and V mode arms (anterior margin: 0.68 mm vs 0.63 mm [p = .94], posterior margin: 0.66 mm vs 0.70 mm [p = .87], respectively). Twenty-seven percent of subjects in each arm developed at least 1 of the clinical end points at 4 weeks, 3 months, or 6 months postoperatively (granulation tissue: 6%-18% vs 8%-21%, induration: 0%-2% vs 4%-5%, infection: 0%-4% vs 0%-10%, dehiscence: 2% vs 0% in the cut/coag and V mode arms, respectively), with no difference between arms (p = 1.0). CONCLUSION: The V mode does not reduce the depth of thermal injury compared with cut/coag electrothermal energy when used for colpotomy incision during total laparoscopic hysterectomy (Clinical Trials.gov ID: NCT02080546).

Patient preferences in advanced or recurrent ovarian cancer.

BACKGROUND: The objective of this study was to elucidate relative preferences of women with ovarian cancer for symptoms, treatment-related side effects, and progression-free survival (PFS) relevant to choosing a treatment regimen. METHODS: Women with advanced or recurrent ovarian cancer participated in a survey that included 3 methods to measure patient preferences (ratings, rankings, and a discrete-choice experiment) for 7 attributes: mode of administration, visit frequency, peripheral neuropathy, nausea and vomiting, fatigue, abdominal discomfort, and PFS. Participants were asked to choose between 2 unlabeled treatment scenarios that were characterized using the 7 attributes. Each participant completed 12 choice questions in which attribute levels were assigned according to an experimental design and a fixed-choice question representing 2 chemotherapy regimens for ovarian cancer. RESULTS: In total, 95 women completed the survey. Participants' ratings and rankings revealed greater concern and importance for PFS than for any other attribute (P < .0001 for all). The discrete-choice experiment revealed that the relative odds that a participant would choose a scenario with 18 months, 21 months, and 24 months of PFS versus 15 months of PFS were 1.5 (P = .01), 3.4 (P < .001), and 7.5 (P < .001), respectively. However, participants' choices indicated that they were willing to accept a shorter PFS to avoid severe side effects: 6.7 months to reduce nausea and vomiting from severe to mild, 5.0 months to reduce neuropathy from severe to mild, and 3.7 months to reduce abdominal symptoms from severe to moderate. CONCLUSIONS: PFS is the predominant driver of patient preferences for chemotherapy regimens. However, women in the current study were willing to trade significant PFS time for reductions in treatment-related toxicity.

HPV genotypes and cervical intraepithelial neoplasia in a multiethnic cohort in the southeastern USA.

PURPOSE: For poorly understood reasons, invasive cervical cancer (ICC) incidence and mortality rates are higher in women of African descent. Oncogenic human papillomavirus (HPV) genotypes distribution may vary between European American (EA) and African-American (AA) women and may contribute to differences in ICC incidence. The current study aimed at disentangling differences in HPV distribution among AA and EA women. METHODS: Five-hundred and seventy-two women were enrolled at the time of colposcopic evaluation following an abnormal liquid-based cytology screen. HPV infections were detected using HPV linear array, and chi-squared tests and linear regression models were used to compare HPV genotypes across racial/ethnic groups by CIN status. RESULTS: Of the 572 participants, 494 (86 %) had detectable HPV; 245 (43 %) had no CIN lesion, 239 (42 %) had CIN1, and 88 (15 %) had CIN2/3. Seventy-three percent of all women were infected with multiple HPV genotypes. After adjusting for race, age, parity, income, oral contraception use, and current smoking, AAs were two times less likely to harbor HPV 16/18 (OR 0.48, 95 % CI 0.21-0.94, p = 0.03) when all women were considered. This association remained unchanged when only women with CIN2/3 lesions were examined (OR 0.22, 95 % CI 0.05-0.95, p = 0.04). The most frequent high-risk HPV genotypes detected among EAs were 16, 18, 56, 39, and 66, while HPV genotypes 33, 35, 45, 58, and 68 were the most frequent ones detected in AAs. CONCLUSIONS: Our data suggest that while HPV 16/18 are the most common genotypes among EA women with CIN, AAs may harbor different genotypes.

Cost of care using prophylactic negative pressure wound vacuum on closed laparotomy incisions.

OBJECTIVE: We wished to determine the reduction in the rate of wound complications that would render the use of prophylactic negative pressure wound vacuum therapy (NPWT) cost saving compared to routine incision care (RC) following laparotomy for gynecologic malignancy. METHODS: A decision tree was designed from a payer perspective to compare strategies for incision management following laparotomy for gynecologic malignancy: (1) RC; (2) prophylactic NPWT. Rates of wound complication, antibiotic use, re-hospitalization, re-operation, and home health use were obtained from a published cohort of 431 women who underwent laparotomy for endometrial cancer 2002-2007. Costs were estimated using Medicare reimbursements; cost of NPWT ($200) was obtained from hospital financial department. A 50% reduction in wound complications using NPWT was assigned initially and varied for sensitivity analysis. RESULTS: The mean BMI was 36. The wound complication rate was 31% (37% for BMI>30, 41% for BMI>40). The overall cost of incision care was $104 lower for NPWT than for RC. At the lowest cost of NPWT ($200), the risk of wound complication must be reduced by 33% (relative risk=0.67) for NPWT to achieve cost savings in this cohort. Modeling obese and morbidly obese cohorts, the NPWT resulted in overall cost savings of $163 and $203, respectively, and the risk of wound complication must be reduced by 28% and 25%, respectively, for NPWT to achieve cost savings. CONCLUSION: If the wound complication rate can be reduced by one-third, prophylactic NPWT is potentially cost saving in high-risk women undergoing laparotomy for gynecologic malignancy.

Relationship between minimally invasive hysterectomy, pelvic cytology, and lymph vascular space invasion: a single institution study of 458 patients.

OBJECTIVE: The aim of this study is to determine whether a minimally invasive approach to hysterectomy is associated with an increased rate of lymph vascular space invasion (LVSI) and/or malignant pelvic peritoneal cytology in endometrial cancer. METHODS: We performed a single institution analysis of 458 women with endometrial cancer who underwent either total abdominal hysterectomy (TAH) or minimally invasive hysterectomy (MIH) with use of a disposable uterine manipulator. All patients had endometrial cancer diagnosed by endometrial biopsy at a single academic institution between 2002 and 2012. Exclusion criteria were pre-operative D&C and/or hysteroscopy, uterine perforation or morcellation, and conversion to laparotomy. Multivariate logistic regression models to determine if type of hysterectomy predicts either LVSI or presence of abnormal cytology were controlled for grade, stage, depth of invasion, tumor size, cervical and adnexal involvement. RESULTS: LVSI was identified in 39/214 (18%) MIH and 44/242 (18%) TAH (p=0.99). Pelvic washings were malignant in 14/203 (7%) MIH and 16/241 (7%) TAH (p=1.0). Washings were atypical or inconclusive in 16/203 (8%) MIH and 6/241 (2.5%) TAH (p=0.014). In multivariate analyses, type of hysterectomy was not a significant predictor of either LVSI (p=0.29) or presence of malignant washings (p=0.66), but was a predictor of atypical or inconclusive washings (p=0.03). CONCLUSION: Minimally invasive hysterectomy with use of a uterine manipulator for endometrial cancer is not associated with LVSI or malignant cytology. Algorithms that better determine the etiology and implications of inconclusive or atypical pelvic cytology are needed to inform the possible additional risk associated with a minimally invasive approach to endometrial cancer.

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.

Anxiety in first year medical students taking gross anatomy.

To study anxiety levels in first-year medical students taking gross anatomy. Thirty medical students per year, for 2 years, completed the Beck Anxiety Inventory (BAI) 10 times during a 13-week gross anatomy course. In addition, behavioral observations were made by a psychiatrist during gross anatomy for demonstrations of assertive, destructive, neutral, or passive behavior. Additional qualitative outcome measures were group exit interviews with the faculty and students. The mean BAI for all 60 students per year, for 2 years, was 2.19 ± 3.76, 93% of the scores indicated minimal anxiety, and 89% of BAI values were less than five which confirmed a minimal level of anxiety. The low level of reported BAI contrasted sharply with verbal reports by the same students and face-to-face exit interviews with the psychiatrist. Symptoms of stress and anxiety emerged as a result of these conversations. The high levels of subjective stress and anxiety revealed by the interviews were unknown to the gross anatomy faculty. The low scores of students on the BAI's stand in sharp contrast to the BAI's reported for medical students in other published reports. Although it is possible that our students were truthfully devoid of anxiety, it is more likely that our students were denying even minimal anxiety levels. There have been reports that medical students feel that admitting stress, depression, or anxiety put their competitiveness for a residency at risk. We conclude that students may be in frank denial of experiencing anxiety and, if so, this behavior is not conducive to good mental health.

Timing of end-of-life care discussion with performance on end-of-life quality indicators in ovarian cancer.

OBJECTIVES: (1) To describe the prevalence, timing and setting of documented end-of-life (EOL) discussions in patients with advanced ovarian cancer; and (2) to assess the impact of timing and setting of documented end-of-life discussions on EOL quality care measures. METHODS: A retrospective study of women who died of ovarian cancer diagnosed between 1999 and 2008 was conducted. The following are the EOL quality measures assessed: chemotherapy in the last 14 days of life, >1 hospitalization in the last 30 days, >1 ER visit in the last 30 days, intensive care unit (ICU) admission in the last 30 days, dying in an acute care setting, admitted to hospice ≤3 days. RESULTS: One hundred seventy-seven (80%) patients had documented end-of-life discussions. Median interval from EOL discussion until death was 29 days. Seventy-eight patients (44%) had EOL discussions as outpatient and 99 (56%) as inpatient. Sixty-four out of 220 (29%) patients' care did not conform to at least one EOL quality measure. An EOL discussion at least 30 days before death was associated with a lower incidence of: chemotherapy in the last 14 days of life (p=0.003), >1 hospitalization in the last 30 days (p<0.001), ICU admission in the last 30 days (p=0.005), dying in acute care setting (p=0.01), admitted to hospice ≤3 days (p=0.02). EOL discussion as outpatient was associated with fewer patients hospitalized >1 in the last 30days of life (p<0.001). CONCLUSIONS: End-of-life care discussions are occurring too late in the disease process. Conformance with EOL quality measures can be achieved with earlier end-of-life care discussions.

Multicenter phase II trial of topotecan, cisplatin and bevacizumab for recurrent or persistent cervical cancer.

OBJECTIVE: We evaluated the activity and safety of the combination of topotecan, cisplatin and bevacizumab in patients with recurrent or persistent carcinoma of the cervix. METHODS: Eligible patients had persistent or recurrent cervical cancer not amenable to curative intent treatment. No prior chemotherapy for recurrence was allowed. Treatment consisted of cisplatin 50 mg/m(2) day 1, topotecan 0.75 mg/m(2) days 1, 2 and 3 and bevacizumab 15 mg/kgday 1 every 21 days until disease progression or limiting toxicity. The primary endpoint was progression free survival at 6 months. We explored PET/CT as a potential early indicator of response to therapy. RESULTS: Twenty-seven eligible patients received a median of 3 treatment cycles (range, 1-19). Median follow-up was 10 months (range, 1.7-33.4). The 6-month PFS was 59% (80% CI: 46-70%). In 26 evaluable patients, we observed 1 CR (4%; 80% CI: 0.4-14%) and 8 PR (31%; 80% CI: 19-45%) lasting a median of 4.4 months. Ten patients had SD (39%; 80% CI: 25-53%) with median duration of 2.2 months. Median PFS was 7.1 months (80% CI: 4.7-10.1) and median OS was 13.2 months (80% CI: 8.0-15.4). All patients were evaluated for toxicity. Grade 3-4 hematologic toxicity was common (thrombocytopenia 82% leukopenia 74%, anemia 63%, neutropenia 56%). Most patients (78%) required unanticipated hospital admissions for supportive care and/or management of toxicities. CONCLUSION: The addition of bevacizumab to topotecan and cisplatin results in an active but highly toxic regimen. Future efforts should focus on identification of predictive biomarkers of prolonged response and regimen modifications to minimize toxicity.