Role of systematic lymphadenectomy at the time of interval debulking surgery for patients with advanced-stage epithelial ovarian carcinoma who achieved complete gross resection.

OBJECTIVE: To evaluate the role of systematic lymphadenectomy at the time of interval cytoreductive surgery for patients with advanced-stage epithelial ovarian carcinoma who achieved complete gross resection. METHODS: The National Cancer DataBase was accessed, and patients diagnosed between 2010 and 2015 with advanced-stage ovarian carcinoma who underwent interval cytoreductive surgery and achieved complete gross resection were identified. Patients who did not undergo lymphadenectomy and those who underwent systematic lymphadenectomy (defined as at least 20 lymph nodes removed) were selected for further analysis. Median overall survival was compared with the log-rank test and controlled for a priori selected confounders. RESULTS: A total of 1060 patients were identified. Systematic lymphadenectomy was performed for 125 (11.8%) patients with a median of 29 lymph nodes (range 20-72) removed. Rate of lymph node metastasis was 62.4%. Patients who underwent systematic lymphadenectomy had higher rate of unplanned readmission (8.9% vs 1.6%, p<0.001), and median hospital stay (6 vs 4 days, p<0.001). Median overall survival for patients who did and did not undergo systematic lymphadenectomy was 44.2 and 40.4 months, respectively, p=0.40. After controlling for confounders, performance of systematic lymphadenectomy was not associated with better survival (HR=0.98, 95% CI 0.80 to 1.19). CONCLUSION: Systematic lymphadenectomy is rarely performed at the time of interval cytoreductive surgery and not associated with a survival benefit for patients who achieved complete gross resection.

Molecular landscape of ERBB2/HER2 gene amplification among patients with gynecologic malignancies; clinical implications and future directions.

OBJECTIVE: Investigate the prevalence of ERBB2/HER2 gene amplification among patients with gynecologic malignancies. METHODS: The American Association of Cancer Research (AACR) Genomics Evidence of Neoplasia Information Exchange (GENIE) (version 13.1) database was accessed and patients with endometrial, ovarian, and cervical cancer were identified. Patients with available data on the presence of copy-number gene alterations were selected for further analysis. Incidence of ERBB2 amplification following stratification by tumor site and histology was evaluated. Data from the OncoKB database, as provided by cBioPortal, was utilized to determine presence of pathogenic genomic alterations. RESULTS: A total of 6961 patients who met the inclusion criteria were identified: 49.1% with ovarian cancer, 45.2% with endometrial cancer and 5.7% with cervical cancer respectively. Overall incidence of ERBB2 amplification was 3.8%. Highest incidence of ERBB2 amplification was observed among patients with mucinous ovarian (14.4%), uterine serous (13.2%), uterine clear cell (9.4%), and uterine carcinosarcoma (7.9%). ERBB2 amplification was rare among patients with TP53 wild-type endometrioid endometrial cancer (0.4%). High incidence of mutations in genes of the PI3K pathway was observed among patients with ERBB2 amplified tumors. CONCLUSION: ERBB2 amplification is frequently encountered among patients with uterine serous carcinoma, and mucinous ovarian carcinoma. In addition, a high incidence was also observed among those with uterine clear cell carcinoma, and uterine carcinosarcoma. For patients with endometrioid endometrial carcinoma, incidence of ERBB2 amplification is low, especially in the absence of TP53 mutations.

Impact of delayed interval cytoreductive surgery on the survival of patients with advanced stage high-grade epithelial ovarian carcinoma.

OBJECTIVE: Our objective was to use real-world data to investigate the impact of delayed interval cytoreductive surgery on the survival of patients with advanced stage high-grade ovarian carcinoma. METHODS: We accessed the National Cancer Database and identified patients diagnosed between 2004-2015 with advanced stage high-grade ovarian carcinoma who received neoadjuvant chemotherapy and underwent interval cytoreductive surgery. Based on timing between surgery and chemotherapy administration patients were categorized into standard (9-13.0 weeks) and delayed (13.01-26 weeks) interval cytoreductive surgery groups. Overall survival was compared with the log-rank test and a Cox model was constructed to control for a priori selected confounders. RESULTS: We identified a total of 5051 patients; 2389 (47.3%) and 2662 (52.7%) in the standard and delayed interval cytoreductive surgery groups respectively. There was no difference in complete gross resection rates (53.2% vs 54.5%, p=0.51). Patients in the delayed interval cytoreductive surgery group were less likely to undergo complex surgery (39.3% vs 45.6%, p<0.001) and had lower rates of unplanned re-admission (4.1% vs 2.6%, p=0.003). There was no difference in overall survival between the standard and delayed interval cytoreductive surgery groups, p=0.13 (median 34.3 vs 33.9 months) even after controlling for confounders (hazard ratio (HR) 1.04, 95% confidence intervals (CIs): 0.97, 1.12). There was no difference in overall survival between the two groups for patients with no gross residual (p=0.95; median overall survival 40.08 vs 39.8 months) or gross residual disease (p=0.16; median overall survival 32.89 and 32.16 months). CONCLUSION: For patients with advanced stage ovarian cancer delayed interval cytoreductive surgery may not be associated with worse overall survival.

Impact of adjuvant chemotherapy on the overall survival of patients with advanced-stage low-grade serous ovarian carcinoma following primary cytoreductive surgery.

OBJECTIVE: To investigate the use and outcomes of adjuvant chemotherapy for patients with advanced-stage low-grade serous ovarian carcinoma following primary cytoreductive surgery. METHODS: Patients diagnosed between 2010 and 2015 with International Federation of Gynecology and Obstetrics stage II-IV low-grade serous ovarian carcinoma who underwent primary debulking surgery with known residual disease status and had at least 1 month of follow-up were identified in the National Cancer Database. Adjuvant chemotherapy was defined as receipt of chemotherapy within 6 months of surgery. Overall survival was evaluated using the Kaplan-Meier method and compared with the log-rank test. A Cox model was constructed to control for a priori-selected confounders. A systematic review of the literature was also performed. RESULTS: In total, 618 patients with stage II-IV low-grade serous ovarian carcinoma who underwent primary cytoreductive surgery were identified; 501 (81.1%) patients received adjuvant chemotherapy, while 117 (18.9%) patients did not. The median follow-up of the present cohort was 47.97 months. There was no difference in overall survival between patients who did and did not receive adjuvant chemotherapy (p=0.78; 4-year overall survival rates were 77.5% and 76.1%, respectively). After controlling for patient age, medical co-morbidities, disease stage, and residual disease status, administration of adjuvant chemotherapy was not associated with better overall survival (HR=0.87, 95% CI 0.55 to 1.38). Based on data from three retrospective studies, omission of adjuvant chemotherapy following cytoreductive surgery was not associated with worse progression-free survival benefit (HR=1.25, 95% CI 0.80 to 1.95) for patients with stage III-V low-grade serous ovarian carcinoma. CONCLUSIONS: Adjuvant chemotherapy may not be associated with an overall survival benefit for patients with advanced-stage low-grade serous ovarian carcinoma following primary cytoreductive surgery.

Role of immunotherapy for lymph node positive vulvar melanoma: utilization and outcomes.

OBJECTIVE: To investigate the utilization and outcomes of adjuvant immunotherapy for patients with vulvar melanoma and inguinal lymph node metastases. METHODS: The National Cancer Database was accessed and patients with vulvar melanoma diagnosed between 2004 and 2015 who did not have distant metastases, underwent inguinal lymphadenectomy, had positive lymph nodes, and at least 1 month of follow-up were identified. Administration of immunotherapy was evaluated and clinicopathological characteristics were compared. Median overall survival was compared with the log-rank test. Stratified analysis based on clinical status of lymph nodes was performed. A Cox model was constructed to evaluate survival after controlling for confounders. RESULTS: A total of 300 patients were identified; the rate of immunotherapy use was 25% (75 patients). Patients who received immunotherapy were younger (median 58 vs 70 years, p<0.001); however, the two groups were comparable in terms of clinical lymph node status, rate of positive tumor margins, presence of tumor ulceration, tumor size, Breslow thickness, and performance of comprehensive lymphadenectomy. There was no overall survival difference between patients who did (median 31.08 months) and did not (median 22.77 months) receive immunotherapy (p=0.18). Following stratification by clinical lymph node status, immunotherapy did not improve overall survival of patients with clinically negative (median 35.35 vs 33.22, p=0.75) or positive lymph nodes (median 23.33 vs 16.99, p=0.64). After controlling for confounders, administration of immunotherapy was not associated with better overall survival (HR 0.81, 95% CI 0.57 to 1.14). CONCLUSIONS: In this study approximately one in four patients received adjuvant immunotherapy. Immunotherapy was not associated with improved overall survival.

Next generation sequencing reveals a high prevalence of pathogenic mutations in homologous recombination DNA damage repair genes among patients with uterine sarcoma.

OBJECTIVE: Investigate the incidence of homologous recombination DNA damage response (HR-DDR) genomic alterations among patients with uterine sarcoma. METHODS: The American Association for Cancer Research GENIE v13.0 database was accessed and patients with uterine leiomyosarcoma, adenosarcoma, undifferentiated uterine sarcoma, high-grade endometrial stromal sarcoma, low-grade endometrial stromal sarcoma, and endometrial stromal sarcoma not otherwise specified were identified. We determined the incidence of pathogenic alterations in the following genes involved in HR-DDR: ATM, ARID1A, ATRX, BAP1, BARD1, BLM, BRCA2, BRCA1, BRIP1, CHEK2, CHEK1, FANCA, FANCC, FANCD2, FANCE, FANCF, FANCG, FANCL, MRE11, NBN, PALB2, RAD50, RAD51, RAD51B, RAD51C, RAD51D, WRN. Data from the OncoKB database, as provided by cBioPortal, was utilized to determine the presence of pathogenic genomic alterations. RESULTS: A total of 509 patients contributing with 525 samples were identified. Median patient age at sample collection was 56 years while the majority were White (80.7%). The most common histologic subtype was leiomyosarcoma (63.8%) followed by adenosarcoma (12.3%). The overall incidence of HR-DDR genomic alterations was 28.2%. The most commonly altered genes were ATRX (18.2%), BRCA2 (4%), and RAD51B (2.6%). The highest incidence of HR-DDR genomic alterations was observed among patients with leiomyosarcoma (35.4%), adenosarcoma (27%) and undifferentiated uterine sarcoma (30%), while those with low-grade endometrial stromal sarcoma had the lowest (2.9%) incidence. CONCLUSIONS: Approximately 1 in 3 patients with uterine sarcoma harbor a pathogenic alteration in HR-DDR genes. Incidence is high among patients with uterine leiomyosarcoma and adenosarcoma.

Awareness and Interest in Uterus Transplantation over Time: Analysis of Those Seeking Surgical Correction for Uterine-Factor Infertility in the US.

This study describes the characteristics of women who contacted an active program performing uterus transplantation (UTx) in the US, expressing interest in becoming a uterus transplant recipient or a living donor. Basic demographic and self-reported clinical information was collected from women who contacted any of the three US UTx programs from 2015 to July 2022. The three centers received 5194 inquiries about becoming a UTx recipient during the study timeframe. Among those reporting a cause of infertility, almost all of the reports (4066/4331, 94%) were absence of a uterus, either congenitally (794/4066, 20%) or secondary to hysterectomy (3272/4066, 80%). The mean age was 34 years, and 49% (2545/5194) had at least one child at the time of application. The two centers using living donors received 2217 inquiries about becoming living donors. The mean age was 34 years, and 60% (1330/2217) had given birth to ≥1 child. While most of the UTx clinical trial evidence has focused on young women with congenital absence of the uterus, these results show interest from a much broader patient population in terms of age, cause of infertility, and parity. These results raise questions about whether and to what extent the indications and eligibility criteria for UTx should be expanded as the procedure transitions from the experimental phase to being offered as a clinical treatment.

Combination ATR (ceralasertib) and PARP (olaparib) Inhibitor (CAPRI) Trial in Acquired PARP Inhibitor-Resistant Homologous Recombination-Deficient Ovarian Cancer.

PURPOSE: Addition of ataxia telangiectasia and Rad3-related kinase inhibitors (ATRi) to PARP inhibitors (PARPi) overcomes PARPi resistance in high-grade serous ovarian cancer (HGSOC) cell and mouse models. We present the results of an investigator-initiated study of combination PARPi (olaparib) and ATRi (ceralasertib) in patients with acquired PARPi-resistant HGSOC. PATIENTS AND METHODS: Eligible patients had recurrent, platinum-sensitive BRCA1/2 mutated or homologous recombination (HR)-deficient (HRD) HGSOC and clinically benefited from PARPi (response by imaging/CA-125 or duration of maintenance therapy; > 12 months first-line or > 6 months ≥ second-line) before progression. No intervening chemotherapy was permitted. Patients received olaparib 300 mg twice daily and ceralasertib 160 mg daily on days 1 to 7 of a 28-day cycle. Primary objectives were safety and objective response rate (ORR). RESULTS: Thirteen patients enrolled were evaluable for safety and 12 for efficacy; 62% (n = 8) had germline BRCA1/2 mutations, 23% (n = 3) somatic BRCA1/2 mutations, and 15% (n = 2) tumors with positive HRD assay. Prior PARPi indication was treatment for recurrence (54%, n = 7), second-line maintenance (38%, n = 5) and first-line treatment with carboplatin/paclitaxel (8%, n = 1). There were 6 partial responses yielding an ORR of 50% (95% confidence interval, 0.15-0.72). Median treatment duration was 8 cycles (range 4-23+). Grade (G) 3/4 toxicities were 38% (n = 5); 15% (n = 2) G3 anemia, 23% (n = 3) G3 thrombocytopenia, 8% (n = 1) G4 neutropenia. Four patients required dose reductions. No patient discontinued treatment due to toxicity. CONCLUSIONS: Combination olaparib and ceralasertib is tolerable and shows activity in HR-deficient platinum-sensitive recurrent HGSOC that benefited and then progressed with PARPi as the penultimate regimen. These data suggest that ceralasertib resensitizes PARPi-resistant HGSOCs to olaparib, warranting further investigation.

A retrospective case series of Mohs micrographic surgery and interdisciplinary management of female genital skin cancers: Local recurrence rates and patient-reported outcomes.

BACKGROUND: Conventional excision of female genital skin cancers has high rates of local recurrence and morbidity. Few publications describe local recurrence rates (LRRs) and patient-reported outcomes (PROs) after Mohs micrographic surgery (MMS) for female genital skin cancers. OBJECTIVE: To evaluate LRRs, PROs, and interdisciplinary care after MMS for female genital skin cancers. METHODS: A retrospective case series was conducted of female genital skin cancers treated with MMS between 2006 and 2021 at an academic center. The primary outcome was local recurrence. Secondary outcomes were PROs and details of interdisciplinary care. RESULTS: Sixty skin cancers in 57 patients were treated with MMS. Common diagnoses included squamous cell cancer (n = 26), basal cell cancer (n = 12), and extramammary Paget disease (n = 11). Three local recurrences were detected with a mean follow-up of 61.1 months (median: 48.8 months). Thirty-one patients completed the PROs survey. Most patients were satisfied with MMS (71.0%, 22/31) and reported no urinary incontinence (93.5%, 29/31). Eight patients were sexually active at follow-up and 75.0% (6/8) experienced no sexual dysfunction. Most cases involved interdisciplinary collaboration 71.7% (43/60). LIMITATIONS: Limitations include the retrospective single-center design, heterogeneous cohort, and lack of preoperative function data. CONCLUSIONS: Incorporating MMS into interdisciplinary teams may help achieve low LRRs and satisfactory function after genital skin cancer surgery.

Facility level variation in the utilization of neoadjuvant chemotherapy is associated with higher surgical morbidity for patients with advanced stage epithelial ovarian carcinoma.

OBJECTIVE: Investigate outcomes for advanced stage epithelial ovarian cancer (EOC) patients based on facility-level utilization of neoadjuvant chemotherapy (NACT). METHODS: Stage III-IV EOC patients diagnosed between 2010 and 2016 were identified in the National Cancer Database. Percentage of patients managed with NACT was calculated for facilities, reporting ≥120 patients. Facilities with lowest and highest quartile of NACT rate comprised the low and high-utilizing groups. Clinico-pathological characteristics were collected, and appropriate statistical analysis performed. RESULTS: High- and low-utilizing facilities managed on average 54.1% and 25.4% of patients with NACT respectively. Patients managed at high-utilizing facilities were significantly more likely to be >65 (p = 0.029), have stage IV disease (p < 0.001) and comorbidities (p < 0.001). Patients managed with primary debulking surgery (PDS) at low-utilizing facilities were significantly more likely to be >65, have stage IV disease, and have comorbidities (all, p < 0.001). Patients undergoing PDS at low-utilizing facilities were significantly less likely to achieve complete gross resection (p < 0.001), and were significantly more likely to experience 90-day mortality (p < 0.001), and unplanned 30-day readmission (p < 0.001). After controlling for age, comorbidities, race, insurance status, stage, grade and histology, high-utilizing facilities trended towards better overall survival (OS) (HR: 0.92, 95% CI: 0.85-0.99). Overall, patients undergoing PDS had better OS compared to those who had NACT (median 42 vs 27 months, p < 0.001). CONCLUSIONS: Despite treating an EOC population with more advanced disease and comorbidities, high-utilizing facilities have lower surgical morbidity and mortality with no detrimental impact on long-term survival. Careful patient selection to minimize the morbidity and mortality associated with PDS is pivotal.

[18F]FluorThanatrace ([18F]FTT) PET Imaging of PARP-Inhibitor Drug-Target Engagement as a Biomarker of Response in Ovarian Cancer, a Pilot Study.

PURPOSE: PARP inhibitors have become the standard-of-care treatment for homologous recombination deficient (HRD) high-grade serous ovarian cancer (HGSOC). However, not all HRD tumors respond to PARPi. Biomarkers to predict response are needed. [18F]FluorThanatrace ([18F]FTT) is a PARPi-analog PET radiotracer that noninvasively measures PARP-1 expression. Herein, we evaluate [18F]FTT as a biomarker to predict response to PARPi in patient-derived xenograft (PDX) models and subjects with HRD HGSOC. EXPERIMENTAL DESIGN: In PDX models, [18F]FTT-PET was performed before and after PARPi (olaparib), ataxia-telangiectasia inhibitor (ATRi), or both (PARPi-ATRi). Changes in [18F]FTT were correlated with tumor volume changes. Subjects were imaged with [18F]FTT-PET at baseline and after ∼1 week of PARPi. Changes in [18F]FTT-PET uptake were compared with changes in tumor size (RECISTv1.1), CA-125, and progression-free survival (PFS). RESULTS: A decrease in [18F]FTT tumor uptake after PARPi correlated with response to PARPi, or PARPi-ATRi treatment in PARPi-resistant PDX models (r = 0.77-0.81). In subjects (n = 11), percent difference in [18F]FTT-PET after ∼7 days of PARPi compared with baseline correlated with best RECIST response (P = 0.01), best CA-125 response (P = 0.033), and PFS (P = 0.027). All subjects with >50% reduction in [18F]FTT uptake had >6-month PFS and >50% reduction in CA-125. Utilizing only baseline [18F]FTT uptake did not predict such responses. CONCLUSIONS: The decline in [18F]FTT uptake shortly after PARPi initiation provides a measure of drug-target engagement and shows promise as a biomarker to guide PARPi therapies in this pilot study. These results support additional preclinical mechanistic and clinical studies in subjects receiving PARPi ± combination therapy. See related commentary by Liu and Zamarin, p. 1384.

Predictive value of 5-Factor modified frailty index in Oncologic and benign hysterectomies.

Background: The 5-factor modified frailty index (mFI-5) has been validated against the original 11-factor modified frailty index in gynecologic surgery, however its utility has not been evaluated between benign versus gynecologic oncology patient populations. Objective: To evaluate the predictive value of the mFI-5 in identifying women at increased risk for major postoperative complications, readmission, or death within 30 days of hysterectomy for benign and oncologic indications. Methods: Patients who underwent hysterectomy between 2015 and 2017 were identified from the NSQIP database and stratified into benign or malignant indications. Demographic and mFI-5 variables were extracted. The mFI-5 was calculated by dividing the sum of all affirmative variables by the total number of input variables in the database. Logistic regression modeling was performed adjusting for confounders. C-statistic with 95% CI was obtained post-regression. Results: 80,293 hysterectomies (59,078 benign and 21,215 oncologic) were identified. The benign group was more likely to have an mFI-5 score of 0 (70 % vs 50 %, p = 0.001) and had shorter operative times (p = 0.001). In the benign group, mFI-5 was a strong predictor of mortality (c = 0.819, CI 0.704-0.933). Within the oncology group, the mFI-5 was a strong predictor of mortality (c = 0.801, CI 0.750-0.851), particularly for uterine and cervical cancers. It was moderately predictive of readmission (c = 0.671, CI 0.656-0.686) and strongly predictive of Clavien-Dindo class III and IV complications (c = 0.732, CI 0.713-0.750). Conclusion: The mFI-5 is a strong predictor of 30-day mortality and serious postoperative complications. These findings have the potential to improve identification of high-risk patients in the preoperative setting.

Addition of External Beam Radiation Therapy to Adjuvant Chemotherapy for Patients With Stage IIIC Uterine Endometrioid Carcinoma: Utilization and Outcomes.

OBJECTIVES: Evaluate whether the addition of external beam radiation (EBRT) to adjuvant chemotherapy with or without vaginal brachytherapy is associated with better survival for patients with stage IIIC endometrioid endometrial carcinoma. MATERIALS AND METHODS: Patients diagnosed between 2010 and 2015 with apparent early-stage endometrioid adenocarcinoma, without a history of another tumor, who underwent hysterectomy with lymphadenectomy and had positive lymph nodes were identified in the National Cancer Database. Those who received adjuvant chemotherapy (defined as receipt of treatment within 6 mo from surgery) and had at least 1 month of follow-up were selected for further analysis. Overall survival was compared between patients who did and did not receive EBRT within 6 months from surgery with the log-rank test. A Cox model was also constructed to control for confounders. RESULTS: A total of 3116 patients were identified; 1458 (46.8%) received chemotherapy without and 1658 (53.2%) with EBRT. Pathologic characteristics (tumor grade, size, endocervical, and lymph-vascular invasion) were comparable between the two groups. Patients who received external beam radiation had better survival compared with those who did not, P =0.001; 5-year overall survival rates were 83.1% and 77.9%, respectively. After controlling for patient age, race, presence of comorbidities, insurance status, tumor size, grade and endocervical invasion, and the presence of lymph-vascular invasion, the addition of EBRT was associated with a survival benefit (HR: 0.75, 95% CI: 0.62, 0.91). CONCLUSIONS: For patients with endometrioid adenocarcinoma metastatic to the lymph nodes, addition of external beam radiation to adjuvant chemotherapy may be associated with a survival benefit.

The First 5 Years of Uterus Transplant in the US: A Report From the United States Uterus Transplant Consortium.

Importance: Uterus transplant is a viable surgical treatment for women affected by absolute uterine-factor infertility, which affects 1 in 500 women. Objective: To review transplant and birth outcomes of uterus transplant recipients in the US since the first case in 2016. Design, Setting, and Participants: In this cohort study, 5 years of uterus transplant outcome data were collected from the 3 centers performing uterus transplants in the US: Baylor University Medical Center, Dallas, Texas; Cleveland Clinic, Cleveland, Ohio; and University of Pennsylvania, Philadelphia. A total of 33 women with absolute uterine-factor infertility who underwent uterus transplant between February 2016 and September 2021 were included. Main Outcomes and Measures: Graft survival, live birth, and neonatal outcome. Results: Of the 33 included uterus transplant recipients, 2 (6%) were Asian, 1 (3%) was Black, 1 (3%) was South Asian, and 29 (88%) were White; the mean (SD) age was 31 (4.7) years; and the mean (SD) body mass index (calculated as weight in kilograms divided by height in meters squared) was 24 (3.6). Most uterus transplant recipients (31 of 33 [94%]) had a congenitally absent uterus (Mayer-Rokitansky-Küster-Hauser syndrome), and 21 of 33 (64%) received organs from living donors. Mean (range) follow-up was 36 (1-67) months. There was no donor or recipient mortality. One-year graft survival was 74% (23 of 31 recipients). Through October 2021, 19 of 33 recipients (58%) had delivered 21 live-born children. Among recipients with a viable graft at 1 year, the proportion with a live-born child was 83% (19 of 23). The median (range) gestational age at birth of neonates was 36 weeks 6 days (30 weeks, 1 day to 38 weeks), and the median (range) birth weight was 2860 (1310-3940) g (median [range], 58th [6th-98th] percentile). No congenital malformations were detected. Conclusions and Relevance: Uterus transplant is a surgical therapy that enables women with uterine-factor infertility to successfully gestate and deliver children. Aggregate data from US centers demonstrate safety for the recipient, living donor, and child. These data may be used to counsel women with uterine-factor infertility on treatment options.

Oncologic outcomes of surgical para-aortic lymph node staging in patients with advanced cervical carcinoma undergoing chemoradiation.

OBJECTIVES: We aimed to evaluate the utilization and impact of surgical para-aortic lymph node staging on the survival of patients with locally advanced stage cervical carcinoma receiving definitive chemoradiation. METHODS: We identified patients in the National Cancer Database diagnosed between January 2010 and December 2015 with locally advanced (FIGO 2009 stage IB2-IVA) cervical carcinoma who did not undergo hysterectomy, received primary chemoradiation and had at least 1 month of follow-up. Two groups of patients were formed based on the assessment method of para-aortic lymph node status - radiologic assessment only versus surgical lymphadenectomy. Overall survival was compared with the log-rank test after Kaplan-Meier curves were generated. A Cox model was constructed to control for a priori selected confounders. RESULTS: We identified a total of 3540 patients who met the inclusion criteria. Para-aortic staging was performed in 333 (9.4%) patients. These patients were younger (median age 46 vs 52 years, p<0.001), less likely to have co-morbidities (8.7% vs 15.6%, p<0.001), more likely to have private insurance (48.9% vs 37.8%, p<0.001) and receive brachytherapy (76.9% vs 70.9%, p=0.022). The rate of para-aortic lymphadenectomy was comparable between patients with stage IB2-II and III-IVA disease (9.4% for both groups, p=0.98). Patients who underwent para-aortic lymphadenectomy were also more likely to have lymph nodes categorized as positive compared with those who had imaging only (27.3% vs 13.2%, p<0.001). There was no difference in overall survival between patients who underwent radiologic only or surgical para-aortic lymph node assessment (p=0.80 from log-rank test); 4 year overall survival rates were 62.9% and 63%. After controlling for confounders, performance of para-aortic lymphadenectomy was not associated with a survival benefit (HR 1.07, 95% CIs: 0.88 to 1.31). CONCLUSIONS: In a large cohort of patients with locally advanced stage cervical carcinoma, para-aortic lymphadenectomy was rarely performed and not associated with a survival benefit.

Safety of ovarian preservation for premenopausal patients with FIGO stage I grade 2 and 3 endometrioid endometrial adenocarcinoma.

OBJECTIVE: To investigate the utilization and outcomes of ovarian preservation for premenopausal patients with International Federation of Gynecology and Obstetrics (FIGO) stage I grade 2 and 3 endometrioid endometrial carcinoma undergoing hysterectomy. METHODS: The National Cancer Database was accessed; patients aged ≤45 years diagnosed between January 2004 and December 2015 with FIGO stage I grade 2 or 3 endometrioid endometrial carcinoma, who underwent hysterectomy with or without bilateral salpingo-oophorectomy and had at least 1 month of follow-up, were identified. Overall survival was assessed following generation of Kaplan-Meier curves and compared with the log-rank test. A Cox model was constructed to control for a priori selected variables. RESULTS: A total of 2941 patients who met the inclusion criteria were identified; 200 (6.8%) patients did not undergo bilateral salpingo-oophorectomy. Rate of ovarian preservation was comparable between patients with grade 2 (n=163, 6.6%) and grade 3 (n=37, 7.7%) tumors (p=0.38). Patients who did not undergo bilateral salpingo-oophorectomy were younger (median 39 vs 41 years, p<0.001) and less likely to undergo surgical lymph node assessment (52% vs 76.2%, p<0.001). There was no difference in overall survival between patients who did and did not undergo bilateral salpingo-oophorectomy (p=0.94); 5 year overall survival rates were 96.6% and 97%, respectively. After controlling for confounders, including tumor grade, ovarian preservation was not associated with worse overall survival (HR 0.92, 95% CI 0.47 to 1.84). CONCLUSIONS: For patients with grade 2 and 3 FIGO stage I endometrioid carcinoma undergoing hysterectomy, ovarian preservation is rarely performed while no clear detrimental effect on overall survival was found.

Adjuvant chemotherapy for stage I high-intermediate risk endometrial carcinoma with lymph-vascular invasion.

OBJECTIVE: The goal of this study was to evaluate if addition of adjuvant chemotherapy to radiation therapy improves overall survival in patients with high-intermediate risk stage I endometrial carcinoma with lymphovascular invasion. METHODS: Patients diagnosed between January 2010 and December 2015 with FIGO (International Federation of Gynecology and Obstetrics) stage I endometrioid endometrial carcinoma with lymphovascular invasion who underwent hysterectomy with lymphadenectomy and met the GOG-99 criteria for high-intermediate risk were identified in the National Cancer Database. Patients who received adjuvant radiotherapy with or without adjuvant chemotherapy (administered within 6 months of surgery) and had at least 1 month of follow-up were selected for further analysis. Overall survival was compared with the log-rank test following stratification by type of radiation treatment. A Cox model was constructed to control for a priori selected confounders. RESULTS: A total of 2881 patients who met the inclusion criteria were identified; 2417 (83.9%) patients received radiation therapy alone while 464 (16.1%) received chemoradiation. Rate of adjuvant chemotherapy administration was comparable between patients who received vaginal brachytherapy alone (16.2%), and external beam radiation therapy (with or without vaginal brachytherapy) (15.8%), p=0.78. Rate of chemoradiation was higher for patients with grade 3 (28.8%) tumors compared with those with grade 2 (9.9%) and grade 1 (8.3%) tumors, p<0.001. After controlling for confounders for patients receiving external beam radiation, addition of chemotherapy was not associated with improved overall survival (HR 0.90, 95% CI 0.56 to 1.46). For patients receiving vaginal brachytherapy addition of chemotherapy was associated with better overall survival (HR 0.644, 95% CI 0.45 to 0.92). Benefit was limited to patients with grade 3 tumors, p=0.026; 4-year overall survival rate was 81.1% versus 74.9%. CONCLUSIONS: In patients with high-intermediate risk FIGO stage I endometrioid endometrial carcinoma and lymphovascular invasion, addition of chemotherapy to radiation therapy was associated with a survival benefit for patients with grade 3 tumors receiving vaginal brachytherapy.

Delay in adjuvant chemotherapy administration for patients with FIGO stage I epithelial ovarian carcinoma is associated with worse survival; an analysis of the National Cancer Database.

OBJECTIVE: The administration of adjuvant chemotherapy within 42 days from surgery is one of the proposed quality measures for patients with epithelial ovarian cancer (EOC). The aim of the present study was to evaluate the impact of chemotherapy delay in the survival of patients with stage I EOC. METHODS: The National Cancer Database was accessed, and patients diagnosed between 2004 and 2015 with FIGO stage I EOC who received multi-agent chemotherapy were identified. Overall survival (OS) was compared between patients who received chemotherapy <6 weeks and 6-12 weeks from surgery with the log-rank test following generation of Kaplan-Meier curves. Cox model was constructed to control for a priori selected confounders. RESULTS: A total of 8549 patients who received adjuvant chemotherapy at a median 35 days from surgery (interquartile range 19) were identified; 67.7% received adjuvant chemotherapy <6 weeks from surgery while 32.3% experienced a delay. Patients who experienced a delay were more likely to have comorbidities (18.4% vs 14.9%, p < 0.001), and be managed in non-academic facilities (57.1% vs 53.2%, p = 0.001). Patients who experienced a delay had worse OS compared to those who did not, p < 0.001; 5-year OS rates 85.7% and 89.7%, respectively. For patients with high-grade serous tumors, those who experienced a delay had a 5-yr OS of 81.9% compared to 88.6% for those who did not, p < 0.001. After controlling for age, race, presence of comorbidities, insurance status, tumor histology and grade, performance of lymphadenectomy and substage, chemotherapy delay was associated with worse survival (HR: 1.25, 95% CI: 1.10, 1.42). CONCLUSIONS: For patients with early stage EOC administration of adjuvant chemotherapy within 6 weeks from surgery was associated with better overall survival, especially for those with stage IC disease.

Interdisciplinary Management of Extramammary Paget's Disease Using Mohs Micrographic Surgery With Frozen Section Cytokeratin-7 Immunostains.

OBJECTIVE: To describe local recurrence rates and patient-reported outcomes when Mohs micrographic surgery with cytokeratin-7 immunostains (MMS-CK7) is included in the interdisciplinary management of extramammary Paget's disease (EMPD) METHODS: A retrospective study was conducted of EMPD treated with MMS-CK7 as part of an interdisciplinary team at an academic medical center between 2009 and 2016. Local recurrence rates and patient-reported outcomes were determined by record review and patient surveys. RESULTS: Twenty tumors in 19 patients were treated using MMS-CK7. After MMS-CK7 defined clear microscopic margins, 75% (15/20) of tumors underwent excision or reconstruction by a surgical colleague. Internal malignancy screening was performed by multiple specialties in 17 patients, with 1 associated malignancy of prostate cancer detected. No local recurrence was detected with a mean follow-up of 75.2 months. Most patients were satisfied with appearance (18/19, 95%) and function (16/19, 84%) after surgery. CONCLUSION: Interdisciplinary teams that include MMS-CK7 can treat EMPD with low local recurrence rates, high patient satisfaction, and thorough internal malignancy screening.

Disparities in cancer-specific and overall survival in black women with endometrial cancer: A Medicare-SEER study.

OBJECTIVES: To examine overall survival (OS) and cancer-specific survival (CSS) for different racial groups of women with surgically staged endometrial cancer by histologic subtype. METHODS: This is a retrospective cohort study of women with stage I-III endometrioid, serous, clear cell, and carcinosarcoma who underwent hysterectomy as primary surgical staging in the 2000-2016 SEER-Medicare database. OS and CSS outcomes were stratified by race (defined as White, Black, Other), stage, and histology. Survival was assessed with descriptive analyses, log-rank tests and unadjusted and adjusted multivariable cox regression models. RESULTS: Of the 24,142 women identified, 85.5% were White, 8.5% Black, and 6% other races. Receipt of adjuvant therapy differed only for stage III endometrioid: Black women were less likely to receive adjuvant treatment after hysterectomy (61.2% vs. 70.1% White, p = 0.03). For stage I, Black women had worse CSS for all histologies other than clear cell in unadjusted and adjusted analyses. For stage II, Black women had worse CSS for endometrioid histology in unadjusted analyses and similar OS. For stage III, Black women with endometrioid carcinoma had worse CSS and OS in unadjusted analyses, but no significant difference in CSS in adjusted analyses. "Other" race showed improved OS for Stage I endometrioid adenocarcinoma without significant differences in outcomes when compared to White women. CONCLUSION: Across histologies other than clear cell, Black women diagnosed with stage I endometrial cancer had consistently worse CSS, despite similar receipt of adjuvant therapy. Differences in CSS and OS at higher stages disappeared once accounting for treatment disparities.