Racial inequities in second-line treatment and overall survival among patients with metastatic breast cancer.

BACKGROUND: Black women in the USA have a higher incidence and mortality of metastatic breast cancer (mBC) than White women, while Hispanic women have lower rates. Previous studies have focused on first-line (1L) treatment, but little is known about racial differences in treatment beyond 1L and their impact on outcomes. METHODS: This analysis utilized data from an electronic health record derived de-identified database and included patients with HR+HER2- mBC initiating 2L treatment (including CDK4/6-inhibitor [CDKi]-based, endocrine monotherapy, everolimus combination therapy, and chemotherapy and other systemic therapies) between 2/3/2015 and 7/31/2021. Real-world overall survival (rwOS) was defined as time from 2L initiation to death. Multinomial logistic regression assessed the likelihood of 2L treatment between race/ethnicity groups. Median rwOS was estimated using the Kaplan-Meier method and adjusted hazard ratios were estimated using multivariable Cox proportional hazards models. RESULTS: Among all patients who received 2L, non-Hispanic Black (NHB) and Hispanic/Latino patients were less likely to receive 2L CDKi compared to non-Hispanic White (NHW) patients (36%, 39% vs 42%, respectively). Median rwOS was 20.4, 37.6, and 25.3 months, in NHB, Hispanic/Latino and NHW patients, respectively. The rwOS remained poorer among NHB patients after adjustment (HR = 1.16; p = 0.009). In stratified analysis, adjusted rwOS was similar between NHB and NHW patients among those who received 1L CDKi. CONCLUSIONS: These findings suggest that among patients with HR+HER2- mBC, NHB patients had worse survival beyond front-line setting, mainly among the subset of women who did not receive CDKi at 1L. This inequities in rwOS between race/ethnicity groups was not observed among patients who received 1L CDKi.

An informatics infrastructure to catalyze cancer control research and practice.

PURPOSE: A disconnect often exists between those with the expertise to manage and analyze complex, multi-source data sets, and the clinical, social services, advocacy, and public health professionals who can pose the most relevant questions and best apply the answers. We describe development and implementation of a cancer informatics infrastructure aimed at broadening the usability of community cancer data to inform cancer control research and practice; and we share lessons learned. METHODS: We built a multi-level database known as The Ohio Cancer Assessment and Surveillance Engine (OH-CASE) to link data from Ohio's cancer registry with community data from the U.S. Census and other sources. Space-and place-based characteristics were assigned to individuals according to residential address. Stakeholder input informed development of an interface for generating queries based on geographic, demographic, and disease inputs and for outputting results aggregated at the state, county, municipality, or zip code levels. RESULTS: OH-CASE contains data on 791,786 cancer cases diagnosed from 1/1/2006 to 12/31/2018 across 88 Ohio counties containing 1215 municipalities and 1197 zip codes. Stakeholder feedback from cancer center community outreach teams, advocacy organizations, public health, and researchers suggests a broad range of uses of such multi-level data resources accessible via a user interface. CONCLUSION: OH-CASE represents a prototype of a transportable model for curating and synthesizing data to understand cancer burden across communities. Beyond supporting collaborative research, this infrastructure can serve the clinical, social services, public health, and advocacy communities by enabling targeting of outreach, funding, and interventions to narrow cancer disparities.

New Baseline Renal Function after Radical or Partial Nephrectomy: A Simple and Accurate Predictive Model.

PURPOSE: Preoperative estimation of new baseline glomerular filtration rate after partial nephrectomy or radical nephrectomy for renal cell carcinoma has important clinical implications. However, current predictive models are either complex or lack external validity. We aimed to develop and validate a simple equation to estimate postoperative new baseline glomerular filtration rate. MATERIALS AND METHODS: For development and internal validation of the equation, a cohort of 7,860 patients with renal cell carcinoma undergoing partial nephrectomy/radical nephrectomy (2005-2015) at the Veterans Affairs National Health System was analyzed. Based on preliminary analysis of 94,327 first-year postoperative glomerular filtration rate measurements, new baseline glomerular filtration rate was defined as the final glomerular filtration rate within 3 to 12 months after surgery. Multivariable linear regression analyses were applied to develop the equation using two-thirds of the renal cell carcinoma Veterans Administration cohort. The simplest model with the highest coefficient of determination (R2) was selected and tested. This model was then internally validated in the remaining third of the renal cell carcinoma Veterans Administration cohort. Correlation/bias/accuracy/precision of equation were examined. For external validation, a similar cohort of 3,012 patients with renal cell carcinoma from an outside tertiary care center (renal cell carcinoma-Cleveland Clinic) was independently analyzed. RESULTS: New baseline glomerular filtration rate (in ml/minute/1.73 m2) can be estimated with the following simplified equation: new baseline glomerular filtration rate = 35 + preoperative glomerular filtration rate (× 0.65) - 18 (if radical nephrectomy) - age (× 0.25) + 3 (if tumor size >7 cm) - 2 (if diabetes). Correlation/bias/accuracy/precision were 0.82/0.00/83/-7.5-8.4 and 0.82/-0.52/82/-8.6-8.0 in the internal/external validation cohorts, respectively. Additionally, the area under the curve (95% confidence interval) to discriminate postoperative new baseline glomerular filtration rate ≥45 ml/minute/1.73 m2 from receiver operating characteristic analyses were 0.90 (0.88, 0.91) and 0.90 (0.89, 0.91) in the internal/external validation cohorts, respectively. CONCLUSIONS: Our study provides a validated equation to accurately predict postoperative new baseline glomerular filtration rate in patients being considered for radical nephrectomy or partial nephrectomy that can be easily implemented in daily clinical practice.

Association between neighborhood disadvantage and fulfillment of desired postpartum sterilization.

BACKGROUND: Adequacy of prenatal care is associated with fulfillment of postpartum sterilization requests, though it is unclear whether this relationship is indicative of broader social and structural determinants of health or reflects the mandatory Medicaid waiting period required before sterilization can occur. We evaluated the relationship between neighborhood disadvantage (operationalized by the Area Deprivation Index; ADI) and the likelihood of undergoing postpartum sterilization. METHODS: Secondary analysis of a single-center retrospective cohort study examining 8654 postpartum patients from 2012 to 2014, of whom 1332 (15.4%) desired postpartum sterilization (as abstracted from the medical record at time of delivery hospitalization discharge) and for whom ADI could be calculated via geocoding their home address. We determined the association between ADI and sterilization completion, postpartum visit attendance, and subsequent pregnancy within 365 days of delivery via logistic regression and time to sterilization via Cox proportional hazards regression. RESULTS: Of the 1332 patients included in the analysis, patients living in more disadvantaged neighborhoods were more likely to be younger, more parous, delivered vaginally, Black, unmarried, not college educated, and insured via Medicaid. Compared to patients living in less disadvantaged areas, patients living in more disadvantaged areas were less likely to obtain sterilization (44.8% vs. 53.5%, OR 0.84, 95% CI 0.75-0.93), experienced greater delays in the time to sterilization (HR 1.23, 95% CI 1.06-1.44), were less likely to attend postpartum care (58.9% vs 68.9%, OR 0.86, CI 0.79-0.93), and were more likely to have a subsequent pregnancy within a year of delivery (15.1% vs 10.4%, OR 1.56, 95% CI 1.10-1.94). In insurance-stratified analysis, for patients with Medicaid, but not private insurance, as neighborhood disadvantage increased, the rate of postpartum sterilization decreased. The rate of subsequent pregnancy was positively associated with neighborhood disadvantage for both Medicaid as well as privately insured patients. CONCLUSION: Living in an area with increased neighborhood disadvantage is associated with worse outcomes in terms of desired postpartum sterilization, especially for patients with Medicaid insurance. While revising the Medicaid sterilization policy is important, addressing social determinants of health may also play a powerful role in reducing inequities in fulfillment of postpartum sterilization.

Revisiting the "July Effect" in Plastic Surgery: New Data to Support Resident Autonomy.

BACKGROUND: The "July Effect" represents a topic of considerable interest across residency programs. This study investigated the frequency of postoperative complications following procedures with plastic surgery resident participation (all postgraduate year [PGY] levels) during the first (quarter 3, July-September) and last academic quarters. METHODS: The American College of Surgeons National Surgical Quality Improvement Program database was used to calculate complication rates from 2006 to 2010. Resident involvement was analyzed as a categorical variable consisting of "juniors" (PGY1-PGY3), and "seniors" (PGY4-PGY6). Outcomes from procedures during Q3 were compared with all quarters. Propensity score matching and adjustment enabled logistic regression identifying the effect of resident involvement and admission. RESULTS: Among all cosmetic and reconstructive procedures (n = 6625), mean operative time was not significantly greater in Q3 compared with all other quarters (P = 0.069); no significant differences in complication rates were observed between Q3 and all other quarters, though superficial surgical site infection (SSI) approached significance (3.3% of procedures in Q3 vs 2.5% in all other quarters, P = 0.063). Among reconstructive procedures only (n = 5677), mean operative time was not significantly greater in Q3 compared with all other quarters (P = 0.119); the same held true for cosmetic procedures only (P = 0.275). Surgical site infection, however, was significantly more likely to occur with reconstructive procedures only, in Q3 compared with all other quarters (3.5% of cases vs 2.3%, P = 0.024). When adjusting for PGY status and matching populations, superficial SSI and return to the operating room were not significantly more common in Q3. When adjusting for quarter of admission, however, superficial SSI was significantly more common among the overall and noncosmetic cases with participation by junior residents (P = 0.013 and 0.020, respectively). CONCLUSIONS: This may represent the first fully reproducible, transparent National Surgical Quality Improvement Program study in plastic surgery that demonstrates the absence of a clinically significant "July Effect," and suggests that an appropriate degree of resident autonomy may pose minimal risk during both cosmetic and reconstructive procedures in residency training. Additionally, the findings encourage the development a plastic surgery-specific database to remedy inherent difficulties with larger, more comprehensive surgical databases.

Applied Deep Learning in Plastic Surgery: Classifying Rhinoplasty With a Mobile App.

BACKGROUND: Advances in deep learning (DL) have been transformative in computer vision and natural language processing, as well as in healthcare. The authors present a novel application of DL to plastic surgery. Here, the authors describe and demonstrate the mobile deployment of a deep neural network that predicts rhinoplasty status, assess model accuracy compared to surgeons, and describe future directions for such applications in plastic surgery. METHODS: A deep convolutional neural network ("RhinoNet") was developed to classify rhinoplasty images using only pixels and rhinoplasty status labels ("before"/"after") as inputs. RhinoNet was trained using a dataset of 22,686 before and after photos which were collected from publicly available sites. Network classification was compared to that of plastic surgery attendings and residents on 2269 previously-unseen test-set images. RESULTS: RhinoNet correctly predicted rhinoplasty status in 85% of the test-set images. Sensitivity and specificity of model predictions were 0.840 (0.79-0.89) and 0.826 (0.77-0.88), respectively; the corresponding values for expert consensus predictions were 0.814 (0.76-0.87) and 0.867 (0.82-0.91). RhinoNet and humans performed with effectively equivalent accuracy in this classification task. CONCLUSION: The authors describe the development of DL applications to identify the presence of superficial surgical procedures solely from images and labels. DL is especially well suited for unstructured, high-fidelity visual and auditory data that does not lend itself to classical statistical analysis, and may be deployed as mobile applications for potentially unbridled use, so the authors expect DL to play a key role in many areas of plastic surgery.

A review of the utility of tacrolimus in the management of adults with autoimmune hepatitis.

BACKGROUND: There is paucity of data on alternative drug therapies for patients with autoimmune hepatitis (AIH). Tacrolimus (TAC) is a promising salvage agent. We present a review of TAC therapy in AIH patients. METHODS: A search for studies with keywords 'autoimmune hepatitis' and 'tacrolimus' was performed. Reviews, studies of AIH post-transplant and AIH in children were excluded. Diagnosis of AIH was based on criteria established by the International Autoimmune Hepatitis Group. Complete biochemical response was defined as normalisation of aspartate aminotransferase (AST <45) and alanine aminotransferase (ALT <50). No biochemical response was defined as failure to return to normalisation at the end of follow-up. Demographic information and details of pre- and post-treatment liver biopsy were collected. RESULTS: Seven articles achieved the inclusion criteria and reported data for a total of 162 adult patients. The majority of studies reported average ages approximately 35 years old. Treatment duration ranged from 1 to 136 months. Indications for therapy were mostly AIH refractory to steroid treatment or inability to tolerate standard steroid treatment. Eighty-three patients (51.2%) were reported to have pre-therapy liver biopsy. Of 49 patients for whom stage was reported, 6 patients were stage 1, 16 were stage 2, 14 were stage 3 and 13 were stage 4. Of 40 patients for whom grade was reported, 1 patient was grade 0, 3 were grade 1, 9 were grade 2, 14 were grade 3 and 13 were grade 4. Dosing regimens were between 1 and 8 mg/day. Target trough TAC serum concentrations ranged from 0.5 to 10.7 ng/mL TAC was discontinued in 28 (17.3%) patients for various reasons. Renal function remained stable in most patients. One hundred and twenty-one patients (74.7%) demonstrated complete biochemical response to treatment. Post-therapy liver biopsy was obtained for 30 (18.5%) patients, and 25 (15.4%) of these patients were noted to have histological remission according to the grade of inflammation or stage of fibrosis. CONCLUSION: TAC is relatively effective in the treatment of AIH refractory to traditional therapy. It appears that liver function can be enhanced at a minimal cost to renal function. Key Points There is a cohort of patients with autoimmune hepatitis (AIH) who do not respond to standard therapy. Alternative treatment options for these patients have been explored, but outcomes have not been comprehensively examined. We report the use and efficacy of tacrolimus (TAC) in patients with AIH. We found that TAC can be safely and effectively used in patients with AIH with minimal side effects. TAC can be a potential treatment option for patients with AIH refractory to standard therapy.

Sex-specific enlarged vestibular aqueduct morphology and audiometry.

OBJECTIVE: Enlargement of the vestibular aqueduct (EVA) is one of the most common congenital malformations in pediatric patients presenting with sensorineural or mixed hearing loss. The relationship between vestibular aqueduct (VA) morphology and hearing loss across sex is not well characterized. This study assesses VA morphology and frequency-specific hearing thresholds with sex as the primary predictor of interest. MATERIALS AND METHODS: A retrospective, longitudinal, and repeated-measures study was used. 47 patients at an academic tertiary care center with hearing loss and a record of CT scan of the internal auditory canal were candidates, and included upon meeting EVA criteria after confirmatory measurements of vestibular aqueduct midpoint and operculum widths. Audiometric measures included pure-tone average and frequency-specific thresholds. RESULTS: Of the 47 patients (23 female and 24 male), 79 total ears were affected by EVA; the median age at diagnosis was 6.60 years. After comparing morphological measurements between sexes, ears from female patients were observed to have a greater average operculum width (3.25 vs. 2.70 mm for males, p = 0.006) and a greater average VA midpoint width (2.80 vs. 1.90 mm for males, p = 0.004). After adjusting for morphology, male patients' ears had pure-tone average thresholds 17.6 dB greater than female patients' ears (95% CI, 3.8 to 31.3 dB). CONCLUSIONS: Though females seem to have greater enlargement of the vestibular aqueduct, this difference does not extend to hearing loss. Therefore, our results indicate that criteria for EVA diagnoses may benefit from re-evaluation. Further exploration into morphological and audiometric discrepancies across sex may help inform both clinician and patient expectations.

Morphology and cochlear implantation in enlarged vestibular aqueduct.

PURPOSE: The purpose of this work is to explore audiometry following cochlear implantation (CI) in patients with enlarged vestibular aqueduct (EVA) and to investigate the effects of inner ear morphological variation on post CI audiometry. METHODS: This was a retrospective review of both natural and cochlear-implant-aided audiometry results, using all available measurements in a mixed-effects model accounting for longitudinal change and the grouping structure of ears. Patients who visited our tertiary academic medical center between 2000 and 2016 were identified as having EVA according to Cincinnati criteria on radiological examination; patients eligible for CI were then selected for analysis. RESULTS: Multivariable modeling showed a statistically significant hearing improvement in ears with EVA undergoing CI with regards to pure tone average (-64.0 dB, p < 0.0001), speech reception threshold (-57.90 dB, p < 0.0001), and word score (34.8%, p > 0.0001). Vestibular aqueduct midpoint size and the presence of incomplete partition type II (IP II) did not have significant independent associations with audiometric findings. However, multivariable modeling revealed a statistically significant interaction between IP II and CI such that IP II ears demonstrated a decrease in WS improvement of 30.2% (p = 0.0059) compared to non-IP II ears receiving CI. CONCLUSION: There is a statistically significant audiometric benefit to ears with EVA receiving CI. Morphology, specifically the presence of IP II, may hinder CI benefit in terms of word score however this finding needs clinical validation. This data improves personalization of surgical counseling and planning for patients with EVA considering CI.

Transjugular Intrahepatic Porto-Systemic Shunt in Patients with Liver Cirrhosis and Model for End-Stage Liver Disease ≥15.

BACKGROUND: It is not known whether transjugular intrahepatic porto-systemic shunt (TIPS) is safe in patients with advanced liver cirrhosis. The aim of our study was to evaluate the impact of TIPS on transplant-free survival in patients with liver cirrhosis and MELD score ≥15. METHODS: All adult patients who underwent TIPS at our institution between 2004 and 2011 were identified (N = 470). A total of 144 patients had MELD ≥15 at the time of TIPS. These patients were matched 1:1 to patients with liver cirrhosis who did not undergo TIPS based on age and MELD score using the greedy algorithm. Patients were followed up until time of death or liver transplantation. Kaplan-Meier curves and log-rank tests were used to test for differences in survival outcome between the two groups. RESULTS: A total of 288 patients with liver cirrhosis were included, of whom 144 underwent TIPS and 144 did not. The two groups were matched based on age and MELD score and were comparable with regard to gender and ethnicity. Mean MELD and Child-Pugh scores in the study population were 20.9 ± 6.5 and 10.5 ± 1.8, respectively. The most common indication for TIPS was varices (49 %), followed by refractory ascites (42 %). In the first 2 months post-TIPS, there was increased mortality or liver transplantation in patients who had TIPS compared to those who did not, but this did not reach statistical significance (p = 0.07). However, after 2 months, TIPS is associated with 56 % lower risk of dying or needing liver transplantation (p < 0.01) than cirrhotic patients who did not undergo TIPS. CONCLUSION: In patients with liver cirrhosis and MELD ≥15, TIPS might improve transplant-free survival for patients who live for at least 2 months after the procedure.

Hearing loss in enlarged vestibular aqueduct and incomplete partition type II.

PURPOSE: The purpose of this work is to identify the role of incomplete partition type II on hearing loss among patients with enlarged vestibular aqueduct (EVA). BACKGROUND: EVA is a common congenital inner ear malformation among children with hearing loss, where vestibular aqueduct morphology in this population has been shown to correlate to hearing loss. However, the impact of incomplete partition between cochlear turns on hearing loss has not been, despite meaningful implications for EVA pathophysiology. METHODS: A retrospective review of radiology reports for patients who had computed tomography (CT) scans with diagnoses of hearing loss at a tertiary medical center between January 2000 and June 2016 were screened for EVA. CT scans of the internal auditory canal (IAC) for those patients with EVA were examined for evidence of incomplete partition type II (IP-II), measurements of midpoint width and operculum width a second time, and patients meeting Cincinnati criteria for EVA selected for analysis. Statistical analysis including chi-square, Wilcoxon rank-sum, and t-tests were used to identify differences in outcomes and clinical predictors, as appropriate for the distribution of the data. Linear mixed models of hearing test results for all available tests were constructed, both univariable and adjusting for vestibular aqueduct morphometric features, with ear-specific intercepts and slopes over time. RESULTS: There were no statistically significant differences in any hearing test results or vestibular aqueduct midpoint and operculum widths. Linear mixed models, both univariable and those adjusting for midpoint and operculum widths, did not indicate a statistically significant effect of incomplete partition type II on hearing test results. CONCLUSIONS: Hearing loss due to enlarged vestibular aqueduct does not appear to be affected by the presence of incomplete partition type II. Our results suggest that the pathophysiological processes underlying hearing loss in enlarged vestibular aqueduct may not be a result of cochlear malformation, and instead are more likely to involve vestibular aqueduct or cellular and molecular-level mechanisms of hearing loss.

Identification of Risk Factors in Lymphatic Surgeries for Melanoma: A National Surgical Quality Improvement Program Review.

INTRODUCTION: Sentinel lymph node biopsy (SLNB) and lymphadenectomy (LAD) are commonly performed in the staging and care of patients with malignant melanoma. These procedures are accompanied by complications that may result in hospital readmission, negatively affecting patient outcomes and potentially affecting surgical procedure reimbursement. The National Surgical Quality Improvement Program (NSQIP) database offers a large data set allowing physicians to evaluate 30-day readmission for surgical complications. We used this database to explore predictors of 30-day hospital readmission for SLNB and LAD in the axillary, cervical, and inguinal regions. METHODS: Data from the years 2005 to 2014 of the American College of Surgeons NSQIP database were used. Cohorts were constructed according to International Classification of Diseases, Ninth Revision, classification and current procedural terminology codes. The outcome of 30-day return to hospital was defined as patients who were readmitted to the hospital or the operating room within 30 days. Multiple logistic regression results are presented for a prespecified set of predictors and predictors that were significant on univariate logistic regression analysis. Odds ratios and confidence intervals were calculated using maximum likelihood estimates, along with Wald test P values. RESULTS: A total of 3006 patients were included. Of those, 151 (5.0%) returned to the hospital. Among 1235 LAD patients, 65 (5.3%) returned; among 1771 SLNB patients, 86 (4.9%) returned. Smoking was a predictor of hospital readmission for overall SLNB and for cervical SLNB on multivariate analysis. Age was a significant predictor for cervical and inguinal LAD. Hypertension was significant for cervical LAD. Diabetes, preoperative hematocrit, and male sex were predictors for inguinal SLNB. There were no significant predictors for axillary SLNB and axillary LAD, as well as overall LAD procedures. CONCLUSIONS: This is the first and largest study using American College of Surgeons NSQIP to examine 30-day readmission after SLNB and LAD for melanoma in 3 commonly operated anatomical regions. We have found several significant risk factors associated with hospital readmission, which are now being used as a quality measure for hospital performance and reimbursement, that may help surgeons optimize patient selection for SLNB and LAD.

Systemic Anticancer Therapy and Overall Survival in Patients With Very Advanced Solid Tumors.

Importance: Two prominent organizations, the American Society of Clinical Oncology and the National Quality Forum (NQF), have developed a cancer quality metric aimed at reducing systemic anticancer therapy administration at the end of life. This metric, NQF 0210 (patients receiving chemotherapy in the last 14 days of life), has been critiqued for focusing only on care for decedents and not including the broader population of patients who may benefit from treatment. Objective: To evaluate whether the overall population of patients with metastatic cancer receiving care at practices with higher rates of oncologic therapy for very advanced disease experience longer survival. Design, Setting, and Participants: This nationwide population-based cohort study used Flatiron Health, a deidentified electronic health record database of patients diagnosed with metastatic or advanced disease, to identify adult patients (aged ≥18 years) with 1 of 6 common cancers (breast cancer, colorectal cancer, non-small cell lung cancer [NSCLC], pancreatic cancer, renal cell carcinoma, and urothelial cancer) treated at health care practices from 2015 to 2019. Practices were stratified into quintiles based on retrospectively measured rates of NQF 0210, and overall survival was compared by disease type among all patients treated in each practice quintile from time of metastatic diagnosis using multivariable Cox proportional hazard models with a Bonferroni correction for multiple comparisons. Data were analyzed from July 2021 to July 2023. Exposure: Practice-level NQF 0210 quintiles. Main Outcome and Measure: Overall survival. Results: Of 78 446 patients (mean [SD] age, 67.3 [11.1] years; 52.2% female) across 144 practices, the most common cancer types were NSCLC (34 201 patients [43.6%]) and colorectal cancer (15 804 patients [20.1%]). Practice-level NQF 0210 rates varied from 10.9% (quintile 1) to 32.3% (quintile 5) for NSCLC and 6.8% (quintile 1) to 28.4% (quintile 5) for colorectal cancer. No statistically significant differences in survival were observed between patients treated at the highest and the lowest NQF 0210 quintiles. Compared with patients seen at practices in the lowest NQF 0210 quintiles, the hazard ratio for death among patients seen at the highest quintiles varied from 0.74 (95% CI, 0.55-0.99) for those with renal cell carcinoma to 1.41 (95% CI, 0.98-2.02) for those with urothelial cancer. These differences were not statistically significant after applying the Bonferroni-adjusted critical P = .008. Conclusions and Relevance: In this cohort study, patients with metastatic or advanced cancer treated at practices with higher NQF 0210 rates did not have improved survival. Future efforts should focus on helping oncologists identify when additional therapy is futile, developing goals of care communication skills, and aligning payment incentives with improved end-of-life care.

Broadening Eligibility Criteria and Diversity among Patients for Cancer Clinical Trials.

BACKGROUND: Certain populations have been historically underrepresented in clinical trials. Broadening eligibility criteria is one approach to inclusive clinical research and achieving enrollment goals. How broadened trial eligibility criteria affect the diversity of eligible participants is unknown. METHODS: Using a nationwide electronic health record-derived deidentified database, we identified a retrospective cohort of patients diagnosed with 22 cancer types between April 1, 2013 and December 31, 2022 who received systemic therapy (N=235,234) for cancer. We evaluated strict versus broadened eligibility criteria using performance status and liver, kidney, and hematologic function around first line of therapy. We performed logistic regression to estimate odds ratios for exclusion by strict criteria and their association with measures of patient diversity, including sex, age, race or ethnicity, and area-level socioeconomic status (SES); estimated the impact of broadening criteria on the number and distribution of eligible patients; and performed Cox regression to estimate hazard ratios for real-world overall survival (rwOS) comparing patients meeting strict versus broadened criteria. RESULTS: When applying common strict cutoffs for eligibility criteria to patients with complete data and weighting each cancer type equally, 48% of patients were eligible for clinical trials. Female (odds ratio, 1.30; 95% confidence interval [CI], 1.25 to 1.35), older (age 75+ vs. 18 to 49 years old: odds ratio, 3.04; 95% CI, 2.85 to 3.24), Latinx (odds ratio, 1.46; 95% CI, 1.39 to 1.54), non-Latinx Black (odds ratio, 1.11; 95% CI, 1.06 to 1.16), and lower-SES patients were more likely to be excluded using strict eligibility criteria. Broadening criteria increased the number of eligible patients by 78%, with the strongest impact for older, female, non-Latinx Black, and lower-SES patients. Patients who met only broadened criteria had worse rwOS versus those with strict criteria (hazard ratio, 1.31; 95% CI, 1.27 to 1.34). CONCLUSIONS: Data-driven evaluation of clinical trial eligibility criteria may optimize the eligibility of certain historically underrepresented groups and promote access to more inclusive trials. (Sponsored by Flatiron Health.).

Sex Differences in Odds of Brain Metastasis and Outcomes by Brain Metastasis Status after Advanced Melanoma Diagnosis.

Sex differences in cancer are well-established. However, less is known about sex differences in diagnosis of brain metastasis and outcomes among patients with advanced melanoma. Using a United States nationwide electronic health record-derived de-identified database, we evaluated patients diagnosed with advanced melanoma from 1 January 2011-30 July 2022 who received an oncologist-defined rule-based first line of therapy (n = 7969, 33% female according to EHR, 35% w/documentation of brain metastases). The odds of documented brain metastasis diagnosis were calculated using multivariable logistic regression adjusted for age, practice type, diagnosis period (pre/post-2017), ECOG performance status, anatomic site of melanoma, group stage, documentation of non-brain metastases prior to first-line of treatment, and BRAF positive status. Real-world overall survival (rwOS) and progression-free survival (rwPFS) starting from first-line initiation were assessed by sex, accounting for brain metastasis diagnosis as a time-varying covariate using the Cox proportional hazards model, with the same adjustments as the logistic model, excluding group stage, while also adjusting for race, socioeconomic status, and insurance status. Adjusted analysis revealed males with advanced melanoma were 22% more likely to receive a brain metastasis diagnosis compared to females (adjusted odds ratio [aOR]: 1.22, 95% confidence interval [CI]: 1.09, 1.36). Males with brain metastases had worse rwOS (aHR: 1.15, 95% CI: 1.04, 1.28) but not worse rwPFS (adjusted hazard ratio [aHR]: 1.04, 95% CI: 0.95, 1.14) following first-line treatment initiation. Among patients with advanced melanoma who were not diagnosed with brain metastases, survival was not different by sex (rwOS aHR: 1.06 [95% CI: 0.97, 1.16], rwPFS aHR: 1.02 [95% CI: 0.94, 1.1]). This study showed that males had greater odds of brain metastasis and, among those with brain metastasis, poorer rwOS compared to females, while there were no sex differences in clinical outcomes for those with advanced melanoma without brain metastasis.

Nonfulfillment of desired postpartum permanent contraception and resultant maternal and pregnancy health outcomes.

BACKGROUND: Up to half of the patients requesting postpartum permanent contraception do not undergo the desired procedure. Although nonfulfillment of desired postpartum permanent contraception is associated with increased risk of pregnancy within 12 months of delivery, its long-term reproductive and maternal health outcomes are less clear. OBJECTIVE: This study aimed to determine the association of fulfillment of postpartum permanent contraception with number and timing of subsequent pregnancies and maternal health outcomes. STUDY DESIGN: This was a retrospective single-center cohort chart review study of health outcomes in the 4 years following delivery (2016-2018) for 1331 patients with a documented contraceptive plan of female permanent contraception at time of postpartum discharge from 2012 to 2014. Rates of permanent contraception fulfillment within 90 days of delivery and clinical and demographic characteristics associated with permanent contraception were calculated. We determined number of and time to subsequent pregnancies, and diagnoses of medical comorbidities (hypertension, diabetes mellitus, depression, anxiety, asthma, anemia), sexually transmitted infection, and pregnancy comorbidities (preterm birth, gestational diabetes mellitus, gestational hypertension, preeclampsia, postpartum hemorrhage, low birthweight, intrauterine fetal demise) in the 4 years following delivery. RESULTS: Of the 1331 patients desiring permanent contraception postpartum, 588 (44.1%) had their requests fulfilled within 90 days of delivery and 743 (55.8%) did not. Patients who achieved permanent contraception fulfillment tended to have attended more outpatient prenatal visits, delivered via cesarean delivery, and were older, married, college-educated, and privately insured. Patients who received their desired postpartum permanent contraception were less likely to have subsequent intrauterine pregnancies (P<.001). In those who did not achieve permanent contraception, 22 (9.0%) subsequent pregnancies occurred within 6 months of previous deliveries, and 223 (91.0%) occurred after short interpregnancy intervals (within 18 months). Of 178 continued pregnancies, 26 (14.6%) were delivered preterm. There were no differences between the 2 groups in terms of ever attending an outpatient, preventive, or emergency room visit, or in most nonreproductive health outcomes investigated. CONCLUSION: Nonfulfillment of desired postpartum permanent contraception is associated with subsequent maternal reproductive and nonreproductive health ramifications. Given the barriers to permanent contraception, alternative plans for contraception should be discussed proactively if permanent contraception is not provided.

End-of-Life Systemic Oncologic Treatment in the Immunotherapy Era: The Role of Race, Insurance, and Practice Setting.

PURPOSE: Receipt of antineoplastic systemic treatment near end of life (EOL) has been shown to harm patient and caregiver experience, increase hospitalizations, intensive care unit and emergency department use, and drive-up costs; yet, these rates have not declined. To understand factors contributing to use of antineoplastic EOL systemic treatment, we explored its association with practice- and patient-level factors. METHODS: We included patients from a real-world electronic health record-derived deidentified database who received systemic therapy for advanced or metastatic cancer diagnosed starting in 2011 and died within 4 years between 2015 and 2019. We assessed use of EOL systemic treatment at 30 and 14 days before death. We divided treatments into three subcategories: chemotherapy alone, chemotherapy and immunotherapy in combination, and immunotherapy (with/without targeted therapy), and estimated conditional odds ratios (ORs) and 95% CIs for patient and practice factors using multivariable mixed-level logistic regression. RESULTS: Among 57,791 patients from 150 practices, 19,837 received systemic treatment within 30 days of death. We observed 36.6% of White patients, 32.7% of Black patients, 43.3% of commercially insured patients, and 37.0% of Medicaid patients received EOL systemic treatment. White patients and those with commercial insurance were more likely to receive EOL systemic treatment than Black patients or those with Medicaid. Treatment at community practices was associated with higher odds of receiving 30-day systemic EOL treatment than treatment at academic centers (adjusted OR, 1.51). We observed large variations in EOL systemic treatment rates across practices. CONCLUSION: In a large real-world population, EOL systemic treatment rates were related to patient race, insurance type, and practice setting. Future work should examine factors that contribute to this usage pattern and its impact on downstream care.[Media: see text].