Training Hematologists/Oncologists for the Academic-Community Hybrid: Creating a Fellowship Framework for the Future.

PURPOSE: Conventional hematology/oncology fellowship training is designed to foster careers in academic practice through intensive exposure to clinical and laboratory research. Even so, a notable proportion of graduating fellows opt to pursue a clinically focused career outside the realm of academic medicine. Given the corresponding shortage of oncologists in nonurban and rural settings, improving the representation of hematologists/oncologists in the community setting is a national priority. METHODS: We reviewed current national challenges and changing models of cancer care delivery in the context of the traditional academic training model along with trends in practice patterns for recent hematology/oncology graduates. We defined the Academic-Community hybrid (ACH) and how it supports the evolution in contemporary models of cancer care. We then drew on the authors' experiences to formulate an innovative goal-concordant training paradigm for fellows seeking careers in the ACH model. RESULTS: The ACH hematology/oncology fellowship training pathway emphasizes and optimizes professional development domains including clinical care, patient safety and quality improvement, business and operations, cancer care equity and community access, healthy policy and alignment with professional organizations, and medical education. CONCLUSION: This novel hematology/oncology training model provides a paradigm for optimizing preparedness for practice in an increasingly complex cancer care delivery environment while addressing workforce shortages and health disparities.

Time to SARS-CoV-2 clearance among patients with cancer and COVID-19.

BACKGROUND: For cancer patients, coronavirus disease 19 (COVID-19) infection can lead to delays in cancer therapy both due to the infection itself and due to the need to minimize exposure to other patients and to staff. Clearance guidelines have been proposed, but expected time to clearance has not been established. METHODS: We identified all patients at a tertiary care hospital cancer center between 25 March 2020 and 6 June 2020 with a positive nasopharyngeal reverse transcriptase polymerase chain reaction (RT-PCR) test for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a cancer-related visit within 3 years, and at least one follow-up assay. We determined the time to clearance using American Society of Clinical Oncology (ASCO), the UK National Institute for Health and Care Excellence (UK-NICE), and Centers for Disease Control and Prevention (CDC) criteria. A matched non-cancer comparison cohort was also identified. RESULTS: Thirty-two cancer patients were identified. Nineteen were cleared by ASCO criteria, with estimated median time to clearance of 50 days. Fourteen patients resumed chemotherapy prior to clearance. Using UK-NICE criteria, median time to clearance would have been 31 days, and using CDC criteria, it would have been 13 days. The matched non-cancer cohort had similar clearance time, but with less frequent testing. CONCLUSION: SARS-CoV-2 clearance times differ substantially depending on the criteria used and may be prolonged in cancer patients. This could lead to a delay in cancer care, increased use of clearance testing, and extension of infection control precautions.

Time to SARS-CoV-2 Clearance Among Patients with Cancer and COVID-19.

QUESTION: What is the median time to clearance of SARS-CoV-2 among cancer patients according to currently used criteria? FINDINGS: In this single-institution retrospective cohort study, the median time to SARS-CoV-2 clearance was 50 days using the ASCO/CDC criteria of 2 negative RT-PCR assays >24 hours apart. Using alternative criteria of 1 negative RT-PCR assay (UK-NICE) or CDC clinical criteria (10 days after first positive RT-PCR and 3 days after last symptoms), median clearance times were 31 days and 13 days, respectively. Meaning: SARS-CoV-2 clearance times differ substantially depending on criteria used and may be prolonged in cancer patients.

Demographic and psychosocial factors associated with limited health literacy in a community-based sample of older Black Americans.

OBJECTIVES: Individuals with limited health literacy often experience suboptimal health outcomes. This study examined the frequency of limited health literacy and demographic and psychosocial factors associated with limited health literacy in a sample of older Black Americans. METHODS: Participants (n = 330) enrolled in a community-based intervention to promote colorectal cancer (CRC) screening completed baseline surveys assessing health literacy with the Rapid Estimate of Adult Literacy in Medicine, Revised (REALM-R) test, CRC awareness, cancer fatalism, Preventive Health Model (PHM) constructs, and demographics. RESULTS: Approximately 52% of participants had limited health literacy, the REALM-R score was 5.4 (SD = 2.7). Univariable correlates of limited health literacy were gender, employment, income, prior screening, cancer fatalism, CRC awareness, and PHM constructs (religious beliefs, salience/coherence, perceived susceptibility). Multivariable correlates of limited health literacy were male gender (OR = 2.3, CI = 1.4-3.8), unable to work (OR = 2.8, CI = 1.3-6.1), lower household income (OR = 3.0, CI = 1.6, 5.5), and higher PHM religious beliefs (OR = 1.1, CI = 1.0-1.2). CONCLUSION: Limited health literacy was associated with multiple complex factors. Interventions should incorporate patient health literacy and low-literacy materials that can be delivered through multiple channels. PRACTICE IMPLICATIONS: Future studies are needed to understand the role of health literacy in an individual's health behavior and the provision of effective healthcare.

Clinical Factors Associated with Urinary Tract Cancer in Individuals with Lynch Syndrome.

BACKGROUND: Lynch syndrome confers markedly increased risks of various malignancies, including urinary tract cancers (UTC; renal pelvis, ureter, bladder, and possibly kidney cancers). It is unknown how to determine which Lynch syndrome carriers are at highest UTC risk. Our aim was to identify clinical factors associated with UTC among Lynch syndrome carriers. METHODS: The study population was a cohort of 52,758 consecutively ascertained individuals undergoing Lynch syndrome testing at a commercial laboratory. Clinical data were obtained from test request forms completed by the ordering provider. Univariate analysis and multivariate logistic regression were performed to identify factors associated with UTC among Lynch syndrome carriers. RESULTS: Compared with noncarriers, Lynch syndrome carriers were significantly more likely to have had UTC (4.1% vs. 1.2%; P < 0.0001). Lynch syndrome-associated UTC was independently associated with male sex [OR 1.95; 95% confidence interval (CI), 1.38-2.76], increased age (OR 2.44 per 10 years; 95% CI, 2.11-2.82), familial burden of UTC (OR 2.69 per first-/second-degree relative with UTC; 95% CI, 1.99-3.63), and pathogenic EPCAM/MSH2 variants (OR 4.01; 95% CI, 2.39-6.72) but not MLH1 variants (OR 1.17; 95% CI, 0.63-2.17), race, or history of other Lynch syndrome-associated malignancy. A total of 143 of 158 (90.5%) Lynch syndrome carriers with UTC had ≥1 of the following characteristics: male sex, EPCAM/MSH2 variants, or family history of UTC; 1,236 of 1,251 (98.8%) Lynch syndrome carriers lacking all of these characteristics had no history of UTC. CONCLUSIONS: Specific clinical factors can reliably identify Lynch syndrome carriers most likely to be at risk for UTC. IMPACT: A predictable subset of Lynch syndrome carriers may be most likely to benefit from UTC surveillance/prevention.

Postoperative hyperglycemia in patients undergoing cytoreductive surgery and HIPEC: A cohort study.

BACKGROUND: Hyperglycemia following elective or emergency surgery is generally associated with an increased risk of complications. The impact of hyperglycemia following surgery for peritoneal surface malignancy remains unclear. MATERIALS AND METHODS: Records of patients undergoing cytoreduction and HIPEC for peritoneal surface malignancy were reviewed at two institutions. Postoperative hyperglycemia was defined as serum glucose >140 mg/dl at the first measurement after surgery. Lengths of stay and 30-day complication rates were recorded. RESULTS: There were 115 total patients included, 65 from Institution A (A) and 50 from Institution B (B). Perioperative steroids were given to 55% (A) and 100% (B) of patients, with postoperative hyperglycemia present in 39% and 86% of patients respectively. Complication rates were not significantly different in patients with hyperglycemia versus patients who were normoglycemic at each site [56% vs. 53%, p = 0.8 at (A); 47% vs. 43%, p = 1.0 at (B)]. Infection rates were also similar between groups [16% vs. 13%, p = 0.72 at (A); 14% vs. 29%, p = 0.31 at (B)]. CONCLUSIONS: Rates of hyperglycemia in patients undergoing cytoreduction and HIPEC are high. This likely represents a stress response but does not seem to have the same adverse impact as seen in other abdominal surgical patient populations.

Functionally distinct patterns of nucleosome remodeling at enhancers in glucocorticoid-treated acute lymphoblastic leukemia.

BACKGROUND: Precise nucleosome positioning is an increasingly recognized feature of promoters and enhancers, reflecting complex contributions of DNA sequence, nucleosome positioning, histone modification and transcription factor binding to enhancer activity and regulation of gene expression. Changes in nucleosome position and occupancy, histone variants and modifications, and chromatin remodeling are also critical elements of dynamic transcriptional regulation, but poorly understood at enhancers. We investigated glucocorticoid receptor-associated (GR) nucleosome dynamics at enhancers in acute lymphoblastic leukemia. RESULTS: For the first time, we demonstrate functionally distinct modes of nucleosome remodeling upon chromatin binding by GR, which we term central, non-central, phased, and minimal. Central and non-central remodeling reflect nucleosome eviction by GR and cofactors, respectively. Phased remodeling involves nucleosome repositioning and is associated with rapidly activated enhancers and induction of gene expression. Minimal remodeling sites initially have low levels of enhancer-associated histone modification, but the majority of these regions gain H3K4me2 or H3K27Ac to become de novo enhancers. Minimal remodeling regions are associated with gene ontologies specific to decreased B cell number and mTOR inhibition and may make unique contributions to glucocorticoid-induced leukemia cell death. CONCLUSIONS: Our findings form a novel framework for understanding the dynamic interplay between transcription factor binding, nucleosome remodeling, enhancer function, and gene expression in the leukemia response to glucocorticoids.

TCR-dependent transformation of mature memory phenotype T cells in mice.

A fundamental goal in cancer research is the identification of the cell types and signaling pathways capable of initiating and sustaining tumor growth, as this has the potential to reveal therapeutic targets. Stem and progenitor cells have been implicated in the genesis of select lymphoid malignancies. However, the identity of the cells in which mature lymphoid neoplasms are initiated remains unclear. Here, we investigate the origin of peripheral T cell lymphomas using mice in which Snf5, a chromatin remodelling-complex subunit with tumor suppressor activity, could be conditionally inactivated in developing T cells. In this model of mature peripheral T cell lymphomas, the cell of origin was a mature CD44hiCD122loCD8⁺ T cell that resembled a subset of memory cells that has capacity for self-renewal and robust expansion, features shared with stem cells. Further analysis showed that Snf5 loss led to activation of a Myc-driven signaling network and stem cell transcriptional program. Finally, lymphomagenesis and lymphoma proliferation depended upon TCR signaling, establishing what we believe to be a new paradigm for lymphoid malignancy growth. These findings suggest that the self-renewal and robust proliferative capacities of memory T cells are associated with vulnerability to oncogenic transformation. Our findings further suggest that agents that impinge upon TCR signaling may represent an effective therapeutic modality for this class of lethal human cancers.