Main Session
Sep
28
PQA 04 - Breast Cancer, Patient Reported Outcomes/QoL/Survivorship, Functional Radiation Medicine, Hematologic Malignancies, Palliative Care, and International/Global Oncology
2843 - ctDNA Evaluation on a Phase I Trial of Pre-Operative Ablative Radiation for Early Stage Hormone Positive Breast Cancer
Presenter(s)
Asal Rahimi, MD, MS - University of Texas Southwestern Medical Center at Dallas, Dallas, TX
A. S. Rahimi1, P. G. Alluri1, B. Dogan2, K. Fletcher3, M. Arbab1, D. Li1, N. Wandrey1, S. Sahoo4, M. Leitch5, and R. D. Timmerman1; 1Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, TX, 2Department of Radiology, University of Texas Southwestern Medical Center, Dallas, TX, 3University of Texas Southwestern Medical Center, Dallas, TX, 4Department of Pathology, University of Texas Southwestern, Dallas, TX, 5Department of Surgery, University of Texas Southwestern Medical Center, Dallas, TX
Purpose/Objective(s):
Investigate pre-op single fraction stereotactic partial breast irradiation (SPBI) dose escalation toxicity and tumor response in early-stage HR+ breast cancer (NCT04040569) on a phase I trial. Our primary objective was to escalate single fraction SPBI to an ablative dose, 38Gy in a single fraction, without exceeding maximum tolerable dose. Secondary endpoints were pathologic complete response(pCR), near complete response, local control, toxicity, and cosmesis. We report on an exploratory endpoint of ctDNA evaluation.Materials/Methods:
Patients(pts) with <3 cm, HR+, Her2-, cN0 invasive breast cancer not requiring chemotherapy were treated. CtDNA blood evaluation testing was evaluated at baseline pre-sPBI, 48-72 hours after sPBI, 1-2 months post SPBI, 4-5 months post SPBI, 7-8 months post SPBI, 1month post-surgery, 6 months post-surgery, and then every 6 months.Results:
From 12/2019 to 5/2024, 14,15 and 15 pts were treated on the 30,34 and 38Gy sPBI arms with median follow-up of 41.5 months. Of the 44 enrolled patients , 12 underwent ct DNA evaluation at various timepoints. 3/12 (25%) had detectable ctDNA, reported as tumor molecules/ml (MTM/ml) of plasma. Patient 1: ctDNA detected at 0.12 MTM/ml 48 hours after sPBI, with levels becoming undetectable on all subsequent blood draws. Patient was later found to have positive lymph nodes at time of sentinel lymph node biopsy(SLNB) ypTisN2a (5/8 LN) and received subsequent whole breast and nodal irradiation. Patient 2: had 0.04 MTM/ml ctDNA at baseline prior to SPBI which cleared by 2 months post- SPBI and remained undetectable. Patient 3: had cT2N0 invasive lobular carcinoma and was found to have 4/4 positive lymph nodes at SLNB (ypT0N+). ctDNA drawn at that time measured 0.07 MTM/mL. Subsequent axillary dissection revealed 10/17 additional metastatic nodes (ypT0N3M0), after which ctDNA became undetectable within one month. She received adjuvant Taxol , Xeloda and whole breast/nodal radiation. ctDNA rose again 9 months post-surgery, declined while on Verzenio then became (+, 0.10) again roughly 2 years after sPBI despite negative PET imaging. To date, no patients in the cohort have developed clinical or radiologically evident recurrent disease.Conclusion:
This exploratory analysis shows a low rate of detectable ctDNA in early stage (cT1-T2N0) breast cancer, with ctDNA identified in 3/12 patients (25%). Most detections occurred in patients who were ultimately found to have higher stage disease, suggesting that ctDNA(+) may indicate occult nodal involvement. Among true stage I-II patients baseline ctDNA detection was rare (1/12, 8.3%) limiting its usefulness for routine monitoring. Our findings suggest that ctDNA in the pre-operative or ablative setting may help raise suspicion for occult lymph node metastasis not identified on imaging and warrants further evaluation.