Matthew P Schlumbrecht

Body mass index and chemotherapy completion among patients with newly diagnosed ovarian cancer

Abstract Background Several ovarian cancer studies have suggested that a body mass index (BMI) of 30 or higher is associated with lower compliance with National Comprehensive Cancer Network–recommended chemotherapy but primarily involved treatment before 2012, when dose capping was recommended for patients with higher body surface areas. Updated analyses in the contemporary treatment era are warranted. Methods In a retrospective cohort of patients with newly diagnosed ovarian cancer receiving curative-intent carboplatin plus paclitaxel in the Yale-Smilow Cancer Network (2012-2022), we evaluated BMI at diagnosis in relation to relative dose intensity (RDI)—the ratio of completed chemotherapy dose intensity to the National Comprehensive Cancer Network–recommended dose intensity—which reflects dose modification both before and during treatment. We also assessed starting RDI (which reflects modifications before treatment) and received RDI (which reflects modifications during treatment). Data on hospitalizations and hematological chemotoxicities were collected. We examined the association between BMI (<25, 25-30, ≥30) and chemotherapy completion, hospitalizations, and toxicities using multivariable linear and logistic regressions. Results Among 327 patients, the average RDI was 79.7%, and 44.3% had an RDI below 85%. Mean (SD) starting and received RDI were 97.9% (9.1%) and 81.8% (25.7%), respectively. Higher BMI was associated with higher RDI (Paggregate = .03) and received RDI (Paggregate = .04). Body mass index was not associated with starting RDI, dose reductions, delays, hospitalizations, or hematological toxicities. Conclusions Among patients with ovarian cancer treated since 2012, the overall RDI was low. Relative dose intensity was higher among patients with a BMI of 25 or higher compared with a BMI below 25. Most dose modifications occurred during treatment and not before initiation. Studies with body composition data and interventions that maximize chemotherapy completion during treatment are warranted.

Unique Considerations in Early Detection, Risk, and Awareness of Endometrial Cancer in Black Women

Endometrial cancer is the most common gynecologic cancer in the United States. Over the last several decades, the incidence of aggressive tumors, and thus the rate of death from disease, has increased significantly. The population most affected by these epidemiologic shifts are Black women. Symptom awareness, lack of treatment access, and failure of providers to provide guideline-concordant care are just some of the drivers behind these changes. Race as a social construct has historically categorized women into groups that are not reflective of the nuanced personalization that is required for cancer prevention strategies and targeted cancer treatments. There is, however, an increasing understanding that disaggregation by place of birth and social context are important to understand care-seeking behaviors, genetic drivers of disease, and factors that lead to deleterious outcomes. In this review, we will focus on specific individual-level influences that impact disease diagnosis and care-seeking among Black women, recognizing that the global disparities which exist in this disease encompass multiple domains. Such considerations are crucial to understanding drivers of self-efficacy and to develop programs for knowledge awareness and empowerment within a framework that is both useful and acceptable to these diverse communities at risk.

The Vaginal Microbiome is Associated with Endometrial Cancer Grade and Histology

The human microbiome has been strongly correlated with disease pathology and outcomes, yet remains relatively underexplored in patients with malignant endometrial disease. In this study, vaginal microbiome samples were prospectively collected at the time of hysterectomy from 61 racially and ethnically diverse patients from three disease conditions: (i) benign gynecologic disease (controls, n = 11), (ii) low-grade endometrial carcinoma (n = 30), and (iii) high-grade endometrial carcinoma (n = 20). Extracted DNA underwent shotgun metagenomics sequencing, and microbial α and β diversities were calculated. Hierarchical clustering was used to describe community state types (CST), which were then compared by microbial diversity and grade. Differential abundance was calculated, and machine learning utilized to assess the predictive value of bacterial abundance to distinguish grade and histology. Both α- and β-diversity were associated with patient tumor grade. Four vaginal CST were identified that associated with grade of disease. Different histologies also demonstrated variation in CST within tumor grades. Using supervised clustering algorithms, critical microbiome markers at the species level were used to build models that predicted benign versus carcinoma, high-grade carcinoma versus benign, and high-grade versus low-grade carcinoma with high accuracy. These results confirm that the vaginal microbiome segregates not just benign disease from endometrial cancer, but is predictive of histology and grade. Further characterization of these findings in large, prospective studies is needed to elucidate their potential clinical applications. Significance: The vaginal microbiome reliably segregates not just benign gynecologic condition from endometrial cancer, but also predicts cancer grade and histology. Patterns of microbial abundance and gene expression should be increasingly considered as a factor in the evolution of precision medicine approaches, especially as they relate to cancer screening, disease pathogenesis, and patient-centered outcomes.

Influence of Race, Ethnicity, and Nativity on Distribution and Outcomes Among Women With Choriocarcinoma in Florida

Introduction While race/ethnicity are established factors of risk and outcomes for multiple cancers in women, nativity may more precisely estimate cancer risk and survival. The role of nativity in choriocarcinoma, a form of gestational trophoblastic neoplasia arising from the placenta, is unexplored. Our objective was to examine how race, ethnicity, and nativity influence disease presentation and survival in women with choriocarcinoma in Florida. Methods Using the Florida Cancer Data System (FCDS), we identified women diagnosed with choriocarcinoma from 1981-2020. Clinicodemographic data were extracted, including nativity (US-born/Non-US-born). Statistical analyses included chi-square, Cox proportional hazards models, and Kaplan-Meier method, with significance set at P < 0.05. Results 262 eligible patients were included. Black women more frequently presented with distant disease vs White women (63.8% vs 46.2%, P = 0.05). Non-US-Born women were older at diagnosis than US-born (32.8 vs 26.7 years, P < 0.01) and received fewer surgical and radiation treatments ( P < 0.05). Nativity, ethnicity, and race were not associated with overall survival (OS) (all P > 0.05). Multivariable analyses adjusted for race and birthplace showed increasing age (HR 1.05 [1.02-1.09], P = 0.023) and surgical treatment (HR 0.28 [0.09-0.79], P = 0.016) were associated with OS. Despite favorable OS, survival curves diverged after initial treatment, favoring White over Black patients, and Hispanic over Non-Hispanic patients, though neither were statistically significant ( P > 0.05). Conclusion Race and nativity are associated with variations in choriocarcinoma presentation and treatment course but do not affect survival. Race and ethnicity may predict post-treatment, long-term survival, though whether this reflects choriocarcinoma biology or broader disparities remain unclear.

Residential segregation and overall survival of women with epithelial ovarian cancer

BackgroundTo the authors' knowledge, the etiology of survival disparities in patients with epithelial ovarian cancer (EOC) is not fully understood. Residential segregation, both economic and racial, remains a problem within the United States. The objective of the current study was to analyze the effect of residential segregation as measured by the Index of Concentration at the Extremes (ICE) on EOC survival in Florida by race and/or ethnicity.MethodsAll malignant EOC cases were identified from 2001 through 2015 using the Florida Cancer Data System (FCDS). Census‐defined places were used as proxies for neighborhoods. Using 5‐year estimates from the American Community Survey, 5 ICE variables were computed: economic (high vs low), race and/or ethnicity (non‐Hispanic white [NHW] vs non‐Hispanic black [NHB] and NHW vs Hispanic), and racialized economic segregation (low‐income NHB vs high‐income NHW and low‐income Hispanic vs high‐income NHW). Random effects frailty models were conducted.ResultsA total of 16,431 malignant EOC cases were diagnosed in Florida among women living in an assigned census‐defined place within the time period. The authors found that economic and racialized economic residential segregations influenced EOC survival more than race and/or ethnic segregation alone in both NHB and Hispanic women. NHB women continued to have an increased hazard of death compared with NHW women after controlling for multiple covariates, whereas Hispanic women were found to have either a similar or decreased hazard of death compared with NHW women in multivariable Cox models.ConclusionsThe results of the current study indicated that racial and economic residential segregation influences survival among patients with EOC. Research is needed to develop more robust segregation measures that capture the complexities of neighborhoods to fully understand the survival disparities in EOC.

Low-grade serous ovarian cancer: State of the science

In January 2019, a group of basic, translational, and clinical investigators and patient advocates assembled in Miami, Florida, to discuss the current state of the science of low-grade serous carcinoma of the ovary or peritoneum-a rare ovarian cancer subtype that may arise de novo or following a diagnosis of serous borderline tumor. The purpose of the conference was to review current knowledge, discuss ongoing research by established researchers, and frame critical questions or issues for future directions. Following presentations and discussions, the primary objective was to initiate future collaborations, uniform database platforms, laboratory studies, and clinical trials to better understand this disease and to advance clinical care outside the boundaries of single academic institutions. This review summarizes the state of the science in five principal categories: epidemiology and patient outcomes, pathology, translational research, patient care and clinical trials, and patients' perspective.

Hereditary Ovarian Carcinoma: Cancer Pathogenesis Looking beyond BRCA1 and BRCA2

Besides BRCA1 and BRCA2, several other inheritable mutations have been identified that increase ovarian cancer risk. Surgical excision of the fallopian tubes and ovaries reduces ovarian cancer risk, but for some non-BRCA hereditary ovarian cancer mutations the benefit of this intervention is unclear. The fallopian tubes of women with hereditary ovarian cancer mutations provide many insights into the early events of carcinogenesis and process of malignant transformation. Here we review cancer pathogenesis in hereditary cases of ovarian cancer, the occurrence of pre-invasive lesions and occult carcinoma in mutation carriers and their clinical management.

Differences in Cervical Cancer Outcomes by Caribbean Nativity in Black and White Women in Florida

Objective Racial disparities among women with cervical cancer have been reported but are understudied in Caribbean immigrants. The objective of this study is to describe the disparities in clinical presentation and outcomes between Caribbean-born (CB) and US-born (USB) women with cervical cancer by race and nativity. Methods An analysis of the Florida Cancer Data Service (FCDS), the statewide cancer registry, was performed to identify women diagnosed with invasive cervical cancer between 1981 and 2016. Women were classified as USB White or Black and CB White or Black. Clinical data were abstracted. Analyses were done using chi square, ANOVA, Kaplan-Meier and Cox proportional hazards models, with significance set at P < .05. Results 14 932 women were included in the analysis. USB Black women had the lowest mean age at diagnosis, while CB Black women were diagnosed at later stages of disease. USB White women and CB White women had better OS (median OS 70.4 and 71.5 months, respectively) than USB Black and CB Black women (median OS 42.4 and 63.8 months, respectively) ( P < .0001). In multivariable analysis, relative to USB Black women, CB Blacks (HR .67, CI .54–.83), and CB White (HR .66, CI .55–.79) had better odds of OS. White race among USB women was not significantly associated with improved survival ( P = .087). Conclusion Race alone is not a determinant of cancer mortality in women with cervical cancer. Understanding the impact of nativity on cancer outcomes is crucial to improve health outcomes.

Normal Risk Ovarian Screening Study: 21-Year Update

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported. PURPOSE The Normal Risk Ovarian Screening Study (NROSS) tested a two-stage screening strategy in postmenopausal women at conventional hereditary risk where significantly rising cancer antigen (CA)-125 prompted transvaginal sonography (TVS) and abnormal TVS prompted surgery to detect ovarian cancer. METHODS A total of 7,856 healthy postmenopausal women were screened annually for a total of 50,596 woman-years in a single-arm study (ClinicalTrials.gov identifier: NCT00539162 ). Serum CA125 was analyzed with the Risk of Ovarian Cancer Algorithm (ROCA) each year. If risk was unchanged and <1:2,000, women returned in a year. If risk increased above 1:500, TVS was undertaken immediately, and if risk was intermediate, CA125 was repeated in 3 months with a further increase in risk above 1:500 prompting referral for TVS. An average of 2% of participants were referred to TVS annually. RESULTS Thirty-four patients were referred for operations detecting 15 ovarian cancers and two borderline tumors with 12 in early stage (I-II). In addition, seven endometrial cancers were detected with six in stage I. As four ovarian cancers and two borderline tumors were diagnosed with a normal ROCA, the sensitivity for detecting ovarian and borderline cancer was 74% (17 of 23), and 70% of ROCA-detected cases (12 of 17) were in stage I-II. NROSS screening reduced late-stage (III-IV) disease by 34% compared with UKCTOCS controls and by 30% compared with US SEER values. The positive predictive value (PPV) was 50% (17 of 34) for detecting ovarian cancer and 74% (25 of 34) for any cancer, far exceeding the minimum acceptable study end point of 10% PPV. CONCLUSION While the NROSS trial was not powered to detect reduced mortality, the high specificity, PPV, and marked stage shift support further development of this strategy.