Al‐Hattab, Eyad

Abstract Introduction Serial assessments of circulating tumor cells (CTCs) in metastatic breast cancer (MBC) provide independent prognostic significance for progression free survival and overall survival. A low CTC burden (<5 CTCs / 7.5mL blood) at baseline is favorable prognostically, and reduction of CTCs during treatment indicates response to treatment (Janni, CCR 2025). Despite increasing evidence supporting its clinical validity, real-time serial CTC enumeration has not been utilized broadly in clinical practice in the U.S. The ACT-MBC study is a prospective observational study to evaluate the impact of serial CTC testing on treatment decisions and response assessment (NCT05662345). Provider (physician or advanced practitioner) perception of CTC testing is measured with questionnaires at baseline (PQ1), and for each pt during the first restaging visit (PQ2), and at the end of the study (PQ3). We previously reported PQ1 results (Giridhar, SABCS 2024). Here, we report on results of PQ2. Methods ACT-MBC prospectively enrolled patients (pts) at Mayo Clinic Rochester and Mayo Clinic Health Systems sites (Mankato, Albert Lea and Eau Claire). Pts with MBC were enrolled at time of progressive disease during any line of therapy (TNBC) or ≥2nd line metastatic therapy for ER+/HER2- disease. Pts were tested for CTCs using the FDA-cleared CellSearch® assay which included enumeration and biomarker testing on CTCs for ER, HER2, and PD-L1. The treating clinician determined the regimen and timing of restaging scans. CTC testing was performed once per cycle (every 3-4 weeks) with results returned to the treating provider within 7 days. We descriptively summarized PQ2 responses from providers who had at least one on-treatment CTC result available by the first restaging visit. We report the proportion (90% CI) of providers who agreed or strongly agreed that assessing CTCs enhanced their ability to determine response to therapy and that the CTC results helped guide their decision to continue or change therapy (co-primary endpoints) while accounting for within provider correlation. Results As of June 25, 2025, 15 providers enrolled a median of 2 pts each (range: 1 to 15 pts) and completed PQ2 surveys on 40 pts. 7 providers (47%) practiced in the community setting and 4 (27%) were nurse practitioners. Most pts were female (98%), White (98%), and had ER+/HER2- MBC (80%). Baseline (C1) CTC results were elevated (≥5 CTCs) in 24 (60%) pts (CTC range 0-609). At C2 (n=39), CTC values remained undetected in 7 pts, decreased in 21 pts, increased in 8 pts, and remained unchanged in 3 pts. At PQ2 (n=40), based on clinician interpretation of radiographic findings, results showed 2.5% of pts with complete response, 20% with partial response, 25% with stable disease, 17.5% with mixed response, and 35% with progressive disease. Clinicians reported that CTC results were concordant with imaging results in 34 (85%) responses, discordant with imaging in 7.5% of responses, and unclear in the remaining 7.5% of responses. Most clinicians (82.5%) agreed or strongly agreed that assessing CTCs enhanced their ability to determine response to therapy (90% CI: 68.3%, 96.7%). Further, 70% of providers agreed or strongly agreed that the CTC results helped guide their decision to continue or change therapy (90% CI: 50.8%, 89.2%). 32.5% of the time, CTCs results influenced the timing of the first restaging scans. In 11/25 pts without progressing disease, CTC results influenced the timing of future scans. In the 7/8 pts with a mixed response at first restaging scans with decreasing CTCs, 4 remained on the same systemic therapy. Conclusions Oncologists in academic and community practice responded that serial CTC assessments enhance ability to determine response of therapy, guide decisions to continue or change treatments, and influence timing of radiographic assessments. Citation Format: K. V. Giridhar, D. Zahrieh, M. Hanna, A. Singh, E. Al-Hattab, P. Schumacher, J. Carroll, J. Hoppenworth, T. Haddad, A. Tevaarwerk, B. Rudder, G. M. Choong, S. Basu, R. A. Leon-Ferre, T. O'Brien, A. Lewis, F. de Snoo, L. Stork-Sloots, F. K. Kuhr, S. Lazaro, R. Prendergast, D. S. Spinner, M. P. Goetz. Assessing the impact of real-time serial circulating tumor cell results on the management of patients with metastatic breast cancer [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS4-03-10.

In 2023, Mayo Clinic in Rochester, MN, cared for over 20,000 patients with hematologic malignancies, roughly 42% of whom were rural. Patients residing in rural areas can face challenges in access to care, financial and time burdens due to treatment-related travel, and limited opportunities to participate in clinical trials. In 2021, The Leukemia & Lymphoma Society launched its IMPACT (Influential Medicine Providing Access to Clinical Trials) grant with Mayo Clinic being among its first recipients. The program provides funding to major cancer centers, in partnership with local community oncology centers, to help increase participation of patients traditionally underrepresented in clinical trials, including those who are rural, minority and/or economically disadvantaged. The award allowed significant changes to be made to clinical trial selection and facilitation models increasing access to trials within the rural setting and reducing the socioeconomic barriers noted above. This program included Rochester (IMPACT Hub) and Mayo Clinic Health System (MCHS) sites in Albert Lea, MN (65 miles to Hub), Eau Claire, WI (96 miles to hub), La Crosse, WI (73 miles to Hub), and Mankato, MN (84 miles to Hub). Methods: Two models were deployed; the full activation model where clinical trials were fully opened at MCHS sites, and the hybrid model where clinical trial participants are consented at the Hub and portions of participant care are conducted at MCHS sites. Initial barriers included limitations in clinical trials support staff, insufficient specimen processing equipment, medication storage and shipping limitations, MCHS catchment population unalignment with the Hub trials portfolio, and reduced bandwidth of providers due to patient care responsibilities. To address barriers to trial conduct, community center site champions were identified to streamline trial review and increase collaboration to better define site catchment areas, trial constraints, and site needs. A feasibility specialist was hired to support the program in trial design/implementation, barrier tracking, and to serve as a liaison between community site providers, study staff, and the program. Results: Since 2021, 20 clinical studies including 14 interventional treatment trials have been activated demonstrating 108 total patients accrued with 42 interventional accruals; 5 within the full activation model (13 accruals) and 15 in the hybrid model (29 accruals). Patients showed an average of 216 miles, with an estimated mileage cost of $142/trip based on the 2023 IRS mileage rate of $0.655/mile to the hub location. Nine of those patients traveled over 260 miles, with an estimated mileage cost of $170/visit to access clinical trials. Under the hybrid model, 8 patients transitioned portions of their care to their home city resulting in reduction of an average of 155 miles/visit, and 7 patients were able to reduce their travel time an average of 216 miles/visit. By estimating at least 10 study visits, the travel burden was reduced by 2,160 miles (4320 driving hours) and $1,420 in driving costs alone for participants. Using participant averages the 108 patients would spend a total of $15,336 in travel costs for just the initial visit, but when factoring in the 10-visit estimate, travel reduction could result in a net savings of $153,360. Based on travel data, it is estimated 11 of these patients would have required overnight accommodation using an average of $149/night hotel stay, a savings of $1,490/patient is estimated for the lifecycle of trial participation or $16,390 for the 11-patient cohort requiring accommodation. These results do not include travel companion and time off work costs. Efforts have been made to further develop the full activation model and 5 clinical trials are in activation. Data gathered from the program is being used to design strategies to reduce the administrative burden of clinical trial participation for community providers and launch screening programs. Conclusion: The Mayo Clinic LLS IMPACT program has demonstrated success in addressing barriers to opening clinical trials in the community-center setting and reduced the travel burden and financial impact to clinical trial participation in a cohort of trial participants. Centralized hub support of study activation and conduct and decentralized care to support treatment of patients in proximity of their home can be extended to other hospital systems and settings.