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Subglottic stenosis (SGS) may arise from both mechanical and inflammatory airway injury. Patients with mast cell activation syndrome (MCAS) are uniquely vulnerable, due to both direct effects of systemic inflammation and indirect effects of repeated intubation for anaphylaxis that can converge to cause life-threatening airway compromise. We describe a sentinel case of a 34-year-old female with MCAS and multiple prior intubations who presented with progressive dyspnea. Flexible laryngoscopy revealed grade III SGS. She underwent urgent endoscopic intervention, including balloon dilation, carbon dioxide (CO 2 ) laser radial incisions, and steroid injection. Airway patency was restored, and postoperative care focused on optimizing systemic mast cell control with cromolyn, fexofenadine, montelukast, and omalizumab. Literature review supports a mechanistic role for mast cell mediators in airway fibrosis and impaired wound healing, compounding the effects of mechanical trauma in MCAS. This sentinel case highlights clinically significant risk of SGS in patients with MCAS. By integrating case findings with mechanistic insights, this report underscores the urgent need for interdisciplinary awareness, proactive airway evaluation, and research into surveillance and prevention strategies in MCAS and related disorders. Level of Evidence: Level V/Case Report and Narrative Review.

Abstract BACKGROUND: Obesity is prevalent in Hispanic patients (pts) with breast cancer (BC), but this population is often underrepresented in studies of weight loss interventions (WLIs). The BWEL trial (Alliance A011401; NCT02750826) is a phase III randomized trial testing the impact of a 2-year (yr) telephone-based WLI on invasive disease-free survival in pts with stage II-III HER2-negative BC and a body mass index (BMI) > 27 kg/m2. At 12 months (mo), Hispanic pts lost less weight than White pts on the WLI. Here, we evaluate differences in intervention engagement over the first 12 mo by language preference and ethnicity among BWEL pts on the WLI. METHODS: BWEL randomized pts 1:1 to WLI + health education (HE) or HE alone. WLI +HE pts received semi-structured telephone-based health coaching in English or Spanish, in addition to access to an activity monitor, wireless scale and meal replacement shakes. Pts self-reported ethnicity and their preferred language for the WLI. Kruskal Wallis and chi-square tests were used to assess language and ethnicity differences in demographic and treatment factors for continuous and categorical variables, respectively. Percent weight change and mean values for intervention attrition, number of calls, call duration, number of shake shipments, and frequency of activity monitor use and weight tracking over 12 mo were compared between Spanish-preferred Hispanic pts (SH), English-preferred Hispanic (EH) pts and non-Hispanic (NH) pts using ANOVA. Pts with missing language, ethnicity or 12 mo weight data were excluded from analysis. RESULTS: 1591 pts were randomized to the WLI + HE from 08/2018 to 02/2021. 80.5% of pts were White, 12.8% Black and 7.1% Hispanic. 1190 pts had 12 mo weight and language available. Among the 87 WLI + HE pts who had available data and identified as Hispanic, 34% were SH and 66% EH. SH WLI pts were younger (in yrs: 49.5 SH, 51.1 EH, 53.9 NH, p=0.006) and had lower BMI (32.2 SH, 35.1 EH, 34.5 NH, p=0.007). At 12 mo, SH WLI pts lost 2.4% of baseline body weight vs 3.3% in EH and 5.1% in NH (p=0.051) (Table). Compared with EH and NH WLI pts, SH WLI pts participated in fewer calls (15.7 SH, 21.1 EH, 24.3 NH, p< 0.0001), had fewer days of activity monitor use (134.2 SH, 177.3 EH, 205.3 NH, p=0.015) and fewer days of weight tracking (65.3 SH, 96.8 EH, 148.2 NH, p<0.0001), but had more shake shipments (3.9 SH, 3.5 EH, 3.0 NH, p=0.015). There were no significant differences in attrition rate or call duration by language preference or ethnicity. CONCLUSIONS: In a large phase III WLI study in breast cancer patients, engagement with the WLI appeared lower in SH pts, despite provision of the intervention in Spanish. More work is needed to improve accessibility and efficacy of WLI studies among non-English speaking populations. Support: U10CA180821, U10CA180882, UG1CA189823; https://acknowledgments.alliancefound.org. Citation Format: A. Odai-Afotey, K. V. Ballman, L. M. McCall, C. Cao, C. Alfano, V. Bernstein, T. E. Crane, L. M. Delahanty, L. Frank, P. J. Goodwin, O. Hahn, D. L. Hershman, J. O. Hopkins, M. Irwin, E. L. Mayer, L. Minasian, L. Nebeling, M. Neuhouser, E. D. Paskett, P. A. Spears, V. Stearns, C. A. Thomson, T. A. Wadden, A. Weiss, J. White, C. Hudis, E. P. Winer, L. Carey, A. H. Partridge, J. Ligibel. Variation in weight loss and intervention engagement in the Breast Cancer Weight Loss (BWEL) trial by language and ethnicity (Alliance) [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS4-09-29.

Abstract Background: Obesity is a poor prognostic factor in early breast cancer (BC). The BWEL trial (Alliance A011401; NCT02750826) is a phase 3 randomized trial testing the impact of a weight loss intervention (WLI) on invasive disease-free survival in women with stage II-III BC and a body mass index (BMI) ≥27 kg/m2. Here we report trajectories of weight change in BWEL WLI participants (pts). Methods: Eligible pts were within 16 months of diagnosis of stage II-III HER2-negative BC, had completed chemotherapy (chemo) and radiation (if given), and were randomized 1:1 to a telephone-based WLI, focused on caloric restriction and exercise, plus health education (HE) or to an HE-alone control group. WLI pts were assigned a trained coach at the BWEL call center and received 42 phone calls over the 2-year (yr) WLI period. Weight and height at baseline, 6 and 24 months were collected by study staff. All WLI pts were provided with a Fitbit wireless scale. Fitbit weight records (FWRs) were automatically imported to the BWEL portal for pts with wireless access and self-reported in the portal for pts without wireless access. FWRs were averaged (avg) by week (wk) from the WLI start date up to 104 wks. Baseline pt factors were self-reported; treatment history was abstracted from the medical record. Linear mixed-effect models were used to evaluate trajectories of weight change over the 104-wk WLI. Principal component analysis and multinomial models were used to examine distinct clusters of weight trajectories. Results: 3180 pts were enrolled from 637 sites between 8/2016 and 2/2021. FWRs were available from 1508 of 1591 WLI pts, with a total of 366,294 FWRs collected during the 2-yr WLI period. In pts with FWRs, mean baseline BMI was 34.4 ± 5.6 kg/m2, mean age was 53.2 ± 10.3 yrs, 10.8% self-identified as Non-Hispanic (NH) Black and 6.1% as Hispanic, 81.1% received chemo and 56.9% were postmenopausal. No statistically significant differences in baseline factors were observed between pts with and without FWRs. Intraclass correlation coefficient of baseline weights collected by study staff and by Fitbit scales was 0.99. In the WLI cohort, avg weekly weight (kg) decreased from 91.4 (95% CI: 90.6-92.3) at baseline to 85.6 (95% CI: 84.8-86.5) by wk 40, corresponding to a peak loss of 6.1% (95% CI: 5.7-6.4) of baseline weight. Weight remained stable until wk 52 and then gradually increased to 87.0 kg (95% CI: 86.2-87.9) at wk 104, corresponding to a 4.4% (95% CI: 4.0-4.8) loss at wk 104 vs. baseline. Principal component analysis identified 3 distinct weight trajectories: 67.6% of pts experienced peak weight loss of 6.6% (95% CI: 6.3-6.9) of baseline weight, 10.0% experienced peak loss of 17.5% (95% CI: 16.8-18.2) of baseline weight, and 22.4% did not achieve weight loss, gaining on avg 2.2% (95% CI: 1.7-2.6) of baseline weight. Pts with college (relative risk ratio [RRR]=1.41, 95% CI: 1.03-1.92) and post-graduate education (RRR= 1.58, 95% CI: 1.13-2.20) and those who were premenopausal (RRR=1.70, 95% CI: 1.28-2.26) were more likely to be in the cluster that did not lose weight. Pts who were NH White (RRR=3.60, 95% CI: 1.95-6.68), postmenopausal (RRR=1.94, 95% CI: 1.28-2.95), had no alcohol use (RRR=1.49, 95% CI: 1.03-2.16), had not received chemo (RRR=1.76, 95% CI: 1.15-2.72), and had <3 chronic conditions (RRR: 2.12, 95% CI: 1.23-3.66) were more likely to be in the cluster with the highest weight loss. Conclusion: Longitudinal weight data from BWEL demonstrate peak weight loss of 6.1% in the WLI cohort at 40 wks, with distinct trajectories indicating differential responses to the WLI. This work demonstrates the feasibility of using digital health tools to track outcomes in the setting of a large-scale weight loss intervention study and informs future precision behavioral interventions in oncology. Support: U10CA180821, U10CA180882, UG1CA189823; U10CA180863. https://acknowledgments.alliancefound.org. Citation Format: C. Cao, K. Ballman, L. McCall, C. Alfano, V. Bernstein, T. Crane, L. Delahanty, L. Frank, P. Goodwin, O. Hahn, D. Hershman, J. Hopkins, M. Irwin, E. Mayer, L. Minasian, L. Nebeling, M. Neuhouser, E. Paskett, P. Spears, V. Stearns, C. Thomson, T. Wadden, A. Weiss, J. White, C. Hudis, E. Winer, A. Partridge, L. Carey, J. Ligibel. Weight Trajectories in the Breast Cancer Weight Loss (BWEL) Trial (Alliance) [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PD8-01.

Abstract Background: Despite its widespread adoption, there is a lack of data as to whether breast MRI for local staging and surgical planning of newly diagnosed breast cancer patients improves oncologic outcomes. The Alliance A011104 phase III trial was designed to test the hypothesis that MRI detection of mammographically occult disease helps to tailor surgical intervention thereby reducing local recurrence and improving local regional control. Here we report on the primary outcome of 5-year local regional recurrence. Methods: Patients with newly diagnosed clinical stage I-II, ER/PR- and HER2- negative (triple- negative) or ER/PR-negative and HER2-positive breast cancer, deemed eligible for breast- conserving surgery (BCS) based on clinical exam, mammography +/- ultrasound were randomized to undergo staging breast MRI or no further local staging. Patients with multifocal tumors that could be encompassed in a single operative resection were eligible. Patients who were carriers of gBRCA 1/2, or who had bilateral breast cancer, or a prior history of breast cancer were excluded. Initial eligibility was limited to patients not scheduled to receive neoadjuvant chemotherapy; however, a subsequent amendment allowed for enrollment after completion of neoadjuvant chemotherapy. Categorical variables were compared between arms with a chi-square or Fisher’s exact test. LRR, distant recurrence and overall survival (OS) were estimated with Kaplan-Meier point estimates and 95% confidence intervals (CIs). Hazard ratios (HRs) and 95% CIs were obtained from Cox proportional hazards models. Results: Of 319 patients enrolled from 2/2014-12/2019,161 were randomized to undergo breast MRI and 158 to no breast MRI evaluation. The mean age at enrollment was 58.9 years (range 29-85). Most patients (72.1%) had T1 tumors, 93.4% were cN0 and 19.7% were HER2 positive. Systemic chemotherapy was utilized in 85% with 17.6% receiving treatment neoadjuvantly; receipt of systemic therapy was unknown for 15 patients (4.7%). Two hundred and ninety-eight patients (93.4%) underwent surgical intervention; 91.9% underwent BCS as initial surgical procedure with no significant differences noted between groups (92.7% in the no MRI group and 91.9% in the MRI group [p=0.62]). Of patients who underwent breast surgery, 293 underwent axillary evaluation with the majority (270 patients, 92%) undergoing sentinel lymph node biopsy as the only axillary intervention. Among patients who received neoadjuvant chemotherapy, the overall pathologic complete response rate was 39.3%, 29.0%in the MRI arm vs. 52.0% no MRI arm (p=0.10). Receipt of adjuvant radiation was comparable between arms, 85.4% and 85.0% receiving radiation in the no MRI and MRI arms, respectively. Among 298 patients evaluable for the primary endpoint, with median follow-up of 61.1 months (0.2, 68.1), there were no differences in rates of LRR; 5-year local regional control was 93.2% (89.0-97.6%) in the MRI group and 95.7% (92.3-99.1%) in the no MRI group (HR: 1.1, 95% CI: 0.3, 3.9). For the entire cohort, 5-year distant recurrence-free rate and OS were 94.3% (91.7, 97.1) and 92.2% (89.1, 95.4), respectively, with no differences between groups. Conclusions: With multimodality therapy, rates of 5-year LRR in patients with early stage triple- negative and HER2-positive breast cancer are very low. Breast MRI for local staging and surgical planning in this setting does not result in improved local regional control. Support: U10CA180821, U10CA180882; UG1CA189823; U10CA180868 (NRG Oncology); ClinicalTrials.gov Identifier: NCT01805076; https://acknowledgments.alliancefound.org Citation Format: I. Bedrosian, K. Ballman, L. M. McCall, C. E. Comstock, G. W. Unzeitig, T. Yen, A. Weiss, B. G. Haffty, J. M. Bensenhaver, S. M. DeSnyder, J. J. Liu, A. H. Partridge, L. A. Carey, K. K. Hunt.Effect of Preoperative Breast MRI Staging on Local Regional Recurrence (LRR) in Early Stage Breast cancer: Alliance A011104/ACRIN 6694 [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr GS2-07.

Abstract Background: The association of TILs with pathologic complete response (pCR) and survival in HER2+ breast cancer is not well established with several prior studies showing inconsistent results. In this secondary analysis of EA1181, we evaluated the association between stromal TILs (sTILs) and pCR rates. Methods: EA1181 (NCT04266249) enrolled patients (pts) with anatomic clinical stage II/III HER2+ breast cancer who preoperatively received 4 cycles of trastuzumab and pertuzumab with 12 weeks of paclitaxel or docetaxel q3w x 4 (THP), followed by surgery. sTILs density was assessed on full-face hematoxylin and eosin (H&E)-stained tumor biopsy sections. sTILs scores were analyzed per protocol as a continuous variable (every 10% increment) and as a categorical variable (<10% vs 10-60% vs >60% as per Denkert et al, 2018), and also with an exploratory 30% cutoff commonly used in TNBC. Cox proportional hazards models were used to examine the association between sTILs and pCR, adjusting for available baseline factors. The associations between sTILs (by category) and clinicopathologic characteristics were examined using Fishers’ exact test. Results: Among 2141 pts with HER2+ BC treated on EA1181, H&E slides were available for 1328 (62%). The study population evaluated for sTILs was comparable to the overall population. pCR rates were 44.5% overall, 64% for HER2+/ER- and 33% for HER2+/ER+ disease. sTILs distribution was: 623 (47%) <10%, 698 (52%) 10-60%, and 7 (0.5%) >60%, which led us to merge the latter two groups (705 [53%] had ≥10% sTILs). In univariable and multivariable analyses, increasing sTILs (as a continuous variable) were associated with increasing pCR rates in both HER2+/ER+ and HER2+/ER- disease (p<0.001; Table). sTILs analyzed as a categorical variable (<10% vs ≥10%) were significantly associated with pCR for all patients (combined) and for those with HER2+/ER+ disease. In exploratory analysis using a cutoff of <30% vs ≥30% sTILs, an association with pCR was also seen in univariable analysis for both HER2+/ER+ disease (p<0.001) and HER2+/ER- disease (p=0.045), though in multivariable analysis with clinical factors, sTILs >30% remained a significant predictor for pCR only in HER2+/ER+ disease. Additional exploratory analysis with other molecular biomarkers, intrinsic subtypes, and immune signatures will be presented. Conclusion: sTILs were associated with pCR after THP, further supporting the important role of immune mechanisms in HER2+ breast cancer, and highlighting a potentially robust predictive tool to assess pathologic response. Baseline sTILs could potentially inform the preoperative design of future trials of therapy optimalization. Association of baseline sTILs with recurrence free survival in EA1181 will be reported in the future. Citation Format: S. S. Badve, F. Zhao, N. Tung, Y. Gokmen-Polar, C. C. O'Sullivan, A. Prat, E. P. Winer, J. L. Wright, A. Recht, A. C. Weiss, J. A. Tjoe, S. M. Feldman, G. B. Rocque, M. Smith, N. Unni, S. Sardesai, S. Tang, S. Modi, W. J. Irvin, P. Villagrassa, C. Battelli, A. K. Krie, N. Bagegni, M. A. George, M. L. Telli, V. F. Borges, N. D’Abreo, P. Shah, K. D. Miller, A. H. Partridge, L. A. Carey, A. M. DeMichele, A. C. Wolff, ECOG-ACRIN.Tumor infiltrating lymphocytes (TILs) and pathologic complete response (pCR) in stage II/III HER2+ breast cancer treated with taxane, trastuzumab, and pertuzumab (THP): secondary results from the ECOG-ACRIN EA1181/CompassHER2 pCR trial [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr GS1-04.

Abstract INTRODUCTION Understanding comorbidities’ combined impacts on dementia risk may offer a more comprehensive understanding of individuals’ risk. Using machine‐learning, we grouped individuals with similar midlife risk profiles into clusters and explored associations with dementia risk. METHODS Participants without dementia at baseline (1987–1989) from the prospective Atherosclerosis Risk in Communities (ARIC) study were included (ages 45–64 years; N = 15,250). Using unsupervised hierarchical cluster analysis, nine clusters were created and defined based on 14 midlife morbidities. The associations with incident dementia ( N = 3272 cases, median follow‐up 25 years) and deaths ( N = 9099) were evaluated using time‐to‐event regression models. RESULTS Compared with the healthiest cluster (Cluster 1), Clusters 2 (smoking) (hazard ratio [HR](95% confidence interval [CI]) = 1.62 (1.08, 2.43)), 5 (obesity, diabetes, hypertension, and hypertriglyceridemia) (HR(95%CI) = 1.91 (1.35,2.70)), and 7/8 (atrial fibrillation/heart failure) (HR(95%CI) = 2.69 (1.59,4.57)) were associated with dementia. Accounting for competing risk of death in the Fine‐Gray subdistribution model negated the cluster‐dementia association. DISCUSSION Midlife morbidity clusters are important for dementia and mortality risk.

Cataracts are the leading cause of blindness worldwide. Obesity, a key component of metabolic syndrome (MetS), may represent a modifiable risk factor for cataracts. However, the evidence regarding the association between MetS or its components and cataracts remains controversial. Therefore, our meta-analysis aims to clarify the relationship between MetS or its components and cataracts. A search was conducted until February 2024 via the MEDLINE, EMBASE, and Cochrane databases. The primary endpoint included the association between MetS or its components, including body mass index (BMI), diabetes mellitus (DM), hypertension (HT), and dyslipidemia (DLP), and cataracts. Secondary endpoints included the association between levels of blood pressure, blood sugar, and lipid profiles and cataracts. A total of 27 studies were included with a total of 1,010,014 patients (134,498 with cataracts and 875,516 without cataracts). Of these, there were 2 prospective cohort studies, 6 case–control studies, and 19 cross-sectional studies. The prevalence of cataracts was 13.3%. MetS was significantly associated with cataracts with an odds ratio (OR) of 1.60 (95% confidence interval [CI]: 1.44–1.77, I 2 = 93%). Among MetS components, high BMI and being diagnosed with DM, HT, and DLP were associated with cataracts with ORs of 1.45 (95% CI: 1.33–1.58, I 2 = 80%), 1.77 (95% CI: 1.69–1.85, I 2 = 51%), 1.23 (95% CI: 1.19–1.28, I 2 = 62%), and 1.38 (95% CI: 1.30–1.46, I 2 = 0%). Among the metabolic parameters, high total cholesterol, high triglycerides, low high-density lipoprotein cholesterol, and high low-density lipoprotein cholesterol were associated with cataracts with ORs of 1.25 (95% CI: 1.04–1.49, I 2 = 48%), 1.05 (95% CI: 1.04–1.06, I 2 = 68%), 1.07 (95% CI: 1.01–1.13, I 2 = 0%), and 1.30 (95% CI: 1.10–1.53, I 2 = 71%), respectively. MetS, obesity, DM, HT, and DLP are associated with cataracts. Prevention or treatment of MetS or its components likely represent a modifiable risk factor in cataract development.

635 Background: [ 212 Pb]VMT-a-NET is an alpha therapy agent targeting somatostatin receptor subtype 2 (SSTR2)-expressing tumors. Here, we report the results of a prospective, open-label, Phase I/IIa trial (NCT05636618), assessing safety, tolerability, pharmacokinetics, and preliminary efficacy of [ 212 Pb]VMT-a-NET in patients with advanced neuroendocrine tumors (NETs). Methods: Adults with well-differentiated unresectable or metastatic SSTR2-expressing NETs, who are peptide receptor radionuclide therapy (PRRT) naïve, and who progressed on at least one prior line of systemic therapy, are eligible. Participants can receive up to four cycles of [ 212 Pb]VMT-a-NET at the assigned dose level. Participants are followed for dose-limiting toxicity (DLT) observation up to 42 days after the first dose. Efficacy is evaluated by investigators according to RECIST criteria v1.1. Results: As of 16-Aug-2025 (data cut-off [DCO]) a total of 48 participants were enrolled into cohorts 1 and 2 and received at least one dose of [ 212 Pb]VMT-a-NET (n=2 in Cohort 1, and n=46 in Cohort 2 at a dose level of 92.5 MBq and 185 MBq, respectively). Among all participants treated with at least one dose of [ 212 Pb]VMT-a-NET (n=48), no DLTs, no grade 4 or 5 adverse events (AEs), and no treatment-related discontinuations, were observed. Median follow-up time was 28 weeks (range: 6-93). Nine participants were followed for DLT observation (n=2 in cohort 1 and n=7 in cohort 2).Seven of these patients were with no progression as of the DCO. Three out of the seven participants enrolled at the dose level of 185 MBq achieved a confirmed partial response (PR). Median follow-up time for participants included in the efficacy group was 72 weeks (range: 6-93). Cohort 3, at a dose level of 222 MBq, has recently been opened for enrollment. At the DCO, 4 participants were enrolled in this cohort. Updated safety outcome for all participants along with updated efficacy findings for participants in Cohort 1 and 2 with sufficient maturity, will be presented during the congress. Conclusions: [ 212 Pb]VMT-a-NET showed a favorable safety profile and promising clinical benefit for patients with advanced SSTR2-expressing NETs treated at the dose levels of 92.5 MBq and 185 MBq. The study is ongoing with Cohort 3 (222 MBq) currently open for enrollment. Clinical trial information: NCT05636618 .

Abstract Background Reference sets are needed to evaluate performance of multi-cancer detection (MCD) assays. The National Cancer Institute funded the Alliance reference set study to assess MCDs for use in future trials. Methods Individuals with cancer and controls were recruited; blood specimens were collected prior to cancer treatment. A performance evaluation study was designed utilizing reference set samples. Companies (n = 6) were selected to participate based on review of performance data and ability to utilize the blood collection tube. Companies received samples from cancer types their assay was designed to detect (“targeted”), plus additional “non-targeted” and control samples. Companies reported positive/negative calls, risk scores, and tissue-of-origin (TOO) predictions. Sensitivity was computed for early (I-II) and late (III-IV) stage cases, based on positive/negative calls (SEPN) and at fixed 98% specificity (SE98). Specificity and TOO accuracy were computed. Results Five hundred and forty nine cases (encompassing 13 cancer types) and 413 controls from the reference set were included in the study. Companies assessed samples from median 6 (range 5-9) targeted cancer types and median 8 (range: 7-11) overall cancer types. Median (range) specificity was 92.3% (76.5%-98.5%). Median (range) SEPN was 32% (25%-42%) for early stage and 73% (48%-89%) for late stage; while median (range) SE98 was 19% (8%-35%) for early stage and 66% (13%-79%) for late stage. Median sensitivity for non-targeted types was 40% (early stage) and 52% (late stage). Median (range) TOO accuracy (primary predicted site) was 75% (64%-78%). Conclusions Sensitivity and specificity varied widely across assays with early-stage sensitivity substantially lower than late-stage sensitivity. Clinical Trial Registration Number ClinicalTrials.gov identifier NCT05334069.

Background/Objective: The COVID-19 pandemic led to a widespread transition to online learning. Yet, it is unclear how this shift in learning format impacted school attendance in adolescents with chronic pain, a group that struggles with school absenteeism. This study compared school attendance and format (e.g., in-person, online) in patients with chronic pain attending an Intensive Interdisciplinary Pain Treatment Program (IIPT) before the pandemic to an age- and gender-matched sample of youth attending the program after the pandemic. Methods: Participants were 226 school aged adolescents (13–18 years; M age = 15.89, SD = 1.46) enrolled in an IIPT before and after the COVID-19 pandemic. Patients admitted before March 2020 (pre-pandemic group; n = 113) were compared to an age- and gender-matched group of patients who were admitted to the IIPT from November 2021 to November 2023 (post-pandemic group = 113). Upon admission to the program, participants completed validated measures of internalizing symptoms and functional disability. They also completed structured questions related to pain and school history. Results: Significantly more patients in the post-pandemic group were attending school through online and home-schooling options (p < 0.01). Youth who attended the IIPT after the pandemic missed fewer school days (p < 0.05) than those who attended before the pandemic. The groups did not differ in functional disability or internalizing symptoms. However, participants in the post-pandemic group who attended online school missed more school days (p < 0.01) and experienced greater functional disability (p < 0.05) than those who attended in person. Conclusions: The findings highlight how the COVID-19 pandemic may lead to sustained changes in the way adolescents with chronic pain attend school, with implications for increased functional disability and school dropout among this vulnerable population.