Whole-body MRI for lung cancer staging: a step in the right direction
Authors: Mathias Meyer, Johannes Budjan
Journal: The Lancet Respiratory Medicine (2019)

The use of imaging for precise staging to determine the most appropriate treatment strategy is of utmost importance in non-small-cell lung cancer (NSCLC), given that it is the leading cause of death in developed countries.1Ferlay JSI Ervik M Dikshit R et al.GLOBOCAN 2012: estimated cancer incidence, mortality and prevalence worldwide in 2012 v1.0.http://publications.iarc.fr/Databases/Iarc-Cancerbases/GLOBOCAN-2012-Estimated-Cancer-Incidence-Mortality-And-Prevalence-Worldwide-In-2012-V1.0-2012Date accessed: April 16, 2019Google Scholar The National Comprehensive Cancer Network and European Society of Medical Oncology recommend intravenous contrast agent-enhanced chest CT, 18-fluorodeoxyglucose ([18F]-FDG)-PET-CT, and—depending on the guidelines—brain MRI studies for staging of NSCLC.2Ettinger DS Wood DE Aisner DL et al.Non-small cell lung cancer, version 5.2017, NCCN Clinical Practice Guidelines in Oncology.J Natl Compr Canc Netw. 2017; 15: 504-535Crossref PubMed Scopus (838) Google Scholar, 3Postmus PE Kerr KM Oudkerk M et al.Early and locally advanced non-small-cell lung cancer (NSCLC): ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up.Ann Oncol. 2017; 28: 1-21Crossref Scopus (982) Google Scholar Additionally, in cases of equivocal findings of metastasis at [18F]-FDG-PET-CT (eg, in the brain, spine, or liver), MRI is indicated. For both patients and health-care providers, it would be desirable to have a single and accurate imaging modality for staging. In The Lancet Respiratory Medicine, Stuart A Taylor and colleagues report the Streamline L study,4Taylor SA Mallett S Ball S et al.Diagnostic accuracy of whole-body MRI versus standard imaging pathways for metastatic disease in newly diagnosed non-small-cell lung cancer: the prospective Streamline L trial.Lancet Respir Med. 2019; (published online May 9.)http://dx.doi.org/10.1016/S2213-2600(19)30090-6Summary Full Text Full Text PDF Scopus (38) Google Scholar providing evidence that whole-body MRI (WB-MRI) might represent such an imaging modality. Compared with previous studies,5Ohno Y Koyama H Yoshikawa T et al.Three-way Comparison of whole-body MR, coregistered whole-body FDG PET/MR, and integrated whole-body FDG PET/CT imaging: TNM and stage assessment capability for non-small cell lung cancer patients.Radiology. 2015; 275: 849-861Crossref PubMed Scopus (56) Google Scholar, 6Usuda K Sagawa M Maeda S et al.Diagnostic performance of whole-body diffusion-weighted imaging compared to PET-CT plus brain MRI in staging clinically resectable lung cancer.Asian Pac J Cancer Prev. 2016; 17: 2775-2780PubMed Google Scholar which compared WB-MRI with [18F]-FDG-PET-CT, Streamline L has a more pragmatic and realistic workflow-based approach. Patients underwent a standard staging pathway, which in most cases included a [18F]-FDG-PET-CT scan, and an additional WB-MRI, which served as a separate approach. Based on the findings of each approach, a multidisciplinary team made treatment decisions, and the outcomes were evaluated after 12 months. Not only did the Streamline L study show equivalent diagnostic performance for tumour size, invasion, and metastatic staging of WB-MRI, but also showed a decreased time interval to complete staging and diagnostic costs when compared with the standard staging pathway. Although WB-MRI was more burdensome than the standard pathway, patients preferred this imaging modality to standard staging, if the staging times were reduced. This finding highlights the importance of improving staging workflow and choosing the appropriate diagnostic approach for each patient individually to minimise the time to treatment decision, because this might cause unnecessary patient anxiety and is directly related to patient outcomes.7Navani N Nankivell M Lawrence DR et al.Lung cancer diagnosis and staging with endobronchial ultrasound-guided transbronchial needle aspiration compared with conventional approaches: an open-label, pragmatic, randomised controlled trial.Lancet Respir Med. 2015; 3: 282-289Summary Full Text Full Text PDF PubMed Scopus (164) Google Scholar Although the Streamline L study is a step in the right direction, some unanswered questions and new problems need to be addressed. First, occult metastatic disease at baseline staging remains an issue, given the low sensitivity of both pathways in Streamline L for metastatic staging (WB-MRI 50% [95% CI 37–63] versus standard care 54% [41–67]). A high sensitivity is crucial, especially in patients undergoing curative surgery. Second, Streamline L highlights the insufficiency of current imaging modalities for lymph node staging in NSCLC, with worse results for WB-MRI compared with the standard of care imaging (agreement: 65% [range depending on lymph node stage 14–80] vs 75% [38–86]). This finding shows the importance of a systematic, invasive approach to assess hilar and mediastinal lymph nodes by endobronchial ultrasound in patients in which lymph node stage has directly influenced treatment decisions (eg, locoregional T1-T2b NSCLCs with unknown node status for the decision if adjuvant chemotherapy is indicated). Third, contraindications to WB-MRI include implanted devices, claustrophobia, and—depending on the system used—obese patients, which restrict universal usage. However, current developments in medical engineering are aiming to reduce those barriers to allow greater access to MRI; for example, by introducing wide-bore systems or by providing MRI-compatible implants. Several MRI techniques have also been introduced, which significantly reduce acquisition times.8Barth M Breuer F Koopmans PJ Norris DG Poser BA Simultaneous multislice (SMS) imaging techniques.Magn Reson Med. 2016; 75: 63-81Crossref PubMed Scopus (315) Google Scholar, 9Feng L Benkert T Block KT Sodickson DK Otazo R Chandarana H Compressed sensing for body MRI.J Magn Reson Imaging. 2017; 45: 966-987Crossref PubMed Scopus (160) Google Scholar Otherwise time-consuming, whole-body examinations could benefit from these techniques. Computer-aided analysis, ideally using artificial intelligence, might facilitate time-efficient and cost-effective interpretation of WB-MRI examinations.10Mazurowski MA Buda M Saha A Bashir MR Deep learning in radiology: an overview of the concepts and a survey of the state of the art with focus on MRI.J Magn Reson Imaging. 2019; 49: 939-954Crossref PubMed Scopus (183) Google Scholar Such techniques might be required to introduce WB-MRI at a larger scale in clinical routine. However, it remains to be seen to what extent these additional costs will be reimbursed by health-care providers. Finally, since the discovery of gadolinium retention in the brain, controversy exists about the application of gadolinium-based contrast agents, as used in the Streamline L study. Gadolinium retention can be seen as persistent T1 signal changes in the deep grey matter of the brain in patients with normal renal function after multiple uses of a gadolinium-based contrast agent.11Davenport MS Choosing the safest gadolinium-based contrast medium for MR imaging: not so simple after all.Radiology. 2018; 286: 483-485Crossref PubMed Scopus (19) Google Scholar Despite the enormous number of diagnostic gadolinium injections (about 450 million), no clinical correlate to these observations is known as yet. Although the application of contrast agents improves staging accuracy and is therefore desired, a class warning for gadolinium retention has been issued by the US Food and Drug Administration and the marketing authorisation for several linear contrast agents has been suspended in the European Union. Alternative protocols have been proposed using morphological sequences without gadolinium-based contrast agents or alternative contrast agents (ie, ultrasmall superparamagnetic iron oxides for lymph node metastasis detection) in combination with functional sequences, such as diffusion-weighted imaging or hybrid PET-MR imaging approaches. Although WB-MRI might be the imaging modality we have been hoping for in NSCLC staging, occult metastases and lymph node staging remain challenging by non-invasive imaging. Further research is needed to improve the diagnostic performance of non-invasive imaging, preferably a one-stop-shop approach, which allows time-efficient and accurate treatment decisions. MM reports speaking fees from Siemens Healthineers and grants to his institution from Siemens Healthineers and Bracco Imaging, outside of the submitted work. JB reports speaking fees from Siemens Healthineers and Ferring Pharmaceuticals, outside of the submitted work. Diagnostic accuracy of whole-body MRI versus standard imaging pathways for metastatic disease in newly diagnosed non-small-cell lung cancer: the prospective Streamline L trialWB-MRI staging pathways have similar accuracy to standard pathways, and reduce the staging time and costs. Full-Text PDF Open Access