e21014 Background: Adolescents and young adults (AYAs, ages 15–39) with cancer face care and outcome disparities due to complex care delivery and limited provider training in AYA-specific needs. Most pediatric and medical oncology training programs lack formal AYA oncology curricula, creating a critical educational gap. To address this, AYA POWER was developed, the first interdisciplinary, virtual curriculum for oncology trainees. AYA POWER provides high-yield education to build provider confidence, identify gaps in care, and improve outcomes for AYAs with cancer. Methods: Informed by prior needs assessments, AYA POWER curriculum has covered 16 sessions on priority topics including disparities, sexual/reproductive health, psychosocial care, financial toxicity, advanced cancer, clinical trials, and survivorship from August 2023-May 2025. Sessions featured 60-minute live monthly virtual lectures, discussion, recorded content, and shared resources. Participation was assessed using registration information, including demographic and website analytics data. Following each session, attendees completed surveys evaluating satisfaction with content and overall value of the program. Results: As of May 2025, AYA POWER has reached 2,135 engagements, reflecting attendance at live virtual sessions as well as views of on-demand lecture recordings. 1,042 participants joined the live lectures, representing 528 unique attendees, as some participants joined multiple lectures. A diverse group of AYA stakeholders attended, including nurses, social workers, pediatric oncology attendings, administrators, advanced practice providers, oncology fellows, researchers, patient advocates, psychologists, and medical oncology attendings and represented 15 countries. Anonymous feedback over the two seasons (216 respondents) was overwhelmingly positive. Respondents noted the relevance, practicality, and depth of the AYA POWER curriculum, highlighting its focus on under-discussed, evidence-based topics and actionable tools for AYA cancer care. Respondents emphasized the rarity and importance of AYA-specific education and expressed strong interest in expanded content, more case-based examples, additional topics, and continued programming. Conclusions: AYA POWER responds to a clear deficit in oncology training by delivering a flexible, scalable curriculum centered on the specialized needs of AYAs with cancer. Because AYA-focused education is often minimal or absent in traditional training programs, this initiative prioritizes topics that are frequently overlooked. Broad participation from a global, interdisciplinary audience demonstrates both the practicality of the virtual format and strong demand for continued learning across roles and regions.

Pediatric acute myeloid leukemia (AML) is a highly heterogeneous malignancy, with cytogenetic and molecular abnormalities playing a critical role in determining prognosis and guiding treatment decisions. Despite therapeutic advances, patients with high-risk genetic mutations and translocations continue to experience suboptimal outcomes. As new targeted therapies emerge, the treatment of pediatric AML could undergo a paradigm shift, where “one-size-fits-all” chemotherapy is no longer the only frontline approach. Identifying genetic markers inform risk stratification and have greater impact on shaping the therapeutic approach, including the integration of targeted therapies such as FLT3 and menin inhibitors into frontline therapy. Furthermore, pediatric AML treatment options are being driven by recent discoveries in adult AML, broadening their clinical trials to include pediatric patients, in part due to the RACE for Children Act that went into effect in August 2020. This review identifies the most prevalent high-risk cytogenetic lesions in pediatric AML, emphasizing their incidence, prognostic significance, and implications for clinical management. By synthesizing current research on these key genetic abnormalities and their associated therapies, we aim to provide an updated perspective on the evolving landscape of high-risk pediatric AML management that can then lead to the establishment of an agile framework to rapidly evaluate, approve, and deploy novel agents.

BackgroundMelanoma, a highly aggressive form of skin cancer, is the second most common type of cancer for adolescent and young adult (AYA, ages 15-39 years) patients. AYA patients with melanoma may turn to internet sources, especially artificial intelligence (AI) chatbots, to manage uncertainty about prognosis and treatment. ObjectiveThis study aims to evaluate the quality, empathy, and readability of responses generated by leading AI chatbots when addressing the top unmet needs of AYA patients with melanoma receiving treatment. MethodsOur research team recently surveyed 152 AYA patients with melanoma using the Needs Assessment Service Bridge, a validated instrument that assesses psychosocial needs for AYA patients with cancer. The survey identified the top 5 needs for advanced AYA patients with melanoma receiving treatment. Each need was reframed into a question and brief clinical history, then entered into each chatbot by 5 individuals who cleared their prequestion and postquestion history. Chatbot responses were evaluated to assess information quality (Global Quality Score [GQS] and DISCERN), accessibility and readability (GQS, Flesch Kincaid Grade Level, Flesch Reading Ease), and perceived empathy (Perceived Empathy of Technology Scale [PETS], including domains of Emotional Responsiveness [PETS-ER], Understanding and Trust [PETS-UT]). ResultsAcross 75 chatbot responses, ChatGPT achieved the highest average quality (mean GQS 4.42, SD 0.32; mean DISCERN 3.24, SD 0.31) and empathy (mean PETS-ER 5.35, SD 1.85; mean PETS-UT 6.36, SD 1.83), though with greater variability. Copilot produced the lowest quality and empathy scores, while Gemini responses were consistently midrange. PETS-UT exceeded PETS-ER across all models, suggesting stronger cognitive empathy than emotional responsiveness. Readability analysis showed outputs exceeded the average US reading level (mean Flesch Kincaid Grade Level 11.82, SD 1.44; mean FRE 38.60, SD 9.00), limiting accessibility. The most readable responses were found in question 2, which also scored higher in quality and empathy, whereas questions 4 and 5 produced the most complex, difficult-to-read responses corresponding with lower quality and empathy ratings. ConclusionsAI chatbots can provide moderately accurate and supportive responses to needs of AYA patients with melanoma, but outputs are inconsistent, written above the recommended reading level for health information, and limited in empathy. Question framing strongly influenced chatbot performance, with more emotional prompts drawing greater empathy, and readability aligning with both quality and empathy. Chatbot use in this population should remain adjunctive, with further research needed to standardize quality, improve readability, and enhance empathetic communication.

BACKGROUND:Anaplastic large cell lymphoma (ALCL) is an aggressive T-cell lymphoma that, rarely, can present with secondary haemophagocytic lymphohistiocytosis (HLH). OBSERVATIONS:A 6-year-old boy with ALK-positive ALCL and HLH required intensive care and chemotherapy, experienced multiple relapses, and ultimately achieved remission with crizotinib, ruxolitinib, dexamethasone, and allogeneic stem cell transplant. CONCLUSIONS:This case illustrates the clinical challenges of treating ALK-positive ALCL with concurrent HLH and highlights the role of targeted therapies. As molecular understanding of ALCL increases, integrating novel targeted agents may improve outcomes, particularly in relapsed or high-risk disease.

Abstract Objective: The development of lung metastasis following primary tumor diagnosis, resection and chemotherapy remain a significant hurdle in the treatment of osteosarcoma. Research indicates that the metastatic progression of osteosarcoma is driven by clonal evolution where selective pressure influences the emergence of distinct subpopulation of cells within the heterogenous tumor population. The absence of a robust in vivo model to accurately identify rare invasive subpopulations and determine how they evolved makes clonal characterization challenging. Methodology: To understand the clonal landscape and genomic architecture driving metastases, we injected barcoded OS17 PDX cells in 25 SCID mice intratibially to monitor primary tumor growth and clonally track the cells during metastatic progression. We hypothesize that tumor cells in the early stage undergo prolonged evolution in the primary tumors producing several distinct subpopulations that ultimately migrate, seed and becoming dominant in the lungs. Next, we performed barcode and deep-whole exome sequencing on 27 samples derived from the mice. We used the data to delineate clonal structure, assess somatic variants and identify mutational signatures and potential drivers of osteosarcoma. Results: In each primary tumor and matched metastases, we identified shared clonal drivers and somatic mutations. Clonal characterization revealed an increased clonal abundance that was followed by a significant reduction in clonal diversity in lung metastatic nodules. A high degree of similarity in the subclonal populations was observed between the lung nodules and the primary tumors. The frequency of the identified clonal drivers was higher in metastases compared to primary tumors. Copy number profile showed higher amplification peaks compared to deletion. C>T, T>C base substitution had the highest proportion compared to T>A. The most common mutational signatures were clock-like SBS1, SBS5 and SBS37. Metastatic nodules additionally harbored private SBS signatures absent in primary tumors. We identified 77 driver genes in the tumors. Shared clonal mutations (KMT2C, THBS1, SDHC) dominated early stages and persisted through metastasis. Each group of primary tumor/metastasis shared both clonal(truncal) and subclonal mutation cluster that expanded in metastases. Shared subclonal variants (ARAP3, SIGLEC12, FANCA, ERCC4) exhibited stage-specific diversification in metastasis and matched primary tumors. Primary-specific subclones (RAD21L1) disappeared after the primary stage, while metastasis-specific subclones (PTEN, BCOR) emerged and dominated in metastases indicating a major evolutionary shift toward aggressive or invasive phenotypes. Conclusion: Clonal expansion of subpopulations in the late passages or metastases suggested that these clones can maintain tumorigenic potential in a favorable environment. The clonal expansion was probably due to mutation in the identified osteosarcoma driver genes. Multiple clones seeded metastasis and there was a direct relationship between the clonal and subclonal drivers in the primary tumors and metastatic lesions. Our model has important implications for the diagnosis and therapeutic treatment of osteosarcoma patients since multiple clones may need to be targeted to inhibit invasion. Citation Format: Sylvester Jusu, Wengdong Zhang, Qi Wang, Xingzhi Song, Zhang Zhongting, Zhaohui Xu, Yifei Wang, Xin Zhou, Michael Roth, Jonathan Gill, Douglas Harrison, Jing Wang, Jianhua Zhang, Richard Gorlick. Portraits of clonal landscape and mutational signature in primary tumors and matched lung metastatic model of osteosarcoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(8_Suppl):Abstract nr LB497.

Abstract Background: ADC development in osteosarcoma has been hindered by the absence of effective, targetable surface antigens. We previously identified CADM1, a cell-surface adhesion molecule, as a promising therapeutic target and generated three CADM1-directed ADCs (CADM1-Tesirine, CADM1-PEG-Exatecan, and CADM1-GGFG-Exatecan) with distinct linker-payload combinations. To select the optimal candidate for clinical translation, we evaluated target engagement and target-dependent cytotoxicity across multiple in vitro models. Methods: Confocal microscopy was used to visualize ADC trafficking through cellular compartments and its lysosomal localization over time. CADM1 knockout (KO) osteosarcoma cell lines (SaOS2 and OS31) were generated using CRISPR/Cas9 and validated by flow cytometry, Western blotting, and mass spectrometry (MS). Cell-surface CADM1 levels were quantified by MS and correlated with ADC cytotoxicity (IC50 values) measured by real-time live-cell imaging on the IncuCyte platform. Spearman correlation analyses across nine osteosarcoma cell lines assessed the relationship between CADM1 expression and ADC potency for all three constructs. Results: Confocal time-course imaging showed ADC trafficking from the plasma membrane (30 min) to lysosomes (6 h) and cytoplasmic dispersion (24 h), absent in CADM1-KO cells, confirming target-mediated internalization and lysosomal processing. CRISPR/Cas9-mediated knockout of CADM1 was achieved in SaOS2 and OS31 osteosarcoma cell lines. Loss of CADM1 expression was confirmed by flow cytometry, Western blotting, and mass spectrometry, showing complete depletion of surface protein. CADM1 loss markedly reduced ADC cytotoxicity (IC50 = 77.41 nM in SaOS2 CADM1-KO vs 0.014 nM in SaOS2), confirming on-target activity. Across nine osteosarcoma models, CADM1 surface abundance strongly correlated with drug potency, most notably for CADM1-GGFG-Exatecan (Spearman ρ = -0.98, p = 0.001). These data identify CADM1 as a determinant of ADC efficacy and highlight the contribution of other ADC components. Conclusions: These data demonstrate potent, target-dependent activity of the generated CADM1-targeted ADCs, validating CADM1 as a rational therapeutic target. Among them, CADM1-GGFG-Exatecan showed the strongest correlation between IC50 and target expression, supporting selective cytotoxic delivery. In vivo efficacy and toxicology studies are ongoing to finalize candidate selection. Citation Format: Caterina Longo, Zhongting Zhang, Wendong Zhang, Yifei Wang, Adil Bahadir, Yi Yanhua, Zhaohui Xu, Xin Zhou, Michael Roth, Jonathan Gill, Richard Gorlick. Surface CADM1 (Cell Adhesion Molecule 1) abundance predicts payload delivery and in-vitro efficacy of CADM1-GGFG-Exatecan ADC in osteosarcoma, aiding optimal candidate selection [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 7883.

Abstract Background: Osteosarcoma outcomes have not improved in over three decades, and prognosis remains poor for patients with pulmonary metastases. B7-H3 is highly expressed on osteosarcoma with limited normal-tissue expression, making it an attractive therapeutic target. This study evaluated the antitumor activity of a B7-H3-targeting antibody-drug conjugate (B7H3 ADC) in osteosarcoma PDX and metastatic models. Methods: The B7-H3 antibody (developed by ORBIT, MD Anderson) was conjugated to the tesirine payload SG3249. In vitro, cell viability was assessed in six PDX-derived osteosarcoma cell lines treated with B7H3 ADC (10-point dilution, 1000 nM start) over 120 h using Incucyte imaging. IC50 values were calculated by nonlinear regression, and dose-response effects were analyzed by one-way ANOVA with η2 and Cohen’s f. In vivo, six PDX models were treated with a single 1 mg/kg IP dose of B7H3 ADC, isotype-ADC, or PBS. Tumor growth inhibition and EFS were evaluated. Metastatic efficacy was assessed in IV and tibial injection models using luciferase-labeled SJSA LM7 cells, with treatment initiated at ∼3 × 106 photons/sec. Results: B7H3 ADC produced strong, dose-dependent cytotoxicity across all six cell lines (IC50 = 0.0795-0.6703 nM), with large effect sizes (η2 = 0.80-0.93; Cohen’s f = 2.01-3.65; p < 0.001). In vivo, three of six PDX models achieved maintained complete response (MCR), two showed partial response (PR), and one exhibited progressive disease (PD). In the IV metastasis model, control mice required euthanasia beginning on day 20, whereas all treated mice remained metastasis-free through day 93. In the tibial model, control mice were euthanized by day 25 with lung metastases detected by day 22. Treated mice showed complete tibial tumor regression by day 17 and remained metastasis-free through day 64. Conclusions: B7H3 ADC demonstrated potent and reproducible antitumor activity in osteosarcoma PDX and metastatic models, inducing durable tumor regression and preventing metastatic progression. These findings support B7-H3 as a promising therapeutic target and justify further development of B7H3 ADC for primary and metastatic osteosarcoma. Citation Format: Wendong Zhang, Adil Bahadir, Zhongting Zhang, Yianhua Yi, Zhaohui Xu, Simon Olivares, Harjeet Singh, AMER NAJJAR, Caterina Longo, Xin Zhou, Jasbir Kaur, Hiroki Torikai, Chunhua Shi, Jonathan Gill, Michael Roth, Tim Heffernan, Richard Gorlick. Antitumor activity of a B7-H3 antibody-drug conjugate in osteosarcoma patient-derived and metastatic models [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 7813.

Background Allogeneic transplantation (HCT) offers cure for hematologic malignancies, yet survivors face persistent physical and psychological challenges. Post-HCT care remains focused on relapse and graft-versus-host disease (GVHD) detection, with limited integration of patient-reported outcomes (PROs). Methods We analyzed 422 adult HCT recipients with completed MD Anderson Symptom Inventory-BMT (MDASI-BMT) at defined intervals post-HCT (median 360; range 30-2922 days). This 23-item tool rates physical and psychologic symptoms from 0-10; moderate distress is 4–6 and severe distress is ≥7. Multivariable mixed effects logistic regression modeled symptom burden by time and clinical variables including age, GVHD, relapse, conditioning intensity, and total body irradiation (TBI). Results Among 115,155,161 and 132 evaluable patients at 3,6,12 and 24mo, moderate-to-severe distress in ≥1 domain occurred in 62%, 76%, 65%, and 58% of patients at each timepoint. Severe symptoms were seen in 23-38%. Multi-domain burden persisted: at 3,6,12 and 24mo, ≥3domains with scores≥4 were reported in 33%, 39%, 46% and 28%; ≥4 in 28%, 34%, 41%, and 25%; ≥5 domains in 22%, 27%, 32%,and 19% and ≥6 in 20%, 23%, 27%, and 16%, indicating substantial morbidity with limited improvement over time. 13% of patients at 12mo and 7% at 24mo reported ≥9 abnormal domains, highlighting a small but vulnerable subset with severe morbidity. Fatigue was the most persistent (32% at 3mo, peaking at 35% at 6mo, and persisting at 30% at 2yrs).At 3mo, symptoms reflected acute effects: physical weakness (24%), dry mouth (18%), drowsiness (21%), and appetite loss (14%). By 2yrs, the burden shifted toward chronic domains: sexual dysfunction (21%), cognitive difficulty (19%), sleep disturbance (20%) and neuropathy (19.8%). Sadness (12%) and distress (11%) persisted at 2yrs, suggesting long-term psychosocial burden.Multivariable modeling found no association between symptom burden and relapse, TBI, GVHD or conditioning intensity. GI and oral symptoms improved over time including appetite (OR0.16,p<0.0001), diarrhea (OR0.18,p<0.0001), and nausea (OR0.2,p=0.005), and muscle weakness (OR0.37,p=0.004). In contrast, sexual dysfunction(OR 2.41,p<0.001), neuropathy(OR2.61,p<0.0001), joint stiffness(OR2.69,p=0.02), and cognitive difficulties(OR2.26,p=0.049) worsened. Importantly, fatigue, sadness, pain and dyspnea showed no improvement at any timepoint. GVHD was significantly associated with eye problems, dry mouth and sleep disturbance, but not with psychological burden or fatigue. Conclusion Despite resolution of acute symptoms, most survivors experience persistent, multi-domain morbidity years post-HCT including emotional, sexual and musculoskeletal effects. Symptoms underscore the need for structured long-term supportive care and routine integration of PROs into survivorship care.

Adolescent and young adult cancer patients (AYAs, aged 15–39) are at an elevated risk of experiencing psychosocial distress. Furthermore, most AYAs receive care in community oncology settings where little is known about distress screening and management for AYAs. We examined distress screening at National Cancer Institute Community Oncology Research Program (NCORP) across 100 practices previously identified as AYA-treating. Using data from the 2022 Landscape Assessment survey, distress screening and availability of mental health care were evaluated. Univariable and multivariable analyses examined associations between on-site availability of mental health services and AYA-relevant practice characteristics (e.g., Children’s Oncology Group affiliation, number of new AYAs annually, AYA program). Nearly all (91

Interventions that teach families to garden and cook may improve fruit and vegetable (FV) intake in children. However, this intervention approach has not been evaluated in childhood cancer survivors (CCS), who frequently have low FV intake. We developed and deployed a remotely delivered, gardening, nutrition, and cooking pilot “Cook-Grow!” for CCS and their families. The program consisted of five weekly educational lessons and activities for CCS and family members to complete. We delivered a gardening kit and groceries to participants’ homes that included a recipe in each lesson. Families completed weekly surveys and participated in semi-structured interviews that assessed the usage and acceptability of the program at the end of the pilot. Nine CCS 7–17 years old with prior diagnoses of acute lymphoblastic leukemia (n = 6), acute myeloid leukemia (n = 1), and Hodgkins lymphoma (n = 2) and their family members completed the study. Almost all (93

While quality of life (QoL) has been well-studied in older adults with melanoma, it has received less attention in adolescents and young adults (AYAs). Understanding QoL trajectories in AYAs with melanoma can help identify care gaps and develop interventions to support patients through cancer treatment and survivorship. A systematic review of MEDLINE, Embase, Cochrane, and Web of Science identified 4283 unique articles. Clinical trials, cohort studies, cross-sectional studies, and qualitative studies were included if the study cohort addressed any aspect of QoL in AYA patients (ages 15-39) with cutaneous, ocular, or mucosal melanoma. Out of 128 full-text articles, 9 met inclusion criteria, representing 1516 AYAs with melanoma. Psychological health was the most reported QoL domain, followed by social health and relationships. Compared with AYAs with other cancers, patients with melanoma, were more likely to experience distress related to body image, fear of cancer recurrence, and higher levels of depression, anxiety, and sexual problems. Eighty-two studies did not stratify QoL outcomes by age, and eight studies included AYA patients with multiple types of cancer, but did not stratify QoL outcomes by cancer type, thus, the AYA patients could not be identified within the larger QoL data pool and excluding at least 374 patients. Gaps remain in our understanding of these challenges, emphasizing the need for additional research investigating distress in this population. Developing a standard QoL battery and stratifying QoL outcomes by age and cancer type are two potential opportunities to improve future QoL outcomes research for this population.

Abstract Background: Adolescent and young adult cancer survivors (AYAs; diagnosed between ages 15-39) report worries regarding the health of their children, particularly regarding their chance of developing cancer. This study describes the frequency of reproductive health concerns among ethnically diverse survivors of AYA cancer and examines how genetic counseling impacts these concerns. Methods: AYAs between 18-39 years at diagnosis were recruited from two NCI-designated comprehensive cancer centers and a safety-net hospital. Concerns regarding the health of future children were evaluated using the three-item Child's Health Subscale (CHS), a subset of the Reproductive Concerns after Cancer Scale. Receipt of genetic counseling was self-reported. Descriptive statistics and mean overall score comparisons were examined, stratified by ethnicity and receipt of counseling. Results: The sample included 58 AYAs (48% Hispanic, 79% female) diagnosed at a mean age of 36 years (SD=5). The most common cancer types were breast (22%) and brain/spinal cord (19%). Additional cancer types included in our sample were cervical, uterine, ovarian, Hodgkin lymphoma, non-Hodgkin lymphoma, colorectal, melanoma, sarcoma, and ovarian. Overall, 56% (n=32) of AYAs reported they did not receive any form of counseling. AYAs had a mean CHS score of 2.11 (SD=0.8; range 1-3, where higher scores reflect greater concern), indicating moderate concern about their future child’s health. Mean CHS scores did not differ significantly for those who had received counseling versus those who had not (2.3 [SD=.7] vs 2.1 [SD=.9], p=.2, respectively). No significant differences were found between mean overall CHS scores and ethnicity. Conclusion: In this study, AYAs expressed moderate concerns about their future child’s health regardless of whether they received genetic counseling, suggesting that current counseling practices may not fully address the factors driving these concerns. Moreover, high concern levels among AYAs who did not receive counseling (presumably those not identified as having an indication for it) highlight potential gaps in how risk information and reassurance are conveyed within survivorship care. These findings indicate the need to strengthen reproductive health and genetic risk discussions across the survivorship continuum, ensuring both indicated and non-indicated survivors receive appropriate guidance, reassurance, and support. Citation Format: Dayanara Ruiz, Kimberly A. Miller, Jonathan Kaslander, Julia Stal, Mariah Bianca Echeverria, Charité N. Ricker, Andrea C. Betts, David Freyer, Michael Roth, Jessica L. Corredor. Parental concerns about hereditary risk in adolescent and young adult cancer survivors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 883.

12006 Background: Adolescent and young adult (AYA) survivors of cancer are at significant risk of adverse psychological outcomes, yet scalable, efficacious interventions to address their needs are limited. We evaluated a self-guided digital health intervention with affective, behavioral, and cognitive skills, “Enhancing Management of Psychological Outcomes With Emotion Regulation” (EMPOWER), for improving psychological outcomes. Methods: We recruited AYAs ( n = 352; 74% female, median age 33 years) from three comprehensive cancer centers between Dec 2021 and Sept 2024. AYAs were diagnosed at and currently aged 15 to 39 years, within 5 years post-curative treatment, and had internet access. In a full factorial design, AYAs were randomly assigned to 5 weekly components, either EMPOWER intervention or attention control (2 5 = 32 arms): 1. positive events, capitalizing & gratitude (vs. cognitive skills); 2. mindfulness (vs. financial literacy); 3. positive reappraisal (vs. nutrition); 4. personal strengths & goal-setting (vs. weight management); 5. acts of kindness (vs. sun protection). Didactic lessons and skills practices were delivered via a website designed specifically for the study. AYAs completed PROMIS measures for positive affect (primary outcome), and depression and anxiety (secondary outcomes) at pre-intervention, post-intervention, and two and four months post-intervention. Using the intent-to-treat principle and a mixed model with linear contrasts, we estimated average within-person changes over time by component (intervention/control) for AYAs and compared changes by component. Results: From pre to post-intervention, positive affect increased (p<0.05) among those in 3 of the 5 EMPOWER and 4 of the 5 control components (mean change = 1.4 to 1.9) and anxiety decreased (p<0.05) for those in 4 of 5 EMPOWER and 4 of 5 control components (mean change = -1.2 to -2.0). Further, anxiety was significantly lower (p<0.05) for all EMPOWER and control components at two and four-months post intervention (mean change = -1.3 to -2.4). There was little change in depression for any group. We found no treatment effects for any outcome whereby AYAs who received intervention content had significantly greater improvements than those receiving attention control content. Instead, some EMPOWER (positive events, capitalizing, & gratitude; acts of kindness) and control components (nutrition) were associated with clinically meaningful changes in outcomes, based on PROMIS metrics. Conclusions: Our findings suggest a range of affective, behavioral, and cognitive strategies drawn from both positive psychology and health education domains are similarly effective in enhancing positive affect and mitigating post-treatment anxiety and highlight the potential benefit of low-touch, self-guided digital health strategies for AYA survivors of cancer. Clinical trial information: NCT04317417 .

Abstract Background: Osteosarcoma is the most common primary bone malignancy in children and young adults. Despite multimodal therapy, survival rates have remained unchanged since the 1980s. Antibody-drug conjugates (ADCs) targeting CADM1 show promise as targeted treatments. This study compares the dose-response effectiveness of two CADM1-targeted ADC formulations, CADM1-GGFG-Exatecan and CADM1-PEG3-VC-Exatecan, in preclinical osteosarcoma models. Both ADCs are conjugated with Exatecan, a potent topoisomerase I inhibitor, but differ in their linker structures (GGFG vs PEG3), which may affect payload release and tumor penetration. Methods: We assessed the cytotoxicity of both ADCs in osteosarcoma cell lines (HOS, OS17, OS31) to determine IC50 values. Internalization studies compared uptake kinetics in the same lines. In vivo testing evaluated both ADCs in six patient-derived xenograft (PDX) osteosarcoma models (OS1, OS2, OS9, OS17, OS31, OS33) at doses of 3 mg/kg and 6 mg/kg. Human-IgG1-GGFG-Exatecan, Human-IgG1-PEG3-VC-Exatecan, and PBS served as isotype and vehicle controls. Tumor growth inhibition and event-free survival (EFS) were measured. Results: CADM1-GGFG-Exatecan showed significantly greater anti-tumor activity than CADM1-PEG3-VC-Exatecan, with lower IC50 values and higher internalization in CADM1-expressing cells. Internalization of CADM1-GGFG-Exatecan reached a steady plateau by day 4, whereas CADM1-PEG3-VC-Exatecan showed minimal uptake. In vivo, both ADCs were well tolerated (≤10% body weight loss). CADM1-GGFG-Exatecan significantly prolonged EFS across all six PDX models (P < 0.05), inducing maintained complete responses (MCR) in OS1, OS31, and OS33, a partial response (PR) in OS2, and progressive disease (PD) in OS9 and OS17. In contrast, PEG3-VC-Exatecan and all controls resulted in PD in all models. Conclusion: CADM1-GGFG-Exatecan demonstrates superior dose-response efficacy versus CADM1-PEG3-VC-Exatecan in both in vitro and in vivo osteosarcoma models. Its enhanced anti-tumor activity, likely driven by improved internalization and potency, supports further development in CADM1-expressing osteosarcoma, including optimization of pharmacokinetics and combination strategies. Citation Format: Zhongting Zhang, Caterina Longo, Wendong Zhang, Yifei Wang, Yanhua Yi, Zhaohui Xu, Xin Zhou, Adil Bahadir, Michael Roth, Jonathan Gill, Richard Gorlick. Dose-response efficacy of cell adhesion molecule 1 (CADM1)-GGFG-Exatecan vs CADM1-PEG3-VC-Exatecan in preclinical osteosarcoma models [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 7874.

10006 Background: Primary malignancies of the breast rarely affect adolescents and are uncommon in young adults. Limited information is available about their clinicopathologic characteristics and outcomes. The 5-year overall survival (OS) for women with breast cancer, not including ductal carcinoma in situ, exceeds 90%. However, it remains unclear whether adolescents and young adults experience similar outcomes compared with older patients. Methods: We conducted a retrospective study of all patients aged 0–25 years with primary breast malignancies seen at MD Anderson Cancer Center between 2000 and 2024. Demographics, histology, staging, treatment, and outcome data were collected. Event-free survival (EFS) and OS were estimated using the Kaplan–Meier method. Log-rank test was used to analyze patient outcomes by histology. Results: A total of 110 patients were identified. Median age at diagnosis was 23.9 years (range, 15.7–25.5). Two patients were male, 44.9% were White, 27.7% Hispanic, and 15.9% Black. The most common tumor histology was invasive ductal carcinoma (n=83, 75.5%), followed by sarcoma and malignant phyllodes tumors (n=14, 12.7%), carcinoma in situ (n=7, 6.4%), and rare histologic subtypes (n=6, 5.5%). Family history of breast cancer was present in 53.6% of patients and ovarian cancer in 9%. Of 81 patients with germline genetic testing, 25 (30.9%) had a cancer predisposition syndrome: Li-Fraumeni (n=9), BRCA1 (n=8), BRCA2 (n=4), ATM (n=2), other (n=2). Eleven patients (10%) had metastatic disease at presentation to bone, lung, distant lymph nodes, and liver. Among the 96 carcinoma cases, 36 (37.5%) were estrogen or progesterone receptor-positive and HER2-negative; 25 (26%) were HER2+, and 32 (33%) were triple-negative. Of the 110 patients, 69 (62.7%) received neoadjuvant chemotherapy, 37.6% of whom achieved a pathologic complete response, and 46.3% a partial response. Most patients (92.7%) had surgery (mastectomy 87.2% or lumpectomy 9.8%), 67.2% received radiotherapy, and 25.4% targeted therapy. Following treatment, 56 (51%) patients received adjuvant endocrine therapy. The 5-year EFS and OS for the cohort were 30% (95% CI, 22.6-39.9) and 71.8% (95% CI 62.9-82), respectively, and are presented by histology in the table. EFS (p=0.023) but not OS (p=0.36) was associated with histologic type. Conclusions: Primary breast malignancies in adolescents and young adults have distinct characteristics with a high frequency of family history and genetic predisposition syndromes and appear to be associated with lower survival compared with breast cancer in older patients. Histology No. of patients 5-year EFS (%) (95% CI) 5-year OS (%) (95% CI) Invasive ductal carcinoma 83 31.3 (22.8, 43.1) 68 (57.9, 80) Sarcoma and malignant phyllodes tumors 14 28.6 (12.5, 65.4) 82.1 (62.1, 100) Carcinoma in situ 7 42.9 (18.2, 100) 100 (100, 100) Rare histologic subtypes 6 NA 100 (100, 100)

Purpose: Pediatric, adolescent, and young adult (PAYA) cancer survivors face complex long-term medical and psychosocial needs for which many health care professionals lack training. This study evaluated the PAYA Cancer Survivorship Extension for Community Health care Outcomes (ECHO) program, a virtual, case-based telementoring program, in improving health care professionals' self-reported knowledge and confidence in survivorship care.Methods: A mixed-methods evaluation was done for the 12-session ECHO program (June 2024-May 2025). Surveys assessed changes in self-reported knowledge and confidence (5-point Likert scale), likelihood of applying learning, implementation barriers, and session impact. Quantitative data were analyzed using descriptive statistics.Results: Participants included 219 health care professionals from 153 organizations across the 36 U.S. states, one federal district, and 5 countries. Average session attendance was 57 (M = 56.83, SD = 13.07). Self-reported knowledge increased from 2.8 to 3.5 with confidence increasing from 2.7 to 3.4; gains were statistically significant across all 11 content sessions (p < 0.05). Participants reported a high likelihood to apply session content (mean ratings 3.1-4.6 on a 5-point scale), with all sessions except Session 1 exceeding 4.2. The most frequently cited barriers to applying content were lack of resources (26%), lack of time (23%), need for more training (23%); 10% reported no opportunities to apply information, and 37% (n = 130) reported no barriers.Conclusion: The ECHO program improved health care professionals' knowledge and confidence in PAYA survivorship care, with high intent to apply learning. Findings informed the launch of additional ECHO programs. Future efforts should further engage primary care providers and address barriers to translating knowledge into practice.

Abstract Purpose: Few studies characterize patient-reported outcomes in long-term survivors of adolescent and young adult (AYA, age 15-39 years at diagnosis) Hodgkin Lymphoma (HL). The present study aims to describe long-term health outcomes of survivors and identify the impact of cancer diagnosis and treatment exposures on health and quality of life (QoL). Methods: This study included AYA HL survivors (N=264) previously treated at MD Anderson Cancer Center who were at least 5 years post diagnosis. At time of study enrollment, participants completed a comprehensive health questionnaire, which included the SF-36 QoL questionnaire. The SF-36 was used to calculate Physical Component Summary (PCS) and Mental Component Summary (MCS) scores. A subset of HL patients (N=44) had also previously completed the SF-12 questionnaire within 6 weeks of diagnosis. In parallel, 67 siblings of cancer survivors completed the same health questionnaire. Clinical characteristics and treatment information were obtained from the medical record. Area deprivation index (ADI) was calculated based on zip code at time of questionnaire completion. Results: The median age at HL diagnosis and questionnaire completion of 26.0 and 41.8 years, respectively. Survivors had a significantly poorer PCS compared to siblings (45.3 vs 47.5, p=0.03), as well as a greater proportion of individuals with extremely poor PCS scores (scores ≤40; 16% vs 10%). Among HL survivors, no difference in PCS was observed by race/ethnicity (p=0.82). However, survivors who resided in neighborhoods with increased deprivation had significantly lower PCS compared to those in the highest resource neighborhoods (p=0.003). Treatment exposures and clinical characteristics were also related to PCS, in which survivors who received radiation treatment and had HL relapse were linked to lower PCS scores compared to survivors who did not (44.5 vs 46.7, p=0.03 and 43.5 vs 45.9, p=0.04). Survivors with extremely poor PCS reported increased prevalence of adverse health outcomes, such as diagnoses impacting cardiovascular, respiratory, and nervous systems (p<0.001 for each) compared to survivors with a PCS >40. These patients also reported increased cholesterol, pain, and depression medication use (p<0.001 for each). No differences in mental QoL defined by the MCS were observed between survivors and siblings. Conclusion: HL is characterized by long-term survival, making health outcomes and QoL integral aspects of their cancer experience. This study showed that long-term survivors of HL experience reduced physical QoL. Moreover, this reduction is related to adverse health outcomes, underscoring the necessity of long-term support and clinical interventions to improve physical health for HL survivors. Citation Format: Carlos Cruz, Amanda Warner, Adiya Rahman, Bryce West, Mia Brumlow, Qian Xiao, Karen Albritton, Gregory Aune, Karen Eshelman-Kent, Sairah Ahmed, Kelly Merriman, Susan Peterson, Michael Roth, Michelle A. T. Hildebrandt. Long-term physical quality of life in survivors of adolescent and young adult Hodgkin lymphoma: Risk factors and associations with adverse health outcomes [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 878.

BACKGROUND:Survivors of young adult (YA) cancer often experience substantial stress during the transition to survivorship, which may impair sleep. Although the stress-sleep link is well established, its role within survivor-spouse dyads remains unclear. Emotional intimacy may influence how couples regulate stress and affect sleep. This study examined dyadic associations between stress and sleep among survivors of YA cancer and their spouses and significant others (hereafter spouses) and tested emotional intimacy as a moderator. METHODS:A total of 103 survivor of YA cancer-spouse dyads completed self-reported measures of stress, emotional intimacy, and sleep quality. An actor-partner interdependence moderation model was used to test how each person's stress was related to their own and their spouse's sleep quality and the moderating role of emotional intimacy. RESULTS:In our model, higher stress was associated with poorer sleep quality among both survivors (β = 0.405, p < 0.001) and spouses (β = 0.172, p = 0.041), indicating significant actor effects, whereas no partner effects from stress were observed. Emotional intimacy moderated the stress-sleep association among survivors (β = -0.224, p = 0.004), but not among spouses (β = -0.012, p = 0.892). CONCLUSIONS:Stress emerged as a key intrapersonal determinant of sleep quality for both survivors of young adult cancer and their spouses, indicating that stress management may benefit sleep in both groups. Emotional intimacy buffered stress-related sleep disruption among survivors, but not spouses, highlighting role-specific mechanisms. Tailored approaches may improve sleep and quality of life.