Department of Pediatric Oncology, Institut d'Hemato-oncologie Pediatrique, Lyon, France.
SIREDO Oncology Center (Care, Innovation and Research for Children, Adolescents and young Adults with Cancer) Institut Curie, PSL University, Paris, France.
Pediatr Blood Cancer. 2023 Mar;70(3):e30117. doi: 10.1002/pbc.30117. Epub 2022 Nov 30.
Chemotherapy for non-seminomatous germ cell tumours (NSGCT) exposes to dose-dependent toxicities. The TGM13-NS protocol (EudraCT 2013-004039-60) aimed to decrease the chemotherapy burden compared to the previous TGM95 protocol while maintaining the 5-year event-free survival (EFS) at 80% or more.
Patients less than 19 years of age with disseminated NSGCT were enrolled (May 2014 to May 2019) and stratified into four groups: two intermediate-risk (IR: localised tumour with low tumour markers [TM]) groups treated with VBP (vinblastine-bleomycin-cisplatin): three courses for IR1 (ovarian tumour any age/testis tumour less than or equal to 10 years) and four courses for IR2 (extragonadal tumour 10 years or less) groups, and two high-risk (HR: metastatic and/or high TM) groups treated with etoposide-cisplatin and either ifosfamide (VIP) or bleomycin (BEP): three courses for HR1 (ovarian tumour any age/testis tumour less than or equal to 10 years and low TM/testis tumour more than 10 years and very low TM) groups and four courses for HR2 (remainder) groups.
One hundred fifteen patients were included: median age of 12.8 years (0.4-18.9); tumour sites: 44 ovaries, 37 testes and 34 extragonadal. The 5-year EFS and overall survival (OS) were 87% (95% CI: 80-92) and 95% (89-98), respectively (median follow-up: 3.5 years, range: 0.2-5.9), similar to those of the TGM95 protocol (5-year EFS 89% (84-93), 5-year OS 93% (89-95), p = .561). The 5-year EFS were 93% (95% CI: 80-98), 88% (71-95) and 79% (62-90) for ovarian, testicular and extragonadal tumours, respectively. The 5-year EFS varied (p = .02) according to the risk groups: 90% (66-97), 64% (30-85), 95% (72-99) and 87% (74-94) for IR1, IR2, HR1 and HR2, respectively. TM decline adjusted to tumour site, and alpha-fetoprotein (AFP) level revealed a prognostic impact of time to normalisation on EFS: HR = 1.03 (1.003-1.007).
Risk-adapted and globally decreased chemotherapy burden maintains excellent outcomes, exclusive of the IR2 group, which warrants more intensive chemotherapy.
非精原细胞瘤生殖细胞肿瘤（NSGCT）的化疗会产生剂量依赖性毒性。TGM13-NS 方案（EudraCT 2013-004039-60）旨在与之前的 TGM95 方案相比降低化疗负担，同时保持 5 年无事件生存率（EFS）在 80%或更高。
招募了年龄小于 19 岁的播散性 NSGCT 患者（2014 年 5 月至 2019 年 5 月），并分为四组：两组中危（IR：局部肿瘤伴低肿瘤标志物 [TM]）患者接受 VBP（长春碱-博莱霉素-顺铂）治疗：IR1 组（任何年龄的卵巢肿瘤/睾丸肿瘤小于或等于 10 岁）接受三个疗程，IR2 组（小于或等于 10 岁的外胚层肿瘤）接受四个疗程，两组高危（HR：转移和/或高 TM）患者接受依托泊苷-顺铂和异环磷酰胺（VIP）或博来霉素（BEP）治疗：HR1 组（任何年龄的卵巢肿瘤/睾丸肿瘤小于或等于 10 岁和低 TM/睾丸肿瘤大于 10 岁和极低 TM）接受三个疗程，HR2 组（其余）接受四个疗程。
共纳入 115 例患者：中位年龄 12.8 岁（0.4-18.9）；肿瘤部位：44 例卵巢，37 例睾丸，34 例外胚层。5 年 EFS 和总生存率（OS）分别为 87%（95%CI：80-92）和 95%（89-98）（中位随访时间：3.5 年，范围：0.2-5.9），与 TGM95 方案相似（5 年 EFS 89%（84-93），5 年 OS 93%（89-95），p=0.561）。卵巢、睾丸和外胚层肿瘤的 5 年 EFS 分别为 93%（95%CI：80-98）、88%（71-95）和 79%（62-90）。5 年 EFS 根据风险组而有所不同（p=0.02）：IR1、IR2、HR1 和 HR2 组分别为 90%（66-97）、64%（30-85）、95%（72-99）和 87%（74-94）。TM 下降与肿瘤部位相适应，甲胎蛋白（AFP）水平揭示了正常化时间对 EFS 的预后影响：HR=1.03（1.003-1.007）。
风险适应和总体降低化疗负担保持了优异的结果，除了 IR2 组外，这需要更强化的化疗。
