Includes Supp Figure 1, Supp Table 1 (representativeness table) and Supp Methods

BACKGROUND:The utility of adaptive radiotherapy (ART) for head and neck squamous cell carcinoma (HNSCC) remains poorly defined. Daily ART (DART) promises both anatomic adaptation and planning target volume (PTV) reduction. In this prospective trial using cone-beam computed tomography-based ART, patients with HNSCC undergoing definitive radiotherapy (RT) or chemoradiotherapy (CRT) were randomly assigned to DART with reduced PTV margins or no ART with standard margins (image-guided RT [IGRT]). METHODS:Eligibility criteria included a diagnosis of oropharynx, larynx, or hypopharynx HNSCC receiving definitive radiotherapy. All individuals received involved nodal radiotherapy per previous institutional study. The PTV margins were 1 mm (2 mm craniocaudal) vs 5 mm in the DART and IGRT arms, respectively. The primary endpoint was patient-reported xerostomia at 1 year, assessed with the Xerostomia Questionnaire (XQ). RESULTS:Fifty patients were enrolled (26 IGRT, 24 DART) between March 2022 and June 2023. The cohort consisted of 38 oropharynx and 12 larynx/hypopharynx patients. The mean ipsilateral parotid gland, ipsilateral and contralateral submandibular gland doses were significantly lower with DART. There was significantly less acute dermatitis in the DART arm (Grade 0/1/2 0%/69%/31% vs 17%/75%/8% DART, P = .01) but no significant difference in any patient-reported outcome at 1 year. The adjusted difference in XQ score at 1 year was 10.0 (95% CI = -4.7 to 24.7, P = .58). CONCLUSION:Online DART for HNSCC is oncologically sound and improved acute toxicity profiles, but it did not reduce patient-reported xerostomia, the primary endpoint. Additional evidence is needed to understand the potential benefits and limitations of this paradigm, including its cost-effectiveness. TRIAL REGISTRATION:clinicaltrials.gov identifier, NCT04883281.

Count outcomes often occur in cluster randomized trials. Particularly in the context of epidemiology, the ratio of incidence rates has been used to assess the effectiveness of an intervention. In practice, cluster sizes typically vary across clusters, and sample size estimation based on a constant cluster size assumption may lead to underpowered studies. To address this issue, we propose a sample size method based on the generalized estimating equation (GEE) approach to test the ratio of two incidence rates. A closed-form sample size formula is presented, which is flexible to account for unbalanced randomization and randomly varying cluster sizes. Simulations were performed to assess its performance. In cluster randomized trials of vaccine efficacy, the ratio of disease incidence rates has been frequently used to demonstrate that the vaccine reduces the occurrence of a disease compared to placebo or active control. An application example to the design of a vaccine efficacy cluster randomized trial is presented.

The 2019 American Society for Colposcopy and Cervical Pathology provides risk-based management guidelines for abnormal cervical cancer screening test result management. It is not known whether populations facing inequities in primary care delivery have the prior screening history needed to take advantage of risk-based management of abnormal cervical cancer screening results. Determine the prevalence and associations of unknown screening history for people with an abnormal cervical cancer screening result. Retrospective multi-center population-based study of three large, structurally diverse healthcare systems in Washington state, Massachusetts, and Dallas County, Texas. Females ages 25–65 at index abnormal Pap cytology or positive Human Papillomavirus (HPV) result from 2010 to 2019 (n = 63,739). Unknown cervical cancer screening history, assessed as missing or insufficient documentation of cervical screening, diagnostic tests, and procedures extracted from administrative data and electronic health records of health systems. Over a third of patients had unknown cervical cancer screening history prior to the index abnormal test during the study period (38.3

Purpose/Objective(s) We report on our early experience of a multi-institutional phase II study of dose escalated five fraction stereotactic partial breast irradiation (S-PBI) for early-stage breast cancer after partial mastectomy using a cobalt stereotactic radiation system. Materials/Methods Patient eligibility included DCIS or invasive epithelial histologies, AJCC clinical stage 0, I, or II with tumor size < 3 cm, and negative margins. Prior safety of Phase I dose escalation has been reported. Dose was 40 Gy delivered in 5 fractions to the CTV, and minimum dose 30 Gy in 5 fractions to the PTV. CTV margin was 1 cm and PTV margin 3 mm. For PTV cavities larger than 100cc, dose was reduced to 35Gy in 5 fractions to the CTV and 30 Gy in 5 fractions to the PTV. Primary endpoint of the study is to determine the 3-year patient global cosmesis score (4-point scale excellent, good, fair, or poor) and adverse cosmesis using a dose escalated approach with smaller PTV margins than conventional methods. Both patients and physicians completed baseline and subsequent cosmesis outcome questionnaires. Treatment related toxicity graded (using the NCI version 5.0 and RTOG/EORTC late radiation scale). Results From March 2019 to October /2021, 74 patients were treated respectively. Of these, 38 were treated to 40 Gy and 36 were treated to 35 Gy. Median follow up (f/u) was 36 months (mo), range (r) 3-58 mo. Median age was 63 years (r = 43-77). Histology included 28 DCIS, and 46 invasive carcinomas. Fort-five of 46 invasive tumors were ER+. Sixty of 74 (81%) patients received endocrine therapy, and 7/74 patient received chemotherapy. There were 225 acute grade 1 toxicities, and 30 Grade 2 toxicities. No grade 3 or higher acute toxicities were reported (< 90 days). The most common Grade 2 toxicities were radiation dermatitis (12), breast pain (8), blister (4), skin infection (2), nipple discharge (2), and fatigue (2). In the late period, there were 103 Grade 1 late toxicities, 3 Grade 2 late toxicities, and no Grade 3 or higher late toxicities. Grade 2 toxicities included fibrosis 1, and pain (2). Three patients developed grade 1 asymptomatic nonpalpable fat necrosis. The most common grade 1 late toxicities were breast pain (25), hyperpigmentation (11), fibrosis (11), and fatigue (5). Physicians scored cosmesis excellent or good 71/74 (95.9%), 59/61 (96.7%), 61/62 (98.3%), 33/33(100%) respectively at baseline, 12 months, 24 months, and 36months post SBRT, while patients scored the same periods 63/72 (87.5%), 54/60 (90.0%), 57/64 (89.0%), 35/37 (94.6%). There have been no local regional or distant disease recurrences. Conclusion Results at 36-month median follow-up, of our dose escalated stereotactic partial breast 5 fraction regimen, has low acute and late toxicity, while maintaining high proportion of excellent/good cosmetic outcomes. Clinical trials.gov identifier is NCT03581136.

Few medical students are exposed to evidence-based, multidisciplinary oncology care, and few studies in oncology education reflect consolidated pre-clinical curricula. We developed a four-week curriculum, “Frontiers in Neoplasia,” for fourth-year medical students, which included didactic lectures, interactive site visits, and team-based simulations of tumor boards and clinical trial design. A mixed methods approach was utilized to investigate the course’s impact on students’ understanding and interest in oncology, involving pre- and post-course responses to Likert-scale and open-ended questions. Quantitative results were analyzed using Wilcoxon rank-sum tests, while open-ended course feedback was analyzed using iterative thematic coding analysis. Of the 107 fourth-year medical students enrolled between 2021 and 2024, 94 (88

The integrated stress response (ISR) is an adaptive pathway hijacked by cancer cells to survive cellular stresses in the tumor microenvironment. ISR activation potently induces PD-L1, leading to suppression of antitumor immunity. In this study, we sought to uncover additional immune checkpoint proteins regulated by the ISR to elucidate mechanisms of tumor immune escape. The ISR coordinately induced cluster of differentiation 155 (CD155) and PD-L1, enhancing translation of both immune checkpoint proteins through bypass of inhibitory upstream open reading frames in their 5 ' untranslated regions. Analysis of primary human lung tumors identified a significant correlation between expression of PD-L1 and CD155. ISR activation accelerated tumorigenesis and inhibited T-cell function, which could be overcome by combining PD-1 and TIGIT blockade with the ISR inhibitor ISRIB. This study uncovers a mechanism by which two immune checkpoint proteins are coordinately regulated and suggests a therapeutic strategy for patients with lung cancer.Significance: The integrated stress response represents a targetable axis to improve the efficacy of immunotherapy in lung cancer by inhibiting the coordinated translational regulation of the PD-L1/PD-1 and CD155/TIGIT immune checkpoint pathways.

Purpose We report the financial toxicity and quality-of-life outcomes of our prospective phase 1 dose-escalation study of 5-fraction stereotactic partial breast irradiation (S-PBI) for early-stage breast cancer. Materials and Methods Women with unifocal in situ or invasive epithelial histologies, clinical stages 0, I, or II with tumor size < 3 cm treated with lumpectomy were enrolled in our phase 1 5-fraction S-PBI dose-escalation trial. Our institutionally generated questionnaire on the “Patient Perspective Cost and Convenience of Care” and the EuroQol 5-Dimension 5-level questionnaire were administered to patients treated at follow-up. Results Between 2010 and 2015, 68 of the 75 patients who enrolled and completed treatment on trial completed at least some component of either the EuroQol 5-Dimension 5-level questionnaire or the “Patient Perspective Cost and Convenience of Care” questionnaire. Nearly all patients reported very high satisfaction with their treatment overall, particularly the shortened length of treatment. Over half of the patients reported some level of financial toxicity (FT) despite a significantly shortened treatment time. Patients who reported any FT were significantly younger than patients with no financial burden of treatment (means 59.2 and 63.7, respectively, P = .03). There was no difference in those who reported any level of FT based on patient race, ethnicity, marital, or employment status. This S-PBI regimen did not significantly affect quality of life over a 4-year follow-up. Conclusions These patient-reported outcomes suggest that the use of accelerated partial breast irradiation may offer low FT rates in breast cancer care, particularly for disadvantaged patient groups.

Peripheral nerves promote mouse bone marrow regeneration by activating β2- and β3-adrenergic receptor signaling, raising the possibility that nonselective β-blockers could inhibit engraftment after hematopoietic cell transplants (HCT). We observed no effect of β-blockers on steady-state mouse hematopoiesis. However, mice treated with a nonselective β-blocker (carvedilol), but not a β1-selective inhibitor (metoprolol), exhibited impaired hematopoietic regeneration after syngeneic or allogeneic HCTs. At two institutions, patients who received nonselective, but not β1-selective, β-blockers after allogeneic HCT exhibited delayed platelet engraftment and reduced survival. This was particularly observed in patients who received posttransplant chemotherapy for graft-versus-host disease prophylaxis, which also accentuated the inhibitory effect of carvedilol on engraftment in mice. In patients who received autologous HCTs, nonselective β-blockers were associated with little or no delay in engraftment. The inhibitory effect of nonselective β-blockers after allogeneic HCT was overcome by transplanting larger doses of hematopoietic cells. Significance: Patients who receive allogeneic HCTs followed by posttransplant chemotherapy for graft-versus-host disease prophylaxis may be at risk of delayed engraftment and increased mortality if administered nonselective β-blockers after transplantation. Transient discontinuation of nonselective β-blockers or transitioning to β1-selective inhibitors after HCT may accelerate engraftment and improve clinical outcomes. See related commentary by Bhatia, p. 666.

Background:Despite high response rates to epidermal growth factor receptor (EGFR) inhibitors, patients with advanced EGFR mutant non-small cell lung cancer (NSCLC) generally experience disease progression within 2 years. We evaluated whether consolidative radiation therapy (RT) to residual sites of disease at the time of expected best response to EGFR inhibition prolongs disease control. Methods:This multicentre, single-arm phase 2 trial was conducted at two sites in the USA. Eligible patients (aged ≥18 years) had advanced EGFR mutant (exon 19 or 21) NSCLC not restricted by number, site, or size of metastases; ECOG 0-2; and no prior treatment with EGFR or immune checkpoint inhibitors. Patients with stable or responding disease after 8 weeks of osimertinib 80 mg orally daily received radiation therapy (RT) to persisting lesions, followed by continued osimertinib until progression or intolerance. The primary endpoint was progression-free survival (PFS) in all participants who received at least one dose of osimertinib, assessed radiographically every 8 weeks. Secondary endpoints were toxicity, duration on osimertinib, and overall survival (OS). This trial is registered with Clinicaltrials.gov, NCT03667820. Findings:Between Oct 15, 2018, and July 1, 2021, 42 patients (32 female, 10 male) were enrolled and initiated osimertinib, of whom 32 (76%) received consolidative RT, primarily stereotactic RT. The most common reasons RT was not administered were insufficient residual disease (10%) and inadequate response (5%). At a median follow-up of 35.7 months, median PFS was 32.3 months (95% CI, 21.9-51.7), median OS was 45 months (95% CI, 39.3-56.4), and median duration of osimertinib was 32.4 months. Osimertinib-related toxicities, including skin, nail, and gastrointestinal events, occurred at expected rates and were almost always grade 1-2. Two patients (5%) developed pneumonitis, including one grade 4 event. Interpretation:These findings show osimertinib plus consolidative RT was well tolerated and demonstrates promising efficacy in patients with advanced EGFR mutant NSCLC. Because this approach may be less complex and less toxic than multi-agent targeted therapy regimens for this population, the results of ongoing randomised trials testing similar strategies are awaited. Funding:AstraZeneca and the Biostatistics Shared Resource, UT Southwestern Harold C. Simmons Comprehensive Cancer Center.

BACKGROUND AND OBJECTIVE:Stereotactic ablative radiotherapy (SAbR) has shown promise in controlling oligometastatic renal cell carcinoma (omRCC). Careful patient selection is critical, and yet the selection criteria remain unknown for patients who will not be harmed by delayed systemic therapy using SAbR. Here, we analyzed long-term follow-up of omRCC patients treated with SAbR to derive the predictors of survival benefit. METHODS:We retrospectively reviewed patients with up to five omRCC sites treated with sequential SAbR from November 2007 to July 2022. Overall survival (OS), progression-free survival (PFS), local control (LC), and toxicity were analyzed. The predictors of PFS were analyzed using a univariate analysis and a Cox proportional hazard (CPH) model-based machine learning approach. KEY FINDINGS AND LIMITATIONS:We analyzed 153 patients who underwent SAbR to 337 metastases with a median follow-up of 27 mo. The median OS and PFS were 61.3 and 32 mo, respectively. The rate of grade ≥3 toxicity was 1.3%, and the 3-yr rate of LC was 98%. Patients with bone and brain metastases had lower PFS on the univariate analysis. When compared with historical controls, the delayed-onset PFS with first-line systemic therapy in this cohort was not compromised. The CPH model found bone, brain, and number of metastases at diagnosis to be the predictors of PFS, with a C-index of 0.66 and 1-yr area under the curve of 0.68. CONCLUSIONS AND CLINICAL IMPLICATIONS:For selected patients, SAbR is effective in controlling omRCC for >2 yr and can delay systemic therapy without compromising patient outcome. Bone and brain metastases, as well as an increasing number of metastases are poor predictive factors for omRCC patients treated with sequential SAbR who may benefit from upfront systemic therapy. Prospective studies are required to verify these findings.

T cell immunoglobulin and ITIM domain (TIGIT) is an inhibitory receptor expressed on lymphocytes and NK cells, and is a candidate compensatory immune checkpoint that may mediate anti-PD-1/L1 resistance in hepatocellular carcinoma (HCC). We conducted the phase 2 LIVERTI trial testing domvanalimab, a monoclonal Fc-silent anti-TIGIT antibody, plus zimberelimab, an anti-PD-1 antibody, in immunotherapy refractory HCC. Here, we report an analysis of the primary endpoint, the confirmed overall response rate (ORR). Secondary endpoints included rates of adverse events, progression-free survival (PFS), 6-month PFS survival, overall survival, and duration of response, of which the latter two endpoints were excluded from this analysis due to the immaturity of long-term survival data. Among the 29 patients enrolled, the confirmed ORR was 17.2% (95% CI 5.8%-35.8%) and the median PFS was 4.4 months (95% CI, 4.1-4.6 months). Treatment-related adverse events occurred in 16 patients (55.2%). Analysis of circulating tumor DNA (ctDNA) demonstrated that ctDNA dynamics may serve as pharmacodynamic markers of response to domvanalimab plus zimberelimab. Despite the primary endpoint failing to meet the protocol-specified threshold, these results indicate that targeting TIGIT in anti-PD-1/L1 therapy refractory HCC is well-tolerated, associated with anti-tumor effects, and may be guided by ctDNA assessment. ClinicalTrials.gov registration: NCT05724563.

Rapid start of antiretroviral therapy (ART) has been associated with improvement in several HIV-related outcomes in clinical trials as well as demonstration projects, but how regional and contextual differences may affect the effectiveness of this intervention necessitates further study. In this study of a large, urban, Southern US clinic-based retrospective cohort, we identified 544 patients with a new diagnosis of HIV during 2016 to 2019 and compared HIV care continuum outcomes for the first 12 months of care before and after rapid start implementation. Kaplan-Meier time-to-event curves were used to summarize time to virologic suppression, and stepwise Cox, linear, and logistic regression models were used to create multivariate models to evaluate the association between rapid start and time to virologic suppression, medication adherence, and retention in care and sustained virologic suppression, respectively. We found that rapid start was significantly associated with improved medication adherence scores (+15.37 points, 95% confidence interval [CI] 9.36-21.39, P < .01) and retention in care (adjusted odds ratio = 1.51, 95% CI 1.05-2.19, P = .03). Time to virologic suppression (median 2.46 months before, 2.56 months after rapid start) and sustained virologic suppression were not associated with rapid start in our setting. Though rapid start was associated with improved medication adherence and retention in care, more support may be needed to achieve the same outcomes seen in other studies and sustained over the entire HIV care continuum, especially in settings with significant patient and systemic barriers to care such as unstable housing, lack of Medicaid expansion, and frequent coverage interruptions.

Background Despite the availability of effective therapies for patients with chronic kidney disease, type 2 diabetes, and hypertension (the kidney-dysfunction triad), the results of large-scale trials examining the implementation of guideline-directed therapy to reduce the risk of death and complications in this population are lacking.Methods In this open-label, cluster-randomized trial, we assigned 11,182 patients with the kidney-dysfunction triad who were being treated at 141 primary care clinics either to receive an intervention that used a personalized algorithm (based on the patient's electronic health record [EHR]) to identify patients and practice facilitators to assist providers in delivering guideline-based interventions or to receive usual care. The primary outcome was hospitalization for any cause at 1 year. Secondary outcomes included emergency department visits, readmissions, cardiovascular events, dialysis, and death.Results We assigned 71 practices (enrolling 5690 patients) to the intervention group and 70 practices (enrolling 5492 patients) to the usual-care group. The hospitalization rate at 1 year was 20.7% (95% confidence interval [CI], 19.7 to 21.8) in the intervention group and 21.1% (95% CI, 20.1 to 22.2) in the usual-care group (between-group difference, 0.4 percentage points; P=0.58). The risks of emergency department visits, readmissions, cardiovascular events, dialysis, or death from any cause were similar in the two groups. The risk of adverse events was also similar in the trial groups, except for acute kidney injury, which was observed in more patients in the intervention group (12.7% vs. 11.3%).Conclusions In this pragmatic trial involving patients with the triad of chronic kidney disease, type 2 diabetes, and hypertension, the use of an EHR-based algorithm and practice facilitators embedded in primary care clinics did not translate into reduced hospitalization at 1 year. (Funded by the National Institutes of Health and others; ICD-Pieces ClinicalTrials.gov number, NCT02587936.) In this trial involving patients with CKD, type 2 diabetes, and hypertension, the use of a personalized algorithm and practice facilitators in primary care clinics did not reduce hospitalization at 1 year.

Introduction: Candida dubliniensis was reclassified from the C. albicans genotype D, and reports show its frequent detection in HIV-positive individuals and easy acquisition of antifungal drug resistance. However, the oral carriage rate in healthy people and contribution to candidiasis in Japan is unclear. Methods: We conducted a cross-sectional survey of the C. dubliniensis carriage rate, performed genotyping and tested antifungal drug susceptibility and protease productivity. Specimens from 2432 Japanese subjects in six regions (1902 healthy individuals, 423 with candidiasis individuals, 107 HIV-positive individuals) were cultured using CHROMagarTMCandida, and the species was confirmed via 25S rDNA amplification and ITS sequences analyzed for genotyping. Results: The C. dubliniensis carriage rate in healthy Japanese was low in the central mainland (0–15%) but high in the most northerly and southerly areas (30–40%). The distribution of these frequencies did not differ depending on age or disease (HIV-infection, candidiasis). Genotype I, previously identified in other countries, was most frequent in Japan, but novel genotypes were also observed. Six antifungal drugs showed higher susceptibility against C. albicans, but protease productivity was low. Conclusions: Oral C. dubliniensis has low pathogenicity with distribution properties attributed to geography and not dependent on age or disease status.

INTRODUCTION: Pts ≥ 60 years (y) of age with AML have poor outcomes with a 5-year overall survival (OS) of 5-20%. VEN combined with a hypomethylating agent (HMA) or low dose cytarabine (LoDAC) is standard of care for older pts who are unfit to receive intensive chemotherapy (IC). Our study aimed to determine clinical characteristics, responses, and survival outcomes in older AML pts who received upfront VEN-based therapy vs IC. METHODS: We conducted a retrospective study of AML pts diagnosed 1/2013 - 1/2023 at UTSW who received upfront VEN-based therapy or IC. Pts < 60y of age at diagnosis were excluded. Composite complete remission (CRc) was defined as CR, CR with partial hematologic recovery (CRh), and CR with incomplete count recovery (CRi) per 2022 European LeukemiaNet (ELN) criteria. Categorical and continuous variables were compared using Chi-square/Fisher's exact test and two sample T-test/Wilcoxon rank-sum test, respectively. OS was estimated by the Kaplan-Meier method and groups were compared by log-rank tests. Univariate and stepwise logistic and Cox regression models were used to assess factors associated with response and OS, respectively. RESULTS: In total, 163 pts were identified; the final analysis included 84 pts per inclusion criteria. Thirty-nine pts (46.4%) received VEN-based therapy (6 VEN/LoDAC; 33 VEN/HMA) and 45 pts (53.6%) received IC. Median age at dx was 71y and was significantly higher in the VEN group vs IC (75y vs 65y, p<0.001). Forty percent were women. Most pts (83.1%) were White, 9.1% were Black, and 6.5% were Asian; 3.8% were of Hispanic/Latino ethnicity. Thirty-seven percent had de novo AML, 19% had therapy-related AML, and 42% progressed from prior myelodysplastic syndrome (MDS) or myeloproliferative neoplasm (MPN). Twenty-six percent of the VEN group and 18% of IC received HMA prior to their AML diagnosis. Almost half (45%) had myelodysplasia-related (MR) cytogenetics and 59.4% had ≥ 1 MR gene mutation. Baseline bone marrow blasts were higher in pts receiving IC vs VEN (p= 0.028). There was a trend towards a higher WBC count at diagnosis in the IC group (p=0.065). Per 2022 ELN stratification, 9.5%, 26.2%, and 64.3% had favorable-, intermediate-, and adverse-risk disease, respectively. The IC group had significantly more pts with favorable risk (15.6% vs 2.6%, p=0.043). The most common mutations were in TET2 (30%), RUNX1 (24%), ASXL1 (18%), DNMT3A (18%), IDH1/2 (18%), NRAS(17%), and TP53 (17%). DNMT3A and IDH1/2 mutations were higher in the VEN group vs IC (28% vs 9%, p=0.021 and 28% vs 11%, p=0.046). Forty-three percent achieved CR, 6% had CRh, 2% had CRi, and 11% had morphologic leukemia-free state. The IC group achieved a higher CR rate (53.3% vs 30.8%, p=0.037) but there was no difference in CRc. Only 9% of the IC group and 3.2% of the VEN group were transplanted in CR1 (p=0.64). Univariate analysis identified de novo AML (odds ratio [OR] 4.7, p=0.0018) and favorable/intermediate risk (OR 3.1, p=0.02) as factors associated with CRc. Stepwise selection identified prior MDS/MPN (OR 0.2, p=0.0004) and mutated TP53 (OR 0.2, p=0.03) to be negatively associated with CRc. Univariate Cox model for OS identified de novo AML (hazard ratio [HR] 0.35, p<0.0001), MR cytogenetics (HR 1.8, p=0.02), and mutated TP53 (HR 2.0, p=0.03) as significant covariates. Stepwise Cox model showed that therapy-related AML (HR 6.12, p<0.0001) and prior MDS/MPN (HR 2.17, p=0.0023) were associated increased HR for death. Median follow-up time was 12.7 months (mo). Median OS for IC vs VEN was 15.4 vs 9.3mo (p=0.10) in all pts, 18 vs 9.3mo (p=0.086) for favorable/intermediate risk, and 11.9 vs 10mo (p=0.81) for adverse risk, respectively. CONCLUSIONS: Older pts with favorable/intermediate risk AML who were offered IC over VEN-based therapy had a trend towards better OS. However, those with adverse risk AML had no difference in OS with either approach; this may support offering VEN-based therapy over IC in pts with adverse risk disease, even to “medically fit” pts, to avoid treatment related toxicity. Our study had only a few pts proceeding to transplant in CR1, limiting our ability to assess the impact of therapy choice on transplant outcomes. Furthermore, 26% of VEN pts received prior HMA, making this group particularly higher risk and accounting for shortened survival. Our findings should be validated prospectively to optimize therapy choice for “medically fit” older adults with AML.

Mental illness (MI) and substance use (SU) are highly prevalent among people with HIV (PWH) and impact care outcomes. The Substance Abuse and Mental Illness Symptoms Screener (SAMISS) is a validated screener for MI and SU, but it is unknown how screening results at entry to care correlate with subsequent HIV outcomes. This is a retrospective chart review of individuals newly diagnosed with HIV between 2016 and 2019 in a Southern US, safety-net clinic. Baseline demographics, HIV risk factors, socioeconomic variables, and SAMISS screening scores were collected. Outcomes included retention in care, achieving virologic suppression (VS), and continuous VS. Data analyses included stepwise Cox and logistic multivariate regression modeling. Among the 544 newly diagnosed PWH, mean age was 35, 76% were male, 46% non-Hispanic Black, 40% Hispanic/other. Overall, 35% screened positive for SU and 41% for MI. A positive SU (odds ratio (OR) 0.66, p = 0.04) or MI (OR 0.65, p = 0.03) SAMISS screening was associated with lower retention in care in univariate analysis, but was not statistically significant after adjusting for other variables. Positive SAMISS screening for SU and MI were both associated with reduced continuous VS in univariate and multivariate analyses (SU: adjusted OR (aOR) 0.67, p = 0.05; MI: aOR 0.66, p = 0.03). SAMISS is a useful tool for prospectively identifying individuals at risk for low retention in care and for not achieving sustained VS. Future interventions guided by SAMISS may improve HIV care continuum outcomes.

Background: The Bayesian group sequential design has been applied widely in clinical studies, especially in Phase II and III studies. It allows early termination based on accumulating interim data. However, to date, there lacks development in its application to stepped-wedge cluster randomized trials, which are gaining popularity in pragmatic trials conducted by clinical and health care delivery researchers. Methods: We propose a Bayesian adaptive design approach for stepped-wedge cluster randomized trials, which makes adaptive decisions based on the predictive probability of declaring the intervention effective at the end of study given interim data. The Bayesian models and the algorithms for posterior inference and trial conduct are presented. Results: We present how to determine design parameters through extensive simulations to achieve desired operational characteristics. We further evaluate how various design factors, such as the number of steps, cluster size, random variability in cluster size, and correlation structures, impact trial properties, including power, type I error, and the probability of early stopping. An application example is presented. Conclusion: This study presents the incorporation of Bayesian adaptive strategies into stepped-wedge cluster randomized trials design. The proposed approach provides the flexibility to stop the trial early if substantial evidence of efficacy or futility is observed, improving the flexibility and efficiency of stepped-wedge cluster randomized trials.