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Despite recent progress in the management of patients with liver cancer mostly in the form of new immuno-oncology drugs, the prognosis remains poor overall. With curative treatment only applicable to a small minority of patients, as the vast majority of patients are diagnosed at more advanced stages of the disease, loco-regional therapies, such as ablation, transarterial chemoembolization or radioembolization remain an essential part of the treatment paradigm especially for patients with early or intermediate stage disease. One such procedure, conventional transarterial chemoembolization or cTACE, which has been used for almost 4 decades to treat patients with liver cancer and in fact is one of the most commonly performed procedures worldwide for liver cancer, was shown to provide survival benefit through the highest level of evidence (level 1a) available in clinical medicine. As a result, TACE has been incorporated in all the treatment guidelines for liver cancer. The procedure consists of creating an emulsion between an oily medium called lipiodol and chemotherapeutic agents, usually doxorubicin and/or cisplatin, which is then delivered under image guidance directly to the tumors exploiting the fact that liver tumors draw their blood supply from arterial rather than venous blood. As a result, the tumors are targeted and treated precisely while the remainder of the liver remains unaffected. A main benefit of cTACE is the fact that lipiodol is also radiopaque and can therefore be directly visualized as it navigates through the arterial system and find its way to the tumors where it remains. One could therefore surmise a biomarker role -for lipiodol- of successful drug delivery and tumor targeting, and possibly as a predictor of tumor response and patient survival. Indeed, existing data suggested that because lipiodol retention within tumors correlated well with tumor necrosis at histopathology, this feature could possibly be used as the ultimate proof of the imaging biomarker role of lipiodol. However direct evidence was still lacking.

How could we prove this? To provide definitive evidence, we designed a prospective clinical trial relying on various imaging methods to assess tumor response after cTACE. This multimodality imaging protocol included computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography (PET). The results of our study provided such definitive proof by demonstrating the “dynamic role of lipiodol as an imaging biomarker across a spectrum of tumor types and sizes within the liver”. By monitoring longitudinally through time the patterns of lipiodol deposition and retention within tumors, we were able to unequivocally demonstrate a correlation between lipiodol deposition and retention in tumors, and ultimately tumor response and patient survival.

As the quest for biomarkers in oncology persists, this study confirmed the existence of such a biomarker specific for cTACE. This invaluable asset can therefore be relied upon as a surrogate marker of patient survival.