Chemoembolization for Lung Neoplasms: Exuberant Expectations versus Meticulous Investigation

HomeRadiologyVol. 301, No. 2 PreviousNext Reviews and CommentaryFree AccessEditorialChemoembolization for Lung Neoplasms: Exuberant Expectations versus Meticulous InvestigationChristos Georgiades Christos Georgiades Author AffiliationsFrom the Division of Vascular and Interventional Radiology, Johns Hopkins University, 1800 Orleans St, Zayed 7203, Baltimore, MD 21287.Address correspondence to the author (e-mail: [email protected]).Christos Georgiades Published Online:Aug 31 2021https://doi.org/10.1148/radiol.2021211488MoreSectionsPDF ToolsImage ViewerAdd to favoritesCiteTrack CitationsPermissionsReprints ShareShare onFacebookTwitterLinked In See also the article by Boas et al in this issue.Dr Georgiades is a professor of radiology, oncology, and surgery at Johns Hopkins University in the Division of Vascular and Interventional Radiology. He is the director of interventional oncology and has served as clinical director and fellowship program director. He has held many institutional, national, and international leadership and volunteer service positions and has led the development of educational, clinical, and research programs. His research interests focus on local-regional treatments for solid tumors.Download as PowerPointOpen in Image Viewer In theory, transarterial chemoembolization (TACE) should be an effective treatment option for pulmonary neoplastic disease. Extrapolating from hepatic TACE experience, there is no reason why it should not live up to expectations. As with the liver, the lung has a dual blood supply, as with hepatic malignancies, the blood supply appears to be mostly from systemic arteries, and as with hepatic metastatic disease, there is a large pool of patients who can potentially benefit. Yet, unlike the way hepatic TACE burst onto the scene in 2002–2003 as a result of the pivotal studies by Llovet et al (1,2) and Lo et al (3), the adoption of pulmonary TACE by the interventional oncology community is slow and enthusiasm is subdued. A critical assessment of the study by Boas et al (4) explains the reasons for, and importantly, the wisdom of this measured approach.This study (4) is a single-arm, single-center prospective investigation of 10 participants with secondary lung neoplasm (nine with colorectal cancer and one with melanoma) who had no remaining standard-of-care options. Pretreatment assessment included pulmonary contrast-enhanced CT, PET/CT, and pulmonary functions tests. Inclusion and exclusion criteria were strict, as they generally should be in phase I studies. Treatment protocol mirrored that of hepatic TACE, with the technical objective of delivering an ethiodized oil chemotherapy emulsion to the target followed by particle embolization to reduce and/or arrest flow. The novelty introduced by this research was the performance of both pulmonary and bronchial (or other systemic) arteriograms, and the correlation of baseline CT and C-arm CT findings with outcomes. In addition to delineating the vascular anatomy of tumor supply, Boas et al (4) investigated drug (ie, mitomycin) in vivo pharmacokinetics, as well as the in vitro emulsion stability.The primary objectives were safety and technical efficacy. No immediate major adverse events were reported, including (and relevantly) spinal cord ischemia. However, at follow-up 4–6 weeks later, forced vital capacity was reduced from 84% predicted (baseline) to 77% (P = .02), and forced expiratory volume in 1 second was reduced from 86% predicted to 81% (P = .05). Saturation on room air remained normal. Technical efficacy (ie, successful delivery of emulsion and particles to slow or to arrest flow) was 100%.Secondary objectives included objective response rate, delineation of blood supply to pulmonary metastases (ie, bronchial vs pulmonary artery), mitomycin pharmacokinetics, and ethiodized oil retention by targeted lesion(s). According to PET Response Criteria in Solid Tumors, or PERCIST, and Response Evaluation Criteria in Solid Tumors, or RECIST, the authors reported a 40% and 10% response, respectively. Nontargeted tumors served as an internal control, showing 0% PERCIST response and an average 10% increase according to RECIST during the short follow-up period of 4–6 weeks. Interestingly, all colorectal lesions showed systemic supply (ie, mainly from the bronchial artery), whereas the single metastatic melanoma lesion had a pulmonary artery supply. Mitomycin pharmacokinetics followed the standard two-compartment model with an initial burst phase, a second rapid clearance phase, and a third longer release phase. In this study, the burst phase consumed 45% of the total drug dose. The in vitro experiment indicated a 7.1-hour release half-life for the remaining 55%, whereas the in vivo release half-life was calculated at longer than 5 hours. Two findings were of particular clinical interest—the authors’ demonstration of a high tumor-to-plasma mitomycin concentration (up to 380) and the correlation between ethiodized oil concentration in the tumor and tumor response. Both of these findings mirror those of early hepatic TACE experience.The limitations of the study are equally instructive. First, the small number of participants and that nine of 10 had colorectal metastases are indicative of inclusion and/or referral hesitation. This was the case during early TACE experience (5), and it remains an issue for other contemporary studies on pulmonary TACE (6). Second (and related to the first) is the perception that pulmonary TACE is technically more challenging than hepatic TACE. This is obviously a correct assessment. Systemic arterial supply (ie, from mostly the bronchial artery) is more difficult to identify, select, and canulate safely. Third, the potential of spinal cord infarction is a major additional concern. Last, any nontarget damage to hepatic parenchyma after TACE is likely to be transient. This is not necessarily the case with pulmonary function after pulmonary TACE. In this study, both forced vital capacity and forced expiratory volume in 1 second were reduced 4–6 weeks after TACE. Studies with longer-term follow-up are necessary to assess the risk, degree, and resilience of pulmonary functions test degradation.In summary, the results of this current phase I study (4) are encouraging, especially when viewed in context with other similar studies. Bie et al (6) and Zeng et al (7) showed a 100% disease response rate plus disease stability among patients with an 8-month progression-free survival (6) after pulmonary TACE. Early results on efficacy are also encouraging, showing improved survival in patients treated with pulmonary TACE plus systemic chemotherapy versus systemic chemotherapy alone (8). Nonetheless, major concerns remain related to generalizability of technical efficacy outcomes and safety. As the novelty of small, low-level evidence studies wears off, additional low-level studies will be of limited value and perhaps even detrimental in this case. One major complication (more likely after pulmonary than hepatic TACE), or many underpowered studies that fail to show benefit in the face of ever-increasing systemic therapy options, could derail the process. Positive results from phase I trials such as this one should be used by the interventional oncology community to support the design and execution of adequately powered, randomized controlled trials instead.Disclosures of Conflicts of Interest: C.G. is a member of the Radiology editorial board.References1. Llovet JM, Real MI, Montaña X, et al. Arterial embolisation or chemoembolisation versus symptomatic treatment in patients with unresectable hepatocellular carcinoma: a randomised controlled trial. Lancet 2002;359(9319):1734–1739. Crossref, Medline, Google Scholar2. Llovet JM, Bruix J. Systematic review of randomized trials for unresectable hepatocellular carcinoma: Chemoembolization improves survival. Hepatology 2003;37(2):429–442. Crossref, Medline, Google Scholar3. Lo CM, Ngan H, Tso WK, et al. Randomized controlled trial of transarterial lipiodol chemoembolization for unresectable hepatocellular carcinoma. Hepatology 2002;35(5):1164–1171. Crossref, Medline, Google Scholar4. Boas FE, Kemeny NE, Sofocleous CT, et al. Bronchial or Pulmonary Artery Chemoembolization for Unresectable and Unablatable Lung Metastases: A Phase I Clinical Trial. Radiology 2021.https://doi.org/10.1148/radiol.2021210213. Published online August 31, 2021. Link, Google Scholar5. Solomon B, Soulen MC, Baum RA, Haskal ZJ, Shlansky-Goldberg RD, Cope C. Chemoembolization of hepatocellular carcinoma with cisplatin, doxorubicin, mitomycin-C, ethiodol, and polyvinyl alcohol: prospective evaluation of response and survival in a U.S. population. J Vasc Interv Radiol 1999;10(6):793–798. Crossref, Medline, Google Scholar6. Bie Z, Li Y, Li B, Wang D, Li L, Li X. The efficacy of drug-eluting beads bronchial arterial chemoembolization loaded with gemcitabine for treatment of non-small cell lung cancer. Thorac Cancer 2019;10(9):1770–1778. Crossref, Medline, Google Scholar7. Zeng Y, Yin M, Zhao Y, et al. Combination of Bronchial Arterial Infusion Chemotherapy plus Drug-Eluting Embolic Transarterial Chemoembolization for Treatment of Advanced Lung Cancer-A Retrospective Analysis of 23 Patients. J Vasc Interv Radiol 2020;31(10):1645–1653. Crossref, Medline, Google Scholar8. Huang R, Li WH, Zhu J, Li CL, Wan HG, Chen LZ. Differences in efficacy between drug-eluting beads transbronchial arterial chemoembolization combined with systemic chemotherapy and systemic chemotherapy alone for unresectable lung squamous cell carcinoma [in Chinese]. Zhonghua Yi Xue Za Zhi 2020;100(15):1164–1168. Medline, Google ScholarArticle HistoryReceived: June 11 2021Revision requested: July 6 2021Revision received: July 7 2021Accepted: July 8 2021Published online: Aug 31 2021Published in print: Nov 2021 FiguresReferencesRelatedDetailsCited ByBronchial artery embolization for hemoptysis caused by metastatic hepatocellular carcinomaSungwonKim, Jin HyoungKim, Gi-YoungKo, Dong IlGwon, Ji HoonShin, Hyun-KiYoon2022 | Scientific Reports, Vol. 12, No. 1Accompanying This ArticleBronchial or Pulmonary Artery Chemoembolization for Unresectable and Unablatable Lung Metastases: A Phase I Clinical TrialAug 31 2021RadiologyRecommended Articles Bronchial or Pulmonary Artery Chemoembolization for Unresectable and Unablatable Lung Metastases: A Phase I Clinical TrialRadiology2021Volume: 301Issue: 2pp. 474-484Bronchial or Pulmonary Artery Chemoembolization for Unresectable and Unablatable Lung MetastasesRadiology: Imaging Cancer2021Volume: 3Issue: 6An Interventionalist’s Guide to Hemoptysis in Cystic FibrosisRadioGraphics2018Volume: 38Issue: 2pp. 624-641CT for Evaluation of HemoptysisRadioGraphics2021Volume: 41Issue: 3pp. 742-761Prediction of Therapeutic Effect of Chemotherapy for NSCLC Using Dual-Input Perfusion CT Analysis: Comparison among Bevacizumab Treatment, Two-Agent Platinum-based Therapy without Bevacizumab, and Other Non-Bevacizumab Treatment GroupsRadiology2017Volume: 286Issue: 2pp. 685-695See More RSNA Education Exhibits Bronchial Artery Embolization: How, Why and WhenDigital Posters2020Uncommon Non-thromboembolic Conditions Affecting the Pulmonary Vasculature - Beyond ThromboembolismDigital Posters2022Pitfalls in Interpreting CT Pulmonary AngiogramsDigital Posters2019 RSNA Case Collection Pulmonary pseudoaneurysmRSNA Case Collection2021Pulmonary AtresiaRSNA Case Collection2022Rasmussen aneurysmRSNA Case Collection2022 Vol. 301, No. 2 Metrics Altmetric Score PDF download