An absence of translated consent forms limits oncologic clinical trial enrollment for limited English proficiency participants.

OBJECTIVES: A lack of diversity amongst participants in cancer clinical trials has raised scrutiny over the past decade. Patients with limited English proficiency (LEP) are further excluded. One modifiable reason for low LEP participation is a lack of non-English consent forms. METHODS: We queried the clinical trials registry database at an academic hospital serving a predominantly Spanish-speaking patient population. Clinical trials related to gynecology oncology were evaluated for the availability of fully translated Spanish consent forms, the racial and ethnic identification of enrolled patients, and the number of signed Spanish consents. Enrolment data was compared before and after 2019, when institutional financial support for document translation was withdrawn. RESULTS: Sixteen gynecologic oncology clinical trials were opened between 2014 and 2022, with 10 trials enrolling 128 patients. Eight trials opened prior to 2019, all with fully translated consent forms. Seven of these trials enrolled 99 participants, 70% of whom identified as Hispanic and 60% who signed a Spanish consent. Eight trials opened after 2019 and one had a fully translated consent form. Three of the trials enrolled 29 participants, with 10% of subjects identifying as Hispanic and none signing a Spanish consent form. CONCLUSIONS: There was a decrease in fully translated clinical trial consent forms for gynecologic oncology studies following the loss of subsidized translation services in our single institution with a predominantly LEP population. This correlated with a decrease in enrollment of Hispanic subjects. To increase enrollment of diverse participants, including those with LEP, simple actions such as fully translating consent forms would help maintain equity in research conduct and improve clinical outcomes through trial involvement.

Cesarean hysterectomy for placenta accreta spectrum: Surgeon specialty-specific assessment.

OBJECTIVE: To assess (i) clinical and pregnancy characteristics, (ii) patterns of surgical procedures, and (iii) surgical morbidity associated with cesarean hysterectomy for placenta accreta spectrum based on the specialty of the attending surgeon. METHODS: The Premier Healthcare Database was queried retrospectively to study patients with placenta accreta spectrum who underwent cesarean delivery and concurrent hysterectomy from 2016 to 2020. Surgical morbidity was assessed with propensity score inverse probability of treatment weighting based on surgeon specialty for hysterectomy: general obstetrician-gynecologists, maternal-fetal medicine specialists, and gynecologic oncologists. RESULTS: A total of 2240 cesarean hysterectomies were studies. The most common surgeon type was general obstetrician-gynecologist (n = 1534, 68.5%), followed by gynecologic oncologist (n = 532, 23.8%) and maternal-fetal medicine specialist (n = 174, 7.8%). Patients in the gynecologic oncologist group had the highest rate of placenta increta or percreta, followed by the maternal-fetal medicine specialist and general obstetrician-gynecologist groups (43.4%, 39.6%, and 30.6%, P < .001). In a propensity score-weighted model, measured surgical morbidity was similar across the three subspecialty groups, including hemorrhage / blood transfusion (59.4-63.7%), bladder injury (18.3-24.0%), ureteral injury (2.2-4.3%), shock (8.6-10.5%), and coagulopathy (3.3-7.4%) (all, P > .05). Among the cesarean hysterectomy performed by gynecologic oncologist, hemorrhage / transfusion rates remained substantial despite additional surgical procedures: tranexamic acid / ureteral stent (60.4%), tranexamic acid / endo-arterial procedure (76.2%), ureteral stent / endo-arterial procedure (51.6%), and all three procedures (55.4%). Tranexamic acid administration with ureteral stent placement was associated with decreased bladder injury (12.8% vs 23.8-32.2%, P < .001). CONCLUSION: These data suggest that patient characteristics and surgical procedures related to cesarean hysterectomy for placenta accreta spectrum differ based on surgeon specialty. Gynecologic oncologists appear to manage more severe forms of placenta accreta spectrum. Regardless of surgeon's specialty, surgical morbidity of cesarean hysterectomy for placenta accreta spectrum is significant.

Prognostic performance of the 2023 FIGO staging schema for endometrial cancer.

OBJECTIVE: To assess the prognostic performance of the 2023 International Federation of Gynecology and Obstetrics (FIGO) endometrial cancer staging schema. METHODS: This retrospective cohort study queried the Commission-on-Cancer's National Cancer Database. Study population was 129,146 patients with stage I-IV endometrial cancer per the 2009 FIGO staging schema. Stage-shifting and overall survival (OS) were assessed according to the 2023 FIGO staging schema. RESULTS: Upstage (IA → II, 21.4 %; IB → II, 53.0 %) and downstage (IIIA→IA3, 22.2 %) occurred in both early and advanced diseases. Inter-stage prognostic performance improved in the 2023 schema with widened 5-year OS rate difference between the earliest and highest stages (68.2 % to 76.9 %). Stage IA1-IIB and IIC had distinct 5-year OS rate differences (85.8-96.1 % vs 75.4 %). The 5-year OS rate of the 2009 stage IIIA disease was 63.9 %; this was greater segregated in the 2023 schema: 88.0 %, 62.4 %, and 55.7 % for IIIA→IA3, IIIA1, and IIIA2, respectively (inter-substage rate-difference, 32.3 %). This 5-year OS rate of stage IA3 disease was comparable to the 2023 stage IB-IIB diseases (88.0 % vs 85.8-89.5 %). In the 2023 stage IIIC schema (micrometastasis rates: 29.6 % in IIIC1 and 15.6 % in IIIC2), micrometastasis and macrometastasis had the distinct 3-year OS rates in both pelvic (IIIC1-i vs IIIC1-ii, 84.9 % vs 71.1 %; rate-difference 13.8 %) and para-aortic (IIIC2-i vs IIIC2-ii, 82.9 % vs 65.2 %; rate-difference 17.7 %) nodal metastasis cases. The 5-year OS rate of the 2009 stage IVB disease was 23.4 %; this was segregated to 25.4 % for stage IVB and 19.2 % for stage IVC in the 2023 staging schema (rate-difference, 6.2 %). CONCLUSION: The 2023 FIGO endometrial cancer staging schema is a major revision from the 2009 FIGO schema. Almost doubled enriched sub-stages based on detailed anatomical metastatic site and incorporation of histological information enable more robust prognostication.

Adjuvant therapy de-escalation for stage I uterine leiomyosarcoma: A systematic review and meta-analysis.

OBJECTIVE: To examine the association between adjuvant chemotherapy and survival outcomes in patients with stage I uterine leiomyosarcoma (uLMS). METHODS: This comprehensive systematic review and meta-analysis through December 31, 2023 (PROSPERO registration number: CRD42024504776) investigated studies that examined survival outcomes in patients with stage I uLMS using 4 public search engines (PubMed, Scopus, Web of Science, and the Cochrane Central Register of Controlled Trials). Two investigators searched the studies independently, and survival outcomes (overall survival [OS] and disease-free survival [DFS]) were compared between the adjuvant chemotherapy and observation groups. Utilization rate of adjuvant chemotherapy and the regimens used were also assessed. Kaplan-Meier survival curves in the two treatment groups were evaluated using ImageJ software. RESULTS: From 1988 to 2022, 16 eligible studies including a total of 5690 patients met the inclusion criteria and evaluated the effect of adjuvant chemotherapy on survival outcomes in patients with stage I uLMS. Adjuvant chemotherapy was utilized in 38.5 % of patients (range, 14.8 % to 70.0 %). Eight studies from 2017 to 2022 compared the survival outcomes between adjuvant chemotherapy and observation. OS was comparable between the two groups in both unadjusted (n = 6, hazard ratio [HR] 1.02, 95 % confidence interval [CI] 0.77-1.35, P = 0.88) and adjusted (n = 4, HR 0.90, 95 %CI 0.56-1.43, P = 0.65) pooled analyses. DFS was also similar between adjuvant chemotherapy and observation in both unadjusted (n = 4, HR 0.78, 95 %CI 0.53-1.13, P = 0.18) and adjusted (n = 2, HR 1.14, 95 %CI 0.67-1.94, P = 0.64) pooled analyses. Adjuvant chemotherapy regimens utilized included doxorubicin, ifosfamide, cisplatin, gemcitabine, and docetaxel as monotherapies or combination therapies. CONCLUSIONS: In this contemporaneous systematic review and meta-analysis, less than 40 % of patients received adjuvant chemotherapy for stage I uLMS and adjuvant chemotherapy which was not associated with improved survival. These results support the current National Comprehensive Cancer Network clinical practice guidelines that recommends de-escalating adjuvant chemotherapy in stage I uLMS after complete resection.

Racial and ethnic differences in early death among gynecologic malignancy.

BACKGROUND: Racial and ethnic differences in early death after cancer diagnosis have not been well studied in gynecologic malignancy. OBJECTIVE: This study aimed to assess population-level trends and characteristics of early death among patients with gynecologic malignancy based on race and ethnicity in the United States. STUDY DESIGN: The National Cancer Institute's Surveillance, Epidemiology, and End Results Program was queried to examine 461,300 patients with gynecologic malignancies from 2000 to 2020, including uterine (n=242,709), tubo-ovarian (n=119,989), cervical (n=68,768), vulvar (n=22,991), and vaginal (n=6843) cancers. Early death, defined as a mortality event within 2 months of the index cancer diagnosis, was evaluated per race and ethnicity. RESULTS: At the cohort level, early death occurred in 21,569 patients (4.7%), including 10.5%, 5.5%, 2.9%, 2.5%, and 2.4% for tubo-ovarian, vaginal, cervical, uterine, and vulvar cancers, respectively (P<.001). In a race- and ethnicity-specific analysis, non-Hispanic Black patients with tubo-ovarian cancer had the highest early death rate (14.5%). Early death racial and ethnic differences were the largest in tubo-ovarian cancer (6.4% for Asian vs 14.5% for non-Hispanic Black), followed by uterine (1.6% for Asian vs 4.9% for non-Hispanic Black) and cervical (1.8% for Hispanic vs 3.8% to non-Hispanic Black) cancers (all, P<.001). In tubo-ovarian cancer, the early death rate decreased over time by 33% in non-Hispanic Black patients from 17.4% to 11.8% (adjusted odds ratio, 0.67; 95% confidence interval, 0.53-0.85) and 23% in non-Hispanic White patients from 12.3% to 9.5% (adjusted odds ratio, 0.77; 95% confidence interval, 0.71-0.85), respectively. The early death between-group difference diminished only modestly (12.3% vs 17.4% for 2000-2002 [adjusted odds ratio for non-Hispanic White vs non-Hispanic Black, 0.54; 95% confidence interval, 0.45-0.65] and 9.5% vs 11.8% for 2018-2020 [adjusted odds ratio, 0.65; 95% confidence interval, 0.54-0.78]). CONCLUSION: Overall, approximately 5% of patients with gynecologic malignancy died within the first 2 months from cancer diagnosis, and the early death rate exceeded 10% in non-Hispanic Black individuals with tubo-ovarian cancer. Although improving early death rates is encouraging, the difference among racial and ethnic groups remains significant, calling for further evaluation.

Stage IC grade 1 endometrioid adenocarcinoma of the ovary: assessment of post-operative chemotherapy de-escalation.

OBJECTIVE: Given limited real-world practice data evaluating the National Comprehensive Cancer Network clinical practice guidelines for possible post-operative chemotherapy omission as a treatment option for patients with stage IC grade 1 endometrioid ovarian carcinoma, this population-based study examined the association between post-operative chemotherapy and overall survival in this tumor group. METHODS: The National Cancer Institute's Surveillance, Epidemiology, and End Results program was retrospectively queried. The study population was 1207 patients with stage IC grade 1-3 endometrioid ovarian carcinoma who received primary cancer-directed surgery from 2007 to 2020. Overall survival was assessed with multivariable Cox proportional hazard regression model. RESULTS: The median age was 52, 54, and 55 years for grade 1, 2, and 3 groups, respectively (p=0.02). Grade 1 and 2 tumors were more common than grade 3 tumors (n=508 (42.1%), n=493 (40.8%), and n=206 (17.1%), respectively). Chemotherapy use rate for grade 1 tumors was lower compared with grade 2-3 tumors (67.9%, 76.5%, and 78.6%, respectively, p<0.001). When nodal evaluation was performed for grade 1 tumors, among patients who did not receive post-operative chemotherapy and among those who did, 5-year overall survival rate exceeded 90% (93.3% and 96.0%, respectively), with statistically non-significant hazard estimates (adjusted hazard ratio (aHR) 1.54, 95% CI 0.63 to 3.73). In contrast, post-operative chemotherapy omission for patients who did not undergo nodal evaluation was associated with decreased overall survival (5-year rates 82.3% vs 96.0%, aHR 5.41, 95% CI 1.95 to 15.06). Results were similar for node-evaluated grade 2 tumors (5-year overall survival rates, 94.6% and 94.4% for node-evaluated post-operative chemotherapy omission and administration, respectively), but not in grade 3 tumors. CONCLUSION: The results of this population-based study may partially support the current clinical practice guidelines for post-operative chemotherapy omission as a possible option for patients with stage IC grade 1 endometrioid adenocarcinoma of the ovary for those who had lymph node evaluation. Observed data were also supportive for node-evaluated grade 2 tumors, warranting further evaluation.

Contraception and sterilization selection at delivery among pregnant patients with malignancy.

INTRODUCTION: Since malignancy during pregnancy is uncommon, information regarding contraception selection or sterilization at delivery is limited. The objective of this study was to examine the type of long-acting reversible contraception or surgical sterilization procedure chosen by pregnant patients with malignancy at delivery. MATERIAL AND METHODS: This cross-sectional study queried the Healthcare Cost and Utilization Project's National Inpatient Sample in the USA. The study population was vaginal and cesarean deliveries in a hospital setting from January 2017 to December 2020. Pregnant patients with breast cancer (n = 1605), leukemia (n = 1190), lymphoma (n = 1120), thyroid cancer (n = 715), cervical cancer (n = 425) and melanoma (n = 400) were compared with 14 265 319 pregnant patients without malignancy. The main outcome measures were utilization of long-acting reversible contraception (subdermal implant or intrauterine device) and performance of permanent surgical sterilization (bilateral tubal ligation or bilateral salpingectomy) during the index hospital admission for delivery, assessed with a multinomial regression model controlling for clinical, pregnancy and delivery characteristics. RESULTS: When compared with pregnant patients without malignancy, pregnant patients with breast cancer were more likely to proceed with bilateral salpingectomy (adjusted odds ratio [aOR] 2.30) or intrauterine device (aOR 1.91); none received the subdermal implant. Pregnant patients with leukemia were more likely to choose a subdermal implant (aOR 2.22), whereas those with lymphoma were more likely to proceed with bilateral salpingectomy (aOR 1.93) and bilateral tubal ligation (aOR 1.76). Pregnant patients with thyroid cancer were more likely to proceed with bilateral tubal ligation (aOR 2.21) and none received the subdermal implant. No patients in the cervical cancer group selected long-acting reversible contraception, and they were more likely to proceed with bilateral salpingectomy (aOR 2.08). None in the melanoma group chose long-acting reversible contraception. Among pregnant patients aged <30, the odds of proceeding with bilateral salpingectomy were increased in patients with breast cancer (aOR 3.01), cervical cancer (aOR 2.26) or lymphoma (aOR 2.08). The odds of proceeding with bilateral tubal ligation in pregnant patients aged <30 with melanoma (aOR 5.36) was also increased. CONCLUSIONS: The results of this nationwide assessment in the United States suggest that among pregnant patients with malignancy, the preferred contraceptive option or method of sterilization at time of hospital delivery differs by malignancy type.

Increasing utilization of intrauterine device insertion at hysteroscopic endometrial evaluation for patients with endometrial hyperplasia.

PURPOSE: To examine the utilization and characteristics related to the use of hysteroscopy at the time of endometrial evaluation for endometrial hyperplasia in the outpatient surgery setting. METHODS: This cross-sectional study queried the Healthcare Cost and Utilization Project's Nationwide Ambulatory Surgery Sample. The study population was 3218 patients with endometrial hyperplasia who underwent endometrial evaluation from January 2016 to December 2019. Performance and clinical characteristics of hysteroscopic endometrial evaluation were assessed with multivariable binary logistic regression models. RESULTS: A total of 2654 (82.5%) patients had hysteroscopic endometrial tissue evaluation. Patients with postmenopausal bleeding, heavy menstrual bleeding, and polycystic ovary syndrome were more likely to undergo hysteroscopic endometrial evaluation in multivariable analysis (all, adjusted-P < 0.001). Uterine injury occurred in 4.9 per 1000 hysteroscopic endometrial evaluations; none had uterine injury in the non-hysteroscopy cohort. Among the 2654 patients who had hysteroscopic endometrial evaluation, 106 (4.0%) patients had intrauterine device insertion at surgery, and the utilization increased from 2.9 to 5.8% during the study period (P-trend < 0.001). Younger age, more recent year surgery, and obesity were independently associated with increased utilization of intrauterine device insertion at hysteroscopic endometrial evaluation (all, adjusted-P < 0.05). Among 2023 reproductive-age patients with endometrial hyperplasia, 1666 (82.4%) patients underwent hysteroscopic endometrial evaluation. On multivariable analysis, patients with heavy menstrual bleeding were more likely to have hysteroscopic endometrial evaluation (adjusted-P < 0.05). Intrauterine device insertion increased from 3.7% in 2016 to 8.0% in 2019 (P-trend = 0.007). CONCLUSION: This nationwide analysis suggests that the insertion of intrauterine devices at the time of hysteroscopic endometrial tissue evaluation for endometrial hyperplasia is increasing among reproductive-age population.

Opportunistic Salpingectomy at the Time of Laparoscopic Cholecystectomy for Ovarian Cancer Prevention: A Cost-effectiveness Analysis.

OBJECTIVE: To perform a cost-effectiveness analysis to examine the utility and effectiveness of OS performed at the time of elective cholecystectomy [laparoscopic cholecystectomy (LAP-CHOL)]. SUMMARY BACKGROUND DATA: OS has been adopted as a strategy to reduce the risk of ovarian cancer in women undergoing hysterectomy and tubal sterilization, although the procedure is rarely performed as a risk reducing strategy during other abdominopelvic procedures. METHODS: A decision model was created to examine women 40, 50, and 60 years of age undergoing LAP-CHOL with or without OS. The lifetime risk of ovarian cancer was assumed to be 1.17%, 1.09%, and 0.92% for women age 40, 50, and 60 years, respectively. OS was estimated to provide a 65% reduction in the risk of ovarian cancer and to require 30 additional minutes of operative time. We estimated the cost, quality-adjusted life-years, ovarian cancer cases and deaths prevented with OS. RESULTS: The additional cost of OS at LAP-CHOL ranged from $1898 to 1978. In a cohort of 5000 women, OS reduced the number of ovarian cancer cases by 39, 36, and 30 cases and deaths by 12, 14, and 16 in the age 40-, 50-, and 60-year-old cohorts, respectively. OS during LAP-CHOL was cost-effective, with incremental cost-effectiveness ratio of $11,162 to 26,463 in the 3 age models. In a probabilistic sensitivity analysis, incremental cost-effectiveness ratio for OS were less than $100,000 per quality-adjusted life-years in 90.5% or more of 1000 simulations. CONCLUSIONS: OS at the time of LAP-CHOL may be a cost-effective strategy to prevent ovarian cancer among average risk women.

Increasing trends of cervical conization with lymph node evaluation for fertility-sparing surgery in early cervical cancer.

OBJECTIVE: To examine uptake, characteristics, and survival outcome of less-radical fertility-sparing surgery with cervical conization and lymph node evaluation (Cone-LN) in reproductive age patients with early cervical cancer. METHODS: This retrospective cohort study examined the National Cancer Institute's Surveillance, Epidemiology, and End Results Program. The study population included 407 patients aged <50 years with stage IA-IB2 (≤4 cm) cervical cancer who received fertility-sparing surgery from 2004 to 2019. The exposure was fertility-sparing surgery type: Cone-LN (n = 196) or trachelectomy with lymph node evaluation (Trach-LN, n = 211). The main co-outcomes were (i) temporal trends of surgery type, assessed with Cochran-Armitage test, and (ii) clinical and tumor characteristics, assessed with multivariable binary logistic regression model. The secondary outcome was overall survival, assessed with inverse probability of treatment weighting propensity score. RESULTS: The number of patients receiving Cone-LN increased from 43.5% in 2004-2007 to 58.4% in 2016-2019 (P-trend = 0.005). Patients receiving conization and sentinel lymph node (SLN) biopsy alone increased from 0% to 14.4% (P-trend < 0.001). In a multivariable analysis, patients in the Cone-LN group were more likely to undergo SLN biopsy (aOR 6.04) compared to those in the Trach-LN group whereas those with adenocarcinoma (aOR 0.49) and T1b tumors (aOR for ≤2 cm 0.21, and aOR for 2.1-4.0 cm 0.10) were less likely to receive Cone-LN. In a propensity score-weighted model, the Cone-LN and Trach-LN groups had comparable overall survival (7-year rates, 98.9% vs 97.8%). Similar associations were observed for patients with squamous, adenocarcinoma / adenosquamous, T1a classification, and T1b(≤2 cm) classification. CONCLUSION: The current population-based analysis suggests that the performance of cervical conization with lymph node evaluation, particularly with SLN biopsy, is gradually increasing for early cervical cancer patients desiring future fertility.

Temporal trends of failure-to-rescue following perioperative complications in vulvar cancer surgery in the United States.

OBJECTIVE: Failure-to-rescue, defined as mortality following a perioperative complication, is a perioperative quality indicator studied in various surgeries, but not in vulvar cancer surgery. The objective of this study was to assess failure-to-rescue in patients undergoing surgical therapy for vulvar cancer. METHODS: This cross-section study queried the National Inpatient Sample. The study population was 31,077 patients who had surgical therapy for vulvar cancer from 1/2001-9/2015. The main outcomes were (i) perioperative morbidity (29 indicators) and (ii) mortality following a perioperative complication during the index admission for vulvar surgery (failure-to-rescue), assessed with a multivariable binary logistic regression model. RESULTS: The cohort-level median age was 69 years, and 14,337 (46.1%) had medical comorbidity. Perioperative complications were reported in 4736 (15.2%) patients during the hospital admission for vulvar surgery. In multivariable analysis, patient factors including older age, medical comorbidity, and morbid obesity, and treatment factors with prior radiotherapy and radical vulvectomy were associated with perioperative complications (P < 0.05). The number of patients with morbid obesity, higher comorbidity index, and prior radiotherapy increased over time (P-trends < 0.001). Among 4736 patients who developed perioperative complications, 55 patients died during the hospital admission for vulvar surgery (failure-to-rescue rate, 1.2%). In multivariable analysis, cardiac arrest (adjusted-odds ratio [aOR] 27.25), sepsis or systemic inflammatory response syndrome (aOR 11.54), pneumonia (aOR 6.03), shock (aOR 4.37), and respiratory failure (aOR 3.10) were associated with failure-to-rescue (high-risk morbidities). There was an increasing trend of high-risk morbidities from 2.0% to 3.7% over time, but the failure-to-rescue from high-risk morbidities decreased from 9.1% to 2.8% (P-trend < 0.05). CONCLUSION: Vulvar cancer patients undergoing surgical treatment had increased comorbidity over time with an increase in high-risk complications. However, failure-to-rescue rate has decreased significantly.

Two staged phase II clinical trial of Eribulin monotherapy in advanced or recurrent cervical cancer.

BACKGROUND: Eribulin a microtubule targeting agent and analog of Halichondrin B, a natural product isolated from marine sponge H. okadai, has proven clinical efficacy in metastatic pretreated breast cancer and liposarcoma. We conducted a 2-stage Phase II study of eribulin in patients with advanced/recurrent cervical cancer to examine its clinical activity and evaluate biomarkers for predictors of response. METHODS: Women with advanced/recurrent cervical cancer after ≤1 prior chemotherapy regimen, measurable disease and ECOG performance status ≤2 were treated with eribulin (1.4 mg/m2 IV day 1 and 8, every 21 days) with tumor assessments every 2 cycles. Primary endpoint was 6-month progression-free survival (PFS6); secondary were best overall response (RECISTv1.1), toxicity (CTCAEv4.03) and overall survival (OS). Exploratory endpoints were associations of biomarkers with clinical activity. Immunohistochemistry was performed on archival tumor samples. Overexpression was defined when both intensity and distribution scores were ≥ 2. RESULTS: 32 patients enrolled from 11/2012-5/2017. 29/32 patients had prior chemotherapy with cisplatin/paclitaxel/bevacizumab (n = 12) or cisplatin/gemcitabine (n = 12) as the most common regimens. 14 patients received prior paclitaxel. 1 (3%) had a complete response, 5 (16%) had a partial response and 13 (41%) had stable disease for ORR of 19% (95% CI 8, 37). Those who are paclitaxel naïve experienced the greatest benefit with a 29% ORR (95% CI 12, 54). Patients who received prior paclitaxel responded less favorably than those who did not (p = .002) and had a shorter PFS and OS. Grade 3/4 adverse events occurring in >10% of patients were anemia (n = 12, 38%), neutropenia (n = 7, 22%) and leukopenia (n = 6, 19%). Analysis of correlative predictors of response revealed that patients who did not overexpress ßII and BAX were significantly more likely to respond to e`ribulin. PFS was significantly shorter in patients with ßII and BAX overexpression, OS was significantly shorter in those with ßIII and BAX overexpression. These associations remained after multivariate analysis. CONCLUSIONS: Eribulin shows modest activity in patients with recurrent/advanced cervical cancer with a favorable toxicity profile. Prior paclitaxel exposure is associated with decreased eribulin response. ßII, ßIII tubulin subtypes and BAX are predictors of response and survival. Eribulin may be an option for women with paclitaxel-naïve recurrent/advanced cervical cancer.

Placenta previa percreta with surrounding organ involvement: a proposal for management.

Placenta accreta spectrum encompasses cases where the placenta is morbidly adherent to the myometrium. Placenta percreta, the most severe form of placenta accreta spectrum (grade 3E), occurs when the placenta invades through the myometrium and possibly into surrounding structures next to the uterine corpus. Maternal morbidity of placenta percreta is high, including severe maternal morbidity in 82.1% and mortality in 1.4% in the recent nationwide U.S. statistics. Although cesarean hysterectomy is commonly performed for patients with placenta accreta spectrum, conservative management is becoming more popular because of reduced morbidity in select cases. Treatment of grade 3E disease involving the urinary bladder, uterine cervix, or parametria is surgically complicated due to the location of the invasive placenta deep in the maternal pelvis. Cesarean hysterectomy in this setting has the potential for catastrophic hemorrhage and significant damage to surrounding organs. We propose a step-by-step schema to evaluate cases of grade 3E disease and determine whether immediate hysterectomy or conservative management, including planned delayed hysterectomy, is the most appropriate treatment option. The approach includes evaluation in the antenatal period with ultrasound and magnetic resonance imaging to determine suspicion for placenta previa percreta with surrounding organ involvement, planned cesarean delivery with a multidisciplinary team including experienced pelvic surgeons such as a gynecologic oncologist, intra-operative assessment including gross surgical field exposure and examination, cystoscopy, and consideration of careful intra-operative transvaginal ultrasound to determine the extent of placental invasion into surrounding organs. This evaluation helps decide the safety of primary cesarean hysterectomy. If safely resectable, additional considerations include intra-operative use of uterine artery embolization combined with tranexamic acid injection in cases at high risk for pelvic hemorrhage and ureteral stent placement. Availability of resuscitative endovascular balloon occlusion of the aorta is ideal. If safe resection is concerned, conservative management including planned delayed hysterectomy at around 4 weeks from cesarean delivery in stable patients is recommended.

Lymph node evaluation for endometrial hyperplasia: a nationwide analysis of minimally invasive hysterectomy in the ambulatory setting.

BACKGROUND: Given the possibility of occult endometrial cancer where nodal status confers important prognostic and therapeutic data, role of lymph node evaluation at hysterectomy for endometrial hyperplasia is currently under active investigation. The objective of the current study was to examine the characteristics related to lymph node evaluation at the time of minimally invasive hysterectomy when performed for endometrial hyperplasia in an ambulatory surgery setting. METHODS: The Healthcare Cost and Utilization Project's Nationwide Ambulatory Surgery Sample was retrospectively queried to examine 49,698 patients with endometrial hyperplasia who underwent minimally invasive hysterectomy from 1/2016 to 12/2019. A multivariable binary logistic regression model was fitted to assess the characteristics related to lymph node evaluation at hysterectomy and a classification tree model with recursive partitioning analysis was constructed to examine the utilization pattern of lymph node evaluation. RESULTS: Lymph node evaluation was performed in 2847 (5.7%) patients. In a multivariable analysis, (i) patient factors with older age, obesity, high census-level household income, and large fringe metropolitan, (ii) surgical factors with total laparoscopic hysterectomy and recent year surgery, (iii) hospital parameters with large bed capacity, urban setting, and Western U.S. region, and (iv) histology factor with presence of atypia were independently associated with increased utilization of lymph node evaluation at hysterectomy (all, P < 0.05). Among those independent factors, presence of atypia exhibited the largest association for lymph node evaluation (adjusted odds ratio 3.75, 95% confidence interval 3.39-4.16). There were 20 unique patterns of lymph node evaluation based on histology, hysterectomy type, patient age, year of surgery, and hospital bed capacity, ranging from 0 to 20.3% (absolute rate difference, 20.3%). CONCLUSION: Lymph node evaluation at the time of minimally invasive hysterectomy for endometrial hyperplasia in the ambulatory surgery setting appears to be evolving with large variability based on histology type, hysterectomy modality, patient factors, and hospital parameters, warranting a consideration of developing clinical practice guidelines.

Utilization of sentinel lymph node biopsy in the early ovarian cancer surgery.

OBJECTIVE: Sentinel lymph node (SLN) biopsy has been incorporated into surgical care for many malignancies; however, the utility has not been examined in ovarian cancer. This study examined population-level trends, characteristics, and outcomes related to SLN biopsy in early stage ovarian cancer. METHODS: This is a retrospective cohort study querying the National Cancer Institute's Surveillance, Epidemiology, and End Result Program from 2003-2018. The study population consisted of 11,512 women with stage I ovarian cancer who had adnexectomy-based surgical staging including lymph node evaluation. Exposure allocation was based on SLN biopsy use. Main outcomes measured were (i) trends and characteristics associated with SLN biopsy use, assessed by multivariable logistic regression model, and (ii) overall survival assessed with inverse provability of treatment weighting propensity score. RESULTS: SLN biopsy was performed in less than 1% of study population. In a multivariable analysis, recent surgery (2011-2018 versus 2003-2010, odds ratio [OR] 1.64, 95% confidence interval [CI] 1.03-2.59), smaller tumor size (< 10 versus ≥ 10 cm, OR 3.07, 95% CI 1.20-7.84), and East registry area (OR 2.74, 95% CI 1.73-4.36) remained independent characteristics for SLN biopsy use. In a propensity score weighted model, 5-year overall survival rate was 90.5% for the SLN biopsy-incorporated group and 88.6% for the lymphadenectomy group (hazard ratio 0.96, 95% CI 0.53-1.73). CONCLUSION: SLN biopsy was rarely performed for early ovarian cancer surgery during the study period with insufficient evidence to interpret the survival effect. SLN biopsy in early ovarian cancer appears to be in early development phase, warranting further study and careful evaluation to assess feasibility and oncologic outcome.

Metastatic extent-specific prognosis of women with stage IVB cervical cancer: multiple versus single distant organ involvement.

PURPOSE: Despite the heterogeneity of anatomical sites that metastases may affect, within the current cancer staging schematic, stage IVB encompasses all distant metastasis. This study examined survival outcomes based on the extent of distant organ metastasis in stage IVB cervical cancer. METHODS: This retrospective cohort study utilized the National Cancer Institute's Surveillance, Epidemiology, and End Result Program from 2010 to 2018. The study population included 1772 women with stage IVB cervical cancer who had tumor metastasis to one or more of the following four organs: bone, brain, liver, or lung. Overall survival was assessed based on the metastatic extent in multivariable analysis. RESULTS: The most common metastatic site was lung (68.3%) followed by bone (35.2%), liver (30.0%), and brain (1.2%). Multiple organ metastases were seen in 26.5% of study population, with lung / liver metastases being the most frequent combination pattern (9.6%) followed by lung / bone (9.4%), and lung / bone / liver (6.4%). A total of 1442 (81.4%) deaths occurred during the follow-up. The cohort-level median overall survival was 7 months, ranging from 3 months in all four organ metastases to 11 months in bone metastasis alone when stratified (absolute difference 8 months, P < 0.001). Multiple organ metastases were independently associated with nearly 50% increased all-cause mortality risk compared to single organ metastasis (adjusted-hazard ratio 1.51, 95% CI 1.34-1.70). CONCLUSION: Survival outcomes in those with stage IVB cervical cancer with distant organ involvement can vary based on the extent of metastasis. Incorporation of single versus multiple distant organ metastasis into the cancer staging schema may be valuable (IVB1 versus IVB2).

Hormonal therapy or chemotherapy for early-stage, low-grade endometrial cancer with malignant peritoneal cytology: A comparative effectiveness study.

OBJECTIVE: To examine trends, characteristics, and outcomes related to hormonal therapy (HT) or chemotherapy (CT) use for early-stage, low-grade endometrial cancer with malignant peritoneal cytology (MPC). METHODS: This is a comparative effectiveness study querying the National Cancer Database from 2010 to 2017. Study population was 2730 women with stage I grade 1-2 endometrioid endometrial cancer who had MPC at primary hysterectomy. Patients were stratified based on postoperative therapy as: CT (n = 348, 12.7%), HT (n = 112, 4.1%), and neither two (n = 2270, 83.2%). Outcome measures included (i) trends and characteristics related to adjuvant therapy, assessed with a multivariable logistic regression model, and (ii) overall survival (OS) assessed with a multivariable Cox proportional hazards regression model. RESULTS: The number of women who received HT (2.7% to 4.5%) or no adjuvant systemic therapy (81.8% to 84.4%) increased while CT use decreased (15.5% to 11.1%)(P = 0.04). In a multivariable analysis, HT use was associated with older age, more recent year of diagnosis, grade 1 lesions, treatment at academic/research facilities, performance of minimally invasive surgery, no lympho-vascular space invasion, and absence of radiotherapy compared to CT use (P < 0.05). Neither HT (adjusted-hazard ratio [aHR] 0.61, 95% confidence interval [CI] 0.27-1.40) nor CT (aHR 1.33, 95% CI 0.92-1.93) were associated with OS compared to no adjuvant systemic therapy. In the low-risk group (stage IA, grade 1-2 tumors, and no lympho-vascular space invasion; n = 1453), 69 (4.7%) women received HT and 117 (8.1%) received CT. OS was similar across the three groups (P = 0.89). CONCLUSION: There was an increasing utilization of HT and decreasing utilization of CT as adjuvant therapy for early-stage, low-grade endometrial cancer with MPC. These two adjuvant therapies were not associated with short-term OS compared to neither two.

Population-level trends and outcomes of sentinel lymph node biopsy in vulvar cancer surgery in the United States.

OBJECTIVE: To examine population-level trends, characteristics, and outcomes related to nodal assessment for vulvar cancer surgery in the United States. METHODS: This is a retrospective cohort study querying the National Cancer Institute's Surveillance, Epidemiology, and End Results Program. The study population was 5604 women with T1b or T2-smaller(≤4 cm) squamous cell carcinoma of the vulva who underwent primary vulvectomy from 2003 to 2018. The exposure allocation was based on nodal evaluation type: lymphadenectomy (LND; n = 3319, 59.2%), sentinel lymph node (SLN) biopsy (n = 751, 13.4%), or no surgical nodal evaluation (n = 1534, 27.4%). The main outcomes were (i) trends and characteristics related to SLN biopsy assessed by multinomial regression model, and (ii) vulvar cancer-specific survival assessed by competing risk analysis and inverse probability of treatment weighting propensity score. Sensitivity analysis included evaluation of external cohort with T1a disease (n = 1291). RESULTS: The utilization of SLN biopsy increased from 5.7% to 23.3% in 2006-2018, while the proportion of LND decreased from 64.1% to 48.8% in 2010-2018, and these associations remained independent in multivariable analysis (adjusted-P < 0.05). In the propensity score weighted model, 5-year cumulative rate for vulvar cancer-specific mortality was 15.2% (interquartile range 12.1-18.9) for the SLN biopsy group and 16.9% (interquartile range 15.6-18.3) for the LND group (subdistribution-hazard ratio 0.90, 95% confidence interval 0.76-1.06, P = 0.217). The increasing SLN biopsy use was also observed in T1a disease from 1.3% to 7.3% during the study period (P < 0.001). CONCLUSION: The landscape of surgical nodal evaluation is shifting from lymphadenectomy to SLN biopsy in vulvar cancer surgery in the United States. SLN biopsy-incorporated treatment approach was not associated with worse survival compared to LND.

Characterizing isolated tumor cells in regional lymph nodes of early endometrial cancer.

OBJECTIVE: To examine the characteristics of isolated tumor cells (ITCs) in regional lymph nodes of early-stage endometrial cancer. METHODS: This is a retrospective cohort study examining the National Cancer Institute's Surveillance, Epidemiology, and End Result Program. The study population was 6472 women with non-metastatic, node-negative T1 endometrial cancer who underwent primary hysterectomy and surgical nodal evaluation. Multivariable binary logistic regression model was used to identify the independent characteristics for ITCs. Postoperative therapy according to ITCs status was also assessed with propensity score weighting. RESULTS: ITCs were seen in 111 (1.7%) cases. In a multivariable analysis, ITCs were largely associated with tumor factors including deep myometrial invasion (T1b versus T1a, 4.0% versus 1.0%, adjusted-odds ratio [aOR] 3.42, P < 0.001) and larger tumor size (>4 versus ≤4 cm, 3.0% versus 1.6%, aOR 1.55, P = 0.037). Moreover, women undergoing sentinel lymph node (SLN) biopsy had a higher likelihood of identifying ITCs compared to those undergoing lymphadenectomy (LND): 2.7% for SLN alone, 3.7% for SLN/LND, and 1.2% for LND alone (aOR ranged 2.60-2.99, P < 0.001). Women who had ITCs identified were more likely to receive postoperative therapy (81.8% versus 31.7%, P < 0.001), including external beam radiotherapy (EBT) alone (25.1% versus 3.2%) and chemotherapy/EBT (16.3% versus 1.9%). Similar associations were observed in the low-risk group (stage IA, grade 1-2 endometrioid, 78.4% versus 9.2%, P < 0.001), including EBT alone (35.3% versus 0.6%). CONCLUSION: This study suggests that a SLN protocol can identify more ITCs in the regional lymph nodes of early endometrial cancer. Deep myometrial invasion and large tumor size were associated with increased risk of ITCs. Postoperative therapy is offered more frequently in the setting of ITCs with variable treatment patterns, warranting further outcome studies and practice guidelines.

Sentinel lymph node biopsy for stage II endometrial cancer: Recent utilization and outcome in the United States.

OBJECTIVE: To examine trends and outcomes related to sentinel lymph node (SLN) biopsy for stage II endometrial cancer. METHODS: This is a retrospective observational cohort study querying the National Cancer Institute's Surveillance, Epidemiology, and End Results Program. The study population was 6,314 women with T2 endometrial cancer who underwent hysterectomy from 2010-2018. Exposure allocation was based on nodal evaluation type: lymphadenectomy (LND; n=4,915, 77.8%), SLN biopsy (n=340, 5.4%), or no surgical nodal evaluation (n=1,059, 16.8%). The main outcomes were (i) trends and characteristics related to nodal evaluation assessed by multinomial regression, and (ii) overall survival (OS) assessed by an inverse probability of treatment weighting propensity score analysis. A sensitivity analysis was performed to examine concurrent LND in women who underwent SLN biopsy. RESULTS: The utilization of SLN biopsy increased from 1.6% to 16.1%, while the number of LND decreased from 81.5% to 65.7% between 2010-2018 (P<0.05). In multivariable analysis, the utilization of SLN biopsy increased 45% annually (adjusted-odds ratio 1.45, 95% confidence interval [CI] 1.37-1.54, P<0.001). The frequency of SLN biopsy alone exceeded the frequency of SLN biopsy with concurrent LND in 2017 (6.8% versus 3.4%), followed by continued increase in SLN biopsy alone (11.2% versus 4.9%) in 2018. In the weighted model, the 3-year OS rate was 79.9% for the SLN biopsy group and 78.6% for the LND group (hazard ratio 0.98, 95%Cl 0.80-1.20, P=0.831). Similarly, the SLN biopsy alone without concurrent LND had comparable OS compared to the LND group (hazard ratio 0.90, 95%CI 0.59-1.36, P=0.615). CONCLUSION: Utilization of SLN biopsy in stage II endometrial cancer increased significantly over time, and SLN biopsy-incorporated nodal assessment was not associated with worsened short-term survival outcome.