抗 G 免疫治疗时代前后的 4N 期神经母细胞瘤。

Stage 4N neuroblastoma before and during the era of anti-G immunotherapy.

机构信息

Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, New York, USA.

Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York, USA.

出版信息

Int J Cancer. 2023 Dec 15;153(12):2019-2031. doi: 10.1002/ijc.34693. Epub 2023 Aug 21.

Abstract

Patients with stage 4N neuroblastoma (distant metastases limited to lymph nodes) stand out as virtually the only survivors of high-risk neuroblastoma (HR-NB) before myeloablative therapy (MAT) and immunotherapy with anti-G monoclonal antibodies (mAbs) became standard. Because no report presents more recent results with 4N, we analyzed our large 4N experience. All 51 pediatric 4N patients (<18 years old) diagnosed 1985 to 2021 were reviewed. HR-NB included MYCN-nonamplified 4N diagnosed at age ≥18 months and MYCN-amplified 4N. Among 34 MYCN-nonamplified high-risk patients, 20 are relapse-free 1.5+ to 37.5+ (median 12.5+) years post-diagnosis, including 13 without prior MAT and 5 treated with little (1 cycle; n = 2) or no mAb (n = 3), while 14 patients (7 post-MAT, 8 post-mAbs) relapsed (all soft tissue). Of 15 MYCN-amplified 4N patients, 7 are relapse-free 2.1+ to 26.4+ (median 11.6+) years from the start of chemotherapy (all received mAbs; 3 underwent MAT) and 4 are in second remission 4.2+ to 21.8+ years postrelapse (all soft tissue). Statistical analyses showed no significant association of survival with either MAT or mAbs for MYCN-nonamplified HR-NB; small numbers prevented these analyses for MYCN-amplified patients. The two patients with intermediate-risk 4N (14-months-old) are relapse-free 7+ years postresection of primary tumors; distant disease spontaneously regressed. The natural history of 4N is marked by NB confined to soft tissue without early relapse in bones or bone marrow, where mAbs have proven efficacy. These findings plus curability without MAT, as seen elsewhere and at our center, support consideration of treatment reduction for MYCN-nonamplified 4N.

摘要

4N 期神经母细胞瘤(远处转移仅限于淋巴结)患者在接受清髓性治疗(MAT)和抗-G 单克隆抗体(mAb)免疫治疗成为标准之前,几乎是高危神经母细胞瘤(HR-NB)中唯一的幸存者。由于没有报告显示最近有更多的 4N 期患者的结果,我们分析了我们的大量 4N 期患者的经验。回顾了 1985 年至 2021 年期间诊断的 51 名儿科 4N 患者(<18 岁)。HR-NB 包括年龄≥18 个月时诊断的 MYCN 非扩增 4N 和 MYCN 扩增 4N。在 34 名 MYCN 非扩增高危患者中,20 名患者在诊断后 1.5+至 37.5+(中位数 12.5+)年无复发,其中 13 名患者未接受 MAT,5 名患者接受了少量(1 个周期;n=2)或没有 mAb(n=3)治疗,而 14 名患者(7 名接受 MAT,8 名接受 mAb 后)复发(均为软组织)。15 名 MYCN 扩增 4N 患者中,7 名患者在开始化疗后 2.1+至 26.4+(中位数 11.6+)年无复发,均接受了 mAb(3 名接受了 MAT),4 名患者在复发后 4.2+至 21.8+年再次缓解(均为软组织)。统计分析显示,MYCN 非扩增 HR-NB 的生存与 MAT 或 mAb 无显著相关性;由于患者数量较少,无法对 MYCN 扩增患者进行这些分析。两名中危 4N 期(14 个月大)患者在切除原发性肿瘤后 7+年无复发,远处疾病自发消退。4N 期的自然病史以局限于软组织的 NB 为特征,骨骼或骨髓中无早期复发,mAb 已被证明在这些部位有效。这些发现加上无需 MAT 即可治愈,与其他地方和我们中心的情况一样,支持考虑减少对 MYCN 非扩增 4N 的治疗。

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