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Poly (ADP-ribose) polymerase inhibitors (PARPis) have demonstrated clinical activity in patients with BRCA1 and/or BRCA2 mutated breast, ovarian, prostate, and pancreatic cancers. Notably, BRCA mutations are associated with defects in the homologous recombination repair (HRR) pathway. This homologous recombination deficiency (HRD) phenotype can also be observed as genomic instability in tumour cells. Accordingly, PARPi sensitivity has been observed in various tumours with HRD, independent of BRCA mutations. Currently, four PARPis are approved by regulatory agencies for the treatment of cancer across multiple tumour types. Most indications are specific to tumours with a confirmed BRCA mutation, mutations in other HRR-related genes, HRD evidenced by genomic instability, or evidence of platinum sensitivity. Regulatory agencies have also approved companion and complementary diagnostics to facilitate patient selection for each PARPi indication. This review aims to summarise the biological basis, clinical validation, and clinical relevance of the available diagnostic methods and assays to assess HRD. • Several biomarker tests are available to determine patient selection for PARPis. • These tests identify tumours with HRD and help determine sensitivity to PARPis. • We reviewed biomarker tests to assess HRD and their relevance for PARPi treatment. [ABSTRACT FROM AUTHOR]

Ovarian cancer is the leading cause of gynecologic cancer–related death in the United States. Historically, studies have demonstrated that ovarian cancer is a heterogeneous disease with several patient and oncologic characteristics, including BRCA status and residual disease at surgery, known to be predictive of clinical outcomes. However, during the last decade, the discovery and approval of bevacizumab and poly(adenosine diphosphate-ribose) polymerase inhibitors have moved the frontline treatment paradigm beyond platinum-doublet therapy for women with advanced ovarian cancer. Subsequently, investigators have sought to assess the therapeutic efficacy of these agents in women who are considered "high" risk and "low" risk to determine which patients may benefit the most from aggressive therapy and in whom additional treatment may be avoided. We reviewed historic and contemporary definitions of "high-risk" and "low-risk" ovarian cancer and how this has been incorporated into the subset analyses of randomized, clinical trials of therapeutic agents, including bevacizumab and poly(adenosine diphosphate-ribose) polymerase inhibitors. Next, we provided an in-depth discussion of landmark trials for frontline maintenance therapy with bevacizumab and/or poly(adenosine diphosphate-ribose) polymerase inhibitors, focusing on the impact of treatment efficacy according to a "high-risk" and "low-risk" paradigm. Furthermore, we highlighted that recent data have challenged this dichotomous classification, notably from the Gynecologic Oncology Group-0218, ICON7, SOLO-1, and PAOLA-1 trials. Although some studies have suggested that certain populations of women with advanced ovarian cancer may have a more favorable prognosis and be considered "low risk," the risk of progression and death remains unacceptably high in all women. Furthermore, in many cases, those considered the lowest risk have the most treatment benefit from maintenance therapy with poly(adenosine diphosphate-ribose) polymerase inhibitors and/or bevacizumab. From these data, we have advocated that virtually all women with advanced ovarian cancer are high risk and that the use of our most effective therapies in the frontline setting holds promise for potentially curing more patients. Lastly, we critically discuss the practice of using subanalyses in clinical trials, with emphasis that although this practice is important for hypothesis generation, caution must be taken before accepting findings from subanalyses as actual treatment effects. [ABSTRACT FROM AUTHOR]

Background: Women with adnexal mass suspected of ovarian malignancy are likely to benefit from consultation with a gynecologic oncologist, but imaging and biomarker tools to ensure this referral show low sensitivity and may miss cancer at critical stages.Objective: The multivariate index assay (MIA) was designed to improve the detection of ovarian cancer among women undergoing surgery for a pelvic mass. To improve the prediction of benign masses, we undertook the redesign and validation of a second-generation MIA (MIA2G).Study Design: MIA2G was developed using banked serum samples from a previously published prospective, multisite registry of patients who underwent surgery to remove an adnexal mass. Clinical validity was then established using banked serum samples from the OVA500 trial, a second prospective cohort of adnexal surgery patients. Based on the final pathology results of the OVA500 trial, this intended-use population for MIA2G testing was high risk, with an observed cancer prevalence of 18.7% (92/493). Coded samples were assayed for MIA2G biomarkers by an external clinical laboratory. Then MIA2G results were calculated and submitted to a clinical statistics contract organization for decoding and comparison to MIA results for each subject. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated, among other measures, and stratified by menopausal status, stage, and histologic subtype.Results: Three MIA markers (cancer antigen 125, transferrin, and apolipoprotein A-1) and 2 new biomarkers (follicle-stimulating hormone and human epididymis protein 4) were included in MIA2G. A single cut-off separated high and low risk of malignancy regardless of patient menopausal status, eliminating potential for confusion or error. MIA2G specificity (69%, 277/401 [n/N]; 95% confidence interval [CI], 64.4-73.4%) and PPV (40%, 84/208; 95% CI, 33.9-47.2%) were significantly improved over MIA (specificity, 54%, 215/401; 95% CI, 48.7-58.4%, and PPV, 31%, 85/271; 95% CI, 26.1-37.1%, respectively) in this cohort. Sensitivity and NPV were not significantly different between the 2 tests. When combined with physician assessment, MIA2G correctly identified 75% of the malignancies missed by physician assessment alone.Conclusion: MIA2G specificity and PPV were significantly improved compared with MIA, while sensitivity and NPV were unchanged. The second-generation test significantly improved the predicted efficiency of triage vs MIA without sacrificing high sensitivity and NPV, which are essential for effectiveness. [ABSTRACT FROM AUTHOR]

Abstract: Aim: Trabectedin in combination with pegylated liposomal doxorubicin (PLD) improves progression-free survival (PFS) compared to PLD alone in recurrent ovarian cancer (J Clin Oncol 2010;28:3107–14). Methods: Women, stratified by performance status (0–1 versus 2) and platinum sensitivity (platinum-free interval [PFI]<6 versus ⩾6months), were randomly assigned to receive PLD 30mg/m2 IV followed by a 3-h infusion of trabectedin 1.1mg/m2 every 3weeks or PLD 50mg/m2 every 4weeks. The study was powered to show a 33% increase in overall survival (OS) after 520 deaths had occurred. Results: After a median follow-up of 47.4months, there were 522 deaths among 672 subjects. The median OS for trabectedin+PLD and PLD arms was 22.2 and 18.9months, respectively (hazard ratio [HR]=0.86; 95% confidence interval [CI]: 0.72–1.02; p =0.0835). An unexpected but significant imbalance in the PFI favouring the PLD arm (mean PFI: PLD=13.3months, trabectedin+PLD=10.6months) was identified. On the basis of this finding, an unplanned hypothesis generating analysis adjusting for the PFI imbalance and other prognostic factors suggested an improvement in OS associated with the trabectedin+PLD arm (HR=0.82; 95%CI: 0.69–0.98; p =0.0285). In another unplanned exploratory analysis, the subset of patients with a PFI of 6–12months had the largest difference in OS (HR=0.64; 95%CI: 0.47–0.86; p =0.0027). Conclusions: The final OS analysis did not meet the protocol-defined criterion for statistical significance. Despite stratification on platinum sensitivity, there was an imbalance in mean platinum free interval that had an effect on OS. [Copyright &y& Elsevier]

With the approval of a vaccine to prevent human papillomavirus (HPV) infection and the pending approval of a second vaccine, an exciting era has dawned that provides clinicians the opportunity to prevent a majority of lower genital tract cancers. Herein, we describe the quadrivalent and bivalent prophylactic HPV vaccines and examine how they can be incorporated into clinical practice. Efficacy and safety of the vaccines are discussed as are potential barriers to vaccination. Future questions and challenges are also reviewed. A quadrivalent virus-like particle vaccine has now been approved for use in girls and women ages 9-26 years. A second bivalent vaccine could be available soon. The development of these vaccines targeted against 2 oncogenic types of HPV infection (HPV 16 and 18) has made it possible to eliminate approximately 70% of all invasive cervical cancers in women worldwide and decrease the incidence of other lower genital tract cancers and precancers. Vaccine efficacy in clinical trials has been outstanding, with nearly 100% protection against high-grade lesions because of HPV vaccine types. It is extremely important that vaccinated and unvaccinated women continue with recommended cervical cancer screening because not all oncogenic HPV types are covered in currently developed vaccines. Prevention of most cervical cancer and a notable proportion of cervical precancers and other lower genital tract cancers is now possible with the clinical availability of prophylactic vaccination for girls and young women. Prevention of genital warts is also possible with the quadrivalent vaccine. However, knowledge about HPV infection and cervical cancer as well as the need to vaccinate against oncogenic HPV infection is still lacking among women and physicians; thus, continued education of patients and clinicians is necessary to optimize vaccine use and assure ongoing cytologic screening. [ABSTRACT FROM AUTHOR]

Background: Opportunistic salpingectomy at the time of hysterectomy or as an alternative to bilateral tubal ligation may reduce the incidence of ovarian cancer, because it has been demonstrated that most serous ovarian cancers begin in the fallopian tubes. However, salpingectomy at the time of sterilization is not always financially covered by third-party payers, and this represents a barrier to adoption. Routine salpingectomy has become more common but is not always practiced at the time of hysterectomy.Objective: This study aimed to determine the impact of opportunistic salpingectomy as an alternative tubal ligation and routine salpingectomy at the time of hysterectomy on ovarian cancer mortality and overall cost.Study Design: An 8-state Markov state transition model was constructed, including hysterectomy, tubal ligation, and ovarian cancer. Transition probabilities were informed by previously reported population data and include age-adjusted rates of elective sterilization and hysterectomy. This model was used to predict ovarian cancer incidence and the cost effectiveness of opportunistic salpingectomy. Testing of this model suggested that it accurately predicted overall life expectancy and closely predicted the rate of hysterectomy in the population. The model may underestimate the rate of tubal sterilization, making it conservative with respect to the benefits of salpingectomy.Results: The recursive Markov model was run from ages 20 to 85 years in 1-year intervals with a half step correction and included age-adjusted rates of tubal ligation, hysterectomy (with and without oophorectomy), and ovarian cancer. The model predicts that opportunistic salpingectomy at the time of tubal ligation will reduce ovarian cancer mortality by 8.13%. Opportunistic salpingectomy at the time of hysterectomy will reduce ovarian cancer mortality by 6.34% for a combined decrease of 14.5%. Both strategies are cost effective when considering only the cost of the opportunistic salpingectomy. The excess cost of opportunistic salpingectomy at the time of tubal ligation was $433.91 with an incremental cost-effective ratio of $6401 per life-year and $5469 per quality-adjusted life year gained when adjusting for ovarian cancer with a utility of 0.64. The incremental cost-effective ratio for opportunistic salpingectomy during hysterectomy at a cost of $124.70 was $2006 per life-year and $1667 per quality-adjusted life year. When considering the impact of ovarian cancer prevention with respect to the cost of ovarian cancer treatment, opportunistic salpingectomy may produce a substantial healthcare savings. Utilizing a 3% discount rate, it is estimated that the total savings for universal salpingectomy could be as high as $445 million annually in the United States. A sensitivity analysis around the benefit of opportunistic salpingectomy suggests that this procedure will be cost effective even if salpingectomy provides only a modest reduction in the risk of ovarian cancer.Conclusion: It is estimated that universal opportunistic salpingectomy may prevent 1854 deaths per year from ovarian cancer and may reduce healthcare costs. Given these data, universal opportunistic salpingectomy should be considered at the time of tubal ligation and hysterectomy and covered by third-party payers. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Patients with locally advanced vulvar carcinoma can be treated with primary surgery or neoadjuvant chemoradiation. Neoadjuvant treatment appears to be associated with decreased morbidity and acceptable long-term outcomes. We examined the patterns of care for women with locally advanced vulvar cancer. STUDY DESIGN: Data from the Surveillance, Epidemiology, and End Results (SEER) database was used to examine women with stage III-IVA vulvar cancer treated from 1988 to 2008, Primary therapy was classified as surgery or radiation. Multivariable logistic regression models were developed to examine the use of primary radiotherapy. RESULTS: We identified a total of 2292 women including 1757 who underwent primary surgery (76,7%) and 535 treated with primary radiation (23.3%). The use of primary radiation increased with time from 18.0% in 1988 to 30.1% in 2008. In a muitivariable model, older women (odds ratio [OR], 1.33; 95% confidence interval [CI], 1.03-1.72), black women (OR, 1.59; 95% CI, 1.14-2.23), and patients with stage IVA tumors (OR, 2.23; 95% CI, 1.78-2.81) were more likely to receive primary radiation. Among women treated with primary radiotherapy, only 17.8% ultimately underwent surgical resection. CONCLUSION: The use of primary radiation for locally advanced vulvar cancer is limited but has increased over time. Multiple patient and tumor factors influence use, The majority of patients with stage III-IVA vulvar cancer treated with primary radiation therapy did not undergo surgical resection, [ABSTRACT FROM AUTHOR]

Objective: We examined the use and cost of autologous blood cell salvage in women who undergo abdominal myomectomy. Study Design: Patients who underwent abdominal myomectomy from 2007-2011 were identified. Use of the cell salvage system and reinfusion of autologous blood in women who had the system set-up were analyzed. Cost was examined by directly reported data. Results: We identified 607 patients who underwent abdominal myomectomy. Four hundred twenty-five women (70%) had the set-up of the cell salvage system. Cell-salvaged blood was processed and reinfused into 85 of these subjects (20%). In a multivariable model, performance of myomectomy by a gynecologic-specific surgeon (odds ratio [OR], 2.14; 95% confidence interval [CI], 1.28–3.59), >5 myomas (OR, 2.49; 95% CI, 1.27–4.89), and larger uterine size statistically were associated significantly with cell-salvage device set-up. Conversely, having a reproductive-endocrinology-infertility specialist as the surgeon was associated with a significant reduction in cell-salvage system set-up (OR, 0.37; 95% CI, 0.21–0.66). For the women who had cell-salvage system set-up, uterine size of >15-19 weeks of gestation (OR, 3.22; 95% CI, 1.56–8.95) or ≥20 weeks of gestation (OR, 4.62; 95% CI, 1.45–14.73), operating time of >120 minutes (OR, 3.98; 95% CI, 1.70–9.29), and intraoperative blood loss of >1000 mL (OR, 26.31; 95% CI, 10.49–65.99) were associated significantly with a higher incidence of reinfusion of cell-salvaged blood. Conclusion: The routine use of cell salvage in women who undergo abdominal myomectomy does not appear to be warranted. Cell-salvage set-up appears to be cost-effective only when reinfused, but clinical characteristics cannot predict accurately which women will require reinfusion of cell-salvaged blood. [Copyright &y& Elsevier]

Objective: There is growing recognition that, in addition to occurrence of perioperative complications, the treatment of patients with complications influences outcome. We examined complications, failure to rescue (death in patients with a complication), and mortality rates for women who underwent abdominal hysterectomy. Study Design: Women who underwent abdominal hysterectomy from 1998-2010 and whose data were recorded in the Nationwide Inpatient Sample were identified. Hospitals were stratified based on risk-adjusted mortality rates into 5 quintiles, and rates of complications and failure to rescue were examined. Results: A total of 664,229 women who had been treated at 741 hospitals were identified. The overall mortality rate for the cohort was 0.17%. The risk-adjusted, hospital-level mortality rate ranged from 0–1.12%. The complication rate was 6.5% at the hospitals with the lowest mortality rates, 9.9% at the second quintile hospitals, 9.5% at both the third and fourth quintile hospitals, and 7.9% at the hospitals with the highest mortality rates. In contrast to complications, the failure-to-rescue rate increased with each successive risk-adjusted mortality quintile. The failure-to-rescue rate was 0% at the hospitals with the lowest mortality rates and increased with each successive quintile to 1.1%, 2.1%, 2.7%, and 4.4% in the hospitals with the highest mortality rates (P < .0001). Conclusion: For women who underwent abdominal hysterectomy, hospital complication rates correlated poorly with mortality rates; failure-to-rescue is strongly associated with in-hospital mortality rates. The treatment of complications, not the actual development of a complication, is the most important factor to use to predict death after major gynecologic surgery. [Copyright &y& Elsevier]

Background: Platinum-based chemotherapy doublets are a standard of care for women with ovarian cancer recurring 6 months after completion of initial therapy. In this study, we aimed to explore the roles of secondary surgical cytoreduction and bevacizumab in this population, and report the results of the bevacizumab component here.Methods: The multicentre, open-label, randomised phase 3 GOG-0213 trial was done in 67 predominantly academic centres in the USA (65 centres), Japan (one centre), and South Korea (one centre). Eligible patients were adult women (aged ≥18 years) with recurrent measurable or evaluable epithelial ovarian, primary peritoneal, or fallopian tube cancer, and a clinical complete response to primary platinum-based chemotherapy, who had been disease-free for at least 6 months following last infused cycle of platinum. Patients were randomly assigned (1:1) to standard chemotherapy (six 3-weekly cycles of paclitaxel [175 mg/m2 of body surface area] and carboplatin [area under the curve 5]) or the same chemotherapy regimen plus bevacizumab (15 mg/kg of bodyweight) every 3 weeks and continued as maintenance every 3 weeks until disease progression or unacceptable toxicity. Individuals who participated in both the bevacizumab objective and surgical objective (which is ongoing) were randomly assigned (1:1:1:1) to receive either of these two chemotherapy regimens with or without prior secondary cytoreductive surgery. Randomisation for the bevacizumab objective was stratified by treatment-free interval and participation in the surgical objective. The primary endpoint was overall survival, analysed by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00565851.Findings: Between Dec 10, 2007, and Aug 26, 2011, 674 women were enrolled and randomly assigned to standard chemotherapy (n=337) or chemotherapy plus bevacizumab (n=377). Median follow-up at the end of the trial on Nov 5, 2014, was 49·6 months in each treatment group (IQR 41·5-62·2 for chemotherapy plus bevacizumab; IQR 40·8-59·3 for chemotherapy), at which point 415 patients had died (214 in the chemotherapy group and 201 in the chemotherapy plus bevacizumab group). Based on pretreatment stratification data, median overall survival in the chemotherapy plus bevacizumab group was 42·2 months (95% CI 37·7-46·2) versus 37·3 months (32·6-39·7) in the chemotherapy group (hazard ratio [HR] 0·829; 95% CI 0·683-1·005; p=0·056). We identified incorrect treatment-free interval stratification data for 45 (7%) patients (equally balanced between treatment groups); a sensitivity analysis of overall survival based on the audited treatment-free interval stratification data gave an adjusted HR of 0·823 (95% CI 0·680-0·996; p=0·0447). In the safety population (all patients who initiated treatment), 317 (96%) of 325 patients in the chemotherapy plus bevacizumab group had at least one grade 3 or worse adverse event compared with 282 (86%) of 332 in the chemotherapy group; the most frequently reported of these in the chemotherapy plus bevacizumab group compared with the chemotherapy group were hypertension (39 [12%] vs two [1%]), fatigue (27 [8%] vs eight [2%]), and proteinuria (27 [8%] vs none). Two (1%) treatment-related deaths occurred in the chemotherapy group (infection [n=1] and myelodysplastic syndrome [n=1]) compared with nine (3%) in the chemotherapy plus bevacizumab group (infection [n=1], febrile neutropenia [n=1], myelodysplastic syndrome [n=1], secondary malignancy [n=1]; deaths not classified with CTCAE terms: disease progression [n=3], sudden death [n=1], and not specified [n=1]).Interpretation: The addition of bevacizumab to standard chemotherapy, followed by maintenance therapy until progression, improved the median overall survival in patients with platinum-sensitive recurrent ovarian cancer. Although the intention-to-treat analysis for overall survival was not significant, our sensitivity analysis based on corrected treatment-free interval stratification indicates that this strategy might be an important addition to the therapeutic armamentarium in these patients.Funding: National Cancer Institute and Genentech. [ABSTRACT FROM AUTHOR]

Objective: We examined the use, safety, and economic impact of same-day discharge for women undergoing laparoscopic hysterectomy. Study Design: We identified women in the Perspective database who underwent laparoscopic hysterectomy from 2000 through 2010. Discharge was classified as same-day, 1 day, and ≥2 days. Multivariable models were used to examine predictors of same-day discharge, reevaluation, and cost. Results: Among 128,634 women, 34,070 (26.5%) were discharged on the day of surgery. Same-day discharge increased from 11.3% in 2000 to 46.0% by 2010 (P < .0001). The rate of reevaluation within 60 days was 4.0% for those discharged same day, 3.6% after a 1-day stay, and 5.1% for patients whose stay was ≥2 days (P < .0001). In a multivariable model, patients discharged on postoperative day 1 were less likely to require reevaluation (risk ratio, 0.89; 95% confidence interval, 0.82–0.96), but costs were $207 (95% confidence interval, $179–234) greater. Conclusion: Same-day discharge after laparoscopic hysterectomy is safe and associated with decreased cost. [ABSTRACT FROM AUTHOR]

Objective: We compared the outcomes of microinvasive squamous cell carcinoma and adenocarcinoma of the cervix and examined the safety of fertility-conserving treatment. Study Design: The Surveillance, Epidemiology, and End Results database was used to identify all women with stage IA1 and IA2 cervical carcinoma diagnosed from 1988 to 2005. The treatment and outcomes of women with adenocarcinomas were compared with squamous cell carcinomas. Results: A total of 3987 women including 988 with adenocarcinomas (24.8%) were identified. Women with adenocarcinoma were more often white and were younger (P < .05 for all). Survival for stage IA1 adenocarcinomas (hazard ratio, 0.79; 95% confidence interval, 0.21–2.94) was similar to that of women with squamous cell tumors. For stage IA2 tumors, survival was similar for squamous cell and adenocarcinomas (hazard ratio, 0.51; 95% confidence interval, 0.18–1.47). For stage IA1 and IA2 adenocarcinomas, survival was similar for conization and hysterectomy. Conclusion: Survival is similar for microinvasive adenocarcinomas and squamous cell carcinomas. Conization appears to be adequate treatment for microinvasive adenocarcinoma. [ABSTRACT FROM AUTHOR]

Objective: We analyzed the effect of lymphadenectomy on the use of adjuvant radiation treatment for women with stage I-II endometrial cancer. Study Design: Women with stage I-II endometrioid adenocarcinomas treated between 1988 and 2006 and recorded in the Surveillance, Epidemiology, and End Results database were identified. The influence of lymphadenectomy (LND) on receipt of external beam radiation and brachytherapy stratified was examined. Results: We identified 58,776 women including 26,043 who underwent LND (44.3%). Among women younger than 60 years of age with stage IA (grades 1, 2, and 3) tumors, LND had no impact on the use of radiation. Patients with stage IB (grade 2 or 3) and stage IC (grade 1 or 2) tumors who underwent lymph node dissection were less likely to undergo external beam radiation and more likely to receive vaginal brachytherapy (P < .05 for all). Furthermore, the extent of lymphadenectomy influenced the receipt of radiation. Conclusion: Women who undergo lymphadenectomy are less likely to receive whole pelvic radiotherapy. [ABSTRACT FROM AUTHOR]

Objective: We performed a population-based analysis to compare the clinical characteristics of women with mucinous tumors with women with other epithelial tumors. Study Design: The Surveillance, Epidemiology, and End Results database was queried to identify all women with epithelial ovarian cancer diagnosed from 1988 to 2007. The natural history, clinical characteristics, and survival of women with serous tumors were compared with women with mucinous carcinomas. Results: A total of 40,571 women including 4811 with mucinous carcinomas (11.9%) were identified. Among women with stage I neoplasms, the presence of mucinous histology had no effect on either cancer-specific survival (hazard ratio, 0.87; 95% confidence interval, 0.74–1.04). Survival was inferior in patients with advanced-stage mucinous compared with serous tumors. The hazard ratio for cancer-specific survival for women with stage III mucinous tumors was 1.55 (95% confidence interval, 1.43–1.96). Conclusion: Although survival for early-stage mucinous and serous tumors is similar, survival for advanced-stage mucinous neoplasms is inferior to that of serous carcinomas. [ABSTRACT FROM AUTHOR]

Objective: We examined the influence of physician and hospital volume on the morbidity and mortality of radical hysterectomy for cervical cancer. Study Design: Women who underwent radical hysterectomy for cervical cancer between 2003 and 2007 were examined. The effect of surgeon and hospital volume on morbidity and mortality was examined using multivariable generalized estimating equations. Results: A total of 1536 women who underwent radical hysterectomy were identified. Patients treated by high-volume surgeons had fewer medical complications (odds ratio, 0.55; 95% confidence interval, 0.34–0.88) and shorter lengths of stay (odds ratio, 0.49; 95% confidence interval, 0.25–0.98). After adjustment for case mix and surgeon volume, hospital volume had no independent effect on any of the variables of interest. Conclusion: High-volume surgeons have fewer postoperative medical complications, shorter lengths of stay, and lower transfusion requirements. Hospital volume appears to have only a minor influence on outcomes after radical hysterectomy. [ABSTRACT FROM AUTHOR]

Objective: We examined predictors of massive blood loss for women with placenta accreta who had undergone hysterectomy. Study Design: A retrospective review of women who underwent peripartum hysterectomy for pathologically confirmed placenta accreta was performed. Characteristics that are associated with massive blood loss (≥5000 mL) and large-volume transfusion (≥10 units packed red cells) were examined. Results: A total of 77 patients were identified. The median blood loss was 3000 mL, with a median of 5 units of red cells transfused. There was no association among maternal age, gravidity, number of previous deliveries, number of previous cesarean deliveries, degree of placental invasion, or antenatal bleeding and massive blood loss or large-volume transfusion (P > .05). Among women with a known diagnosis of placenta accreta, 41.7% had an estimated blood loss of ≥5000 mL, compared with 12.0% of those who did not receive the diagnosis antenatally with ultrasound scanning (P = .01). Conclusion: There are few reliable predictors of massive blood loss in women with placenta accreta. [ABSTRACT FROM AUTHOR]

Objective: Although endometrial cancer commonly occurs in elderly women, little is known about the perioperative outcomes of the oldest women (>80 years of age) who are treated surgically. Study Design: We performed an analysis of women ≥65 years of age with endometrial cancer who underwent hysterectomy from 1998–2007 and who were registered in the Nationwide Inpatient Sample. Results: A total of 25,698 women were identified. Compared with women who were 65-69 years old, women who were ≥85 years old were more likely to have perioperative surgical complications (12% vs 17%), postoperative medical complications (24% vs 34%), and a longer length of stay (3 vs 5 days) and to require a transfusion (6% vs 10%; P < .05 for all). The perioperative mortality rate was 0.4% in women who were 65-69 years old compared with 1.6% in women who were ≥85 years old (P < .0001). Conclusion: The morbidity that is associated with surgery for endometrial cancer is significantly higher in women who are >80 years old, even after medical comorbidities have been considered. [ABSTRACT FROM AUTHOR]

Objective: We examined the prognostic significance of uterine risk factors (RF) compared to nodal metastases in endometrial cancer. Study Design: Women with stage I–IIIC endometrioid cancer were stratified based on the presence of positive or negative lymph nodes. Each patient was characterized by the number of RF present: myoinvasion ≥50%, cervical stromal involvement, and grade 3 histology. Results: A total of 26,967 women were identified. In a multivariable model, uterine RF strongly influenced survival but nodal disease was a more important negative prognostic factor. Five-year overall survival was 68% (95% confidence interval [CI], 63–72%) for group 1 (node positive/no RF) vs 69% (95% CI, 66–72%) for group 5 (node negative/multiple RF). Five–year survival was lower for node–positive patients with RF (58%; 95% CI, 54–61%) than node–positive patients without RF (68%; 95% CI, 63–72%). Conclusion: Uterine RF strongly influenced survival both in the presence and absence of nodal metastasis. [ABSTRACT FROM AUTHOR]

Objective: The optimal management of stage II endometrial cancer remains uncertain. We examined the role of radical hysterectomy and adjuvant radiotherapy for stage II endometrial cancer. Study Design: The Surveillance, Epidemiology, and End Results database was used to identify 1577 women with stage II endometrioid type endometrial adenocarcinoma who underwent surgical staging. Results: The cohort included 1198 women who underwent simple hysterectomy (76%) and 379 who underwent radical hysterectomy (24%). Radical hysterectomy had no effect on survival (hazard ratio [HR], 0.86; 95% confidence interval [CI], 0.61-1.23). Patients who did not receive radiation were 48% (HR, 1.48; 95% CI, 1.14-1.93) more likely to die than those who underwent adjuvant radiotherapy. The survival benefit from radiation was most pronounced in women who underwent radical hysterectomy. Conclusion: Adjuvant radiation improves survival. Although the routine performance of radical hysterectomy does not appear to be justified, patients with high-risk stage II tumors appear to benefit from combination therapy with radical hysterectomy and radiotherapy. [Copyright &y& Elsevier]

Objective: We examined the effect of radiation on survival for early-stage uterine carcinosarcomas and leiomyosarcomas. Study Design: The surveillance, epidemiology, and end results database was used to identify patients with stage I/II carcinosarcomas and leiomyosarcomas. Logistic regression and Cox models were developed to determine radiation use and survival. Results: Among 1819 women with carcinosarcomas and 1088 women with leiomyosarcomas, radiation was administered to 667 of the patients (37%) with carcinosarcomas and to 235 of the patients (22%) with leiomyosarcomas. In a multivariate model, adjuvant radiation reduced the risk of death by 21% in women with carcinosarcomas (hazard ratio, 0.79; 95% CI, 0.7-0.9). Radiation reduced mortality rates in patients with carcinosarcomas who had not undergone node dissection but had only a marginal effect on survival in node-negative women. Adjuvant radiation had no effect on survival for early-stage leiomyosarcomas (hazard ratio, 1.1; 95% CI, 0.9-1.4). Conclusion: Adjuvant radiotherapy improves survival for select patients with early-stage carcinosarcomas but is of limited value for leiomyosarcomas. [Copyright &y& Elsevier]

To explore safety and tolerability parameters for the niraparib individualized starting dose (ISD) in patients with newly diagnosed advanced ovarian cancer that responded to platinum-based chemotherapy who participated in the phase 3 PRIMA/ENGOT-OV26/GOG-3012 trial (NCT02655016). The PRIMA protocol was amended so newly enrolled patients received an ISD based on baseline body weight/platelet count. In this ad hoc analysis, the timing, duration, and resolution of the first occurrence of common any-grade hematologic (thrombocytopenia, anemia, neutropenia) and nonhematologic (nausea, asthenia/fatigue, constipation, insomnia, hypertension) treatment-emergent adverse events (TEAEs) were evaluated by treatment arm in the ISD safety population (data cutoff, November 17, 2021; median follow-up, 3.5 years). Of 733 randomized patients, 255 were enrolled after the ISD protocol amendment and received ≥ 1 dose of study treatment (niraparib, 169; placebo, 86). In the niraparib arm, median times to first events were 22.0–35.0 days for hematologic TEAEs and 7.0–56.0 days for nonhematologic TEAEs. First events resolved in ≥ 89.8% of patients for hematologic TEAEs; for nonhematologic TEAEs, resolution rates ranged from 55.3% (insomnia) to 86.0% (nausea). Median durations of first hematologic TEAEs were ≤ 16.0 days, but for first nonhematologic TEAEs ranged from 18.0 days (nausea) to 134.0 days (insomnia). The niraparib ISD was generally well tolerated and TEAEs were manageable. Common hematologic and nonhematologic TEAEs occurred early and first events of hematologic TEAEs had a short duration (≈ 2 weeks) and a high resolution rate. These findings support close monitoring immediately following niraparib initiation and may help inform patient expectations for niraparib safety. [Display omitted] • Tolerability of niraparib individualized starting dose (ISD) in PRIMA/ENGOT-OV26/GOG-3012. • Evaluated timing, duration, and resolution of first occurrence of common TEAEs. • Hematologic and nonhematologic TEAEs occurred early after niraparib ISD treatment initiation. • First events of hematologic TEAEs had short durations and high rates of resolution. • Niraparib ISD was well tolerated, and common TEAEs were generally manageable. [ABSTRACT FROM AUTHOR]

Background: Angiogenesis is a valid target in the treatment of epithelial ovarian cancer. Trebananib inhibits the binding of angiopoietins 1 and 2 to the Tie2 receptor, and thereby inhibits angiogenesis. We aimed to assess whether the addition of trebananib to single-agent weekly paclitaxel in patients with recurrent epithelial ovarian cancer improved progression-free survival. Methods: For this randomised, double-blind phase 3 study undertaken between Nov 10, 2010, and Nov 19, 2012, we enrolled women with recurrent epithelial ovarian cancer from 32 countries. Patient eligibility criteria included having been treated with three or fewer previous regimens, and a platinum-free interval of less than 12 months. We enrolled patients with a computerised interactive voice response system, and patients were randomly assigned using a permuted block method (block size of four) in a 1:1 ratio to receive weekly intravenous paclitaxel (80 mg/m²) plus either weekly masked intravenous placebo or trebananib (15 mg/kg). Patients were stratified on the basis of platinum-free interval (≥0 and ≤6 months vs >6 and ≤12 months), presence or absence of measurable disease, and region (North America, western Europe and Australia, or rest of world). The sponsor, investigators, site staff, and patients were masked to the treatment assignment. The primary endpoint was progression-free survival assessed in the intention-to-treat population. The trial is registered with ClinicalTrials.gov, NCT01204749, and is no longer accruing patients. Findings: 919 patients were enrolled, of whom 461 were randomly assigned to the trebananib group and 458 to the placebo group. Median progression-free survival was significantly longer in the trebananib group than in the placebo group (7·2 months [5·8-7·4] vs 5·4 months [95% CI 4·3-5·5], respectively, hazard ratio 0·66, 95% CI 0·57-0·77, p<0·0001). Incidence of grade 3 or higher adverse events was similar between treatment groups (244 [54%] of 452 patients in the placebo group vs 258 [56%] of 461 patients in the trebananib group). Trebananib was associated with more adverse event-related treatment discontinuations than was placebo (77 [17%] patients vs 27 [6%], respectively) and higher incidences of oedema (294 [64%] patients had any-grade oedema in the trebananib group vs 127 [28%] patients in the placebo group). Grade 3 or higher adverse events included ascites (34 [8%] in the placebo group vs 52 [11%] in the trebananib group), neutropenia (40 [9%] vs 26 [6%]), and abdominal pain (21 [5%] vs 22 [5%]). We recorded serious adverse events in 125 (28%) patients in the placebo group and 159 (34%) patients in the trebananib group. There was a difference of 2% or less in class-specific adverse events associated with anti-VEGF therapy (hypertension, proteinuria, wound-healing complications, thrombotic events, gastrointestinal perforations), except bleeding, which was more common in the placebo group than in the trebananib group (75 [17%] vs 46 [10%]). Interpretation: Inhibition of angiopoietins 1 and 2 with trebananib provided a clinically meaningful prolongation in progression-free survival. This non-VEGF anti-angiogenesis option for women with recurrent epithelial ovarian cancer should be investigated in other settings and in combination with additional agents. Although oedema was increased, typical anti-VEGF associated adverse events were not prominent. Funding: Amgen. [ABSTRACT FROM AUTHOR]

Purpose: To compare the outcome of patients with cervical cancer and negative lymph nodes by fluorodeoxyglucose-positron emission tomography (FDG-PET) treated with irradiation (RT) and concurrent chemotherapy or RT alone. Methods and Materials: This was a prospective data registry of 65 patients with cervical cancer and negative lymph nodes by whole-body FDG-PET. The tumor stage was IB2 in 11, IIB in 37, and IIIB in 17 patients. RT alone was administered to 15 and RT with concurrent weekly cisplatin to 50 patients. Results: The 5-year overall survival estimate was 85% with RT and 81% with RT and concurrent chemotherapy (p = 0.91). The corresponding 5-year cause-specific survival estimates were 78% and 74% (p = 0.98). The differences in the sites of recurrence (pelvis vs. distant metastasis) were not statistically significant between the two groups (p = 0.77). A Cox proportional hazards model of survival outcome did not identify chemotherapy, overall treatment time, or radiation dose as statistically significant prognostic factors. Severe complications included one rectovaginal fistula, one rectal stricture requiring colostomy (both in the concurrent chemotherapy group), and one death from chemotherapy-related complications. Conclusion: Irradiation with concurrent cisplatin was not advantageous compared with RT alone in patients with negative lymph nodes on FDG-PET. [ABSTRACT FROM AUTHOR]

: PurposeTo evaluate the outcome of patients with International Federation of Gynecology and Obstetrics (FIGO) clinical Stage IIIb cervical carcinoma as a function of site of initial regional lymph node metastasis as detected by 2[18F]fluoro-2-deoxy-d-glucose (FDG)-positron emission tomography (PET).: Methods and materialsForty-seven patients with FIGO Stage IIIb cervical cancer were evaluated before therapy with whole-body FDG-PET. Most patients were treated with external beam irradiation, intracavitary brachytherapy, and weekly cisplatin for six cycles. Overall and cause-specific survival rates were calculated by the Kaplan-Meier method.: ResultsThe pretreatment whole-body FDG-PET demonstrated that all patients had FDG uptake in the cervix. Of 47 patients, 13 (28%) had no evidence of lymph node metastasis, 20 (43%) had metastasis to pelvic lymph nodes only, 7 (15%) had pelvic and para-aortic lymph node metastases, and 7 (15%) had metastases to pelvic, para-aortic, and supraclavicular lymph nodes. The 3-year estimate of cause-specific survival was 73% for those with no lymph node metastasis, 58% for those with only pelvic lymph node metastasis, 29% for those with pelvic and para-aortic lymph node metastases, and 0% for those with pelvic, para-aortic, and supraclavicular lymph node metastasis (p = 0.0005).: ConclusionThe cause-specific survival for patients with FIGO Stage IIIb carcinoma is highly dependent on the extent of lymph node metastasis as demonstrated by whole-body FDG-PET. [Copyright &y& Elsevier]