LBA 09 - Neoadjuvant Radiotherapy in Breast Cancer: A Study on the Optimal Sequencing of Radiation in Breast Cancer (NeoORB)

03:05pm - 03:15pm ET

Room 210

Presenter(s)

Rishi Nair, MBBS - All India Institute of Medical Sciences, Jodhpur, Jodhpur, Rajasthan

R. P. Nair, P. Pareek, B. Devnani, A. Solanki, J. R. Vishnoi, D. R. Poonia, N. Sharma, P. Kumar, T. Yadav, and P. Elhence; All India Institute of Medical Sciences, Jodhpur, Rajasthan, India

Purpose/Objective(s):

The optimal radiotherapy sequencing in breast cancer is unresolved. Neoadjuvant radiotherapy (NART) may boost pathological complete response(pCR) and nodal clearance. The NeoORB trial assesses the impact of sequencing on pathological response, surgical outcomes, patient-reported outcomes, and long-term outcomes.

Materials/Methods:

This prospective, randomized, open-label trial compared neoadjuvant ultrahypofractionated radiotherapy after NACT with standard postoperative radiotherapy sequencing. All patients underwent standard diagnostic work-up (mammography, axillary ultrasound, biopsy with IHC ± FISH for HER2, and PET-CT/CECT when indicated). Following NACT ± anti-HER2 therapy, patients were randomized:

Experimental arm (NART): RT delivered ~2 weeks post-NACT (26 Gy/5 fractions with Boost dose of 10 Gy/5).

cN0: Whole-breast irradiation + Tumor Boost
cN+: Whole-breast + regional nodal irradiation + Tumor Boost After 3–4 weeks: restaging imaging, then surgery (BCS or mastectomy) with SLNB ± axillary dissection.

Control arm (Adjuvant RT): Surgery 3–4 weeks after NACT (BCS/MRM with SLNB ± AD). After 3–4 weeks of wound healing:

BCS: Whole-breast irradiation + boost ± regional nodal irradiation
MRM: Postmastectomy RT ± boost ± regional nodal irradiation.

Contouring followed RTOG guidance;

Primary endpoint: Pathological complete response.

Secondary endpoints: Nodal pCR, locoregional recurrence, DFS, DMFS, OS, DSS, CTCAE-graded toxicity, QoL (EORTC QLQ-C30/BR42), dosimetry, R0 rate, SLNB yield, and health-economic metrics. Sample size with pCR improvement (?20%) and 80% power was n˜152. Analyses were ITT using Chi-Square/Fisher and Kaplan-Meier/Cox methods.

Results:

This is an interim analysis of the Phase 3 open-label RCT involving 60 patients (Arm A: NART, n=27; Arm B: adjuvant RT, n=33). Baseline characteristics were balanced (Table 1). Arm A had higher breast pCR (51.9% vs 27.3%; p=0.046) and higher nodal pCR (23/26, 88.5% vs 13/33, 39.4%; p<0.001). Arm A also had lower post-treatment tumour volume (mean 2.31 vs 22.48 cc; p=0.014). BCS rates were similar (26.3% vs 26.1%); MRM 73.7% vs 69.6%. Grade =3 Clavin Diendo complications occurred in 4/27 (14.8%) vs 2/33 (6.1%). Subtype distribution was balanced. There was only a single Grade 2 acute RT toxicity (Arm B), rest were Grade 1 toxicities.

Table 1

Conclusion:

Neoadjuvant RT yielded gains in primary pCR, nodal pCR and tumour regression with no significantly greater toxicity, indicating a biologically superior sequencing strategy vs conventional postoperative RT. These findings support a paradigm shift to preoperative radiotherapy to maximise response and enable surgical de-escalation.

Variable	Arm A	Arm B	p-value
Age (mean, years)	51.57	53.65	0.227
Postmenopausal	57.1%	63.6%	0.605
Multifocal disease	21.1%	26.1%	0.692
Luminal subtype	73.7%	52.2%	0.356
HER2-enriched	15.8%	30.4%	0.356
TNBC	5.3%	17.4%	0.356
Pre-op tumour volume (cc, mean)	50.07	20.43	0.097
Post-op tumour volume (cc, mean)	2.31	22.48	0.014