Currently, there is no possibility to detect early tumor response in lung cancer patients within the first days after chemotherapy (CTx) or tyrosine kinase inhibitor (TKI) therapy induction. Using the current gold standard for therapy monitoring, i.e. the measurement of morphologic differences according to RECIST 1.1 by CT and MRI, changes are detected only after weeks or months. Thus, patients may undergo eventually ineffective treatment and suffer from unnecessary toxicity, with both causing relevant costs. This highlights the importance of early response detection to guide and optimize therapy. Monitoring treatment response with diffusion-weighted and dynamic contrast perfusion MR imaging has been proposed for some time as a new powerful tool that will allow determining tumor response much earlier than RECIST.
This is an observational, prospective, multicenter, non-randomized, open clinical study. 150 patients with non-squamous NSCLC undergoing systemic treatment receive MRI before and after 1st-line therapy. The first follow-up (FU) MRI for patients undergoing chemotherapy is performed 24 hours post treatment. Patients treated with TKIs undergo MRI at days 7 and 14 after therapy induction. A thoracic MRI protocol is performed, including navigated diffusion-weighted imaging with the acquisition of 6 b-values, while the evaluation will focus on the non-perfusion sensitive b-values 400 and 800 (online calculated trace images) and the apparent diffusion coefficient (ADC). Software-based analysis of user-defined ROIs is used to assess the ADC value inside the tumor. ROIs are put in the solid part of the tumorous lesion. So far, 54 patients (28 TKI, 26 CTx) have been included. Findings will be correlated with routinely performed FU CT-imaging and the clinical outcome during FU visits. Further, an accompanying biomarker program aims to elucidate ultra-early blood-bound signs of apoptosis in correlation with MRI signals. This multicenter study will address the unmet clinical need of ultra-early detection of therapy response in NSCLC in order to translate this promising approach into broad clinical practice.
Clinical trial identification
Legal entity responsible for the study
Claus Peter Heussel.
German Center for Lung Research (DZL).
H-U. Kauczor: Grant: Siemens; Speakers bureau: Boehringer Ingelheim, Philips; Grant, speakers' bureau: Bracco, Bayer. M. Thomas: Speaker: Lilly, BMS, MSD, Roche, Pfizer, AstraZeneca; Advisory board: Lilly, BMS, MSD, Roche, Pfizer, AstraZeneca, Cellgene, Mediolanum. H. Golpon: Advisory boards: Roche, AstraZeneca, Boehringer Ingelheim, BMS. A. Tufman: Advisory boards: Roche, AstraZeneca, Boehringer Ingelheim. C.P. Heussel: Consultation or other fees: Schering-Plough, Pfizer, Basilea, Boehringer Ingelheim, Novartis, Roche, Astellas, Gilead, MSD, Lilly, Intermune, Fresenius; Research funding: Siemens, Pfizer, MeVis, Boehringer Ingelheim; Lecture fees: Gilead, Essex, Schering-Plough, AstraZeneca, Lilly, Roche, MSD, Pfizer , Bracco, Meda Pharma, Intermune, Chiesi, Siemens, Covidien, Pierre Fabre, Boehringer Ingelheim, Grifols, Novartis, Basilea, Bayer. F. Bozorgmehr: Research funding: BMS; Honoraria: MSD, Novartis. All other authors have declared no conflicts of interest.