Assessment of tumour response with imaging-based tumour-specific response criteria is a crucial step to identify the value of a new therapy and to help clinicians to predict the prognosis of an individual patient, writes Christoph Zech.
In former times, the size of the lesion was supposed to provide the best (most robust and accurate) information about tumour response. Based on this assumption, the RECIST guidelines were introduced as a minimal, easy, and reproducible standard to assess tumour response. However, with new treatment strategies over the past few years, the limitations of using tumour size alone have become evident. Special challenges have been recognised for the assessment of recently introduced liver-directed locoregional therapies like transarterial chemoembolization (TACE) or radioembolization.
Basically, assessment of tumour response can be categorised into morphological criteria (WHO, RECIST 1.0, RECIST 1.1), functional criteria (Choi-criteria, EASL, mRECIST, DWI, perfusion-MRI) and metabolic criteria (PERCIST). Which category is best suitable for the individual situation is influenced by the therapy, but also by the tumour biology. Looking with more detail in suitable criteria for tumour-response after liver-directed therapies, we have to acknowledge that morphological criteria do not seem most suitable, since the tumour is usually devitalised by a combination of ischaemia from embolization and drug (TACE) or radiation (radioembolization) effects. Still, RECIST is the standard to assess tumour response in many scientific studies and in daily clinical routine.
When considering the tumour biology, then primary liver-tumours in general (especially HCC) are characterised by neo-angiogenesis and hypervascularization, whilst FDG (18F-FluorDesoxyGlucose) metabolism is variable. Therefore HCC functional criteria, like EASL or mRECIST, are most important and have nowadays a wide distribution and good evidence. One the other hand, FDG metabolism does not play a major role to assess tumour response after liver-directed treatment of HCC. The situation is different for liver metastases. Here the majority of primary tumours and also of corresponding liver metastases do show increased FDG metabolism and FDG-PET (positron emission tomography) plays a huge role in assessing tumour response and is the subject of many scientific studies. On the other hand, for most liver metastases “easy” functional criteria do not work well due to the lack of apparent hypervasculariation. In such cases the established and robust functional criteria like EASL and mRECIST have limitations. With regard to the more sophisticated functional approaches like diffusion-weighted imaging or perfusion MRI, we can find many good single-centre studies with excellent results to predict long-term outcome or long-term morphological response already quite early after the intervention. However, there is a lack of standardisation—which means that the methodology cannot be exactly replicated in other centres and, therefore, the use of these new methods is hampered in clinical reality.
Since tumour response in daily routine is still assessed based on morphological criteria, it is crucial for diagnostic radiologists and clinicians to know about the imaging behaviour of liver malignancies after liver-directed therapies. This is of special relevance for the imaging appearance of liver metastases after radioembolization, since the variations of imaging findings in early follow-up studies can be substantial. Classical signs of a good response to treatment would be a decrease in tumour size. However, often we can observe only an increase in necrotic areas and a lack of enhancement. Frequently, a newly observed ring enhancement can be seen in metastatic disease post-radioembolization, which at first glance might be mistaken for tumour progress. In the end, sometimes even a paradoxical increase in size in early follow-up can be noticed, despite a good long-term tumour response. In all those unclear situations FDG-PET can help to differentiate between post-therapeutic changes in responders and potential tumour progress in non-responders.
A firm knowledge of the different response systems, a broad experience with patients post liver-directed therapies and often a multimodal imaging strategy is needed to successfully judge the tumour response in patients after liver-directed minimally invasive interventional radiology therapies.
Christoph Zech is an associate professor of Radiology, and division head of Interventional Radiology, Radiology und Nuclear Medicine, University Hospital Basel, Basel, Switzerland. He has reported no disclosures pertaining to this article.