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ABSTRACT Introduction and Methods Cancer therapy–related cardiac dysfunction (CTRCD) is a well established and potentially life‐threatening complication of contemporary oncologic treatment. Although comprehensive cardio‐oncology guidelines have been developed, their integration into routine hematology and oncology practice remains inconsistent. This consensus statement, developed by a multidisciplinary panel of cardio‐oncology experts, aims to provide practical, case‐based guidance to help oncology providers recognize, assess, and manage CTRCD across a spectrum of malignancies and cardiovascular presentations. Clinical Scenarios and Discussion We present representative clinical scenarios that illustrate real‐world challenges in cardio‐oncology and apply evidence‐based recommendations from current guidelines, including those from the European Society of Cardiology (ESC) and the International Cardio‐Oncology Society (ICOS)—to support informed decision‐making. Key areas of focus include baseline cardiovascular risk stratification prior to initiating potentially cardiotoxic therapies, with an emphasis on biomarker and imaging surveillance strategies tailored to individual risk profiles. Also, this document outlines the application of guideline‐directed medical therapy (GDMT) for cancer patients with heart failure. Conclusion By offering a structured, user‐friendly framework, this document seeks to bridge the implementation gap between oncology and cardiology disciplines. Our goal is to equip oncology providers with accessible tools that facilitate early recognition, consistent surveillance, and timely referral, thereby preserving cancer treatment intensity while minimizing cardiovascular morbidity.

230 Background: The burden of symptoms and financial toxicity are well-documented adverse effects of cancer treatments. Recently, logistic toxicity has emerged, referring to the detrimental impact of logistical demands associated with cancer treatment on patient well-being. For non- English speaking patients, language barriers can affect their treatment experience, increasing logistic burdens. Methods: Between September 2024 and May 2025, semi-structured qualitative interviews were conducted with 21 low English proficiency (LEP)/non-English speaking adults with cancer. The interviews explored logistic challenges faced due to LEP and its impact on patients' cancer care experience. Transcripts were analyzed using an inductive thematic analysis approach. Results: Of the 39 identified eligible individuals, 26 provided consent, and 21 (81%) completed the interview. The most common primary language of the participants was Spanish (9, 43%), followed by Somali (3, 14%), Arabic and Korean (2, 9%), and Amharic, Mandarin, Hmong, Russian, and Vietnamese (1, 5%). Seven major themes emerged regarding the logistic burdens of cancer care: (1) communication challenges, (2) navigating healthcare systems, (3) emotional distress from diagnosis and communication barriers, (4) financial toxicity, (5) transportation challenges, (6) adverse treatment effects, and (7) concerns about the political climate and its impact on resources. Conclusions: The increase in non-English languages in the U.S. highlights the need to understand the unique challenges faced by these patients. This study identified logistic toxicity themes consistent with previous research, while also revealing unique challenges. Further research is necessary to explore strategies to mitigate logistic burdens among those with LEP. Theme Illustrative Quotes Communication challenges “Communication with the psychologist was challenging … I couldn’t express myself effectively and it left me unsatisfied with the interaction.” Navigating healthcare systems “dealing with the insurance, it has been difficult … I have to depend on another person to help me” Emotional distress from diagnosis and communication barriers “In addition to my sickness, the lack of communication and understanding… makes me very sad.” Financial toxicity “...there's no income. There is nothing to feed our children.” Transportation challenges “I have to leave home 2 or 3 hours in advance because people will help me, not within my time, but within their own time.” Adverse treatment effects “I noticed weird feelings in my limbs. I'm not able to write down or hold anything. It makes everything difficult.” Concerns about current political climate and its impact on existing resources “… that they don't want Spanish spoken in the United States. They're not going to provide help for people like me at the hospitals…”

PURPOSE Neoadjuvant immunotherapy (IO) has become the standard of care for early-stage triple-negative breast cancer (TNBC), but not yet for other subtypes. We previously developed a clinical-grade mRNA-based immune classifier (ImPrint) predicting response to IO that is now being used in I-SPY2.2 as part of the response predictive subtypes. We report the performance of ImPrint in hormone receptor–positive and human epidermal growth factor receptor 2–negative (HR+HER2–) patients from five IO arms. METHODS A total of 204 HR+HER2– (MammaPrint high-risk) patients from five IO arms (anti–PD-1, anti–PD-L1/poly [ADP-ribose] polymerase inhibitor combination, anti–PD-1/toll-like receptor 9 dual-IO combination, and anti–PD-1 ± lymphocyte activation gene 3 dual-IO combination) and 191 patients from the chemotherapy-only control arm were included in this analysis. Patients were classified as ImPrint+ (likely sensitive) versus ImPrint– (likely resistant), using pretreatment mRNA. Performance of ImPrint for predicting pathologic complete response (pCR) to IO-containing arms was characterized and compared with tumor grade (III), MammaPrint (ultra) High2 risk (MP2), and estrogen receptor (ER)-low (ER ≤ 10%). RESULTS Overall, the pCR rate across the five IO arms was 33%. 26% of HR+HER2– patients were ImPrint+, and pCR rates with IO were 75% in ImPrint+ versus 17% in ImPrint–, with the highest pCR rate >90% in a dual-IO arm. In the control arm, pCR rates were 33% in ImPrint+ and 8% in ImPrint–. Tumor grade (III), MP2, and ER-low showed pCR rates in IO of 45%, 56%, and 63%, respectively, with lower pCR odds ratios (OR < 7.5) compared with ImPrint (OR = 14.5). CONCLUSION Using an accurate selection strategy, HR+HER2– patients could achieve pCR rates similar to what is seen with best neoadjuvant therapies in TNBC and HER2+ (ie, pCR rate >65%-70%). ImPrint, an Food and Drug Administration IDE-enabled assay, may represent a way to identify HR+HER2– patients for IO that best balances likely benefit versus risk of serious immune-related adverse events.

610 Background: The adverse event (AE) landscape in oncology is changing due to the introduction of immunotherapy and antibody drug conjugates. These AEs come with both short and long-term symptoms that significantly impact patient quality of life. Monitoring for early onset of symptoms could optimize therapy for a particular patient, maximizing potential efficacy while mitigating toxicity. It is also possible that some toxicities are directly associated with drug sensitivity. We sought to identify symptoms associated with pathologic complete response (pCR) using patient-reported outcomes (PROs) in early-stage high-risk breast cancer patients. Methods: Our study population included 288 stage II/III high-risk breast cancer patients enrolled on the I-SPY2 trial from 2021-2024, who received novel neoadjuvant therapies ± standard paclitaxel. pCR was assigned if tumor was absent in breast and nodes at surgery following neoadjuvant treatment. Patients (n = 288, pCR rate = 29%, 89% administered immunotherapy) were sent electronic PROs. 33 patient-reported AEs were measured using NCI's Patient Reported Outcomes - Common Terminology Criteria for Adverse Events (PRO-CTCAE). Each symptom was evaluated using severity, frequency, and interference on a Likert Scale. Presence of early PRO symptoms (cycles 1-3 of treatment) were binarized (at least one of moderate or greater), and odds ratios were computed with pCR as outcome. To assess whether higher grade AEs were enriched in patients that achieved a pCR, we also performed the Wilcoxan rank sum test using maximum (worst) symptom severity. Results: Of 288 patients included in our analysis (median age = 48 years, range = 20-78), 203 (70.5%) were White, 17 (5.9%) were Asian, 33 (11.5%) were Black or African American, and 35 (12.2%) were Hispanic. PRO analysis revealed that patients that had moderate to severe muscle pain (27% vs 10% OR = 3.15, p < 0.05), joint pain (22% vs 8% OR = 3.23, p < 0.05), headache (27% vs 12.5% OR = 2.59, p < 0.05), or mouth/throat sores (16% vs 5% OR = 3.56, p < 0.05) within weeks 1-3 had higher odds of achieving a pCR. When we looked at maximum severity between weeks 1-3, patients that achieved a PCR had higher grade muscle pain (p = 0.04), heart palpitations (p = 0.035), and significantly lower grade numbness and tingling (p = 0.002). Beyond 6 weeks, associations were weaker or insignificant. Conclusions: Our study utilizes an analysis framework that was able to determine sentinel symptoms such as muscle and joint pain, mouth/throat sores and palpitations as early as weeks 1-3 associated with increased efficacy. This may suggest an early immune reaction in patients that eventually respond favorably to treatment. Our work can help provide earlier proactive monitoring to mitigate toxicities, treatment redirection if needed, and a potential symptom-based early understanding to personalize treatment efficacy. A similar analysis is underway to predict immune related AEs. Clinical trial information: NCT01042379 .

1015 Background: T-DXd is an antibody-drug conjugate approved for advanced HER2+/low/ultra-low breast cancer and multiple other solid tumors. T-DXd carries a rare but serious risk of ILD (incidence 12-15%), requiring frequent imaging and symptom evaluation. For > grade (G) 2 ILD, guidelines recommend permanent drug discontinuation. For asymptomatic G1 ILD, drug is held with the option for rechallenge (RC) if imaging findings resolve. Limited data exist on outcomes of RC after ILD in diverse real-world patients (pts). Methods: In this multi-center retrospective study, we analyzed pts with T-DXd related ILD treated from 2017-2024. Pts with ILD were identified via chart/ICD code review. Adjudication of T-DXd related ILD was based on treating providers’ assessment and graded via CTCAE v5. We collected pt demographics, T-DXd and steroid dosing, imaging results, and outcomes after RC. Statistical analysis was performed using Wilcoxon rank sum and Fisher’s exact tests. Results: Four centers treated 712 pts with T-DXd, with a 9.1% rate of any grade ILD (n=65). One other center reported only RC data in 18 pts with ILD. In total, 47 pts were RC; 38 after G1 ILD (81%), 9 after G2. Median (med) time to initial ILD was 145 days (d) after 1st dose (interquartile range [IQR] 78-205). Demographics for pts RC are shown in the table. Among 50 pts with G1 ILD, including pts not RC, 28/50 (56%) received steroids for a med of 36d (IQR 27-79). Radiographic improvement was seen at a med of 24d (IQR 19-63) for pts treated with steroids vs 82d (IQR 48-94) without (p<0.01); and a med of 35d (IQR 22-82) for pts RC vs 81d (IQR 68-105) for pts not RC (p=0.01). Among pts with G1 ILD, 38/50 (76%) were RC at a med of 42d (IQR 36-57) from last dose; 23/38 (61%) were dose reduced. After RC, pts remained on T-DXd for a med of 215d (IQR 60-334); 10/38 (26%) developed recurrent ILD (7-G1, 2-G2, 1-G3) at a med of 211d (IQR 47-273) from RC. No statistically significant differences were seen between ILD onset, time to RC, or demographics for pts with recurrent ILD vs not. Of the 9 pts RC after G2 ILD, T-DXd was continued for a med of 129d (IQR 49-171); 2/9 (22%) developed recurrent ILD (1-G2, 1-G3). No G5 toxicity was seen with RC. Conclusions: In this multi-center study, high RC rates were seen after G1 ILD with long duration of clinical benefit. Pts treated with steroids had faster radiographic ILD improvement, highlighting the importance of early steroid use. Among pts RC after G1 ILD, recurrent ILD rates were low, with the majority G1 and no G5 events. Notably, 9 pts with G2 ILD were RC, with a similar rate of recurrent ILD; this must be interpreted cautiously. Our large cohort data further supports the safety of T-DXd RC in diverse real-world settings. RC Pt Characteristics (n=47) n (%) or Median (IQR) Cancer typeBreastGIGyn 43 (91)3 (6)1 (2) Age (yrs) 57 (52-68) Prior # therapy lines in the advanced/metastatic setting 3 (1-5) Renal impairment (CrCl < 60 mL/min) 8 (17)

271 Background: Many studies have shown that fatigue is associated with poor outcomes such as quality of life and physical function in breast cancer survivors.Early treatment of symptoms that result in persistent fatigue may be a strategy to mitigate long-term fatigue.As a result, we studied symptoms and developed risk estimates for patients that are most likely to develop fatigue by pre-surgery and follow up among patients treated on the I-SPY 2 neoadjuvant trial. I-SPY 2 is a phase-II adaptive trial for high-risk early-stage breast cancer patients. Methods: In this retrospective cohort study of 306 women undergoing neoadjuvant chemotherapy +/- targeted therapy, patients complete electronic surveys of symptoms via 34 PRO-CTCAE items and QOL via 9 PROMIS instruments. Fatigue is collected as part of the PROMIS survey and scored using Health Measures. Study timepoints are screening (SC), weekly study treatment (ST), 12 weeks (12w), pre-surgery (PS) and at 1, 6, 12 and 24 months (FU1-FU4) following surgery. Correlation between symptoms and fatigue at equal timepoints was quantified using spearman correlations and BH-adjusted p-values. For symptom odds analysis, symptoms were binarized such that those that had an average grade of mild or above (severity), rarely or above (frequency) or a little bit or above (interference) between ST weeks 1-6 were considered present. Clinically significant (CS) increase in fatigue was defined as an increase >=0.5 standard deviation (SD) in mean from baseline. Logistic regression was used to determine odds ratios of factors associated with fatigue. Results: Baseline PROMIS fatigue mean score was 47.14 (SD 9.31) with a median of 47.45. A CS increase in fatigue from baseline was seen in 55% of patients at 12w, and 61% of patients pre-surgery. Of the patients that had a CS increase in fatigue at any point prior to surgery, 45.7% had persistent fatigue through FU1-4. Symptoms associated with Fatigue at 12w were shortness of breath, headache, and nausea (P< 0.03). At PS, fatigue was significantly correlated with GI symptoms, neuropathy, and shortness of breath (P< 0.03). Risk estimates for patients that filled out symptom surveys at early timepoints (weeks 1-6) and also had fatigue were evaluated. Patients with early GU (genitourinary) symptoms had higher risk of fatigue at IR (OR=9.33, p=0.02, 88.9% in cases vs 33.3% in controls). Patients with early GI symptoms at PS (OR=8.56, p=0.03, 90.1% vs 50%), or FU2-4 (OR= 5.88 and 7.36, p= 0.04 and 0.02, 80% vs 39.1% and 81.8% vs 36.3%) also had a higher risk of developing fatigue. Conclusions: A CS increase in fatigue during treatment and follow up is seen in the majority of patients and is associated with a large number of persistent symptoms.

Abstract Objectives We describe the development and implementation of a system for monitoring patient-reported adverse events and quality of life using electronic Patient Reported Outcome (ePRO) instruments in the I-SPY2 Trial, a phase II clinical trial for locally advanced breast cancer. We describe the administration of technological, workflow, and behavior change interventions and their associated impact on questionnaire completion. Materials and Methods Using the OpenClinica electronic data capture system, we developed rules-based logic to build automated ePRO surveys, customized to the I-SPY2 treatment schedule. We piloted ePROs at the University of California, San Francisco (UCSF) to optimize workflow in the context of trial treatment scenarios and staggered rollout of the ePRO system to 26 sites to ensure effective implementation of the technology. Results Increasing ePRO completion requires workflow solutions and research staff engagement. Over two years, we increased baseline survey completion from 25% to 80%. The majority of patients completed between 30% and 75% of the questionnaires they received, with no statistically significant variation in survey completion by age, race or ethnicity. Patients who completed the screening timepoint questionnaire were significantly more likely to complete more of the surveys they received at later timepoints (mean completion of 74.1% vs 35.5%, P &lt; .0001). Baseline PROMIS social functioning and grade 2 or more PRO-CTCAE interference of Abdominal Pain, Decreased Appetite, Dizziness and Shortness of Breath was associated with lower survey completion rates. Discussion and Conclusion By implementing ePROs, we have the potential to increase efficiency and accuracy of patient-reported clinical trial data collection, while improving quality of care, patient safety, and health outcomes. Our method is accessible across demographics and facilitates an ease of data collection and sharing across nationwide sites. We identify predictors of decreased completion that can optimize resource allocation by better targeting efforts such as in-person outreach, staff engagement, a robust technical workflow, and increased monitoring to improve overall completion rates. Trial Registration https://clinicaltrials.gov/study/NCT01042379.

Abstract Background The legal climate for cannabis use has dramatically changed with an increasing number of states passing legislation legalizing access for medical and recreational use. Among cancer patients, cannabis is often used to ameliorate adverse effects of cancer treatment. Data are limited on the extent and type of use among cancer patients during treatment and the perceived benefits and harms. This multicenter survey was conducted to assess the use of cannabis among cancer patients residing in states with varied legal access to cannabis. Methods A total of 12 NCI-Designated Cancer Centers, across states with varied cannabis-access legal status, conducted surveys with a core questionnaire to assess cannabis use among recently diagnosed cancer patients. Data were collected between September 2021 and August 2023 and pooled across 12 cancer centers. Frequencies and 95% confidence intervals for core survey measures were calculated, and weighted estimates are presented for the 10 sites that drew probability samples. Results Overall reported cannabis use since cancer diagnosis among survey respondents was 32.9% (weighted), which varied slightly by state legalization status. The most common perceived benefits of use were for pain, sleep, stress and anxiety, and treatment side effects. Reported perceived risks were less common and included inability to drive, difficulty concentrating, lung damage, addiction, and impact on employment. A majority reported feeling comfortable speaking to health-care providers though, overall, only 21.5% reported having done so. Among those who used cannabis since diagnosis, the most common modes were eating in food, smoking, and pills or tinctures, and the most common reasons were for sleep disturbance, followed by pain and stress and anxiety with 60%-68% reporting improved symptoms with use. Conclusion This geographically diverse survey demonstrates that patients use cannabis regardless of its legal status. Addressing knowledge gaps concerning benefits and harms of cannabis use during cancer treatment is critical to enhance patient-provider communication.

11113 Background: Patient-reported outcomes (PROs) are valuable for understanding treatment tolerability and toxicity. I-SPY2 is a phase-II neoadjuvant clinical trial for breast cancer with electronic PROs and quality of life (QOL) assessments. We sought to understand how well the GP5 self-reported tolerability item reflected toxicity burden and QOL during treatment and follow-up in I-SPY 2 participants. Methods: Our study included 306 patients who completed the FACIT Item GP5 and answered PROMIS surveys at two or more timepoints. Analysis timepoints included screening (SC), inter-regimen (IR), pre-surgery (PS), 1-month post-surgery (FU1), and 6-months post-surgery (FU2). Symptoms were assessed weekly using PRO-CTCAE and CTCAEv4.0. QOL was evaluated using PROMIS. The GP5: “I am bothered by side effects of treatment,” was used to estimate tolerability, where worse tolerability is a higher score. Odds ratios, Spearman correlation, and regularized multi-variate regression were used to evaluate the associations between individual symptoms and adverse events with GP5 scores. Results: Demographic information was available for 243 of the 306 (70.2%) participants (median age=47,73.7% white). In the 306, tolerability scores worsened over study treatment, with a maximum mean score of 1.71 at Cycle 11. Tolerability improved after treatment cessation at FU1(1.09). Mean tolerability at week 6 was 1.53. The only clinical factor that was associated with early change in tolerability (week 6 to PS) was age >50 (mean score ranged from 1.55-1.70 vs 1.29-1.45 (age<50), p<0.05). PRO-CTCAE and GP5 correlative analysis suggested that higher grade abdominal pain, decreased appetite, dizziness and blurry vision significantly associated with higher GP5 scores at multiple timepoints (p<0.05). Symptoms not associated with tolerability were nail loss, acne, hair loss, and rash (p>0.05). Additionally, the total number of low-grade (mild to moderate) symptoms a patient experienced during study treatment was significantly correlated to poor tolerability (p<0.00001). Among patients with CTCAE data, 9% had adrenal insufficiency, and higher GP5 was found across all study timepoints in those with (compared to without) adrenal insufficiency (mean GP5 = [1.7-1.9] vs [1.3-1.5] respectively). Similarly, among patients with neuropathy (14%), higher GP5 scores were reported across all study timepoints (mean GP5 = [1.8-2.3] vs [1.3-1.5] respectively). Higher GP5 scores during treatment were correlated with higher fatigue scores at PS and FU1 (p<0.02 and p<0.001) and lower physical functioning at PS (p<0.01). Conclusions: TheGP5 measure is associated with self-reported symptoms, higher grade adverse events and quality of life scores. Furthermore, greater accumulation of lower grade symptoms can lead to poor tolerability. The single measure GP5 composite score reflects multiple components of treatment toxicity.

10026 Background: Childhood cancer survivors are at high risk for developing subsequent breast cancer with higher mortality than females in the general population with primary breast cancer. Whether therapeutic tradeoffs in treating primary versus subsequent breast cancer alter survival is unknown. Methods: Breast cancer treatment data were abstracted from medical records for female survivors from the CCSS and a multi-institutional sample of females with primary breast cancer matched one-to-one by demographics, diagnosis age/year, and breast cancer characteristics. Survivors’ excess mortality risk was evaluated as hazard ratios (HRs), adjusting for receipt of historically-appropriate guideline-concordant treatment established for primary breast cancer. Results: Subsequent breast cancers were diagnosed between 1981-2016 among 431 survivors, with a median diagnosis age of 40 years (IQR: 35-44). Most subsequent breast cancers were invasive (77%), with hormone receptor profiles similar to the general population (78% ER-positive; 26% HER2-positive). Guideline-concordant breast cancer treatment did not differ between survivors and controls (N = 688; 94% versus 93%), but treatment selection differed, reflecting survivors’ complex clinical history and guidelines’ multiple treatment options. Anthracyclines were used in 47% of survivors (controls 66%), mastectomy in 81% of survivors (controls 60%), and radiotherapy in 18% of survivors (controls 61%). In the subgroup treated with surgery and chemotherapy (survivors 31%, controls 26%), survivors did not have greater likelihood of dose reductions or omissions, treatment delays, or hospitalization for fever and neutropenia, but they were more likely to experience hematological toxicities (21% vs. 9%, p = 0.033) and other organ system-specific toxicities (36% vs. 11%, p < 0.001). Over one-third (38%) of survivors died during follow-up (median follow-up 9 years, IQR 6-14) after breast cancer. Strikingly higher all-cause mortality was observed among survivors than controls (HR = 3.5, 95% CI 2.2-5.6), especially after in situ disease (HR = 9.9, 95% CI 2.2-44.2). Among survivors with invasive disease, breast cancer accounted for most deaths (51%), followed by other subsequent malignancies (15%) and cardiovascular diseases (15%). Other health conditions accounted for 67% of deaths following in situ disease. Conclusions: Childhood cancer survivors with subsequent breast cancer generally receive guideline-concordant breast cancer treatment. While the treatments survivors receive differ from females with primary breast cancer, they do not experience higher rates of on-therapy treatment modifications. Despite this, they face excess mortality, primarily driven by other health conditions. Managing comorbidities is critical to enhancing long-term survival for this high-risk population.