Department of Radiation Oncology, Brigham and Women's Hospital, Dana-Farber Cancer Institute, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
Department of Radiation Oncology & Molecular Radiation Sciences, Johns Hopkins Medicine, Baltimore, MD, USA.
Radiother Oncol. 2024 Sep;198:110384. doi: 10.1016/j.radonc.2024.110384. Epub 2024 Jun 15.
Prognosis for patients with high-risk neuroblastoma (HR-NBL) is guarded despite aggressive therapy, and few studies have characterized outcomes after radiotherapy in relation to radiation treatment fields.
Multi-institutional retrospective cohort of 293 patients with HR-NBL who received autologous stem cell transplant (ASCT) and EBRT between 1997-2021. LRR was defined as recurrence at the primary site or within one nodal echelon beyond disease present at diagnosis. Follow-up was defined from the end of EBRT. Event-free survival (EFS) and OS were analyzed by Kaplan-Meier method. Cumulative incidence of locoregional progression (CILP) was analyzed using competing risks of distant-only relapse and death with Gray's test.
Median follow-up was 7.0 years (range: 0.01-22.4). Five-year CILP, EFS, and OS were 11.9 %, 65.2 %, and 77.5 %, respectively. Of the 31 patients with LRR and imaging review, 15 (48.4 %) had in-field recurrences (>12 Gy), 6 (19.4 %) had marginal failures (≤12 Gy), and 10 (32.3 %) had both in-field and marginal recurrences. No patients receiving total body irradiation (12 Gy) experienced marginal-only failures (p = 0.069). On multivariable analyses, MYCN amplification had higher risk of LRR (HR: 2.42, 95 % CI: 1.06-5.50, p = 0.035) and post-consolidation isotretinoin and anti-GD2 antibody therapy (HR: 0.42, 95 % CI: 0.19-0.94, p = 0.035) had lower risk of LRR.
Despite EBRT, LRR remains a contributor to treatment failure in HR-NBL with approximately half of LRRs including a component of marginal failure. Future prospective studies are needed to explore whether radiation fields and doses should be defined based on molecular features such as MYCN amplification, and/or response to chemotherapy.
尽管采用了积极的治疗方法，高危神经母细胞瘤（HR-NBL）患者的预后仍不容乐观，而且很少有研究描述与放射治疗相关的放射治疗野与治疗结果之间的关系。
本研究为多机构回顾性队列研究，纳入了 1997 年至 2021 年间接受自体干细胞移植（ASCT）和 EBRT 的 293 例 HR-NBL 患者。局部复发率（LRR）定义为在初发病灶或在诊断时已存在的疾病的一个淋巴结级内复发。从 EBRT 结束时开始随访。通过 Kaplan-Meier 方法分析无事件生存（EFS）和总生存（OS）。使用 Gray 检验的竞争风险分析局部区域进展的累积发生率（CILP）。
中位随访时间为 7.0 年（范围：0.01-22.4）。5 年时的 CILP、EFS 和 OS 分别为 11.9%、65.2%和 77.5%。在 31 例有 LRR 且进行影像学复查的患者中，15 例（48.4%）为野内复发（>12 Gy），6 例（19.4%）为边缘失败（≤12 Gy），10 例（32.3%）为野内和边缘复发均有。没有接受全身照射（12 Gy）的患者出现边缘失败（p=0.069）。多变量分析显示，MYCN 扩增与 LRR 风险较高相关（HR：2.42，95%CI：1.06-5.50，p=0.035），巩固后使用异维 A 酸和抗 GD2 抗体治疗与 LRR 风险较低相关（HR：0.42，95%CI：0.19-0.94，p=0.035）。
尽管进行了 EBRT，但 LRR 仍是 HR-NBL 治疗失败的原因之一，约一半的 LRR 包括边缘失败的成分。未来需要前瞻性研究来探讨是否应根据 MYCN 扩增等分子特征以及（或）对化疗的反应来确定放射治疗野和剂量。
