Preliminary qualification of a novel, hypoxic-based radiologic signature for trans-arterial chemoembolization in hepatocellular carcinoma

Abstract

BackgroundSurvival advantage following trans-arterial chemoembolization (TACE) is variable in patients with hepatocellular carcinoma (HCC). We combined pre-TACE radiologic features to derive a novel prognostic signature in HCC.MethodsA multi-institutional dataset of 98 patients was generated from two retrospective cohorts from United Kingdom (65%) and Italy (36%). The prognostic impact of a number baseline imaging parameters was assessed and factors significant on univariate analysis were combined to create a novel radiologic signature on multivariable analyses predictive of overall survival (OS) following TACE.ResultsMedian OS was 15.4 months. Tumour size > 7 cm (p < 0.001), intra-tumour necrosis (ITN) (p = 0.02) and arterial ectatic neovascularisation (AEN) (p = 0.03) emerged as individual prognostic factors together with radiologic response (p < 0.001) and elevated alpha-fetoprotein (AFP) (p = 0.01). Combination of tumour size > 7 cm, ITN and AEN identified patients with poor prognosis (p < 0.001).ConclusionsWe identified a coherent signature based on commonly available imaging biomarkers likely to be reflective of differential patterns of relative hypoxia and neovascularisation. Large tumours displaying AEN and ITN are characterised by a shorter survival after TACE.

<p>Development and Verification of the Hypoxia-Related and Immune-Associated Prognosis Signature for Hepatocellular Carcinoma</p>

“…30,31 Therefore, one single biomarker can hardly accurately examine the hypoxia status. 32,33 Notably, t-SNE, the machine learning algorithm, has provided the refined and potent way of dimensionality reduction, thus assisting in exploring the possible subtypes within prostate cancer 34 as well as breast cancer (BC). 35 According to our results, t-SNE helped to identify different hypoxia TME patterns on the basis of 200 hallmark genes of hypoxia.…”

RAP1GAP is a novel marker of trabecular pattern and poor sorafenib treatment response in hepatocellular carcinoma

“…The MaT subtype has recently been shown to exhibit higher AFP levels, early recurrence, and worse overall survival than the MiT subtype [6]. MTM-HCC is characterised by a predominant > 50 % MaT (trabeculae of more than 6 cells thick) architectural pattern and is associated with an aggressive phenotype and particular biology (high AFP in serum levels and strong angiogenesis activation) [7,8]. Microscopically, we linked gene expression data to H&E images from TCGA.…”

“…We divided MTM-HCCs into MaTM (MTM-HCC without necrosis) and MaTN (MTM-HCC with necrosis). The reduced oxygen concentration that characterises larger and highly proliferating tumours is the main trigger for hypoxia-related factor expression [8]. HIF1α is an important hypoxia-inducible gene that is mainly expressed in neoplastic tissues.…”

Efficacy and safety of apatinib combined with transarterial chemoembolization (TACE) in treating patients with recurrent hepatocellular carcinoma

“…Transarterial chemoembolization (TACE) has been developed as a readily available treatment option with good tolerance, limited liver toxicity, and demonstrated efficacy for intermediate-stage HCC, even in recurrent patients with borderline liver function (5)(6)(7). However, the local hypoxia environment caused by interventional embolization could stimulate tumor angiogenesis and increase the expression of vascular endothelial growth factor (VEGF), which in turn promotes tumor recurrence and metastasis (8,9). Short-term tumor progression has been reported in some patients after TACE treatment, and the overall effect remains unsatisfactory (8,10).…”

“…However, the local hypoxia environment caused by interventional embolization could stimulate tumor angiogenesis and increase the expression of vascular endothelial growth factor (VEGF), which in turn promotes tumor recurrence and metastasis (8,9). Short-term tumor progression has been reported in some patients after TACE treatment, and the overall effect remains unsatisfactory (8,10). Therefore, it is reasonable that the therapy of TACE combined with anti-angiogenic drugs would be conducive to augment the clinical benefit of TACE alone.…”