Lipiodol as an Imaging Biomarker of Tumor Response After Conventional Transarterial Chemoembolization: Prospective Clinical Validation in Patients with Primary and Secondary Liver Cancer

Miszczuk, Milena; Chapiro, Julius; Geschwind, Jean-Francois H.; Thakur, Vinayak; Nezami, Nariman; Laage-Gaupp, Fabian; Kulon, Michal; Breugel, Johanna M. M. van; Fereydooni, Arash; Lin, MingDe; Savic, Lynn Jeanette; Tegel, Bruno R; Wahlin, T.; Funai, E. F.; Schlachter, Todd

doi:10.1016/j.tranon.2020.01.003

Cited by 25 publications

(21 citation statements)

References 35 publications

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“…The main limitations of ethiodized oil as an intra-arterial drug carrier are the heterogeneous uptake and early washout seen in some tumors. Poor ethiodized oil uptake or retention after lung TACE was associated with lower response rates in our study, similar to what has been seen after hepatic artery TACE (23). Experimental drug carriers with improved tumor uptake and specificity (27) could result in more effective local drug delivery.…”

Section: Discussionsupporting

confidence: 85%

“…Thus, ethiodized oil serves as a tumor-targeting drug carrier. Similarly, intra-arterial ethiodized oil is also specifically retained in hepatocellular carcinoma (20), colorectal liver metastases (21), other liver tumors (22,23), and also in tumors outside the liver such as pancreatic (24,25) and renal (26) tumors. Ethiodized oil appears to specifically localize in tumors versus normal tissue but is nonspecific for the type of tumor.…”

Section: Discussionmentioning

confidence: 99%

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Bronchial or Pulmonary Artery Chemoembolization for Unresectable and Unablatable Lung Metastases: A Phase I Clinical Trial

Boas¹,

Kemeny²,

Sofocleous³

et al. 2021

Radiology

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M ost patients with lung metastases have unresectable disease (1). Patients with unresectable and unablatable lung metastases have poor survival and limited treatment options when the metastases stop responding to systemic chemotherapy (2).Transarterial chemoembolization (TACE) of the pulmonary or bronchial arteries is an emerging treatment option for large and multifocal lung tumors (Table E1 [online]). Like the liver, the lung has a dual blood supply. However, unlike liver tumors, which are mostly supplied by the hepatic artery, lung tumors can be supplied by either the bronchial artery or pulmonary artery (3). Response rates are 17% after pulmonary artery chemoembolization (4,5) and 39% after bronchial artery chemoembolization (6-8), bland embolization (9), or chemoinfusion (10-12). The highest reported response rates have been seen with primary lung cancer, treated via the bronchial artery (Table E1 [online]).A major limitation of existing studies of lung chemoembolization is the low response rate. We hypothesize that the low response rate is because of the dual blood supply of lung tumors. Lung tumors primarily supplied by the pulmonary artery will presumably have a low response rate to bronchial artery chemoembolization and Background: Lung chemoembolization is an emerging treatment option for lung tumors, but the optimal embolic, drug, and technique are unknown.Purpose: To determine the technical success rate and safety of bronchial or pulmonary artery chemoembolization of lung metastases using ethiodized oil, mitomycin, and microspheres. Materials and Methods:Patients with unresectable and unablatable lung, endobronchial, or mediastinal metastases, who failed systemic chemotherapy, were enrolled in this prospective, single-center, single-arm, phase I clinical trial (December 2019-September 2020). Pulmonary and bronchial angiography was performed to determine the blood supply to the lung metastases. Based on the angiographic findings, bronchial or pulmonary artery chemoembolization was performed using an ethiodized oil and mitomycin emulsion, followed by microspheres. The primary objectives were technical success rate and safety, according to the National Cancer Institute Common Terminology Criteria for Adverse Events. CIs of proportions were estimated with the equal-tailed Jeffreys prior interval, and correlations were evaluated with the Spearman test. Results:Ten participants (median age, 60 years; interquartile range, 52-70 years; six women) were evaluated. Nine of the 10 participants (90%) had lung metastases supplied by the bronchial artery, and one of the 10 participants (10%) had lung metastases supplied by the pulmonary artery. The technical success rate of intratumoral drug delivery was 10 of 10 (100%) (95% CI: 78, 100). There were no severe adverse events (95% CI: 0, 22). The response rate of treated tumors was one of 10 (10%) according to the Response Evaluation Criteria in Solid Tumors and four of 10 (40%) according to the PET Response Criteria in Solid Tumors. Ethiodized oil retention at 4-6 w...

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Section: Discussionsupporting

confidence: 85%

Section: Discussionmentioning

confidence: 99%

Bronchial or Pulmonary Artery Chemoembolization for Unresectable and Unablatable Lung Metastases: A Phase I Clinical Trial

Boas¹,

Kemeny²,

Sofocleous³

et al. 2021

Radiology

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“…The role of Lipiodol as potential imaging biomarker has been previously suggested with evidence from both retrospective and prospective data. Previous studies indicate that Lipiodol coverage on CT is correlated with subsequent necrosis on follow-up imaging and histopathology [10][11][12][13]28,32,33 . Unlike particulate-form embolic agents that usually fail to effectively penetrate the small intra-tumoral vasculature and tissue, Lipiodol, due to its oily nature, enters the tumor more readily and is retained within the tissue in a likely tumor-specific manner.…”

Section: Discussionmentioning

confidence: 98%

“…Overall reduction in viable tumor tissue was quantified as the percentage decrease in viable tumor volume between baseline and follow-up MRI. To assess radiographic tumor response of individual lesions the qEASL criteria were used because enhancement based response criteria have be shown to predict tumor necrosis after cTACE most accurate 25,[27][28][29] . According to qEASL, lesions were considered responders if they had a reduction of enhancing tumor volume of at least 65%.…”

Section: Tumor Segmentation and Mr Image Analysismentioning

confidence: 99%

Automated feature quantification of Lipiodol as imaging biomarker to predict therapeutic efficacy of conventional transarterial chemoembolization of liver cancer

Stark

Wang

Savic

et al. 2020

Sci Rep

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Conventional transarterial chemoembolization (cTACE) is a guideline-approved image-guided therapy option for liver cancer using the radiopaque drug-carrier and micro-embolic agent Lipiodol, which has been previously established as an imaging biomarker for tumor response. To establish automated quantitative and pattern-based image analysis techniques of Lipiodol deposition on 24 h post-cTACE CT as biomarker for treatment response. The density of Lipiodol deposits in 65 liver lesions was automatically quantified using Hounsfield Unit thresholds. Lipiodol deposition within the tumor was automatically assessed for patterns including homogeneity, sparsity, rim, and peripheral deposition. Lipiodol deposition was correlated with enhancing tumor volume (ETV) on baseline and follow-up MRI. ETV on baseline MRI strongly correlated with Lipiodol deposition on 24 h CT (p < 0.0001), with 8.22% ± 14.59 more Lipiodol in viable than necrotic tumor areas. On follow-up, tumor regions with Lipiodol showed higher rates of ETV reduction than areas without Lipiodol (p = 0.0475) and increasing densities of Lipiodol enhanced this effect. Also, homogeneous (p = 0.0006), non-sparse (p < 0.0001), rim deposition within sparse tumors (p = 0.045), and peripheral deposition (p < 0.0001) of Lipiodol showed improved response. This technical innovation study showed that an automated threshold-based volumetric feature characterization of Lipiodol deposits is feasible and enables practical use of Lipiodol as imaging biomarker for therapeutic efficacy after cTACE.

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“…Our team previously showed that lipiodol deposition is higher in patients with HCC who responded to cTACE on both conventional and cone-beam computed tomography (CT) (8,11). The degree of lipiodol deposition after cTACE in patients with NET was recently shown to predict response (17), although it is still unknown if lipiodol deposition is also a predictor of response in hepatic cholangiocarcinoma and liver metastases from colorectal tumors. Moreover, the rate of lipiodol washout (beyond absolute lipiodol uptake) has not been rigorously investigated as a potential indicator of response (18).…”

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confidence: 99%

Lipiodol Deposition and Washout in Primary and Metastatic Liver Tumors After Chemoembolization

Nezami

Breugel

Konstantinidis

et al. 2021

In Vivo

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Background/Aim: Lipiodol is the key component of conventional trans-arterial chemoembolization. Our aim was to evaluate lipiodol deposition and washout rate after conventional trans-arterial chemoembolization in intrahepatic cholangiocarcinoma and hepatic metastases originating from neuroendocrine tumors and colorectal carcinoma. Patients and Methods: This was a retrospective analysis of 44 patients with intrahepatic cholangiocarcinoma and liver metastasis from neuroendocrine tumors or colorectal carcinoma who underwent conventional trans-arterial chemoembolization. Lipiodol volume (cm 3 ) was analyzed on non-contrast computed tomography imaging obtained within 24 h post conventional trans-arterial chemoembolization, and 40-220 days after conventional trans-arterial chemoembolization using volumetric image analysis software. Tumor response was assessed on contrast-enhanced magnetic resonance imaging 1 month after conventional trans-arterial chemoembolization.Results: The washout rate was longer for neuroendocrine tumors compared to colorectal carcinoma, with half-lives of 54.61 days (p<0.00001) and 19.39 days (p<0.001), respectively, with no exponential washout among intrahepatic cholangiocarcinomas (p=0.83). The half-life for lipiodol washout was longer in tumors larger than 300 cm 3 compared to smaller tumors (25.43 vs. 22.71 days). Lipiodol wash out half-life was 54.76 days (p<0.01) and 29.45 days (p<0.00001) for tumors with a contrast enhancement burden of 60% or more and less than 60%, respectively. A negative exponential relationship for lipiodol washout was observed in nonresponders (p<0.00001). Conclusion: Lipiodol washout is a time-dependent process, and occurs faster in colorectal carcinoma tumors, tumors smaller than 300 cm 3 , tumors with baseline contrast enhancement burden of less than 60%, and non-responding target lesions.Lipiodol is the key component of conventional trans-arterial chemoembolization (cTACE) for primary and metastatic liver tumors (1, 2). This agent serves as a tumor-seeking, embolic and drug carrier agent, and is used in combination with chemotherapy for cTACE (3). In addition, the radiopacity of lipiodol helps to easily visualize and track it (4, 5). It has been shown that lipiodol retention in the treated tumor is related to tumor necrosis (6). Therefore, it could be considered as an imaging surrogate for response (7). While there are different one-dimensional (1D), two-dimensional 3261 This article is freely accessible online.

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Lipiodol as an Imaging Biomarker of Tumor Response After Conventional Transarterial Chemoembolization: Prospective Clinical Validation in Patients with Primary and Secondary Liver Cancer

Cited by 25 publications

References 35 publications

Bronchial or Pulmonary Artery Chemoembolization for Unresectable and Unablatable Lung Metastases: A Phase I Clinical Trial

Bronchial or Pulmonary Artery Chemoembolization for Unresectable and Unablatable Lung Metastases: A Phase I Clinical Trial

Automated feature quantification of Lipiodol as imaging biomarker to predict therapeutic efficacy of conventional transarterial chemoembolization of liver cancer

Lipiodol Deposition and Washout in Primary and Metastatic Liver Tumors After Chemoembolization

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