Intervention Trial Research Articles

Developing an international consensus reporting guideline for intervention Fidelity in non-drug, non-surgical trials: The ReFiND protocol

BackgroundInadequate reporting of fidelity to interventions in trials limits the transparency and interpretation of trial findings. Despite this, most trials of non-drug, non-surgical interventions lack comprehensive reporting of fidelity. If fidelity is poorly reported, it is unclear which intervention components were tested or implemented within the trial, which also hinders research reproducibility. This protocol describes the development process of a reporting guideline for fidelity of non-drug, non-surgical interventions (ReFiND) in the context of trials. MethodsThe ReFiND guideline will be developed in six stages. Stage one: a guideline development group has been formed to oversee the guideline methodology. Stage two: a scoping review will be conducted to identify and summarize existing guidance documents on the fidelity of non-drug, non-surgical interventions. Stage three: a Delphi study will be conducted to reach consensus on reporting items. Stage four: a consensus meeting will be held to consolidate the reporting items and discuss the wording and structure of the guideline. Stage five: a guidance statement, an elaboration and explanation document, and a reporting checklist will be developed. Stage six: different strategies will be used to disseminate and implement the ReFiND guideline. DiscussionThe ReFiND guideline will provide a set of items developed through international consensus to improve the reporting of intervention fidelity in trials of non-drug, non-surgical interventions. This reporting guideline will enhance transparency and reproducibility in future non-drug, non-surgical intervention research.

Genomic Insights for Personalized Care: Motivating At-Risk Individuals Toward Evidence-Based Health Practices.

Lung cancer and tobacco use pose significant global health challenges, necessitating a comprehensive translational roadmap for improved prevention strategies. Polygenic risk scores (PRSs) are powerful tools for patient risk stratification but have not yet been widely used in primary care for lung cancer, particularly in diverse patient populations. We propose the GREAT care paradigm, which employs PRSs to stratify disease risk and personalize interventions. We developed PRSs using large-scale multi-ancestry genome-wide association studies and standardized PRS distributions across all ancestries. We applied our PRSs to 796 individuals from the GISC Trial, 350,154 from UK Biobank (UKBB), and 210,826 from All of Us Research Program (AoU), totaling 561,776 individuals of diverse ancestry. Significant odds ratios (ORs) for lung cancer and difficulty quitting smoking were observed in both UKBB and AoU. For lung cancer, the ORs for individuals in the highest risk group (top 20% versus bottom 20%) were 1.85 (95% CI: 1.58 - 2.18) in UKBB and 2.39 (95% CI: 1.93 - 2.97) in AoU. For difficulty quitting smoking, the ORs (top 33% versus bottom 33%) were 1.36 (95% CI: 1.32 - 1.41) in UKBB and 1.32 (95% CI: 1.28 - 1.36) in AoU. Our PRS-based intervention model leverages large-scale genetic data for robust risk assessment across populations. This model will be evaluated in two cluster-randomized clinical trials aimed at motivating health behavior changes in high-risk patients of diverse ancestry. This pioneering approach integrates genomic insights into primary care, promising improved outcomes in cancer prevention and tobacco treatment.

Informal Caregivers of People with Dementia in Germany: Psychosocial Characteristics and Unmet Needs.

Caregivers of people with dementia living at home (CPwDh) are likely to be affected by a range of health problems. However, CPwDh are often regarded as accompanying persons and receive less attention in research and care. Little is known about this population and their needs in Germany. However, better knowledge of CPwDH is needed to design effective interventions. The objective of this report is to describe the situation of CPwDh and highlight differences based on sex and living situation. This was a cross-sectional analysis of the psychosocial characteristics of participants in the GAIN trial, a cluster-randomized, controlled intervention trial investigating the effectiveness of a care management program. A total of n = 192 CPwDh were recruited in GP offices, memory clinics or through public campaigns in the German federal state of Mecklenburg-Western Pomerania. The inclusion criteria were an age of 18 years or above, being a CPwDh, written informed consent. In a comprehensive digital assessment, psychosocial variables, burden, and care needs were assessed. Partners, women, and people living in the same household represented the majority of caregivers, and their mean number of needs was 8.7. Overall, participants indicated a mild to moderate burden. There are differences in burden based on sex and living situation, with caregivers living with people with dementia showing less burden and different psychosocial demographics. There is a need for interventions to reduce caregivers' unmet needs in the CPwDh. Such interventions should consider differences in sex and living situation to better address individual caregiver needs.

Will you get what you want? Treatment goals and expectations of patients with femoroacetabular impingement syndrome regarding physiotherapist-led treatment.

OBJECTIVE: To (i) investigate the goals and expectations of participants enrolled in a clinical trial of physiotherapist-led treatment for femoroacetabular impingement (FAI) syndrome and (ii) explore associations between their expectations and self-reported hip burden and kinesiophobia. METHODS: Data from 150 participants with FAI syndrome who participated in a clinical trial were analysed. Participants described their most important treatment goal and the expectation of achieving this goal throughout physiotherapy treatment. The International Hip Outcome Tool (iHOT-33) subscales were used to assess self-reported hip burden. The Tampa Scale for Kinesiophobia was used to assess kinesiophobia. Participants goals were qualitatively analysed using content analysis. Linear regression was used to explore associations between patient expectations and iHOT and Tampa Scale for Kinesiophobia scores. RESULTS: Participants with FAI syndrome reported goals relating to exercise (52%), improving activities of daily living quality (23%), improving physical function (15%), and reducing pain (10%). Negative expectations regarding physiotherapist-led treatment were reported by 68% of participants. Those with negative expectations reported worse scores for the iHOT-Total score (mean difference = 12 points, 95%CI = [4 to 19]), and iHOT-Symptoms (14 points, [7 to 21]) and iHOT-Social (11 points, [2 to 21]) subscales compared to those with positive expectations. Treatment expectations were not associated with iHOT-Sport, iHOT-Job, and Tampa Scale for Kinesiophobia scores (p > 0.05). CONCLUSION: Patients with FAI syndrome had a generally negative expectation of physiotherapist-led treatment. There was a mismatch between patients' goals and current treatment approaches. Participants with FAI syndrome and negative expectations reported worse quality of life, symptoms, and social concerns than those with positive expectations.

Alcohol Consumption Among Persons Living with HIV: Perceptions, Messages and Interventions-A Qualitative Study at an HIV Treatment Clinic in South Western Uganda.

In Sub-Saharan Africa, efficacy trials of brief interventions to reduce unhealthy drinking among persons living with HIV (PLWH) have yielded mixed results. A better understanding of the perceptions of drinking, especially by PLWH, and how drinking is talked about at HIV treatment clinics in this setting, may guide more optimal designs for future trials. We conducted a qualitative study at an HIV treatment clinic in South Western Uganda to better understand perceptions of drinking, how drinking is talked about, and perceptions of interventions, especially a protocolled screening and brief intervention (SBI) for unhealthy drinking among PLWH. We conducted in-depth interviews with 17 PLWH who engaged in unhealthy drinking and 6 health workers, and one focus group discussion with 3 community advisory-board members. We performed manual preliminary data analysis and computer-assisted detailed thematic analysis to identify emergent themes. Four themes emerged: perceptions of alcohol use in the general population; perceptions of alcohol use in PLWH; interaction between PLWH and health workers about alcohol use; perceptions of interventions for unhealthy drinking including SBI. Unhealthy drinking was seen as a problem in the general population and among those with HIV, where it was negatively perceived. Communication about drinking was done by counselors, but doctors participated in screening for unhealthy alcohol use. Messages about drinking covered reduction and abstinence. Participants expressed positive attitudes towards SBI and preference for person-delivered SBI over technological alternatives. A protocolled SBI for unhealthy alcohol use among PLWH would be well-received but successful implementation may depend on mode of delivery.

Changes in Stigma and Social Support among Participants in a Randomized Trial of a Novel Expanded Social Network-based HIV Testing Intervention in KwaZulu-Natal, South Africa.

HIV-related stigma is a well-documented barrier to HIV testing in South Africa, and may be particularly likely to create reluctance to test among South African men, who have reported feeling blamed for HIV by their partners and communities. The present study presents a novel expanded social network recruitment to HIV testing (E-SNRHT) intervention explicitly designed to reduce stigma as a barrier to testing by asking people to recruit anyone they know to testing, thus allowing them to avoid the potential for increased stigma and/or blame associated with direct risk partner recruitment, and helping to normalize openly discussing HIV among social networks. We examined baseline and 6-10-week follow-up data from a 2022-2023 randomized trial in KwaZulu-Natal, South Africa that recruited 110 individuals who had been newly diagnosed with HIV and randomly assigned them to recruit people to HIV testing either via the E-SNRHT intervention or via risk network recruitment. Participants in the E-SNRHT intervention reported significant decreases in anticipated and enacted HIV-related stigma between baseline and follow-up; and the E-SNRHT intervention was more effective at decreasing enacted HIV-related stigma than was risk network recruitment. Individuals newly diagnosed with HIV by the E-SNRHT intervention reported significant increases in social support between intervention enrollment and follow-up, and all of these individuals reported participating in positive conversations about HIV services with peers in the 6-10 weeks after intervention enrollment. These findings suggest that E-SNRHT is a potentially important strategy to reduce HIV-related stigma as a barrier to HIV testing among peer networks in KwaZulu-Natal.

Gut microbiome and inflammation among athletes in wheelchair in a crossover randomized pilot trial of probiotic and prebiotic interventions

Disorders related to gut health are a significant cause of morbidity among athletes in wheelchair. This pilot feasibility trial aims to investigate whether probiotics compared to prebiotics can improve inflammatory status and gut microbiome composition in elite athletes in wheelchair. We conducted a 12-week, randomized, cross-over controlled trial involving 14 elite Swiss athletes in wheelchair. Participants were given a multispecies-multistrain probiotic or prebiotic (oat bran) daily for 4 weeks (Clinical trials.gov NCT04659408 09/12/2020). This was followed by a 4-week washout and then crossed over. Thirty inflammatory markers were assessed using bead-based multiplex immunoassays (LegendPlex) from serum samples. The gut microbiome was characterized via 16S rRNA sequencing of stool DNA samples. Statistical analyses were conducted using linear mixed-effect models (LMM). At baseline, most athletes (10/14) exhibited low levels of inflammation which associated with higher gut microbiome alpha diversity indices compared to those with high inflammation levels. The use of probiotic had higher decrease in 25 (83%) inflammatory markers measured compared to prebiotic use. Probiotic has the potential in lowering inflammation status and improving the gut microbiome diversity. The future trial should focus on having sufficient sample sizes, population with higher inflammation status, longer intervention exposure and use of differential abundance analysis.

Results from a Pilot Randomized Controlled Trial of a Single-Session Growth-Mindset Intervention for Internalizing Symptoms in Autistic Youth.

Autistic youth experience elevated rates of co-occurring internalizing symptoms. Interventions to treat internalizing symptoms in autistic youth are almost uniformly costly and time-intensive, blunting dissemination of intervention and highlighting the need for scalable solutions. One promising option is a relatively new class of evidence-based treatments, single-session interventions (SSIs), however, no study has examined SSIs for depression symptoms in autistic youth. Participants included 40 autistic adolescents ranging in age from 11 to 16 (Mage = 14.22, Nmale = 32). Eligible youth who agreed to participate were randomized to either the active intervention (Project Personality), or an active control designed to mimic supportive therapy. Participants and their caregiver completed questionnaires immediately before, after, and three months post intervention. All participants completed the intervention independently and largely reported enjoying it. The intervention was delivered with 100% fidelity. Findings demonstrated improvements in perceived primary control, malleability of personality, and social competence relative to the active control group immediately post-intervention. Further, results revealed improvements in self-reported depression symptoms and parent reported emotional regulation at 3-month follow up. This study was the first to assess a GM-SSI designed to treat depression symptoms in autistic adolescents. Results indicated improvements in perceived control immediately post-intervention and downstream improvements in depression. Nonetheless, we did not find improvements in symptoms of anxiety, suggesting that autistic adolescents may require modifications to the intervention to maximize benefit. Findings demonstrate the utility of GM-SSI for internalizing symptoms for autistic youth and hold considerable promise as a low-intensity and scalable intervention.

Interventions to Prevent Falls in Older Adults: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force.

Falls are the most common cause of injury-related morbidity and mortality in older adults. To systematically review evidence on the effectiveness and harms of fall prevention interventions in community-dwelling older adults. MEDLINE, Cumulative Index for Nursing and Allied Health Literature, and Cochrane Central Register of Controlled Clinical Trials for relevant English-language literature published between January 1, 2016, and May 8, 2023, with ongoing surveillance through March 22, 2024. Randomized clinical trials of interventions to prevent falls in community-dwelling adults 65 years or older. Critical appraisal and data abstraction by 2 independent reviewers. Random-effects meta-analyses with Knapp-Hartung adjustment. Falls, injurious falls, fall-related fractures, hospitalizations or emergency department visits, people with 1 or more falls, people with injurious falls, people with fall-related fractures, and harms. Eighty-three fair- to good-quality randomized clinical trials (n = 48 839) examined the effectiveness of 6 fall prevention interventions in older adults. This article focuses on the 2 most studied intervention types: multifactorial (28 studies; n = 27 784) and exercise (37 studies; n = 16 117) interventions. Multifactorial interventions were associated with a statistically significant reduction in falls (incidence rate ratio [IRR], 0.84 [95% CI, 0.74-0.95]) but not a statistically significant reduction in individual risk of 1 or more falls (relative risk [RR], 0.96 [95% CI, 0.91-1.02]), injurious falls (IRR, 0.92 [95% CI, 0.84-1.01]), fall-related fractures (IRR, 1.01 [95% CI, 0.81-1.26]), individual risk of injurious falls (RR, 0.92 [95% CI, 0.83-1.02]), or individual risk of fall-related fractures (RR, 0.86 [95% CI, 0.60-1.24]). Exercise interventions were associated with statistically significant reductions in falls (IRR, 0.85 [95% CI, 0.75-0.96]), individual risk of 1 or more falls (RR, 0.92 [95% CI, 0.87-0.98]), and injurious falls (IRR, 0.84 [95% CI, 0.74-0.95]) but not individual risk of injurious falls (RR, 0.90 [95% CI, 0.79-1.02]). Harms associated with multifactorial and exercise interventions were not well reported and were generally rare, minor musculoskeletal symptoms associated with exercise. Multifactorial and exercise interventions were associated with reduced falls in multiple good-quality trials. Exercise demonstrated the most consistent statistically significant benefit across multiple fall-related outcomes.

Meniscal Transplant surgery or Optimised Rehabilitation full randomised trial (MeTeOR2): a study protocol

IntroductionPain and disability after meniscectomy can be a substantial lifelong problem. There are few treatment options, especially for young people. Non-surgical management (rehabilitation) is an option but increasingly surgeons are...

Sleep as an Important Target or Modifier in Alcohol Use Disorder Clinical Treatment: Example From a Recent Gabapentin Randomized Clinical Trial.

Alcohol consumption affects sleep both in healthy populations and in patients with alcohol use disorder (AUD). However, sleep has typically not been considered within AUD pharmacotherapy trials. We used data from a completed gabapentin clinical treatment trial to explore the medication's effect on patient-rated insomnia measured by a standard insomnia rating (Insomnia Severity Index [ISI]) and whether this influenced gabapentin's effects on alcohol consumption. This study included 90 individuals with current Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition AUD criteria reporting current or past alcohol withdrawal. Participants were assigned to placebo or gabapentin (up to 1200 mg/day) for a 16-week randomized controlled trial with percent heavy drinking days (PHDD) and percent abstinent days (PDA) as outcomes. Utilizing mixed-effects models, this study assessed medication effects on ISI over the trial. We then examined the interaction of baseline ISI and medication on drinking. Finally, given our previous finding of alcohol withdrawal influencing gabapentin efficacy, we added change in ISI as a potential "moderator" of the interaction of medication effects and alcohol withdrawal on drinking. Sleep (ISI) improved more in those treated with gabapentin (60.6% reduction) compared with placebo (37.8% reduction; P = 0.013). Higher baseline ISI predicted drinking in gabapentin-treated individuals (lower PHDD [P = 0.026] and higher (PDA [P = 0.047]). ISI was an independent predictor of PHDD decrease and PDA increase (P < 0.001; P = 0.002), but this did not significantly moderate gabapentin's effectiveness. Although gabapentin positively impacts both alcohol use and sleep, its effect on drinking is not fully dependent on sleep improvement, implying a direct biological mechanism on alcohol use.

Unexplained Residual Risk In Type 2 Diabetes: How Big Is The Problem?

What is new? Cardiovascular disease (CVD) is the leading cause of mortality in type 2 diabetes (T2D) individuals. Of the major risk factors for CVD, less than 10% of T2D people meet the American Diabetes Association/American Heart Association recommended goals of therapy. The present review examines how much of the absolute cardiovascular (CV) risk in type 2 diabetes patients can be explained by major CV intervention trials. Multiple long-term cardiovascular (CV) intervention trials have examined the effect of specific target-directed therapies on the MACE endpoint. Only one prospective study, STENO-2, has employed a multifactorial intervention comparing intensified versus conventional treatment of modifiable risk factors in T2D patients, and demonstrated a 20% absolute CV risk reduction. If the absolute CV risk reduction in these trials is added to that in the only prospective multifactorial intervention trial (STENO-2), the unexplained CV risk is 44.1%. What are the clinical implications? Potential explanations for the unaccounted-for reduction in absolute CV risk in type 2 diabetes (T2D) patients are discussed. failure to take into account synergistic interactions between major cardiovascular risk factors is responsible for the unexplained CV risk in T2D patients. Simultaneous treatment of all major CV risk factors to recommended AHA/ADA guideline goals is required to achieve the maximum reduction in CV risk.

Racial disparities in the intervention trials in colon cancer.

e13718 Background: Colorectal cancer (CRC) is the third-leading cancer worldwide and racial minorities bear a disproportionate burden of this disease. Methods: We searched the clinicaltrials.gov database for all the completed clinical trials conducted on adult patients until 2023 in the United States. In intervention trials, we manually abstracted data on the racial distribution of enrollees, phases, tumor histology, intervention type, and year of completion. We divided interventions into chemotherapy, radiotherapy, surgery, immunotherapy, behavioral, diagnostic tests, and others. To quantify the racial disparity, we calculated the enrolment ratio (ER) as the observed ratios of racial participation in the study compared to the prevalence in colorectal cancer per the 2009-2019 Surveillance, Epidemiology and End Results (SEER) database. We also conducted subgroup racial enrollment based on clinical trial and type of intervention. Results: We identified 394 studies, of which 252 studies (64%) had racial distribution published, including 138814 participants. Most studies were phase 2 trials (168), followed by phase 1/2 trials (49) and phase 3 studies (43). The racial breakdown included 88677 White participants (63.9%), 23230 were African Americans (16.7%), 9963 were Asians (7.1%), 4398 were of other races (3.2%), and 12546 were of unknown race (9.0%). The frequency of including racial data was 100% in Phase 1 studies, 56.5% in Phase 2, 58.1% in Phase 3, and only 16% in Phase 4. A total of 185 were immunotherapy trials, out of which 63 studied chemotherapies, radiotherapy and/ or surgery along with immunotherapy. Racial enrolment data was reported in 68.6 %, 58% and 59.3% in immunotherapy, chemotherapy, and radiotherapy interventions respectively. The ERs of whites, blacks, and Asians were 0.8, 1.3, and 0.9, respectively (Table). However, ER in subgroups with specific interventions, such as chemotherapy, immunotherapy, and radiotherapy, were 0.5, 0.4, and 0.6, respectively. Conclusions: African Americans are underrepresented in CRC intervention trials. Equal access and tailored strategies for cultural and linguistic differences are needed for fair participation. [Table: see text]

Creating and establishing a sustainable culture of clinical and translational research at an academic cancer center.

e23220 Background / Objectives: At the Ellis Fischel Cancer Center (EFCC) at the Univ. of Missouri (MU) School of Medicine (SOM), our recent (2016 - 2020) accurals to interventional oncology clinical trials (CT) have been suboptimal. Hence, the EFCC research leadership undertook a number of initiatives since 2021 to improve the function and productivity of the oncology CT enterprise. The objective of our retrospective review was to determine the impact of our initiatives including improving enrollments to clinical trials. Methods: These major programmatic initiatives have included the following: (1) CT portfolio analysis; (2) faculty survey to assess concerns/ needs related to enrollment; (3) Development of a "One-Pager" list of open CT; (4) Working with faculty leader "champions"; (5) Increasing the number of clinical research staff; (6) Initiation of a monthly "Clinical Trials Working Group (CTWG)" to monitor enrollment to clinical trials, troubleshooting obstacles to accruals and on-going CT portfolio analysis and adjustments; (7) Development of multi-disciplinary "Disease Working Groups" (DWGs) in Breast, GU, GYN-Onc., Lung, GI and CNS cancers to establish a Protocol Review &amp; Monitoring System (PRMS) with the objective of aligning our clinical trials with our patient population; (9) Initiation of a monthly “Investigator Education Workshop” (IEW) to educate our faculty on the conduct of investigator initiated CT and pharma sponsored CT; (10) Initiation of a "Top Enrolling Ceremony" to honor the top enrollers to clinical trials. Results: The analysis of our CT portfolio revealed that in both December 2020 and May 2021, more than half [i.e., 52% (n = 17/33 and n = 13/25, respectively] of our CT had never enrolled a patient in the lifetime of the protocol. Since the implementation of the PRMS in late 2021, we have observed a continual decrease in the status of those clinical trials with “never” any enrollments from a historical average of 52% to 34% in January 2022, to 32% in January 2023 and to 28% in October 2023, p = 0.0173. In addition, implementation of the PRMS also had an immediate significant impact such that only 53% of all of the protocols reviewed by the Protocol Review and Monitoring Committee were approved in 2021 vs. a historical average of 75% from 2018 - 2020. Moreover, between 2021 and 2023, an average total of 82 patients were enrolled to interventional oncology clinical trials vs. the historical average of 42 patients per year from 2016- 2020, representing an overall increase of 95% p = 0.0004. Conclusions: The development and establishment of the PRMS within the last 3 years has had a very positive impact on our clinical trial enterprise at the EFCC by reducing active clinical trials that are not suitable for our patient population and significantly increasing our enrollment to interventional oncology clinical trials. For 2024, we will continue our implementation of the PRMS at the EFCC.

Racial/ethnic distribution of participants in NRG oncology clinical trials: 2014-2023.

e13706 Background: External validity and applicability of clinical research relies upon characteristics of trial participants matching those of the respective disease groups in the general population. Understanding the racial/ethnic distribution of patients enrolled in recent US-based, federally sponsored Phase II and III clinical trials could inform strategies to further align characteristics of trial participants with those of disease group populations. As such, we report the racial/ethnic distribution of participants in NRG Oncology studies during 2014-2023 and compare the distribution to that from the Surveillance, Epidemiology, and End Results (SEER) program data during 2014-2020 (most recent data available). Methods: Proportions of self-reported race/ethnicity were summarized for the 33,370 trial participants enrolled since Mar 1, 2014 (NRG Oncology inception) to therapeutic, symptoms management, and other interventional trials. SEER proportions were used to benchmark NRG trials for representativeness of disease burden in the population. Results: Among NRG trial participants, 71.5% were non-Hispanic (NH) White, 9.7% NH Black, 4.9% Hispanic, and 7.8% N-H Asian (Table). Examining distributions within selected cancer sites relative to cancer proportional incidence in 2014-2020 SEER data, NRG accrual to prostate, lung, cervix, and breast cancer trials is commensurate with observed disease burden for NH Blacks and modestly lower for Asians. For other sites shown, representation was 2 to 5 percentage points lower than SEER frequencies for Blacks and Asians. For all sites, accrual of individuals of Hispanic background was lower than that reported in SEER. As the NRG trials do not reflect sampling across stages and other features of a given cancer in the population, further analysis to be presented will consist of more detailed breakdowns of trial participant disease-specific cancer stage and tumor subtype and comparison to relevant observations from the 2014-2020 SEER database. Conclusions: This high-level comparison of the racial/ethnic distribution of NRG trial participants provides supportive information for population representative enrollment in several cancer sites, but also identifies opportunities to improve enrollment diversity to represent more closely the respective affected population. Areas of success identified merit further investigation to understand if there are best practices which may be applied more broadly towards expanding access to federally funded clinical trials. [Table: see text]

Ultra-sensitive ctDNA mutation tracking to identify molecular residual disease and predict relapse in patients with early breast cancer.

1010 Background: Circulating tumor DNA (ctDNA) based detection of Molecular Residual Disease (MRD) in breast cancer patients presents a strategy to identify patients at high risk of relapse, although current assays have limited sensitivity for low level ctDNA detection. In this study we profile early breast cancer patients with an ultra-sensitive, whole genome sequencing-based, tumor-informed ctDNA platform, and correlate the findings with clinical outcomes. Methods: We analysed 598 plasma samples (median 8 samples/patient, range 2-14) from 76 patients with early breast cancer (23 TNBC, 33 HER2+, 16 HR+ and 4 unknown) enrolled in the ChemoNEAR study. Samples were collected at diagnosis before therapy, at Cycle 2 of neoadjuvant chemotherapy (NAC), post-surgery after neoadjuvant therapy if administered, and every 3 months during follow-up for the first year, and subsequently every 6 months for up to five years. Plasma cfDNA was analysed using the NeXT Personal ctDNA based MRD platform, a tumour-informed approach leveraging whole-genome sequencing of tumor and normal samples to produce personalised ctDNA sequencing panels, with each bespoke panel consisting of up to ~1,800 selected variants that enable ultra-sensitive MRD detection. MRD detection was correlated with clinical outcomes and histopathological data. Results: We detected a broad range of ctDNA levels ranging from 204,900 PPM to 2.2 PPM (median 296 PPM). 40% of all ctDNA detections were in the ultra-low range of &lt;100 PPM. 97.8% (45/46) of patients had ctDNA detected at baseline prior to treatment, including 100% TNBC, 100% HER2+, and 83% of HR+ patients. At a median follow-up of 76 months (range 5-113) from study entry, detection of ctDNA associated with high risk of future relapse (HR undefined, p&lt;0.0001; log-rank test) and shortened overall survival (p&lt;0.0001; log-rank test) with median lead-time from ctDNA detection to clinical relapse of 12.5 months (range 1-60). MRD was identified in 100% (10/10) of patients who relapsed. Of the relapsed patients, the median level of ctDNA at first MRD detection was 18.5 PPM. No ctDNA undetected patients relapsed throughout follow up (58/58). Three patients had ctDNA detected in follow-up but had not relapsed at the time of data cut off. For patients that were ctDNA undetected at post-surgical landmark, 94% (31/33) patients did not relapse. Conclusions: NeXT Personal detected breast cancer relapse with a long lead-time over clinical relapse, and strongly associated with relapse free survival. The assay demonstrated high rates of ctDNA detection at diagnosis. The strong negative predictive value at landmark suggests potential use in de-escalation studies. Several prospective, interventional trials are being conducted to assess whether treatment based on MRD detection improves outcome.

Characterization of social determinants of health in patients considered for participation in treatment clinical trials at a community cancer center serving the Great Plains.

e13704 Background: Avera Cancer Institute, a community-based cancer network comprised of six rural cancer centers in SD and MN, provides care to a five-state region in the upper mid-west covering 72,000 square miles and offers several clinical trials to patients to offer access to advanced treatment for malignancies. Malignances are known to disproportionally affect patients that are older, rural, minorities, and have lower socioeconomic status, which are all less likely to enroll into clinical trials. Methods: Patients evaluated for participation in clinical trials from 2018-2022 were identified in an institutional database. Trial type was designated as either a treatment or nontreatment trial. Status of trial involvement was designated between enrolled or screened. Their demographic information was obtained from the electronic health record (EHR). Demographic information obtained from the EHR includes race, ethnicity, language spoken, gender, employment status, insurance type, and if they live in an urban or rural area as defined by the US Census Bureau. Clinical trial portfolio during this time includes trials for breast, gynecological, gastrointestinal, lung, and hematologic malignancies. Results: 4,397 patients were considered for participation in a clinical trial at our institution in the studied timeframe. Of these patients, 1887 were screened for treatment trials and of that group, 773 were enrolled. 35% of participants considered for clinical trials were from urban areas while 65% considered were rural. 48% of the urban population ultimately were enrolled on a clinical trial while 44% of rural population participated. Participants who lived in an urban area 25-50 miles from our study site had an enrollment rate of 49% compared to rural enrollment of 33%, from 50-100 miles rates of 53% and 37%, from 100-250 miles rates of 29% and 41%, and from greater than 250 miles rates of 44% and 33%, respectively. 99.5% of the population was non-Hispanic, 97% were White, and 99% were English speaking. 74% of the total population were female and 26% were male. Females had an enrollment rate of 51% while males had an enrollment of 29%. Patients with no insurance enrolled in trial 62% compared to 36% of those with commercial insurance The average national Area Deprivation Index percentile for screened patients was 57 vs 59 for enrolled patients. Conclusions: This retrospective study demonstrates a greater likelihood for females, urban patients, and white, English-speaking patients to enroll into clinical trials. Our data also demonstrate a preference for uninsured patients to enroll into clinical trials, possibly due to the financial benefits they may provide. Further directions include comparing our patients considered for clinical trials to all patients treated at our institution to identify potential disparities in care.

Geriatric enrollment patterns in clinical trials at a National Cancer Institute.

e13762 Background: Despite the majority of new cancer diagnoses occurring within the geriatric population, there is a disproportionate rate of clinical trial enrollment within this population. Previous data has estimated enrollment rate to be 18.9% in treatment trials among all adult cancer patients at designated National Cancer Institute Cancer Centers. The objective of this study is to assess geriatric cancer patient clinical trial enrollment rates in a single National Cancer Institute and highlight inequities within cancer care delivery. Methods: We performed a retrospective review of the electronic health record and included patients with cancer ≥ 65 years of age who died at our institution between January 2020 and July 2022. We examined the relationship between cancer type, patient race/ethnic identity, and age and analyzed enrollment in clinical trials. Analyses were conducted using descriptive statistics. Results: Of 117 decedent records analyzed, 11 (9%) were enrolled in treatment clinical trials of which 5 (4.3%) identified as White, 4 (3.4%) Other, and 2 (1.7%) Hispanic. Among the 117 geriatric patient records reviewed, there were 21 Black patients (17.9%) of which 0 (0%) Black patients were enrolled in clinical trials. In comparing enrollment by malignancy type, 5 patients had a hematologic malignancy (leukemia, lymphoma, or multiple myeloma), 3 patients had a genitourinary malignancy, 1 patient had a pancreatic malignancy, 1 patient had an endometrial malignancy, and 1 patient had a breast malignancy. Among all patients analyzed, 37 patients (31.6%) had a hematologic malignancy and 80 patients (68.4%) had a solid tumor malignancy. The average age of enrolled patients was 73, consistent with the average age of all patients analyzed (73.78). Conclusions: Geriatric patients with cancer are disproportionately underrepresented in treatment clinical trials. The inequity is exacerbated when analyzing enrollment among minoritized patients. There was a greater proportion of clinical trial enrollment in patients with hematologic malignancies than solid tumor malignancies, however analysis in larger population samples is necessary. Additional research to identify barriers to clinical trials and methods of increasing geriatric enrollment, including the use of geriatric specific performance scales, is necessary to ensure equitable access and representation in clinical trials. While these results may be skewed in the setting of the COVID-19 pandemic and selection of a decedent population, further research into geriatric accessibility in clinical trials is paramount.

Start low, go slow: A systematic review and meta-analysis of upfront tailored treatment dosing in older adults with advanced cancer.

1625 Background: Older adults aged ≥65 with advanced cancer are underrepresented in treatment trials. This gap limits informed decision-making regarding the dose and tolerability of proposed therapies. Standard chemotherapy is associated with &gt;50% serious adverse event rate among older adults, with frequent dose reduction and early treatment discontinuation. A "start low, go slow" (SLGS) approach begins systemic therapy at lower-than-standard doses and increases the dose if well-tolerated. This alternative dosing strategy has shown value in minimizing adverse events and functional decline without compromising the overall effectiveness of treatments. We conducted the first systematic review and meta-analysis of SLGS effectiveness among older adults across advanced cancers. Methods: This review, was registered with PROSPERO and adhered to PRISMA criteria, covering PubMed, Journal of Geriatric Oncology and EMBASE from January 2000 until December 15, 2024. Eligible study designs were randomized controlled trials, retrospective trials, and non-randomized clinical trials with patients with advanced cancers who underwent systemic therapy. We reported all studies that studied the SLGS approach. Our studied outcomes were overall survival (OS), progression-free survival (PFS), treatment discontinuation, and toxicity. Data extraction included author, patient, cancer type, treatment, and survival outcomes. A meta-analysis using fixed effects and risk ratios (RR) was performed when sufficient data was available; significant outcomes had α&lt;0.05. Results: Our search identified 13 studies testing SLGS strategies in oncology, including 3,508 patients, with a median age 63-78 years. The -represented cancers included colorectal (6 studies, 3059 patients total), lung (2 studies, 113 pts), chronic myeloid leukemia (2 studies, 127 pts), non-Hodgkin lymphoma (1 study, 45 pts), and prostate (2 studies, 164 pts) cancers. Ten (77%) studies assessed OS and PFS. Five studies (39%) compared SLGS against standard doses, finding no significant differences in PFS and OS across all trials. Dose escalation rates for SLGS ranged from 5% to 60%. The ability to complete planned cycles was higher with SLGS compared to standard dose (1 study, 43% vs 26%, p=0.04). Treatment discontinuation was not different for SLGL vs. standard dose (5 studies, meta-analysis RR 1.07, 95% CI 0.90-1.27, p=0.42). Toxicity ranged from 5% to 89% across studies; SLGS had lower grade ≥3 adverse events compared to standard dose (4 studies, meta-analysis RR 0.88, 95% CI 0.80-0.94, p &lt; 0.001). Conclusions: This is the first systematic review and meta-analysis analyzing the SLGS approach to systemic therapy dosing in older adults with advanced cancer. Compared to standard-dose systemic therapy, older adults pursuing a SLGS strategy had greater completion of planned cycles, reduced toxicity, and similar survival.

SNF-CLIMEDIN: A prospective randomized trial of digital intervention in patients with advanced NSCLC—A HeCOG study.

1520 Background: The purpose of this trial is to investigate the effectiveness of online digital intervention to NSCLC patients in terms of quality of life (QoL), cost and the interrelation with clinical and molecular characteristics. Methods: This prospective randomized trial recruited 200 advanced NSCLC patients (3/22-10/23). All had NGS tissue analysis for 161 genes and received standard treatment (predominantly immuno-chemotherapy). Through the CareAcross online platform they received information about their disease and treatment, and periodically reported any of 22 preplanned adverse events (AEs). Patients were randomized 1:1 in the intervention (A) and control (B) arm; patients in arm A received digitally, additionally, evidence-based guidance for the reported AEs. The study was designed to assess QoL improvement (measured per patient as reduction of the number of AEs reported at last contact, compared to those previously reported). EQ5D-5L scores were collected. Patient-case level hospitalizations data were collected and costs were estimated based on reimbursed costs as defined by the Ministry of Health. Results were correlated with patients’ clinical and molecular characteristics. Results: Clinical and molecular characteristics will be presented during ASCO Congress. For all patients, responses were: CR: 2%, PR: 35.5%, SD: 35%, PD: 10.5%. Median PFS was 7.0 months (95%CI: 5-8), 1-year 18% (38%-55%). Median OS: 12 months (11-14), 1-year 47% (38%-55%). No difference was found between the two arms in any of the above, nor in OS in relation to clinical and molecular characteristics. The most common AEs that patients reported were fatigue, cough, anorexia, nausea. More patients submitted AE reports online than their clinicians (89% vs 68% of patients, p&lt;0.01); more AEs were reported per submission, compared to their clinicians. Patients in arm Α reported marginally higher improvement compared to B (77.2% vs 75.7%); 15 of 22 AEs were associated with higher (14) or same (1) improvement in arm A vs B (not statistically significant); of the most common: fatigue (61.3% vs 48.6%), anorexia (86.5% vs 70.2%; p&lt;0.05) and nausea (93.0% vs 87.2%). Baseline EQ5D was similar in both arms; comparing post-treatment (6th cycle) results shows higher improvement in all 5 dimensions in arm A vs B, especially in Anxiety/Depression (final values: 1.9 vs 2.2). The mean AE-related costs in Euros in arm A vs B were: hospitalization: 455.4 (95%CI: 91.9-941.5) vs 779.5 (346.6-1328.5) (p&lt;0.001); diagnostics: 20.3 (0.5-50.8) vs 73.3 (1.3-186.1) (p&lt;0.001). Follow up is ongoing. Conclusions: Digital oncology is feasible, cost-effective by reducing hospitalizations, improves certain AEs and tends to improve QoL of NSCLC patients regardless of clinical and molecular status. Patients report digitally more informative AEs for clinical and research analysis. Online platforms can complement the Oncology team. Clinical trial information: NCT05372081 .