Pre-specified Goal Research Articles

P1207 Therapy goals and Quality of Life among older patients with Inflammatory Bowel Disease: results of an international EFCCA survey

Abstract Background The number of older patients with Inflammatory Bowel Disease (IBD) is rapidly growing, however they are underrepresented in research. To enhance more personalized and patient-centered care, it is important to study the disease burden and therapy goals of this population. Therefore, the aim of this study was to explore prioritized therapy goals, clusters of therapy goals and determinants of quality of life (QoL) in older patients with IBD. Methods This was an international, anonymous, online survey in older patients (age ≥ 60 years) with IBD, proposed and conducted by the European Federation of Crohn’s and Ulcerative Colitis Associations (EFCCA), between May 2023 and November 2023. Patients were asked to select three out of twelve pre-specified therapy goals. A cluster analysis was performed to identify patterns or combinations of therapy goals that were reported together, using a binary distance and an agglomerative clustering algorithm. QoL was assessed by one question about general well-being (five-point Likert scale). We assessed the influence of the therapy goal clusters on QoL by an ordinal regression model adjusting for common confounders. Results Of 1997 included respondents from 34 countries, with a median age of 66 years (IQR 63-71), 297 (14.8%) reported poor-terrible QoL. Older patients with IBD most often prioritized therapy goals related to decreasing fatigue (56%), preserving/restoring a good mood (43%) and decrease diarrhea/incontinence (32%). Six clusters of therapy goals were identified and labelled: 1 - Inflammation control, 2 - IBD-symptom control, 3 - Mobility capacity, 4 - Bodily perception, 5 - Mood and energy, 6 - Activity engagement. The proportion of patients with very well QoL was highest in cluster 6 (60%) and the lowest in cluster 2 (17%). Low QoL was independently associated with therapy goal clusters related to Inflammation control (adjusted Odds Ratio (aOR) 1.86 95% confidence interval (95%CI): 1.24-2.77), IBD-symptom control (aOR: 3.19, 95%CI: 2.13-4.79), Mobility capacity (aOR: 2.14, 95%CI: 1.41-3.24) and Mood and energy (aOR: 1.82, 95%CI: 1.19-2.78), compared to the Activity engagement cluster. Conclusion Older patients with IBD prioritize therapy goals focused on reducing fatigue, improving mood and decreasing diarrhea/incontinence. Low QoL was significantly associated with therapy goal clusters emphasizing inflammation control, IBD symptoms, mobility, and mood/energy. These results are indicative for the need to evaluate the QoL in older patients with IBD in the context of their therapy goals.

Clinical and dosimetric feasibility of sparing submandibular gland in patients with oral cavity squamous cell carcinoma

Background To investigate the incidence of submandibular gland (SMG) involvement and explore the feasibility of sparing SMG in the oral cavity squamous cell carcinoma (OSCC). Methods This study retrospectively analyzed patients between January 2018 to October 2022. Ten patients with tongue squamous cell carcinoma receiving postoperative radiotherapy were replanned to investigate the feasibility of sparing SMG. The dose constraint for the SMG was a mean dose (Dmean) <39 grey (Gy). Results A total of 238 patients were identified and 105 had metastatic neck lymph nodes. Level II was the most common site of metastasis (n = 94, 89.5%), followed by level IB (n = 37, 35.2%), level III (n = 26, 24.8%), level IA (n = 3, 2.6%), and level IV (n = 2, 1.9%). A total of 50 metastatic lymph nodes were located at the level IB, of which 18 (36.0%), 29 (58.0%), and 3 (6%) were located in the lateral, anterior, and inferior aspect of the SMG. No metastatic lymph nodes were found within or on the medial aspect of the SMG. The Dmean of the SMG was <39 Gy in all patients with a Dmean of 38.8 Gy. The median dose of PTV54 D95% was 53.8 Gy, which met the prespecified allowable coverage goal. Conclusions Our study suggests that SMG involvement is rare in OSCC. With strict imaging and clinical evaluation, sparing SMG during radiotherapy is feasible.

Feasibility and acceptability of a parent-child intervention to improve step count in childhood cancer survivors exposed to cardiotoxic therapy: The STEP UP for FAMILIES Study.

Late morbidity after childhood cancer may be mitigated by healthy lifestyle behaviors. We piloted a game-based, parent-child digital intervention to increase activity in sedentary survivors. Survivors aged 10-16 treated with cardiotoxic therapy and not meeting US physical activity guidelines were enrolled in a single-arm study with a parent. Following a 14-day run-in, participants chose a prespecified step goal and wore an accelerometer daily for 24weeks (12-week game-based intervention; 12-week follow-up). Participants completed the Acceptability of Intervention Measure (AIM) at 24weeks; a subset of dyads completed qualitative interviews. Among 129 eligible survivors, 27 enrolled (20.9% participation rate) with a parent. Four dyads were removed during the 14-day run-in period due to noncompliance. Among the 23 dyads who continued to the study, the tracker was worn for 95% of days during the 12-week intervention (95% confidence interval [CI]: 94-96) and 81% during the 12-week follow-up (95% CI: 79-82). Overall, the prespecified step goal was met for 64% (95% CI: 63-66) of days during the intervention and 37% (95% CI: 35-38) during the follow-up. At the end of study, 17/23 dyads responded to AIM; 82% of survivors and 94% of parents reported the intervention as acceptable. During qualitative interviews (n=5), dyads noted that they liked the accountability of the "buddy system," but would have liked more personalized goal-setting. Despite high ratings of acceptability among participants, difficulties with sustained adherence and retention were encountered in this parent-child gamification intervention. Alternate, tailored designs should be considered in the future.

Rating writing: Comparison of holistic and analytic grading approaches in pre-service teachers

BackgroundIn a typical instructional setting, teachers are responsible for making ongoing decisions that involve judgments of students’ capabilities, knowledge, learning needs, and progress toward a certain pre-specified goal. However, there is a significant within-teacher as well as a great between-teacher variability in the actual determination of grades. Grades appear to be an amalgam of characteristics of a student, filtered through a range of teacher personality variables. AimsThe purpose of this study was to investigate the extent to which pre-service teachers agreed on students’ grades in writing task between holistic and analytic grading approaches and how their individual characteristics and beliefs about features of assessment explained the variability in grading practices. SampleTeacher candidates (N = 231, 65% female) enrolled in a training program in 2020 and 2021 cohorts at the University of València, Spain, were asked to read two essays, identified by experts as being of low and high quality, and assign holistic and analytic grades. Resultsalthough teacher candidates provided grades consistently across the two approaches (intra-individual differences), there was a high variability in the distribution among participants (inter-individual differences). We found that, gender, area of specialization, attitudes toward feedback, and extraversion were significant predictors of grading variability. ConclusionThis study highlights the considerable variation in grading practices among pre-service teachers, indicating the influence of individual factors such as gender, specialization, feedback receptivity, and extraversion. Despite consistent grading within specific approaches, the inter-individual differences in scores were substantial. Due to the consequential nature of teacher grades, our findings offer important insights and have critical implications for teacher preparation and professional development programs.

Intralesional administration of L19IL2/L19TNF in high-risk locally advanced basal cell carcinoma or cutaneous squamous cell carcinoma.

TPS9617 Background: Basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC) account for 99% of skin neoplasms, with a rising incidence due to increased sun exposure and growing life expectancy. Approximately 0.8-5% of patients (pts) develop high-risk locally advanced (LA) disease, which is treated with surgery, radiotherapy, sonic hedgehog inhibitors, PD1-based immune checkpoint blockade, or chemotherapy. While surgery offers high cure rates, factors such as location, functional and cosmetic impairment, or patient factors including age, comorbidities, and personal preferences may preclude surgery. Intralesional treatment with immunostimulatory drugs represents an attractive therapeutic approach to treat LA BCC and LA cSCC. Here, we investigate a combination of two immunocytokines (Bifikafusp alfa (L19IL2) and Onfekafusp alfa (L19TNF)) targeting the extradomain B of fibronectin (EDB) for the treatment of high-risk locally advanced BCC and cSCC. EDB is an oncofetal antigen that is undetectable in virtually all healthy adult tissues but becomes highly expressed in tumors, including BCC and cSCC. Methods: In a single-arm phase II study (NCT04362722), pts with locally advanced, non-metastatic, node-negative, single, or multifocal BCC or cSCC not eligible for surgery or radiotherapy are treated with four weekly intratumoral administrations of L19IL2/L19TNF. The study is divided into two parts: a first exploratory part with a total of 40 pts with laBCC or lacSCC, and a second part where the laBCC cohort has been expanded to up to 72 pts not eligible for surgery or radiotherapy. The first part of the trial has been completed with 28 laBCC pts and 12 lacSCC pts evaluable for safety and efficacy. The pre-specified activity goal for the first stage of accrual was met, and the second stage of accrual began in September 2023, with a total of 39 BCC and 18 cSCC pts enrolled so far. Clinical trial information: NCT04362722 .

Establishing a protocol to increase racial/ethnic minority enrollment on an active radiation oncology randomized clinical trial.

TPS1638 Background: In the United States (US), underrepresented racial/ethnic groups lack ample enrollment in clinical trials, yielding ungeneralizable trial results. Barriers to increasing minority enrollment include decreased awareness of clinical trials, lack of access, financial burden and toxicity, medical system mistrust, and discordant physician-patient demographics. The ongoing Spine Patient Optimal Radiosurgery Treatment for Symptomatic Metastatic Neoplasms (SPORTSMEN) clinical trial (NCT05617716) has a study design to actively accrue minority patients. We present our protocol addressing key targets to increase minority enrollment on this randomized, phase II clinical trial. Methods: Adults with evidence of symptomatic spine metastases are eligible. Baseline demographics (including race/ethnicity) are reported for statistical analysis. Our protocol seeks to minimize barriers to minority enrollment and targets four key areas. Access to care: SPORTSMEN involves institutions located in zip codes with diverse ethnic populations, presently located in regions 46% and 70% African American. Clinical trial design: SPORTSMEN has a prespecified goal of accruing patients to mirror US census representation. The rate of minority enrollment will be reviewed periodically at the discretion of the Data Safety and Monitoring Board. Community outreach and engagement: The trial team will engage with local health care systems to create an alliance within different oncology specialties to provide the basis and benefit for SPORTSMEN and patient-centered education on eligibility criteria, rationale, and intended outcomes. Our principal focus will be providers in prostate, breast, and lung cancers as minorities with these primary site malignancies have a higher propensity to be trial-eligible. Furthermore, we understand the historical mistrust of minorities for the medical community. Therefore, we will engage local grassroot organizations such as churches, community outreach centers, and social clubs to increase awareness of clinical trials and to help foster trust. Financial burden and toxicity: SPORTSMEN does not have direct enrollment costs. A short-course treatment regimen is used to minimize the number of treatment visits required allowing for decreased resources for travel, time lost at work, and additional childcare or eldercare needs. Financial toxicity will be objectively quantified using the validated COST-Functional Assessment of Chronic Illness Therapy survey. Increasing clinical trial diversity is a challenge that must be addressed with meaningful intent to present robust Level 1 data that broadens the understanding of treatment response in all demographics. Our protocol takes a patient-centered approach to achieve the objective of concordant racial/ethnic representation in a randomized clinical trial. Clinical trial information: NCT05617716 .

A Modular Communicative Leadless Pacing–Defibrillator System

BackgroundThe subcutaneous implantable cardioverter–defibrillator (ICD) is associated with fewer lead-related complications than a transvenous ICD; however, the subcutaneous ICD cannot provide bradycardia and antitachycardia pacing. Whether a modular pacing–defibrillator system comprising a leadless pacemaker in wireless communication with a subcutaneous ICD to provide antitachycardia and bradycardia pacing is safe remains unknown.MethodsWe conducted a multinational, single-group study that enrolled patients at risk for sudden death from ventricular arrhythmias and followed them for 6 months after implantation of a modular pacemaker–defibrillator system. The safety end point was freedom from leadless pacemaker–related major complications, evaluated against a performance goal of 86%. The two primary performance end points were successful communication between the pacemaker and the ICD (performance goal, 88%) and a pacing threshold of up to 2.0 V at a 0.4-msec pulse width (performance goal, 80%).ResultsWe enrolled 293 patients, 162 of whom were in the 6-month end-point cohort and 151 of whom completed the 6-month follow-up period. The mean age of the patients was 60 years, 16.7% were women, and the mean (±SD) left ventricular ejection fraction was 33.1±12.6%. The percentage of patients who were free from leadless pacemaker–related major complications was 97.5%, which exceeded the prespecified performance goal. Wireless-device communication was successful in 98.8% of communication tests, which exceeded the prespecified goal. Of 151 patients, 147 (97.4%) had pacing thresholds of 2.0 V or less, which exceeded the prespecified goal. The percentage of episodes of arrhythmia that were successfully terminated by antitachycardia pacing was 61.3%, and there were no episodes for which antitachycardia pacing was not delivered owing to communication failure. Of 162 patients, 8 died (4.9%); none of the deaths were deemed to be related to arrhythmias or the implantation procedure.ConclusionsThe leadless pacemaker in wireless communication with a subcutaneous ICD exceeded performance goals for freedom from major complications related to the leadless pacemaker, for communication between the leadless pacemaker and subcutaneous ICD, and for the percentage of patients with a pacing threshold up to 2.0 V at a 0.4-msec pulse width at 6 months. (Funded by Boston Scientific; MODULAR ATP ClinicalTrials.gov NCT04798768.)

Inclisiran administration potently and durably lowers LDL-C over an extended-term follow-up: the ORION-8 trial.

Data describing the long-term efficacy and tolerability of inclisiran are limited. This was explored in ORION-8, an open-label extension of preceding Phase 2 and Phase 3 placebo-controlled and open-label extension trials. Following completion of the parent trial, adult patients with atherosclerotic cardiovascular disease (ASCVD), ASCVD risk equivalent, or heterozygous familial hypercholesterolaemia received open-label inclisiran twice yearly (after initial and 3-month doses) until Day 990, followed by an end-of-study visit at Day 1080 or ≥ 90 days after the last dose. The study endpoints included the proportion of patients achieving pre-specified low-density lipoprotein cholesterol (LDL-C) goals [ASCVD: < 1.8 mmol/L (< 70 mg/dL); ASCVD risk equivalent: < 2.6 mmol/L (< 100 mg/dL)], percentage and absolute changes in LDL-C at end-of-study, and safety of inclisiran. Of 3274 patients, 2446 (74.7%) were followed until end-of-study. Mean age was 64.9 ± 9.9 years, 82.7% (n = 2709) had ASCVD, and mean baseline LDL-C was 2.9 ± 1.2 mmol/L. Mean cumulative exposure to inclisiran (including parent trials) was 3.7 years; maximum exposure was 6.8 years. With inclisiran, 78.4% [95% confidence interval (CI): 76.8, 80.0] of patients achieved pre-specified LDL-C goals and mean percentage change in LDL-C was -49.4% (95% CI: -50.4, -48.3). No attenuation of LDL-C lowering over time was observed. Treatment-emergent adverse events at injection site (all mild/moderate) occurred in 5.9% of the patients. Inclisiran-associated anti-drug antibodies were infrequent (5.5%) and had no impact on the efficacy or safety of inclisiran. No new safety signals were identified. In the largest and longest follow-up to date with >12 000 patient-years exposure, inclisiran demonstrated consistent and effective LDL-C lowering with a favourable long-term safety and tolerability profile. ClinicalTrials.gov identifier: NCT03814187.

Current treatment goals are achieved by the majority of patients with atopic dermatitis treated with tralokinumab: results from a multicentric, multinational, retrospective, cohort study

ABSTRACT Background Tralokinumab is a human monoclonal antibody targeting interleukin-13 that is approved for the treatment of moderate-severe atopic dermatitis. Studies analyzing the efficacy and safety of tralokinumab in a real-world setting are scarce. Research design and methods A European, multicentric, real-world, retrospective cohort study was defined to assess the effectiveness and safeness profile of tralokinumab, investigating the achievement of pre-specified treatment goals; and to detect potential differences in terms of effectiveness and safeness across some selected patient subcohorts. Results A total of 194 adult patients were included in this study. A significant improvement in physician-assessed disease severity was detected at each follow-up visit as compared with baseline and similar trend was observed for patient-reported outcomes and quality of life. No meaningful difference in effectiveness was found when considering patient age (<65 versus ≥65 years), neither dissecting patient cohort in dupilumab-naive vs dupilumab-treated subjects. Among tralokinumab-treated patients, 88% achieved at least one currently identified real-world therapeutic goal at week 16. Conclusions This retrospective multicenter study confirmed the effectiveness and safeness of tralokinumab throughout 32 weeks of observation, showing the achievement of therapeutic goals identified in both trial and real-world settings in a large proportion of tralokinumab-treated patients.

Early Experience with CBCT-Guided Online Adaptive Radiotherapy for Muscle Invasive Bladder Cancer.

Radiation therapy for muscle-invasive bladder cancer (MIBC) requires substantial planning target volume (PTV) margins to account for variability in bladder filling as well as other anatomic changes. We hypothesized that CBCT-guided online adaptive RT (oART) may both improve target coverage and reduce normal tissue exposure as compared to non-adaptive RT. The purpose of this study is to report the dosimetric results of our initial experience utilizing oART for treatment of MIBC. Seven patients with MIBC were treated with oART over a 1-year period. Patients were simulated with an empty bladder and were asked to void prior to each treatment. Five patients received 55 Gy in 20 fractions to a clinical target volume (CTV) expanded from the TURBT bed and 46 Gy simultaneously to the remaining bladder and for 2 patients the high dose CTV was the entire bladder. PTVs consisted of a 7mm isometric expansion of the CTV. The oART delivery process initially coregisters the daily CBCT to the treatment planning CBCT using skeletal alignment. Target volumes and organs-at-risk (OARs) were modified at each treatment session and the plan re-optimized to meet prespecified clinical goals. Target coverage and OAR dosimetric parameters for the adaptive were compared non-adaptive (scheduled) plan for each fraction using the Wilcoxon paired test of means. The adapted plan was selected for delivery for all fractions across all patients. Daily bladder volumes differed from the bladder volume at simulation by a mean of 60cc ± 66cc. At least 95% of the high dose CTV was covered by the prescription dose for 139 (99.3%) fractions with the oART plan as compared to 70 (50%) fractions with scheduled. A portion of the high dose CTV was outside of the 80% isodose line for 13 (9.3%) of scheduled fractions and was outside of the 50% isodose line for 2 (0.01%) of scheduled fractions. There were no cases of oART plans where any portion of the high dose CTV was outside of the 90% isodose line. A comparison of selected target and OAR dosimetric parameters is shown in the Table. oART treatment plans were associated with greater target coverage and less OAR exposure for all metrics. In this initial experience, oART resulted in acceptable delivered dosimetry to target volumes with a reduced PTV margin of 7mm despite considerable daily variation in bladder volume. As expected, oART plans were associated with improved target coverage and OAR dosimetry. Future patient-centered studies should explore the clinical impact of reduced margin oART for patients with MIBC.

Early Clinical Experience of Utilizing Online Adaptive Radiotherapy for Accelerated Partial Breast Irradiation with Stereotactic Body Radiation Therapy for Early-Stage Breast Cancer Patients

Accelerated partial breast irradiation (APBI) with stereotactic body radiation therapy (SBRT) is becoming popular for early-stage breast cancer (ESBC) due to decreased treatment time and dose to healthy breast tissue. With variability in lumpectomy cavity size post-surgery, CBCT-guided online adaptive RT (oART) may improve target coverage and reduce normal tissue exposure by accounting for inter- and intrafractional cavity variations. In this study, we report our initial clinical experience utilizing APBI oART for patients with ESBC. A total of 15 patients with 17 ESBC cavities (2 with bilateral disease) were treated with SBRT using oART over one year. Patients were immobilized using standard breast simulation setup with free breathing and breath hold (if left sided). The clinical target volume consisted of an isometric 1 cm expansion off the lumpectomy cavity, which was expanded another 3 mm (cropped 3mm from surface) to create the planning target volume (PTV). 95% of the PTV received prescription dose (30 Gy in 5 fractions). The oART delivery process (supervised by physician and physicist) initially coregisters the daily CBCT to the treatment planning CT with alignment to lumpectomy cavity. Target volumes and organs-at-risk were modified at each treatment and the plan re-optimized. Either the re-optimized oART plan or scheduled plan was chosen for each fraction pending which plan best met prespecified clinical goals. Acute toxicity was assessed at one-month follow-up using CTCAE. Patients were age 56 or older, ECOG 0-1, with no known genetic abnormality, and with anatomic stage 0-1A ESBC. Most tumors were located in the upper outer quadrant (n = 12, 70.6%) at middle or posterior depth (n = 15, 88.2%). Final margins were negative. 88% had tantalum clips placed. One patient had an Oncotype DS score of 34 and received systemic therapy. 82.3% met suitable APBI criteria and 3 met cautionary criteria due to high grade, of which 2 had ipsilateral trimodality treatment 10+ years prior and denied mastectomy at recurrence. Mean time to starting RT after lumpectomy was 2.5 months. Mean PTV to breast ratio was 0.12. From simulation to end of treatment, lumpectomy cavity size decreased a median of 27%. oART plans were chosen 89% of the time. VMAT was utilized 52.9% of the time compared to static-field IMRT (47.1%). Three patients were treated with breath hold. 93% of patients were treated on non-consecutive days with average treatment lasting 9.1 ± 2.2 days. CTCAE grade 1 toxicities were hyperpigmentation (n = 6, 40%), breast pain (n = 2, 13.3%), persistent seroma (n = 1, 6.7%), and fatigue (n = 7, 46.7%). No patients experienced fat necrosis, telangiectasias, breast shrinkage, lymphedema, or CTCAE grade 2+ toxicities. oART for APBI using SBRT for patients with ESBC is clinically feasible and allows for variations in lumpectomy cavity size. Nearly half of patients had no complaints or breast changes at one-month follow-up and the remaining had CTCAE grade 1 toxicities alone.

Neoadjuvant carboplatin in triple-negative breast cancer: results from NACATRINE, a randomized phase II clinical trial

BackgroundNeoadjuvant chemotherapy (NACT) is the mainstay of treatment of stages II and III triple-negative breast cancer (TNBC). This study aims to evaluate if the addition of carboplatin to NACT is associated with an increase in the pathological complete response (pCR) rates in TNBC.MethodsWe conducted an open-label phase II randomized clinical trial in a single center in Brazil. Patients with stage II and III TNBC were randomized to receive standard NACT with or without carboplatin. All the patients received doxorubicin (60 mg/m2) plus cyclophosphamide (600 mg/m2) both intravenously (i.v.) q21 days for four cycles. Patients were then randomized for additional treatment with weekly (wk) paclitaxel (80 mg/m2 i.v., for 12 cycles) plus wk carboplatin AUC 1.5 (experimental arm) or without wk carboplatin (control arm). Randomization was stratified according to gBRCA status, age, and AJCC 8th edition clinical stage (II vs. III). The primary endpoint was the pathologic complete response (pCR) rate. Secondary endpoints included recurrence-free survival and overall survival.ResultsBetween 2017 and 2021, 146 patients were randomized, 73 on each arm. The median age was 45 years. Most patients (66.4%) had locally advanced stage III disease, 67.1% had T3/T4 tumors, and 56.2% had clinically positive axillary lymph nodes. Germline BRCA status was available for all patients, and 19.9% had pathogenic BRCA1/2 variants. The pCR rate (ypT0ypN0) was numerically increased by 13.7%, being 43.8% (31 of 73 patients) in the experimental and 30.1% (22 of 73 patients) in the control arm, not meeting the prespecified goal of increasing the pCR in 15% (p-value = 0.08). Survival outcomes are immature.ConclusionThe addition of carboplatin to standard NACT in stages II and III TNBC was associated with a non-statistically significant numerical increase in the pCR rate. Follow-up for survival outcomes and translational research initiatives are ongoing.

Implementation of geriatric screening in the emergency department using the Consolidated Framework for Implementation Research.

Implementation of evidence-based care processes (EBP) into the emergency department (ED) is challenging and there are only a few studies of real-world use of theory-based implementation frameworks. We report final implementation results and sustainability of an EBP geriatric screening program in the ED using the Consolidated Framework for Implementation Research (CFIR). The EBP involved nurses screening older patients for delirium (Delirium Triage Screen), fall risk (4-Stage Balance Test), and vulnerability (Identification of Seniors at Risk score) with subsequent appropriate referrals to physicians, therapy specialists, or social workers. The proportions of screened adults ≥65 years old were tracked monthly. Outcomes are reported January 2021-December 2022. Barriers encountered were classified according to CFIR. Implementation strategies were classified according to the CFIR-Expert Recommendations for Implementing Change (ERIC). Implementation strategies increased geriatric screening from 5% to 68%. This did not meet our prespecified goal of 80%. Change was sustained through several COVID-19 waves. Inner setting barriers included culture and implementation climate. Initially, the ED was treated as a single inner setting, but we found different cultures and uptake between ED units, including night versus day shifts. Characteristics of individuals barriers included high levels of staff turnover in both clinical and administrative roles and very low self-efficacy from stress and staff turnover. Initial attempts with individualized audit and feedback were not successful in improving self-efficacy and may have caused moral injury. Adjusting feedback to a team/unit level approach with unitwide stretch goals worked better. Identifying early adopters and conducting on-shift education increased uptake. Lessons learned regarding ED culture, implementation in interconnected health systems, and rapid cycle process improvement are reported. The pandemic exacerbated barriers to implementation in the ED. Cognizance of a large ED as a sum of smaller units and using the CFIR model resulted in improvements.

Postapproval Study of a Subcutaneous Implantable Cardioverter-Defibrillator System

BackgroundThe subcutaneous implantable cardioverter-defibrillator (S-ICD) was developed to avoid complications related to transvenous implantable cardioverter-defibrillator (TV-ICD) leads. Device safety and efficacy were demonstrated previously with atypical clinical patients or limited follow-up. ObjectivesThe S-ICD PAS (Subcutaneous Implantable Cardioverter-Defibrillator System Post Approval Study) is a real-world, multicenter, registry of U.S. centers that was designed to assess long-term S-ICD safety and efficacy in a diverse group of patients and implantation centers. MethodsPatients were enrolled in 86 U.S. centers with standard S-ICD indications and were observed for up to 5 years. Efficacy endpoints were first and final shock efficacy. Safety endpoints were complications directly related to the S-ICD system or implantation procedure. Endpoints were assessed using prespecified performance goals. ResultsA total of 1,643 patients were prospectively enrolled, with a median follow-up of 4.2 years. All prespecified safety and efficacy endpoint goals were met. Shock efficacy rates for discrete episodes of ventricular tachycardia or ventricular fibrillation were 98.4%, and they did not differ significantly across follow-up years (P = 0.68). S-ICD–related and electrode-related complication-free rates were 93.4% and 99.3%, respectively. Only 1.6% of patients had their devices replaced by a TV-ICD for a pacing need. Cumulative all-cause mortality was 21.7%. ConclusionsIn the largest prospective study of the S-ICD to date, all study endpoints were met, despite a cohort with more comorbidities than in most previous trials. Complication rates were low and shock efficacy was high. These results demonstrate the 5-year S-ICD safety and efficacy for a large, diverse cohort of S-ICD recipients. (Subcutaneous Implantable Cardioverter-Defibrillator [S-ICD] System Post Approval Study [PAS]; NCT01736618)

ID: 203617 One-Year Safety Analysis Using DRG-Stimulation for the Treatment of Lower Limbs CRPS I and II

Dorsal root ganglion stimulation (DRG-S) is effective for the treatment of chronic focal pain conditions1 and superior to traditional spinal cord stimulation (SCS) in the treatment of CRPS types I and II (causalgia).2,3 To provide continued evidence of safety after FDA approval, a post-market, prospective, single-arm, observational study in patients with CRPS types I or II of the lower limbs treated with DRG-S was designed (NCT02800863). The primary goal of the study was to show that the proportion of serious adverse effects (SAEs) in subjects who received a permanent implant was lower than a pre-specified goal of 15.5% after 12 months. SAEs were defined as safety-related device and non-device events that result in the subject's death or a serious deterioration in health that is life-threatening, results in permanent impairment, or requires medical intervention and hospitalization. The study descriptive endpoint was the proportion of subjects with device, procedure, or stimulation-related SAEs (SADE) or AE (ADE)

Defibrillation effectiveness and safety of the shock waveform used in a contemporary wearable cardioverter defibrillator: Results from animal and human studies.

The wearable cardioverter defibrillator (WCD) is used to protect patients at risk for sudden cardiac arrest. We examined defibrillation efficacy and safety of a biphasic truncated exponential waveform designed for use in a contemporary WCD in three animal studies and a human study. Animal (swine) studies: #1: Efficacy comparison of a 170J BTE waveform (SHOCK A) to a 150J BTE waveform (SHOCK B) that approximates another commercially available waveform. Primary endpoint first shock success rate. #2: Efficacy comparison of the two waveforms at attenuated charge voltages in swine at three prespecified impedances. Primary endpoint first shock success rate. #3: Safety comparison of SHOCK A and SHOCK B in swine. Primary endpoint cardiac biomarker level changes baseline to 6 and 24 hours post-shock. Human Study: Efficacy comparison of SHOCK A to prespecified goal and safety evaluation. Primary endpoint cumulative first and second shock success rate. Safety endpoint adverse events. Animal Studies #1: 120 VF episodes in six swine. First shock success rates for SHOCK A and SHOCK B were 100%; SHOCK A non-inferior to SHOCK B (entire 95% CI of rate difference above -10% margin, p < .001). #2: 2,160 VF episodes in thirty-six swine. Attenuated SHOCK A was non-inferior to attenuated SHOCK B at each impedance (entire 95% CI of rate difference above -10% margin, p < .001). #3: Ten swine, five shocked five times each with SHOCK A, five shocked five times each with SHOCK B. No significant difference in troponin I (p = 0.658) or creatine phosphokinase (p = 0.855) changes from baseline between SHOCK A and SHOCK B. Human Study: Thirteen patients, 100% VF conversion rate. Mild skin irritation from adhesive defibrillation pads in three patients. The BTE waveform effectively and safely terminated induced VF in swine and a small sample in humans. Human study clinical trial registration: URL: https://clinicaltrials.gov; Unique identifier: NCT04132466.

Trial in progress: A phase II, multicenter, open-label study of PolyPEPI1018 in combination with atezolizumab in participants with relapsed or refractory microsatellite-stable metastatic colorectal (MSS mCRC) cancer (Oberto-301).

TPS283 Background: Colorectal cancer (CRC) is among the top three most commonly occurring cancers globally. CRC is now routinely classified as MSI-high (MSI-H) or microsatellite-stable (MSS) based on the detection or absence of molecular markers of genetic instability, respectively. The efficacy of checkpoint inhibitor immunotherapy in MSI-H CRC has not been replicated in MSS CRC. Therefore, additional interventions are needed to convert immunologically “cold” MSS CRC to “hot” tumors resembling MSI-H tumors. PolyPEPI1018 is an off-the-shelf, multi-peptide vaccine containing 12 immunogenic epitopes derived from 7 cancer testis antigens (CTAs) frequently expressed in patients with CRC. PolyPEPI1018 successfully restored and boosted pre-existing anticancer immunity of MSS mCRC subjects and triggered recruitment and infiltration of cytotoxic T cells into the tumor. In first line metastatic MSS CRC, PolyPEPI1018 in combination with fluoropyrimidine/bevacizumab vaccine was safe and demonstrated early evidence of clinical activity. Therefore, we hypothesized that the combination of PolyPEPI1018 and atezolizumab will convert a “cold” MSS mCRC to a “hot” tumor and may increase the likelihood of inducing favorable antitumor immunity and subsequent clinical benefit. Methods: The study is a phase 2, multicenter, single-arm clinical trial of PolyPEPI1018 vaccine (1.2 mg, sc, every 3 weeks) and atezolizumab (1200 mg, iv, every 3 weeks) for patients with advanced or metastatic MSS CRC who have progressed on 2 or 3 lines of prior standard regimens. 28 patients will be enrolled at 3 US sites with a primary objective to assess the safety and tolerability of multiple doses of PolyPEPI1018 in combination with atezolizumab. Secondary endpoints include objective response rate (ORR) assessed by RECIST v1.1, vaccine induced immunological response rate (IRR), progression-free survival and overall survival. Correlative aims include assessing blood and tissue biomarkers (PD-L1, Immunoscore®IC, ctDNA, clinical tumor markers) for association with clinical benefit. An exploratory study is being conducted for co-development of a companion diagnostic based on HLA-genotype and computational personal epitope (PEPI) prediction test. A Simon 2-stage design will be used for the initial assessment of ORR. If pre-specified activity goal for the first stage of accrual (n = 18) is met, additional 10 participants will be enrolled to the second stage. A formal review of safety will be performed after the initial 6 participants have received at least 2 cycles of study therapy. The study is open with 10 patients enrolled at time of submission. Clinical trial information: NCT05243862 .

Vaccines for all: A formative evaluation of a multistakeholder community-engaged COVID-19 vaccine outreach clinic for migrant communities

BackgroundRacialized, low-income, and migrant populations experience persistent barriers to vaccines against COVID-19. These communities in East and Northeast Calgary were disproportionately impacted by COVID-19, yet faced vaccine access barriers. Diverse multi-stakeholder coalitions and community partnerships can improve vaccine outreach strategies, but how stakeholders perceive these models is unknown. MethodsWe conducted a formative evaluation of a low-barrier, community-engaged vaccine outreach clinic in Calgary, Alberta, Canada, on June 5–6, 2021. We delivered an online post-clinic survey to clinic stakeholders, to assess whether the clinic achieved its collectively derived pre-specified goals (effective, efficient, patient-centered, and safe), to asses whether the clinic model was scalable, and to solicit improvement recommendations. Survey responses were analyzed using descriptive statistics and thematic analysis. ResultsOverall, 166/195 (85%) stakeholders responded. The majority were from non-healthcare positions (59%), between 30 and 49 years of age (87/136; 64%), and self-identified as racialized individuals (96/136; 71%). Respondents felt the clinic was effective (99.2%), efficient (96.9%), patient-centered (92.3%), and safe (90.8%), and that the outreach model was scalable 94.6% (123/130). There were no differences across stakeholder categories. The open-ended survey responses supported the scale responses. Improvement suggestions describe increased time for clinic planning and promotion, more multilingual staff, and further efforts to reduce accessibility barriers, such as priority check-in for people with disabilities. ConclusionDiverse stakeholders almost universally felt that this community-engaged COVID-19 vaccine outreach clinic achieved its goals and was scalable. These findings support the value of community-engaged outreach to improve vaccine equity among other marginalized newcomer communities.

Development of a booster intervention for graded sensorimotor retraining (RESOLVE) in people with persistent low back pain: A nested, randomised, feasibility trial.

Low back pain contributes to an increasing global health burden exacerbated by unsustained improvements from current treatments. There is a need to develop, and test interventions to maintain initial improvements from low back pain treatments. One option is to implement a booster intervention. This study aimed to develop and test the feasibility of implementing a booster intervention delivered remotely to supplement the benefits from a complex intervention for chronic low back pain. This study was nested in the RESOLVE trial. The booster intervention was developed by an expert group, including a clinical psychologist, exercise physiologist and physiotherapists, and based on a motivational interviewing framework. We developed a conversational flow chart to support the clinician to guide participants towards achieving their pre-specified personal goals and future low back pain self-management. Participants with chronic low back pain who were aged over 18years and fluent in English were recruited. The booster intervention was delivered in one session, remotely, by telephone. The intervention was considered feasible if: participants were able to be contacted or <3 contacts were necessary to arrange the booster session; there were sufficient willing participants (<15% of sample unwilling to participate); and participants and research clinicians reported a perceived benefit of >7/10. Fifty participants with chronic non-specific low back pain were recruited to test the feasibility of implementing the booster intervention. Less than three contact attempts were necessary to arrange the booster session, only one participant declined to participate. Participants perceived the session to be beneficial; on a 0 to 10 scale of perceived benefit, the average score recorded was 8.3 (SD 2.0). Clinicians also reported a moderate perceived benefit to the participant; the average score recorded by clinicians was 6.3 (SD 1.6). We developed a step by step, simple booster intervention that was perceived to be beneficial to participants with chronic low back pain. The booster can feasibly be delivered remotely following a complex intervention.

WIN Symposium 2022 - Abstract Poster Presentations.

WIN Symposium 2022 - Abstract Poster Presentations.