Pediatric Hematology and Oncology, Hospital Universitari Vall d'Hebron, Barcelona, Spain.
Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Harvard Medical School, Boston, Massachusetts.
Pediatr Blood Cancer. 2021 Mar;68(3):e28794. doi: 10.1002/pbc.28794. Epub 2020 Nov 18.
Long-term outcome remains poor for children with high-risk neuroblastoma (five-year overall survival [OS] ∼50%). Our objectives were to (a) identify prognostic biomarkers and apply them in a nomogram to identify the subgroup of ultra-high-risk patients at highest risk of disease progression/death, for whom novel frontline therapy is urgently needed; and (b) validate the nomogram in an independent cohort.
A total of 1820 high-risk patients (≥18 months old with metastatic neuroblastoma), diagnosed 1998-2015, from the International Neuroblastoma Risk Groups (INRG) Data Commons were analyzed in a retrospective cohort study. Using multivariable Cox regression of OS from diagnosis, a nomogram was created from prognostic biomarkers to predict three-year OS. External validation was performed using the SIOPEN HR-NBL1 trial cohort (n = 521), evidenced by receiver operating characteristic curves.
The nomogram, including MYCN status (P < 0.0001), lactate dehydrogenase (LDH) (P = 0.0007), and presence of bone marrow metastases (P = 0.004), had robust performance and was validated. Applying the nomogram at diagnosis (a) gives prognosis of an individual patient and (b) identifies patients predicted to have poor outcome (three-year OS was 30% ± 5% for patients with a nomogram score of > 82 points; 58% ± 1% for those ≤82 points). Median follow-up time was 5.5 years (range, 0-14.1).
In high-risk neuroblastoma, a novel, publicly available nomogram using prognostic biomarkers (MYCN status, LDH, presence of bone marrow metastases; https://neuroblastoma.shinyapps.io/High-Risk-Neuroblastoma-Nomogram/) has the flexibility to apply a clinically suitable and context-specific cutoff to identify patients at highest risk of death. This will facilitate testing urgently needed new frontline treatment options to improve outcome for these children.
高危神经母细胞瘤（五年总生存率[OS]约为 50%）患儿的长期预后仍较差。我们的目标是：（a）鉴定预后生物标志物，并将其应用于列线图，以确定疾病进展/死亡风险最高的超高危患者亚组，他们急需新型一线治疗；（b）在独立队列中验证该列线图。
本回顾性队列研究共分析了来自国际神经母细胞瘤风险组（INRG）数据共享库的 1820 例高危患儿（18 个月以上伴转移性神经母细胞瘤），这些患儿的诊断时间为 1998 年至 2015 年。采用 OS 的多变量 Cox 回归，从预后生物标志物中创建预测三年 OS 的列线图。使用 SIOPEN HR-NBL1 试验队列（n=521）进行外部验证，通过接受者操作特征曲线证实。
包括 MYCN 状态（P<0.0001）、乳酸脱氢酶（LDH）（P=0.0007）和骨髓转移存在（P=0.004）的列线图具有良好的性能并得到验证。在诊断时应用该列线图（a）可以预测个体患者的预后，（b）可以识别出预计预后不良的患者（列线图评分>82 分的患者三年 OS 为 30%±5%；评分≤82 分的患者为 58%±1%）。中位随访时间为 5.5 年（范围，0-14.1 年）。
在高危神经母细胞瘤中，一种新的、基于预后生物标志物（MYCN 状态、LDH、骨髓转移存在；https://neuroblastoma.shinyapps.io/High-Risk-Neuroblastoma-Nomogram/）的、可公开获取的列线图具有灵活性，可应用临床合适且具体背景的截止值，以识别死亡风险最高的患者。这将有助于测试急需的新型一线治疗方案，以改善这些儿童的预后。
