背景:非精原细胞生殖细胞肿瘤(NSGCT)的化疗暴露于剂量依赖性毒性。TGM13-NS方案(EudraCT2013-004039-60)旨在与以前的TGM95方案相比降低化疗负担,同时将5年无事件生存率(EFS)保持在80%或更高。
方法:纳入年龄小于19岁的播散性NSGCT患者(2014年5月至2019年5月),并分为四组:两个中等风险组(IR:具有低肿瘤标志物的局部肿瘤[TM])接受VBP(长春碱-博来霉素-顺铂)治疗的组:Ituma3个疗程(卵巢肿瘤任何年龄/睾丸或小于或小于或等于10年和使用依托泊苷-顺铂和异环磷酰胺(VIP)或博来霉素(BEP)治疗的两个高风险(HR:转移性和/或高TM)组:HR1三个疗程(任何年龄的卵巢肿瘤/睾丸肿瘤小于或等于10年,低TM/睾丸肿瘤超过10年,TM非常低)组,HR2(其余)组四个疗程。
结果:115例患者包括:中位年龄为12.8岁(0.4-18.9);肿瘤部位:44个卵巢,37个睾丸和34个性腺外。5年EFS和总生存率(OS)分别为87%(95%CI:80-92)和95%(89-98),分别(中位随访时间:3.5年,范围:0.2-5.9),与TGM95协议相似(5年EFS89%(84-93),5年OS93%(89-95),p=.561)。5年EFS为93%(95%CI:80-98),88%(71-95)和79%(62-90)的卵巢,睾丸和性腺外肿瘤,分别。5年EFS根据风险组而变化(p=0.02):90%(66-97),64%(30-85),IR1、IR2、HR1和HR2分别为95%(72-99)和87%(74-94)。TM下降根据肿瘤部位调整,和甲胎蛋白(AFP)水平显示了EFS正常化时间的预后影响:HR=1.03(1.003-1.007)。
结论:风险适应和整体降低的化疗负担维持了良好的预后,不包括IR2基团,这需要更密集的化疗。
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.