Disease Extent in Stage IV Lobular Carcinoma: the Aid of Imaging and Liquid Biopsy Analyses (DELILA)

Metastatic invasive lobular carcinoma (ILC) is a distinct breast cancer subtype characterized by loss of E-cadherin and a diffuse growth pattern that makes metastases difficult to detect with standard imaging such as computed tomography (CT) or 18F-Fluorodeoxyglucose Positron Emission Tomography (18F-FDG PET)/CT. As a result, disease burden in patients with ILC is frequently underestimated, progression is identified later than clinically optimal, and many patients are excluded from clinical trials due to insufficiently measurable disease.

Whole-body diffusion-weighted magnetic resonance imaging (WB-DWI/MRI) is a radiation-free imaging technique that has demonstrated improved sensitivity for detecting metastases-including peritoneal, bone, and nodal disease-in ILC. Retrospective studies suggest that WB-DWI/MRI can identify clinically relevant progression not visible on standard imaging. However, prospective evidence in ILC is lacking. Circulating tumor DNA (ctDNA) has also shown promise as a minimally invasive biomarker for monitoring treatment response, with early molecular changes often preceding radiologic progression, but data specific to ILC remain limited.

The DELILA study is a prospective, multicenter clinical trial conducted at University Hospitals Leuven and Institut Jules Bordet. The study aims to enroll 43 patients starting first-line systemic therapy for metastatic hormone receptor positive human epidermal growth factor receptor 2 negative (HR+/HER2-) ILC. Participants undergo serial dual imaging-WB-DWI/MRI and standard-of-care imaging-at baseline, at 1 month, and approximately every 3 months for up to 30 months or until disease progression. At each imaging time point, blood samples are collected for ctDNA analysis and Ca15.3 tumor marker assessment. Patient-reported psychological burden related to repeated imaging and blood sampling is evaluated using validated questionnaires.

The primary objective is to assess the added value of WB-DWI/MRI in detecting disease progression that informs clinical decision-making compared to standard imaging. Secondary objectives include evaluating whether ctDNA or Ca15.3 dynamics reflect disease evolution, assessing measurability of lesions with Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and MRI-specific criteria, identifying early biomarkers of treatment response using Apparent Diffusion Coefficient (ADC) changes and ctDNA kinetics, and characterizing the psychological impact of trial procedures.

This study will provide the first adequately powered prospective evidence on the clinical utility of WB-DWI/MRI and liquid biopsy monitoring in metastatic ILC. Results may support implementation of WB-DWI/MRI as a routine imaging strategy, guide imaging frequency through biomarker-informed approaches, and improve patient experience and trial eligibility for individuals living with metastatic ILC.

Study Overview

• Status: Not yet recruiting
• Conditions: Invasive Lobular Breast Carcinoma
• Intervention / Treatment: Diagnostic test: whole body diffusion weighted MRI; Diagnostic test: ctDNA

• Study Type: Interventional
• Enrollment (Estimated): 43
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Voluntary written informed consent of the participant or their legally authorized representative has been obtained prior to any screening procedures
2. At least 18 years of age at the time of signing the Informed Consent Form (ICF)
3. ECOG from 0 to 2
4. Patient with stage IV ILC, either de novo or after prior (curative) treatment for early ILC. Histological subtype confirmed on primary tumor or on metastatic tissue. Patients that are diagnosed with stage IV breast cancer that have a mixed ILC/IBC-NST histology of the primary tumor (mixed histology within the same primary lesion) will also be able to participate and will be analyzed in an exploratory cohort.
5. Confirmation of hormone receptor positive (HR+)/HER2- disease either on new biopsy or archival tissue (e.g. primary tumor)
6. Multifocal or bilateral disease is allowed if all evaluated foci present with HR+/HER2- ILC
7. Starting first line of treatment for metastatic ILC

Exclusion Criteria:

1. Presence of a contraindication to perform WB-DWI/MRI
2. Presence of severe claustrophobia
3. Presence of a contraindication to use IV contrast for CT or PET/CT (e.g. allergy, severe renal failure) in case a non-contrast PET/CT cannot be performed
4. Patients considered to have oligometastatic disease who are expected to undergo locoregional treatment
5. Presence of other malignancies in recent medical history (<5 years)
6. Female who is pregnant, breast-feeding or intends to become pregnant or is of child-bearing potential and not using an adequate, highly effective contraceptive
7. Adults who are the subject of a legal protection measure or who are unable to express their consent.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Standard-of-care Imaging + Whole-body diffusion-weighted MRI; Participants will undergo dual imaging at baseline and then every three months during first-line treatment for metastatic ILC, continuing until either 30 months of follow-up or documented disease progression. At these same timepoints, ctDNA levels and Ca15.3 will also be assessed.	Diagnostic test: whole body diffusion weighted MRI; Frequency: at baseline, after 1 month and every 3 months until 30 months of follow-up or disease progression; Diagnostic test: ctDNA; Frequency: at baseline, after 1 month and every 3 months until 30 months of follow-up or disease progression

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Percentage of cases where WB-DWI/MRI contributed solely to the decision of progression and/or treatment change assessed by questionnaires filled out by the treating oncologist at the time of progression	At the time of progression

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ctDNA dynamics	ctDNA levels will be assessed at baseline and every 3 months. Changes in levels will be correlated with findings on imaging.	At baseline, after 1 month of treatment, and every 3 months of treatment until disease progression or a maximum follow-up of 30 months (end of trial).
Measurability according to RECISTv1.1 criteria		At baseline and every 3 months of treatment until disease progression or a maximum follow-up of 30 months (end of trial).
Measurability according to MRI-specific criteria	Measurability will be assessed on MRI by use of RECIST v1.1 criteria and RECISTv1.1 extended with MRI-specific criteria (similar to MY-RADS and MET-RADS-P).	At baseline and every 3 months of treatment until disease progression or a maximum follow-up of 30 months (end of trial).
Disease extent on WB-DWI/MRI compared to SOC imaging	Disease extent on whole-body DWI/MRI (WB-DWI/MRI) is analyzed and compared with standard-of-care (SOC) imaging (e.g., CT, PET/CT, bone scan) using a combination of lesion detection, segmentation, and quantitative scoring methods. First, all visible lesions are identified on WB-DWI/MRI and SOC images using predefined anatomical regions. Lesions are counted and, where feasible, segmented to estimate tumor burden (e.g., total tumor volume).	At baseline and every 3 months of treatment until disease progression or a maximum follow-up of 30 months (end of trial).
Lesion-level ADC dynamics	Quantitative assessment using ADC measurements will be incorporated to support treatment response evaluation. Diffusion-weighted images acquired at baseline and early follow-up are used to generate ADC maps; the lesion is segmented, and quantitative metrics (e.g., mean or percentile ADC) are extracted. The change in ADC (absolute or percentage) is then calculated, with a significant increase typically indicating response, while stable or decreased ADC suggests resistance.	At baseline and after 1 month of treatment
Scores of psychological assessment questionnaires compared to baseline	Anxiety related to the imaging modalities will be assessed using the STAI-6 and Likert-10 scales, including evaluation of potential stressors associated with each imaging technique. The EORTC QLQ-COMU26 questionnaire will be used to assess patients' perceptions of imaging-related communication.	At baseline, after 1 month of treatment, and every 3 months of treatment until disease progression or a maximum follow-up of 30 months (end of trial).
Scores of psychological assessment questionnaires compared between imaging modalities	Anxiety related to the imaging modalities will be assessed using the STAI-6 and Likert-10 scales, including evaluation of potential stressors associated with each imaging technique. The EORTC QLQ-COMU26 questionnaire will be used to assess patients' perceptions of imaging-related communication.	At baseline and every 3 months of treatment until disease progression or a maximum follow-up of 30 months (end of trial).

Collaborators and Investigators

• Sponsor: KU Leuven
• Collaborators: Jules Bordet Institute
• Investigators: Principal Investigator: Hans Wildiers, MD/PHD, UZ Leuven; Principal Investigator: Philippe Aftimos, MD, Jules Bordet Institute; Principal Investigator: Elia Biganzoli, PHD, University of Milan

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): June 30, 2030
• Study Completion (Estimated): June 30, 2030

Study Registration Dates

• First Submitted: May 27, 2026
• First Submitted That Met QC Criteria: June 3, 2026
• First Posted (Actual): June 9, 2026

Study Record Updates

• Last Update Posted (Actual): June 9, 2026
• Last Update Submitted That Met QC Criteria: June 3, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Imaging; Liquid biopsy; Invasive lobular carcinoma; WB-DWI MRI
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Skin Diseases; Breast Diseases; Carcinoma; Neoplasms, Ductal, Lobular, and Medullary; Breast Neoplasms; Skin and Connective Tissue Diseases; Carcinoma, Lobular
• Other Study ID Numbers: S71975

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No