IBISCO trial: immune and pathological response in breast cancer after preoperative irradiation with stereotactic technique and neoadjuvant chemotherapy

INTRODUCTION Pathological complete response (pCR) after neoadjuvant systemic therapy is a predictor of disease outcomes and survival in breast cancer (BC) aggressive subtypes and for this reason it has become the standard of care for most triple-negative and Her2-positive BC. However, pCR after neoadjuvant chemotherapy (NAC) is still difficult to obtain in Luminal B BC, leading to the need for new strategies development. In this setting, the IBISCO trial evaluates the combination of preoperative stereotactic radiotherapy (SBRT) boost and standard NAC to enhance pCR. METHODS IBISCO is a phase II trial that aims to demonstrate an increase in pCR rates from 15% to 35% in Luminal B BC patients by adding a preoperative SBRT boost to the standard scheme of NAC. The primary endpoint is evaluated with the Residual Cancer Burden index, and explorative analysis of the tumour-associated inflammatory microenvironment and tumour genomic profile modifications post-SBRT is conducted as well. Surgery and adjuvant therapies will be performed for clinical practice after the completion of neoadjuvant treatments. RESULTS Between February and February 2024, ten patients with Luminal B BC addressed to NAC were enrolled. The majority had cT2 tumours. The preoperative RT boost for all patients was planned between the third and fourth administration of paclitaxel. The SBRT treatments were delivered with Volumetric Arc Modulated Therapy (VMAT) technique with flattening filter free (FFF) to optimize target coverage and using Deep Inspiration Breath Hold to minimize organs-at-risk exposure to higher RT doses. CONCLUSIONS Preliminary IBISCO trial results suggest safe integration of preoperative SBRT boost with NAC for Luminal B BC. No acute skin toxicities were observed, affirming the potential of modern RT techniques for delivering precise and effective treatment. The final results of the study will hopefully lead to an optimized integration of RT and NAC in this specific setting.