Letter to the Editor: “The PPRD score stratifies patients with hepatocellular carcinoma and portal vein tumor thrombus treated with sorafenib plus transarterial chemoembolization”

by Jin-Kai Feng, Zong-Han Liu, Ju-Xian Sun, Shu-Qun Cheng (chengshuqun@aliyun.com)

The PPRD score stratifies patients with hepatocellular carcinoma and portal vein tumor thrombus treated with sorafenib plus transarterial chemoembolization

Dear Editor-in-Chief,

We read with great interest the recently published article in European Radiology by Zhang et al [1], in which they constructed a novel scoring system (called the PPRD score) to select hepatocellular carcinoma (HCC) patients with portal vein tumor thrombus (PVTT) who would gain survival benefit from the combination therapy of transarterial chemoembolization (TACE) with sorafenib. The authors identified that four predictive factors, including Eastern Cooperative Oncology Group performance status (ECOG-PS), extension of PVTT, initial radiological response to TACE and sorafenib-related dermatologic toxicity, were independently associated with post-treatment overall survival (OS) for patients with HCC and PVTT. Using this prognostic scoring model, the authors stratified patients into three distinct groups: favorable prognosis (0 points), intermediate prognosis (1–4 points), and dismal prognosis (5–11 points). This article, with its great novelty and clinical implication, adds to the present literature and assists in the identification and selection of optimal candidates for this treatment approach. However, we would like to raise the following concerns.

First, ECOG-PS is a common indicator to evaluate the general condition and physical activity of patients before treatment. Many high-quality clinical trials took ECOG-PS less than 2 as one of the inclusion criteria for HCC patients treated with TACE and sorafenib, in order to guarantee the therapeutic safety and tolerability [2, 3]. In the study conducted by Zhang et al, the ECOG-PS was classified as 0–1 and 2. The sample size between the ECOG-PS 0–1 and 2 groups was distinctly imbalanced (93.5% vs. 6.5% for the primary cohort and 91.7% vs. 8.3% for the validation cohort), which may influence the result of multivariate analysis and introduce a significant bias. Therefore, we suggest the authors include patients with ECOG-PS 0–1 only.

Second, the objective response rate (ORR, the sum of complete response [CR] and partial response [PR]) was applied in their study to calculate the early initial radiological response to TACE. How come the results if the patients were categorized according to whether or not the disease was radiologically controlled? In that way, the disease control rate (DCR, the sum of CR, PR and stable disease [SD]) is to be used to reflect the short-term therapeutic effect of TACE. Thus, we suggest the authors add some essential information regarding the association of radiological control and post-treatment survival.
Third, sorafenib-related dermatologic toxicity was found to be a significant factor associated with OS for HCC patients with PVTT receiving TACE plus sorafenib in their study. This finding was consistent with prior studies which demonstrated that skin adverse events (hand-foot-skin reaction [HFSR], rash, folliculitis, pruritus, alopecia, etc.) were closely related to better treatment response and survival outcomes in advanced HCC treated with sorafenib [4, 5]. However, as shown in Supplementary Table 1, the authors solely regarded HFSR and rash as the dermatologic toxicities and listed alopecia as an independent adverse event, which did not conform with the current knowledge. Hence, we suggest the authors add alopecia to the category of dermatologic toxicity.

Last but not least, a prognostic nomogram, which is consisted of tumor size, albumin-bilirubin (ALBI) grade and PVTT type, has also been recently established for HCC patients with PVTT undergoing TACE plus sorafenib [6]. Currently, the ALBI grade is a widely used composite index that provides a simple and objective hepatic functional reserve estimation for HCC patients [7]. Consequently, we suggest the authors supplement ALBI grade besides Child-Pugh class here.

In summary, this study by Zhang et al [1] was the first work in the world focusing on developing a scoring system using pre- and post-treatment variables for the prognostic prediction in HCC patients with PVTT who underwent TACE plus sorafenib. We appreciate the authors’ great endeavor because the proposed PPRD score can aid to decision-making on TACE-sorafenib treatment for this particular population of patients in the era of precision medicine and individualized therapy. However, due to the retrospective nature and relatively small sample size of their study, it is vital to validate this scoring model in the real-world clinical practice.