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Item Assessment of Racial Disparity in Survival Outcomes for Early Hormone Receptor–Positive Breast Cancer After Adjusting for Insurance Status and Neighborhood Deprivation(American Medical Association, 2022) Sadigh, Gelareh; Gray, Robert J.; Sparano, Joseph A.; Yanez, Betina; Garcoa, Sofia F.; Timsina, Lava R.; Obeng-Gyasi, Samilia; Gareen, Ilana; Sledge, George W.; Whelan, Timothy J.; Cella, David; Wagner, Lynne I.; Carlos, Ruth C.; Surgery, School of MedicineImportance: Racial disparities in survival outcomes among Black women with hormone receptor-positive breast cancer have been reported. However, the association between individual-level and neighborhood-level social determinants of health on such disparities has not been well studied. Objective: To evaluate the association between race and clinical outcomes (ie, relapse-free interval and overall survival) adjusting for individual insurance coverage and neighborhood deprivation index (NDI), measured using zip code of residence, in women with breast cancer. Design, setting, and participants: This was a post hoc analysis of 9719 women with breast cancer in the Trial Assigning Individualized Options for Treatment, a randomized clinical trial conducted from April 7, 2006, to October 6, 2010. All participants received a diagnosis of hormone receptor-positive, ERBB2-negative, axillary node-negative breast cancer. The present data analysis was conducted from April 1 to October 22, 2021. Main outcomes and measures: A multivariate model was developed to evaluate the association between race and relapse-free interval and overall survival adjusting for insurance and NDI level at study entry, early discontinuation of endocrine therapy 4 years after initiation, and clinicopathologic characteristics of cancer. Median follow-up for clinical outcomes was 96 months. Results: A total of 9719 women (4.2% [n = 405] Asian; 7.1% [n = 693] Black; 84.3% [n = 8189] White; 4.4% [n = 403] others/not specified) were included; 9.1% of included women [n = 889] were Hispanic or Latino. Median (SD) age was 56 (9.2) years. In multivariate models, Black race compared with White race was associated with statistically significant shorter relapse-free interval (hazard ratio [HR], 1.39; 95% CI, 1.05-1.84; P = .02) and overall survival (HR, 1.49; 95% CI, 1.10-2.99; P = .009), adjusting for insurance and NDI level at study entry and other factors. Although uninsured status was not associated with clinical outcomes, patients with Medicare (HR, 1.30; 95% CI, 1.01-1.68; P = .04) and Medicaid (HR, 1.44; 95% CI, 1.01-2.05; P = .05) had shorter overall survival compared with those with private insurance. Participants living in neighborhoods in the highest NDI quartile experienced shorter overall survival compared with those in the lowest quartile (HR, 1.34; 95% CI, 1.01-1.77; P = .04), regardless of self-identified race. Conclusions and relevance: The findings of this post hoc analysis of a randomized clinical trial suggest that Black women with breast cancer have significantly shorter relapse-free interval and overall survival compared with White women. Early discontinuation of endocrine therapy, clinicopathologic characteristics, insurance coverage, and NDI do not fully explain the observed disparity.Item Association of Circulating Tumor DNA and Circulating Tumor Cells After Neoadjuvant Chemotherapy With Disease Recurrence in Patients With Triple-Negative Breast Cancer: Preplanned Secondary Analysis of the BRE12-158 Randomized Clinical Trial(American Medical Association, 2020-09) Radovich, Milan; Jiang, Guanglong; Hancock, Bradley A.; Chitambar, Christopher; Nanda, Rita; Falkson, Carla; Lynce, Filipa C.; Gallagher, Christopher; Isaacs, Claudine; Blaya, Marcelo; Paplomata, Elisavet; Walling, Radhika; Daily, Karen; Mahtani, Reshma; Thompson, Michael A.; Graham, Robert; Cooper, Maureen E.; Pavlick, Dean C.; Albacker, Lee A.; Gregg, Jeffrey; Solzak, Jeffrey P.; Chen, Yu-Hsiang; Bales, Casey L.; Cantor, Erica; Shen, Fei; Storniolo, Anna Maria V.; Badve, Sunil; Ballinger, Tarah J.; Chang, Chun-Li; Zhong, Yuan; Savran, Cagri; Miller, Kathy D.; Schneider, Bryan P.; Medical and Molecular Genetics, School of MedicineImportance: A significant proportion of patients with early-stage triple-negative breast cancer (TNBC) are treated with neoadjuvant chemotherapy. Sequencing of circulating tumor DNA (ctDNA) after surgery, along with enumeration of circulating tumor cells (CTCs), may be used to detect minimal residual disease and assess which patients may experience disease recurrence. Objective: To determine whether the presence of ctDNA and CTCs after neoadjuvant chemotherapy in patients with early-stage TNBC is independently associated with recurrence and clinical outcomes. Design, setting, and participants: A preplanned secondary analysis was conducted from March 26, 2014, to December 18, 2018, using data from 196 female patients in BRE12-158, a phase 2 multicenter randomized clinical trial that randomized patients with early-stage TNBC who had residual disease after neoadjuvant chemotherapy to receive postneoadjuvant genomically directed therapy vs treatment of physician choice. Patients had blood samples collected for ctDNA and CTCs at time of treatment assignment; ctDNA analysis with survival was performed for 142 patients, and CTC analysis with survival was performed for 123 patients. Median clinical follow-up was 17.2 months (range, 0.3-58.3 months). Interventions: Circulating tumor DNA was sequenced using the FoundationACT or FoundationOneLiquid Assay, and CTCs were enumerated using an epithelial cell adhesion molecule-based, positive-selection microfluidic device. Main outcomes and measures: Primary outcomes were distant disease-free survival (DDFS), disease-free survival (DFS), and overall survival (OS). Results: Among 196 female patients (mean [SD] age, 49.6 [11.1] years), detection of ctDNA was significantly associated with inferior DDFS (median DDFS, 32.5 months vs not reached; hazard ratio [HR], 2.99; 95% CI, 1.38-6.48; P = .006). At 24 months, DDFS probability was 56% for ctDNA-positive patients compared with 81% for ctDNA-negative patients. Detection of ctDNA was similarly associated with inferior DFS (HR, 2.67; 95% CI, 1.28-5.57; P = .009) and inferior OS (HR, 4.16; 95% CI,1.66-10.42; P = .002). The combination of ctDNA and CTCs provided additional information for increased sensitivity and discriminatory capacity. Patients who were ctDNA positive and CTC positive had significantly inferior DDFS compared with those who were ctDNA negative and CTC negative (median DDFS, 32.5 months vs not reached; HR, 5.29; 95% CI, 1.50-18.62; P = .009). At 24 months, DDFS probability was 52% for patients who were ctDNA positive and CTC positive compared with 89% for those who were ctDNA negative and CTC negative. Similar trends were observed for DFS (HR, 3.15; 95% CI, 1.07-9.27; P = .04) and OS (HR, 8.60; 95% CI, 1.78-41.47; P = .007). Conclusions and relevance: In this preplanned secondary analysis of a randomized clinical trial, detection of ctDNA and CTCs in patients with early-stage TNBC after neoadjuvant chemotherapy was independently associated with disease recurrence, which represents an important stratification factor for future postneoadjuvant trials.Item Melanotic neuroectodermal tumor of infancy(American Society of Neuroradiology, 1995) George, Joseph C.; Edwards, Mary K.; Jakacki, Regina I.; Kho-Duffin, Jennie; Radiology and Imaging Sciences, School of MedicineWe present a case of malignant melanotic neuroectodermal tumor of infancy arising in the skull and secondarily invading brain. The central tumor was hyperintense to brain on T1-weighted images and hypointense to brain on T2-weighted images. This appearance corresponded to the surgical and histologic findings of melanin-containing tumor.Item Thyroid Lobectomy for Low-Risk Papillary Thyroid Cancer: A National Survey of Low- and High-Volume Surgeons(Springer, 2021) McDow, Alexandria D.; Saucke, Megan C.; Marka, Nicholas A.; Long, Kristin L.; Pitt, Susan C.; Surgery, School of MedicineBackground: The 2015 American Thyroid Association guidelines endorsed lobectomy for patients with low-risk papillary thyroid cancer (PTC) measuring 1-4 cm. Attitudes about the use of lobectomy for these patients are lacking, particularly from low-volume surgeons who perform the majority of thyroidectomies in the US. Methods: A survey was mailed to 1000 surgeons stratified by specialty (500 general surgeons and 500 otolaryngologists) registered with the American Medical Association, to evaluate beliefs and practices about the extent of surgery for low-risk PTC. Comparisons examined differences by surgeon volume. Results: Of 320 respondents who have performed thyroidectomy since 2015 (150 general surgeons, 170 otolaryngologists), 206 (64.4%) were low volume (< 26 thyroidectomies/year). The proportion of surgeons recommending lobectomy for low-risk PTC measuring 1.1 to < 4 cm ranged from 43.1 to 2.6%. High-volume surgeons recommended lobectomy more frequently for PTC measuring 1.1-3 cm, although this was not statistically significant. Thirty-three percent of respondents believed lobectomy is underused for low-risk PTC, while 10.0% believed it is overused. Additionally, 19.6% of respondents believed recurrence is more likely after lobectomy than total thyroidectomy, and 3.3% believed mortality is higher. Few believed quality of life is better after lobectomy (12.3%). Low-volume surgeons were less likely to be aware guidelines support lobectomy for low-risk PTC 1-4 cm (p < 0.001) and less likely to use clinical practice guidelines (p = 0.004). Conclusions: Most surgeons do not support lobectomy for patients with low-risk PTC > 1 cm. Awareness of guidelines and concerns about increased risk of recurrence after lobectomy may drive surgeons' preference for total thyroidectomy.