Standardizing Research Training: a Pilot Curriculum Within a Hematology/Oncology Fellowship Program.

While scholarly activity is recognized as critical in cancer education, there is an outstanding need for methods to define research learning competencies and tools for formal research productivity and competency assessment. We piloted and studied a novel educational initiative within the University of Wisconsin Hematology/Oncology fellowship program, establishing a professional learning community (PLC) of research mentors and developing a formative evaluation tool, a research portfolio. We developed a PLC engaged in reflective conversations about intended learning outcomes and effective instructional strategies. Subsequently, a research portfolio was piloted with four first-year Hematology/Oncology fellows at the start of the 2020 academic year in which trainees document, critically evaluate, and reflect upon the knowledge, skills, confidence, and productivity acquired during research training. We employed surveys to evaluate the initiative. Seven Hematology/Oncology fellows (7/12, 58%) completed pre-intervention and six-month interim evaluation surveys, with 43% (3/7) identifying an increased confidence in quality of research training strategies following the pilot initiation. All four first-year fellows that piloted the research portfolio (4/4, 100%) completed interim evaluation surveys that demonstrated benefits of the research portfolio including self-reflection and goal setting. Research portfolio scoring correlated with other markers of academic success, suggesting its potential to predict research success. Our data suggest that bringing together a community of research mentors to generate shared learning goals and develop the framework for a formative evaluation portfolio may meet critical needs research training needs in cancer education. Given promising results, we aim to create a new educational tool for research training.

The Timing, Trajectory, and Incidence of Immune-Related Adverse Events in NSCLC Treated With Atezolizumab.

Introduction: Immune-related adverse events (irAEs) due to immune checkpoint inhibitors can have complicated clinical courses. We comprehensively evaluated the timing, trajectory, and incidence of both single and multiple irAEs for NSCLC treated with atezolizumab. Methods: Data were pooled from 2457 patients who participated in the IMpower130, IMpower132, and IMpower150 clinical trials investigating the use of atezolizumab in metastatic NSCLC as part of a chemoimmunotherapy regimen. Longitudinal irAE data with landmark analysis, time-to-onset, changes in grading severity, and occurrence of multiple events were summarized. Results: In general, 1557 patients were treated with atezolizumab and 900 patients were in the control groups. Median follow-up was 32.3 and 23.5 months, respectively. In the atezolizumab group, 753 patients (48.4%) experienced at least one irAE. In the control group, 289 patients (32.1%) experienced at least one nonimmune adverse event that was attributed to an irAE. In the atezolizumab group, the most common irAEs were rash, hepatitis, and hypothyroidism. Furthermore, 13% of the patients experienced two irAEs and 4% experienced three irAEs. Within 5 months of treatment, the cumulative incidence for any irAE was 39.2%. Median time-to-onset varied from 1 to 10 months based on the specific irAE. Grade 1 to 2 irAEs increased in severity for 33% of the patients. Conclusions: We identified dynamic clinical patterns for irAEs in patients treated with atezolizumab, including variations in time-to-onset, incidence of multiple irAEs, and frequency of irAEs increasing in severity. These results can guide clinical management and future reporting of adverse events to enable comprehensive longitudinal analyses.

Succinct Cancer Clinical Trial Consent Forms in Rural Patients With Cancer: A Secondary Analysis of a Randomized, Double-Blinded study.

Rural patients are often underrepresented in cancer clinical trials. This is a secondary analysis of a study that tested short (2000 word) versus long (6000 word) consent forms with a focus on rurality. Among 240 patients, 89 (37%) were rural. Seventy-one (80%) rural and 117 (77%) nonrural patients signed a consent form of any length (P = .68). Forty-one of 47 (87%) rural patients signed a short consent form; in contrast, 30 of 42 (71%) signed a long form. These trends suggest rural patients are more likely to sign short consent forms. Further study is indicated.

Inhibition of B-cell lymphoma 2 family proteins alters optical redox ratio, mitochondrial polarization, and cell energetics independent of cell state.

SIGNIFICANCE: The optical redox ratio (ORR) [autofluorescence intensity of the reduced form of nicotinamide adenine dinucleotide (phosphate) (NAD(P)H)/flavin adenine dinucleotide (FAD)] provides a label-free method to quantify cellular metabolism. However, it is unclear whether changes in the ORR with B-cell lymphoma 2 (Bcl-2) family protein inhibition are due to metabolic stress alone or compromised cell viability. AIM: Determine whether ABT-263 (navitoclax, Bcl-2 family inhibitor) changes the ORR due to changes in mitochondrial function that are independent of changes in cell viability. APPROACH: SW48 colon cancer cells were used to investigate changes in ORR, mitochondrial membrane potential, oxygen consumption rates, and cell state (cell growth, viability, proliferation, apoptosis, autophagy, and senescence) with ABT-263, TAK-228 [sapanisertib, mammalian target of rapamycin complex 1/2 (mTORC 1/2) inhibitor], and their combination at 24 h. RESULTS: Changes in the ORR with Bcl-2 inhibition are driven by increases in both NAD(P)H and FAD autofluorescence, corresponding with increased basal metabolic rate and increased mitochondrial polarization. ABT-263 treatment does not change cell viability or induce autophagy but does induce a senescent phenotype. The metabolic changes seen with ABT-263 treatment are mitigated by combination with mTORC1/2 inhibition. CONCLUSIONS: The ORR is sensitive to increases in mitochondrial polarization, energetic state, and cell senescence, which can change independently from cell viability.

Current Trends in HPV Vaccine Uptake: Wisconsin and United States, 2016-2019.

BACKGROUND: Human papillomavirus (HPV) is a recognized cause of cancer in both males and females. HPV vaccination prevents development of HPV-associated diseases. METHODS: Wisconsin HPV vaccination rates (2016-2019) were obtained from the Wisconsin Immunization Registry. Data was stratified by age, sex, Medicaid status, race/ethnicity, and ZIP code. Wisconsin vaccination rates were compared with national trends using data from the 2016, 2018, and 2019 National Immunization Survey-Teen. RESULTS: Wisconsin HPV vaccination rates remain consistently below national averages. HPV vaccination rates are improving-especially among males; however, vaccine coverage at the recommended age of 11-12 remains low. Rates of vaccine uptake differ by race/ethnicity, rurality/urbanicity, and Medicaid status. CONCLUSION: Further initiatives are needed to increase awareness and acceptance of HPV vaccination for cancer prevention throughout Wisconsin.

Concurrent Central Diabetes Insipidus and Acute Myeloid Leukemia.

Central diabetes insipidus (CDI) is a rare reported complication of acute myeloid leukemia (AML). The onset of AML-associated CDI often precedes the diagnosis of AML by weeks or months and is considered an adverse prognostic indicator in this setting. The mechanism of AML-associated CDI is not known; however, it is often reported in the setting of cytogenetic events resulting in MDS1 and EVI1 complex locus protein (MECOM) gene overexpression. Here, we describe a case of new onset CDI which preceded a diagnosis of AML by 1 month. We detail the clinical and laboratory evaluation of the patient's CDI, and we describe the pathological and laboratory workup of their AML, which ultimately yielded a diagnosis of AML with myelodysplasia-related changes. Additional cytogenetic findings included the identification of the t (2;3)(p23;q27), which leads to MECOM gene overexpression and which to our knowledge has not previously been reported in the setting of AML-associated CDI. The patient received induction chemotherapy followed by allogeneic hematopoietic stem cell transplantation but experienced disease relapse and passed away nine months after initial diagnosis. We emphasize that new onset CDI can occur as a rare complication of AML where it portends a poor prognosis and may be related to AML subtypes displaying MECOM gene dysregulation.