Based on this result and similar findings within the validation cohort, the investigators concluded that patients with SRD or 6 months or longer should be designated as responders following cTACE. And, those with SRD of a period at least this long could allow patients in need of a liver transplant to remain on the donor list for an extended period of time, which could also contribute to improved survival in HCC.

The nearly 7-fold improvement in OS for those with SRD of 6 months or more is something remarkable, according to Jesse Berlin, ScD, who wrote an editorial accompanying the article by Dr Zhang and colleagues.2 “In more than 30 years as a statistician and epidemiologist, I have only very rarely seen HRs and [area under the receiver operating characteristic curve] of such a large magnitude.” Despite this fact, he noted it may still be too soon to begin using SRD as a surrogate end point. “We would have to see that a treatment effect on SRD at the trial level, which might be the HR comparing cTACE with some novel treatment, is reflected by a similar treatment effect on OS,” he wrote.

Dr Berlin also pointed out that the prognostic utility of SRD may not help physicians make actual clinical decisions about medications; rather, it just identifies patients with more indolent disease. The only way to know for sure if SRD could be a good surrogate end point, he concluded, would be by conducting a randomized clinical trial comparing a treatment algorithm based on SRD with treatment administered at regular intervals.

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“An important caution is that this paper doesn’t show that SRD can be a surrogate for OS in HCC trials,” Bishal Gyawali, MD, PhD, Brigham and Women’s Hospital and Harvard Medical School in Boston, Massachusetts, wrote in a note to Cancer Therapy Advisor (Dr Gyawali was not involved in the study). “This study shows that SRD can be a good patient-level surrogate … However, this doesn’t prove that SRD can be a trial-level surrogate.”

Showing that the treatment effects on SRD translate into treatment effects on OS could make SRD a trial-level surrogate, added Dr Gyawali, echoing the sentiments of the editorial authored by Dr Berlin. “For that, we need a comparison of treatment outcomes versus the control for SRD and OS across trials.”


  1. Zhang Y, Zhang M, Chen M, et al. Association of sustained response duration with survival after conventional transarterial chemoembolization in patients with hepatocellular carcinoma. JAMA Netw Open. 2018;1(6):e183213.
  2. Berlin JA. Evaluating the potential benefits of using sustained response as a prognostic factor in intermediate hepatocellular carcinoma following treatment with conventional chemoembolization. JAMA Netw Open. 2018;1(6):e183209.