Citations

1617 Background: Large language models (LLMs) are increasingly evaluated for oncology decision support, yet guideline concordance and hallucinations remain variable across cancer types and tasks. Retrieval-augmented generation (RAG) may improve safety by constraining the evidence base used during generation. Prior oncology LLM studies report discordance with guideline-based care, but few describe a reproducible health-system “vetting mechanism” that couples guideline-only retrieval with clinician-scored safety rubrics across multiple oncology domains. Methods: We assembled 316 de-identified oncology cases in a tumor-board template: medical oncology (breast, GI, GU, leukemia; n=216), gynecologic oncology (n=50), and neuro-oncology/CNS metastatic cancer (n=50). Each case was run on three systems: baseline GPT-4 (O1), NCCN-guideline anchored RAG (O2; guideline-constrained retrieval), and a literature-anchored system (OpenEvidence; O3). Oncologists independently scored outputs using a modified Generative Performance Score (mGPS; −1 to +1) combining guideline concordance with hallucination penalties; readability/rationality was scored on a 1–5 Likert scale. Inter-rater reliability was assessed (κ =.63). This workflow was designed as a pre-deployment model credentialing step for health-system governance (source policy → case bank → clinician-scored acceptance criteria). Results: Across all 316 cases (case-averaged), O2 achieved the highest mean total mGPS (0.75) compared with O1 (0.43) and O3 (0.59). In the medical oncology cohort (n=216), O2 outperformed O1 and O3 (mean mGPS 0.72 vs 0.35 and 0.54), with higher guideline concordance (0.85 vs 0.68 and 0.75) and lower hallucination penalties (−0.09 vs −0.25 and −0.19); readability was also highest for O2 (4.17 vs 3.22 and 3.86). In gynecologic oncology (n=50), O2 again performed best (mGPS 0.827) relative to O3 (0.697) and O1 (0.647). In the CNS cohort (n=50), mean composite mGPS favored O2 (0.82) over O3 (0.68) and O1 (0.55), while readability remained stable across models (3.55–3.73). Severe hallucination/unsafe recommendation rate: O1 [26%], O2 [5%], O3 [17%] (pre-specified definition; e.g., major fabricated citation or guideline-discordant harmful recommendation). Conclusions: In a 316-case, multi-domain clinician-scored evaluation, limiting retrieval to oncology guideline sources improved safety-aligned performance relative to unconstrained generation or literature-only anchoring. A guideline-constrained RAG configuration paired with clinician-scored rubrics and tail-risk reporting can serve as a practical health-system vetting mechanism for governance, re-validation, and change control of LLM decision support, including in resource-limited settings where reliable guideline-consistent recommendations are essential.

1591 Background: The 21-gene OncotypeDX (ODX) recurrence score (RS) is the standard for chemotherapy decision-making in HR+/HER2- early breast cancer (EBC), but cost limits accessibility in resource-constrained settings. The Magee equations (MEs) use routine pathology features (Nottingham grade and IHC; ER/PR/HER2/Ki-67) to estimate RS. We performed a meta-analysis to validate MEs performance as a triage tool for ODX testing and a qualitative synthesis to identify sources of discordance, highlighting the transition toward objective digital pathology AI models. Methods: A systematic review identified validation studies comparing MEs with RS in HR+ EBC. Studies with sufficient data to construct a 2X2 contingency table were included; neoadjuvant trials were excluded. Primary outcomes were Negative Predictive Value (NPV) for identifying low-risk cases (RS <26 for the current TAILORx cutoff and RS<31 for the historical cutoff) and ODX test sparing rate (TSR). Data were pooled using random-effects models. Qualitative themes regarding interpretation variability were extracted from study results and discussion sections. Results: Thirteen studies met the inclusion criteria, representing 5396 patients in global cohorts from the USA, Mexico, Colombia, Jordan, France, Belgium, and Canada. For RS >26, Magee <18 achieved pooled NPV of 0.96 (95% CI: 0.94-0.97) and TSR 61% (95% CI:51%-69%). For RS >31, NPV increased to 0.99 (95% CI: 0.97-1.00) and TSR 52% (95% CI: 44%-59%). Pooled diagnostic performance for Magee <18 predicting RS <26 demonstrated 83% sensitivity and 71% specificity (AUC 0.81, LR+:2.53, LR-:0.28). Qualitative analysis of discordance identified: (1) Inter-observer variability: Nottingham mitotic counts and Ki-67 scoring were the primary drivers of score fluctuations. (2) IHC quantification: Variations in H-score calculation and Allred-to-H-score conversion introduced heterogeneity (3) Pre-analytical and biological factors: Inflammation and stromal proliferation occasionally inflated genomic RS; selection of non-representative blocks and intratumor heterogeneity further contributed to discordance (4) Technological solutions: Digital pathology and AI models emerge as solutions to standardize these variables. Conclusions: Magee-based triage provides a safe and cost-effective strategy for HR+ EBC risk stratification, with NPV up to 99% for excluding high-risk disease and sparing up to 61% of ODX testing. These results confirm a robust histopathological signal. Transitioning to objective digital pathomics provides a pathway to reduce manual subjectivity and democratize precision oncology globally. Pooled diagnostic accuracy of Magee equations by cutoff. Magee score and RS cutoff Number of studies Total patients Pooled NPV (95% CI) ODX test sparing rate (95% CI) Magee <18/ RS>26 8 4153 0.96 (0.94-0.97) 61% (51%-69%) Magee <18/ RS>31 5 1243 0.99 (0.97-1.00) 52% (44%-59%)

1587 Background: Rehabilitation services (physical medicine and rehabilitation [PM&R], physical therapy [PT], occupational therapy [OT], and speech-language pathology [SLP]) improve physical function, symptom burden, and quality of life for cancer survivors, yet utilization remains low due to persistent barriers. The collaborative care model–based Enhanced Electronic Health Record–Facilitated Cancer Symptom Control (E2C2) pragmatic trial improved symptom burden and palliative care utilization. Using post hoc exploratory analyses of population-level trial data, we evaluated whether this EHR-facilitated approach also increased rehabilitation service use. Methods: E2C2 was conducted across Mayo Clinic Midwest medical oncology practices using an unblinded, stepped-wedge, cluster-randomized cohort design. The EHR-embedded intervention targeted SPPADE symptoms (sleep interference, pain, impaired physical function, anxiety, depression, and fatigue). Symptoms and physical function were assessed using 11-point numerical rating scales linked to oncology encounters. Patients received self-management materials for moderate symptoms (4–6/10) and care manager support for severe symptoms (7–10/10). All outpatient rehabilitation encounters across the Mayo Clinic Enterprise were abstracted. Mixed-effects Poisson models estimated intervention effects on rehabilitation visits during the first 365 days of exposure. Results: Between March 28, 2019, and January 31, 2023, 50,207 patients were enrolled. Intervention and control conditions included 31,719 and 28,938 patients, respectively, with 10,450 contributing data to both periods. Cross-sectionally, 25% of participants reported moderate and 9% severe physical function impairment. Of 91,220 rehabilitation encounters scheduled, 57,669 (63.3%) were completed. Completed encounters were predominantly PT (68.3%), followed by OT (16.4%), physician visits (9.4%), and SLP (4.2%). The intervention was associated with a more than fourfold increase in completed rehabilitation encounters during the six weeks following index symptom assessment (adjusted mean 2.22 [95% CI, 0.14–4.29] vs 0.54 [0.40–0.68]; incidence rate ratio 4.11 [1.43–11.82]; P =0.009). Scheduled encounters also favored the intervention but did not reach statistical significance. Conclusions: An EHR-embedded symptom surveillance intervention increased short-term rehabilitation service completion, but overall utilization remained low relative to the prevalence of physical function impairment, highlighting the need for system-level strategies to translate symptom identification into sustained rehabilitation engagement.

1557 Background: Immunotherapy is now a standard-of-care treatment for lung cancer across most stages. Access to immunotherapy and molecular diagnostic tests in conflict-affected countries such as Syria remains poorly described. As the principal cancer center in Syria, Al-Bairouni University Hospital (ABUH) provides care for nearly three-quarters of all cancer cases nationally. We conducted this study to evaluate access to immunotherapy and molecular diagnostic services at ABUH. Methods: A mixed-methods study was performed between 2022 and 2024 at ABUH. This study included a retrospective cohort of all patients diagnosed with lung adenocarcinoma. Quantitative data included disease stage at diagnosis, molecular testing rates, and immunotherapy utilization. In addition, a qualitative patient survey was thematically analyzed to explore barriers to treatment access in a separate cohort of patients with mixed tumor types. Results: Among 2,920 patients diagnosed with lung cancer, 1,393 (47.7%) had lung adenocarcinoma. The median age at diagnosis was 61 years; 79.7% of patients were male. Smoking history was as follows: Current 792 (56.9%), Former 268 (19.2%), never smoked 318 (22.8%) At presentation, 3 patients (0.2%) had stage I disease, 40 (2.9%) stage II, 174 (12.5%) stage III, and 778 (55.8%) stage IV disease, staging was unknown for the rest of the patients. EGFR mutation testing was performed by ABUH for 226/1393 patients (16.2%) only, with positive results identified in 124 cases (8.9%). PD-L1 testing was conducted by ABUH in only 32/1393 patients (2.3%) and was positive in 23 (1.65%). Of all patients with lung adenocarcinoma, only 5 patients (0.6%) with stage IV disease received immunotherapy. All were treated with nivolumab. Thematic analysis of qualitative data (35 patients) revealed that high treatment costs and limited drug availability are the primary barriers to accessing immunotherapy. Conclusions: This study represents the first evaluation of access to immunotherapy for patients with lung cancer in Syria. Even at ABUH, the country's main cancer center, access to immunotherapy and molecular testing remains markedly limited. International collaboration is necessary to expand diagnostic infrastructure, standardize data reporting, and enhance financial protection mechanisms. These are critical steps toward achieving better cancer care in Syria.

1584 Background: Decades of evidence demonstrate that patients across the cancer continuum may benefit from validated rehabilitation services, yet delivery remains inconsistent. Prior reports of underuse have largely relied on small, single-site cohorts and have lacked population-level estimates of service need, referral, and visit completion, contributing to the assumption that provider reluctance to refer is a primary driver. Using post hoc exploratory analyses of population-level trial data, we evaluated patient- and system-level factors associated with non-use of rehabilitation services. Methods: This secondary analysis used data from the Enhanced Electronic Health Record–Facilitated Cancer Symptom Control (E2C2) pragmatic trial, an unblinded, stepped-wedge, cluster-randomized cohort study comparing an EHR-embedded symptom surveillance and management system with usual care. All patients receiving care in Mayo Clinic Midwest medical oncology practices were enrolled regardless of cancer stage or phase. Symptoms and physical function were assessed using 11-point numerical rating scales linked to oncology encounters. Sociodemographic and clinical characteristics and all outpatient rehabilitation encounters across the Mayo Clinic Enterprise were extracted from the EHR. Rates and types of completed, canceled, and no-show rehabilitation encounters were examined. Results: Between March 28, 2019, and January 31, 2023, 50,207 patients were enrolled; 34% reported moderate or severe physical function impairment during follow-up. Despite this, only 8,818 patients (17.6%) completed at least one rehabilitation encounter. Of 91,220 encounters scheduled, 57,669 (63.3%) were completed (mean 6.5; median 3 per participant), leaving a substantial proportion canceled or no-showed (n=33,523, 36.7%). Completed encounters were predominantly physical therapy (68.3%), with fewer occupational therapy (16.4%), physician (9.4%), and speech therapy (4.2%) visits. Encounters were concentrated among patients with breast, hematologic, gastrointestinal, and genitourinary cancers. Completion was more likely among patients who were older, female, partnered, retired, and federally insured, whereas cancellations and no-shows were more common among younger, racial or ethnic minority, urban, unpartnered, employed, college-educated, and commercially insured patients (all P <0.001). Virtual visits and encounters in community (vs academic) settings were more likely to be completed (all P <0.001). Conclusions: A substantial gap persists between cancer survivors’ rehabilitation needs and service receipt, varying by cancer type and sociodemographic factors. High cancellation and no-show rates suggest that underuse extends beyond referral and underscore the need for redesigned, more accessible rehabilitation delivery models.

1564 Background: Adolescent and young adult (AYA) females with early-stage ER-negative and/or HER2-positive breast cancer commonly receive chemotherapy to reduce risk of recurrence. Fertility concerns, counseling, and preservation may influence chemotherapy decisions and time to chemotherapy (TTC) initiation. Methods: We surveyed AYA survivors of stage I–III premenopausal ER-negative and/or HER2-positive breast cancer treated at Kaiser Permanente Northern and Southern California (2013-2022). Fertility concerns were defined as not having completed desired family size or being unsure about having completed desired family size at diagnosis. We summarized receipt of fertility counseling, receipt of chemotherapy, and use of oocyte/embryo cryopreservation for fertility preservation (FP). Among fertility-concerned patients who received chemotherapy, TTC (days from diagnosis) was assessed separately for neoadjuvant chemotherapy (NAC) vs for adjuvant chemotherapy (AdjC). Time to NAC was natural log–transformed and modeled with multivariable log-linear regression to estimate relative differences in TTC, adjusting for stage, study site, ER, HER2, age, and diagnosis year. Results: Of 363 respondents, 197 (54%) had fertility concerns at diagnosis; 183/197 (93%) received chemotherapy, similar to 153/166 (92%) among those without concerns (p=0.7). Of the concerned chemotherapy recipients, 45 (25%) saw a fertility specialist but did not pursue FP while 55 (30%) underwent FP. For the 112 fertility-concerned NAC recipients, FP was associated with longer TTC than no fertility specialist counseling (mean=41 vs. 30 days; adjusted ratio=1.39; 95% CI 1.15–1.69), whereas fertility specialist counseling without FP was not (mean= 31 vs. 30 days, adjusted ratio=1.04; 95% CI 0.86–1.25). For the 71 fertility-concerned AdjC recipients, TTC was similar for patients who did not see a fertility specialist (mean=63 days), those who froze oocytes/embryos (mean=65 days), and those who saw a fertility specialist but did not pursue FP (mean=69 days). Conclusions: In this AYA breast cancer cohort, there was no evidence that fertility concerns led patients to decline chemotherapy. FP was associated with a modest delay in NAC initiation (<2 weeks on average). Time to chemotherapy (TTC) among 183 AYA patients with ER− and/or HER2+ breast cancer and fertility concerns. Fertility-focused care N (n=183) Neoadjuvant chemotherapy (n=112) Mean TTC, days Relative difference in TTC, adjusted ratio (95%CI) Adjuvant chemotherapy (n=71) Mean TTC, days No fertility counseling from a specialist 83 (45%) 55 (49%) 29.6 Reference 28 (39%) 62.6 Received fertility counseling from a specialist No fertility preservation 45 (25%) 28 (25%) 30.7 1.04 (0.86,1.25) 17 (24%) 68.6 Fertility preservation 55 (30%) 29 (26%) 41.2 1.39 (1.15,1.69) 26 (37%) 64.6

1503 Background: CAR T-cell therapy has revolutionized treatment outcomes in hematological malignancies, but has traditionally required inpatient post-infusion monitoring, which is associated with significant cost and time toxicity. Outpatient CAR T infusion and monitoring has been the standard approach at Mayo Clinic site in Rochester, MN, with demonstrated feasibility and safety (Bansal et al., ASCO 2023). We present data comparing healthcare utilization between CAR T recipients who underwent outpatient remote monitoring and those with traditional inpatient monitoring. Methods: Electronic medical records were retrospectively analyzed for 293 patients who received CAR T-cell therapy for a hematological malignancy at any of the 3 Mayo Clinic sites (MN, AZ, FL) between 2020 and 2024 . Healthcare utilization was compared between patients who received outpatient CAR T with remote patient monitoring in Rochester, MN (N = 125) and those who received inpatient CAR T in the Arizona (n = 90) and Florida (n = 78) sites. Per protocol, patients in the inpatient group underwent mandatory inpatient monitoring for 7 days, with extension per provider discretion. Data was analyzed through Chi-Square and Wilcoxon tests. P values < 0.05 were considered statistically significant. Results: There was no significant difference in baseline sex, age, ethnicity, LDH, platelets, or neutrophils among the 293 patients. Diagnoses included lymphoma (n = 175), multiple myeloma (n = 106), and B-ALL (n = 12). The most common CAR T-cell products used were axicabtagene ciloleucel (n = 138) idecabtagene vicleucel (n = 56), and ciltacabtagene autoleucel (n = 50). Median hospital days were lower in the outpatient group vs the inpatient group at 30 days (4.4 vs 13.3, P < 0.001) and 90 days (4.6 vs 13.6, P < 0.001). ICU admission occurred in 1 outpatient patient ( < 1%) vs 18 inpatient patients (11%) in the first 30 days (P < 0.001). In the first 30 days, 22% of patients in the outpatient group did not require hospitalization, while 56%, 15%, and 6% required 1, 2, and 3 hospitalizations, respectively. Similarly, only 11 (8.8%) patients in the outpatient group had ≥1 ED visit in the first 30 days compared with 32 (20%) pts in the inpatient group (P = 0.009). At 30 days, there was no difference in patient portal use, with 58% of patients using the portal at least once and a median of 1 message in both groups. Within the first 30 days, 53% and 2% of patients in the outpatient group required 1 and 2 outpatient visits, respectively, vs 29% and 2% in the inpatient group (P < 0.001). There was no difference in 30-day mortality (1.6% outpatient vs 2.4% in inpatient) between the 2 groups (P = 1.00) Conclusions: Outpatient CAR T-cell therapy monitoring was associated with significantly fewer hospital days without increased ED visits, ICU stays, portal use, or 30-day mortality. This demonstrates lower healthcare utilization for outpatient CAR-T therapy.

12122 Background: Aromatase Inhibitors (AI) have become the standard of care to reduce breast cancer recurrence in hormone receptor-positive (HR+) breast cancer patients. AIs have been shown to be effective in reducing the risk of breast cancer recurrence by 47%. However, up to 52% of patients prematurely discontinue their use due to AI-associated musculoskeletal pain symptoms called Aromatase Inhibitor-associated musculoskeletal pain syndrome (AIMSS). No effective treatment exists to treat AIMSS. The present study examined the effectiveness of a multicomponent pain treatment program in reducing symptoms of AIMSS with the goal of improving adherence to AI medication. Methods: This trial enrolled breast cancer survivors with AIMSS in an intensive multicomponent pain treatment program. Pain, impact on functioning, fatigue, and mood were assessed with the Brief Pain Inventory, Center for Epidemiologic Studies of Depression- Revised Questionnaire, Pain Catastrophizing Scale, Symptom Impact Questionnaire Revised, and Fatigue Questionnaire at baseline, 3-month, 6-month, 9-month, and 12-month intervals. Adherence to AI medication was obtained from patients’ self-reports. The treatment program consisted of a two-day structured intervention focused on Cognitive-Behavioral skills to address strategies to improve pain control, fatigue, sleep disturbance, and stress while educating patients on the efficacy of Aromatase Inhibitors in prolonging cancer-free survival. Results: A total of 73 patients were enrolled, with a median age of 63 years (range 31-79). Participants were primarily white, married, and highly educated. The measures showed elevated levels of pain, fatigue, and psychological distress at baseline with decrements in self-reported levels of functioning. Significant improvements across all measures were observed at the 3-month follow-up after participation in the multicomponent pain treatment program. Significant improvements in painrelated outcomes were observed at 3 months (WPI Δ −1.6; SS Δ −4.0; both p < 0.001), with sustained reductions in symptom severity through 6-month, 9-month, and 12-month follow-up. Self-report of AI medication adherence at one year showed that 77.9% of patients were still taking their prescribed medication. Conclusions: Patients with AIMSS experienced substantial emotional distress, pain, fatigue, and functional impairment at baseline. Following the intervention, significant improvements were observed across pain, physical functioning, fatigue, and psychological distress, with benefits sustained at one year. Importantly, the intervention was associated with high long-term adherence at one-year follow-up, highlighting its potential to improve both quality of life and treatment persistence.

12010 Background: BWEL (Alliance A011401; NCT02750826) is a Phase III trial that randomizes patients (pts) with stage II-III breast cancer and body mass index (BMI) ≥27 kg/m 2 1:1 to a 24-month (mo) lifestyle-based WLI + health education (HE) or HE alone. Here we report prespecified secondary outcomes of the impact of the WLI on patient-reported QOL and symptoms. Methods: The first 540 BWEL pts (randomized between 9/2016 and 7/2017) were included in this substudy that collected PROMIS 29 Profile 2.0 and Global Health scores at enrollment, 6 and 24 mos. Adjusting for baseline scores, mean physical function (predefined substudy primary outcome), global physical and mental health, fatigue and other scores were compared at 6 and 24 mos using analysis of covariance (ANCOVA). P-values <0.05 were considered significant. Positive differences in positive attributes (e.g., physical function) and negative differences in negative attributes (e.g., anxiety) represented better outcomes in the WLI arm. Results: At baseline, median BMI was 32.9 kg/m 2 (26.5 – 69.1), median age was 53 (25 - 78) years; 83.9% of pts were non-Hispanic White, 10.7% were Black and 5.9% were Hispanic. At 6 mos, the WLI (vs HE) arm had significantly better physical function (ANCOVA-based mean difference between arms 1.9 [95% CI 0.8, 3.0]; p<0.001), global physical health (2.0 [95% CI 0.9, 3.0]; p<0.001), global mental health (1.30 [95% CI 0.2, 2.4], p=0.03), social roles and activities (2.3 [95% CI 1.1, 3.6]; p<0.001), and fatigue (-1.7 [95% CI -3.1, -0.4], p=0.01) (Table). Improvements were generally maintained at 24 mos. Similar findings were seen in analyses using longitudinal mixed modeling. Conclusions: The BWEL WLI demonstrated QOL benefits for patients with breast cancer, resulting in significantly better physical function, global physical and mental health, and symptoms. Future analyses will evaluate which populations experienced the most benefit, as well as the relationships among QOL, symptoms, and weight loss. Support: U10CA180821, U10CA180882, UG1CA189823; U10CA180820; U10CA180868; U10CA180863, CCS 707213; U10CA180888; UG1CA189858; https://acknowledgments.alliancefound.org. Clinical trial information: NCT02750826 . Analysis of covariance-adjusted least squares means values at 6-mos adjusted for baseline scores. QOL/Symptom Attributes HE WLI Between arm difference (95% CI)* P value Physical Function 47.1 49.0 1.9 (0.8, 3.0) <0.001 Global Physical Health 46.2 48.1 2.0 (0.9, 3.0) <0.001 Global Mental Health 48.6 49.9 1.3 (0.2, 2.4) 0.03 Social Roles and Activities 52.7 55.0 2.3 (1.1, 3.6) <0.001 Anxiety 50.2 50.0 -0.2 (-1.6, 1.2) 0.77 Depression 47.5 47.5 -0.0 (11.2, 1.2) 0.96 Fatigue 50.6 48.9 -1.7 (-3.1, -0.4) 0.01 Sleep Disturbance 51.0 51.1 0.1 (-0.6, 0.8) 0.80 Pain Interference 51.3 50.3 -1.0 (-2.4, 0.4) 0.15 *Positive differences in positive attributes and negative differences in negative attributes favor WLI arm.

12007 Background: YAs with cancer, defined as those diagnosed prior to the age of 40, may experience greater symptom burden compared to those diagnosed at older ages. We evaluated the impact of an ePROM-triggered, CC-based, supportive care intervention on symptom burden in YAs with cancer. Methods: The Enhanced, Electronic Health Record-facilitated Cancer Symptom Control (E2C2) trial was a cluster-randomized, pragmatic trial (NCT03892967) that enrolled oncology patients seen at Mayo Clinic Rochester and within the Mayo Clinic Health System (sites in Minnesota and Wisconsin) between March 2019 and January 2023. Patients routinely reported the severity of six SPPADE symptoms (Sleep deficit, Pain, Physical function impairment, Anxiety, Depression, and Energy deficit/fatigue) on 11-point numerical rating scales. Symptom severity was classified as none to mild (0-3), moderate (4-6), or severe (7-10). Those with moderate or severe symptoms were offered symptom management education, while those with severe symptoms were also offered the option to work virtually with a symptom care manager. In this post hoc analysis, we examined the effects of the intervention on change in symptom scores among YAs and time to improvement to a mild/moderate level in those with at least one severe symptom. Results: Among 40,659 patients who responded to at least one survey, 2,598 were YAs and 38,061 were adults ≥ 40 years. Among YAs, 10.7%, 24.3%, and 65.1% were 18-24 years, 25-31 years, and 32-39 years, respectively. A greater proportion of YA patients were female (61.5% vs 57.0%), of a non-white race (12.4% vs 5.3%), living in an urban setting (65.7% vs 55.1%), single (36.4% vs 9.6%), on non-government insurance (78.1% vs 36.6%), employed (72.6% vs 37.4%), and had a Bachelor’s degree or greater (37.8% vs 28.3%, p < 0.001 for all). Fewer YA patients had metastatic disease compared to older patients (24.2% vs 35.2%, p < 0.001). Compared to a pre-intervention baseline, the mean change in symptom score for YA patients following the intervention demonstrated improvements in anxiety (-0.195) and depression (-0.168, p < 0.0001 for both), while physical function impairment worsened over the intervention period (0.101, p = 0.014). Compared to adults ≥ 40 years, YAs experienced greater intervention effects for management of depression ( p < 0.001), fatigue ( p = 0.01), pain ( p < 0.0001), and physical function impairment ( p < 0.0001). Among YAs with a severe symptom during the intervention period, median time to improvement to a mild/moderate level was longer for anxiety compared to those ≥ 40 years (3.5 vs 2.7 months, p = 0.009). Conclusions: Routine ePROM surveillance, coupled with CC-based symptom management, led to improvements in anxiety and depression among YAs with cancer, although, time to improvement was longer for anxiety compared to adults ≥ 40 years.