Faculty Bibliography

PURPOSE/OBJECTIVE:Emergency department (ED) visits by patients with cancer frequently end in hospitalization. As concerns about ED and hospital crowding increase, observation unit care may be an important strategy to deliver safe and efficient treatment for eligible patients. In this investigation, we compared the prevalence and clinical characteristics of cancer patients who received observation unit care with those who were admitted to the hospital from the ED. METHODS:We performed a multicenter prospective cohort study of patients with cancer presenting to an ED affiliated with one of 18 hospitals of the Comprehensive Oncologic Emergency Research Network (CONCERN) between March 1, 2016 and January 30, 2017. We compared patient characteristics with the prevalence of observation unit care usage, hospital admission, and length of stay. RESULTS:Of 1,051 enrolled patients, 596 (56.7%) were admitted as inpatients, and 72 (6.9%) were placed in an observation unit. For patients admitted as inpatients, 23.7% had a length of stay ≤2 days. The conversion rate from observation to inpatient was 17.1% (95% CI 14.6-19.4) among those receiving care in an observation unit. The average observation unit length of stay was 14.7 hours. Patient factors associated ED disposition to observation unit care were female gender and low Charlson Comorbidity Index. CONCLUSION/CONCLUSIONS:In this multicenter prospective cohort study, the discrepancy between observation unit care use and short inpatient hospitalization may represent underutilization of this resource and a target for process change.

BACKGROUND:Despite significant increase in COVID-19 publications, characterization of COVID-19 infection in patients with gynecologic cancer remains limited. Here we present an update of COVID-19 outcomes among people with gynecologic cancer in New York City (NYC) during the initial surge of severe acute respiratory syndrome coronavirus 2 (coronavirus disease 2019 [COVID-19]). METHODS:Data were abstracted from gynecologic oncology patients with COVID-19 infection among 8 NYC area hospital systems between March and June 2020. Multivariable logistic regression was utilized to estimate associations between factors and COVID-19 related hospitalization and mortality. RESULTS:Of 193 patients with gynecologic cancer and COVID-19, the median age at diagnosis was 65.0 years (interquartile range (IQR), 53.0-73.0 years). One hundred six of the 193 patients (54.9%) required hospitalization; among the hospitalized patients, 13 (12.3%) required invasive mechanical ventilation, 39 (36.8%) required ICU admission. Half of the cohort (49.2%) had not received anti-cancer treatment prior to COVID-19 diagnosis. No patients requiring mechanical ventilation survived. Thirty-four of 193 (17.6%) patients died of COVID-19 complications. In multivariable analysis, hospitalization was associated with an age ≥ 65 years (odds ratio [OR] 2.12, 95% confidence interval [CI] 1.11, 4.07), Black race (OR 2.53, CI 1.24, 5.32), performance status ≥2 (OR 3.67, CI 1.25, 13.55) and ≥ 3 comorbidities (OR 2.00, CI 1.05, 3.84). Only former or current history of smoking (OR 2.75, CI 1.21, 6.22) was associated with death due to COVID-19 in multivariable analysis. Administration of cytotoxic chemotherapy within 90 days of COVID-19 diagnosis was not predictive of COVID-19 hospitalization (OR 0.83, CI 0.41, 1.68) or mortality (OR 1.56, CI 0.67, 3.53). CONCLUSIONS:The case fatality rate among patients with gynecologic malignancy with COVID-19 infection was 17.6%. Cancer-directed therapy was not associated with an increased risk of mortality related to COVID-19 infection.

Material hardship and stress, associated with poor infant outcomes, increased during the Coronavirus Disease 2019 pandemic. Chinese American families were vulnerable to racism-driven disparities. Little is known about maternal perceptions of pandemic impacts on their infants, family, and community. Purposive sampling of low-income Chinese American mothers (n = 25) with infants (1-15 months). Semi-structured qualitative interviews conducted in Mandarin, Cantonese, or English were audio-recorded, transcribed, and translated. Transcripts coded using applied thematic analysis in an iterative process of textual analysis until thematic saturation. Three themes emerged: (1) Heightened family hardship included financial strain, disruption of transnational childcare, experiences of racism; (2) Altered infant routines/developmental consequences included using protective equipment on infants, concerns about infant socio-emotional development; (3) Coping strategies included stockpiling essentials, adapting family diets. Strategies to mitigate disparities include expanding social needs screening, correcting misinformation, strengthening support networks, and including low-income Chinese Americans in these efforts.

Background: Metastatic colorectal (CRC), pancreatic (PANC), and gastroesophageal (GE) cancers are the leading causes of GI cancer- related mortality (5-yr survival rate, 14%, 3% and 5-6%, respectively). T-cell immunotherapy targeting GI-associated tumor antigens has been attempted, but efficacy has been constrained by on-target off-tumor toxicity, limiting the therapeutic window. The Tmod (TM) platform is an AND-NOT logic-gated CAR T modular system, versions of which have a CEA-or MSLN-targeting CAR activator and a separate HLA-A*02-targeting blocker receptor to protect normal cells. Tmod CAR T exploits HLA LOH, common in GI malignancies (10-33% in primary solid tumors [TCGA]) and can kill tumor cells without harming healthy cells in vitro and in vivo. However, the prevalence of HLA LOH across GI tumors is unknown in the real-world setting. We utilized the Tempus xT oncology NGS database of patients with multiple GI tumors. From a standard-of-care NGS assay, GI cancer patients can be readily identified for HLA LOH and future treatment with Tmod CAR T therapy.
Method(s): The occurrence of HLA LOH in GI tumors of 1439 patients was assessed using paired germline and somatic DNA sequencing using a research assay [6]. CRC, PANC and GE patients with >= stage 3 were then extracted, and rates of HLA LOH were identified (ie, whether loss occurred across high-frequency HLA-A alleles). In addition, mutations in KRAS and BRAF, as well as MSI status were stratified to determine any association with HLA-A LOH.
Result(s): HLA-A LOH was detected in 830 (17.3%) of all solid tumor records, and a similar proportion when all GI cancer records were analyzed (17.0%). For GI subtypes, these values ranged from 13.5% to 23.1% (Table). No high-frequency HLA-A allele (A*01, A*02, A*03, A*11) was more likely to be lost. Clinical biomarkers (KRAS, BRAF and MSI status) were not associated with HLA-LOH.
Conclusion(s): The frequency of HLA LOH among advanced solid tumor cancers in this dataset is 17.3%, with a range of 13.5-23% between CRC, PANC and GE. The HLA LOH frequency observed in these GI tumors is consistent with that in primary tumors from TCGA, which also used germline-matched and tumor samples. Clinical biomarkers were not associated with HLA LOH. Tempus NGS was able to identify HLA LOH, which can be used for Tmod CAR T therapy to an enhanced therapeutic window. Identification of these patients in BASECAMP-1 (NCT04981119) will enable novel Tmod CAR T therapy. (Table Presented)

BACKGROUND:Multiparametric MRI localizes cancer in the prostate, allowing for MRI guided biopsy (MRI-GB) 43 alongside transrectal ultrasound-guided systematic biopsy (TRUS-GB). Three MRI-GB approaches exist; visual estimation (COG-TB); fusion software-assisted (FUS-TB) and MRI 'in-bore' biopsy (IB-TB). It is unknown whether any of these are superior. We conducted a systematic review and meta-analysis to address three questions. First, whether MRI-GB is superior to TRUS-GB at detecting clinically significant PCa (csPCa). Second, whether MRI-GB is superior to TRUS-GB at avoiding detection of insignificant PCa. Third, whether any MRI-GB strategy is superior at detecting csPCa. METHODS:A systematic literature review from 2015 to 2019 was performed in accordance with the START recommendations. Studies reporting PCa detection rates, employing MRI-GB and TRUS-GB were included and evaluated using the QUADAS-2 checklist. 1553 studies were found, of which 43 were included in the meta-analysis. RESULTS:For csPCa, MRI-GB was superior in detection to TRUS-GB (0.83 vs. 0.63 [p = 0.02]). MRI-GB was superior in detection to TRUS-GB at avoiding detection of insignificant PCa. No MRI-GB technique was superior at detecting csPCa (IB-TB 0.87; COG TB 0.81; FUS-TB 0.81, [p = 0.55]). There was significant heterogeneity observed between the included studies. CONCLUSIONS:In patients with suspected PCa on MRI, MRI-GB offers superior rates of csPCa detection and reduces detection of insignificant PCa compared to TRUS-GB. No individual MRI-GB technique was found to be better in csPCa detection. Prospective adequately powered randomized controlled trials are required.

BACKGROUND:Public health measures to control the COVID-19 pandemic have led to feelings of loneliness among older adults, which, prior to COVID, has been associated with subsequent morbidity and mortality. We sought to identify differences in feelings of loneliness, sadness, and social disconnection early in the pandemic across racial groups, and possible mitigating factors. METHODS:We performed a cross-sectional analysis using the weighted nationally-representative Medicare Current Beneficiaries Survey COVID-19 supplement, collected summer 2020. We included all Medicare beneficiaries aged 65 years and older who did not respond by proxy. We examined changes in loneliness, sadness, or feelings of social disconnection. Multivariable logistic regression models accounted for sociodemographic variables, access to primary care and the internet, and history of depression or dementia. RESULTS:Among 8125 beneficiaries, representative of 43.7 million Medicare beneficiaries, 22.6% reported loneliness or sadness, and 37.1% feeling socially disconnected. In fully-adjusted models, Hispanic/Latinx beneficiaries were most likely to report loneliness or sadness (OR = 1.3, CI: 1.02-1.65; p = 0.02) and Black beneficiaries were least likely to report feeling socially disconnected (OR = 0.55; CI: 0.42-0.73; p < 0.001). Internet access was associated with increased odds of both (OR = 1.29, 95 CI: 1.07-1.56; p = 0.009; and OR = 1.42, 95 CI: 1.24-1.63; p < 0.001, respectively). Access to primary care was associated with lower odds of both (OR = 0.77, 95 CI: 0.61-0.96; p = 0.02; and OR = 0.72, 95 CI: 0.61-0.87; p < 0.001). CONCLUSIONS:Loneliness, sadness, and feelings of social disconnection were common among older Medicare beneficiaries early in the COVID-19 pandemic. Differences by race/ethnicity may be driven by different living structures and social networks, and warrant further study. Policy makers and clinicians should consider facilitating connection by phone or in person, as internet access did not diminish feelings of loneliness, particularly for those living alone. Access to primary care, and tools for clinicians to address loneliness should be prioritized.

BACKGROUND:Extended-release buprenorphine (XRB) offers a novel approach to sustained monthly treatment for people who use opioids in criminal justice settings (CJS). This study explores the experiences of adults receiving XRB as a jail-to-community treatment. METHODS AND FINDINGS:In-depth qualitative interviews were conducted among adult participants with opioid use disorder (OUD; n  = 16) who were recently released from NYC jails and maintained on XRB after switching from daily sublingual buprenorphine (SLB). Interviews elaborated on the acceptability and barriers and facilitators of XRB treatment pre- and post-release. Interviews were audio recorded, transcribed, and analyzed for content related to factors influencing XRB treatment uptake and community reentry. Important themes were grouped into systems, medication, and patient-level factors. Key systems-level factors influencing initiation of XRB in jail included an alternative to perceived stigmatization and privacy concerns associated with daily in-jail SLB administration and less concerns with buprenorphine diversion. In-jail peer networks positively influenced participant adoption of XRB. XRB satisfaction was attributed to reduced in-jail clinic and medication administration visits, perceived efficacy and blockade effects upon the use of heroin/fentanyl following release, and averting the risk of criminal activities to fund opioid use. Barriers to retention included post-injection withdrawal symptoms and cravings attributed to perceived suboptimal medication dosing, injection site pain, and lack of in-jail provider information about the medication. CONCLUSION:Participants were generally favorable to XRB initiation in jail and retention post-release. Further studies are needed to address factors influencing access to XRB in criminal justice settings, including stigma, ensuring patient privacy following initiation on XRB, and patient-, provider-, and correctional staff education pertaining to XRB. Trial Registration ClinicalTrials.gov Identified: NCT03604159.

OBJECTIVE:To further the precision medicine goal of tailoring medical treatment to individual patient characteristics by providing a method of analysis of the effect of test treatment, T, compared to a reference treatment, R, in participants in a RCT who are likely responders to T. METHODS:Likely responders to T are individuals whose expected response at baseline exceeds a prespecified minimum. A prognostic score, the expected response predicted as a function of baseline covariates, is obtained at trial completion. It is a balancing score that can be used to match likely responders randomized to T with those randomized to R; the result is comparable treatment groups that have a common covariance distribution. Treatments are compared based on observed outcomes in this enriched sample. The approach is illustrated in a RCT comparing two treatments for opioid use disorder. RESULTS:A standard statistical analysis of the opioid use disorder RCT found no treatment difference in the total sample. However, a subset of likely responders to T were identified and in this group, T was statistically superior to R. CONCLUSION/CONCLUSIONS:The causal treatment effect of T relative to R among likely responders may be more important than the effect in the whole target population. The prognostic score function provides quantitative information to support patient specific treatment decisions regarding T furthering the goal of precision medicine.