Radiology-based prediction of HER2 level and T‑DXd benefit in metastatic breast cancer

RADIomics to Predict HER2 Status And T-DXd Efficacy in Metastatic Breast Cancer: the RADIOSPHER2 Study

This study tests whether patterns in CT or FDG‑PET images can show HER2 level and help predict response to trastuzumab deruxtecan for people with metastatic breast cancer.

Quick facts

• Study type: Observational
• Enrollment: 500 (estimated)
• Sex: All
• Sponsor: Fondazione IRCCS Istituto Nazionale dei Tumori, Milano (other)
• Drugs / interventions: trastuzumab
• Locations: 1 site (Milan)
• Trial ID: NCT07030569 on ClinicalTrials.gov

What this trial studies

RADIOSPHER2 is a single-center retrospective observational project that aims to derive a ‘‘radiobiopsy’’ radiomic signature from CT and/or FDG‑PET images to predict HER2 status across metastatic sites such as liver, lung, pleura, and bone. The radiobiopsy model will be applied to baseline scans of HER2+ and HER2‑low patients who received trastuzumab deruxtecan, assigning lesions to HER2‑0, HER2‑low, or HER2‑overexpressed groups. Investigators will compare progression-free survival between radiobiopsy-assigned cohorts using Cox regression and build multivariate models including clinical covariates. Pathology slides from biopsied metastatic sites will be reviewed and digitized for pathomics analyses to explore microscopic HER2 spatial heterogeneity and correlate imaging and tissue features.

Who should consider this trial

Good fit: Ideal candidates are patients with metastatic breast cancer who had a liver, lung, pleural, or bone metastatic biopsy between 01Jan2005 and 01Jan2024, have CT and/or FDG‑PET imaging within three months before the biopsy, known HER2 status, and available clinical records (including T‑DXd treatment data).

Not a fit: Patients without recent imaging, with unknown HER2 status, whose biopsy was from lymph nodes/soft tissue or other non-specified sites, or lacking pathology or image records will not be evaluable and are unlikely to benefit from this analysis.

Why it matters

Potential benefit: If successful, this approach could provide a noninvasive way to estimate HER2 expression and help identify patients more likely to benefit from trastuzumab deruxtecan when tissue biopsy is difficult.

How similar studies have performed: Radiomics studies have shown promising links between imaging features and molecular markers in cancer, but applying radiomics specifically to predict HER2 status and trastuzumab deruxtecan response is relatively novel and not yet validated.

Eligibility criteria

Inclusion Criteria:

* Patients with metastatic breast cancer underwent a liver, lung, pleural or bone biopsy in the metastatic setting, performed from 01Jan2005 to 01Jan2024.

Exclusion Criteria:

* Not available imaging (CT scan and/or PET-FdG scan) in the three months before the biopsy or before the last previous treatment interruption;
* Unknown HER2 status;
* Node, soft tissue or other visceral as biopsy site.

Where this trial is running

Milan

• Fondazione IRCCS Istituto Nazionale Tumori — Milan, Italy (RECRUITING)

Study contacts

• Study coordinator: Claudio Vernieri, MD, PhD

Conditions: Radiomic, Radiomics, Breast Cancer Metastatic, Breast Cancer Stage IV, Breast Carcinoma, Breast Neoplasms, Breast Cancer, Breast Cancer With Bone Metastasis