American Journal of Clinical Oncology

Prognostic Value of Preoperative Imaging

Objective: 18F-fluorodeoxyglucose positron emission tomography-computed tomography (PET-CT) increases the sensitivity for preoperative detection of lymph nodes and distant metastases in endometrial cancer. The objective of this investigation was to determine the prognostic value of preoperative PET-CT compared with computed tomography (CT) alone for high-risk endometrial carcinoma. Materials and Methods: We performed a retrospective review of high-risk histology endometrial cancer from 2008 to 2015. Clinical variables including surgical procedure, preoperative imaging modality, and outcome were collected. Survival analysis was performed utilizing the Kaplan-Meier and Cox proportional hazards methodologies. Results: Of the 555 women treated for high-risk histology endometrial cancer, 88 (16%) had preoperative PET-CT, and 97 (17%) CT without PET available. PET-CT demonstrated positive findings in 37 women (42%) compared with 33 (30%) with preoperative CT alone. PET-CT had a positive predictive value of 96% for nodal metastasis compared with 60% for CT alone. The median follow-up time for the entire cohort was 59 months (range, 12 to 96 mo). Patients with a negative preoperative PET-CT (n=54) had a median progression-free survival (PFS) that was not reached, whereas the median PFS in the PET-CT positive group was 13 months (n=34). Women with a negative PET-CT had a longer median overall survival (OS) not yet reached compared with 34 months in the PET-CT positive cohort (hazard ratio, 2.4; P<0.001). CT findings did not associate with PFS or OS. Conclusions: PET-CT demonstrated superior sensitivity for lymph node metastasis and detecting distant disease compared with CT. Preoperative PET-CT, whether positive or negative, offered OS and PFS prognostic value not observed with CT alone.

Does the Interval Between Hysterectomy and Start of Adjuvant Radiation Treatment Influence Survival in Women With Endometrial Carcinoma?

Objective: The objective of this study was to analyze the impact of the time interval (TI) between hysterectomy and initiation of adjuvant radiation treatment (ART) on overall survival (OS) among women with early stage endometrial carcinoma (EC) using the National Cancer Database (NCDB). Materials and Methods: The NCDB was queried for women with the International Federation of Gynecology and Obstetrics (FIGO) stage I to II EC who underwent hysterectomy followed by ART. We examined the prognostic impact of TI on OS using the cutoff ≤8 or >8 weeks to initiate radiation treatment (RT). Two groups of patients were created. Kaplan-Meier curves were created for OS analysis. Predictors of OS were identified. Results: A total 16,520 women were identified. The median follow-up time for the entire cohort was 59.1 months. Median age was 63 years, and 82% were FIGO stage I. Pelvic external beam RT alone was used in 9569 (58%) and vaginal brachytherapy alone in 4265 women (26%). In total, 10,040 women (61%) received RT ≤8 weeks. Delay in initiating RT >8 weeks was associated with shorter 5-year OS (P=0.048). Independent predictors of shorter OS includes older age, African American race, higher comorbidity burden, higher tumor grade, the presence of lymphovascular invasion and stage II tumors. Although TI in initiating RT was a significant predictor for OS in univariate analysis, its independent significance of OS was lost on multivariate analysis (P=0.28). Conclusion: Our study suggests that TI between hysterectomy and initiation of ART was not an independent predictor of OS in women with early stage EC.

Refusal of Radiation Results in Inferior Survival in Endometrial Cancer

Objective: We sought to understand factors associated with refusal of adjuvant radiotherapy in endometrial cancer and its impact on outcomes. Methods: Data from the National Cancer Database for patients who underwent surgery for nonmetastatic endometrial cancer between 2004 and 2015 were pooled. The Pearson χ2 test and multivariate logistic regression analyses were used to assess demographic, clinical, and treatment factors. Inverse probability of treatment weighting was used to account for differences in baseline characteristics. Kaplan-Meier analyses and doubly-robust estimation with multivariate Cox proportional hazards modeling were used to analyze overall survival (OS). Results: We identified 4739 of 80,803 patients (5.9%) who refused radiotherapy. Factors associated with refusal were: no insurance (relative risk [RR]=1.66, P<0.01), Medicare (RR=1.42, P<0.01), living >50 miles from treatment (RR=1.34, P<0.01), Charlson-Deyo Comorbidity Scores of 1 (RR=1.16, P<0.01) or ≥2 RR=1.38, P<0.01), age above 60 years (RR=1.28, P<0.01), International Federation of Gynecology and Obstetrics (FIGO) stages IIIA (RR=1.63, P<0.01) and IIIC (RR=1.65, P<0.01) disease, papillary (RR=1.69, P<0.01) and clear cell histology (RR=1.64, P<0.01). Factors associated with radiation therapy receipt included: Hispanic race (RR=0.61, P<0.01), income >$63,000 (RR=0.89, P=0.044), undergoing chemotherapy (RR=0.17, P<0.01), FIGO stages IB (RR=0.81, P<0.01) and II (RR=0.70, P<0.01) disease, and lymphadenectomy (RR=0.79, P<0.01). After weighting, 5-year OS was significantly lower with refusal (74.3% vs. 79.7%, P<0.01). This survival decrement was maintained across FIGO stages. Conclusions: We identified characteristics associated with radiation refusal, including socioeconomic barriers, advanced disease stage, and histology. Refusal of radiotherapy conferred decreased OS across FIGO stages.

The Reliability of Intraoperative Assessment on Predicting Tumor Size, Myometrial Invasion, and Cervical Involvement in Patients With a Preoperative Diagnosis of Complex Atypical Hyperplasia or (Clinical Stage I) Endometrial Cancer

Objectives: The objective of this study is to assess the reliability of intraoperative uterine assessment compared with the final pathologic evaluation in patients with endometrial cancer (EC) and whether assessment improves with experience. Methods: After Institutional Review Board approval, a prospective cohort study of women surgically managed with biopsy-proven complex atypical hyperplasia (CAH) or EC between March 2015 and December 2016 was performed. Demographics, preoperative biopsy results, procedure, intraoperative and final pathologic evaluation of lesion size, myometrial invasion, and lower uterine segment/cervical involvement were abstracted. The agreement between the intraoperative and final pathologic evaluation of tumor involvement of the uterus was determined using the kappa statistic and the intraclass correlation coefficient. Results: A total of 264 patients with a preoperative diagnosis of CAH or EC were included—71 (26.9%) with CAH and 193 (73.1%) with EC. The mean age was 62.6±11.5, and mean body mass index was 37.2±10.1. The majority of women were white (67%). A total of 227 (85.9%) patients underwent a laparoscopic or robotic hysterectomy, whereas 36 (13.6%) underwent an abdominal hysterectomy. 233 (88.3%) patients had EC and 21 (7.9%) patients had CAH on final pathology. There was a fair agreement between the intraoperative estimation of myometrial invasion (κ=0.37). A moderate agreement exists between the intraoperative estimation of lower uterine segment/cervical involvement (κ=0.57). There was a strong agreement between intraoperative tumor size assessment and the final path (intraclass correlation coefficient=0.74). The intraoperative correlation of tumor size was similar for the first half of the cohort (κ=0.50) and the second half (κ=0.46) chronologically. Conclusions: Despite only a fair correlation in the myometrial invasion, intraoperative assessment of cervical involvement and especially tumor size is more readily identified and overall accurate. Therefore, intraoperative evaluation is an additional tool to use when making the decision to proceed with surgical staging.

Treatment of Recurrent Low-grade Serous Ovarian Cancer With MEK Inhibitors

Objective: Low-grade serous ovarian cancer (LGSC) represents 5% of all epithelial ovarian cancers. They are characterized by indolent growth and KRAS and BRAF mutations, differing from high-grade serous ovarian cancer both clinically and molecularly. LGSC has low response rates to traditional systemic therapies, including chemotherapy and hormonal therapy. The objective of this systematic review was to appraise the literature describing the efficacy of MEK inhibitors in the treatment of LGSC. Methods: A comprehensive search was conducted of the following databases: Medline ALL, EMBASE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Web of Sciences, ClinicalTrials.gov, International Clinical Trials Registry Platform (ICFRP), and International Standard Randomized Controlled Trials Number (ISRCTN) Registry. All studies investigating MEKi in the treatment of LGSC in the adjuvant or recurrent setting for patients 18 years of age or older were included. All titles/abstracts were then screened by 2 independent reviewers (A.K. and C.C.). The full-text articles were then screened. All disagreements were resolved by a third independent reviewer (T.Z.). Two independent reviewers (A.K. and C.C.) extracted data from the studies deemed eligible for final review. Results: A total of 2108 studies were identified in the initial search. Of these, a total of 4 studies met the eligibility criteria for systematic review. In these studies, 416 patients were treated with an MEKi alone. All patients included in the studies were being treated for LGSC in the recurrent setting. Varied results and efficacy of the MEKi were reported in each study. Conclusions: The results highlighted in this systematic review demonstrate varied responses to MEKi for recurrent LGSC. Further research is needed in this field comparing the efficacy to current therapies, as well as to further evaluate the safety and toxicity profile with long-term use of MEKi.

Radiation Proctitis in Patients With Locally Advanced Cervical Cancer Treated by Chemoradiation

Objectives: Radiation proctitis is a misunderstanding complication of chemoradiation in locally advanced cervical cancer. The objective of our study is to provide a detailed description and analysis of predictive factors associated with radiation proctitis in a retrospective cohort of patients treated by chemoradiation for locally advanced cervical cancer. Methods: All patients treated by exclusive chemoradiation or chemoradiation followed by brachytherapy for locally advanced cervical cancer from 2011 to 2017 were included in the study. A bivariate analysis was conducted to establish correlations between the occurrence of radiation proctitis and various clinical and technical variables. Results: A total of 128 patients were included in the study. The mean dose (SD) to the planning target volume was 47.1 Gy (6.2). Fifty-nine (46.1%) patients underwent brachytherapy. Sixteen patients (12.5%) developed radiation proctitis, grade 2 or higher in 12 patients (9.3%). In univariate analysis, anticoagulant or antiplatelet treatments (P=0.039), older age (P=0.049), rectal volume irradiated at 40 Gy (P=0.01) and 30 Gy (P=0.037) were significantly associated with the occurrence of a grade ≥2 radiation proctitis. The delivered dose to 2 cm3 of rectum (D2cm3) showed a potential association with the occurrence of radiation proctitis of all grades (P=0.064). Conclusions: This study highlights clinical and technical factors that should be considered in assessing the risk of radiation proctitis. These results contribute to a better understanding of this complication.

Cardiac Metastatic Tumors

Cardiac tumors are a heterogeneous group of pathologic masses of the heart that contain primary tumors—benign or malignant, and secondary tumors. Metastases are significantly more frequent, mostly originating from lung, breast, gastrointestinal tract, or ovary carcinomas. Secondary cardiac tumors may be asymptomatic or may cause cardiovascular, systemic, or embolic symptoms. The study is a summary of the available knowledge on cancerous metastatic lesions of the heart. Pleural mesothelioma (48.4%), adenocarcinoma (19.5%), or squamous cell carcinoma (18.2%) of lung, breast carcinoma (15.5%), ovarian carcinoma (10.3%), and bronchoalveolar carcinomas (9.8%) are cited as the most common origin of secondary heart tumors. Masses can spread by direct tumor invasion, by lymphatic vessels, veins, or arteries. Patients with cancer and nonspecific cardiovascular symptoms should be particularly vigilant, and the possibility of metastasis in an unusual location such as the myocardium should be considered in the diagnosis. Diagnostic methods include echocardiography, cardiac magnetic resonance, computed tomography, positron emission tomography, and histologic evaluation. Treatment of choice is managing primary carcinoma, due to the poor outcomes of surgical methods.

PARP Inhibitors in Newly Diagnosed and Recurrent Ovarian Cancer

Ovarian cancer is the most lethal gynecologic malignancy, characterized by a high death-to-incidence ratio. Platinum-based chemotherapy is the mainstay of treatment for newly diagnosed and platinum-sensitive recurrent ovarian cancer. Poly (ADP-ribose) polymerase inhibitors (PARP inhibitors) have been incorporated into the treatment strategy for ovarian cancer. PARP inhibitors showed particular benefit for patients harboring defects in DNA repair pathways. Accumulating evidence showed that PARP inhibitors provide a benefit in newly diagnosed advanced ovarian cancer, even in the absence of BRCA mutation, as reported in the PRIMA, PRIME, and ATHENA-mono trials. Interestingly, the PAOLA-1 study provides another important finding, supporting the adoption of olaparib plus bevacizumab in patients with homologous recombination deficiency. Although those results are exciting, several patients develop resistance to PARP inhibitors. Hence, new combinations are under investigation to identify new treatment strategies to overcome this resistance. Currently, researchers are focused on the possibility to adopt PARP inhibitors even in the setting of platinum-resistant disease. The present critical review aims to report the current landscape and further perspective for strengthening PARP inhibitors' effectiveness in newly diagnosed and recurrent ovarian cancer.

Association Between Metabolic Syndrome and Endometrial Cancer Survival in a SEER-Medicare Linked Database

Background: Metabolic syndrome has previously been linked to increased risk of endometrial cancer. This study examines the association between metabolic syndrome and cancer-specific survival (CSS) in early stage and locoregionally advanced endometrial cancer. Methods: The SEER-Medicare linked database was used to identify a cohort of patients with endometrial cancer between 1992 and 2011 who underwent hysterectomy. Patients with incomplete stage or grade information were excluded. Patients were stratified into early stage (stage I to II) or locoregionally advanced (stage III to IVa) disease. Metabolic syndrome status was determined through Medicare claims 1 year before diagnosis. The relationship between metabolic syndrome and CSS was evaluated using univariable and multivariable Cox proportional hazards regression analyses. Results: A total of 10,090 patients with endometrial cancer were identified. The mean age was 75 and the majority (91.5%) were white. At diagnosis, 86.6% of patients were early stage and 13.4% were locoregionally advanced. Sixteen percent of patients had metabolic syndrome. On stage stratified multivariable analysis, race, income quartile, year of diagnosis, histopathology, and adjuvant treatment were associated with CSS in early stage disease. Presence of metabolic syndrome was associated with worse CSS in early stage disease (hazard ratio=1.28, 95% confidence interval: 1.09-1.53); this difference did not exist for locoregionally advanced disease (hazard ratio=1.18, 95% confidence interval: 0.93-1.49). Conclusions: In elderly early stage endometrial cancer patients, metabolic syndrome is associated with worse CSS. Control of metabolic syndrome through lifestyle and pharmacologic therapies may improve cancer prognosis in this population.

The Prognostic Significance of the Depth of Cervical Stromal Invasion in Women With FIGO Stage II Uterine Endometrioid Carcinoma

Objective: The objective of this study was to investigate the prognostic significance of the depth of cervical stromal invasion (CSI) in women with FIGO stage II uterine endometrioid adenocarcinoma (EC). Methods: Our database of women with EC was quired for patients with stage II EC. Pathologic slides were retrieved and reviewed by gynecologic pathologists to determine cervical stromal thickness and depth of CSI as a percentage of stromal thickness (%CSI). Kaplan-Meier, univariate, and multivariate analyses were used to compare recurrence-free, disease-specific (DSS), and overall survival (OS) between women who had<50% versus ≥50% CSI. Univariate and multivariate analyses were used to assess other prognostic variables associated with survival endpoints. Results: A total of 117 patients were included in our study who had hysterectomy between 1/1990 and 8/2021. Seventy-nine patients (68%) with <50% and 38 (32w%) with ≥50% CSI. After a median follow-up of 131 months, 5-year DSS was significantly worse for women with ≥50% CSI (78% vs. 91%; P=0.04). However, %CSI was not an independent predictor for any of the studied survival endpoints. Independent predictors of worse 5-year recurrence-free survival and DSS included FIGO grade 3 tumors (P=0.02) and the presence of lymphovascular space invasion (P=0.03). Grade 3 tumors were the only independent predictor of worse 5-year OS (P=0.02). Conclusions: Our results suggest that deep CSI is not an independent prognostic factor for survival endpoints in women with stage II uterine endometroid adenocarcinoma. The lack of independent prognostic significance of the depth CSI needs to be validated in a multi-institutional analysis.

Risk Factors for Postoperative Venous Thromboembolism in Patients With Gynecologic Malignancies

To systematically evaluate the risk factors for postoperative complications of venous thromboembolism in patients with gynecologic malignancies. Cohort studies and case-control studies on the risk factors of postoperative venous thromboembolism in gynecologic malignancy patients were included in the search of China Knowledge, Wanfang, Wipro, China Biomedical Literature Database, PubMed, Cochrane Library, Embase, and Web of Science databases from inception to March 2025, and were analyzed. Studies. Data were statistically analyzed using RevMan 5.2 software. A total of 19 studies involving 123,329 patients with gynecologic malignancies were included. The analysis showed that advanced age (OR=3.08, 95% CI=2.85-3.32, P <0.00001), open surgery (OR=9.18, 95% CI=2.38-35.34, P =0.001), high surgical complexity (OR=9.97, 95% CI=5.80-17.15, P <0.00001), and surgical duration (OR=3.33, 95% CI=2.97-3.73, P <0.00001), high BMI (OR=4.77, 95% CI=3.47-6.57, P <0.00001), comorbidities (OR=21.02, 95% CI=8.72-50.70, P <0.00001), and prolonged bed rest in the postoperative period ( OR=25.16, 95% CI=10.32-61.32, P <0.00001), high intraoperative bleeding (OR=107.53, 95% CI=17.71-652.85, P <0.00001), and high D-dimer level (OR=5.55, 95% CI=3.27-9.43, P <0.00001), advanced tumor stage (OR=7.58, 95% CI=2.22-25.90, P =0.001), high tumor grade (OR=27.67, 95% CI=8.39-91.18, P <0.00001), and occurrence of lymph node metastasis (OR=31.21, 95% CI=9.54-102.15, P <0.00001) were all were risk factors for postoperative venous thrombosis in patients with gynecologic malignancies. Clinical staff should take into account the 12 risk factors identified in this study to actively identify gynecologic malignant tumor patients at high risk for venous thromboembolism after surgery and provide targeted measures to prevent or reduce the risk of postoperative DVT.

Sequencing of Adjuvant Chemoradiation for Advanced Stage Endometrial Cancer

Objectives: Radiation is frequently added to chemotherapy for adjuvant treatment of advanced stage endometrial cancer. Multiple adjuvant therapy sequencing options exist, and little data is available to compare these. We compared outcomes and toxicities after “sandwich” chemoradiation (chemotherapy, then radiation, then chemotherapy) and nonsandwich sequences (chemotherapy then radiation, radiation then chemotherapy, or concurrent chemoradiation). Materials and Methods: We recorded baseline characteristics, adjuvant treatment details, clinical outcomes, and toxicities for stage III to IVA patients who underwent surgical staging followed by both adjuvant chemotherapy and radiation therapy at our institution. Effects of adjuvant treatment order (sandwich or nonsandwich) on these outcomes were analyzed. Toxicities were graded according to CTCAE v4.0. Results: We identified 107 patients with a median follow-up of 3.2 years. Five-year local, regional, and distant recurrence were 7%, 15%, and 33%; disease-free and overall survival were 61% and 68%, respectively. Outcomes did not differ by sequence group. The overall rate of acute toxicity did not differ by sequence group. The overall rate of chronic toxicity was significantly lower for sandwich patients (P<0.001), as were overall rates of chronic genitourinary (P=0.048) and gynecologic (P<0.001) toxicities. There were no grade 4 or 5 acute or chronic toxicities. Conclusions: Advanced stage endometrial cancer is an aggressive disease and adjuvant chemotherapy and radiation therapy are indicated. Clinical outcomes were similar amongst the different sequences; however, sandwich therapy led to less chronic toxicity, offering an opportunity for improved quality of life in survivorship.

Impact of Surgeon Type and Rurality on Treatment and Survival of Ovarian Cancer Patients

Background: National Comprehensive Cancer Network guidelines recommend ovarian cancer patients receive cancer-directed surgery from a gynecologic oncologist surgeon. We aimed to determine if rurality impacts type of surgeon and estimate if the interaction between rurality and type of surgeon impacts cytoreductive surgery, chemotherapy initiation, and survival. Methods: Our population-based cohort of Iowan (N=675) ovarian cancer patients included women diagnosed with histologically confirmed stages IB-IV cancer in 2010 to 2016 at the ages of 18 to 89 years old and who received cancer-directed surgery in Iowa. Multivariable logistic regression analysis and Cox proportional hazards models were used. Results: Rural (vs. urban) patients were less likely to receive surgery from a gynecologic oncologist (adjusted odds ratio [OR]: 0.48; 95% confidence interval [CI]: 0.30-0.78). Rural patients with a gynecologic oncologist (vs. nongynecologic oncologist) surgeon were more likely to receive cytoreduction (OR: 2.84; 95% CI: 1.31-6.14) and chemotherapy (OR: 4.22; 95% CI: 1.82-9.78). Gynecologic oncologist-provided surgery conferred a 3-year cause-specific survival advantage among rural patients (adjusted hazard ratio: 0.57; 95% CI: 0.33-0.97) and disadvantage among urban patients (hazard ratio: 1.77; 95% CI: 1.02-3.06) in the model without treatment covariates. Significance dissipated in models with treatment variables. Discussion: The variation in the gynecologic oncologist survival advantage may be because of treatment, referral, volume, or nongynecologic oncologist surgeons’ specialty difference by rurality. This is the first study to investigate the ovarian cancer survival advantage of having a gynecologic oncologist surgeon by rurality.

A Simple, Novel Prognostic Score in Platinum Sensitive Relapsed Ovarian Cancer

Objectives: Epithelial ovarian cancer is one of the commonest gynecologic cancers and one with the highest mortality. This retrospective cohort study was done to identify predictors of outcomes in platinum-sensitive relapsed ovarian cancer patients (PS-ROC). Methods: Data regarding baseline characters, laboratory findings, therapeutic details and survival outcomes was obtained from the medical records of PS-ROC patients presented between January 2015 and December 2019. Prognostic score was constructed using factors which were significant on multivariate analysis to predict survival outcomes. Results: A total of 71 (PS-ROC) patients were included in the study with a median age of 50 years. Relapse treatment was either chemotherapy alone (n=53, 75%) or chemotherapy plus surgery (n=18, 25%). The estimated progression-free survival (PFS) and overall survival were 10 and 29 months, respectively. The overall response rate after treatment of relapse was 59%. Prognostic score was created with the 3 factors (each scoring 1 point) which were predictive of PFS (higher lymphocyte-monocyte ratio, longer platinum-free interval and secondary cytoreduction). Patients with low score (0,1) had better PFS than those with higher score (2,3) (13 vs. 7 mo [P=0.0001]). Conclusions: A composite prognostic score could predict outcomes in PS-ROC and potentially identify a subgroup with very poor prognosis. Future studies with a greater number of patients are needed to validate these findings. This information could help tailor more intense therapies to the high-risk patients and attempt to improve outcomes and serve as stratification factors for prospective trials.

Surveillance Only for High-risk FIGO Stage IA/IB Malignant Ovarian Germ Cell Tumors

Objectives: Investigate the use and outcomes of a surveillance only strategy for patients with high-risk stage I malignant ovarian germ cell tumors. Methods: Patients with International Federation of Gynecology and Obstetrics stage IA/IB grade 2 or 3 immature teratoma, yolk sac, or mixed germ cell tumor diagnosed between 2004 and 2014 who had at least 1 month of follow-up were drawn from the National Cancer Database. Overall survival (OS) was evaluated for each histologic subtype using Kaplan-Meier curves, and compared with the log-rank test. Results: A total of 497 patients were identified; 115 (23.1%) with grade 2 immature teratoma, 157 (31.6%) with grade 3 immature teratoma, 101 (20.3%) with yolk sac tumor, 124 (25%) with mixed germ cell tumor. Rate of adjuvant chemotherapy was 68.2% (655 patients), while rate of lymph node biopsy/dissection was 55.2%. A total of 19 (3.8%) deaths were observed at a median of 29.8 months. There was no difference in OS between patients who did and did not receive adjuvant chemotherapy with grade 2 (P=0.35) and grade 3 immature teratoma (P=0.47) or mixed germ cell tumors (P=0.55). Patients with yolk sac tumors those who received chemotherapy had better OS compared with those who did not, P=0.019; 5-year OS rates were 92.7% and 79.6%, respectively. Conclusions: A surveillance only strategy for patients with stage I malignant ovarian germ cell tumors is associated with excellent survival outcomes for patients with grade 2 or 3 immature teratoma or mixed germ cell tumors.

Prognostic Value of Lymph Node Parameters in Elderly Patients With Stage III Serous Ovarian Cancer Based on Competing Risk Model

Objectives: Competing risk models were used in this study. The purpose of this study was to assess the predictive usefulness of lymph node characteristics in elderly patients with stage III serous ovarian cancer. Methods: We conducted a retrospective analysis on 148,598 patients from 2010 to 2016 using the surveillance, epidemiology, and end results database. Lymph node characteristics were collected and examined, including the number of lymph nodes retrieved the number of lymph nodes examined (ELN) and the number of positive lymph nodes (PN). Using competing risk models, we evaluated the connection between these variables and overall survival (OS) and disease-specific survival (DSS). Results: This study included a total of 3457 ovarian cancer patients. Multivariate analysis using the COX proportional hazards model found that ELN>22 was an independent predictive factor for both OS (hazard ratio [HR] [95% CI]=0.688 [0.553 to 0.856], P<0.05) and DSS (HR [95% CI]=0.65 [0.512 to 0.826], P<0.001), PN>8 was identified as a significant risk factor for both OS (HR [95% CI]=0.908 [0.688 to 1.199], P=0.497) and DSS (HR [95% CI]=0.926 [0.684 to 1.254], P=0.62). Subsequently, using the competing risk model, ELN>22 was found to be an independent protective factor for DSS (HR [95% CI]=0.738 [0.574 to 0.949], P=0.018), while PN>8 was identified as a risk factor for DSS (HR [95% CI]=0.999 [0.731 to 1.366], P=1). Conclusions: Our findings demonstrate the robustness of the competing risk model to evaluate the results of the COX proportional hazards model analysis.

Local Control and Use of External Beam Parametrial Boost in the Era of Image-Guided Brachytherapy for Locally Advanced Cervical Cancer

Objective: Historically, external beam parametrial boost (EBPB) has been used in locally advanced cervical cancers to supplement radiation dose. However, it has become controversial in the era of image-guided brachytherapy. Modern 3D imaging and brachytherapy techniques have improved delineation and coverage of tumor. Outcomes with and without parametrial boost were analyzed. Methods: Women with cervical cancer involving the parametria (clinically or radiographically) diagnosed between 2001 and 2017 were identified. Clinicopathologic and treatment features, survival and patterns of failure data were collected. Univariate and multivariable data analysis was performed to evaluate association of these variables, including parametrial boost, with local failure-free survival and overall survival. Competing risks analysis was performed for cumulative incidence of local failure, with death and other failures treated as competing events. Results: A total of 100 women were identified (median follow-up 26.8 mo). Forty-one (41%) received EBPB; these patients were less likely to have received magnetic resonance imaging, positron emission tomography, interstitial, or high-dose rate brachytherapy. Magnetic resonance imaging, positron emission tomography, dose rate, and treatment era were highly correlated (Cramer’s V: 0.43 to 0.68, P<0.01). Two-year overall survival and local failure were 78% and 12% for the entire cohort. While the use of EBPB was not associated with any outcome on multivariable analysis, treatment year after 2009 was highly associated with improved outcomes in all models. Conclusions: In this study, omission of EBPB did not compromise local control or survival in the modern era, supporting a decreased need for standardized use of parametrial boost.

Tumor Necrotic Debris and High Nuclear Grade

Objective: Invasive pattern of endocervical adenocarcinomas (EACs) is known to influence lymph node metastasis and cancer recurrence. In this study we describe the prognostic significance of necrotic tumor debris (NTD) and tumor nuclear grade on recurrence risk stratification of early-stage cervical adenocarcinoma. Methods: Patients who underwent surgery from 2007 to 2018 for International Federation of Gynecology and Obstetrics (FIGO) stage IA1-IB2 EAC, for whom pathology was available for review were included in this study. Clinico-pathologic variables and clinical recurrence risk stratification (low, intermediate, or high risk) were correlated to intraluminal NTD and tumor nuclear grade (N3). Results: Among 50 patients meeting inclusion criteria, all were managed surgically and clinically risk stratified as low (n=33), intermediate (n=13), and high risk (n=4). Twenty-three patients (46%) were NTD-N3 negative and 27 (54%) were NTD-N3 positive. NTD-N3 was significantly associated with higher stage, tumor grade, larger tumor size, positive lymphovascular space invasion, and recurrence of disease (P=0.025). Patients with stage IB1 EAC who were stratified as intermediate or high-risk for recurrence were positive for NTD-N3. Lack of NTD-N3 had 100% negative predictive value for disease recurrence. Conclusions: NTD-N3, a novel pathologic finding, may be used to further stratify overall recurrence risk, and may play a role in individualization of patient care in early-stage EAC.

Impact of p53, HIF1a, Ki-67, CA-9, and GLUT1 Expression on Treatment Outcomes in Locally Advanced Cervical Cancer Patients Treated With Definitive Chemoradiation Therapy

Purpose/Objective: The objective of this study was to assess the association between pretreatment p53, hypoxia inducible factor 1a (HIF1a), Ki-67, carbonic anhydrase-9 (CA-9), and glucose transporter 1 (GLUT1) expression in locally advanced cervical cancer patients treated definitively with concurrent chemoradiation therapy (CRT) and treatment outcomes including overall survival (OS), progression-free survival (PFS), local-regional control (LC), and distant metastases–free survival (DMFS). Patients and Methods: Twenty-eight patients treated definitively and consecutively for cervical cancer with CRT had p53, HIF1a, Ki-67, CA-9, and GLUT1 protein expression assessed and scored semiquantitatively by 3 pathologists, blinded to the treatment outcomes. Outcomes were stratified by p53 (H-score: <15 vs. ≥15), HIF1a (H-score: <95 vs. ≥95), Ki-67 (labeling index <41% vs. ≥41%), CA-9 (H-score: <15 vs. ≥15), and GLUT1 (H-score: <175 vs. ≥175) expression. OS, PFS, LC, and DMFS rates were calculated using the Kaplan-Meier method, and differences between groups were evaluated by the log-rank test. Results: Notable clinical characteristics of the cohort included median age of 51 years (range: 32 to 74 y), FIGO stage IIB disease (57.2%), clinical node-negative disease (64.3%), squamous cell carcinoma (89.3%), and adenocarcinoma (10.7%). Treatment outcomes included 5-year OS (57.2%), PFS (48.1%), LC (72.1%), and DMFS (62.9%). For HIF1a H-score <95 and ≥95, the 5-year OS (52.0% and 68.4%, P=0.58), PFS (53.0% and 40.9%, P=0.75), LC (71.6% and 68.2%, P=0.92), and DMFS (59.7% and 52.0%, P=0.91) were not significantly different. For Ki-67 labeling index <41% and ≥41%, the 5-year OS (44.9% and 66.6%, P=0.35), PFS (38.9% and 55.4%, P=0.53), LC (57.7% and 85.7%, P=0.22), and DMFS (67.3% and 61.0%, P=0.94) were not significantly different. For CA-9 H-score <15 and ≥15, the 5-year OS (54.4% and 66.7%, P=0.39), PFS (57.3% and 40.0%, P=0.87), LC (70.0% and 70.0%, P=0.95), and DMFS (70.0% and 46.7%, P=0.94) were not significantly different. For GLUT1 H-score <175 and ≥175, the 5-year OS (43.6% and 43.6%, P=0.32), PFS (55.6% and 49.5%, P=0.72), LC (72.9% and 71.5%, P=0.97), and DMFS (62.5% and 59.6%, P=0.76) were not significantly different. For p53, H-score <15 and ≥15, the 5-year OS (62% and 53%), PFS (63% and 30.3%), LC (87.5% and 52%), and DMFS (79.6% and 41.6%). Conclusions: In this study population, HIF1a, Ki-67, CA-9, and GLUT1 expression did not predict treatment response or outcomes in locally advanced cervical cancer patients treated definitively with CRT. There was a nonstatistically significant trend towards worse outcomes with p53 expression.

An Exploratory Study of Neoadjuvant Cetuximab Followed by Cetuximab and Chemoradiotherapy in Women With Newly Diagnosed Locally Advanced Cervical Cancer

Objectives: This study explored the feasibility of cetuximab with chemoradiation in women with cervical carcinoma and evaluated fluorine-18 fluorodeoxyglucose-positron emission tomography/computed tomography (18F-FDG-PET/CT) to assess early response to cetuximab (NCT00292955). Patients and Methods: Eligible patients with International Federation of Gynecology and Obstetrics (FIGO) stage IB-IVB invasive carcinoma of the uterine cervix were treated on 1 of 3 dose levels (DL). DL1 consisted of neoadjuvant cetuximab, then concurrent radiotherapy with cetuximab 250 mg/m2/cisplatin 40 mg/m2, followed by weekly cetuximab. DL2 consisted of radiotherapy with cetuximab 200 mg/m2 and cisplatin 30 mg/m2. DL3 consisted of radiotherapy with cetuximab 250 mg/m2 and cisplatin 30 mg/m2. Patients underwent 18F-FDG-PET/CT before treatment, after neoadjuvant cetuximab, and at the end of treatment. Results: Of the 21 patients enrolled, 9, 3, and 9 were treated in DL1, DL2, and DL3, respectively. DL1 required dose reductions due to gastrointestinal toxicities. DL2 and 3 were tolerated with 1 dose-limiting toxicity (grade 4 renal failure) at DL3. Following 3 weekly treatments of neoadjuvant cetuximab in DL1, 7 patients had maximum standardized uptake value changes on 18F-FDG-PET/CT consistent with response to cetuximab. Of the 12 patients with locally advanced disease, eleven evaluable patients had no evidence of disease on 18F-FDG-PET/CT at treatment end. Five-year progression-free survival and overall survival rates for all patients were 57.5% and 58.5%, respectively. Conclusions: Cetuximab with cisplatin 30 mg/m2 and radiotherapy was tolerated. 18F-FDG-PET/CT demonstrated early evidence of response to neoadjuvant cetuximab. With advances in precision oncology and the recent approval of pembrolizumab in metastatic cervical cancer, dual-target inhibition with an epidermal growth factor receptor inhibitor may be a promising treatment in the future.

Breast and Cervical Cancer Screening Disparities in Transgender People

Objectives: The population of individuals who identify as transgender (TG) is increasing in the United States, yet disparities in cancer screening services are widening. It is imperative that interpersonal and systemic barriers to cancer care are identified and removed for this vulnerable population. Our study sought to examine the difference in self-reported breast and cervical cancer screening rates between TG and cisgender (CG) people. Materials and Methods: Cross-sectional data from the 2014 to 2016 and 2018 Behavioral Risk Factor Surveillance System (BRFSS) was obtained on individuals who identified as CG or TG (male-to-female [MTF] and female-to-male [FTM]), including their responses to questions regarding breast and cervical screening history and their primary care access and associated barriers. Results: Compared with the CG population, TG participants were less likely to adhere to or have undergone breast (FTM: odds ratio [OR] 0.47 and 0.32; MTF: OR 0.04 and 0.02, respectively; all P<0.001) and cervical cancer (FTM: OR 0.42 and 0.26, respectively; all P<0.001) screening. They were also less likely to have a primary care physician (FTM: OR 0.79; MTF: OR 0.58; all P<0.001) and less likely to seek primary care within a year owing to medical costs (FTM: OR 1.44; MTF: OR 1.36; all P<0.001). Conclusions: Disparities exist in the uptake of routine cancer screening in the TG population despite their increased risk for breast and cervical cancer. Interventions are urgently needed to mitigate delays to cancer screening, close gaps in provider and patient knowledge about cancer screening, and improve health care experiences of gender minorities in the United States.

Prognostic Significance of Nuclear Factor Kappa B Expression in Locally Advanced Cervical Cancer Patients Treated Definitively With Concurrent Chemoradiation

Objectives: Nuclear factor kappa B (NFkB) is a transcription factor shown to confer treatment resistance in tumors. A previous report suggested an association between pretreatment NFkB and poorer outcomes for cervical cancer patients treated with chemoradiation therapy (CRT). We aimed to validate their findings in a larger patient cohort. Materials and Methods: This Institutional Review Board approved study included patients with locally advanced cervical cancer patients treated with CRT. Evaluation of both nuclear and cytoplasmic immunoreactivity for NFkB was scored semiquantitatively by 3 pathologists. Cytoplasmic positivity incorporated both the intensity and percentage of immunoreactivity in invasive carcinoma (H-score), whereas nuclear positivity was assessed by percentage of positive cells. Outcomes were stratified by NFkB overexpression and tumor characteristics. Overall survival (OS), progression-free survival (PFS), distant metastases-free survival (DMFS), and local regional control (LC) were obtained using Kaplan-Meier and differences between groups were evaluated by the log-rank test. Hazard ratios were obtained using Cox regression for both univariate and multivariate analyses. Results: The mean age was 51 years old and most (78.57%) had locally advanced disease. Five-year OS, PFS, LC, and DMFS in the entire cohort were 57.18% (confidence interval [CI], 34.06%-74.82%), 48.07% (CI, 25.50%-67.52%), 72.11% (CI, 49.96%-85.73%), and 62.85% (CI, 36.33%-80.82%), respectively. There was no significant association between NFkB expression (H-index ≥180) and 3-year and 5-year OS (P-value=0.34), PFS (P-value=0.21), LC (P-value=0.86), or DMFS (P-value=0.18). Conclusions: Our study demonstrated that cytoplasmic NFkB-p65 expression (H-index ≥180) was associated with a nonstatistically significant trend toward poor clinical outcomes in locally advanced cervical cancer patients treated definitively with CRT.

Regional Variation in Access to Oncologic Care and Racial Disparities Among Cervical Cancer Patients

Objectives: The goal of this study was to determine whether access to gynecologic oncologists is correlated with disparate outcomes among cervical cancer patients, especially among Black women. Materials and Methods: An ecological study was performed using the National Cancer Database among stage I-IVA cervical cancer patients from 2004 to 2014. Data from the National Cancer Institute, the Society of Gynecologic Oncology, and the United States Census were compiled to describe access to care by region. Factors associated with receipt of optimal treatment (defined as surgery and/or radiation for stage IA-IB1 and IIA1; radiation and chemotherapy for stage IB2, IIA2, IIB-IVA or node positive disease) were identified using multivariate logistic regressions stratified by region, controlling for confounding factors including the number of gynecologic oncologists per states in each subregion. Cox multivariate survival analyses stratified by region were also performed. Results: Of 42,213 women, 17.0% were Black. On multivariate analysis controlling for confounders, all Southern women were less likely to receive optimal treatment (adjusted odds ratio [aOR]: 0.80, 95% confidence interval [95% CI]: 0.75–0.85, P<0.001) compared with Northeastern women. Black women in the South (aOR: 0.76, 95% CI: 0.70–0.83, P<0.001) and Midwest (aOR: 0.78, 95% CI: 0.68–0.90, P<0.001) were less likely to receive optimal treatment compared with non-Black women in those regions. Black women in the South (adjusted hazard ratio [aHR]: 1.11, 95% CI: 1.04-1.18, P<0.001) and West (aHR: 1.34, 95% CI: 1.11–1.62, P=0.002) had worse mortality compared with non-Black women in those regions, despite controlling for access to gynecologic oncologists. The South, Midwest, and West had proportionally fewer cancer centers and gynecologic oncologists compared with the Northeast. Conclusions: Southern women are at risk of inadequate treatment for cervical cancer, and Black Southern women are at even higher risk of inadequate treatment and worse overall survival despite controlling for access to gynecologic oncologists. Social determinants of health and other barriers besides access to oncologists likely contribute to observed regional and racial disparities among cervical cancer patients.

Cost-Effectiveness Analysis of Tumor Testing for BRCA Pathogenic Variants in Epithelial Ovarian Cancer

Objectives: Approximately 15% of women with epithelial ovarian cancer (EOC) have a germline BRCA1/2 pathogenic variant. Genetic testing for BRCA is recommended for all EOC patients, but not routinely performed. This study estimates the cost-effectiveness of BRCA screening with primary tumor testing versus routine germline testing. Methods: The model used literature-based probability estimates and published cost data. Effectiveness was the probability of testing completion for each strategy, providing cost per additional woman tested. A strategy was favored if it cost ≤$5000 per additional woman tested, reflecting costs of 100% receiving germline testing and 85% subsequently receiving tumor testing. Results: In the base case, primary tumor testing costs $3057 per additional woman tested. While more costly, primary tumor testing increased efficacy 2.67-fold with an incremental cost of $1500. In sensitivity analyses, results were most sensitive to varying testing costs. Tumor testing costs ≤$5000 per additional woman tested when individually varying all parameters through clinically plausible ranges. Primary germline testing was favored in >60% of cases (base case 30%) when it occurred. In probabilistic sensitivity analysis, varying all parameters simultaneously over plausible ranges 5000 times, tumor testing cost ≤$5000 per additional woman tested in 100% of model iterations. Conclusion: Cost effectiveness data already support BRCA1/2 screening for EOC with clear implications for cancer prevention. On the basis of this model, primary tumor testing leads to a 2.67-fold increase in testing with an incremental cost of $1500, supporting this strategy as a cost-effective way to improve BRCA testing.

Bevacizumab Combination Therapy Versus Standard Chemotherapy for Ovarian Cancer in Shorter and Longer Follow-Up Duration

Objective: This systematic review and meta-analysis aims to evaluate the efficacy and safety of bevacizumab in patients with ovarian cancer over a shorter and longer follow-up period. Methods: We searched Medline, Cochrane CENTRAL, Scopus, and Google Scholar for all phase 3 randomized controlled trials (RCTs) that administered bevacizumab to women with ovarian cancer. Review Manager 5.4 was used to calculate risk ratios (RR) and hazard ratios (HR) with 95% CIs. We assessed the quality of the included studies using version 2 of the Cochrane Risk of Bias tool (RoB 2). Results: After screening the titles, abstracts, and full texts, we included nine RCTs in our systematic review and meta-analysis. Four RCTs had a low risk of bias, while 5 had some concerns. Bevacizumab was associated with a progression free survival benefit for <36 months (HR: 0.59, 95% CI: 0.45-0.76, P<0.0001, I 2=90%) and >36 months (HR: 0.66, 95% CI: 0.55-0.80, P<0.0001, I 2=80%), and an overall survival benefit for <36 months (HR: 0.87, 95% CI: 0.78-0.98, P=0.02, I 2=0%) but not for >36 months (HR: 0.98, 95% CI: 0.89-1.09, P=0.77, I 2=30%). There was no difference in deaths between intervention and control groups <36 months (RR: 0.95, 95% CI: 0.86-1.04, P=0.26, I 2=10%) or >36 months (RR: 1.02, 95% CI: 0.97-1.06, P=0.50, I 2=0%). Bevacizumab reduced disease progression <36 months (RR: 0.82, 95% CI: 0.72-0.92, P=0.0008, I 2=82%) but not at >36 months (RR: 0.83, 95% CI: 0.58-1.19, P=0.30, I 2=94%). The adverse events reported with Bevacizumab use included thrombocytopenia, neutropenia, leukocytopenia, anemia, hypertension, bleeding or hemorrhage, and gastrointestinal, cardiac, and dermatological adverse events. Conclusion: Bevacizumab may improve progression-free survival within and after 36 months, overall survival within 36 months, and reduce disease progression within 36 months.

The Impact of Racial Disparities on Outcome in Patients With Stage IIIC Endometrial Carcinoma

Objective: To report the impact of race on clinical outcomes in patients with stage IIIC endometrial carcinoma. Materials and Methods: A retrospective multi-institutional study included 90 black and 568 non-black patients with stage IIIC endometrial carcinoma who received adjuvant chemotherapy and radiation treatments. Overall survival (OS) and recurrence-free survival (RFS) were calculated by the Kaplan-Meier method. Propensity score matching (PSM) was conducted. Statistical analyses were conducted using SPSS version 27. Results: The Median follow-up was 45.3 months. black patients were significantly older, had more nonendometrioid histology, grade 3 tumors, and were more likely to have >1 positive paraaortic lymph nodes compared with non-black patients (all P <0.0001). The 5-year estimated OS and RFS rates were 45% and 47% compared with 77% and 68% for black patients versus non-black patients, respectively (P <0.001). After PSM, the 2 groups were well-balanced for all prognostic covariates. The estimated hazard ratios of black versus non-black patients were 1.613 (P value=0.045) for OS and 1.487 (P value=0.116) for RFS. After PSM, black patients were more likely to receive the “Sandwich” approach and concurrent chemoradiotherapy compared with non-black (P=0.013) patients. Conclusions: Black patients have higher rates of nonendometrioid histology, grade 3 tumors, and number of involved paraaortic lymph nodes, worse OS, and RFS, and were more likely to receive the “Sandwich” approach compared with non-black patients. After PSM, black patients had worse OS with a nonsignificant trend in RFS. Access to care, equitable inclusion on randomized trials, and identification of genomic differences are warranted to help mitigate disparities.

Decision-making for Subsequent Therapy for Patients With Recurrent or Advanced Endometrial Cancer Based on the Platinum-free Interval

Objective: The aim of this study was to evaluate the progression-free survival (PFS) and overall response rate (ORR) of patients with recurrent endometrial cancer (REC) or advanced endometrial cancer (AEC) retreated with platinum-containing chemotherapy (PCC) based on the platinum-free interval (PFI). We compared our results with those reported in the KEYNOTE-775 study (that used pembrolizumab plus lenvatinib). Methods: A retrospective analysis was conducted of 65 patients with REC or AEC retreated with PCC between 2005 and 2020 at our hospital. Various clinicopathologic variables were analyzed: (1) age, (2) performance status, (3) histology, (4) history of pelvic irradiation in the adjuvant setting, (5) PFI, (6) chemotherapy regimen, (7) PFS and overall survival after retreatment with PCC, and (8) best ORR. Survival analyses were performed using Kaplan-Meier curves and log-rank tests. Results: The best ORR and PFS were 43.3% and 9.5 months, respectively, in patients with REC/AEC with a PFI ≥6 months. These results were comparable with those of patients treated with pembrolizumab and lenvatinib. The best ORR and PFS of patients with a PFI of <6 months appeared to be inferior to those of patients treated with pembrolizumab plus lenvatinib. Conclusions: Pembrolizumab plus lenvatinib seems to be a better treatment choice for patients with REC or AEC with a PFI of <6 months. For a PFI of ≥6 months, pembrolizumab plus lenvatinib or PCC can be used depending on the degree of residual side -effects associated with cytotoxic agents.

Prognostic Value of the Cutoffs for HALP in Endometrial Cancer

Objectives: Using preoperative hemoglobin, albumin, lymphocyte, and platelet (HALP) scores, a cutoff value of HALP in endometrial cancer was identified, and the significance of HALP value in endometrial cancer prognosis was evaluated to guide the management of patients. Materials and Methods: This study included 626 patients with endometrial cancer who underwent surgery at the First Affiliated Hospital of Chongqing Medical University between June 2015 and June 2020. A Cox regression model was used to analyze the correlation between HALP endometrial cancer recurrence and death, and the receiver operating characteristic curve was used to determine the optimal cutoff value of HALP for predicting the lymph node metastasis (LNM), recurrence, and death of endometrial cancer. Survival analysis was performed using the Kaplan-Meier method and log-rank test. Results: Univariate analysis revealed that HALP was associated with a lower risk of recurrence and death of endometrial cancer. Multivariate analysis indicated that HALP was an independent protective factor for predicting recurrence and death in endometrial cancer. The thresholds of HALP for predicting LNM, recurrence, and death in endometrial cancer patients are around 33.8. Kaplan-Meier survival curves showed that the recurrence-free and the overall survival rates were significantly lower in the low-HALP group than that in the high-HALP group (P<0.001). Conclusions: Preoperative HALP values in patients with endometrial cancer are important in predicting LNM, recurrence, and death of patients. HALP scores combined with traditional pathologic factors can better guide the prognostic management of patients.

Real-world Outcomes Associated With Poly(ADP-ribose) Polymerase Inhibitor Monotherapy Maintenance in Patients With Primary Advanced Ovarian Cancer

Objective: This study used real-world population data to assess the trends of first-line (1L) poly(ADP-ribose) polymerase inhibitor (PARPi) maintenance treatment uptake and outcomes in patients with primary advanced ovarian cancer (AOC). Methods: Patients diagnosed with AOC between January 1, 2017, and June 30, 2021, who completed 1L chemotherapy were selected from a real-world database. Descriptive analyses were performed to evaluate patient demographics, clinicopathological characteristics, and 1L treatment patterns. Time to next treatment or death was used as a proxy for real-world progression-free survival (rwPFS). Kaplan-Meier methods and Cox models were used for statistical analyses. Results: Of 705 patients who completed 1L chemotherapy, 166 received PARPi monotherapy and 539 underwent active surveillance (AS). Median follow-up was 10.9 months for PARPi monotherapy and 20.6 months for AS. PARPi monotherapy use increased from 6% in 2017 to 53% in 2021. Overall, patients receiving PARPi monotherapy had longer rwPFS than those who underwent AS (not reached vs 9.53 mo) respectively. rwPFS was also longer in patients who received PARPi monotherapy compared with AS in patients with BRCA-mutated disease (not reached vs 11.4 mo), BRCA–wild-type disease (13.5 vs 9.1 mo), homologous recombination-deficient tumors (not reached vs 10.2 mo), and homologous recombination-proficient or unknown status tumors (13.5 vs 9.3 mo). Conclusions: Our real-world analysis suggested that 47% of patients with primary AOC did not receive PARPi maintenance in the year 2021. PARPi use was associated with significantly improved outcomes compared with AS.

Laparoscopic Versus Abdominal Radical Hysterectomy for Cervical Cancer

Background: Laparoscopic radical hysterectomy (LRH) and open abdominal radical hysterectomy (ARH) have been used for cervical cancer treatment. We aimed to perform a meta-analysis to compare the efficacy and safety of LRH and ARH in the treatment of cervical cancer to provide reliable evidence to the clinical cervical cancer treatment. Methods: Two investigators independently searched PubMed and other databases for randomized controlled trials (RCTs) comparing LRH and ARH for cervical cancer treatment up to May 31, 2022. The risk of bias assessment tool recommended by Cochrane library was used for quality assessment. RevMan 5.3 software was used for meta-analysis. Results: Fourteen RCTs with a total of 1700 patients with cervical cancer were finally included. Meta-analyses indicated that compared with ARH, LRH reduced the intraoperative blood loss (mean difference [MD]=−58.08; 95% CI, −70.91, −45.24), the time to first passage of flatus (MD=−14.50; 95% CI, −16.55, −12.44) (all P<0.05), and increase the number of lymph nodes removed (MD=3.47; 95% CI, 0.51, 6.43; P=0.02). There were no significant differences in the duration of surgery (MD=27.62; 95% CI, −6.26, 61.49), intraoperative complications (odd ratio [OR]=1.10; 95% CI, 0.17, 7.32), postoperative complications (OR=0.78; 95% CI, 0.33, 1.86), relapse rate (OR=1.45; 95% CI, 0.56, 3.74), and survival rate (OR=0.75; 95% CI, 0.52, 1.08) between LRH group and ARH group (all P>0.05). Conclusions: LRH has more advantages over ARH in the treatment of cervical cancer. Still, the long-term effects and safety of LRH and ARH need more high-quality, large-sample RCTs to be further verified.

Assessing Geographic Variation in Rates of Cervical Cancer and Recurrent or Metastatic Cervical Cancer Among Medicaid Enrollees

Objective: The objective of this study was to evaluate trends in prevalence of cervical cancer (CC) and rates of recurrent or metastatic cervical cancer (r/mCC) treatment initiation at the state and metropolitan statistical area (MSA) levels among Medicaid enrolled females from 2016 to 2019. Methods: Retrospective analyses of nationwide Medicaid claims data were used to identify adult CC and r/mCC patients from 2016 to 2019. CC prevalence was estimated as the proportion of females diagnosed with CC out of all adult female Medicaid beneficiaries, and r/mCC by the proportion of CC patients who initiated a systemic treatment not associated with surgery or radiation to the number of enrollees with CC diagnosis in each state or MSA. Overall and annual rates were calculated for each state and MSA from 2016 to 2019. Results: The analytic cohort included 70,865 adult female Medicaid beneficiaries with CC from 2016 to 2019, among whom 3375 were identified as r/mCC patients. Nationwide annual prevalence of CC remained relatively stable from 2016 to 2019, while r/mCC decreased slightly over the study period. Several MSAs experienced increasing rates of r/mCC from 2016 to 2019, including Mayaguez, PR, Aguadeilla-Isabela, PR, and Green Bay, WI. Conclusions: Claims data demonstrate areas in the United States with disproportionately high or increasing CC or r/mCC burden, indicating a potential gap in preventative care for females and an unmet need for education and health care resource allocation. Future research should evaluate associations between community-level factors and r/mCC burden.

Racial Disparities in Endometrial Cancer Clinical Trial Representation

Objective: This study aimed to determine whether Black patients with recurrent endometrial cancer were more likely than White patients to be ineligible for a recently published clinical trial due to specific eligibility criteria. Methods: Patients with recurrent or progressive endometrial cancer diagnosed from January 2010 to December 2021 who received care at a single institution were identified. Demographic and clinicopathologic information was abstracted and determination of clinical trial eligibility was made based on 14 criteria from the KEYNOTE-775 trial. Characteristics of the eligible and ineligible cohorts were compared, and each ineligibility criterion was evaluated by race. Results: One hundred seventy-five patients were identified, 89 who would have met all inclusion and no exclusion criteria for KEYNOTE-775, and 86 who would have been ineligible by one or more exclusion criteria. Patients in the ineligible cohort were more likely to have lower BMI (median 26.5 vs. 29.2, P<0.001), but were otherwise similar with regard to insurance status, histology, and stage at diagnosis. Black patients had 33% lower odds of being eligible (95% CI: 0.33-1.34) and were more likely to meet the exclusion criterion of having a previous intestinal anastomosis, but the result was not statistically significant. If this criterion were removed, the racial distribution of those ineligible for the trial would be more similar (46.4% Black vs. 42.2% White). Conclusions: Clinical trial eligibility criteria may contribute to the underrepresentation of racial groups in clinical trials, but other factors should be explored. Studies to quantify and lessen the impact of implicit bias are also needed.

Preliminary Analysis of Cervical Cancer Immunotherapy

Cervical cancer is one of the most common gynecologically malignancies worldwide. Although vaccine and cervical cancer screening including human papillomavirus testing, cytology testing, and colposcopy have developed rapidly in recent years, effectively reducing cervical cancer mortality, cervical cancer remains a malignancy with higher female fatality rates worldwide and has a high risk for socioeconomically disadvantaged groups. The combination of platinum-paclitaxel and chemotherapy, possibly with the addition of bevacizumab, is currently the treatment of choice for advanced cervical cancer, but it only has remission purposes. Therefore, new therapeutic strategies are needed for both locally advanced and metastatic cervical cancer. Here, we make a preliminary analysis of cervical cancer immunotherapy.

Nomogram Predicting Grade ≥2 Acute Radiation Enteritis in Patients With Cervical Cancer Receiving Concurrent Chemoradiotherapy

Objective: To analyze the risk factors for grade ≥2 ARE in patients with cervical cancer receiving concurrent chemoradiotherapy. Methods: A total of 273 patients with cervical cancer receiving concurrent chemoradiotherapy at our hospital were retrospectively enrolled. The patients were divided into training and validation groups. Clinical parameters were analyzed using univariate analysis and multivariate logistic regression analysis. A nomogram model was established based on the independent risk factors selected using multivariate logistic regression. The areas under the receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA) were used to evaluate the nomogram. The patients were divided into low-score and high-score groups based on the scores calculated using the nomogram model and compared. Results: Malnutrition, monocyte-lymphocyte ratio ≥0.82 after radiotherapy, platelet-lymphocyte ratio <307.50 after radiotherapy, and bowelbag volume receiving at least 5 and 40 Gy were independent risk factors for grade ≥2 ARE and were incorporated into the nomogram (P<0.05). The ROC curve, calibration curve, and DCA suggested that the nomogram had good discrimination, concordance, and net benefit in the clinical. A medium nomogram score of 146.50 points was used as the cutoff point, and the incidence of grade ≥2 ARE in the high-score group was higher than that in the low-score group (P<0.05). Conclusion: The nomogram model for grade ≥2 ARE has good predictive ability and clinical utility, and is convenient for clinicians to identify high-risk groups and develop early prevention and treatment strategies.

The Efficacy and Safety of Pazopanib Plus Chemotherapy in Treating Recurrent or Persistent Ovarian Cancer

Background: Patients with recurrent or persistent ovarian cancer often have poor prognoses, and their optimal treatment regimen remains unclear. Inhibition of angiogenesis is a valuable strategy for treating ovarian cancer, and the drug pazopanib is a potent, multitarget tyrosine kinase inhibitor. However, treatment with pazopanib in combination with chemotherapy remains controversial. We performed a systematic review and meta-analysis to clarify the efficacy and side effects of pazopanib combined with chemotherapy in the treatment of advanced ovarian cancer. Methods: The PubMed, Embase, and Cochrane databases were systematically searched for relevant randomized controlled trials published up to September 2, 2022. The primary outcomes of eligible studies included overall response rate (ORR), disease control rate, 1-year progression-free survival (PFS) rate, 2-year PFS rate, 1-year overall survival (OS) rate, 2-year OS rate, and adverse events. Result: Outcomes from a total of 518 recurrent or persistent ovarian cancer patients from 5 studies were analyzed in this systematic review. Pooled results showed that pazopanib plus chemotherapy, when compared with chemotherapy alone, significantly improved the ORR (pooled risk ratio=1.400; 95% CI, 1.062-1.846; P = 0.017) but not the disease control rate, 1-year PFS, 2-year PFS, 1-year OS, or 2-year OS. Moreover, pazopanib increased the risk of neutropenia, hypertension, fatigue, and liver dysfunction. Conclusion: Pazopanib plus chemotherapy improved patient ORR but did not improve survival; it also increased the occurrence of several adverse events. Further large-sample clinical trials are needed to verify these results to guide pazopanib use in patients with ovarian cancer.

Use of “Repurposed” Drugs in the Treatment of Epithelial Ovarian Cancer

Epithelial ovarian cancer has poor outcomes with standard therapy and limited options for treatment of recurrent disease. This systematic review summarizes the data on the clinical use of repurposed drugs. We searched for clinical studies using “repurposed” agents for the treatment of ovarian cancer in the following databases: PubMed, clinicaltrials.gov, Clinical Trial Registry of India, European Clinical Trials Registry, and Chinese Clinical Trial Registry. We excluded reviews, preclinical studies, and non-English language studies. We assessed the quality of included studies. The following agents/class of agents were included: statins, hydroxychloroquine, metformin, itraconazole, nonsteroidal anti-inflammatory drugs, vitamin D, proton pump inhibitors, beta-blockers, and sodium valproate. Only one randomized controlled trial investigated metformin, which found no benefit of metformin. However, this had a high risk of bias (no details of randomization). Among the observational studies, 70% were of high quality (Newcastle-Ottawa scale ≥7). Clinical benefit was seen for itraconazole, beta-blockers, metformin, statins, and proton pump inhibitors. Though multiple studies aim to repurpose agents in epithelial ovarian cancer, the most published literature is observational, and none are practice-changing. Given the solid preclinical data regarding the anticancer efficacy of these agents, well-designed clinical trials are urgently required.

Comprehensive Analysis of Conditional Survival in Radiation-treated Patients With Gynecologic Malignancies Using the SEER Database

Objectives: In this study, we report conditional survival rate for gynecologic malignancies using Surveillance, Epidemiology, and End Results (SEER) database for patients who have received treatment with radiation therapy. Methods: Utilizing the SEER 22 database and SEER*Stat 8.4.3, regional gynecologic malignancies (cervix uteri, corpus uteri, vagina, vulva) treated with external beam radiation therapy (EBRT), brachytherapy, or both, were identified between 2000 and 2020. 5-year CS was calculated annually for each type of cancer treated with different types of therapies up to 5 years post diagnosis. The timeframes for percentages of survived patients are 12 to 72, 24 to 84, 36 to 96, 48 to 108, and 60 to 120 months, which gives the percentage of patients surviving up to 5 years at 1 to 5 years from when patients received diagnosis. Results: There were 59,441 patients who received radiation in the initial cohort. This was further subdivided into 24,073 (40%) patients who received EBRT only, 18,528 (31%) who received brachytherapy only, and 16,840 (28%) who received combined EBRT and brachytherapy. 5-year CS was calculated each year after initial diagnosis up to 5 years after. For all types of cancers that were analyzed, the 5-year CS increased as the year after diagnosis increased. Conclusions: CS is an effective method to prognosticate patients over time. In our cohort of patients with gynecologic malignancies treated with radiation, the overall trends for 5-year CS were similar across any treatment modality. These findings may help elucidate statistics for survivorship care and may help develop evidence-based policies.

Impact of Brachytherapy Boost and Dose-escalated External Beam Radiotherapy in Margin Positive Cervical Cancer Treated With Chemotherapy and Radiation

Objectives: We examined the impact of brachytherapy boost (BB) and external beam radiotherapy (EBRT) dose-escalation on overall survival (OS) for women with cervical cancer receiving postoperative chemotherapy and radiation (CRT) for a positive margin following hysterectomy. Materials and Methods: The National Cancer Database (NCDB) was queried from 2004 to 2015 for women with nonmetastatic squamous cell carcinoma or adenocarcinoma of the cervix who had a positive margin following hysterectomy and received postoperative CRT. Patient and treatment characteristics were assessed with multivariate logistic regression. Survival analyses were performed with univariate Cox regression and Kaplan-Meier analyses. Propensity-score weighted cohorts were generated with inverse probability of treatment weighting via generalized boosted regression modeling. Results: Of 630 women receiving CRT, 331 (53%) received EBRT alone and 299 (47%) received EBRT+BB. Eighty-two percent had chemotherapy initiation within 2 weeks of radiation, suggesting concurrent delivery. Median EBRT dose was 5040 cGy. Intracavitary high-dose rate was the most common BB (67%). Inclusion of BB was more likely with larger tumor sizes (odds ratio=1.03, P=0.002). Women receiving EBRT+BB had improved OS compared to EBRT alone for both unweighted (hazard ratio [HR], 0.72; P=0.020) and propensity-score weighted cohorts (HR, 0.70; P=0.017), and this finding was consistent across multiple patient subsets. EBRT dose-escalation >5040 cGy was not found to be associated with OS (unweighted HR, 1.38; P=0.065 and weighted HR, 1.16; P=0.450). Conclusion: The addition of BB to standard CRT improved OS for women with cervical cancer and a positive margin after hysterectomy. No consistent survival benefit was seen to EBRT dose-escalation beyond 5040 cGy.

Long-Term Survival Rates and Prognostic Factors of Cervix Cancer Treated by Different Modalities

Objective: To assess the overall survival (OS) and prognostic factors in patients with cervix cancer treated by different modalities. Material and Methods: The authors studied a cohort of patients with cervix cancer International Federation of Gynecology and Obstetrics stage I-IVa treated in the last 15 years. Patients were treated with surgery followed by radiotherapy (S+RT), or surgery plus chemoradiation (S+CRT), or radiotherapy alone (RT), or chemoradiation alone (CRT). Univariate and multivariate analyses were conducted to identify significant prognostic factors (P<0.05). Results: A total of 380 patients with cervix cancer were included. The treatment groups were S+CRT (37.5%), CRT (33%), RT (20%), and S+RT (9.5%). The median follow-up was 7.6 years, the OS in 5 and 10 years according to the treatment groups was 43.3%, and 17.3% for S+RT, 47.8% and 41.9% for S+CRT, 40.7% and 27.9% for CRT, and 29.1% and 19.4% for RT (P<0.0001). The stage IIb-IVa, age 60 years or older, RT, and 2DRT were significant factors in the univariate and multivariate analyses. In stage I-IIa, no significant difference was found among the treatment groups (P=0.907). In stage IIb-IVa, a significant difference was observed (P=0.0001). CRT versus RT had significance, and no difference between S+RT versus S+CRT, and S+CRT versus CRT was seen for stage IIb-IVa. Conclusions: In a long-term follow-up, no significant difference among the treatment modalities was found for early disease. For stage IIb-IVa, significant differences were observed, with RT having the worst survival, and CRT similar to S+CRT. These outcomes show that tumor and patients characteristics can be used to decide the best treatment option outside a clinical trial.

Disparities in the Use of Adjuvant External Beam Radiation Therapy in Node-positive Cervical Cancer Patients Following Hysterectomy

Objective: The objective of this study was to investigate the use of adjuvant external beam radiation therapy (EBRT) among patients with early-stage cervical carcinoma metastatic to regional lymph nodes (LNs). Materials and Methods: The National Cancer Database was accessed and patients with early-stage cervical carcinoma diagnosed between 2004 and 2015 were identified. Those with regional LN metastases who had a hysterectomy were selected and administration of adjuvant EBRT was evaluated. Travel distance from the reporting facility was categorized into short (<12.5 miles), intermediate (12.5 to 49.9 miles) and long (>49.9 miles). Results: A total of 3436 patients met the inclusion criteria; the rate of EBRT use was 69.7%. Black women were less likely to receive EBRT compared with white (64.2% vs. 70.6%, P=0.037), while patients who had radical hysterectomy were more likely to receive EBRT compared with those who had simple hysterectomy (72.6% vs. 66%, P<0.001). Rates of EBRT administration for patients who traveled short distance was 74.3% compared with 68.9% and 56.9% for those who traveled intermediate and long distance, respectively (P<0.001). On multivariate analysis, patients who traveled long (odds ratio: 0.44, 95% confidence interval [CI]: 0.36, 0.54) or intermediate (OR: 0.73, 95% CI: 0.61, 0.86) distances were less likely to receive EBRT. After controlling for age, race, insurance, presence of comorbidities, stage, histology, and type of hysterectomy, omission of EBRT was associated with worse survival (hazard ratio: 1.53, 95% CI: 1.32, 1.78). Conclusions: A large percentage of patients with early-stage cervical cancer and positive LNs did not receive EBRT following hysterectomy. Black women were less likely to receive EBRT than white women. Travel burden may negatively influence appropriate treatment.

Predictors and Patterns of Recurrence in Vulvar Cancer

Objective: To identify prognostic factors predicting recurrence in vulvar cancer patients undergoing surgery. Methods: We retrospectively evaluated data from consecutive patients with vulvar cancer treated between 2002 and 2024 in 2 Italian centers. Basic descriptive statistics and multivariable analysis were used to create predictive models for patient outcomes. Five-year disease-free survival (DFS) and overall survival (OS) were analyzed using a Cox proportional hazards model. Results: The study included 283 patients diagnosed with vulvar cancer (239 with squamous cell carcinoma). The most frequent stages were stage I (50.9%) and stage III (30.4%). After a median follow-up of 27 months, 91 (32.2%) recurrences were observed, of which 20% were local, 6% were regional, and 6% were distant. The five-year DFS and OS were 46% and 60%, respectively. Multivariate analysis identified the presence of positive lymph nodes (hazard ratio [HR]: 3.54, 95% confidence interval [CI]: 1.04-12.08), age (HR: 1.02, 95% CI: 1-1.04), FIGO stage II (HR: 3.12, 95% CI: 1.24-7.87), and FIGO stage IV (HR: 3.85, 95% CI: 1.19-12.43) as factors associated with worse DFS. Positive nodes (HR: 2.64, 95% CI: 1.2-5.8) and tumor diameter >4 cm (HR: 1.89, 95% CI: 1.05-3.42) were associated with OS. FIGO stage >I was predictive of regional and distant recurrences, but no factor was found to correlate with local recurrence. Conclusions: FIGO stage >I was predictive of regional and distant recurrences, while no factors influencing local recurrence were identified. Positive nodes, age, and FIGO stage >I correlated with DFS, whereas tumor diameter >4 cm and positive nodes influenced OS.

Surgical Margins After Neoadjuvant Radiation for Locally Advanced Vulvar Carcinoma

Objective: We aim to explore whether the surgical tumor free margin is important for overall survival (OS) and local control in patients who undergo neoadjuvant radiation (RT) for vulvar cancer. Methods: A retrospective review from 2004 to 2021 of patients who underwent RT followed by surgical resection was performed. Patients were categorized into groups based on margin status (no residual disease, >8 mm, close margins defined as 1 to 7 mm, or positive). Local control and OS were analyzed using the Kaplan-Meier with log rank test. Multivariate analysis was performed with cox hazards model. Results: Eighty-three patients were included. A complete pathologic response (pCR) was found in 56% (n=46) of patients. The median follow-up time was 35 months (range: 4 to 216). The median OS for the entire cohort was 46 months (95% CI: 32.3-59.7). Having a pCR improved both OS and disease-free survival (DFS) compared with residual disease by 81 and 91 months, respectively (P<0.001). In the 2 patients with a margin >8 mm, there was no statistical difference in survival between those with close margins (46 vs. 25 mo, P=0.485). Factors that significantly impacted both OS and DFS were depth of invasion (DOI) and LVSI. On multivariate analysis of those with residual disease, there was no difference in OS or DFS by margin status but having a DOI >9 mm showed decreased OS (HR: 3.654; 95% CI: 1.317-10.135). Conclusions: In this cohort, response to RT, not margin status drives survival and recurrence. Given residual disease, the optimal margin is not clear, as there were only 2 patients with >8 mm margins. A close or positive margin had no impact on OS or local recurrence. A DOI >9 mm significantly impacts both OS and local recurrence even when accounting for other factors.

Genomic and Molecular Characteristics of Ovarian Carcinosarcoma

Ovarian carcinosarcoma (OCS) is a rare malignancy with a poor prognosis. It is a biphasic tumor with malignant epithelial and mesenchymal components. A few mutations commonly seen in cancer have been identified in OCS, including TP53, PIK3CA, c-myc, ZNF217, ARID1A, and CTNNB1. Some OCS tumors have shown vascular endothelial growth factor positivity and limited HER2 expression. There is evidence of homologous recombination deficiency in OCS. This malignancy can be categorized as copy number high but has not been shown to have a high tumor mutational burden. There are mixed findings regarding the presence of biomarkers targeted by immune checkpoint inhibitors in OCS. For treatments other than systemic chemotherapy, the data available are largely based on in vitro and in vivo studies. In addition, there are case reports citing the use of poly-ADP ribose polymerase inhibitors, vascular endothelial growth factor inhibitors, and immunotherapy with varying degrees of success. This review paper will discuss the molecular and genomic characteristics of OCS, which can guide future treatment strategies.

The Role of Adjuvant Chemotherapy in Endometrial Cancer Following Preoperative Neoadjuvant Chemoradiation Therapy

Objectives: In patients with surgically unresectable disease who undergo neoadjuvant chemoradiation (CRT) or neoadjuvant radiation therapy (RT) before surgical staging, little is known about whether adjuvant chemotherapy confers a survival benefit. We aim to explore the survival impact of adjuvant chemotherapy in patients with locally advanced endometrial cancer who undergo neoadjuvant CRT or RT. Methods: A retrospective, single-institution review of all patients from April 2008 to October 2021 who underwent neoadjuvant RT or CRT before surgical resection of endometrial cancer was performed. Kaplan-Meier method with log-rank test was used to determine differences in overall survival (OS) and disease-free survival (DFS) between the group that received adjuvant chemotherapy and the group that did not. Subgroup analysis was performed to assess whether specific subgroups benefited from adjuvant chemotherapy. Results: Eighty-nine patients, 48 (54%) of whom received adjuvant chemotherapy, were identified. There was no statistically significant difference in OS (P=0.062) between those who received adjuvant chemotherapy and those who did not. Adjuvant chemotherapy had a significant association with worse DFS (P=0.037). On subgroup analysis, there were no statistically significant differences in OS or DFS in any subgroups when examining the impact of adjuvant chemotherapy. Conclusions: After receiving neoadjuvant CRT or RT for advanced and high-grade endometrial cancers, adjuvant chemotherapy was not predictive of improved OS, but was predictive of worse DFS. A larger cohort and longer follow-up are needed to ascertain whether certain high-risk subgroups of patients benefit from adjuvant chemotherapy.

Recurrence Risk Stratification for Women With FIGO Stage I Uterine Endometrioid Carcinoma Who Underwent Surgical Lymph Node Evaluation

Objective: The aim of this study was to estimate the recurrence risk based on the number of prognostic factors for patients with stage I uterine endometrioid carcinoma (EC) who underwent surgical lymph node evaluation (SLNE) and were managed with observation. Methods: We queried our database for women with FIGO-2009 stage I EC who underwent surgical staging including SLNE. Multivariate analysis with stepwise model selection was used to determine independent risk factors for 5-year recurrence-free survival (RFS). Study groups based on risk factors were compared for RFS, disease-specific survival, and overall survival. Results: A total of 706 patients were identified: median age was 60 years (range, 30 to 93 y) and median follow-up was 120 months. Median number of examined lymph nodes was 8 (range, 1 to 66). 91% were stage IA, 75% had grade 1 and lymphovascular space invasion was detected in 6%. Independent predictors of 5-year RFS included age 60 years and above (P=0.038), grade 2 (P=0.003), and grade 3 (P<0.001) versus grade 1. Five-year RFS for group 0 (age less than 60 y and grade 1) was 98% versus 92% for group 1 (either: age 60 y and older or grade 2/3) versus 84% for group 2 (both: age 60 y and above and grade 2/3), respectively (P<0.001). Five-year disease-specific survival was 100% versus 98% versus 95%, (P=0.012) and 5-year overall survival was 98% versus 90% versus 81%, for groups 0, 1, and 2, respectively (P<0.001). Conclusions: In patients with stage I EC who received SLNE and no adjuvant therapy, only age 60 years and above and high tumor grade were independent predictors of recurrence and can be used to quantify individualized recurrence risk, whereas lymphovascular space invasion was not an independent prognostic factor in this cohort.

Effect of Mismatch Repair Status on Outcome of Early-Stage Grade 1 to 2 Endometrial Cancer Treated With Vaginal Brachytherapy

Objectives: The objective of this study was to determine if deficiency of mismatch repair (dMMR) proteins in patients with early-stage favorable endometrial cancer treated with vaginal brachytherapy (VB) is associated with increased recurrence. Materials and Methods: A multi-institutional retrospective cohort study of 141 patients with stage I to II grade 1 and 2 endometrioid adenocarcinoma treated with surgery and adjuvant VB was performed to compare recurrence risk in dMMR (n=41) versus MMR-preserved (pMMR) (n=100). Additional clinical and pathologic risk factors were also collected. Univariate analysis and multivariable analysis Cox regression analysis was performed to identify factors associated with any recurrence. Kaplan-Meier method and log rank test were used to compare recurrence free survival and overall survival (OS). Results: Median follow up was 42 months. Forty-one patients (29%) were dMMR. There were 7 recurrences (17%) in dMMR versus 4 recurrences (4%) in pMMR (P=0.009). On univariate analysis of any recurrence, both dMMR (hazard ratio: 5.3, P=0.008) and stage (hazard ratio: 3.8, P=0.05) were statistically significantly associated with time to first recurrence. The 5-year recurrence free survival was 90% (95% CI: 73%-96%) in pMMR versus 61.0% (95% CI: 19%-86%) in dMMR (P=0.003). Five-year OS was 96% (95% CI: 76%-99%) in pMMR versus 86% (95% CI: 62%-95%) in dMMR (P=0.03). Conclusions: MMR deficiency in stage I to II grade 1 to 2 endometrial cancer patients treated with adjuvant VB alone was associated with statistically significant increased risk for any recurrence and worse OS. MMR status may be an important prognosticator in this cohort of patients warranting adjuvant treatment intensification in the clinical trial 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.

Endometrial Cancer, BRCA1, and BRCA2 in the UK Biobank Cohort

Objectives: Endometrial cancer (EC) risk in BRCA1/2 mutation carriers has been uncertain. EC risk in women with germline BRCA1 or BRCA2 mutations was recently assessed in a multicenter cohort study. BRCA1/2 mutation carriers had a 2- to 3-fold increased risk for EC, with highest risk observed for the rare subgroups of serous-like and p53-abnormal EC in BRCA1 mutation carriers. To further evaluate risk, we looked at EC and BRCA1/2 in the UK Biobank cohort. Methods: EC diagnosis was ascertained using the 10th Revision of the International Classification of Diseases. We analyzed the single nucleotide polymorphisms (SNPs) rs799917 (BRCA1) and rs144848 (BRCA2). A case-control study found a possible association of rs799917 but not rs144848 with EC. Data processing was performed on Minerva, a Linux mainframe with Centos 7.6, at the Icahn School of Medicine at Mount Sinai. Results: Percentage ECs within genotypes for SNPs rs799917 and rs144848 was 0.6%. The variability within SNP genotypes was insignificant (P=0.288 for rs799917, 2-tailed Fisher exact test; P=0.931 for rs144848). In comparison, an estimated 70,200 women who had been diagnosed with uterine cancer between 1991 and 2010 were alive in the UK at the end of 2010. A total of 21,892,000 UK residents were ages 50 to 92; approximately half were women. Therefore, prevalence of EC in these UK women was 0.6%, identical to percentage EC within 6 genotypes for SNPs rs799917 and rs144848. Conclusion: Although we cannot rule out an increase in several rare types of EC, our analysis suggests that the overall incidence or risk of EC does not appear to be increased by the presence of BRCA1 or BRCA2 mutations.