Immuno-Molecular Targeted Therapy Use and Survival Benefit in Patients with Stage IVB Cervical Carcinoma in Commission on Cancer®-Accredited Facilities in the United States.

PURPOSE: To investigate IMT use and survival in real-world stage IVB cervical cancer patients outside randomized clinical trials. METHODS: Patients diagnosed with stage IVB cervical cancer during 2013-2019 in the National Cancer Database and treated with chemotherapy (CT) ± external beam radiation (EBRT) ± intracavitary brachytherapy (ICBT) ± IMT were studied. The adjusted hazard ratio (AHR) and 95% confidence interval (CI) for risk of death were estimated in patients treated with vs. without IMT after applying propensity score analysis to balance the clinical covariates. RESULTS: There were 3164 evaluable patients, including 969 (31%) who were treated with IMT. The use of IMT increased from 11% in 2013 to 46% in 2019. Age, insurance, facility type, sites of distant metastasis, and type of first-line treatment were independently associated with using IMT. In propensity-score-balanced patients, the median survival was 18.6 vs. 13.1 months for with vs. without IMT (p < 0.001). The AHR was 0.72 (95% CI = 0.64-0.80) for adding IMT overall, 0.72 for IMT + CT, 0.66 for IMT + CT + EBRT, and 0.69 for IMT + CT + EBRT + ICBT. IMT-associated survival improvements were suggested in all subgroups by age, race/ethnicity, comorbidity score, facility type, tumor grade, tumor size, and site of metastasis. CONCLUSIONS: IMT was associated with a consistent survival benefit in real-world patients with stage IVB cervical cancer.

Short-Term Outcomes After Hysterectomy for Endometrial Cancer/EIN With Concomitant Pelvic Floor Disorder Surgery.

IMPORTANCE: Endometrial cancer and precancer are common gynecologic problems for many women. A majority of these patients require surgery as the mainstay of treatment. Many of these patients often have concurrent pelvic floor disorders. Despite the prevalence and shared risk, fewer than 3% of women undergo concomitant surgery for PFDs at the time of surgery for endometrial cancer or endometrial intraepithelial neoplasia/hyperplasia. OBJECTIVE: This study aimed to evaluate postoperative morbidity of concomitant pelvic organ prolapse (POP) and/or urinary incontinence (UI) procedures at the time of hysterectomy for endometrial cancer (EC) or endometrial intraepithelial neoplasia/endometrial hyperplasia (EIN/EH). METHODS: This retrospective analysis of women undergoing hysterectomy for EC or EIN/EH between 2017 and 2022 used the American College of Surgeons National Surgical Quality Improvement Program database. The primary outcome was any major complication within 30 days of surgery. Comparisons were made between 2 cohorts: hysterectomy with concomitant pelvic organ prolapse/urinary incontinence procedures (POPUI) versus hysterectomy without concomitant POP or UI procedures (HYSTAlone). A subgroup analysis was performed in patients with EC. A propensity score matching cohort was also created. RESULTS: A total of 23,144 patients underwent hysterectomy for EC or EIN/EH: 1.9% (n = 432) had POP and/or UI procedures. Patients with POPUI were older, were predominantly White, had higher parity, and had lower body mass index with lower American Society of Anesthesiologists class. Patients with POPUI were less likely to have EC (65.7% vs 78.3%, P < 0.0001) and more likely to have their hysterectomy performed by a general obstetrician- gynecologists or urogynecologists. Major complications were low and not significantly different between POPUI and HYSTAlone (3.7% vs 3.6%, P = 0.094). A subgroup analysis of EC alone found that the HYSTAlone subset did not have more advanced cancers, yet the surgeon was more likely a gynecologic oncologist (87.1% vs 68.0%, P < 0.0001). There were no statistically significant differences between the 2 cohorts for the primary and secondary outcomes using propensity score matching analysis. CONCLUSIONS: Concomitant prolapse and/or incontinence procedures were uncommon and did not increase the rate of 30-day major complications for women undergoing hysterectomy for EC/EH.

Survival disparities in non-Hispanic Black and White cervical cancer patients vary by histology and are largely explained by modifiable factors.

PURPOSE: We investigated racial disparities in survival by histology in cervical cancer and examined the factors contributing to these disparities. METHODS: Non-Hispanic Black and non-Hispanic White (hereafter known as Black and White) patients with stage I-IV cervical carcinoma diagnosed between 2004 and 2017 in the National Cancer Database were studied. Survival differences were compared using Cox modeling to estimate hazard ratio (HR) or adjusted HR (AHR) and 95% confidence interval (CI). The contribution of demographic, socioeconomic and clinical factors to the Black vs White differences in survival was estimated after applying propensity score weighting in patients with squamous cell carcinoma (SCC) or adenocarcinoma (AC). RESULTS: This study included 10,111 Black and 43,252 White patients with cervical cancer. Black patients had worse survival than White cervical cancer patients (HR = 1.40, 95% CI = 1.35-1.45). Survival disparities between Black and White patients varied significantly by histology (HR = 1.20, 95% CI = 1.15-1.24 for SCC; HR = 2.32, 95% CI = 2.12-2.54 for AC, interaction p < 0.0001). After balancing the selected demographic, socioeconomic and clinical factors, survival in Black vs. White patients was no longer different in those with SCC (AHR = 1.01, 95% CI 0.97-1.06) or AC (AHR = 1.09, 95% CI = 0.96-1.24). In SCC, the largest contributors to survival disparities were neighborhood income and insurance. In AC, age was the most significant contributor followed by neighborhood income, insurance, and stage. Diagnosis of AC (but not SCC) at ≥65 years old was more common in Black vs. White patients (26% vs. 13%, respectively). CONCLUSIONS: Histology matters in survival disparities and diagnosis at ≥65 years old between Black and White cervical cancer patients. These disparities were largely explained by modifiable factors.

Analysis of Sociodemographic Factors Affecting Ambulatory Surgical Center Discharge Patterns for Endometrial Cancer Hysterectomies.

STUDY OBJECTIVE: Investigate outcomes for patients undergoing minimally invasive hysterectomies (MIHs) performed for endometrial cancer at ambulatory surgery centers (ASCs). DESIGN: Our study aimed to explore the feasibility and discharge outcomes for MIHs for endometrial cancer in an ASC setting by using same-day discharge data. SETTING: The prevalence of MIH for endometrial cancer between 2016 and 2019 was estimated from the Nationwide Ambulatory Surgery Sample. PATIENTS: Patients who underwent MIHs for endometrial cancer at an ASC were included. INTERVENTIONS: N/A MEASUREMENTS MAIN RESULTS: Weighted estimates of prevalence and association between discharge status and sociodemographic factors were explored. Same-day discharge was defined as discharge on the day of surgery, and delayed discharge was defined as discharge after the day of surgery. An estimated 95 041 MIHs for endometrial cancer were performed at ASCs between 2016 and 2019. Notably, 91.9% (n = 87 372) resulted in same-day discharge, 1.2% (n = 1121) had delayed discharge, and 6.9% (n = 6548) had missing discharge information; 78.7% procedures (n = 68 812) were performed at public hospitals. The proportion of delayed discharges were lower in private, not-for profit ASCs (0.8%, p = .03) than public hospitals. Patients who had delayed discharges on average were older (69.7 vs 62.4 years, p <.001), more likely to have comorbid conditions including diabetes (adjusted odds ratio [aOR] 1.48, 95% confidence interval [CI] 1.25-1.75) and overweight or obese body mass indices (aOR 1.18, 95% CI 1.01-1.39), and more likely to have public insurance (aOR 1.78, 95% CI 1.40-2.25). CONCLUSION: MIHs for endometrial cancer are feasible in an ASC. Optimal candidates for receipt of MIHs for endometrial cancer at an ASC are patients who are younger and have less comorbidities, lower body mass index, and private insurance.

Improving Risk Assessment for Metastatic Disease in Endometrioid Endometrial Cancer Patients Using Molecular and Clinical Features: An NRG Oncology/Gynecologic Oncology Group Study.

Objectives: A risk assessment model for metastasis in endometrioid endometrial cancer (EEC) was developed using molecular and clinical features, and prognostic association was examined. Methods: Patients had stage I, IIIC, or IV EEC with tumor-derived RNA-sequencing or microarray-based data. Metastasis-associated transcripts and platform-centric diagnostic algorithms were selected and evaluated using regression modeling and receiver operating characteristic curves. Results: Seven metastasis-associated transcripts were selected from analysis in the training cohorts using 10-fold cross validation and incorporated into an MS7 classifier using platform-specific coefficients. The predictive accuracy of the MS7 classifier in Training-1 was superior to that of other clinical and molecular features, with an area under the curve (95% confidence interval) of 0.89 (0.80-0.98) for MS7 compared with 0.69 (0.59-0.80) and 0.71 (0.58-0.83) for the top evaluated clinical and molecular features, respectively. The performance of MS7 was independently validated in 245 patients using RNA sequencing and in 81 patients using microarray-based data. MS7 + MI (myometrial invasion) was preferrable to individual features and exhibited 100% sensitivity and negative predictive value. The MS7 classifier was associated with lower progression-free and overall survival (p ≤ 0.003). Conclusion: A risk assessment classifier for metastasis and prognosis in EEC patients with primary tumor derived MS7 + MI is available for further development and optimization as a companion clinical support tool.

Diagnostic Utility of Endocervical Curettage During Colposcopy Among Patients of Varying Risk Factors.

OBJECTIVE: Endocervical curettage (ECC) during colposcopy is recommended in certain circumstances; however, diagnostic use remains unclear. We evaluate the utility of ECC among patients with non-fully visualized squamocolumnar junction (SCJ) and certain patient socioeconomic factors. METHODS: Retrospective chart analysis was completed for patients aged older than 21 years who underwent a colposcopy at 2 study sites between 2012 and 2021. Demographics and histopathologic results were analyzed. RESULTS: A total of 1,516 colposcopies were reviewed; 73.8% (n = 1,119) had an ECC with colposcopy. Of those, 92.1% (n = 1,031) had benign ECC whereas 13.9% (n = 156) had a positive ECC at time of colposcopy. Most patients with benign ECC had benign/low-grade squamous intraepithelial lesion pathology on colposcopy biopsy (82.3%; n = 914; p < .001), and most patients with high-grade squamous intraepithelial lesion (HSIL) on ECC had HSIL on colposcopy biopsy (63.4%; n = 52; p < .001) However, when looking at patients with high-grade pathology on colposcopy biopsy, it was seen that most had benign or low-grade squamous intraepithelial lesion on ECC (79.5%; n = 205; p < .001). Most patients with adequately visualized SCJ on colposcopy were noted to have HSIL on biopsy and negative ECC (73%; n = 81; p < .001). This result was similar in patients with non-fully visualized SCJ, although not statistically significant. When stratified by socioeconomic status, most patients with high-grade lesions had a benign ECC. CONCLUSIONS: Endocervical curettage has been described to increase the identification of high-grade lesions at time of colposcopy. This descriptive study shows that many high-grade lesions at time of excisional procedure had a benign ECC on colposcopy, with no demonstrated clear additional utility in high-risk groups.

Trends in guideline-adherent chemoradiation therapy for locally advanced cervical cancer before and after the affordable care act.

OBJECTIVE: To assess trends in guideline-adherent chemoradiation therapy (GA-CRT) for locally advanced cervical cancer relative to Patient Protection and Affordable Care Act (ACA) implementation. METHODS: National Cancer Database patients treated with chemoradiation for locally advanced cervical cancer (FIGO 2018 Stage IB3-IVA) from 2004 to 2016 were included. GA-CRT was defined according to NCCN guidelines and included: 1) delivery of external beam radiation, 2) brachytherapy, and 3) chemotherapy, 4) no radical hysterectomy. Logistic regression was used to determine trends in GA-CRT relative to the ACA. Survival was also estimated using Kaplan-Meier analysis. RESULTS: 37,772 patients met inclusion criteria (Pre-ACA:16,169; Post-ACA:21,673). A total of 33,116 patients had squamous cell carcinoma and 4626 patients had other histologies. Forty-five percent of patients had lymph node-positive disease. A total of 14.6% of patients had Stage I disease, 41.8% had Stage II disease, 36.4% had Stage III disease, and 7.9% had Stage IVA disease. On multivariable analysis, medicare insurance (OR 0.91; 95%CI: 0.84-0.99 compared to commercial insurance), non-squamous histology (OR 0.83; 95%CI: 0.77-0.89 for adenocarcinoma) and increasing Charlson-Deyo score were associated with decreased odds of receiving GA care. Increasing T-stage was associated with greater receipt of GA-CRT. The percentage of the population that received guideline adherent care increased post-ACA (Pre-ACA 28%; Post-ACA 34%; p < 0.001). Adherence to treatment guidelines increased 2-year survival by 15% (GA 76%; Not GA 61%; p < 0.001). Increased 2-year survival was seen in the post-ACA cohort (Pre-ACA 62%; Post-ACA 69%; p < 0.001). CONCLUSIONS: Implementation of the ACA was associated with improved GA-CRT and survival in patients with locally advanced cervical cancer.

Polypoid endometriosis mimicking invasive cancer in an obese, postmenopausal tamoxifen user.

BACKGROUND: Tamoxifen is a medication often used for the treatment and prevention of breast cancer. It is classically associated with several gynecological side effects to include a thickened endometrial stripe, increased uterine polyp formation, and an increased risk of uterine cancer. Rarely tamoxifen use has been associated with proliferation of endometriosis often severe enough to mimic a late-stage gynecologic malignancy. CASE: A 62-year-old Gravida 0 postmenopausal female with a medical history of severe obesity, infertility, and preventative tamoxifen use presented for evaluation of gross hematuria. A CT urogram was performed and demonstrated findings concerning for carcinomatosis, likely gynecologic in origin. Cervical cancer screening was up-to-date and she had a negative colonoscopy within the prior 2 years. Serum tumor markers were remarkable only for a mildly elevated CA125 of 37.6. Diagnostic laparoscopy demonstrated apparent operable carcinomatosis limited to the pelvis. The procedure was converted to an exploratory laparotomy, where radical tumor cytoreduction was performed to no gross residual disease. Frozen sections performed intraoperatively were unclear of origin but suggestive of low malignant potential. Final pathology resulted for endometriosis. CONCLUSION: This case illustrates a presentation of endometriosis in a postmenopausal woman mimicking advanced mullerian malignancy. The patient's estrogenic state from obesity in combination with the agonist action of the tamoxifen likely contributed to her rare presentation. While findings such as a thickened endometrial stripe are typical of tamoxifen use, such widespread proliferation of endometriosis resulting in a pelvic mass, genito-urinary obstruction, and plaque-like pelvic spread are not. PRÉCIS: Endometriosis is a benign estrogen dependent condition rarely problematic in a postmenopausal patient. Tamoxifen use in the setting of an obese patient may contribute to a proliferation of pre-existing endometriosis which resembles an aggressive late-stage gynecological malignancy.

Actinomyces-Related Tubo-Ovarian Abscess in a Poorly Controlled Type II Diabetic With a Copper Intrauterine Device.

BACKGROUND: The historic association of Actinomyces israelii infection with intrauterine devices (IUDs) has long been recognized. In recent years, the risk of developing pelvic inflammatory disease with a copper or levonorgestrel IUD has been less than 1% in women who are low risk for sexually transmitted infections. IUD-related pelvic infections secondary to actinomyces have largely vanished from contemporary practice. CASE: A 49-year-old using a copper IUD for contraception with poorly controlled type II diabetes mellitus was admitted for suspected tubo-ovarian abscess on the basis of abdominopelvic pain, leukocytosis, and computed tomography findings. After she was treated with intravenous and outpatient antibiotics with clinical improvement, repeat imaging 1 month later revealed a persistent complex left adnexal mass. Tumor markers were negative but given the persistence and complex nature of the mass, surgical management was recommended. A robotic-assisted hysterectomy with bilateral salpingo-oophorectomy was performed. Adhesiolysis, profuse irrigation, and ureteral stenting were required. Pathology revealed bilateral tubo-ovarian abscesses with actinomyces species identified on intraoperative culture. The patient had a total of 10 days of postoperative antibiotics and improved glucose control with no further signs of infection. CONCLUSION: Although actinomyces-related IUD PID is considered an outdated diagnosis, there are intermittent case reports of bizarre presentations in older women, often mimicking malignancy. Actinomyces should be a consideration in tubo-ovarian abscesses or pelvic inflammatory disease in patients with an IUD in place, particularly those who have poor glucose control or are otherwise immunosuppressed. Early identification and treatment of actinomyces tubo-ovarian abscesses may reduce surgical morbidity and overall improve patient outcomes and safety.

Are different methotrexate regimens as first line therapy for low risk gestational trophoblastic neoplasia more cost effective than the dactinomycin regimen used in GOG 0174?

OBJECTIVES: Gynecologic Oncology Group (GOG) 0174 compared weekly intramuscular methotrexate (MTX) with biweekly pulsed intravenous dactinomycin (Act-D) as single-agent chemotherapy for low-risk gestational trophoblastic neoplasia (GTN). Act-D had a higher rate of initial complete response (CR) (70% vs. 53%, p=0.01), but multi-day regimens of MTX have higher historic success rates. We assessed the cost-effectiveness of Act-D vs. MTX per GOG 0174 and explored multi-day MTX regimens. METHODS: A cost effectiveness decision model was constructed with data from GOG 0174. Outcome was cost per first-line treatment success expressed in terms of incremental cost-effectiveness ratio (ICER). Front-line failures were assumed to receive cross-over single agent therapy, second line failures; multi-agent chemotherapy. GOG 0174 had no quality of life (QOL) evaluation, so equal QOL (utility 1.0) was assumed but varied in sensitivity analysis. A second exploratory model included 5-day and 8-day MTX regimens. RESULTS: Act-D ($18,505) was more expensive compared to weekly MTX ($8950) with an ICER of $56,215 per first-line treatment success compared to weekly MTX. Small decreases in QOL dramatically increased the ICER during sensitivity analysis. Models with multi-day MTX regimens were also more cost-effective than Act-D. If effectiveness was redefined as avoidance of multi-agent chemotherapy, weekly MTX was more effective. CONCLUSIONS: With a complete cure rate for low-risk GTN regardless of initial agent, our model supports provider hesitation toward first line Act-D for low risk GTN. While Act-D is more effective for first line treatment success, it is more costly, and does not decrease rate of multi-agent chemotherapy use.

Is FDA-Approved Bevacizumab Cost-Effective When Included in the Treatment of Platinum-Resistant Recurrent Ovarian Cancer?

PURPOSE: Although the Food and Drug Administration has approved incorporation of bevacizumab (BEV) into the treatment of platinum-resistant ovarian cancer (PROC), cost-value measures are an essential consideration, as evidenced by the recent ASCO Value Framework initiative. We assessed the cost-effectiveness and reviewed the net health benefit (NHB) of this expensive treatment. METHODS: A cost-effectiveness decision model was constructed using results from a phase III trial comparing BEV plus cytotoxic chemotherapy with chemotherapy alone in patients with PROC. The Avastin Use in Platinum-Resistant Epithelial Ovarian Cancer (AURELIA) trial demonstrated improvement in progression-free survival and quality of life in patients receiving BEV. Costs, paracentesis rates, and adverse events were incorporated, including subgroup analysis of different partner chemotherapy agents. RESULTS: Inclusion of BEV in the treatment of platinum-resistant recurrent ovarian cancer meets the common willingness-to-pay incremental cost-effectiveness ratio (ICER) threshold of $100,000 per progression-free life-year saved (LYS) for 15-mg/kg dosing and approaches this threshold for 10-mg/kg dosing, with an ICER of $160,000. In sensitivity analysis, reducing the cost of BEV by 13% (from $9,338 to $8,100 per cycle) allows 10-mg/kg dosing to reach a $100,000 ICER. Exploratory analysis of different BEV chemotherapy partners showed an ICER of $76,000 per progression-free LYS (6.5-month progression-free survival improvement) and $54,000 per LYS (9.1-month overall survival improvement) for the addition of BEV to paclitaxel once per week. Using the ASCO framework for value assessment, the NHB score for BEV plus paclitaxel once per week is 48. CONCLUSION: Using a willingness-to-pay threshold of $100,000 ICER, the addition of BEV to chemotherapy either demonstrates or approaches cost-effectiveness and NHB when added to the treatment of patients with PROC.

Mitochondrial proteomic analysis of cisplatin resistance in ovarian cancer.

Epithelial ovarian cancer (EOC) is the leading cause of death among women with gynecologic malignancies and accounts for approximately 6% of cancer deaths among women. Cisplatin and its analogues form the backbone of the most active chemotherapy regimens in advanced EOC; however, development of platinum resistance is common and typically marks a transition in which curing the patient is no longer possible. An emerging theme in many cancers is that mitochondrial dysfunction contributes to an aggressive carcinogenic phenotype. We hypothesized that changes in the mitochondrial proteome are required to support development of cisplatin resistance in human EOC. To investigate this hypothesis, an organellar proteomics approach was utilized to quantify alterations in protein abundance in mitochondria enriched from isogenic cisplatin-sensitive (A2780) and -resistant (A2780-CP20) human EOC cells. Protein isolates from mitochondria-enriched fractions were analyzed by high resolution liquid chromatography-tandem mass spectrometry (LC-MS/MS), and relative abundance of identified proteins was quantified by spectral counting. Pathway analyses revealed significant increases in notch signaling pathways, cell survival, and alternate apoptotic pathways in the A2780-CP20 subtype. Among the alterations identified in the mitochondrial proteomic composition in cisplatin-resistant EOC cells, activated leukocyte cell adhesion molecule (AKAP12) and A kinase anchoring protein 12 (AKAP12) were elevated, while nestin was diminished in the mitochondrial fraction of A2780-CP20 relative to A2780. This was verified by immunoblot analysis. These results confirm that important changes in the mitochondrial proteome, many of which promote evasion of apoptosis and tumor invasiveness and metastasis, are present in cisplatin-resistant EOC.