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

Abstract

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 weeks was correlated with reduced tumor size (ρ = -0.83, P = .003) and metabolic activity (ρ = -0.71, P = .03). Pharmacokinetics showed that 45% of the mitomycin dose underwent burst release in 2 minutes, and 55% of the dose was retained intratumorally with a half-life of more than 5 hours. The initial tumor-to-plasma ratio of mitomycin concentration was 380. Conclusion Lung chemoembolization was technically successful for the treatment of lung, mediastinal, and endobronchial metastases, with no severe adverse events. Clinical trial registration no. NCT04200417 © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Georgiades et al in this issue.

Graphical abstract

Figure 1:

Flowchart of study enrollment and follow-up.

Figure 2:

Diagram of blood supply to lung metastases (arrows). Tumors were classified into three categories, according to their appearance at angiography. TACE = transarterial chemoembolization.

Figure 3:

Right bronchial artery chemoembolization in 50-year-old man with colon cancer and growing chemorefractory lung metastases. (A) Right bronchial angiogram shows lung metastases (arrow). (B) Selective right bronchial angiogram shows lung metastases (arrow). (C) Catheter CT angiogram shows blood supply to lung, hilar lymph node, and subcarinal lymph node (arrows). (D) Unenhanced CT scan after transarterial chemoembolization shows retained lipiodol (arrow) in right lung metastases. (E) Pretreatment PET/CT scan shows hypermetabolic lung metastases (arrow). (F) PET/CT scan after transarterial chemoembolization shows partial metabolic response (arrow), with tumor necrosis resulting in intratumoral gas.

Figure 4:

Graph shows plasma concentration of mitomycin after chemoembolization of lung metastases, measured with liquid chromatography–mass spectrometry.

Figure 5:

(A) Pharmacokinetics model for transarterial chemoembolization, with parameters (means ± standard deviations) fit to experimental data in Figure 4. Arrows are color coded to match labels in B and C. (B) Graph shows plasma mitomycin concentration (log scale), using parameters from A. (C) Graph shows mitomycin retained in tumor (log scale), using parameters from A.

Figure 6:

Emulsion separation and drug release in vitro. (A) Photographs of lipiodol and mitomycin emulsion (top syringe) and separated emulsion (bottom syringe). In separated emulsion, lipiodol is top layer and aqueous phase is bottom layer. (B) Graph shows emulsion separation kinetics. Volume of aqueous phase was fit to cumulative distribution function of gamma distribution (α = 69, β = 0.10 days). (C) Graph shows drug release kinetics.