Abstract OT1-03-02: Combining MRI and liquid biopsies for prediction of response to neoadjuvant chemotherapy in early stage breast cancer: The LIMA study
Authors: Janssen Liselore Maria , Suelmann Britt Berendine Maria , Janse Markus Hendrik Adriaan , Elias Sjoerd Geert , van Diest Paul J , Veldhuis Wouter Bernard , van der Wall Elsken , Gilhuijs Kenneth George Antonius 
Published: March 2020

Background The response to neoadjuvant chemotherapy (NAC) in early stage breast cancer has important prognostic implications1-3. Early, dynamic prediction of response allows for adaption of the treatment plan before completion, or even before the start of treatment. This strategy can help prevent overtreatment and related toxicity and correct for undertreatment with an ineffective regimen. We hypothesize that accurate dynamic response prediction may be reached by combining multi-parametric MRI with liquid biopsies prior to, during and after NAC, in addition to conventional clinical and pathological information. Magnetic resonance imaging (MRI) is non-invasive and is typically used for response evaluation in current clinical practice. It shows the size and perfusion of the tumor as they change during treatment. However, tumor size on MRI has limited predictive value for response to therapy4. Multi-parametric MRI uses different imaging protocols in one session to measure more functional items than perfusion alone, addressing different aspects of tumor biology, and possibly improving predictive value. With this improvement, imaging still only visualizes macroscopic disease. Therefore, in the LIMA study, MRI will be combined with liquid biopsies containing circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA), which have both shown prognostic and predictive values in early stage breast cancer5-7. Since the ctDNA may originate from cells in every part of the tumor, it may capture tumor heterogeneity. Liquid biopsies are minimally invasive and provide insight into microscopic tumor load and the tumor’s genetic picture. There is an abundance of clinical studies investigating the predictive value of liquid biopsies and MRI. On breast cancer however, no studies have been published that combine these two modalities.

Aim show proof of concept for combining multi-parametric MRI with liquid biopsies in addition to conventional clinical and pathologic information, to accurately predict response to NAC at different time points.

Trial design A multicenter prospective observational cohort study. Multi-parametric MRI will be performed prior to NAC, halfway and after completion of NAC. Liquid biopsies will be obtained before start of treatment, every 2 weeks during treatment and after completion of NAC.

Statistical methods The primary endpoint is Residual Cancer Burden (RCB) in the surgical resection specimen after NAC. Collected data will be analyzed with efficient statistical methods dedicated to sparse datasets primarily using penalized regression techniques.

Eligibility criteria Non-pregnant, non-lactating women ≥18 years of age with non-metastatic, histologically proven invasive breast cancer who are planned to be treated with NAC (and in case of a HER2-positive tumor: addition of trastuzumab and/or pertuzumab) who have:

- no luminal A breast cancer

- no inflammatory breast cancer

- no other active malignant disease in the past 5 years (excluding squamous cell or basal cell carcinoma of the skin)

-no contra-indications for MRI or gadolinium-based contrast agents

Target accrual 100 patients (present: 0)

References 1von Minckwitz 2012 J Clin Oncol; 2Cortazar 2014 Lancet; 3Symmans 2007 J Clin Oncol; 4Gu 2017 Clin Breast Cancer; 5Bidard 2018 J Natl Cancer Inst; 6Garcia-Murillas 2015 Sci Transl Med 7Magbanua 2018 SABCS p. Abstract No. PD2-01

Acknowledgements Funding from the European Union Horizon 2020 research and innovation program under grant agreement no. 755333 (LIMA). In collaboration with Philips, INSERM, ICM, Agena Bioscience, ANGLE, Stilla Technologies, DiaDx and ALS Automated Lab Solutions.

Citation Format: Liselore Maria Janssen, Britt Berendine Maria Suelmann, Markus Hendrik Adriaan Janse, Sjoerd Geert Elias, Paul J van Diest, Wouter Bernard Veldhuis, Elsken van der Wall, Kenneth George Antonius Gilhuijs. Combining MRI and liquid biopsies for prediction of response to neoadjuvant chemotherapy in early stage breast cancer: The LIMA study [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr OT1-03-02.