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We are grateful to Tabone et al. for sharing their results on the prevention of intrahepatic recurrence of hepatocellular carcinoma (HCC) with intra-arterial injection of iodine-131-labeled lipiodol (131-I-Lip). Their findings are in line with earlier reports.1–3 Unfortunately, we still lack statistical power so a large randomized trial will be needed before we can consider this option as standard. We fully agree with the concerns expressed by Tabone et al. about the timing of 131-I-Lip administration after resection and the standardization of the radiation dose to the remnant liver.

When we decided to use this adjuvant treatment, the timing dilemma was paramount. Delivering the adjuvant treatment too late could allow time for early recurrence, and delivering it too early could impair postoperative liver regeneration. Looking back at data from our report2 and the study by Lau et al.,3 postoperative adjuvant lipiodol radiation therapy mainly decreased the rate of early recurrence. Differences in disease-free survival between the observational and treatment arms occurred very early and remained stable. Thus, early adjuvant treatment appears to have a better effect on small pre-existing cancer foci than on transformation of dysplastic nodules. Nevertheless, a second injection delivered later to destroy small recurrent nodules when their diameter reaches a few millimetres could be discussed.

The problem of injected activity is another important issue. In their work Tabone et al. and Partensky et al.3 used low activity. In this adjuvant postoperative setting, tumor foci are small and do not retain lipiodol. Treatment efficacy is related to global radiation of the hepatic parenchyma by 131-I. Since 131-I has a short cytotoxic range and lipiodol distributes unevenly, radiation dose would have to be high to achieve an effective dose throughout the remnant liver. At the same time, however, we have to avoid toxicity. As stated by Tabone et al., the volume of the remnant liver is of importance. If small, it would probably be prudent to use median activity (1.0-1.5 mBq of 131-I). We do not know how the liver tolerates brachytherapy, but after injection of 90Y-microspheres, radiation doses as high as 15,000 cGy have been well tolerated4! In the adjuvant setting, we are far from the toxic dose when delivering less than 5,000 cGy.

We can conclude that the best time to treat these patients is probably rather early (second or third month) to avoid recurrence and/or a little later (sixth or twelfth month) to treat tiny recurrences (but is this still an adjuvant treatment?). Using an injected activity of 2.4 GBq, we have not had any problem with toxicity. Nevertheless, if the remnant liver in a patient with cirrhosis who had a difficult postoperative period is very small, a lower activity could be preferable. But, as mentioned by Tabone et al. in their conclusion, timing and activity level are totally empirical, so we are far from a tailored treatment.

The main goal now is to determine through a large-scale randomized study whether these preliminary results can be confirmed.

References

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  • 1
    Lau WY, Leung TW, Ho SK, Chan M, Machin D, Lau J, et al. Adjuvant intra-arterial iodine-131-labeled lipiodol for respectable hepatocellular carcinoma. A prospective randomised trial. Lancet 1999; 353: 797801.
  • 2
    Boucher E, Corbinais S, Rolland Y, Bourguet P, Guyader D, Boudjema K, et al. Adjuvant intra-arterial injection of iodine-131-labeled lipiodol after resection of hepatocellular carcinoma. HEPATOLOGY 2003; 38: 12371241.
  • 3
    Partensky C, Sassolas G, Henry L, Paliard P, Maddern GJ. Intra-arterial iodine 131-labeled-lipiodol as adjuvant therapy after curative liver resection for hepatocellular carcinoma. Arch Surg 2000; 135: 12981300.
  • 4
    Goin JE, Salem R, Carr BI, Dancey JE, Soulen MC, Geschwind JF, et al. Treatments of unresectable hepatocellular carcinoma with intrahepatic yttrium 90 microspheres: factors associated with liver toxicities. J Vasc Interv Radiol 2005; 16: 205213.

Eveline Boucher*, Harvey J. Turner†, Patrick Bourguet‡, Jean-Luc Raoul*, * Department of Medical Oncology, Centre E Marquis, Rennes, France, † Department of Nuclear Medicine, Fremantle Hospital, Fremantle, Australia, ‡ Department of Nuclear Medicine, Centre E Marquis, Rennes, France.