Identifying and Treating Those at Risk: Disparities in Rapid Relapse Among TNBC Patients in the National Cancer Database.

PURPOSE: This study was designed to characterize features of rapid relapse TNBC (rrTNBC), an aggressive, poor prognosis breast cancer subset using the National Cancer Database (NCDB). METHODS: Patients diagnosed with TNBC between 2010 and 2019 within NCDB were included in analyses. rrTNBC was defined as all-cause mortality ≤24 months from diagnosis. Patient demographic, tumor, and treatment association with rrTNBC were evaluated in univariate, bivariate analyses, and multiple logistic regression models. Two-part models are used to compare receipt of treatment (i.e., receipt of both chemotherapy and breast surgery) versus not in its relationship with rrTNBC. RESULTS: Overall, 14.5% of patients were categorized as rrTNBC. Age older than 75 years (-41.3%), Black race (-1.4%), Medicare (-2.6%), and Charlson-Deyo score ≥2 (-4.9%) were associated with a lower probability of receiving both chemotherapy and breast surgery. Not receiving both treatments (vs. receiving both chemotherapy and breast surgery) was associated with a two-to-three-fold higher probability of rrTNBC among patients aged older than 75 years (16.6% vs. 6%), having Medicare (3.6% vs. 1.6%), and Charlson-Deyo score ≥2 (16.6% vs. 5.9%). CONCLUSIONS: Age, insurance, and comorbidity were related to a lower likelihood of treatment; yet receiving treatment reduced the risk of rrTNBC threefold for each. These findings might be valuable to inform clinical care delivery, as well as future research that examines treatment protocols among diverse patients.

The Implications of Racialized Economic Segregation and Allostatic Load on Mortality in Patients with Breast Cancer.

BACKGROUND: The objective of this study was to examine the association between racialized economic segregation, allostatic load (AL), and all-cause mortality in patients with breast cancer. PATIENTS AND METHODS: Women aged 18+ years with stage I-III breast cancer diagnosed between 01/01/2012 and 31/12/2020 were identified in the Ohio State University cancer registry. Racialized economic segregation was measured at the census tract level using the index of concentration at the extremes (ICE). AL was calculated with biomarkers from the cardiac, metabolic, immune, and renal systems. High AL was defined as AL greater than the median. Univariable and multivariable regression analyses using restricted cubic splines examined the association between racialized economic segregation, AL, and all-cause mortality. RESULTS: Among 4296 patients, patients residing in neighborhoods with the highest racialized economic segregation (Q1 versus Q4) were more likely to be Black (25% versus 2.1%, p < 0.001) and have triple-negative breast cancer (18.2% versus 11.6%, p < 0.001). High versus low racialized economic segregation was associated with high AL [adjusted odds ratio (aOR) 1.40, 95% confidence interval (CI) 1.21-1.61] and worse all-cause mortality [adjusted hazard ratio (aHR) 1.41, 95% CI 1.08-1.83]. In dose-response analyses, patients in lower segregated neighborhoods (relative to the 95th percentile) had lower odds of high AL, whereas patients in more segregated neighborhoods had a non-linear increase in the odds of high AL. DISCUSSION: Racialized economic segregation is associated with high AL and a greater risk of all-cause mortality in patients with breast cancer. Additional studies are needed to elucidate the causal pathways and mechanisms linking AL, neighborhood factors, and patient outcomes.

Racial disparities in disease-specific mortality and surgical management of patients with ductal carcinoma in situ with microinvasion.

BACKGROUND AND OBJECTIVES: Given persistent racial disparities in breast cancer outcomes, this study explores racial differences in disease-specific mortality and surgical management among patients with microinvasive ductal carcinoma in situ (DCIS-MI). METHODS: The Surveillance, Epidemiology, and End Results Program was queried for patients aged 18+ years with DCIS-MI between January 1, 2010 and December 31, 2018. The study cohort was divided into non-Hispanic Black (NHB) and non-Hispanic White (NHW) patients. Disease-specific mortality was evaluated using Cox proportional hazards models. RESULTS: A total of 3400 patients were identified, of which 569 (16.7%) were NHB and 2831 (83.3%) were NHW. Compared with NHW patients, NHB patients had more positive lymph nodes (7.6% vs. 3.9% p < 0.001). In addition, NHB women were more likely to undergo axillary lymph node dissection (6.0% vs. 3.8%, p = 0.044) and receive chemotherapy (11.8% vs. 7.2%, p < 0.001). There were no racial differences in breast surgery type (p = 0.168), reconstructive surgery (p = 0.362), or radiation therapy (p = 0.342). Overall, NHB patients had worse disease-specific mortality (adjusted hazard ratio 2.13, 95% confidence interval [CI]: 1.10-4.14) with mortality risks diverging from NHW women after 3 years (6 years rate ratio [RR] 2.12, 95% CI: 1.13-4.34; 9 years RR 2.32, 95% CI: 1.24-4.35). CONCLUSIONS: NHB women with DCIS-MI present with higher nodal disease burden and experience worse disease-specific mortality than NHW women.

Association Between Neighborhood Opportunity, Allostatic Load, and All-Cause Mortality in Patients With Breast Cancer.

PURPOSE: Adverse neighborhood contextual factors may affect breast cancer outcomes through environmental, psychosocial, and biological pathways. The objective of this study is to examine the relationship between allostatic load (AL), neighborhood opportunity, and all-cause mortality among patients with breast cancer. METHODS: Women age 18 years and older with newly diagnosed stage I-III breast cancer who received surgical treatment between January 1, 2012, and December 31, 2020, at a National Cancer Institute Comprehensive Cancer Center were identified. Neighborhood opportunity was operationalized using the 2014-2018 Ohio Opportunity Index (OOI), a composite measure derived from neighborhood level transportation, education, employment, health, housing, crime, and environment. Logistic and Cox regression models tested associations between the OOI, AL, and all-cause mortality. RESULTS: The study cohort included 4,089 patients. Residence in neighborhoods with low OOI was associated with high AL (adjusted odds ratio, 1.21 [95% CI, 1.05 to 1.40]). On adjusted analysis, low OOI was associated with greater risk of all-cause mortality (adjusted hazard ratio [aHR], 1.45 [95% CI, 1.11 to 1.89]). Relative to the highest (99th percentile) level of opportunity, risk of all-cause mortality steeply increased up to the 70th percentile, at which point the rate of increase plateaued. There was no interaction between the composite OOI and AL on all-cause mortality (P = .12). However, there was a higher mortality risk among patients with high AL residing in lower-opportunity environments (aHR, 1.96), but not in higher-opportunity environments (aHR, 1.02; P interaction = .02). CONCLUSION: Lower neighborhood opportunity was associated with higher AL and greater risk of all-cause mortality among patients with breast cancer. Additionally, environmental factors and AL interacted to influence all-cause mortality. Future studies should focus on interventions at the neighborhood and individual level to address socioeconomically based disparities in breast cancer.

Allostatic Load as a Predictor of Postoperative Complications in Patients with Breast Cancer.

BACKGROUND: Allostatic load (AL) is a biological measure of cumulative exposure to socioenvironmental stressors (e.g., poverty). This study aims to examine the association between allostatic load (AL) and postoperative complications (POC) among patients with breast cancer. METHODS: Assigned females at birth ages 18 + with stage I-III breast cancer who received surgical management between 01/01/2012-12/31/2020 were identified in the Ohio State Cancer registry. The composite AL measure included biomarkers from the cardiovascular, metabolic, immune, and renal systems. High AL was defined as composite scores greater than the cohort's median (2.0). POC within 30 days of surgery were examined. Univariable and multivariable regression analysis examined the association between AL and POC. RESULTS: Among 4,459 patients, 8.2% had POC. A higher percentage of patients with POC were unpartnered (POC 44.7% vs no POC 35.5%), government-insured (POC 48.2% vs no POC 38.3%) and had multiple comorbidities (POC 32% vs no POC 20%). Patients who developed POC were more likely to have undergone sentinel lymph node biopsy followed by axillary lymph node dissection (POC 51.2% vs no POC 44.6%). High AL was associated with 29% higher odds of POC (aOR 1.29, 95% CI 1.01-1.63). A one-point increase in AL was associated with 8% higher odds of POC (aOR 1.08, 95% CI 1.02-1.16) and a quartile increase in AL was associated with 13% increased odds of POC (aOR 1.13, 95% CI 1.01-1.26). CONCLUSION: Among patients undergoing breast cancer surgery, increased exposure to adverse socioenvironmental stressors, operationalized as AL, was associated with higher odds of postoperative complications.

Allostatic load as a predictor of postoperative complications in patients with breast cancer.

Allostatic load (AL) is a biological measure of cumulative exposure to socioenvironmental stressors (e.g., poverty). This study aims to examine the association between allostatic load (AL) and postoperative complications (POC) among patients with breast cancer. Females ages 18+ with stage I-III breast cancer who received surgical management between 01/01/2012-12/31/2020 were identified in the Ohio State Cancer registry. The composite AL measure included biomarkers from the cardiovascular, metabolic, immune, and renal systems. High AL was defined as composite scores greater than the cohort's median (2.0). POC within 30 days of surgery were examined. Univariable and multivariable regression analysis examined the association between AL and POC. Among 4459 patients, 8.2% had POC. A higher percentage of patients with POC were unpartnered (POC 44.7% vs no POC 35.5%), government-insured (POC 48.2% vs no POC 38.3%) and had multiple comorbidities (POC 32% vs no POC 20%). Patients who developed POC were more likely to have undergone sentinel lymph node biopsy followed by axillary lymph node dissection (POC 51.2% vs no POC 44.6%). High AL was associated with 29% higher odds of POC (aOR 1.29, 95% CI 1.01-1.63). A one-point increase in AL was associated with 8% higher odds of POC (aOR 1.08, 95% CI 1.02-1.16) and a quartile increase in AL was associated with 13% increased odds of POC (aOR 1.13, 95% CI 1.01-1.26). Among patients undergoing breast cancer surgery, increased exposure to adverse socioenvironmental stressors, operationalized as AL, was associated with higher odds of postoperative complications.

Cabozantinib plus ipilimumab/nivolumab in patients with previously treated advanced differentiated thyroid cancer.

BACKGROUND: This investigator-initiated phase II trial aimed to evaluate the efficacy of cabozantinib in combination with nivolumab and ipilimumab (CaboNivoIpi) in previously treated patients with radioactive iodine (RAI)-refractory differentiated thyroid cancer (DTC) (NCT03914300). METHODS: Eligible patients with RAI-refractory DTC who progressed on 1 prior line of VEGFR-targeted therapy received a 2-week run-in of cabozantinib monotherapy followed by CaboNivoIpi for 4 cycles (cycle length = 6 weeks), followed by cabozantinib plus nivolumab (cycle length = 4 weeks) until disease progression. The primary endpoint was objective response rate (ORR) within the first 6 months of treatment. A Simon optimal 2-stage design allowed for an interim analysis after accrual of 10 evaluable patients. At least 5 responses were needed to proceed to stage 2. RESULTS: Among 11 patients enrolled, the median age was 69 years. Prior VEGFR-targeted therapies included lenvatinib, pazopanib, and sorafenib plus everolimus. Median follow-up was 7.9 months. Among 10 evaluable patients, ORR within the first 6 months of treatment was 10% (1 partial response). Median progression-free survival was 9 months [95% CI: 3.0, not reached] and median overall survival was 19.2 months [(95% CI: 4.6, not reached]. Grade 3/4 treatment-related adverse events (AEs) were noted in 55% (6/11) and grade 5 AEs in 18% (2/11) of patients. The most common treatment-related AE was hypertension. The study did not reach its prespecified efficacy threshold. CONCLUSION: CaboNivoIpi had low ORRs and a high rate of grade ≥3 treatment-related AEs. CLINICAL TRIAL REGISTRATION: NCT03914300.

Persistent Neighborhood Poverty and Breast Cancer Outcomes.

IMPORTANCE: Patients with breast cancer residing in socioeconomically disadvantaged communities often face poorer outcomes (eg, mortality) compared with individuals living in neighborhoods without persistent poverty. OBJECTIVE: To examine persistent neighborhood poverty and breast tumor characteristics, surgical treatment, and mortality. DESIGN, Setting, and Participants: A retrospective cohort analysis of women aged 18 years or older diagnosed with stage I to III breast cancer between January 1, 2010, and December 31, 2018, and followed up until December 31, 2020, was conducted. Data were obtained from the Surveillance, Epidemiology, and End Results Program, and data analysis was performed from August 2023 to March 2024. EXPOSURE: Residence in areas affected by persistent poverty is defined as a condition where 20% or more of the population has lived below the poverty level for approximately 30 years. MAIN OUTCOME AND MEASURES: All-cause and breast cancer-specific mortality. RESULTS: Among 312 145 patients (mean [SD] age, 61.9 [13.3] years), 20 007 (6.4%) lived in a CT with persistent poverty. Compared with individuals living in areas without persistent poverty, patients residing in persistently impoverished CTs were more likely to identify as Black (8735 of 20 007 [43.7%] vs 29 588 of 292 138 [10.1%]; P < .001) or Hispanic (2605 of 20 007 [13.0%] vs 23 792 of 292 138 [8.1%]; P < .001), and present with more-aggressive tumor characteristics, including higher grade disease, triple-negative breast cancer, and advanced stage. A higher proportion of patients residing in areas with persistent poverty underwent mastectomy and axillary lymph node dissection. Living in a persistently impoverished CT was associated with a higher risk of breast cancer-specific (adjusted hazard ratio [AHR], 1.10; 95% CI, 1.03-1.17) and all-cause (AHR, 1.13; 95% CI, 1.08-1.18) mortality. As early as 3 years following diagnosis, mortality risks diverged for both breast cancer-specific (rate ratio [RR], 1.80; 95% CI, 1.68-1.92) and all-cause (RR, 1.62; 95% CI, 1.56-1.70) mortality. CONCLUSIONS AND RELEVANCE: In this cohort study of women aged 18 years or older diagnosed with stage I to III breast cancer between 2010 and 2018, living in neighborhoods characterized by persistent poverty had implications on tumor characteristics, surgical management, and mortality.

A Prospective Registry Study of 68Ga-DOTATATE PET/CT Incorporation Into Treatment Planning of Intracranial Meningiomas.

PURPOSE: The current standard for meningioma treatment planning involves magnetic resonance imaging-based guidance. Somatostatin receptor ligands such as 68Ga-DOTATATE are being explored for meningioma treatment planning due to near-universal expression of somatostatin receptors 1 and 2 in meningioma tissue. We hypothesized that 68Ga-DOTATATE positron emission tomography (PET)-guided treatment management for patients with meningiomas is safe and effective and can identify which patients benefit most from adjuvant radiation therapy. METHODS AND MATERIALS: A single-institution prospective registry study was created for inclusion of patients with intracranial meningiomas who received a 68Ga-DOTATATE PET/CT to assist with radiation oncologist decision making. Patients who received a PET scan from January 1, 2018, to February 25, 2022, were eligible for inclusion. RESULTS: Of the 60 patients included, 40%, 47%, and 5% had World Health Organization grades 1, 2, and 3 meningiomas, respectively, and 8% (5 patients) had no grade assigned. According to Radiation Therapy Oncology Group 0539 criteria, 22%, 72%, and 7% were categorized as high, intermediate, and low risk, respectively. After completing their PET scans, 48 patients, 11 patients, and 1 patient proceeded with radiation therapy, observation, and redo craniotomy, respectively. The median follow-up for the entire cohort was 19.5 months. Of the 3 patients (5%) who experienced local failure between 9.2 and 28.5 months after diagnosis, 2 had PET-avid disease in their postoperative cavity and elected for observation before recurrence, and 1 high-risk patient with multifocal disease experienced local failure 2 years after a second radiation course and multiple previous recurrences. Notably, 5 patients did not have any local PET uptake and were observed; none of these patients experienced recurrence. Only 1 grade 3 toxicity was attributed to PET-guided radiation. CONCLUSIONS: This study examined one of the largest known populations of patients with intracranial meningiomas followed by physicians who used 68Ga-DOTATATE PET-guided therapy. Incorporating 68Ga-DOTATATE PET into future trials may assist with clinician decision making and improve patient outcomes.

Comparison of Fixed Dosing vs Train of Four Titration of Cisatracurium in COVID-19 ARDS Patients.

Background: Early neuromuscular blockade with cisatracurium has been associated with improved outcomes in moderate-severe acute respiratory distress syndrome (ARDS). Previous studies have demonstrated increased drug utilization without benefits in oxygenation using fixed dose cisatracurium compared to train-of-four (TOF) titration. Objective: We sought to compare a novel, lower fixed dose cisatracurium protocol to TOF titration evaluating the impact on PaO2:FiO2 ratio (P/F). Methods: We conducted a single-center retrospective cohort study comparing fixed dose cisatracurium to TOF titration. We included patients aged 18-89 treated for COVID-19 ARDS with a baseline P/F≤200 who received a cisatracurium infusion for ≥12 h. The primary outcome was change in P/F at 48 h from baseline. Secondary outcomes included change in P/F at 24 h and 7 days, need for mechanical ventilation at day 28, and cisatracurium utilization. Results: Analyses included 125 patients (fixed dose = 65, TOF = 60). Severe ARDS was common with a baseline median P/F of 73.7 vs 79.5, P = .133. The change in P/F at 48 h was larger in the TOF cohort in the adjusted analysis (24.9 vs 70.8, P < .005). The rate and total cumulative dose of cisatracurium were higher in the fixed dose cohort (5 vs 3 mcg/kg/min, P < .001; 1034 vs 612 mg, P < .001) despite similar infusion durations (44.1 h vs 48.5 h, P = .642). Conclusions: Patients in the TOF cisatracurium cohort had improved P/F at 48 h compared to the fixed dose cohort, while also using only 60% of the cumulative dose. Future directions should include analysis of the implications of increased cisatracurium exposure on patient outcomes.

Low Hospital Volume Is Associated with Higher All-Cause Mortality in Black Women with Triple Negative Breast Cancer.

INTRODUCTION: This study examines the association between hospital volume and all-cause mortality in Black women with triple negative breast cancer (TNBC) who received surgery and chemotherapy. METHODS: Black women ages 18+ with stage I-III TNBC who received both surgery and chemotherapy were identified in the National Cancer Database (NCDB). Hospital volume was determined using the number of annual breast cancer cases divided by the number of years the hospital participated in the NCDB. Hospital annual volume quartiles ranged from Q1 (lowest) to Q4 (highest). Univariable analysis and multivariable logistic regression modeling with restricted cubic splines examined the effect of hospital volume on all-cause mortality. RESULTS: Sixteen thousand five hundred fifty-six patients met the study criteria. All-cause mortality incidence was lower at higher volume compared to lower volume hospitals Q1 24.1% (95% CI: 22.8 to 25.4), Q2 21.8% (95% CI: 20.5 to 23.1), Q3 20.9% (95% CI: 19.6 to 22.1), Q4 19.0% (95% CI: 17.7 to 20.1), p<0.001. On multivariable analysis, treatment at the highest hospital volume quartile was associated with a 21% reduction in the odds of death compared to the lowest quartile [Q4 Vs. Q1, OR=0.79 (95% CI: 0.67 to 0.92)]. For every 100-patient increase in annual volume, all-cause mortality was reduced by 4% [OR=0.96 (95% CI: 0.94 to 0.98)]. There was a significant linear dose-dependent relationship between increasing hospital volume and all-cause mortality. CONCLUSION: Black women treated at high-volume hospitals have lower all-cause mortality than those at low-volume hospitals. Future studies should examine the characteristics of high-volume hospitals associated with improved outcomes.