Sep 30

SS 31 - Breast Cancer 3: Refining Radiation in Early-Stage Breast Cancer: Personalization, Precision, and De-escalation

280 - Phase I Pre-Operative Single Fraction Dose Escalation Ablative Stereotactic Partial Breast Irradiation (S-PBI) Trial for Early-stage Breast Cancer

08:10am - 08:20am PT

Room 24

Presenter(s)

Asal Rahimi, MD, MS - University of Texas Southwestern Medical Center at Dallas, Dallas, TX

A. S. Rahimi¹, M. Leitch², B. Dogan³, P. G. Alluri¹, M. Arbab¹, D. Li¹, D. D. M. Parsons¹, N. Wandrey¹, D. Farr², D. W. N. Kim⁴, S. Seiler³, R. Wooldridge², N. Unni⁵, C. R. Nwachukwu⁶, I. Patel⁵, W. Lu⁷, A. Nguyen², T. D. Chiu⁶, M. Stein¹, E. Pina⁸, S. Bahrami¹, H. E. Morgan⁹, Y. Liu¹⁰, H. L. McArthur⁵, S. Sahoo¹¹, and R. D. Timmerman¹; ¹Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, TX, ²Department of Surgery, University of Texas Southwestern Medical Center, Dallas, TX, ³Department of Radiology, University of Texas Southwestern Medical Center, Dallas, TX, ⁴Vanderbilt University Medical Center, Nashville, TN, ⁵University of Texas Southwestern Medical Center, Medical Oncology, Dallas, TX, ⁶University of Texas Southwestern Department of Radiation Oncology, Dallas, TX, ⁷Medical Artificial Intelligence and Automation (MAIA) Lab, Department of Radiation Oncology, UT Southwestern Medical Center, Dallas, TX, ⁸University of Texas Southwestern Medical Center, Dallas, TX, ⁹CARTI Cancer Center, Little Rock, AR, ¹⁰Department of Population and Data Sciences, University of Texas Southwestern, Dallas, TX, ¹¹Department of Pathology, University of Texas Southwestern, Dallas, TX

Purpose/Objective(s): Investigate pre-op single fraction SPBI dose escalation on toxicity and tumor response in early-stage HR+ breast cancer. Primary objective was escalate single fraction SPBI to an ablative dose without exceeding maximum tolerable dose(MTD). Secondary endpoints were pathologic complete response (pCR=RCB 0 or Miller Payne(MP) 5), near complete response (nCR=RCB 1 or MP 4), local control, toxicity, and cosmesis.

Materials/Methods: Patients(pts) with <3 cm, HR+, Her2-, cN0 invasive breast cancer not requiring chemotherapy were treated on MR LINAC, robotic radiosurgery, or cobalt stereotactic breast unit with 30, 34, or 38Gy. Pts underwent endocrine therapy, and surgery post-SPBI. Median time to Surgery (MTS) was recorded.

Dose limiting toxicity (DLT) defined as grade =3 toxicity attributed to SPBI. Each cohort enrolled 7-15 pts. Dose escalation permitted if 0/7, 2/9, =3/12, or =4/15 patients experienced DLT within 90 days of SPBI. MTD exceeded if more DLTs occur in any cohort.

Results: From 12/2019 to 5/2024, 14,15 and 15 pts were treated with median follow-up of 35,36,12.6 mo for 30,34 and 38Gy, achieving pCR+nCR rates of 64.3%, 93.3% and 93.3% respectively. For the 30Gy group, MTS post-SPBI was 5.9 mo (range 2.8-11.7) with 35.7% (5/14) achieving pCR and 64.3% (9/14) achieving pCR/nCR. MTS for 34Gy was 7.3mo(range 5.3-12): 7/15 (46.7%) had pCR while 14/15 (93.3%) had pCR/nCR. MTS for 38Gy was 11.4mo (range 8.4–12.9):10/15 (66.7%) pCR, while 14/15(93.3%) had pCR/nCR.

A time-to-surgery cutoff of 277 days best distinguished MP grade 5 (pCR), yielding an AUC of 0.765 (95% CI: 0.617 – 0.912), sensitivity 0.818, specificity 0.727. When evaluating pts who had surgery >270 days post radiation, 100%, 66.7% and 64.3% achieved pCR (p = 0.40) and 100%, 83.3%, and 92.9% achieved pCR/nCR when treated with 30Gy, 34Gy and 38Gy respectively (p = 0.69).

Tumor size >11.5mm (AUC=0.56, 95% CI: 0.37-0.74) is less likely to have a MPS of 5, but only has a sensitivity of 0.67 and +predictive value 0.58, suggesting that tumor size alone is not the best predictor of pCR. Combining MTS + size results in AUC of 0.79(95% CI:0.63-.93), with sensitivity=0.91and specificity=0.64.

Of the 15 pts with a nCR 53.3% had =3mm of residual disease. The mean ki67 was 11.0% at diagnosis and 1.8% at surgery.

There were 59 acute grade 1; 3 acute grade 2 (breast pain and dermatitis); 2 late grade 2 (breast pain and surgical washout), and 1 grade 3 (slow healing wound ulceration in a pt with uncontrolled diabetes in the 30 Gy cohort).

Conclusion: Longer elapsed time from pre-op ablative SPBI/hormonal therapy to surgery (>9 months), leads to significantly higher pCR/nCR (>90%), suggesting potential tumor eradication with radiation/endocrine therapy alone. Incomplete biological effect are seen at earlier time points. This paves the way for possible non-surgical management for selected early-stage HR+ breast cancer pts. (NCT04040569)

	30Gy	34 Gy	38 Gy	All Cohorts
nCR+pCR >270 days MTS	5 out of 5 (100.00%)	5 out of 6 (83.33%)	13 out of 14 (92.9%)	23 out of 25 (92.0%)