DataSheet_1_Intracranial non-germinomatous germ cell tumors in children and adolescents: how can the experience from an uppermiddle-income country contribute to the worldwide effort to improve outcomes?.pdf

BackgroundNon-germinomatous germ cell tumors (NGGCT) accounts for one third of intracranial GCT. While the germinoma group have an excellent overall survival, the standard of practice for children with NGGCT is still under evaluation.
AimsDescribe the results of the of the Brazilian consortium protocol.
MethodsSince 2013, 15 patients with a diagnosis of NGGCT by histopathology and/or serum/cerebrospinal fluid (CSF) tumor markers, βHCG >200mlU/ml and/or positive alpha-fetoprotein were treated with neoadjuvant chemotherapy with carboplatin, cyclophosphamide and etoposide followed by ventricular radiotherapy (RTV) of 18Gy with boost (32Gy) to the primary site. Metastatic patients underwent craniospinal irradiation (CSI) and “slow responders” to the four initial cycles of CT, to autologous stem cell transplantation (ASCT) followed by CSI.
ResultsMean age, 13.1 years. Thirteen males. Primary sites: pineal (n=12), suprasellar (n=2) and bifocal (n=1). Four patients were metastatic at diagnosis. Eight patients had CSF and/or serum alpha-fetoprotein levels > 1,000ng/ml. Tumor responses after chemotherapy demonstrated complete in six cases and partial in seven, with “second-look” surgery being performed in five cases, and two patients presenting viable lesions being referred to ASCT. The main toxicity observed was hematological grades 3/4. Two patients with metastatic disease, one with Down Syndrome and AFP > 1,000ng/ml and the other with choriocarcinoma and pulmonary metastases, developed progressive disease resulting in death, as well as two other patients without evidence of disease, due to endocrinological disorders. Event-free and overall survival at 2 and 5 years were 80% and 72.7%, respectively, with a mean follow-up of 48 months (range, 7-107).
ConclusionsDespite the small number of patients, in our series, treatment with six cycles of chemotherapy and RTV with focal boost for localized disease (n=11) and ACST for identified slow responders (n=2) seem to be effective strategies contributing to the overall effort to improve outcomes of this group of patients.

背景 非生殖细胞瘤性生殖细胞肿瘤（Non-germinomatous germ cell tumors, NGGCT）约占颅内生殖细胞肿瘤（intracranial germ cell tumors, GCT）的三分之一。尽管生殖细胞瘤患者群体总体生存率优异，但针对儿童非生殖细胞瘤性生殖细胞肿瘤的临床诊疗标准仍有待进一步评估。
研究目的 描述巴西协作组方案的临床应用结果。
方法 自2013年起，研究团队纳入经组织病理学确诊，或符合血清/脑脊液（cerebrospinal fluid, CSF）肿瘤标志物判定标准（β-HCG＞200mIU/ml，和/或甲胎蛋白（alpha-fetoprotein, AFP）阳性）的15例非生殖细胞瘤性生殖细胞肿瘤患者，予以卡铂、环磷酰胺联合依托泊苷的新辅助化疗方案；随后针对原发灶给予18Gy脑室放疗（ventricular radiotherapy, RTV），并追加32Gy局部推量照射。伴远处转移的患者则接受全脑脊髓放疗（craniospinal irradiation, CSI）；对于初始4周期化疗疗效不佳的应答迟缓者，先实施自体干细胞移植（autologous stem cell transplantation, ASCT），再予以全脑脊髓放疗。
结果 本队列患者的平均年龄为13.1岁，其中男性13例。原发灶部位包括松果体区（n=12）、鞍上区（n=2）及双灶性病变（n=1）。4例患者确诊时即存在远处转移。8例患者的脑脊液和/或血清甲胎蛋白水平＞1000ng/ml。化疗后肿瘤应答情况为：6例获得完全缓解，7例获得部分缓解；其中5例患者接受了二次探查手术，另有2例病灶仍存活的患者被推荐行自体干细胞移植。本研究观察到的主要不良反应为3/4级血液学毒性。2例伴远处转移的患者出现疾病进展并死亡：其中1例合并唐氏综合征且甲胎蛋白＞1000ng/ml，另1例为绒毛膜癌伴肺转移；另有2例无疾病残留证据的患者因内分泌紊乱死亡。患者的2年无事件生存率与5年总生存率分别为80%与72.7%，平均随访时间为48个月（范围7~107个月）。
结论 尽管本研究队列的患者例数较少，但针对局限性病变患者（n=11）采用6周期化疗联合局部推量脑室放疗的方案、针对应答迟缓者（n=2）采用自体干细胞移植联合全脑脊髓放疗的策略，展现出较好的临床疗效，为改善该类患者的预后提供了可行的治疗思路。