Evaluation of diffusion-weighted MRI and (18F) fluorothymidine-PET biomarkers for early response assessment in patients with operable non-small cell lung cancer treated with neoadjuvant chemotherapy

Dominic Carlin; Alexander Weller; Gem Kramer; Yan Liu; John C Waterton; Arturo Chiti; Martina Sollini; A Joop de Langen; Mary E R O'Brien; Maria Urbanowicz; Bart Km Jacobs; Nandita deSouza

doi:10.1259/bjro.20190029

Evaluation of diffusion-weighted MRI and (18F) fluorothymidine-PET biomarkers for early response assessment in patients with operable non-small cell lung cancer treated with neoadjuvant chemotherapy

BJR Open. 2019 Jul 20;1(1):20190029. doi: 10.1259/bjro.20190029. eCollection 2019.

Affiliations

¹ CRUK Imaging Centre, The Institute of Cancer Research, Sutton, Surrey SM2 5NG, UK.
² Department of Respiratory Diseases, VU University Medical Center, Amsterdam, The Netherlands.
³ EORTC Headquarters, Brussels, Belgium.
⁴ Centre for Imaging Sciences, Division of Informatics Imaging & Data Sciences, School of Health Sciences, Faculty of Biology Medicine & Health, University of Manchester, Manchester Academic Health Sciences Centre, Oxford Road Manchester M13 9PL UK.
⁵ Department of Biomedical Sciences, Humanitas University, Milan, Italy.
⁶ The Royal Marsden Hospital, Downs Road, Sutton, Surrey SM2 5PT, UK.

Abstract

Objective: To correlate changes in the apparent diffusion coefficient (ADC) from diffusion-weighted (DW)-MRI and standardised uptake value (SUV) from fluorothymidine (¹⁸FLT)-PET/CT with histopathological estimates of response in patients with non-small cell lung cancer (NSCLC) treated with neoadjuvant chemotherapy and track longitudinal changes in these biomarkers in a multicentre, multivendor setting.

Methods: 14 patients with operable NSCLC recruited to a prospective, multicentre imaging trial (EORTC-1217) were treated with platinum-based neoadjuvant chemotherapy. 13 patients had DW-MRI and FLT-PET/CT at baseline (10 had both), 12 were re-imaged at Day 14 (eight dual-modality) and nine after completing chemotherapy, immediately before surgery (six dual-modality). Surgical specimens (haematoxylin-eosin and Ki67 stained) estimated the percentage of residual viable tumour/necrosis and proliferation index.

Results: Despite the small numbers,significant findings were possible. ADC_median increased (p < 0.001) and SUV_mean decreased (p < 0.001) significantly between baseline and Day 14; changes between Day 14 and surgery were less marked. All responding tumours (>30% reduction in unidimensional measurement pre-surgery), showed an increase at Day 14 in ADC75^th centile and reduction in total lesion proliferation (SUV_mean x proliferative volume) greater than established measurement variability. Change in imaging biomarkers did not correlate with histological response (residual viable tumour, necrosis).

Conclusion: Changes in ADC and FLT-SUV following neoadjuvant chemotherapy in NSCLC were measurable by Day 14 and preceded changes in unidimensional size but did not correlate with histopathological response. However, the magnitude of the changes and their utility in predicting (non-) response (tumour size/clinical outcome) remains to be established.

Advances in knowledge: During treatment, ADC increase precedes size reductions, but does not reflect histopathological necrosis.