Supplementary Material for: Prognostic value of pathological response for patients with unresectable hepatocellular carcinoma undergoing conversion surgery

Introduction: Transarterial chemoembolization combined with lenvatinib and PD-1 inhibitor (triple therapy) has displayed encouraging clinical outcomes for unresectable hepatocellular carcinoma (uHCC). We aim to explore the prognostic value of pathologic response (PR) in patients with initially uHCC who underwent conversion surgery following triple therapy, and identify predictors of major pathologic response (MPR).
Methods: A total of 76 patients with initially uHCC who underwent conversion surgery following triple therapy were retrospectively analyzed. PR was calculated as the proportion of non-viable tumor cell surface area of the whole tumor bed surface area. MPR was identified when PR was ≥ 90%. Pathological complete response (pCR) was defined as the absence of viable tumor cells.
Results: MPR and pCR were identified in 53 (69.7%) and 25 (32.9%) patients, respectively. The 1- and 2-year overall survival in patients with MPR was significantly higher than in those without MPR (100.0% and 91.3% vs. 67.7 % and 19.4%; p <0.001). The corresponding recurrence-free survival was also improved in patients with MPR compared to those without (75.9% and 50.8% vs. 22.3 and 11.2%; p < 0.001). Similar results were observed among patients with pCR and those without. Patients who achieved MPR without pCR exhibited survival rates comparable to those of patients who achieved pCR. Baseline neutrophil-to-lymphocyte ratio ≥ 2.6 (p = 0.016) and preoperative alpha-fetoprotein ≥ 400 ng/mL (p = 0.015) were independent predictors of MPR.
Conclusion: The presence of MPR or pCR could improve prognosis in patients with initially uHCC who underwent conversion surgery following triple therapy. The PR may become a surrogate marker for predicting the prognosis of these patients.

### 引言
经动脉化疗栓塞联合仑伐替尼和PD-1抑制剂（三联疗法）治疗不可切除肝细胞癌（unresectable hepatocellular carcinoma, uHCC）已展现出令人鼓舞的临床结局。本研究旨在探讨经三联疗法转化治疗后接受转化手术的初诊不可切除肝细胞癌患者的病理缓解（pathologic response, PR）预后价值，并明确主要病理缓解（major pathologic response, MPR）的预测因素。

### 方法
本研究回顾性分析了76例经三联疗法转化治疗后接受转化手术的初诊不可切除肝细胞癌患者。病理缓解率以非存活肿瘤细胞占整个瘤床表面积的比例计算。当病理缓解率≥90%时判定为主要病理缓解。病理完全缓解（pathologic complete response, pCR）定义为无存活肿瘤细胞残留。

### 结果
共有53例（69.7%）患者达到主要病理缓解，25例（32.9%）患者达到病理完全缓解。达到主要病理缓解的患者1年、2年总生存率显著高于未达到者（100.0%、91.3% vs 67.7%、19.4%；p<0.001）。其无复发生存率同样显著优于未达到主要病理缓解的患者（75.9%、50.8% vs 22.3%、11.2%；p<0.001）。病理完全缓解患者与非病理完全缓解患者也观察到相似结果。达到主要病理缓解但未达到病理完全缓解的患者，其生存率与达到病理完全缓解的患者相当。基线中性粒细胞与淋巴细胞比值≥2.6（p=0.016）及术前甲胎蛋白≥400 ng/mL（p=0.015）是主要病理缓解的独立预测因素。

### 结论
对于经三联疗法转化治疗后接受转化手术的初诊不可切除肝细胞癌患者，达到主要病理缓解或病理完全缓解可改善其预后。病理缓解率有望成为预测此类患者预后的替代标志物。