Citations

Background: There are limited evidence-based data to guide treatment recommendations for breast cancer (BC) patients ≥80 years (P80+). Identifying and addressing unmet needs are critical. Aims: Advocate-BREAST80+ compared the needs of P80+ vs. patients < 80 years (P80−). Methods: In 12/2021, a REDCap survey was electronically circulated to 6918 persons enrolled in the Mayo Clinic Breast Disease Registry. The survey asked about concerns and satisfaction with multiple aspects of BC care. Results: Overall, 2437 participants responded (35% response rate); 202 (8.3%) were P80+. P80+ were less likely to undergo local regional and systemic therapies vs. P80− (p < 0.01). Notably, P80+ were significantly less satisfied with information about the short and long-term side effects of BC therapies and managing toxicities. P80+ were also less likely to have participated in a clinical trial (p < 0.001) or to want to do so in the future (p = 0.0001). Conclusions: Although P80+ experienced less anxiety and symptom-related distress compared with P80−, they were significantly less satisfied with information regarding the side effects of BC therapies and their management. P80+ were significantly less likely to have participated in a clinical trial or be open to considering this option. Future studies should address educational needs pertaining to side effects and barriers to research participation in P80+.

Objectives The aim of this study was to create and validate a 3-dimensional (3D) ultrasound model with normal and abnormal pediatric hip joint anatomy that is comparable to a pediatric hip joint in appearance and anatomy and replicates sonographic characteristics of a pediatric hip joint. Methods A 3D rendering of the bone and soft tissue was created from a computed tomography pelvic scan of a pediatric patient. This rendering was modified to include a unilateral joint effusion. The bone was 3D printed with a photopolymer plastic, whereas the soft tissue was cast with a silicone mixture in a 3D-printed mold. The effusion was simulated by injecting saline into the soft tissue cavity surrounding the bone. The ultrasound model was validated by pediatric point-of-care ultrasonographers at an international pediatric ultrasound conference. Results A pediatric hip ultrasound model was developed that simulates both normal and abnormal pediatric hip joint anatomy, each with an appropriately sized, measurable joint effusion. Validation by pediatric point-of-care ultrasonographers showed that the key aspects of a normal pediatric hip joint (femoral physis, sloped femoral neck, and adequate soft tissue) with an identifiable and measurable effusion were included in the ultrasound model. Conclusions In this study, we successfully created a cost-effective, reusable, and reproducible 3D pediatric hip ultrasound model. The majority of pediatric point-of-care ultrasonographers who evaluated the model agreed that this model is comparable to a pediatric patient for the purpose of teaching ultrasound skills and joint space measurement.

PURPOSE Long-term outcomes of patients with stage I human epidermal growth factor receptor 2 (HER2)–positive breast cancer receiving adjuvant trastuzumab emtansine (T-DM1) remain undefined, and prognostic predictors represent an unmet need. METHODS In the ATEMPT phase II trial, patients with stage I centrally confirmed HER2-positive breast cancer were randomly assigned 3:1 to adjuvant T-DM1 for 1 year or paclitaxel plus trastuzumab (TH). Coprimary objectives were to compare the incidence of clinically relevant toxicities between arms and to evaluate invasive disease-free survival (iDFS) with T-DM1. Correlative analyses included the HER2DX genomic tool, multiomic evaluations of HER2 heterogeneity, and predictors of thrombocytopenia. RESULTS After a median follow-up of 5.8 years, 11 iDFS events were observed in the T-DM1 arm, consistent with a 5-year iDFS of 97.0% (95% CI, 95.2 to 98.7). At 5 years, the recurrence-free interval (RFI) was 98.3% (95% CI, 97.0 to 99.7), the overall survival was 97.8% (95% CI, 96.3 to 99.3), and the breast cancer-specific survival was 99.4% (95% CI, 98.6 to 100). Comparable iDFS was observed with T-DM1 irrespective of tumor size, hormone receptor status, centrally determined HER2 immunohistochemical score, and receipt of T-DM1 for more or less than 6 months. Although ATEMPT was not powered for this end point, the 5-year iDFS in the TH arm was 91.1%. Among patients with sufficient tissue for HER2DX testing (n = 187), 5-year outcomes significantly differed according to HER2DX risk score, with better RFI (98.1% v 81.8%, hazard ratio [HR], 0.10, P = .01) and iDFS (96.3% v 81.8%, HR, 0.20, P = .047) among patients with HER2DX low-risk versus high-risk tumors, respectively. CONCLUSION Adjuvant T-DM1 for 1 year leads to outstanding long-term outcomes for patients with stage I HER2-positive breast cancer. A high HER2DX risk score predicted a higher risk of recurrence in ATEMPT.

Thyroid Ultrasound (US) is the primary method to evaluate thyroid nodules. Deep learning (DL) has been playing a significant role in evaluating thyroid cancer. We propose a DL-based pipeline to detect and classify thyroid nodules into benign or malignant groups relying on two views of US imaging. Transverse and longitudinal US images of thyroid nodules from 983 patients were collected retrospectively. Eighty-one cases were held out as a testing set, and the rest of the data were used in five-fold cross-validation (CV). Two You Look Only Once (YOLO) v5 models were trained to detect nodules and classify them. For each view, five models were developed during the CV, which was ensembled by using non-max suppression (NMS) to boost their collective generalizability. An extreme gradient boosting (XGBoost) model was trained on the outputs of the ensembled models for both views to yield a final prediction of malignancy for each nodule. The test set was evaluated by an expert radiologist using the American College of Radiology Thyroid Imaging Reporting and Data System (ACR-TIRADS). The ensemble models for each view achieved a mAP0.5 of 0.797 (transverse) and 0.716 (longitudinal). The whole pipeline reached an AUROC of 0.84 (CI 95%: 0.75–0.91) with sensitivity and specificity of 84% and 63%, respectively, while the ACR-TIRADS evaluation of the same set had a sensitivity of 76% and specificity of 34% (p-value = 0.003). Our proposed work demonstrated the potential possibility of a deep learning model to achieve diagnostic performance for thyroid nodule evaluation.

TPS3633 Background: For patients with oligometastatic colorectal cancer (CRC), aggressive local therapy of isolated metastases, particularly in the liver, has been associated with long-term progression-free and overall survival (OS) primarily based on retrospective evidence. However, in patients with limited metastatic CRC that is deemed inoperable or those with additional disease outside of the liver or lungs, the role of local ablative therapies, including microwave ablation (MWA) and stereotactic body radiation therapy (SBRT), to render patients disease free is less clear. Further, despite the long history of treating oligometastatic CRC with local therapy, which is provider biased and not evidence based, questions remain regarding the benefit of extending the paradigm of metastatic directed therapy to patients with more extensive disease. This trial seeks to use a pragmatic multimodality approach that mirrors the current clinical dilemma. This study is designed to evaluate the safety and efficacy of adding total ablative therapy (TAT) of all sites of disease to standard of care systemic treatment in those with limited metastatic CRC. Methods: A022101/NRG-GI009 is a National Clinical Trials Network randomized phase III study planned to enroll 364 patients with newly diagnosed metastatic CRC (BRAF wild-type, microsatellite stable) with ≤4 sites of metastatic disease on baseline imaging. Liver-only metastatic disease is not permitted, and lesions must be amenable to any combination of surgical resection, MWA, and/or SBRT with SBRT required for at least 1 lesion. Patients receive first-line systemic therapy for 16-26 weeks and are then randomized 1:1, stratified by number of metastatic organ sites (1-2 vs. 3-4), timing of metastatic disease diagnosis (de novo vs. secondary), and presence of metastatic disease outside the liver/lungs in at least 1 site. Patients in Arm 1 will receive TAT consisting of treatment of all metastatic sites with SBRT ± MWA ± surgical resection followed by standard of care systemic therapy. Patients in Arm 2 will continue with standard of care systemic therapy alone. The primary endpoint is OS. Secondary endpoints include event-free survival, treatment-related toxicities, and local recurrence with exploratory biomarker analyses. The study needs 346 evaluable patients combined in the 2 arms to demonstrate an improvement in OS with a hazard ratio of 0.7 to provide 80% power with a one-sided alpha of 5%. The trial utilizes a group sequential design with two interim analyses (25% and 50% of events) for futility. The trial activated in January 2023 and recruitment is ongoing. Support: U10CA180821, U10CA180882; https://acknowledgments.alliancefound.org. U10CA180820 (ECOG-ACRIN); U10CA180868 (NRG); U10CA180888 (SWOG); Clinicaltrials.gov identifier: NCT05673148 Clinical trial information: NCT05673148 .

Introduction: Spontaneous coronary artery dissection (SCAD) is a nonatherosclerotic cause of myocardial infarction. Migraine headache has been reported to be common among patients with SCAD, but the degree of migraine-related disability has not been quantified. Methods: Clinical data and headache variables were obtained from the baseline assessment of the prospective, multicenter iSCAD Registry. Migraine-related disability was quantified using the self-reported Migraine Disability Assessment (MIDAS). Demographic, clinical, psychosocial, and medical characteristics from data entry forms were compared between patients with and without migraine. Results: Of the 773 patients with available data, 46% reported previous or current migraines. Those with migraines were more likely to be women (96.9% vs 90.3%, p = 0.0003). The presence of underlying carotid fibromuscular dysplasia was associated with migraine (35% vs 27%, p = 0.0175). There was not a significant association with carotid artery dissection and migraine. Current migraine frequency was less than monthly (58%), monthly (24%), weekly (16%), and daily (3%). Triptan use was reported in 32.5% of patients, and 17.5% used daily migraine prophylactic medications. Using the MIDAS to quantify disability related to migraine, 60.2% reported little or no disability, 14.4% mild, 12.7% moderate, and 12.7% severe. The mean MIDAS score was 9.9 (mild to moderate disability). Patients with SCAD had higher rates of depression and anxiety (28.2% vs 17.7% [ p = 0.0004] and 35.3% vs 26.7% [ p = 0.0099], respectively). Conclusions: Migraines are common, frequent, and a source of disability in patients with SCAD. The association between female sex, anxiety, and depression may provide some insight for potential treatment modalities.

12079 Background: Many troublesome symptoms experienced by men with prostate cancer are not specific to a particular disease state or treatment modality. As such, these issues' scope is neither fully appreciated nor characterized in the reporting of clinical trial data. A modern accounting of poorly controlled symptoms is needed to better inform survivorship and supportive care efforts. Methods: Data are drawn from the Enhanced, EHR-facilitated Cancer Symptom Control (E2C2) study, a cluster-randomized stepped wedge trial examining the effectiveness of routine symptom assessment and management on patient-centered outcomes and healthcare utilization (NCT03892967). This is a population-level study supporting patients with cancer, who are cared for in medical oncology clinics across the Midwest United States. The trial utilizes an automated symptom monitoring system with EHR-enabled algorithms for symptom triage and intervention. The current analysis focuses on pre-intervention surveys. The cohort includes E2C2 participants with prostate cancer (as determined by the Mayo Clinic Cancer Registry) receiving curative or palliative-intent therapies, along with prostate cancer survivors who previously completed their treatment. The prevalence of SPPADE symptoms (sleep disturbance, pain, impaired physical function, anxiety, depression, fatigue [low energy]) was assessed using 0 to 10 numerical rating scales (NRS), with scores of 4-6 indicating moderate symptoms and 7-10 indicating severe symptoms. Results: A total of 1,388 men with prostate cancer completed a pre-intervention survey between March 2019 and January 2023. The median age at completion of first survey was 74 years. The cohort includes patients living in diverse settings, including urban (n=718, 52%), micropolitan (n=250, 18%), small town (n=218, 16%), and rural (n=200, 14%) environments. The proportion of patients experiencing moderate-to-severe symptoms (NRS score ≥4) was 47% for fatigue, 40% for impaired physical function, 32% for sleep disturbance, 27% for pain, 22% for anxiety, and 20% for depression/emotional distress. The three domains with the highest prevalence of severe symptoms (NRS score ≥7) were fatigue (17%), impaired physical function (12%), and sleep disturbance (10%). Conclusions: Proactive symptom monitoring identifies a high overall burden of moderate-to-severe symptoms, particularly fatigue and impaired physical function, among prostate cancer patients and survivors. Collaborative care approaches and symptom control trials are needed to mitigate and manage these burdensome symptoms. Clinical trial information: NCT03892967 . [Table: see text]

12065 Background: Incidence of cancer, including colorectal, breast, pancreas, kidney, and uterine cancer, is increasing in younger populations. Adolescents and young adults (AYA, defined as age 15-39) with cancer face unique challenges. This study aimed to characterize how symptom burden differs between AYA and non-AYA (aged 40+) patients with cancer. Methods: We performed a subgroup analysis of the E2C2 study, a cluster-randomized, pragmatic trial examining the effectiveness of routine symptom assessment and guideline-based management on patient-centered and healthcare utilization metrics during and following cancer treatment. Six symptoms [Sleep disturbance, Pain, Physical function impairment, Anxiety, Depression, and Energy deficit/fatigue (SPPADE)] were evaluated using 11-point numerical rating scales (NRS). Symptom severity was classified as mild (0-3), moderate (4-6), or severe (7-10). We conducted a subgroup analysis of symptom burden among AYA patients (defined as age 18-39 in this study), using their first-reported NRS scores. Results: The E2C2 cohort included 2,598 AYA patients and 38,061 non-AYA patients who completed >1 SPPADE NRS on at least one survey. AYA patients were more likely than non-AYA patients to report severe anxiety ( p<0.0001) and depression ( p<0.0001) (Table). Non-AYA patients were more likely to report severe pain ( p=0.02179), fatigue ( p=0.0022), and physical function limitations ( p<0.0001). Sociodemographic differences were also noted. A higher proportion of AYA patients held a bachelor’s degree or higher (38% vs 28%), were employed (73% vs 37%), and lived in an urban setting (67% vs 56%), compared to non-AYA patients. Non-AYA patients were more likely to have government insurance (63% vs 21%) and to be married (72% vs 59%). Conclusions: AYA patients with cancer were more likely to report severe depression and anxiety compared to their counterparts age 40 and above, underscoring the need for targeted and tailored psycho-oncology care for this population. [Table: see text]

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.

TPS8125 Background: Sarcomatoid mesothelioma is the most aggressive form of pleural mesothelioma and is associated with the worst prognosis of the histologic variants of this disease. In the Checkmate 743 clinical trial the patients with sarcomatoid mesothelioma who received ipilimumab and nivolumab had survival outcomes that were similar to those of patients with epithelioid mesothelioma. In comparison, the patients with sarcomatoid mesothelioma who received chemotherapy had the worst outcomes in this trial, highlighting the known limited efficacy of chemotherapy against this histologic variant. Checkmate 743 demonstrated that ipilimumab and nivolumab is a new standard of care for non-epithelioid mesothelioma. Surgery typically has not been offered to this group of patients given their historically poor outcomes. With the significant survival gains seen patients with sarcomatoid mesothelioma treated with immunotherapy, we hypothesized that surgery may extend the benefits seen with immunotherapy. Methods: Alliance for Clinical Trials in Oncology A082101 is a prospective, phase 2 nonrandomized clinical trial for patients with sarcomatoid mesothelioma. The co-primary objectives are to determine the percentage of patients with potentially resectable sarcomatoid mesothelioma able to proceed with surgery after neoadjuvant ipilimumab and nivolumab, and the progression-free survival (PFS) at 12 months (12-month PFS) after the initiation of ipilimumab and nivolumab. For sample size determination, we assumed that if the true rate of surgery is 75% or greater, it would indicate that neoadjuvant immunotherapy is feasible to be given prior to surgery. On the other hand, if the true rate of surgery is 50% or less it would indicate that neoadjuvant immunotherapy is not worthy of further investigation. Twenty-six (26) eligible patients will be needed to receive neoadjuvant immunotherapy. If 16 or fewer of the 26 eligible patients proceed to surgery, it will be concluded that the experimental therapy is not worthy of further investigation. Otherwise, it will be concluded that the experimental therapy is worthy of further investigation. Safety monitoring will be done through a 6-week run-in for the first 10 patients to assess for pre-operative and post-operative toxicities and complications. Sequential boundaries will be used to monitor severe toxicity and complication rates. Accrual will be halted if excessive numbers of severe toxicity and complications in pre-operative and post-operative phases are seen. The accrual and safety data will be summarized in reports for semiannual reviews by Alliance Data and Safety Monitoring Board. Tumor and blood-based biomarkers will be included as exploratory biomarkers. Support: U10CA180821, U10CA180882, U24 CA196171; https://acknowledgments.alliancefound.org . Clinical trial information: NCT05647265 .