USA Mitchell Cancer Institute

Background: Lenalidomide maintenance after autologous stem cell transplantation (ASCT) improves progression-free survival (PFS) and overall survival (OS) in multiple myeloma; however, these benefits are attenuated in high-risk multiple myeloma (HRMM). No standard post-transplant maintenance strategy is established for HRMM, and some centers employ doublet maintenance with bortezomib plus lenalidomide (VR). We evaluated outcomes with VR versus lenalidomide alone (R) in HRMM. Methods: We conducted a multicenter retrospective study through the US Myeloma Innovations Research Collaborative (USMIRC), including adults with HRMM who received R or VR maintenance following ASCT between January 2009 and January 2024. HRMM was defined by del(17p), t(4;14), t(14;16), or t(14;20), with or without 1q gain. PFS and OS were estimated using Kaplan-Meier methods. Median follow-up was 91 months. Baseline characteristics, induction regimens, and post-transplant response depth were well balanced between the groups. Median PFS was 51 months (95% CI, 20-NR) with VR and 36 months (95% CI, 31-56) with R (p > 0.05). Median OS was 103 months (95% CI, 90-NR) and 110 months (95% CI, 94-NR), respectively (p > 0.05). VR was associated with numerically longer PFS, although the difference was not statistically significant. No treatment-related mortality occurred within 100 days post-ASCT. Conclusions: In this multicenter real-world analysis of HRMM, VR maintenance did not result in statistically significant improvements in PFS or OS compared with lenalidomide alone. These findings underscore the need for prospective, risk-adapted trials incorporating novel maintenance strategies, including CD38- and BCMA-directed therapies, in high-risk disease.

With increasing incidence of harmful algal blooms (HABs) and their associated illnesses such as ciguatera poisoning (CP), there is need for educating current and future clinicians. This study sought to assess medical and physician assistant (PA) students' knowledge, attitudes, and beliefs toward HABs and their related illnesses. A survey of medical students and PA students at the University of South Alabama (USA) was conducted using an online questionnaire on climate change, HABs/associated illnesses, and CP. Response rate was calculated using fully executed questionnaires. Frequency data was utilized for demographics and knowledge-based questions; stratified analysis was used for associations. Three hundred three medical students received the questionnaire; 27% (n = 81) completed it. One hundred seventy-one PA students received the questionnaire; 19% (n = 33) completed the survey. These students were demographically representative of their student bodies. Out of 10 questions regarding knowledge of HABs, the percent correct was 30.7% for medical students and 20.3% for PA students. 34.6% of medical students and 47.1% of PA students had never heard of HABs. 90.1% of medical students and 84.8% of PA students believed climate change will impact human health in the future and more knowledge is needed about the relationship between health and climate change. Seventy six percentage of medical students and 51.6% of PA students expressed that HAB education should be part of health professional school curriculum. Future clinicians have little knowledge of HABs and their associated illnesses despite recognizing that climate change is a vital health issue. Medical and health professional schools should consider adding HAB education for future clinicians.

Value-based health care increasingly requires electronic patient-reported outcome-based remote symptom monitoring (RSM) to improve health care utilization in patients with cancer. However, data on the impact of RSM in clinical practice are lacking. To evaluate the association of RSM with 3- and 6-month health care utilization among patients receiving systemic cancer treatment. This nonrandomized controlled trial used a hybrid, type 2 implementation-effectiveness design. Participants were patients with cancer at 2 Alabama-based academic institutions receiving chemotherapy, targeted therapy, or immunotherapy; the exposure group received standard-of-care delivered RSM from 2021 to 2024, and historical controls were patients who received cancer treatment prior to RSM implementation from 2017 to 2021. Data were analyzed from May to October 2024. RSM using electronic patient-reported outcomes. Health care utilization at 3 and 6 months after RSM enrollment (intensive care unit [ICU] admissions, hospitalizations, emergency department [ED] visits). Adjusted modified Poisson models estimated the relative risk (RR) and 95% CI of health care utilization overall. Penalized logistic regression was used for stratified analyses by patient race, residence, neighborhood deprivation, insurance type, and comorbid conditions. A total of 5949 patients were assessed. From May 2021 to May 2024, 1392 patients (median [IQR] age at index date, 61 [51-69] years; 933 [67%] female) were enrolled in RSM, including 378 Black patients (27%) and 922 White patients (66%), with 262 patients (19%) living in rural areas and 372 patients (27%) living in areas with high neighborhood disadvantage; RSM patients were compared with 4557 controls (median [IQR] age at index date, 62 [53-69] years; 2654 [58%] female), including 1177 Black patients (26%) and 3151 White patients (69%), with 1012 patients (22%) living in rural areas, and 1281 patients (28%) living in areas with high neighborhood disadvantage. Compared with historical controls, hospitalizations among patients receiving RSM were 19% lower at 3 months (RR, 0.81; 95% CI, 0.73-0.91) and 13% lower at 6 months (RR, 0.87; 95% CI, 0.80-0.96). ICU admissions were not significantly different among the RSM populations compared with controls (3 months: RR, 0.82; 95% CI, 0.59-1.13; 6 months: RR, 0.83; 95% CI, 0.65-1.06). ED visits were similar for both groups (3 months: RR, 1.02; 95% CI, 0.89-1.16; 6 months: RR, 1.03; 95% CI, 0.92-1.15). Subset analyses showed similar patterns in 3- and 6-month RR for hospitalizations, ED visits, and ICU admissions. In this nonrandomized controlled trial, RSM implementation was associated with reduced risk of hospitalizations for patients with cancer, supporting the need to expand implementation nationally.

Globally, lung cancer is the most prevalent cause of cancer-related death. There are two large histological groups of lung cancer: small-cell lung cancer (SCLC) and non-small-cell lung cancer (NSCLC). Based on histopathological and molecular features, adenocarcinoma (ADC) and squamous cell carcinoma (SCC) are the two major histologic subtypes of NSCLC. Various epidemiological and environmental factors are linked with an increased risk of lung cancer. However, these risk factors show disparities in patients with divergent racial and ethnic backgrounds. Interestingly, different populations were found to harbor distinct molecular features as evidenced by variations in genetic mutation profiles. Moreover, diverse histological and molecular progression patterns are identified in lung cancer, which could be crucial in improving diagnosis, prognosis, and therapeutic planning. In concert with a plethora of nuclear genetic alterations, mitochondrial alteration, epigenetic reprogramming, microbial dysbiosis, and immune alteration signatures have been identified in various lung cancer types. This review article provides a comprehensive overview of screening tests and the treatment strategies for NSCLC and SCLC, including surgery, radiation therapy, chemotherapy, targeted therapies, and immunotherapies. Through the unification of these diverse aspects, this review article aspires to a complete understanding of lung cancer's genomics, biology, microbial landscapes, and racial disparity and seeks to understand the essential role of racial and ethnic factors in lung cancer occurrence and treatment.

DNA damage and repair have been central themes in cellular biology research. Broadly, DNA damage is understood as modifications to canonical nucleotides that disrupt their function during transcription and replication. A deeper biochemical understanding of DNA damage is essential, as the genome governs all cellular processes. We can classify DNA damage according to whether the modifications to the nucleic acid scaffold are chemically or enzymatically initiated. This distinction is important because chemical modifications are often irreversible, sometimes sparse, and difficult to detect or control spatially and replicate systematically. This can result in genomic damage or modifications to nucleotides in the nucleotide pool, which is less commonly studied. In contrast, enzymatic modifications are typically induced by the cell for specific purposes and are under strong regulatory control. Enzymatic DNA modifications also present a degree of sequence specificity and are often reversible. However, both types of DNA modifications contribute to cellular aging when poorly repaired and, as a result, remain incompletely understood. This review hopes to gather less studied mechanisms in nucleotide modifications and show research gaps in our current understanding of nucleotide biology. By examining the implications of these mechanisms on DNA modifications, in the nucleotide pool and genome, we may gain insights into innovative strategies for mitigating the effects of cellular aging.

Colorectal cancer (CRC) is the second leading cause of cancer-related deaths worldwide. The gold standard for diagnosis is tissue biopsy during colonoscopy and subsequent histopathology. Limitations of current techniques include the turnaround time required for histopathology and the limited ability to detect flat lesions due to inadequate contrast provided by traditional white light endoscopy (WLE). The focus of this work was to assess detection accuracy for differentiating CRC and noncancerous tissues using excitation-scanning hyperspectral imaging (Ex-HSI) of autofluorescence compared to current diagnostic methods. Fluorescence Ex-HSI permits detection of all emitted light above a cut-off wavelength. Ex-HSI has been shown to reduce acquisition time, improve signal-to-noise ratio, and increase spectral information compared to emission-scanning HSI. This study utilized a mouse CRC model in which Azoxymethane/Dextran sodium sulfate (AOM/DSS) treatments induced colitis with subsequent nodule formation. Ex-HSI images were validated using transmitted light images, confocal "z-stack" images, and histology sectioning with H&E staining. Ex-HSI images were corrected to a flat spectral response, and excitation spectra were extracted from selected regions within each field of view (FOV). Inflammation and rectal bleeding were observed in the initial 31-day timepoint consistent with the AOM/DSS treatment. Colorectal nodules were visible using 4x and 20x magnification objectives and confocal "z-stack" imaging. Extracted spectra displayed two to several peak excitation wavelengths, likely indicating the presence of multiple autofluorescent molecules. Further investigation will utilize principal component analysis (PCA) and convolutional neural networks (CNN) to assess detection performance.

BackgroundThe addition of immune checkpoint inhibitors to standard‐of‐care chemoradiation (CRT) is established as the new standard of care in high‐risk, locally advanced cervical cancer. However, the optimal sequencing of therapies is unknown. Defining safety and feasibility of the combination was a primary objective of this study examining concurrent versus sequential schedules.MethodsPembrolizumab was given after or during CRT in a randomized phase 2 design. Patients aged 18 years and older with locally advanced cervical cancer, stages IB–IVA (according to 2009 International Federation of Gynecology and Obstetrics staging) were randomized 1:1 to treatment regimens. CRT was identical for both arms. Pembrolizumab was administered every 3 weeks for three doses; no maintenance was allowed. Safety assessments included the incidence and severity of adverse events (AEs), and feasibility was measured by the completion of treatment in a predefined timeframe. Translational specimens (blood and tissue) were collected.ResultsIn total, 94 evaluable patients completed treatment. Treatment‐related grade ≥2 toxicity was experienced by 85 of 94 patients (90%); 40 patients (43%) had at least one grade 3 AE, and 22 (23%) had at least one grade 4 AE. There were no grade 5 AEs. Eighty percent of patients completed radiotherapy within 56 days, and 85% completed five or six doses of cisplatin and three doses of pembrolizumab (74 of 94 patients; 79%).ConclusionsThe final results of this study support the safety and feasibility of adding pembrolizumab to pelvic CRT, concurrently and sequentially. Progression‐free and overall survival were not affected or different between treatment arms. An analysis of the translational end points is ongoing and will inform future study designs.

328 Background: Disparities in pain management for Black patients with cancer are well-documented, but less is known about other symptom clusters like gastrointestinal (GI), respiratory, and urinary symptoms. This study assessed racial disparities in electronically reported symptom clusters among Black and White patients with cancer enrolled in a Remote Symptom Monitoring (RSM) program. Methods: Patients with cancer at the University of Alabama at Birmingham (UAB) and the Mitchell Cancer Institute (MCI) reported symptoms weekly using the Patient Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAEs). The GI symptom cluster included decreased appetite, nausea, vomiting, constipation, and diarrhea; the respiratory cluster included cough and shortness of breath; the urinary cluster included frequent urinary problems. We assessed the presence of any moderate/severe symptoms or any severe symptoms (triggering a nurse alert) in the clusters. The study evaluated surveys submitted within the first six months after RSM enrollment. Generalized linear mixed effects modeling with random effects adjusting for cancer type, sex, and age were used to calculate the odds of reporting any moderate/severe pain between Black and White patients. Results: Among 1454 patients (31% Black, 69% White), 17,937 surveys were analyzed. The median age for Black patients was 59 (IQR 47-66) and 63 (IQR 54-71) for White patients. Breast cancer was most common in both groups (36% Black, 23% White), followed by gynecological (20% Black, 17% White) and gastrointestinal cancers (19% Black, 18% White). At baseline, both races reported similar proportions of moderate/severe or severe symptom for all clusters (Table). During the first six months in the RSM program, symptom proportions remained similar (Table). These findings were consistent in adjusted analysis for the GI (OR 0.85; 95% CI 0.68-1.07), respiratory (OR 1.18; 95% CI 0.87-1.61), and urinary clusters (OR 0.92; 95% CI 0.61-1.39). Conclusions: Our findings suggest no significant racial disparities in reporting moderate/severe or severe symptoms among Black and White patients with cancer at baseline or within their initial six months in the RSM program across GI, respiratory, and urinary symptom clusters. Survey characteristics. Total Surveys(N=17,937) Baseline Surveys 6 Months Surveys White (n=999) Black(n=455) White(n=11,344) Black(n=5139) Gastrointestinal Symptoms, No. (%) Severe 1376 (8) 121 (12) 59 (13) 783 (7) 413 (8) Moderate/Severe 4701 (26) 300 (30) 130 (29) 2971 (26) 1300 (25) Respiratory Symptoms, No. (%) Severe 438 (2) 28 (3) 29 (6) 241 (2) 140 (3) Moderate/Severe 1612 (9) 90 (9) 62 (14) 996 (8) 464 (9) Urinary Symptoms, No. (%) Severe 333 (2) 31 (3) 13 (3) 184 (2) 105 (2) Moderate/Severe 620 (3) 44 (4) 21 (5) 372 (3) 183 (4)

Nicotinamide adenine dinucleotide (NAD+) depletion has been postulated as a contributor to the severity of COVID‐19; however, no study has prospectively characterized NAD+ and its metabolites in relation to disease severity in patients with COVID‐19. We measured NAD+ and its metabolites in 56 hospitalized patients with COVID‐19 and in two control groups without COVID‐19: (1) 31 age‐ and sex‐matched adults with comorbidities, and (2) 30 adults without comorbidities. Blood NAD+ concentrations in COVID‐19 group were only slightly lower than in the control groups (p < 0.05); however, plasma 1‐methylnicotinamide concentrations were significantly higher in patients with COVID‐19 (439.7 ng/mL, 95% CI: 234.0, 645.4 ng/mL) than in age‐ and sex‐matched controls (44.5 ng/mL, 95% CI: 15.6, 73.4) and in healthy controls (18.1 ng/mL, 95% CI 15.4, 20.8; p < 0.001 for each comparison). Plasma nicotinamide concentrations were also higher in COVID‐19 group and in controls with comorbidities than in healthy control group. Plasma concentrations of 2‐methyl‐2‐pyridone‐5‐carboxamide (2‐PY), but not NAD+, were significantly associated with increased risk of death (HR = 3.65; 95% CI 1.09, 12.2; p = 0.036) and escalation in level of care (HR = 2.90, 95% CI 1.01, 8.38, p = 0.049). RNAseq and RTqPCR analyses of PBMC mRNA found upregulation of multiple genes involved in NAD+ synthesis as well as degradation, and dysregulation of NAD+‐dependent processes including immune response, DNA repair, metabolism, apoptosis/autophagy, redox reactions, and mitochondrial function. Blood NAD+ concentrations are modestly reduced in COVID‐19; however, NAD+ turnover is substantially increased with upregulation of genes involved in both NAD+ biosynthesis and degradation, supporting the rationale for NAD+ augmentation to attenuate disease severity.