Neoadjuvant Radiotherapy Challenges the Surgery-First Paradigm in Breast Cancer

In an interview with CancerNetwork® at the 2026 American Society for Radiation Oncology (ASTRO) Annual Meeting, Leah Katz, MD, MPH, vice chair of Faculty Development and an attending radiation oncologist in the Department of Radiation Oncology at the University of Miami Miller School of Medicine, discussed interim findings from the randomized, open-label phase 3 NeoORB trial (CTRI/2024/06/068847). Conducted at the All-India Institute of Medical Sciences, Jodhpur, the study evaluated the optimal sequencing of radiation in breast cancer. Patients in the experimental arm received neoadjuvant ultrahypofractionated radiotherapy (26 Gy in 5 fractions plus a tumor boost) after neoadjuvant chemotherapy and before surgery, whereas patients in the control arm received standard postoperative radiotherapy.

In an interim analysis of 60 patients, neoadjuvant radiotherapy was associated with higher breast pathologic complete response (pCR) rates (51.9% vs 27.3%; P = .046) and nodal pCR rates (88.5% vs 39.4%; P <.001), as well as smaller mean posttreatment tumor volume (2.31 cc vs 22.48 cc; P = .014). Grade 3 or higher surgical complications occurred in 14.8% vs 6.1% of patients, respectively.

Katz said these findings suggest the field may be thinking too narrowly about the conventional surgery-then-radiation framework.

Transcript:

CancerNetwork: NeoORB looks at optimal sequencing of neoadjuvant radiation, why does timing matter so much here?

Katz: It’s the same story, in that neoadjuvant radiation offered a greater tumor volume reduction than systemic therapy alone. It was a little bit of a similar story to TARGIT-B, in that it also reduced nodal recurrence. It raises the question: Is something happening at the interface of radiation and an intact tumor that allows for lower recurrence down the line? That’s quite interesting.

As I say in my summary slides, we may be thinking too narrowly about the conventional breast surgery and radiation framework, which is surgery with negative margins, then radiation to kill microscopic disease. Radiation may offer all sorts of treatment paradigms and opportunities if we deliver it at a different time, at a different moment during the breast tumor, meaning in the breast vs out of the breast.

Reference

Nair RP, Pareek P, Devnani B, et al. Neoadjuvant radiotherapy in breast cancer: a study on the optimal sequencing of radiation in breast cancer (NeoORB). Presented at: 2026 ASTRO Annual Meeting; September 26-30, 2026; Boston, MA. Abstract LBA 09.