International Pleuropulmonary Blastoma/DICER1 Registry, Children's Minnesota, Minneapolis, MN.
International Ovarian and Testicular Stromal Tumor Registry, Children's Minnesota, Minneapolis, MN.
J Clin Oncol. 2023 Feb 1;41(4):778-789. doi: 10.1200/JCO.21.02925. Epub 2022 Sep 22.
Pleuropulmonary blastoma (PPB) is the most common primary lung neoplasm of infancy and early childhood. Type II and type III PPB have historically been associated with a poor prognosis.
Patients with known or suspected PPB were enrolled in the International PPB/ Registry. Medical records were abstracted with follow-up ascertained annually. All PPB diagnoses were confirmed by central pathology review. Beginning in 2007, the IVADo regimen (ifosfamide, vincristine, actinomycin-D, and doxorubicin) was recommended as a potential treatment regimen for children with type II and type III PPB. This regimen was compared with a historical control cohort.
From 1987 to 2021, 314 children with centrally confirmed type II and type III PPB who received upfront chemotherapy were enrolled; 132 children (75 with type II and 57 with type III) received IVADo chemotherapy. Adjusted analyses suggest improved overall survival for children treated with IVADo in comparison with historical controls with an estimated hazard ratio of 0.65 (95% CI, 0.39 to 1.08). Compared with localized disease, distant metastasis at diagnosis was associated with worse PPB event-free survival and overall survival with hazard ratio of 4.23 (95% CI, 2.42 to 7.38) and 4.69 (95% CI, 2.50 to 8.80), respectively.
The use of IVADo in children with type II and type III PPB resulted in similar-to-improved outcomes compared with historical controls. Inferior outcomes with metastatic disease suggest the need for novel therapies. This large cohort of uniformly treated children with advanced PPB serves as a benchmark for future multicenter therapeutic studies for this rare pediatric tumor.
肺胚细胞瘤（PPB）是婴儿和幼儿最常见的原发性肺部肿瘤。II 型和 III 型 PPB 历来与预后不良相关。
在国际 PPB/注册中心招募了已知或疑似 PPB 的患者。通过每年进行一次随访来提取病历。所有 PPB 诊断均通过中心病理审查确认。自 2007 年以来，IVADo 方案（异环磷酰胺、长春新碱、放线菌素-D 和多柔比星）被推荐作为 II 型和 III 型 PPB 患儿的潜在治疗方案。该方案与历史对照队列进行了比较。
从 1987 年到 2021 年，共招募了 314 名经中心确认的 II 型和 III 型 PPB 患儿，这些患儿均接受了一线化疗；132 名患儿（75 名 II 型，57 名 III 型）接受了 IVADo 化疗。调整后的分析表明，与历史对照相比，接受 IVADo 治疗的患儿总生存率有所提高，估计风险比为 0.65（95%CI，0.39 至 1.08）。与局限性疾病相比，诊断时出现远处转移与较差的 PPB 无事件生存率和总生存率相关，风险比分别为 4.23（95%CI，2.42 至 7.38）和 4.69（95%CI，2.50 至 8.80）。
在 II 型和 III 型 PPB 患儿中使用 IVADo 与历史对照相比，结果相似或有所改善。转移性疾病的不良结局表明需要新的治疗方法。本研究为该罕见儿科肿瘤的未来多中心治疗研究提供了一个基准。
