Conditional Risk and Predictive Factors Associated with Late Toxicity for Prostate Cancer Patients Treated with External Beam Radiotherapy Alone on Randomized Trial RTOG 0126.

PURPOSE: The objective of this study was to characterize the conditional risk of developing a grade 2+ urinary or gastrointestinal toxicity for patients treated with external beam radiotherapy on RTOG 0126. A secondary objective was to analyze baseline patient and treatment characteristics and determine their relevance in predicting toxicity both at the time of trial enrollment and later points of follow up. METHODS AND MATERIALS: 1,532 patients with localized prostate cancer were enrolled between March 2002 and August 2008, of whom 1,499 were eligible and included in data analysis with a median follow up of 8.4 years (range 0.02-13). Patients were treated with either 3DCRT or IMRT according to institutional practice without the addition of androgen deprivation and randomized to receive either standard dose radiotherapy of 70.2 Gy or dose escalated radiotherapy of 79.2 Gy of radiotherapy to the prostate only with standard fractionation. UVA and MVA analyses were determine if initial factors were predictive of late toxicity at time of treatment and at later timepoints. RESULTS: As patients proceed further from completion of radiotherapy without the development of toxicity, the subsequent risk of both grade 2+ GU and GI toxicity decreased with time. At time of enrollment the risk of developing a grade 2+ toxicity over the next 5 years was 9.57 and 17.89% respectively. After five years of toxicity free survival, the risk of developing a grade 2+ GU or GI toxicity in the subsequent five years was 3.02% and 1.54% respectively. Baseline treatment and patient related factors predicted late toxicity both at trial enrollment and after two years of toxicity free survivorship. Baseline urinary dysfunction and dose escalated radiotherapy were associated with increased late GU toxicity. Acute GI toxicity and dose escalated radiotherapy were associated with increased risk of late GI toxicity. Treatment with IMRT was associated with reduced risk of either toxicity. CONCLUSIONS: The conditional risk of grade 2+ toxicities decrease as patients proceed further from treatment with most toxicities occurring in the first few years after treatment completion. Baseline patient and treatment characteristics remain relevant at both enrollment and later time points.

Radiomic biomarkers of locoregional recurrence: prognostic insights from oral cavity squamous cell carcinoma preoperative CT scans.

Introduction: This study aimed to identify CT-based imaging biomarkers for locoregional recurrence (LR) in Oral Cavity Squamous Cell Carcinoma (OSCC) patients. Methods: Computed tomography scans were collected from 78 patients with OSCC who underwent surgical treatment at a single medical center. We extracted 1,092 radiomic features from gross tumor volume in each patient's pre-treatment CT. Clinical characteristics were also obtained, including race, sex, age, tobacco and alcohol use, tumor staging, and treatment modality. A feature selection algorithm was used to eliminate the most redundant features, followed by a selection of the best subset of the Logistic regression model (LRM). The best LRM model was determined based on the best prediction accuracy in terms of the area under Receiver operating characteristic curve. Finally, significant radiomic features in the final LRM model were identified as imaging biomarkers. Results and discussion: Two radiomics biomarkers, Large Dependence Emphasis (LDE) of the Gray Level Dependence Matrix (GLDM) and Long Run Emphasis (LRE) of the Gray Level Run Length Matrix (GLRLM) of the 3D Laplacian of Gaussian (LoG σ=3), have demonstrated the capability to preoperatively distinguish patients with and without LR, exhibiting exceptional testing specificity (1.00) and sensitivity (0.82). The group with LRE > 2.99 showed a 3-year recurrence-free survival rate of 0.81, in contrast to 0.49 for the group with LRE ≤ 2.99. Similarly, the group with LDE > 120 showed a rate of 0.82, compared to 0.49 for the group with LDE ≤ 120. These biomarkers broaden our understanding of using radiomics to predict OSCC progression, enabling personalized treatment plans to enhance patient survival.

Radiomic Biomarkers of Locoregional Recurrence: Prognostic Insights from Oral Cavity Squamous Cell Carcinoma preoperative CT scans.

This study aimed to identify CT-based imaging biomarkers for locoregional recurrence (LR) in Oral Cavity Squamous Cell Carcinoma (OSCC) patients. Our study involved a retrospective review of 78 patients with OSCC who underwent surgical treatment at a single medical center. An approach involving feature selection and statistical model diagnostics was utilized to identify biomarkers. Two radiomics biomarkers, Large Dependence Emphasis (LDE) of the Gray Level Dependence Matrix (GLDM) and Long Run Emphasis (LRE) of the Gray Level Run Length Matrix (GLRLM) of the 3D Laplacian of Gaussian (LoG σ = 3), have demonstrated the capability to preoperatively distinguish patients with and without LR, exhibiting exceptional testing specificity (1.00) and sensitivity (0.82). The group with LRE > 2.99 showed a 3-year recurrence-free survival rate of 0.81, in contrast to 0.49 for the group with LRE ≤ 2.99. Similarly, the group with LDE > 120 showed a rate of 0.82, compared to 0.49 for the group with LDE ≤ 120. These biomarkers broaden our understanding of using radiomics to predict OSCC progression, enabling personalized treatment plans to enhance patient survival.

The quality of care delivered to residents in long-term care in Australia: an indicator-based review of resident records (CareTrack Aged study).

BACKGROUND: This study estimated the prevalence of evidence-based care received by a population-based sample of Australian residents in long-term care (LTC) aged ≥ 65 years in 2021, measured by adherence to clinical practice guideline (CPG) recommendations. METHODS: Sixteen conditions/processes of care amendable to estimating evidence-based care at a population level were identified from prevalence data and CPGs. Candidate recommendations (n = 5609) were extracted from 139 CPGs which were converted to indicators. National experts in each condition rated the indicators via the RAND-UCLA Delphi process. For the 16 conditions, 236 evidence-based care indicators were ratified. A multi-stage sampling of LTC facilities and residents was undertaken. Trained aged-care nurses then undertook manual structured record reviews of care delivered between 1 March and 31 May 2021 (our record review period) to assess adherence with the indicators. RESULTS: Care received by 294 residents with 27,585 care encounters in 25 LTC facilities was evaluated. Residents received care for one to thirteen separate clinical conditions/processes of care (median = 10, mean = 9.7). Adherence to evidence-based care indicators was estimated at 53.2% (95% CI: 48.6, 57.7) ranging from a high of 81.3% (95% CI: 75.6, 86.3) for Bladder and Bowel to a low of 12.2% (95% CI: 1.6, 36.8) for Depression. Six conditions (skin integrity, end-of-life care, infection, sleep, medication, and depression) had less than 50% adherence with indicators. CONCLUSIONS: This is the first study of adherence to evidence-based care for people in LTC using multiple conditions and a standardised method. Vulnerable older people are not receiving evidence-based care for many physical problems, nor care to support their mental health nor for end-of-life care. The six conditions in which adherence with indicators was less than 50% could be the focus of improvement efforts.

Assessing Associations Between Health Information Technology Maturity and Nursing Home Survey Deficiencies.

One in three nursing home (NH) residents experience adverse events. One strategy for safer NH care is health information technology (HIT). Two national NH surveys measuring HIT maturity were administered in 2020 (N = 719) and 2021 (N = 312). Quarterly NH survey deficiencies from the same years were linked to HIT maturity surveys. Descriptive statistics and logistic regression were used in analysis. NHs were of similar size and location, with more for-profit facilities. Most (67.5% and 61.9%, respectively) NH administrators reported having capabilities to share data internally within their facility, and not externally. Mean HIT maturity scores increased from Year 1 to Year 2. Over 2 years, 5,406 deficiencies were reported, mostly (31.3%) for nutrition and dietary deficiencies. There were negative associations between HIT maturity and deficiency scope. With a 1-unit increase in HIT maturity, relative risk of widespread scope decreased by 14%. Among covariates, bed size, staffing, and year were significant factors associated with deficiency scope. [Journal of Gerontological Nursing, 50(1), 8-14.].

A Survey of Technology Abandonment in US Nursing Homes.

OBJECTIVE: Adoption of health information technology (HIT) in nursing homes (NHs) improves quality of care. Although there is a robust body of research on HIT adoption, the closely related process of technology abandonment is not well understood. As NHs grow more reliant on HIT, problems of technology abandonment, defined as failure to scale up, spread, and sustain HIT need to be studied. Our objective is to describe HIT abandonment and its associations with organizational characteristics among a national sample of US NHs. DESIGN: Longitudinal, retrospective analysis of data from 2 sources: HIT Maturity Survey and Staging model and public data from the Care Compare database. SETTING AND PARTICIPANTS: Random sample of NHs (n = 299) representing each US state that completed the HIT maturity survey in 2 consecutive years: year 1 (Y1) was June 2019-August 2020 and year 2 (Y2) was June 2020-August 2021. METHODS: The primary dependent variable was technology abandonment, operationalized by using total HIT maturity score, HIT maturity stage, and subscale scores within each dimension/domain. Independent variables were NH organizational characteristics including bed size, type of ownership, urbanicity, Centers for Medicare & Medicaid Services Five-Star Overall Rating and Staffing Rating. RESULTS: Over the 2-year period, HIT abandonment occurred in 28% (n = 85) of NHs compared with 44% (n = 133) that experienced growth in HIT systems. HIT capabilities in resident care were abandoned most frequently. Using multivariable multinomial logistic regression, we found that large NHs (bed size greater than 120) were more likely to experience technology abandonment in administrative activities. CONCLUSIONS AND IMPLICATIONS: Technology abandonment can increase strain on scarce resources and may impact administrators' ability to oversee clinical operations, especially in large NHs. This study contributes to the limited understanding of technology abandonment and can serve as a building block for others working to ensure limited resources are used effectively to improve care for NH residents.

Identification of CT-based non-invasive radiomic biomarkers for overall survival prediction in oral cavity squamous cell carcinoma.

This study addresses the limited non-invasive tools for Oral Cavity Squamous Cell Carcinoma (OSCC) survival prediction by identifying Computed Tomography (CT)-based biomarkers to improve prognosis prediction. A retrospective analysis was conducted on data from 149 OSCC patients, including CT radiomics and clinical information. An ensemble approach involving correlation analysis, score screening, and the Sparse-L1 algorithm was used to select functional features, which were then used to build Cox Proportional Hazards models (CPH). Our CPH achieved a 0.70 concordance index in testing. The model identified two CT-based radiomics features, Gradient-Neighboring-Gray-Tone-Difference-Matrix-Strength (GNS) and normalized-Wavelet-LLL-Gray-Level-Dependence-Matrix-Large-Dependence-High-Gray-Level-Emphasis (HLE), as well as stage and alcohol usage, as survival biomarkers. The GNS group with values above 14 showed a hazard ratio of 0.12 and a 3-year survival rate of about 90%. Conversely, the GNS group with values less than or equal to 14 had a 49% survival rate. For normalized HLE, the high-end group (HLE > - 0.415) had a hazard ratio of 2.41, resulting in a 3-year survival rate of 70%, while the low-end group (HLE ≤ - 0.415) had a 36% survival rate. These findings contribute to our knowledge of how radiomics can be used to predict the outcome so that treatment plans can be tailored for patients people with OSCC to improve their survival.

Recurrence risk stratification of hepatocellular carcinomas based on immune gene expression and features extracted from pathological images.

BACKGROUND: Immune-based therapy is a promising type of treatment for hepatocellular carcinoma (HCC) but has only been partially successful due to the high heterogeneity in HCC tumor. The differences in the degree of tumor cell progression and in the activity of tumor immune microenvironment could lead to varied clinical outcome. Accurate subgrouping for recurrence risk is an approach to address the issue of such heterogeneity. It remains under investigation as whether integrating quantitative whole slide image (WSI) features with the expression profile of immune marker genes can improve the risk stratification, and whether clinical outcome prediction can assist in understanding molecular biology that drives the outcome. METHODS: We included a total of 231 patients from the Cancer Genome Atlas Liver Hepatocellular Carcinoma (TCGA-LIHC) project. For each patient, we extracted 18 statistical metrics corresponding to a global region of interest and 135 features regarding nucleus shape from WSI. A risk score was developed using these image features with high-dimensional survival modeling. We also introduced into the model the expression profile of 66 representative marker genes relevant to currently available immunotherapies. We stratified all patients into higher and lower-risk subgroup based on the final risk score selected from multiple models generated, and further investigated underlying molecular mechanisms associated with the risk stratification. RESULTS: One WSI feature and three immune marker genes were selected into the final recurrence-free survival (RFS) prediction model following the best integrated modeling framework. The resultant score showed a significantly improved prediction performance on the test dataset (mean time-dependent AUCs = 0.707) as compared to those of other types (e.g: mean time-dependent AUCs of AJCC tumor stage = 0.525) of input data integration. To assess that the risk score could provide a higher-resolution risk stratification, a lower-risk subgroup (or a higher-risk subgroup) was arbitrarily assigned according to score falling below (or above) the median score. The lower risk subgroup had significantly longer median RFS time than that of the higher-risk patients (median RFS = 903 vs. 265 days, log-rank test p-value< 0.0001). Additionally, the higher-risk subgroup, in contrast to the lower-risk patients were characterized with a significant downregulation of immune checkpoint genes, suppressive signal in tumor immune response pathways, and depletion of CD8 T cells. These observations for the higher-risk subgroup suggest that new targets for adoptive or checkpoint-based combined systemic therapies may be useful. CONCLUSION: We developed a novel prognostic model to predict RFS for HCC patients, using one feature that can be automatically extracted from routine histopathological images, as well as the expression profiles of three immune marker genes. The methodology used in this paper demonstrates the feasibility of developing prognostic models that provide both useful risk stratification along with valuable biological insights into the underlying characteristics of the subgroups identified.

Post-treatment PET/CT for p16-positive oropharynx cancer treated with definitive proton therapy.

Objectives: Given emerging data suggesting that uncertainty in the relative biologic effectiveness at the distal end of the Bragg peak results in increased mucosal injury in patients with oropharynx cancer receiving adjuvant proton therapy, we evaluated the results of post-treatment positron emission tomography-computed tomography (PET/CT) in patients with p16-positive oropharynx cancer (p16+OPC) treated with definitive intensity-modulated proton therapy (IMPT). Material and Methods: A retrospective cohort study of patients with p16+OPC treated with definitive IMPT between 2016 and 2022 was performed at a single institution. Patients with PET/CT scans within 6 months following completion of IMPT were included in the study. Positive post-treatment scans were defined by a maximum standard uptake values (SUVmax) >4.0 or a <65% reduction in SUVmax in either the primary tumor or lymph node. The Fisher's exact test was used to evaluate factors associated with positive post-treatment PET/ CT values. Results: Sixty-two patients were included for analysis. Median follow-up was 21 months (range: 3-71 months) with a median time to post-treatment PET/CT of 3 months (range: 2-6 months). Median post-treatment SUVmax of the primary disease and nodal disease was 0 (mean: 0.8, range: 0-7.7) and 0 (mean: 0.7, range: 0-9.5), respectively. Median post-treatment percent reduction in SUVmax for the primary site and lymph node was 100% (mean: 94%, range: 31.3-100%) and 100% (mean: 89%, range: 23-100%), respectively. Eleven patients had a positive post-treatment PET/CT with one biopsy-proven recurrence. Negative and positive predictive values (NPV and PPV) were 98% and 9.1%, respectively. There were no factors associated with positive post-treatment PET/CT. Conclusion: Similar to patients treated with photon-based radiation therapy, post-treatment PET/CT has a high NPV for patients with p16+OPC treated with definitive proton therapy and should be used to guide patient management. Additional patients and more events are needed to confirm the PPV of a post-treatment PET/CT in this favorable patient cohort.

Identification of CT-based non-invasive Radiographic Biomarkers for Overall Survival Stratification in Oral Cavity Squamous Cell Carcinoma.

This study addresses the limited non-invasive tools for Oral Cavity Squamous Cell Carcinoma OSCC survival prediction by identifying Computed Tomography (CT)-based biomarkers for improved prognosis. A retrospective analysis was conducted on data from 149 OSCC patients, including radiomics and clinical. An ensemble approach involving correlation analysis, score screening, and the Sparse-L1 algorithm was used to select functional features, which were then used to build Cox Proportional Hazards models (CPH). Our CPH achieved a 0.70 concordance index in testing. The model identified two CT-based radiomics features, Gradient-Neighboring-Gray-Tone-Difference-Matrix-Strength (GNS) and normalized-Wavelet-LLL-Gray-Level-Dependence-Matrix-Large-Dependence-High-Gray-Level-Emphasis (HLE), as well as smoking and alcohol usage, as survival biomarkers. The GNS group with values above 14 showed a hazard ratio of 0.12 and a 3-year survival rate of about 90%. Conversely, the GNS group with values less than or equal to 14 had a 49% survival rate. For normalized HLE, the high-end group (HLE > -0.415) had a hazard ratio of 2.41, resulting in a 3-year survival rate of 70%, while the low-end group (HLE <= -0.415) had a 36% survival rate. These findings contribute to our knowledge of how radiomics can be used to anticipate the outcome and tailor treatment plans from people with OSCC.

Conditional Risks of Biochemical Failure and Prostate Cancer-Specific Death in Patients Undergoing External Beam Radiotherapy: A Secondary Analysis of 2 Randomized Clinical Trials.

Importance: As patients achieve years of survival after treatment for prostate cancer, the risk of biochemical failure (BF) or prostate cancer-specific death (PCSD) may evolve over time, with clinical relevance to both patients and clinicians. Objective: To determine conditional BF-free survival, PSCD, and overall survival estimates for patients with low- or intermediate-risk prostate cancer enrolled in the Radiation Therapy Oncology Group (RTOG) 0126 and RTOG 0415 clinical trials. A secondary objective was to determine whether prognostic factors at diagnosis remain relevant at later points in follow-up. Design, Setting, and Participants: A pooled secondary analysis of patients treated with external-beam radiotherapy alone and enrolled in the prospective randomized clinical trials RTOG 0126 and RTOG 0415 was performed. Patients included for analysis were enrolled between March 2002 and December 2009 with a median follow-up of 6.9 years. Overall survival was calculated using the Kaplan-Meier method at various survivorship time points. Cumulative incidence was used to calculate BF rates using the Phoenix definition, as well as PCSD. Risk factors such as Gleason score, tumor (T) stage, prostate-specific antigen level, and the equivalent dose in 2 Gy fractions of prescribed dose were analyzed at different time points using multivariable Cox proportional hazards modeling. Data were analyzed from November 2021 to February 2023. Main Outcomes and Measures: Conditional risks of BF and PCSD after completion of external-beam radiotherapy. Results: A total of 2591 patients (median [IQR] age, 69 [63-73] years) were included in the study with a mean (range) PSA level of 7.1 (4.7-8.9) ng/mL, 1334 patients (51.5%) with a Gleason score 6 disease, and 1706 patients (65.8%) with T1 disease. Rates of BF from time of treatment were 1.63% (95% CI, 1.20%-2.18%) at 1 year, 7.04% (95% CI, 6.09%-8.08%) at 3 years, 12.54% (95% CI, 11.28%-13.88%) at 5 years, and 22.32% (95% CI, 20.46%-24.24%) at 8 years. For patients surviving 1, 3, and 5 years without BF, the rates of BF in the next 5 years were 14.20% (95% CI, 12.80%-15.66%), 17.19% (95% CI, 15.34%-19.14%), and 18.85% (95% CI, 16.21%-21.64%), respectively. At the initial time point, the rate of PCSD in the next 5 years was 0.66% (95% CI, 0.39%-1.04%). For patients who achieved 1, 3, 5, and 8 years of survivorship, the rates of PCSD in the next 5 years were 1.16% (95% CI, 0.77-1.67) at 1 year, 2.42% (95% CI, 1.74%-3.27%) at 3 years, 2.88% (95% CI, 2.01%-3.99%) at 5 years, and 3.49% (95% CI, 0.98%-8.73%) at 8 years. Conclusions and Relevance: In this secondary analysis of 2 randomized clinical trials of patients undergoing external beam radiotherapy for prostate cancer, the conditional risks of BF and death from prostate cancer increased with time for patients with low- and intermediate-risk prostate cancer treated with radiotherapy alone. These results could inform optimal trial design and may be helpful information for patients evaluated in follow-up. Trial Registration: ClinicalTrials.gov Identifier: NCT00033631; NCT00331773.

Advancement of research on nurse practitioners: Setting a research agenda.

BACKGROUND: Primary care delivered by nurse practitioners (NPs) helps to meet the United States' growing demand for care and improves patient outcomes. Yet, barriers impede NP practice. Knowledge of these barriers is limited, hindering opportunities to eliminate them. PURPOSE: We convened a 1.5-day conference to develop a research agenda to advance evidence on the primary care NP workforce. METHODS: Thirty experts gathered in New York City for a conference in 2022. The conference included plenary sessions, small group discussions, and a prioritization process to identify areas for future research and research questions. DISCUSSION: The research agenda includes top-ranked research questions within five categories: (a) policy regulations and implications for care, quality, and access; (b) systems affecting NP practice; (c) health equity and the NP workforce; (d) NP education and workforce dynamics, and (e) international perspectives. CONCLUSION: The agenda can advance evidence on the NP workforce to guide policy and practice.

Examining the Use of Text Messages Among Multidisciplinary Care Teams to Reduce Avoidable Hospitalization of Nursing Home Residents with Dementia: Protocol for a Secondary Analysis.

BACKGROUND: Reducing avoidable nursing home (NH)-to-hospital transfers of residents with Alzheimer disease or a related dementia (ADRD) has become a national priority due to the physical and emotional toll it places on residents and the high costs to Medicare and Medicaid. Technologies supporting the use of clinical text messages (TMs) could improve communication among health care team members and have considerable impact on reducing avoidable NH-to-hospital transfers. Although text messaging is a widely accepted mechanism of communication, clinical models of care using TMs are sparsely reported in the literature, especially in NHs. Protocols for assessing technologies that integrate TMs into care delivery models would be beneficial for end users of these systems. Without evidence to support clinical models of care using TMs, users are left to design their own methods and protocols for their use, which can create wide variability and potentially increase disparities in resident outcomes. OBJECTIVE: Our aim is to describe the protocol of a study designed to understand how members of the multidisciplinary team communicate using TMs and how salient and timely communication can be used to avert poor outcomes for NH residents with ADRD, including hospitalization. METHODS: This project is a secondary analysis of data collected from a Centers for Medicare & Medicaid Services (CMS)-funded demonstration project designed to reduce avoidable hospitalizations for long-stay NH residents. We will use two data sources: (1) TMs exchanged among the multidisciplinary team across the 7-year CMS study period (August 2013-September 2020) and (2) an adapted acute care transfer tool completed by advanced practice registered nurses to document retrospective details about NH-to-hospital transfers. The study is guided by an age-friendly model of care called the 4Ms (What Matters, Medications, Mentation, and Mobility) framework. We will use natural language processing, statistical methods, and social network analysis to generate a new ontology and to compare communication patterns found in TMs occurring around the time NH-to-hospital transfer decisions were made about residents with and without ADRD. RESULTS: After accounting for inclusion and exclusion criteria, we will analyze over 30,000 TMs pertaining to over 3600 NH-to-hospital transfers. Development of the 4M ontology is in progress, and the 3-year project is expected to run until mid-2025. CONCLUSIONS: To our knowledge, this project will be the first to explore the content of TMs exchanged among a multidisciplinary team of care providers as they make decisions about NH-to-hospital resident transfers. Understanding how the presence of evidence-based elements of high-quality care relate to avoidable hospitalizations among NH residents with ADRD will generate knowledge regarding the future scalability of behavioral interventions. Without this knowledge, NHs will continue to rely on ineffective and outdated communication methods that fail to account for evidence-based elements of age-friendly care. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/50231.

Analytical validation of a multi-cancer early detection test with cancer signal origin using a cell-free DNA-based targeted methylation assay.

The analytical validation is reported for a targeted methylation-based cell-free DNA multi-cancer early detection test designed to detect cancer and predict the cancer signal origin (tissue of origin). A machine-learning classifier was used to analyze the methylation patterns of >105 genomic targets covering >1 million methylation sites. Analytical sensitivity (limit of detection [95% probability]) was characterized with respect to tumor content by expected variant allele frequency and was determined to be 0.07%-0.17% across five tumor cases and 0.51% for the lymphoid neoplasm case. Test specificity was 99.3% (95% confidence interval, 98.6-99.7%). In the reproducibility and repeatability study, results were consistent in 31/34 (91.2%) pairs with cancer and 17/17 (100%) pairs without cancer; between runs, results were concordant for 129/133 (97.0%) cancer and 37/37 (100%) non-cancer sample pairs. Across 3- to 100-ng input levels of cell-free DNA, cancer was detected in 157/182 (86.3%) cancer samples but not in any of the 62 non-cancer samples. In input titration tests, cancer signal origin was correctly predicted in all tumor samples detected as cancer. No cross-contamination events were observed. No potential interferent (hemoglobin, bilirubin, triglycerides, genomic DNA) affected performance. The results of this analytical validation study support continued clinical development of a targeted methylation cell-free DNA multi-cancer early detection test.

Multi-institutional study of clinical outcomes of patients with head and neck cancer presenting with cN3 disease.

BACKGROUND: To evaluate disease control, toxicities, and variables associated with clinical outcomes for patients with head and neck squamous cell carcinoma and clinical N3 disease (HNSCC N3) treated with definitive chemoradiation therapy. METHODS: We performed a retrospective review of patients with HNSCC N3 treated at two high-volume academic centers between 1996 and 2019. RESULTS: We identified 85 patients with a median follow-up of 2.8 years. Five-year overall survival, regional control, and freedom from distant metastases rates were 38%, 80%, and 80%, respectively. Severe complications were identified in 19% of patients. CONCLUSIONS: Favorable regional control is achievable with definitive chemoradiation therapy for patients with HNSCC N3 disease. Distant metastases are a common pattern of failure and should be a focus of prospective study.

What is the level of information technology maturity in Ontario's long-term care homes? A cross-sectional survey study protocol.

INTRODUCTION: The number of Canadians 75 years and older is expected to double over the next 20 years, putting continuing care systems such as long-term care (LTC) homes under increasing pressure. Health information technology (IT) has been found to improve the quality, safety and efficiency of care in numerous clinical settings and could help optimise LTC for residents. However, the level of health IT adoption in Ontario's LTC homes is unknown and, as a result, requires an accurate assessment to provide a baseline understanding for future planning. METHODS AND ANALYSIS: We will use a cross-sectional design to investigate the level of IT maturity in Ontario's LTC homes. IT maturity will be assessed with the LTC IT Maturity Instrument, a validated survey examining IT capabilities, the extent of IT use and degree of internal/external IT integration across the domains of resident care, clinical support and administrative activities. All LTC homes in Ontario will be invited to participate. The Director of Care for each home will be directly contacted for recruitment. The survey will be distributed online (or by paper, if preferred) to LTC homes and completed by a staff member designated by the LTC to be knowledgeable about its IT systems. Analyses will consist of descriptive statistics characterising IT maturity across LTC homes and inferential statistics to examine the association between key facility-level characteristics (size, ownership, rurality) and IT maturity. ETHICS AND DISSEMINATION: This study was reviewed by the Ottawa Health Science Network Research Ethics Board and was exempt from full ethics review. Findings will be disseminated through peer-reviewed publication and presentations to the scientific community and stakeholders. Dissemination of our findings will not only inform provincial planning for harnessing the potential of technology in LTC but may also enable quality improvement initiatives in individual LTC homes.

Gross tumor volume margin and local control in p16-positive oropharynx cancer patients treated with intensity modulated proton therapy.

BACKGROUND: To determine if the extent of high-dose gross tumor volume (GTV) to clinical target volume (CTV) expansion is associated with local control in patients with p16-positive oropharynx cancer (p16+ OPC) treated with definitive intensity modulated proton therapy (IMPT). METHODS: We performed a retrospective analysis of patients with p16+ OPC treated with IMPT at a single institution between 2016 and 2021. Patients with a pre-treatment PET-CT and restaging PET-CT within 4 months following completion of IMPT were analyzed. RESULTS: Sixty patients were included for analysis with a median follow-up of 17 months. The median GTV to CTV expansion was 5 mm (IQR: 2 mm). Thirty-three percent of patients (20 of 60) did not have a GTV to CTV expansion. There was one local failure within the expansion group (3%). CONCLUSION: Excellent local control was achieved using IMPT for p16+ OPC independent of GTV expansion. IMPT with minimal target expansions represent a potential harm-minimization technique for p16-positive oropharynx cancer.

Scoping review: Positive and negative impact of technology on clinicians.

BACKGROUND: Unnecessary electronic health record (EHRs) documentation burden and usability issues have negatively impacted clinician well-being (e.g., burnout and moral distress). PURPOSE: This scoping review was conducted by members from three expert panels of the American Academy of Nurses to generate consensus on the evidence of both positive and negative impact of EHRs on clinicians. METHODS: The scoping review was conducted based on Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) Extension for Scoping Reviews guidelines. RESULTS: The scoping review captured 1,886 publications screened against title and abstract 1,431 excluded, examined 448 in a full-text review, excluded 347 with 101 studies informing the final review. DISCUSSION: Findings suggest few studies that have explored the positive impact of EHRs and more studies that have explored the clinician's satisfaction and work burden. Significant gaps were identified in associating distress to use of EHRs and minimal studies on EHRs' impact on nurses. CONCLUSION: Examined the evidence of HIT's positive and negative impacts on clinician's practice, clinicians work environment, and if psychological impact differed among clinicians.