Association of Race, Ethnicity, Language, and Insurance with Time to Treatment Initiation Among Women with Breast Cancer at an Urban, Academic, Safety-Net Hospital.

INTRODUCTION: Initial treatment for nonmetastatic breast cancer is resection or neoadjuvant systemic therapy, depending on tumor biology and patient factors. Delays in treatment have been shown to impact survival and quality of life. Little has been published on the performance of safety-net hospitals in delivering timely care for all patients. METHODS: We conducted a retrospective study of patients with invasive ductal or lobular breast cancer, diagnosed and treated between 2009 and 2019 at an academic, safety-net hospital. Time to treatment initiation was calculated for all patients. Consistent with a recently published Committee on Cancer timeliness metric, a treatment delay was defined as time from tissue diagnosis to treatment of greater than 60 days. RESULTS: A total of 799 eligible women with stage 1-3 breast cancer met study criteria. Median age was 60 years, 55.7% were non-white, 35.5% were non-English-speaking, 18.9% were Hispanic, and 49.4% were Medicaid/uninsured. Median time to treatment was 41 days (IQR 27-56 days), while 81.1% of patients initiated treatment within 60 days. The frequency of treatment delays did not vary by race, ethnicity, insurance, or language. Diagnosis year was inversely associated with the occurrence of a treatment delay (OR: 0.944, 95% CI 0.893-0.997, p value: 0.039). CONCLUSION: At our institution, race, ethnicity, insurance, and language were not associated with treatment delay. Additional research is needed to determine how our safety-net hospital delivered timely care to all patients with breast cancer, as reducing delays in care may be one mechanism by which health systems can mitigate disparities in the treatment of breast cancer.

Overall Volume of Upper Gastrointestinal Surgery Positively Impacts Gastric Cancer Outcomes at Centers with Low Gastrectomy Volume.

BACKGROUND: The relationship between hospital volume and surgical mortality is well documented. However, complete centralization of surgical care is not always feasible. The present study investigates how overall volume of upper gastrointestinal surgery at hospitals influences patient outcomes following resection for gastric adenocarcinoma. PATIENTS AND METHODS: National Cancer Database (2010-2019) patients with pathologic stage 1-3 gastric adenocarcinoma who underwent gastrectomy were identified. Three cohorts were created: low-volume hospitals (LVH) for both gastrectomy and overall upper gastrointestinal operations, mixed-volume hospital (MVH) for low-volume gastrectomy but high-volume overall upper gastrointestinal operations, and high-volume gastrectomy hospitals (HVH). Chi-squared tests were used to analyze sociodemographic factors and surgical outcomes and Kaplan-Meier method for survival analysis. RESULTS: In total, 26,398 patients were identified (LVH: 20,099; MVH: 539; HVH: 5,760). The 5-year survival was equivalent between MVH and HVH for all stages of disease (MVH: 56.0%, HVH 55.6%; p = 0.9866) and when stratified into early (MVH: 69.9%, HVH: 65.4%; p = 0.1998) and late stages (MVH: 24.7%, HVH: 32.0%; p = 0.1480), while LVH had worse survival. After matching patients, postoperative outcomes were worse for LVH, but there was no difference between MVH and HVH in terms of adequate lymphadenectomy, margin status, readmission rates, and 90-day mortality rates. CONCLUSIONS: Despite lower gastrectomy volume for cancer, postoperative gastrectomy outcomes at centers that perform a high number of upper gastrointestinal cancer surgeries were similar to hospitals with high gastrectomy volume. These hospitals offer a blueprint for providing equivalent outcomes to high volume centers while enhancing availability of quality cancer care.

The Impact of the COVID-19 Pandemic on Hepatocellular Carcinoma Time to Treatment Initiation: A National Cancer Database Study.

BACKGROUND: The COVID-19 pandemic strained oncologic care access and delivery, yet little is known about how it impacted hepatocellular carcinoma (HCC) management. Our study sought to evaluate the annual effect of the COVID-19 pandemic on time to treatment initiation (TTI) for HCC. METHODS: The National Cancer Database was queried for patients diagnosed with clinical stages I-IV HCC (2017-2020). Patients were categorized based on their year of diagnosis as "Pre-COVID" (2017-2019) and "COVID" (2020). TTI based on stage and type of treatment first received was compared by the Mann-Whitney U test. A logistic regression model was used to evaluate factors of increased TTI and treatment delay (> 90 days). RESULTS: In total, 18,673 patients were diagnosed during Pre-COVID, whereas 5249 were diagnosed during COVID. Median TTI for any first-line treatment modality was slightly shorter during the COVID year compared with Pre-COVID (49 vs. 51 days; p < 0.0001), notably in time to ablation (52 vs. 55 days; p = 0.0238), systemic therapy (42 vs. 47 days; p < 0.0001), and radiation (60 vs. 62 days; p = 0.0177), but not surgery (41 vs. 41 days; p = 0.6887). In a multivariate analysis, patients of Black race, Hispanic ethnicity, and uninsured/Medicaid/Other Government insurance status were associated with increased TTI by factors of 1.057 (95% CI: 1.022-1.093; p = 0.0013), 1.045 (95% CI: 1.010-1.081; p = 0.0104), and 1.088 (95% CI: 1.053-1.123; p < 0.0001), respectively. Similarly, these patient populations were associated with delayed treatment times. CONCLUSIONS: For patients diagnosed during COVID, TTI for HCC, while statistically significant, had no clinically significant differences. However, vulnerable patients were more likely to have increased TTI.

Axillary Lymph Node Dissection is Associated with Improved Survival Among Men with Invasive Breast Cancer and Sentinel Node Metastasis.

BACKGROUND: Male breast cancer (MBC) is rare, and management is extrapolated from trials that enroll only women. It is unclear whether contemporary axillary management based on data from landmark trials in women may also apply to men with breast cancer. This study aimed to compare survival in men with positive sentinel lymph nodes after sentinel lymph node biopsy (SLNB) alone versus complete axillary dissection (ALND). PATIENTS AND METHODS: Using the National Cancer Database, men with clinically node-negative, T1 and T2 breast cancer and 1-2 positive sentinel nodes who underwent SLNB or ALND were identified from 2010 to 2020. Both 1:1 propensity score matching and multivariate regression were used to identify patient and disease variables associated with ALND versus SLNB. Survival between ALND and SLNB were compared using Kaplan-Meier methods. RESULTS: A total of 1203 patients were identified: 61.1% underwent SLNB alone and 38.9% underwent ALND. Treatment in academic centers (36.1 vs. 27.7%; p < 0.0001), 2 positive lymph nodes on SLNB (32.9 vs. 17.3%, p < 0.0001) and receipt or recommendation of chemotherapy (66.5 vs. 52.2%, p < 0.0001) were associated with higher likelihood of ALND. After propensity score matching, ALND was associated with superior survival compared with SLNB (5-year overall survival of 83.8 vs. 76.0%; log-rank p = 0.0104). DISCUSSION: The results of this study suggest that among patients with early-stage MBC with limited sentinel lymph node metastasis, ALND is associated with superior survival compared with SLNB alone. These findings indicate that it may be inappropriate to extrapolate the results of the ACOSOG Z0011 and EORTC AMAROS trials to MBC.

Impact of the COVID-19 Pandemic on Delays to Breast Cancer Surgery: Ripples or Waves?

BACKGROUND: Adherence to current recommendations for optimal time from diagnosis to treatment for patients with breast cancer may have been disrupted by the COVID-19 pandemic. This study aimed to evaluate the impact of the pandemic on time to surgery or systemic treatment with chemotherapy or immunotherapy for patients diagnosed with breast cancer. METHODS: Using the National Cancer Database, patients diagnosed with breast cancer in 2020 were compared to those diagnosed from 2018-2019 (Pre-COVID). Sub-analyses were performed for patients who were tested for COVID-19 and those who had a positive result in 2020. Multivariate logistic regression was used assess odds ratios for delayed time to surgery (DTS, defined as > 90 days) or systemic therapy (defined as > 120 days). RESULTS: In total, 230,997 patients were diagnosed with breast cancer in 2018 and 2019 compared to 102,065 in 2020. Of the 2020 cohort, 47,659 (46.7%) received COVID-19 testing; of which, 3,158 (6.6%) resulted positive. A larger proportion of COVID-tested or COVID-positive patients had higher stage at diagnosis. DTS was more likely for patients who were diagnosed in 2020, uninsured or underinsured, non-white, Hispanic, less educated, or age < 70 years. Similar factors were predictive of delay to systemic therapy (less age < 70 years); however, diagnosis in 2020 was not. CONCLUSION: The COVID-19 pandemic was associated with significant DTS for breast cancer but spared time to systemic therapy. Delays disproportionately impacted vulnerable and underserved patient populations. The true clinical effects of these delays may yet be realized for breast cancer patients.

Combined High-Volume Common Complex Cancer Operations Safeguard Long-Term Survival in a Low-Volume Individual Cancer Operation Setting.

BACKGROUND: We previously demonstrated the importance of combined complex surgery volume on short-term outcomes of high-risk cancer operations. This study investigates the impact of combined common complex cancer operation volume on long-term outcomes at hospitals with low cancer-specific operation volumes. PATIENTS AND METHODS: A retrospective cohort of National Cancer Data Base (2004-2019) patients undergoing surgery for hepatocellular carcinoma, non-small cell lung cancers, or pancreatic, gastric, esophageal, or rectal adenocarcinomas was utilized. Three separate cohorts were established: low-volume hospitals (LVH), mixed-volume hospitals (MVH) with low-volume individual cancer operations and high-volume total complex operations, and high-volume hospitals (HVH). Survival analyses were performed for overall, early-, and late-stage disease. RESULTS: The 5 year survival was significantly better at MVH and HVH compared with LVH, for all operations except late-stage hepatectomy (HVH survival > LVH and MVH). The 5 year survival probability was similar between MVH and HVH for operations on late-stage cancers. Early and overall survival for gastrectomy, esophagectomy, and proctectomy were equivalent between MVH and HVH. While early and overall survival for pancreatectomy were benefited by HVH over MVH, the opposite was true for lobectomy/pneumonectomy, which were benefited by MVH over HVH; however, none of these differences were likely to have an effect clinically. Only hepatectomy patients demonstrated statistical and clinical significance in 5 year survival at HVH compared with MVH for overall survival. CONCLUSIONS: MVH hospitals performing sufficient complex common cancer operations demonstrate similar long-term survival for specific high-risk cancer operations to HVH. MVH provide an adjunctive model to the centralization of complex cancer surgery, while maintaining quality and access.

Localizing Positive Axillary Lymph Nodes in Breast Cancer Patients Post Neoadjuvant Therapy.

INTRODUCTION: Multiple trials demonstrated the feasibility of sentinel lymph node biopsy (SLNB) after neoadjuvant chemotherapy. Those trials reported > 10% false-negative rate; however, a subset analysis of the Z1071 trial demonstrated that removing the clipped positive lymph node (LN) during SLNB reduces the false-negative rate to 6.8% post neoadjuvant chemotherapy. This study examines the factors that might contribute to the ability to identify the clipped nodes post neoadjuvant therapy (NAT). MATERIALS AND METHODS: Breast cancer patients with biopsy-proven metastatic axillary LN who underwent NAT, converted to N0, had preoperative localization, and then SLNB between 2018 and 2020 at a single institution were identified. A retrospective chart review was performed. Demographic and preoperative variables were compared between localization and nonlocalization groups. RESULTS: Eighty patients who met inclusion criteria were included. A total of 39 patients were localized after NAT completion (49%). Only half of the patients with ultrasound-detectable marker clips were able to be localized. Minimal LN abnormality was seen in imaging after NAT completion in 39 patients and is significantly associated with localization; 26 (67%) were localized (Odds Ratio 4.31, P = 0.002, 95% Confidence Interval 1.69-10.98). CONCLUSIONS: Our study suggests that radiologically abnormal LNs on preoperative imaging after NAT completion are more likely to be localized. Nodes that ultimately normalize by imaging criteria remain a significant challenge to localize, and thus localization before starting NAT is suggested. A better technology is needed for LN localization after prolonged NAT for best accuracy and avoids repeated procedures.

A majority of trauma-related deep venous thromboses resolve prior to discharge.

Post-traumatic DVTs present unique challenges in patient populations with specific high-risk injury patterns. Duplex ultrasound (US) can be used to assess evolution of DVTs and may guide treatment for high-risk patients. We hypothesized that many DVTs resolve during the initial admission. Weekly duplex US are ordered on all trauma inpatients regardless of prior DVT at our facility. We reviewed US and outcomes data on all patients with lower extremity DVTs at our Level I trauma center from January 2012-December 2021. 392 patients were diagnosed with lower extremity DVT by US. 261 (67%) patients received follow-up US with a mean time to repeat US of 6 days. Of these, 91 (35%) patients experienced DVT resolution prior to the first follow-up US, and 141 (54%) patients experienced resolution prior to discharge. Mean time to resolution was 10 days. Over 50% of DVTs resolve before discharge and are detected by US. Further studies and post-discharge follow-up are needed to determine if patients with resolved DVTs can be managed without therapeutic anticoagulation.

Skeletal muscle relaxant drug-drug-drug interactions and unintentional traumatic injury: Screening to detect three-way drug interaction signals.

AIM: The aim of this study was to identify skeletal muscle relaxant (SMR) drug-drug-drug interaction (3DI) signals associated with increased rates of unintentional traumatic injury. METHODS: We conducted automated high-throughput pharmacoepidemiologic screening of 2000-2019 healthcare data for members of United States commercial and Medicare Advantage health plans. We performed a self-controlled case series study for each drug triad consisting of an SMR base-pair (i.e., concomitant use of an SMR with another medication), and a co-dispensed medication (i.e., candidate interacting precipitant) taken during ongoing use of the base-pair. We included patients aged ≥16 years with an injury occurring during base-pair-exposed observation time. We used conditional Poisson regression to calculate adjusted rate ratios (RRs) with 95% confidence intervals (CIs) for injury with each SMR base-pair + candidate interacting precipitant (i.e., triad) versus the SMR-containing base-pair alone. RESULTS: Among 58 478 triads, 29 were significantly positively associated with injury; confounder-adjusted RRs ranged from 1.39 (95% CI = 1.01-1.91) for tizanidine + omeprazole with gabapentin to 2.23 (95% CI = 1.02-4.87) for tizanidine + diclofenac with alprazolam. Most identified 3DI signals are new and have not been formally investigated. CONCLUSION: We identified 29 SMR 3DI signals associated with increased rates of injury. Future aetiologic studies should confirm or refute these SMR 3DI signals.

Uterine Artery-sparing Minimally Invasive Radical Trachelectomy: A Case Report and Review of the Literature.

Radical trachelectomy is considered in patients with early-stage cervical cancer who desire future fertility. This article is accompanied by a video that provides step-by-step demonstration of a uterine artery-sparing robotic-assisted radical trachelectomy in a patient with stage IB1 squamous cell carcinoma of the cervix, a 2-cm mass, and a desire for future fertility. We also conducted a review of the literature examining the use of uterine artery-sparing techniques among minimally invasive radical trachelectomies. Using PubMed, Google Scholar, and Ovid search tools, 28 total publications were reviewed, of which 16 were eligible for use in our comparison. With the addition of our case report, a total of 154 cases sparing the uterine artery and 40 cases sacrificing the uterine artery were examined, including both conventional laparoscopic and robotic-assisted approaches. Data describing patient demographics as well as surgical, oncologic, and fertility outcomes were collected. The mean age was 30 years for the spared group and 32 years for the sacrificed group. At least 42% of the women in the spared and 53% of the uterine artery-sacrificed group were nulliparous. The majority of cases in both the spared and sacrificed groups represented squamous cell histology (71% for spared and 51% for sacrificed) followed by adenocarcinoma (24% vs 43%). The majority of the patients in both groups had stage IB1 disease (79% for spared vs 65% for sacrificed). The operative times among the 2 groups were similar, with a mean time of 314 minutes (range, 170-420 minutes) in the spared group and 283 minutes (range, 172-345 minutes) in the sacrificed group. The mean estimated blood loss was 173 mL (range, 23-300 mL) in the spared group and 77 mL (range, 50-250 mL) in the sacrificed group. The recurrence rates for the uterine artery-sparing and -sacrificing groups were equal at 2.6% after a mean follow-up of 42 months and 26 months, respectively. The methods of reporting fertility outcomes were varied among the different publications, with 41 patients achieving pregnancy in the spared group and 2 patients achieving pregnancy in the sacrificed group. Among patients who were not trying to conceive or had not conceived, 15 patients in the spared group and 6 patients in the sacrificed group were reported to have normal menses. The successful preservation of uterine arteries supports the maintenance of uterine arterial blood flow and is used by many gynecologic surgeons performing minimally invasive radical trachelectomy, with promising oncologic and obstetric outcomes.

Identification and validation of genetic variants that influence transcription factor and cell signaling protein levels.

Many genetic variants associated with human disease have been found to be associated with alterations in mRNA expression. Although it is commonly assumed that mRNA expression changes will lead to consequent changes in protein levels, methodological challenges have limited our ability to test the degree to which this assumption holds true. Here, we further developed the micro-western array approach and globally examined relationships between human genetic variation and cellular protein levels. We collected more than 250,000 protein level measurements comprising 441 transcription factor and signaling protein isoforms across 68 Yoruba (YRI) HapMap lymphoblastoid cell lines (LCLs) and identified 12 cis and 160 trans protein level QTLs (pQTLs) at a false discovery rate (FDR) of 20%. Whereas up to two thirds of cis mRNA expression QTLs (eQTLs) were also pQTLs, many pQTLs were not associated with mRNA expression. Notably, we replicated and functionally validated a trans pQTL relationship between the KARS lysyl-tRNA synthetase locus and levels of the DIDO1 protein. This study demonstrates proof of concept in applying an antibody-based microarray approach to iteratively measure the levels of human proteins and relate these levels to human genome variation and other genomic data sets. Our results suggest that protein-based mechanisms might functionally buffer genetic alterations that influence mRNA expression levels and that pQTLs might contribute phenotypic diversity to a human population independently of influences on mRNA expression.