Background and aims

Prognosis of hepatoblastoma patients has increased with cisplatin-based chemotherapy and high-quality resection including liver transplant. Consequently current risk-adapted therapeutic strategy aims to reduce long-term side effects in patients with standard risk disease.

Methods

We report long-term mortality and morbidity data concerning 151 2-year hepatoblastoma survivors treated with SIOPEL risk-adapted strategies (sex-ratio M/F = 1.6, median age at diagnosis = 2.6 years [range 0–17.7], median year at diagnosis = 2008 [1994–2017]). Fifty-three patients had loco-regional risk factors VPEFR, 12 were PRETEXT-IV and 30 were metastatic. All received cisplatin and 84 anthracyclines. Twelve had liver transplant. To assess hearing, renal and cardiac functions, audiograms were performed in 116/151 patients (76.8%), glomerular filtration rate in 113/151 (74.8%) and cardiac ultrasound in 65/84 (77.4%) anthracycline-exposed patients.

Results

With a median follow-up of 9.4 years (range 2.1–25.8), four late relapses, one second malignancy (Acute Myeloid Leukemia AML-M5) and two deaths (one from hepatoblastoma, one from AML) occurred. The 10-years event free survival and overall survival probabilities were 95.5% (95% CI 91.9–99.1) and 98.7% (95% CI 96.8–100), respectively. Sixty-eight non-oncologic health-events included 57 cases of hearing loss (including 25 Brock 3–4), three liver cirrhosis, three pre-operative portal cavernoma, two focal nodular hyperplasia, two grade-1 chronic kidney diseases and one asymptomatic cardiac dysfunction were reported. Ototoxicity was significantly associated with cisplatin cumulative dose (OR = 2.07, 95% CI 1.32–3.24, p = 0.001) and carboplatin exposure (OR = 3.14, 95% CI 1.30–7.58, p = 0.01) in multivariable analysis adjusted for sex and age at diagnosis.

Conclusions

With current risk-adapted strategies, hepatoblastoma is a highly curable disease, with very rare relapses, and few late effects except hearing loss which remains a serious condition in these very young patients.

中文翻译：

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接受 SIOPEL 风险适应策略治疗的 2 年肝母细胞瘤幸存者的长期发病率和死亡率

背景和目标

以顺铂为基础的化疗和包括肝移植在内的高质量切除术增加了肝母细胞瘤患者的预后。因此，目前的风险适应治疗策略旨在减少患有标准风险疾病的患者的长期副作用。

方法

我们报告了 151 名接受 SIOPEL 风险适应策略治疗的 2 年肝母细胞瘤幸存者的长期死亡率和发病率数据（性别比M/F  = 1.6，诊断时的中位年龄 = 2.6 岁 [范围 0-17.7]，中位年诊断 = 2008 [1994-2017]）。53 名患者具有局部区域风险因素 VPEFR，12 名患者为 PRETEXT-IV，30 名患者为转移性患者。所有人都接受了顺铂和 84 种蒽环类药物。十二人进行了肝移植。为了评估听力、肾脏和心脏功能，对 116/151 名患者（76.8%）进行了听力图检查，对 113/151 名（74.8%）患者进行了肾小球滤过率检查，对 65/84 名（77.4%）蒽环类药物暴露患者进行了心脏超声检查。

结果

中位随访时间为 9.4 年（范围 2.1-25.8），发生 4 次晚期复发、1 次恶性肿瘤（急性髓性白血病 AML-M5）和 2 例死亡（1 例来自肝母细胞瘤，1 例来自 AML）。10 年无事件生存率和总生存率分别为 95.5% (95% CI 91.9–99.1) 和 98.7% (95% CI 96.8–100)。68 例非肿瘤健康事件包括 57 例听力损失（包括 25 例 Brock 3-4）、3 例肝硬化、3 例术前门静脉海绵状血管瘤、2 例局灶性结节性增生、2 例 1 级慢性肾脏疾病和 1 例无症状报告了心功能不全。耳毒性与顺铂累积剂量 (OR = 2.07, 95% CI 1.32–3.24, p  = 0.001) 和卡铂暴露显着相关 (OR = 3.14, 95% CI 1.30–7.58, p = 0.01）在多变量分析中根据诊断时的性别和年龄进行了调整。

结论

根据目前的风险适应策略，肝母细胞瘤是一种高度可治愈的疾病，复发率非常低，除了听力损失之外几乎没有后期影响，听力损失在这些非常年轻的患者中仍然是一种严重的疾病。