Bartels Ute, Onar-Thomas Arzu, Patel Sunita K, Shaw Dennis, Fangusaro Jason, Dhall Girish, Souweidane Mark, Bhatia Aashim, Embry Leanne, Trask Christine L, Murphy Erin S, MacDonald Shannon, Wu Shengjie, Boyett James M, Leary Sarah, Fouladi Maryam, Gajjar Amar, Khatua Soumen
Department of Paediatrics, The Hospital for Sick Children, Toronto, Ontario, Canada.
Department of Biostatistics, St Jude Children's Research Hospital, Memphis, Tennessee, USA.
Neuro Oncol. 2022 Jun 1;24(6):974-983. doi: 10.1093/neuonc/noab270.
BACKGROUND: The study aimed to evaluate whether simplified chemotherapy followed by dose-reduced irradiation was effective for treating patients (ages 3-21 years) with localized germinoma. The primary endpoint was 3-year progression-free survival (PFS) rate. METHODS: Patients with a complete response to chemotherapy with carboplatin and etoposide received 18 Gy WVI + 12 Gy boost to the tumor bed. Patients with partial response proceeded to 24 Gy WVI + 12 Gy. Longitudinal cognitive functioning was evaluated prospectively on ALTE07C1 and was a primary study aim. RESULTS: One hundred and fifty-one patients were enrolled; 137 were eligible. Among 90 evaluable patients, 74 were treated with 18 Gy and 16 with 24 Gy WVI. The study failed to demonstrate noninferiority of the 18 Gy WVI regimen compared to the design threshold of 95% 3-year PFS rate, where, per design, patients who could not be assessed for progression at 3 years were counted as failures. The Kaplan-Meier (KM)-based 3-year PFS estimates were 94.5 ± 2.7% and 93.75 ± 6.1% for the 18 Gy and 24 Gy WVI cohorts, respectively. Collectively, estimated mean IQ and attention/concentration were within normal range. A lower mean attention score was observed at 9 months for patients treated with 24 Gy. Acute effects in processing speed were observed in the 18 Gy cohort at 9 months which improved at 30-month assessment. CONCLUSIONS: While a failure according to the prospective statistical noninferiority design, this study demonstrated high rates of chemotherapy responses, favorable KM-based PFS and OS estimates in the context of reduced irradiation doses and holds promise for lower long-term morbidities for patients with germinoma.
背景:本研究旨在评估简化化疗后降低剂量放疗对治疗局限性生殖细胞瘤患者(3至21岁)是否有效。主要终点是3年无进展生存率(PFS)。 方法:对卡铂和依托泊苷化疗完全缓解的患者接受18 Gy全腹照射(WVI)+ 12 Gy肿瘤床追加照射。部分缓解的患者接受24 Gy WVI + 12 Gy照射。前瞻性地在ALTE07C1上评估纵向认知功能,这是一项主要研究目标。 结果:共纳入151例患者;137例符合条件。在90例可评估患者中,74例接受18 Gy照射,16例接受24 Gy WVI照射。该研究未能证明18 Gy WVI方案与95%的3年PFS率设计阈值相比具有非劣效性,根据设计,3年无法评估进展的患者被计为失败。基于Kaplan-Meier(KM)法的18 Gy和24 Gy WVI队列的3年PFS估计值分别为94.5 ± 2.7%和93.75 ± 6.1%。总体而言,估计的平均智商和注意力/专注力在正常范围内。接受24 Gy治疗的患者在9个月时观察到较低的平均注意力评分。18 Gy队列在9个月时观察到处理速度方面的急性效应,在30个月评估时有所改善。 结论:虽然根据前瞻性统计非劣效性设计该研究失败,但在降低放疗剂量的情况下,本研究显示出高化疗反应率、基于KM法的良好PFS和总生存期(OS)估计值,有望降低生殖细胞瘤患者的长期发病率。
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