West Cancer Center

BackgroundMobile health (mHealth) technologies are increasingly used in paediatric oncology to promote physical activity, with growing evidence supporting their feasibility and effectiveness. Augmented reality (AR) is emerging as a promising addition, offering interactive features that may enhance participation in exercise for young people. As mHealth tools evolve, understanding user experiences and implementation challenges is essential to inform wider adoption in healthcare. The FORTEe clinical trial evaluates an individualised exercise programme designed for children, adolescents and young adults with cancer (CAYA). This sub-study explores the perspectives of CAYA and exercise and healthcare professionals involved in delivering the exercise intervention (exercise professionals) on the use of a novel AR application (app), designed to facilitate home-based exercise as part of the broader intervention. Key app features include personalised exercise programmes, AR demonstrations using a child-like avatar, and an integrated exercise diary.MethodsCAYA (9–21 years), and exercise professionals from the FORTEe trial's technology sub-study (six centres) were eligible. To explore experiences and perceptions of the AR app, half-structured interviews were conducted with CAYA and an anonymous online survey administered to exercise professionals. Interview data and open-ended text from survey was analysed using inductive qualitative content analysis. Survey data was analysed using descriptive statistics.ResultsA total of 46 CAYA (mean age 13.6 ± 2.7 years, 39% female) provided feedback on the AR app via interviews, and 31 exercise professionals completed the survey. CAYA and exercise professionals reported generally positive experiences, finding the AR demonstrations novel and engaging. The personalised workouts were valued by both groups. However, both groups reported some technical difficulties that impacted reliability, and that some features, such as the exercise diary, lacked usability. Exercise professionals emphasised the app should complement rather than replace face-to-face sessions. To enhance the app further, both groups suggested incorporating gamification and avatar customisation.ConclusionThis study emphasises the potential of AR technology to increase engagement in exercise among CAYA and highlights ways to optimise the technology. While AR shows promise in paediatric oncology care, it should complement in-person exercise interventions. Future development should prioritise user-friendly design, personalised approaches, and equal access for young patients.

545 Background: The LITESPARK-013 study (NCT04489771) showed similar efficacy and safety between 200 mg and 120 mg (approved dose) doses of the HIF-2α inhibitor bel in pts with pretreated advanced ccRCC. We report exploratory biomarker analyses (including HIF-2α IHC, RNAseq, and WES) from this study. Methods: Pts with advanced ccRCC whose disease progressed after 1-3 prior systemic therapies (including an anti–PD-[L]1 therapy) were randomly assigned 1:1 to bel 200 mg or 120 mg QD. Treatment arms were pooled for biomarker analyses. Association of HIF-2α tumor proportion score (TPS; IHC D6T8V) and H-score (sum of each percentage multiplied by its corresponding intensity [0, 1+, 2+, 3+]) with clinical outcomes (ORR, PFS, OS) were tested at prespecified multiplicity-adjusted α = 0.05. Associations of RNAseq-based HIF-2α co-expression and HIF-2α cancer cell scores, glycolysis, angiogenesis, and other HIF-2α–related genes and signatures were tested at prespecified multiplicity-adjusted α = 0.10. Associations for molecular subtypes (Motzer et al. Cancer Cell . 2020;38:803) were tested at nominal α = 0.05. DNA mutations were evaluated by WES. Results: Of 154 pts, HIF-2α IHC was evaluable in 136, RNAseq in 109, and WES in 113 pts. HIF-2α TPS and H-score were positively associated with PFS ( P = 0.016 and 0.012, respectively), but not ORR or OS. HIF-2α cancer cell score was positively associated with ORR ( P = 0.085), but not PFS or OS. No associations with clinical outcome were observed for HIF-2α co-expression score. Glycolysis and angiogenesis were positively associated with ORR ( P = 0.036) and PFS ( P = 0.070), respectively, but these were no longer significant after adjustment of other signatures. ORR was consistent across molecular subtypes and by DNA mutation status (Table), with notably higher ORR in the BAP1 mutant vs wild-type group. Conclusions: In this first RNA and WES biomarker analysis of bel, HIF-2α TPS and H-score were potentially associated with PFS, and BAP1 mutation was potentially predictive of improved ORR in pts with RCC. Molecular subtypes, other RCC-related signatures, and VHL mutation showed no associations or trends with ORR, PFS, or OS. Prospective biomarker evaluations are needed to confirm these findings. Clinical trial information: NCT02853344 . n ORR, % (95% CI) All RNAseq evaluable 109 26.6 (18.6-35.9) Molecular subtypes Angiogenic 12 33.3 (9.9-65.1) Angiogenic/stromal 24 25.0 (9.8, 46.7) Immune/proliferative 22 27.3 (10.7-50.2) Stromal/proliferative 17 23.5 (6.8-49.9) Proliferative 17 23.5 (6.8-49.9) Other (unassignable to a subtype) 17 29.4 (10.3-56.0) VHL Mut 80 25.0 (16.0-35.9) WT 33 24.2 (11.1-42.3) PBRM1 Mut 59 23.7 (13.6-36.3) WT 54 25.9 (15.0-39.7) SETD2 Mut <jats:td colspan="1" rowspan=

Abstract Background: Treatment approaches for early-stage breast cancer (EBC) have advanced significantly in recent decades, with the addition of HER2-targeted therapies, immunotherapy, and personalized chemotherapy. However, despite these advances, many questions related to treatment cannot be practically or ethically addressed in prospective, randomized clinical trials. The required extended follow-up in EBC treatment trials may delay the dissemination of practice-changing results. Additionally, many EBC trials have poor representation of less common tumor subtypes (such as invasive lobular carcinoma, ILC) and limited enrollment of patients of diverse racial/ethnic backgrounds. In this context, observational registry Real-World Data clinical trials, such as FLEX, which analyze clinical and pathologic data, treatment history, outcomes, and other metadata such as whole transcriptomics can provide actionable evidence that can inform clinical practice. The ongoing, multi-center, FLEX study (NCT03053193) seeks to enroll 30,000 EBC patients to create a large-scale, diverse, population-based registry of whole transcriptome data matched with clinical data with 10 years of follow-up to investigate new gene expression signatures of prognostic and/or predictive value in a real-world setting. Efforts are focused on enriching enrollment of diverse racial/ethnic minorities, historically underrepresented groups, and uncommon EBC tumor histologies. An additional objective is supporting investigator-initiated sub-studies to address clinically relevant questions in EBC with up to 10 years of follow-up. Methods: FLEX is a large prospective, observational trial that enrolls patients (male or female) who are ≥ 18 years old with stage I-III breast cancer. Patients who receive standard of care MammaPrint® (70-gene signature risk of recurrence), with or without BluePrint® (80-gene signature molecular subtype) on their primary breast tumor and consent to clinically annotated whole transcriptome data collection are eligible for enrollment. Within 7 years of trial initiation, FLEX has enrolled over 20,000 patients across 102 sites in the US, 3 sites in Canada, and 1 site each in Greece and Israel. Of the total FLEX population, 9495 (47%) have reached 3 years of follow-up, and 4047 (20%) have reached 5 years of follow-up. To address racial/ethnic disparities in clinical trials, a concerted effort has led to the inclusion of 1892 Black/African American, 1722 Latin American/Hispanic, and 490 Asian American/Pacific Islander EBC patients of self-reported racial/genetic ancestry, making FLEX a highly diverse study of EBC patients. Similarly, FLEX represents one of the largest cohorts of ILCs, composed of 2196 ILC and 649 mixed ILC/ductal histology tumors. Studies from FLEX have led to 3 peer-reviewed publications, with 3 submitted in 2025 currently under review. Fourteen FLEX investigator-initiated sub-study abstracts have been presented in 2025. Additionally, over 53 FLEX abstracts have been accepted at congresses internationally (2018-2025), including 11 presentations focused on therapy selection, 12 on differences in tumor biology and clinical outcomes by race/ethnicity, and 2 on ILC, among others. Data generated from FLEX include important new findings in EBC management. Among these findings are the prediction of absolute chemotherapy benefit in genomically high-risk patients, prediction of survival benefit from adjuvant anthracyclines, associations of genomic signatures that predict resistance to CDK4/6 inhibition, and overrepresentation of aggressive ER+ basal-type tumors in Black/African American patients. Citation Format: L. P. Gold, L. Samiian, K. Hoskins, S. Diab, L. Lee, V. K. Gadi, E. A. Brown, J. R. Ramadurai, J. A. Elayoubi, R. E. Kaczynski, R. E. Fine, T. Bah, L. Matt-Amaral, B. J. Lieblong, W. Audeh, J. O'Shaughnessy. Flex: from genomic profiling to real-world insights in 30,000 patients with early-stage breast cancer [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 PS5-09-19.

Abstract Background The first-line standard of care (SOC) for patients (pts) with estrogen receptor-positive, HER2-negative advanced breast cancer (ER+, HER2- aBC) is CDK4/6 inhibitor (i) + endocrine therapy (ET) but effective post-CDK4/6i options remain limited. Giredestrant (GIRE) targets the ER pathway while everolimus (E) targets the PI3K/AKT/mTOR pathway; both of which are implicated in driving resistance in the post-CDK4/6i setting. evERA BC (NCT05306340) is the first Phase III trial to demonstrate statistically significant and clinically meaningful improvement in investigator-assessed progression-free survival (INV-PFS) with an all-oral selective ER antagonist and degrader combination of GIRE + E vs SOC ET + E in pts with ER+, HER2- aBC post-CDK4/6i + ET, both in pts whose tumors had a detectable ESR1 mutation (m) and in the intent-to-treat (ITT) population (Mayer ESMO 2025). The safety profile of GIRE + E was manageable with no unexpected findings (Mayer ESMO 2025). We report results from prespecified exploratory subgroup analyses. Methods Pts who had ER+, HER2- aBC with disease progression (PD) post-CDK4/6i + ET in the aBC setting, or relapse during/after CDK4/6i + ET in the adjuvant setting, were randomized 1:1 to once-daily oral 30 mg GIRE + 10 mg E or SOC ET (exemestane, fulvestrant, or tamoxifen) + E until PD or unacceptable toxicity. Mutational status was determined using circulating tumor DNA at baseline. The co-primary endpoints were INV-PFS per Response Evaluation Criteria in Solid Tumors v1.1 in pts whose tumors had detectable ESR1m and in the ITT population. INV-PFS was assessed by subgroup analyses. Results Three-hundred-and-seventy-three pts were randomized; 183 pts were randomized to GIRE + E and 190 to SOC ET + E. A total of 207 pts (55%) had tumors with ESR1m, 115 (31%) had PIK3CAm, and 137 (37%) had alterations (alt) in the PI3K pathway genes (PIK3CA/AKT1/PTEN). Sixty-four pts (17%) had both ESR1m and PIK3CAm; 76 (20%) had both ESR1m and PIK3CA/AKT1/PTEN alt. Ninety-eight percent of pts received a CDK4/6i in the metastatic setting. INV-PFS benefit was observed for GIRE + E vs SOC ET + E regardless of PIK3CAm status or PIK3CA/AKT1/PTEN alt in both the ESR1m and ITT populations (Table). Consistent benefit was observed regardless of duration of prior CDK4/6i (Table). Data for additional subgroup analyses for prior therapy will be presented. Conclusions GIRE + E led to clinically meaningful improvements in INV-PFS vs SOC ET + E irrespective of PIK3CAm and PIK3CA/AKT1/PTEN alt, and other key relevant subgroups, regardless of ESR1m status. These data support the use of GIRE + E vs SOC ET + E in pts with ER+, HER2- aBC post-CDK4/6i + ET. Citation Format: H. S. Rugo, S. M. Tolaney, K. L. Jhaveri, M. Martin, G. A. Vidal, L. Moscetti, A. Brufsky, W. J. Gradishar, A. Schneeweiss, N. Niikura, A. Favret, M. Alfie, K. S. Lee, S. Khan, M. Feldman, B. M. Day, L. H. Lam, W. C. Darbonne, T. M. Fernando, P. Perez-Moreno, E. L. Mayer.Clinical and biomarker subgroup analysis of evERA Breast Cancer: A Phase III trial of giredestrant plus everolimus in patients with estrogen receptor-positive, HER2-negative advanced breast cancer previously treated with a CDK4/6 inhibitor [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 GS3-09.

Objectives/HypothesisTotal laryngectomy has traditionally been recommended for patients with recurrent larynx cancer after radiation or chemoradiation. Some patients refuse salvage surgery. Historically, these patients have been placed on hospice or palliative chemotherapy. Immunotherapy has recently added another treatment modality to our armamentarium.Methods8 patients with recurrent larynx cancer declined salvage laryngectomy. They were started on immunotherapy alone. We recorded their demographics, initial cancer stage, initial cancer treatment, combined positive score (CPS) values, need for tracheostomy, addition of chemotherapy to their immunotherapy, and response to therapy.Results62.5% were African American, while 37.5% were Caucasian. Most had early (stage 1 or 2 disease) at the time of initial diagnosis. 75% had radiation alone as their initial treatment, while 25% had chemoradiation. All of these patients had high CPS scores. 37.5% progressed on 4 rounds of immunotherapy and are deceased. Chemotherapy was added to the regimen of 50% of the patients after poor response to immunotherapy. 75% of these patients are all still alive after 1 year of treatment. 75% of all patients needed tracheostomy while on salvage treatment. One patient (12.5%) has had a long-lasting positive response to immunotherapy alone.ConclusionsOur patients with nonmetastatic recurrent larynx cancer were found to have high CPS scores, which suggests favorable response to immunotherapy. Most patients with recurrent larynx cancer on immunotherapy required a tracheostomy. These patients had poor response on immunotherapy alone, but had prolonged survival with added chemotherapy. Salvage laryngectomy is the only curative option for these patients, but for those patients that refuse surgery, chemotherapy with immunotherapy has better results than immunotherapy alone. Our results reveal a possible clinical phenomenon, which needs to be confirmed by large sample studies.

Abstract BACKGROUND Glioblastoma are hallmarked by clonal evolution and transcriptional heterogeneity linked to genetic and environmental diversity resulting in therapy resistance and disease progression. In this study, we integrate heritable molecular barcoding and spatial transcriptomics to enable high-resolution cell lineage tracing in the spatial context of the glioblastoma TME. MATERIAL AND METHODS Patient-derived glioblastoma cells from two individual cases were isolated from anatomically and pathologically distinct regions: the primary tumor core, the tumor periphery, and the recurrent lesion. Each subline was transduced with predefined FlexTrack lentiviral plasmids encoding GFP, resulting in uniquely barcoded (9N) cell lines. Immediately before injection, the barcoded glioblastoma populations were pooled and introduced into ex vivo human cortical slices. Live-imaging was used to trace GFP-positive, barcoded cell populations. After incubation, the fresh-frozen slices were processed for spatial transcriptomics and the line-specific barcodes were mapped according to the 3′ poly(A) tails of captured transcripts. Graph neural networks based on single-cell deconvolution were employed to spatially analyze the cellular ecosystems. RESULTS We successfully deconvoluted and reconstructed the trajectories of injected glioblastoma cells linking their transcriptome phenotypes along with clonal identity. Multi-omic integration of spatial copy-number alterations and barcoding based pseudo-trajectories enabled reconstruction of the temporal transcriptional dynamics linked to the heterogeneity of tumor ecosystems. CONCLUSION This study serves as a proof-of-concept for integrating molecular barcoding and spatial transcriptomics in cortical slice culture. Our approach to molecular barcoding in complex model systems opens new avenues to investigate the contextual dynamics of clonal evolution in glioblastoma.

In this study, we evaluate the utility of ctDNA analysis in a large cohort of patients for whom ctDNA testing was ordered commercially with real-world application. Circulating tumor DNA (ctDNA) has emerged as a prognostic and predictive biomarker for assessing post-surgical molecular residual disease (MRD) and response to treatment. A real-world data analysis was performed using commercial ctDNA testing (SignateraTM) from patients (N=795, n=5,971 plasma samples) with stage I-III colon cancer treated at multiple US institutions. The association of ctDNA detection within the MRD window, during surveillance, and the impact of ACT was correlated with patient outcomes. ctDNA-positive patients during the MRD window and surveillance showed significantly shorter DFS compared to ctDNA-negative patients (hazard ratio (HR): 9.85, P<0.0001; HR: 26.91, P<0.0001). Multivariate analysis of the MRD window revealed ctDNA-positivity as the most significant factor associated with inferior DFS (adjHR: 7.7, P<0.001). MRD-positive patients who received ACT showed improved DFS compared to patients observed post-surgery (adjHR: 6.1, FDR adj P=0.0007). No ACT benefit was observed in MRD-negative patients (adj HR: 1.20, FDR adj P=0.768). On evaluating ctDNA dynamics from MRD to surveillance, patients who remained ctDNA-positive or converted from negative to positive showed a significantly inferior DFS (HR: 34.40, P<0.0001; HR: 13.65, P<0.0001) compared to persistently ctDNA-negative patients. Postsurgical ctDNA detection is prognostic of relapse and potentially predictive of ACT benefit in patients with resectable colon cancer, which may enable personalized surveillance, intervention, and/or trial options, ultimately improving patient outcomes.