Disparities in PI3K/mTOR inhibitor use, toxicities, and outcomes among patients with metastatic breast cancer.

PURPOSE: Novel agents such as PI3K and mTOR inhibitors (PI3K/mTORi) have expanded treatment options in metastatic breast cancer (MBC). Nevertheless, mortality rates remain disproportionately high for Black patients and patients with lower socioeconomic status. Furthermore, clinical trials for these novel agents lacked diversity, so their toxicity profile in minority populations is uncertain. METHODS: We conducted a retrospective analysis of EHR-derived data from the Flatiron Health Database for patients with HR+, HER2- MBC. Multivariable logistic regression was used to evaluate factors associated with PI3K/mTORi use and toxicity outcomes. RESULTS: A total of 9169 patients with MBC were included in our analysis, of which 1780 (19.4%) received a PI3K/mTORi. We estimated the conditional total effect of insurance through Medicaid, and found lower odds of use of PI3K/mTORi among patients on Medicaid compared to those with commercial insurance (OR 0.73, 95% CI 0.54-0.99, p = 0.049). Odds of PI3K/mTORi use were higher for patients treated at an academic center (OR 1.28, CI 1.06-1.55, p = 0.01). Modeled as a controlled direct effect, Black/African American (Black/AA) race had no impact on odds of PI3K/mTOR use. Black/AA patients had twice the odds of developing hyperglycemia on PI3K/mTORi compared to White patients (OR 2.02, CI 1.24-3.39, p < 0.01). CONCLUSION: This analysis of real-world data suggests that the use of PI3K/mTORi is influenced by socioeconomic factors. We also found racial disparities in toxicity outcomes, with Black/AA patients having twice the risk of hyperglycemia. Our findings call for greater efforts to ensure access to novel treatments and improve their tolerability in diverse populations.

Disparities with influenza vaccine use in long-term survivors of metastatic breast cancer.

PURPOSE: Elderly women diagnosed with metastatic breast cancer (MBC) are living longer, however their primary care management may be sub-optimal. Influenza results in preventable hospitalizations and deaths. Guidelines recommend the influenza vaccine for those > 65 years and those with cancer but use is unknown. METHODS: A retrospective analysis was conducted using the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked data. Patients were included if they were diagnosed with MBC from 1/1/2008-12/31/2017 and were ≥ 65 years of age. The primary outcome was influenza vaccine use among patients surviving ≥ 3-years. We conducted multivariable analyses using demographic and clinical factors to identify associations with vaccine use. We compared utilization to cancer-free controls. RESULTS: We identified 1,970 patients with MBC that survived for ≥ 3 years. The median age at diagnosis was 73 years. Furthermore, 1,742 (88%) patients were White, and 153 (8%) patients were Black. Only 1,264 (64%) received an influenza vaccine at least one time and 51% received the vaccine at least two times. A multivariable model found lower odds of vaccine receipt for Black patients (OR = 0.48; 95% CI 0.34-0.68, p < 0.001) and higher odds for patients that saw primary care in the year prior to diagnosis (OR = 1.91, 95% CI 1.57-2.33, p < 0.001). Patients with MBC had lower odds of vaccine use compared to cancer free controls (OR = 0.85, 95% CI 0.74-0.97, p < 0.001). CONCLUSION: Over 1/3 of long-term MBC survivors in our cohort did not receive the influenza vaccine. Black patients are about half as likely to be vaccinated. Given the known benefit of the vaccine, improving uptake could be an important strategy to improve outcomes.

Robot-Assisted Surgery and Racial and Ethnic Disparities in Post-Prostatectomy Outcomes Among Prostate Cancer Patients.

BACKGROUND: We sought to determine whether the differences in short-term outcomes between patients undergoing robot-assisted radical prostatectomy (RARP) and those treated with open radical prostatectomy (ORP) differ by race and ethnicity. METHODS: This observational study used New York State Cancer Registry data linked to discharge records and included patients undergoing radical prostatectomy for localized prostate cancer during 2008-2018. We used logistic regression to examine the association between race and ethnicity (non-Hispanic White [NHW], non-Hispanic Black [NHB], Hispanic), surgical approach (RARP, ORP), and postoperative outcomes (major events, prolonged length of stay [pLOS], 30-day re-admission). We tested interaction between race and ethnicity and surgical approach on multiplicative and additive scales. RESULTS: The analytical cohort included 18,926 patients (NHW 14,215 [75.1%], NHB 3195 [16.9%], Hispanic 1516 [8.0%]). The average age was 60.4 years (standard deviation 7.1). NHB and Hispanic patients had lower utilization of RARP and higher risks of postoperative adverse events than NHW patients. NHW, NHB, and Hispanic patients all had reduced risks of adverse events when undergoing RARP versus ORP. The absolute reductions in the risks of major events and pLOS following RARP versus ORP were larger among NHB {relative excess risk due to interaction (RERI): major events -0.32 [95% confidence interval (CI) -0.71 to -0.03]; pLOS -0.63 [95% CI -0.98 to -0.35]) and Hispanic (RERI major events -0.27 [95% CI -0.77 to 0.09]; pLOS -0.93 [95% CI -1.46 to -0.51]) patients than among NHW patients. The interaction was absent on the multiplicative scale. CONCLUSIONS: RARP use has not penetrated and benefited all racial and ethnic groups equally. Increasing utilization of RARP among NHB and Hispanic patients may help reduce disparities in patient outcomes after radical prostatectomy.

Black-White differences in uterine cancer symptomatology and stage at diagnosis.

OBJECTIVE: To examine whether uterine cancer symptoms differ between Black and White patients and how this may influence their stage at diagnosis. METHODS: Using the Surveillance, Epidemiology and End Results-Medicare database, we identified 2328 Black and 21,774 White patients with uterine cancer in 2008-2017. Their symptoms in the 18 months before diagnosis were categorized as postmenopausal bleeding (PMB) alone, PMB together with other symptoms (e.g., abdominal/pelvic pain, bloating), non-PMB symptoms alone, or no symptoms. Stage at diagnosis was dichotomized as advanced (i.e., regional/distant) versus localized. The association between race and stage was analyzed using regression models incrementally adjusting for symptoms and other patient characteristics. RESULTS: A larger proportion of Black than White patients experienced PMB together with other symptoms (63.1% versus 58.0%) or experienced non-PMB symptoms alone (13.1% versus 9.4%) (p < 0.001). Black patients had a higher risk of advanced-stage diagnosis than White patients (45.0% versus 30.3%, unadjusted RR = 1.52, 95% CI: 1.44-1.59). Adjusting for Black-White differences in symptoms attenuated the RR to 1.46 (95% CI: 1.39-1.53). Compared to PMB symptoms alone, having additional non-PMB symptoms (RR = 1.21, 95% CI: 1.15-1.26) and having non-PMB symptoms alone (RR = 1.99, 95% CI: 1.88-2.10) were associated with increased risk of advanced-stage diagnosis. Further adjusting for histology and other patient characteristics reduced Black-White disparity in advanced-stage diagnosis to 1.08 (95% CI: 1.03-1.14) but symptoms remained significantly associated with stage at diagnosis. CONCLUSIONS: Having non-PMB symptoms was associated with more advanced stage at diagnosis. Non-PMB symptoms were more common among Black than White patients, which might hinder symptom recognition/evaluation.

Survival rates in Hispanic/Latinx subpopulations with cervical cancer associated with disparities in guideline-concordant care.

BACKGROUND: Failure to deliver guideline-concordant treatment may contribute to disparities among Hispanic/Latinx cervical cancer patients. This study investigated the association between survival rates in Hispanic/Latinx subpopulations and the provision of guideline-concordant care. METHODS: We analyzed patients with primary cervical cancer from 2004 to 2019 (National Cancer Database). We developed nine quality metrics based on FIGO staging (2009). Clinical and demographic covariates were analyzed using Chi-squared tests. Adjusted associations between receipt of guideline-concordant care and races and ethnicities were analyzed using multivariable marginal Poisson regression models. Adjusted Cox proportional hazard models were utilized to evaluate survival probability. RESULTS: A total of 95,589 patients were included. Hispanic/Latinx and Non-Hispanic Black (NHB) populations were less likely to receive guideline-concordant care in four and five out of nine quality metrics, respectively. Nonetheless, the Hispanic/Latinx group exhibited better survival outcomes in seven of nine quality metrics. Compared to Mexican patients, Cuban patients were 1.17 times as likely to receive timely initiation of treatment in early-stage disease (RR 1.17, 95% CI 1.04-1.37, p < 0.001). Puerto Rican and Dominican patients were, respectively, 1.16 (RR 1.16, 95% CI 1.07-1.27, p < 0.001) and 1.19 (RR 1.19, 95% 1.04-1.37, p > 0.01) times as likely to undergo timely initiation of treatment in early-stage disease. Patients of South or Central American (RR 1.18, 95% CI 1.10-1.27, p < 0.001) origin were more likely to undergo timely initiation of treatment in locally advanced disease. CONCLUSION: Significant differences in survival were identified among our cohort despite the receipt of guideline concordant care, with notably higher survival among Hispanic/Latinx populations.

Prognostic performance of the 2023 FIGO staging schema for endometrial cancer.

OBJECTIVE: To assess the prognostic performance of the 2023 International Federation of Gynecology and Obstetrics (FIGO) endometrial cancer staging schema. METHODS: This retrospective cohort study queried the Commission-on-Cancer's National Cancer Database. Study population was 129,146 patients with stage I-IV endometrial cancer per the 2009 FIGO staging schema. Stage-shifting and overall survival (OS) were assessed according to the 2023 FIGO staging schema. RESULTS: Upstage (IA → II, 21.4 %; IB → II, 53.0 %) and downstage (IIIA→IA3, 22.2 %) occurred in both early and advanced diseases. Inter-stage prognostic performance improved in the 2023 schema with widened 5-year OS rate difference between the earliest and highest stages (68.2 % to 76.9 %). Stage IA1-IIB and IIC had distinct 5-year OS rate differences (85.8-96.1 % vs 75.4 %). The 5-year OS rate of the 2009 stage IIIA disease was 63.9 %; this was greater segregated in the 2023 schema: 88.0 %, 62.4 %, and 55.7 % for IIIA→IA3, IIIA1, and IIIA2, respectively (inter-substage rate-difference, 32.3 %). This 5-year OS rate of stage IA3 disease was comparable to the 2023 stage IB-IIB diseases (88.0 % vs 85.8-89.5 %). In the 2023 stage IIIC schema (micrometastasis rates: 29.6 % in IIIC1 and 15.6 % in IIIC2), micrometastasis and macrometastasis had the distinct 3-year OS rates in both pelvic (IIIC1-i vs IIIC1-ii, 84.9 % vs 71.1 %; rate-difference 13.8 %) and para-aortic (IIIC2-i vs IIIC2-ii, 82.9 % vs 65.2 %; rate-difference 17.7 %) nodal metastasis cases. The 5-year OS rate of the 2009 stage IVB disease was 23.4 %; this was segregated to 25.4 % for stage IVB and 19.2 % for stage IVC in the 2023 staging schema (rate-difference, 6.2 %). CONCLUSION: The 2023 FIGO endometrial cancer staging schema is a major revision from the 2009 FIGO schema. Almost doubled enriched sub-stages based on detailed anatomical metastatic site and incorporation of histological information enable more robust prognostication.

Cesarean hysterectomy for placenta accreta spectrum: Surgeon specialty-specific assessment.

OBJECTIVE: To assess (i) clinical and pregnancy characteristics, (ii) patterns of surgical procedures, and (iii) surgical morbidity associated with cesarean hysterectomy for placenta accreta spectrum based on the specialty of the attending surgeon. METHODS: The Premier Healthcare Database was queried retrospectively to study patients with placenta accreta spectrum who underwent cesarean delivery and concurrent hysterectomy from 2016 to 2020. Surgical morbidity was assessed with propensity score inverse probability of treatment weighting based on surgeon specialty for hysterectomy: general obstetrician-gynecologists, maternal-fetal medicine specialists, and gynecologic oncologists. RESULTS: A total of 2240 cesarean hysterectomies were studies. The most common surgeon type was general obstetrician-gynecologist (n = 1534, 68.5%), followed by gynecologic oncologist (n = 532, 23.8%) and maternal-fetal medicine specialist (n = 174, 7.8%). Patients in the gynecologic oncologist group had the highest rate of placenta increta or percreta, followed by the maternal-fetal medicine specialist and general obstetrician-gynecologist groups (43.4%, 39.6%, and 30.6%, P < .001). In a propensity score-weighted model, measured surgical morbidity was similar across the three subspecialty groups, including hemorrhage / blood transfusion (59.4-63.7%), bladder injury (18.3-24.0%), ureteral injury (2.2-4.3%), shock (8.6-10.5%), and coagulopathy (3.3-7.4%) (all, P > .05). Among the cesarean hysterectomy performed by gynecologic oncologist, hemorrhage / transfusion rates remained substantial despite additional surgical procedures: tranexamic acid / ureteral stent (60.4%), tranexamic acid / endo-arterial procedure (76.2%), ureteral stent / endo-arterial procedure (51.6%), and all three procedures (55.4%). Tranexamic acid administration with ureteral stent placement was associated with decreased bladder injury (12.8% vs 23.8-32.2%, P < .001). CONCLUSION: These data suggest that patient characteristics and surgical procedures related to cesarean hysterectomy for placenta accreta spectrum differ based on surgeon specialty. Gynecologic oncologists appear to manage more severe forms of placenta accreta spectrum. Regardless of surgeon's specialty, surgical morbidity of cesarean hysterectomy for placenta accreta spectrum is significant.

Comparing survival of older ovarian cancer patients treated with neoadjuvant chemotherapy versus primary cytoreductive surgery: Reducing bias through machine learning.

OBJECTIVE: To develop and evaluate a multidimensional comorbidity index (MCI) that identifies ovarian cancer patients at risk of early mortality more accurately than the Charlson Comorbidity Index (CCI) for use in health services research. METHODS: We utilized SEER-Medicare data to identify patients with stage IIIC and IV ovarian cancer, diagnosed in 2010-2015. We employed partial least squares regression, a supervised machine learning algorithm, to develop the MCI by extracting latent factors that optimally captured the variation in health insurance claims made in the year preceding cancer diagnosis, and 1-year mortality. We assessed the discrimination and calibration of the MCI for 1-year mortality and compared its performance to the commonly-used CCI. Finally, we evaluated the MCI's ability to reduce confounding in the association of neoadjuvant chemotherapy (NACT) and all-cause mortality. RESULTS: We included 4723 patients in the development cohort and 933 in the validation cohort. The MCI demonstrated good discrimination for 1-year mortality (c-index: 0.75, 95% CI: 0.72-0.79), while the CCI had poor discrimination (c-index: 0.59, 95% CI: 0.56-0.63). Calibration plots showed better agreement between predicted and observed 1-year mortality risk for the MCI compared with CCI. When comparing all-cause mortality between NACT with primary cytoreductive surgery, NACT was associated with a higher hazard of death (HR: 1.13, 95% CI: 1.04-1.23) after controlling for tumor characteristics, demographic factors, and the CCI. However, when controlling for the MCI instead of the CCI, there was no longer a significant difference (HR: 1.05, 95% CI: 0.96-1.14). CONCLUSIONS: The MCI outperformed the conventional CCI in predicting 1-year mortality, and reducing confounding due to differences in baseline health status in comparative effectiveness analysis of NACT versus primary surgery.

Estrogen replacement therapy and non-hormonal medication use among patients with uterine cancer.

OBJECTIVE: As the prognosis for endometrial cancer is excellent, management of the effects of estrogen deprivation has an important influence on quality of life. We examined the trends in the use of estrogen replacement therapy (ERT) and non-hormonal medications among patients with uterine cancer following surgery. METHODS: The MarketScan Database was used to identify patients 18-49 years who underwent hysterectomy plus oophorectomy and those aged 50-75 years who underwent hysterectomy between 2008 and 2020. ERT and non-hormonal treatments of menopause were identified preoperatively and postoperatively. After propensity score balancing, difference-in-differences (DID) analyses were performed to compare the pre-and-postoperative changes in ERT and non-hormonal medication use between groups. The trends in postoperative use of ERT were assessed and tested using Cochran-Armitage trend tests. RESULTS: A total of 19,700 patients with uterine cancer and 185,150 controls were identified. Overall, postoperative ERT use decreased for both age groups and for patients with and without uterine cancer. The DID in ERT use between those with uterine cancer and those with benign pathology after hysterectomy was -37.1% (95% CI, -40.5 to -33.6%) for patients 18-49 years of age and - 10.4% (95% CI, -10.9 to -9.9%) for those 50-75 years. The DID for non-hormonal medication use between those with uterine cancer and those with benign pathology after hysterectomy was 11.2% (95% CI, 7.8 to 14.7%) for younger patients and 3.4% (95% CI, 2.9 to 4.0%) for those 50-75 years. The postoperative new ERT use has been declining over time in patients with uterine cancer in those 18-49 years of age (P = .02) and those 50-75 years of age (P < .001). CONCLUSIONS: The use of ERT is uncommon and has declined over time in patients with uterine cancer. Conversely, non-hormonal medications are more commonly used among patients with uterine cancer.

Trends in uterine cancer incidence in the United States: The contribution of age, period and cohort effects.

OBJECTIVE: In the U.S., uterine cancer incidence is rising, with racial and ethnic minorities experiencing the largest increases. We performed age-period-cohort analyses using novel methods to examine the contribution of age at diagnosis (age), year of diagnosis (period), and birth cohort (cohort), to trends in uterine cancer incidence. METHODS: We used uterine cancer incidence data from the Surveillance, Epidemiology, and End Result (SEER) 12 database (1992-2019), and performed hysterectomy-correction. We generated hexamaps to visualize age, period, and cohort effects, and used mutual information to estimate the percent contribution of age, period, and cohort effects, individually and combined, on uterine cancer incidence, overall and by race and ethnicity and histology. RESULTS: Hexamaps showed an increase in uterine cancer in later time periods, and a cohort effect around 1933 showing a lower incidence compared with earlier and later cohorts. Age, period, and cohort effects combined contributed 86.6% (95% CI: 86.4%, 86.9%) to the incidence. Age effects had the greatest contribution (65.1%, 95% CI: 64.3%, 65.9), followed by cohort (20.7%, 95% CI: 20.1%, 21.3%) and period (14.2%, 95% CI: 13.7%, 14.8%) effects. Hexamaps showed higher incidence in recent years for non-Hispanic Blacks and non-endometrioid tumors. CONCLUSIONS: Age effects had the largest contribution to uterine cancer incidence, followed by cohort and period effects overall and across racial and ethnic groups and histologies. IMPACT: These findings can inform uterine cancer modeling studies on the effects of interventions that target risk factors which may vary across age, period, or cohort.

Cost-effectiveness of lenvatinib plus pembrolizumab versus chemotherapy for recurrent mismatch repair-proficient endometrial cancer after platinum-based therapy.

OBJECTIVE: The recent Study 309-KEYNOTE-775 showed improved survival for lenvatinib plus pembrolizumab compared to chemotherapy in patients with recurrent endometrial cancer. We created a decision model to compare the cost-effectiveness of lenvatinib plus pembrolizumab in patients with recurrent mismatch repair-proficient (pMMR) endometrial cancer who had progressed after first-line chemotherapy. METHODS: A Markov model was created to simulate the clinical trajectory of 10,000 patients with recurrent pMMR endometrial cancer. The initial decision point in the model was treatment with ether lenvatinib plus pembrolizumab or chemotherapy (doxorubicin or dose-dense paclitaxel). Model probabilities, utility values and costs were derived with assumptions drawn from published literature. A cycle length of 3 months and a time horizon of 2 years was used. The effectiveness was calculated in terms of average quality adjusted life years (QALYs) gained. The primary outcome was incremental cost-effectiveness ratios (ICERs), expressed in 2020 US dollars/QALYs. One-way, two-way and probabilistic sensitivity analyses were performed. RESULTS: Chemotherapy was the least costly strategy at $66,693 followed by lenvatinib plus pembrolizumab ($193,590). Lenvatinib plus pembrolizumab resulted in more patients being alive at 2 years (lenvatinib plus pembrolizumab: 367, chemotherapy: 109). Chemotherapy was cost-effective compared with lenvatinib plus pembrolizumab (ICER: $164,493/QALYs). Lenvatinib plus pembrolizumab became cost-effective when its cost was reduced by $1553 per month (7.8% reduction). CONCLUSION: For patients with recurrent pMMR endometrial cancer Lenvatinib plus pembrolizumab is associated with greater survival but is more costly than chemotherapy. The cost of lenvatinib and pembrolizumab would have to be reduced by approximately 7% to be considered cost-effective.

Racial and ethnic differences in early death among gynecologic malignancy.

BACKGROUND: Racial and ethnic differences in early death after cancer diagnosis have not been well studied in gynecologic malignancy. OBJECTIVE: This study aimed to assess population-level trends and characteristics of early death among patients with gynecologic malignancy based on race and ethnicity in the United States. STUDY DESIGN: The National Cancer Institute's Surveillance, Epidemiology, and End Results Program was queried to examine 461,300 patients with gynecologic malignancies from 2000 to 2020, including uterine (n=242,709), tubo-ovarian (n=119,989), cervical (n=68,768), vulvar (n=22,991), and vaginal (n=6843) cancers. Early death, defined as a mortality event within 2 months of the index cancer diagnosis, was evaluated per race and ethnicity. RESULTS: At the cohort level, early death occurred in 21,569 patients (4.7%), including 10.5%, 5.5%, 2.9%, 2.5%, and 2.4% for tubo-ovarian, vaginal, cervical, uterine, and vulvar cancers, respectively (P<.001). In a race- and ethnicity-specific analysis, non-Hispanic Black patients with tubo-ovarian cancer had the highest early death rate (14.5%). Early death racial and ethnic differences were the largest in tubo-ovarian cancer (6.4% for Asian vs 14.5% for non-Hispanic Black), followed by uterine (1.6% for Asian vs 4.9% for non-Hispanic Black) and cervical (1.8% for Hispanic vs 3.8% to non-Hispanic Black) cancers (all, P<.001). In tubo-ovarian cancer, the early death rate decreased over time by 33% in non-Hispanic Black patients from 17.4% to 11.8% (adjusted odds ratio, 0.67; 95% confidence interval, 0.53-0.85) and 23% in non-Hispanic White patients from 12.3% to 9.5% (adjusted odds ratio, 0.77; 95% confidence interval, 0.71-0.85), respectively. The early death between-group difference diminished only modestly (12.3% vs 17.4% for 2000-2002 [adjusted odds ratio for non-Hispanic White vs non-Hispanic Black, 0.54; 95% confidence interval, 0.45-0.65] and 9.5% vs 11.8% for 2018-2020 [adjusted odds ratio, 0.65; 95% confidence interval, 0.54-0.78]). CONCLUSION: Overall, approximately 5% of patients with gynecologic malignancy died within the first 2 months from cancer diagnosis, and the early death rate exceeded 10% in non-Hispanic Black individuals with tubo-ovarian cancer. Although improving early death rates is encouraging, the difference among racial and ethnic groups remains significant, calling for further evaluation.

Excess morbidity and mortality associated with underuse of estrogen replacement therapy in premenopausal women who undergo surgical menopause.

BACKGROUND: Contrary to clinical guidelines, there has been a decrease over time in estrogen therapy use in premenopausal women undergoing bilateral oophorectomy for benign indications. OBJECTIVE: This study aimed to estimate the excess morbidity and mortality associated with current patterns of estrogen therapy use in women who undergo bilateral oophorectomy with hysterectomy for benign indications. STUDY DESIGN: We developed 2 Bayesian sampling Markov state-transition models to estimate the excess disease incidence (incidence model) and mortality (mortality model). The starting cohort for both models were women who had undergone bilateral oophorectomy with hysterectomy for benign indications at the age of 45 to 49 years. The models tracked outcomes in 5-year intervals for 25 years. The incidence model estimated excess incidence of breast cancer, lung cancer, colorectal cancer, coronary heart disease, and stroke, whereas the mortality model estimated excess mortality due to breast cancer, lung cancer, coronary heart disease, and all-other-cause mortality. The models compared current rates of estrogen therapy use with optimal (100%) use and calculated the mean difference in each simulated outcome to determine excess disease incidence and death. RESULTS: By 25 years after bilateral oophorectomy with hysterectomy, there were an estimated 94 (95% confidence interval, -158 to -23) fewer colorectal cancer cases, 658 (95% confidence interval, 339-1025) more coronary heart disease cases, and 881 (95% confidence interval, 402-1483) more stroke cases. By 25 years after bilateral oophorectomy with hysterectomy, there were an estimated 189 (95% confidence interval, 59-387) more breast cancer deaths, 380 (95% confidence interval, 114-792) more coronary heart disease deaths, and 759 (95% confidence interval, 307-1527) more all-other-cause deaths. In sensitivity analyses where we defined estrogen therapy use as a duration of >2 years of use, these differences increased >2-fold. CONCLUSION: Underuse of estrogen therapy in premenopausal women who undergo oophorectomy is associated with substantial excess morbidity and mortality.

Cost-effectiveness of BRCA1 testing at time of obstetrical prenatal carrier screening for cancer prevention.

BACKGROUND: Improved technologies paired with an increase in access to genetic testing have led to the availability of expanded carrier screening evaluating hundreds of disorders. Currently, most autosomal dominant mutations, such as BRCA1, are not included in expanded carrier assays. Screening pregnant or preconception reproductive-aged women for BRCA1 may present a unique opportunity to perform population-based screening for patients at a time when precancer screening, chemoprevention, and/or risk-reducing surgery may be beneficial. OBJECTIVE: This study aimed to inform clinical decision-making as to whether the universal incorporation of BRCA1 testing at the time of obstetrical prenatal carrier screening is cost-effective. STUDY DESIGN: A decision analysis and Markov model was created. The initial decision point in the model was BRCA1 testing at the time of expanded carrier screening. Model probabilities, cost, and utility values were derived from published literature. For BRCA1-positive patients, the model simulated breast cancer screening and risk-reducing surgical interventions. A cycle length of 1 year and a time horizon of 47 years were used to simulate the lifespan of patients. The setting was obstetrical clinics in the United States, and the participants were a theoretical cohort of 1,429,074 pregnant patients who annually underwent expanded carrier screening. RESULTS: Among our cohort, BRCA1 testing resulted in the identification of an additional 3716 BRCA1-positive patients, the prevention of 1394 breast and ovarian cancer cases, and 1084 fewer deaths. BRCA1 testing was a cost-effective strategy compared with no BRCA1 testing with an incremental cost-effectiveness ratio of $86,001 per quality-adjusted life years. In a 1-way sensitivity analysis, we varied the prevalence of BRCA1 in the population from 0.00% to 20.00% and found that BRCA1 testing continued to be the cost-effective strategy until the prevalence rate was reduced to 0.16%. Multiple additional sensitivity analyses did not substantially affect the cost-effectiveness. CONCLUSION: The addition of BRCA1 testing to obstetrical prenatal carrier screening is a cost-effective management strategy to identify at-risk women at a time when cancer screening and preventive strategies can be effective. Despite the burden of additional genetic counseling, prenatal care represents a unique opportunity to implement population-based genetic testing.

Prevalence and Predictors of Follow-up Endoscopic Biopsy in Patients With Celiac Disease in the United States.

OBJECTIVE: To characterize the frequency and predictors of follow-up endoscopic biopsy in patients with celiac disease. BACKGROUND: The utility of routine follow-up biopsy in patients after a diagnosis of celiac disease is uncertain, especially in patients whose symptoms resolve on the gluten-free diet. PATIENTS AND METHODS: Using the Merative MarketScan U.S. commercial insurance and Medicare databases, we identified 30,737 patients with biopsy-diagnosed celiac disease. We followed them until they had a second duodenal biopsy (our primary outcome) or insurance coverage ended. RESULTS: Among the patients with celiac disease we identified, 5976 (19.4%) underwent a follow-up biopsy. The median time between initial and follow-up biopsies was 16.8 months. Compared with younger patients, those aged 20 years or older had an increased likelihood of undergoing a follow-up biopsy (cumulative incidence rate at 5 y for patients age ≥20 y was 36.0%, 95% CI: 35.0%-37.1% vs 21.9%, 95% CI: 20.5%-23.4% in patients age ≤19 y). Follow-up biopsies occurred less frequently in more recent calendar years. Follow-up biopsy was more common among patients with an Elixhauser Comorbidity Index of 1 (hazard ratio: 1.09; 95% CI: 1.01-1.17) or ≥2 (hazard ratio: 1.28; 95% CI: 1.20-1.37) compared with patients with an index of zero. Among patients who had a follow-up biopsy, 57% had a celiac disease-related symptom recorded in the 30 days before the procedure. CONCLUSIONS: Follow-up duodenal biopsy is performed in a substantial minority of U.S. patients with celiac disease. Adult age and increased comorbidity burden were associated with a greater likelihood of follow-up biopsy. Just under half of follow-up biopsies are performed for routine surveillance, in the absence of persistent symptoms.

Adverse delivery hospitalisation outcomes in 2020 during the COVID-19 pandemic.

OBJECTIVE: To evaluate risk for adverse obstetric outcomes associated with the coronavirus disease 2019 (COVID-19) pandemic period and with COVID-19 diagnoses. DESIGN: Serial cross-sectional study. SETTING: A national sample of US delivery hospitalisations before (1/2016 to 2/2020) and during the first 10 months of (3/2020 to 12/2020) the COVID-19 pandemic. POPULATION: All 2016-2020 US delivery hospitalisations in the National Inpatient Sample. METHODS: Delivery hospitalisations were identified and stratified into pre-pandemic and pandemic periods and the likelihood of adverse obstetric outcomes was compared using logistic regression models with adjusted odds ratios (aOR) with 95% confidence intervals (CI) as measures of association. Risk for adverse outcomes was also analysed specifically for 2020 deliveries with a COVID-19 diagnosis. MAIN OUTCOME MEASURE: Adverse maternal outcomes including respiratory complications and cardiac morbidity. RESULTS: Of an estimated 18.2 million deliveries, 2.9 million occurred during the pandemic. The proportion of delivery hospitalisations with a COVID-19 diagnosis increased from 0.1% in March 2020 to 3.1% in December. Comparing the pandemic period to the pre-pandemic period, there were higher adjusted odds of transfusion (aOR 1.12, 95% CI 1.05-1.19), a respiratory complication composite (aOR 1.37, 95% CI 1.29-1.46), cardiac severe maternal morbidity (aOR 1.30, 95% 1.20-1.39), postpartum haemorrhage (aOR 1.19, 95% CI 1.15-1.24), placental abruption/antepartum haemorrhage (OR 1.04, 95% CI 1.00-1.08), and hypertensive disorders of pregnancy (OR 1.23, 95% CI 1.21-1.26). These associations were similar to unadjusted analysis. Risk for these outcomes during the pandemic period was significantly higher in the presence of a COVID-19 diagnosis. CONCLUSIONS: In a national estimate of delivery hospitalisations, the odds of cardiac and respiratory outcomes were higher in 2020 compared with 2016-2019. COVID-19 diagnoses were specifically associated with a range of serious complications.

Ambient particulate matter air pollution exposure and ovarian cancer incidence in the USA: An ecological study.

OBJECTIVE: To investigate associations between air particulate matter of ≤2.5 µm in diameter (PM2.5 ) and ovarian cancer. DESIGN: County-level ecological study. SETTING: Surveillance, epidemiology, and end results from a collection of state-level cancer registries across 744 counties. Data from the Environmental Protection Agency's network for PM2.5 monitoring was used to calculate trailing 5- and 10-year PM2.5 county-level values. County-level data on demographic characteristics were obtained from the American Community Survey. POPULATION: A total of 98 751 patients with histologically confirmed ovarian cancer as a primary malignancy from 2000 to 2016. METHODS: Generalised linear regression models were developed to estimate the association between PM2.5 and PM10 levels, over 5- and 10-year periods of exposure, and ovarian cancer risk, after accounting for county-level covariates. MAIN OUTCOME MEASURES: Risk ratios for associations between ovarian cancer (both overall and specifically epithelial ovarian cancer) and PM2.5 levels. RESULTS: For the 744 counties included, the average PM2.5 level from 1990 through 2018 was 11.75 µg/m3 (SD = 3.7) and the average PM10 level was 22.7 µg/m3 (SD = 5.7). After adjusting for county-level covariates, the overall annualised ovarian cancer incidence was significantly associated with increases in 5-year PM2.5 (RR = 1.11 per 10 units (µg/m3 ) increase, 95% CI 1.06-1.16). Similarly, when the analysis was limited to epithelial cell tumours and adjusted for county-level covariates there was a significant association with trailing 5-year PM2.5 exposure models (RR = 1.12 per 10 units increase, 95% CI 1.08-1.17). Likewise, 10-year PM2.5 exposure was associated with ovarian cancer overall and with epithelial ovarian cancer. CONCLUSIONS: Higher county-level ambient PM2.5 levels are associated with 5- and 10-year incidences of ovarian cancer, as measurable in an ecological study.

Patterns of use of primary and first-line chemotherapy for recurrence among patients with cervical cancer.

BACKGROUND: Little is known about real-world patterns of chemotherapy use in patients with cervical cancer. OBJECTIVE: To examine the patterns of chemotherapy use in patients with cervical cancer METHODS: We identified patients with cervical cancer in the IBM MarketScan Database who underwent primary hysterectomy or radiation therapy between 2011 and 2020 and described their treatment in the primary setting and at first recurrence. RESULTS: We identified 5390 patients: 2667 (49.5%) underwent primary hysterectomy and 2723 (50.5%) primary radiotherapy. Among patients who underwent primary hysterectomy, 979 (36.7%) received adjuvant radiation, and 617 (23.1%) received primary chemotherapy. The most common chemotherapy regimens were single-agent platinum (51.7%), platinum combination therapy (42.9%), and non-platinum (3.4%). Among patients treated with primary radiation, 73.6% received primary/concurrent chemotherapy, either platinum alone (66.4% of those who received chemotherapy), platinum combinations (32.2%), or non-platinum (1.4%). The median duration of primary chemotherapy was 1.2 months. Therapy for recurrent cervical cancer was initiated in 959 patients. The most common regimens were platinum combination (63.9%), non-platinum cytotoxic agents (16.5%), single-agent platinum (14.9%), targeted therapy with bevacizumab (6.0%), and immunotherapy with pembrolizumab (3.2%). Overall, the proportion of patients treated with single-agent platinum therapy increased from 17.4% in 2011 to 32.1% in 2019, while platinum combinations decreased from 64.1% to 41.5% over the same years. Use of non-platinum agents increased from 18.5% in 2011 to 32.9% in 2018 and 26.4% in 2019. CONCLUSIONS: Platinum-based chemotherapy is the most commonly used therapy in patients with cervical cancer in the primary setting and at the time of recurrence. The rate of use of non-platinum agents at first recurrence has increased over time.

Understanding sex and gender: concepts and terminology for gender affirming care.

Lesbian, gay, bisexual, trans, queer, intersex, asexual, and other diverse individuals (LGBTQIA+) people face lower healthcare utilization rates due to discrimination, poor experiences in healthcare, and barriers to accessing care. There is an increasing need to improve care and reduce health care disparities for the LGBTQIA+ population. The medical community can begin by educating themselves on LGBTQIA+ terminology, using inclusive language and developing cultural competence in clinical settings. In order to achieve this, it is first important to understand that sex and gender are distinct and that both sex and gender exist on continuums. This article will build on this understanding by introducing basic and widely accepted terminology that will provide a foundation for providing care to LGBTQIA+ populations. By thoughtfully incorporating this knowledge into our research and clinical practice, the radiology community will enhance the healthcare experiences of all patients.

Advocacy in gender affirming care.

Healthcare advocacy is the duty and privilege of all healthcare providers, but especially for those who care for children. Intersex and gender diverse youth face significant barriers across many aspects of life, with access to competent gender affirming healthcare chief among them. Understanding the importance of both institutional and individual efforts in healthcare advocacy is paramount to improving healthcare access and outcomes for this population.