Mary Katherine Anastasio

Robotic sentinel lymph node mapping with sensitive Firefly for endometrial cancer staging

Antibody-Drug Conjugates in Gynecologic Cancers

Antibody-drug conjugates (ADCs) are a novel class of targeted cancer therapies with the ability to selectively deliver a cytotoxic drug to a tumor cell using a monoclonal antibody linked to a cytotoxic payload. The technology of ADCs allows for tumor-specificity, improved efficacy, and decreased toxicity compared to standard chemotherapy. Common toxicities associated with ADC use include ocular, pulmonary, hematologic, and neurologic toxicities. Several ADCs have been approved by the United States Food and Drug Administration (FDA) for the management of patients with recurrent or metastatic gynecologic cancers, a population with poor outcomes and limited effective treatment options. The first FDA-approved ADC for recurrent or metastatic cervical cancer was tisotumab vedotin, a tissue factor-targeting agent, after demonstrating response in the innovaTV 204 trial. Mirvetuximab soravtansine targets folate receptor alpha and is approved for use in patients with folate receptor alpha-positive, platinum-resistant, epithelial ovarian cancer based on results from the SORAYA trial. While there are no FDA-approved ADCs for the treatment of uterine cancer, trastuzumab deruxtecan, an anti-human epidermal growth factor receptor 2 (HER2) agent, is actively being investigated. In this review, we will describe the structure and mechanism of action of ADCs, discuss their toxicity profiles, review ADCs both approved and under investigation for the management of gynecologic cancers, and discuss mechanisms of ADC resistance.

Adjuvant treatment and outcomes for patients with stage IIIA grade 1 endometrioid endometrial cancer

The role and type of adjuvant therapy for patients with International Federation of Gynecology and Obstetrics (FIGO) stage IIIA grade 1 endometrioid endometrial adenocarcinoma are controversial. This retrospective cohort study aimed to determine associations between adjuvant therapy use and survival among patients with stage IIIA grade 1 endometrial cancer. Patients who underwent primary surgery for stage IIIA (FIGO 2009 staging) grade 1 endometrial cancer between January 2004 and December 2016 were identified in the National Cancer Database. Demographics and receipt of adjuvant therapy were compared. Overall survival was analyzed using Kaplan-Meier curves, log-rank test, and multivariable Cox proportional hazard models. Of 1120 patients, 248 (22.1%) received no adjuvant treatment, 286 (25.5%) received chemotherapy alone, 201 (18.0%) radiation alone, and 385 (34.4%) chemotherapy and radiation. Five-year overall survival rate was 83.0% (95% CI 80.1% to 85.6%). Older age, increasing comorbidity count, and lymphovascular space invasion status were significant negative predictors of survival. Over time, there was an increasing rate of chemotherapy (45.4% in 2004-2009 vs 69.2% in 2010-2016; p<0.001). In the multivariable analysis, chemotherapy was associated with significantly improved overall survival compared with no adjuvant therapy (HR 0.49 (95% CI 0.31 to 0.79); p=0.003). There was no survival association when comparing radiation alone with no treatment, and none when adding radiation to chemotherapy compared with chemotherapy alone. Those with lymphovascular space invasion (n=124/507) had improved overall survival with chemotherapy and radiation (5-year overall survival 91.2% vs 76.7% for chemotherapy alone and 27.3% for radiation alone, log-rank p<0.001), but there was no survival difference after adjusting for age and comorbidity (HR 0.25 (95% CI 0.05 to 1.41); p=0.12). The use of adjuvant chemotherapy for the treatment of stage IIIA grade 1 endometrial cancer increased over time and was associated with improved overall survival compared with radiation alone or chemoradiation. Patients with lymphovascular space invasion may benefit from combination therapy.

Geographic and racial disparities in the quality of surgical care among patients with nonmetastatic uterine cancer

Although the rates of minimally invasive surgery and sentinel lymph node biopsy have increased considerably over time in the surgical management of early-stage uterine cancer, practice varies significantly in the United States, and there are disparities among low-volume centers and patients of Black race. A significant number of counties in the United States are without a gynecologic oncologist, and almost half of the counties with the highest gynecologic cancer rates lack a local gynecologic oncologist. This study aimed to evaluate the relationships of distance traveled and proximity to gynecologic oncologists with the receipt of and racial disparities in the quality of surgical care among patients who underwent a hysterectomy for nonmetastatic uterine cancer. Patients who underwent a hysterectomy for nonmetastatic uterine cancer in Kentucky, Maryland, Florida, and North Carolina were identified in the 2012 to 2018 State Inpatient Database and the State Ambulatory Surgery Services Database files. County-to-county distances were used as the distances traveled to the nearest gynecologic oncologist. Factors associated with the receipt of minimally invasive surgery and lymph node dissection were analyzed using multivariable logistic regression models, as was the assessment of the interaction between travel for surgery and patient race. Among 21,837 cases, 45.5% lived in a county without a gynecologic oncologist; overall, 55.5% traveled to another county for surgery, including 88% of those who lacked a local gynecologic oncologist. Patients who lacked access to a local gynecologic oncologist in their county who did not travel for surgery were more likely to receive open surgery and no lymph node dissection, and those in counties without access in any surrounding county were affected even more. Among patients in counties without a gynecologic oncologist, those who traveled for surgery had a similar likelihood of undergoing minimally invasive surgery (71%) but had a greater likelihood of undergoing lymph node dissection (64.7% vs 57.2%) than nontravelers. Among those in counties without a gynecologic oncologist, a longer distance traveled was associated with receipt of a lymph node assessment. When compared with non-Black patients, Black patients were less likely to undergo minimally invasive surgery (57.0% vs 74.1%). In adjusted regression models that controlled for a diagnosis of fibroids, Black race was an independent risk factor for the receipt of open surgery. There was a significant interaction between Black race and travel for surgery, and Black patients who lived in counties without a gynecologic oncologist who did not travel faced an incrementally lower likelihood of receiving minimally invasive surgery (odds ratio, 0.57 when compared with non-Black patients who traveled for surgery; odds ratio, 0.60 as interaction term; P<.001 for both). Similar disparities in surgical quality by race were noted for Black patients who lived in counties with a gynecologic oncologist who traveled out of county for surgery. Patients, particularly those of Black race, who lacked local access to gynecologic oncologist specialty care benefitted from traveling to specialty centers to ensure access to high-quality surgery for nonmetastatic uterine cancer. Further work is needed to ensure equitable and universal access to high-quality care through patient travel or specialist outreach.

Use of the Frailty “Timed Up and Go” Test to Predict Perioperative Complications in Patients Undergoing Gynecologic Cancer Surgery

To assess the predictive value of frailty measured by the timed up and go (TUG) test on perioperative outcomes versus other perioperative screening methods. Retrospective cohort study SETTING: Duke University Hospital and Duke Raleigh Hospital PATIENTS: Patients who underwent surgery with gynecologic oncologists at our institution from October 2019 to October 2023 with a preoperative TUG time recorded were included. TUG times were recorded preoperatively. TUG time >12 seconds was considered frail. American Society of Anesthesiologists scores were extracted from the medical record. Modified frailty index (mFI) was calculated using 11 variables extracted from the medical record. Outcomes included postoperative complications, length of stay, and postoperative disposition. Comparisons between TUG times dichotomized at 8 and 12 seconds were made using Wilcoxon rank sum or chi-square; logistic regression was used to predict TUG time using these dichotomizations. Overall, 174 patients were included; 39 (22.4%) underwent laparotomy, 123 (70.6%) underwent laparoscopy, and 12 (6.9%) underwent other minor surgeries. Frail patients (TUG time > 12 seconds) were older and had higher mFI scores and lower preoperative albumin than nonfrail patients. There were no differences in major or minor complication rates after laparoscopic surgery between frail and nonfrail patients. American Society of Anesthesiologists and mFI were not associated with the need for transfusion (p > .05). Frail patients were more likely to receive a perioperative blood transfusion compared to nonfrail patients in the overall cohort (19.2% vs 4.1%, p = .0034). TUG time did not predict length of stay or postoperative disposition. Slower TUG times were associated with comorbidities, older age, and malnutrition. Frailty was not associated with complications in those who underwent laparoscopic surgery. Our findings support the use of this easy-to-administer practical frailty screening tool compared to more traditional methods.