DOI: 10.1148/radiol.2372050845
(Radiology 2005;237:381-382.)
© RSNA, 2005
Can Combination Therapy for Colorectal Liver Metastases Improve Results over Chemoembolization or Ablation Alone?
Scott O. Trerotola, MD
1 Department of Radiology, Division of Interventional Radiology, University of Pennsylvania Medical Center, 1 Silverstein, 3400 Spruce St, Philadelphia, PA 19104 streroto{at}uphs.upenn.edu
The Setting
Due to published evidence, including randomized trials showing improved survival for patients receiving local-regional therapy (1,2) and the lack of effective systemic chemotherapy, chemoembolization and ablation and combination therapy are reasonably well-established treatment techniques for primary liver tumors. Reasons why the same is not true for liver metastases from colorectal cancer include rapid progress in defining more effective multidrug systemic chemotherapeutic regimens such as FOLFIRI and FOLFOX, prolonged benefit from use of sequential regimens, and the recent approval of growth factor antibodies such as bevaciximab and cetuximab (3). While case series of catheter-based and ablative therapies for liver metastases abound, there is very little published evidence in the form of randomized controlled trials (RCTs) that supports liver-directed techniques in the treatment of liver metastases.
Chemoembolization for liver metastases may not "kill" the entire tumor for a variety of reasons, and direct ablation therapies such as radiofrequency ablation, chemical ablation, cryoablation, and laser ablation may be limited by tumor size and the extent of the zone of necrosis produced. Combining these approaches has been successful in the treatment of primary liver tumors and thus might improve results in liver metastases as well. In this issue of Radiology, Maataoui et al (4) investigated the combination of transarterial chemoembolization (TACE) using mitomycin C and iodized oil and laser interstitial tumor therapy (LITT) in a rat model of colorectal metastases.
The Science
In their study, Maataoui et al (4) compared the results of treatment with TACE alone, LITT alone, and TACE followed by LITT (combination therapy), using magnetic resonance imaging–measured tumor volumes as the measure of success. They showed that the inhibition of tumor growth was greatest with combination therapy, as compared with the individual therapies. In addition, they showed that tumor necrosis, which was only visible after LITT or combination therapy, was greater in the latter. Finally, intrahepatic metastases were seen in one animal each in the individual therapy groups but in none in the combination group. However, continued tumor growth occurred in all groups, and there was no untreated control group to assess the natural history of the tumors in this model. Moreover, other limitations of the model included nonhematogenous tumor implantation and the small size of the tumors, both of which favor all forms of local-regional therapy.
The Practice
Clinical use.—
The results of this experiment are encouraging but too preliminary to warrant widespread clinical use. Indeed, oncologists are highly unlikely to refer their patients for local-regional therapy in the absence of proved benefit from RCTs. The results of the study by Maataoui et al (4) and of subsequent animal work may lay the groundwork for such trials. Their study suggests, as does previously published evidence for hepatoma (5–7), that better outcomes can be achieved with combination, rather than individual, therapy techniques. Thus, in order to have the best chance of proving benefit in an RCT, investigators planning such trials would do well to consider combination therapy as the treatment arm of these trials. Practitioners who have a referral stream of patients with colorectal metastases should consider combination therapy (ie, TACE plus radiofrequency, chemical, cryo-, or laser ablation) pending the results of such trials.
Future opportunities and challenges.—
By far the greatest challenge to the widespread application of any local-regional therapy for colorectal metastases is the burden of proof that such therapy improves outcomes (survival or quality of life), as compared with standard therapies (eg, intravenous chemotherapy). The interventional radiology community has the opportunity to rise to this challenge. By using the basic science and animal research foundation laid by the study of Maataoui et al (4) and others, interventional radiologists can construct and carry out these trials.
Summary
Colon cancer remains a killer, despite advances in surgery, chemotherapy, and local-regional therapy. The latter therapy is not in widespread use for many reasons, but studies such as that by Maataoui et al (4) may help advance local-regional therapy, especially the combination form, by providing a basis for future research.
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ACKNOWLEDGMENTS
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I thank Michael Soulen, MD, for his assistance with this manuscript.
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References
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- Llovet JM, Real MI, Montana 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]
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- Rossi S, Garbagnati F, Lencioni R, et al. Percutaneous radio-frequency thermal ablation of nonresectable hepatocellular carcinoma after occlusion of tumor blood supply. Radiology 2000; 217(1):119–126.[Abstract/Free Full Text]
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Radiology 2005 237: 479-484.
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