Guideline-Discordant Care in Early-Stage Vulvar Cancer.

OBJECTIVE: To describe the use of National Comprehensive Cancer Network guideline-concordant inguinofemoral lymph node (LN) evaluation in individuals with early-stage vulvar cancer. METHODS: This retrospective cohort study identified patients with T1b and T2 vulvar squamous cell carcinoma diagnosed between 2012 and 2018 using the National Cancer Database. Factors associated with LN evaluation were examined using logistic regression analyses, adjusting for patient, disease, and facility-level characteristics. Kaplan-Meier survival analysis using log rank test and Cox regression was performed for the entire cohort and a subgroup of older patients , defined as individuals aged 80 years or older. RESULTS: Of the 5,685 patients with vulvar cancer, 3,756 (66.1%) underwent guideline-concordant LN evaluation. In our adjusted model, age 80 years or older (odds ratio [OR], 0.30; 95% CI 0.22-0.42) and Black race (OR 0.72; 95% CI 0.54-0.95) were associated with lower odds of LN evaluation. High-volume hospitals were associated with increased odds of LN evaluation compared with low-volume hospitals (OR 1.62; 95% CI 1.28-2.05). Older individuals who did not undergo LN evaluation had significantly worse overall survival than those with pathologically negative LNs (hazard ratio [HR] 0.45; 95% CI 0.37-0.55) and similar overall survival as those with pathologically positive LNs (HR 1.05; 95% CI 0.77-1.43). CONCLUSION: Guideline-concordant LN evaluation for early-stage vulvar squamous cell carcinoma is low. Lower utilization is associated with older age, Black race, and care at a low-volume hospital.

Association of an Acute Myocardial Infarction Readmission-Reduction Program With Mortality and Readmission.

BACKGROUND: Reducing hospital readmission after acute myocardial infarction (AMI) has the potential to both improve quality and reduce costs. As such, readmission after AMI has been a target of financial penalties through Medicare. However, substantial concern exists about potential adverse effects and efficacious readmission-reduction strategies are not well validated. METHODS AND RESULTS: We started an AMI readmissions reduction program in November 2017. Between July 2016 and February 2019, hospital billing data were queried to detect all inpatient hospitalizations at the Massachusetts General Hospital for AMI. Thirty-day readmission was identified through hospital billing data, and mortality was extracted from our electronic health record. The data set was merged with claims data for patients in accountable care organizations to detect readmission at other hospitals. We performed segmented linear regression, adjusting for secular trend and case mix, to assess the independent association of our program on both outcome variables. After inclusion and exclusion criteria were applied, the study population included 2020 patients. The overall 30-day readmission rate was higher before the intervention than after the intervention (15.5% versus 10.7%, P=0.002). The overall 30-day mortality rate was similar in both time periods (1.8% versus 1.4%, P=0.457). The program was associated with initial reduction in 30-day readmission (-9.8%, P=0.0002) and 30-day mortality (-2.6%, P=0.041). The program did not change trend in 30-day readmission (+0.19% readmissions/mo, P=0.554) and trend in 30-day mortality (-0.21% deaths/mo, P=0.119). CONCLUSIONS: An AMI readmissions reduction program that increases outpatient and emergency department (ED) access to cardiology care is associated with reduced 30-day readmission and 30-day mortality. Similar statistical techniques can be used to conduct a rigorous, mechanistic program evaluation of other quality improvement initiatives.

Real-Time Single-Walled Carbon Nanotube-Based Fluorescence Imaging Improves Survival after Debulking Surgery in an Ovarian Cancer Model.

Improved cytoreductive surgery for advanced stage ovarian cancer (OC) represents a critical challenge in the treatment of the disease. Optimal debulking reaching no evidence of macroscopic disease is the primary surgical end point with a demonstrated survival advantage. Targeted molecule-based fluorescence imaging offers complete tumor resection down to the microscopic scale. We used a custom-built reflectance/fluorescence imaging system with an orthotopic OC mouse model to both quantify tumor detectability and evaluate the effect of fluorescence image-guided surgery on post-operative survival. The contrast agent is an intraperitoneal injectable nanomolecular probe, composed of single-walled carbon nanotubes, coupled to an M13 bacteriophage carrying a modified peptide binding to the SPARC protein, an extracellular protein overexpressed in OC. The imaging system is capable of detecting a second near-infrared window fluorescence (1000-1700 nm) and can display real-time video imagery to guide intraoperative tumor debulking. We observed high microscopic tumor detection with a pixel-limited resolution of 200 µm. Moreover, in a survival-surgery orthotopic OC mouse model, we demonstrated an increased survival benefit for animals treated with fluorescence image-guided surgical resection compared to standard surgery.

Prognostic determinants in patients with uterine and ovarian carcinosarcoma.

OBJECTIVE: To analyze and compare the demographics, treatment, recurrence, and survival rates in patients with carcinosarcoma of the uterus and ovary. STUDY DESIGN: All patients with uterine and ovarian carcinosarcoma who underwent surgical staging at the 2 participating institutions between 1995 and 2007 were identified. The Kaplan-Meier method was used to generate overall survival (OS) data. Factors predictive of outcome were compared using the Cox proportional hazards model. RESULTS: Analysis of 87 women with uterine carcinosarcoma and 71 with ovarian carcinosarcoma was performed. Of those, 47% of the patients with uterine carcinosarcoma, compared to 14% of the patients with ovarian carcinosarcoma, were diagnosed with localized disease (p < 0.001). Age > 65 years old (p < 0.001), tumor extension (local versus regional versus distant, p < 0.001), and platinum-based chemotherapy (p = 0.05) were all independent predictors of survival. In a multivariate Cox regression model, age > 65 years old (hazard ratio [HR] = 2.5, p < 0.001), tumor extension (locoregional versus distant, HR = 3.9, p = 0.006), and uterine versus ovarian carcinosarcoma (HR = 2.2, p = 0.009) were identified as independent predictors of OS. CONCLUSION: Uterine carcinosarcoma presents at an earlier stage than does ovarian carcinosarcoma. In the multivariate analysis uterine carcinosarcoma demonstrated shorter survival than did ovarian carcinosarcoma after adjustment for extent of disease spread, age, and platinum-based chemotherapy.

Recurrent endometrial cancer.

Endometrial cancer is the most common gynecologic malignancy in the United States. The majority of women are diagnosed with early-stage, low-grade endometrioid tumors that are highly curable with primary surgery. Patients with more advanced and/or higher grade disease require multimodality therapy and have a higher risk for recurrence. Although uterine papillary serous carcinoma and clear cell carcinoma are diagnosed infrequently, they account for almost half of all relapses. As women with recurrent endometrial cancer constitute a heterogeneous group, an individualized approach is required. We review the treatment options of surgery, radiation, hormonal therapy, cytotoxic chemotherapy, and biological agents.

Synergism of epidermal growth factor receptor-targeted immunotherapy with photodynamic treatment of ovarian cancer in vivo.

BACKGROUND: Epithelial ovarian cancer often develops resistance to standard treatments, which is a major reason for the high mortality associated with the disease. We examined the efficacy of a treatment regimen that combines immunotherapy to block the activity of epidermal growth factor receptor (EGFR), overexpression of which is associated with the development of resistant ovarian cancer, and photodynamic therapy (PDT), a mechanistically distinct photochemistry-based modality that is effective against chemo- and radioresistant ovarian tumors. METHODS: We tested a combination regimen consisting of C225, a monoclonal antibody that inhibits the receptor tyrosine kinase activity of EGFR, and benzoporphyrin derivative monoacid A (BPD)-based PDT in a mouse model of human ovarian cancer. Therapeutic efficacy was evaluated in acute treatment response and survival studies that used 9-19 mice per group. Analysis of variance and Wilcoxon statistics were used to analyze the data. All statistical tests were two-sided. RESULTS: Mice treated with PDT + C225 had the lowest mean tumor burden compared with that in the no-treatment control mice (mean percent tumor burden = 9.8%, 95% confidence interval [CI] = 2.3% to 17.3%, P < .001). Mean percent tumor burden for mice treated with C225 only or PDT only was 66.6% (95% CI = 58.7% to 74.4%, P < .001) and 38.2% (95% CI = 29.3% to 47.0%, P < .001), respectively. When compared with PDT only or C225 only, PDT + C225 produced synergistic reductions in mean tumor burden (P < .001, analysis of variance) and improvements in survival (P = .0269, Wilcoxon test). Median survival was approximately threefold greater for mice in the PDT + C225 group than for mice in the no-treatment control group (80 days versus 28 days), and more mice in the PDT + C225 group were alive at 180 days (3/9; 33% [95% CI = 7% to 70%]) than mice in the C225-only (0/12; 0% [95% CI = 0% to 22%]) or PDT-only (1/10; 10% [95% CI = 0.2% to 44%]) groups. CONCLUSION: A mechanistically nonoverlapping combination modality consisting of receptor tyrosine kinase inhibition with C225 and BPD-PDT is well tolerated, effective, and synergistic in mice.