Clinical Features And Treatment Of Primary Intracranial Germ Cell Tumors: A Retrospective Series Of 34 Cases In Children

Background:Primary intracranial germ cell tumors(ICGCTs)is a rare heterogeneous tumor common in children and adolescents,mainly involving two peak ages of 0~6 years old and 10~12 years old.ICGCTs showed great differences in geographical and gender distribution,histological composition and treatment results.The incidence of ICGCTs in Japan and other East Asian countries is eight times higher than that in Western countries.It is generally believed that the pineal region is the first common site of ICGCTs,followed by the suprasellar region.The ratio of male to female is about 3~4:1.The ratio of male to female is even much higher in tumors located in pineal region.According to the 2016 WHO classification of central nervous system tumors,intracranial germ cell tumors can be divided into germinoma and non-germinomatous germ cell tumors(NGGCTs)in histopathology.NGGCTs can be further divided into yolk sac tumor,choriocarcinoma,embryonal carcinoma,teratoma(mature and immature),teratoma with malignant transformation of and mixed germ cell tumors.Germ cell tumors are occult and develop relatively slowly.Most of them are low-grade malignant tumors,invasive growth,and can be accompanied by various degrees of metastasis often along the ependyma or implantation metastasis.In general,ICGCTs is a curable disease,but the treatment varies from place to place around the world.In the past two decades,with the development of neuroimaging,microsurgery and neoadjuvant therapy,the prognosis of ICGCTs has been significantly improved.However,the clinical manifestations of ICGCTs are atypical and lack of specific radiologic manifestations,which makes it difficult for doctors to make accurate diagnosis and standard treatment.At the same time,the area where ICGCTs is located is adjacent to some fragile and important structures,so there are some risks and difficulties in surgical resection or obtaining tissues for biopsy.At present,the diagnosis,treatment and prognosis evaluation of ICGCTs are still facing challenges.Objective:In this study,we collected data of patients with ICGCTs at the First Affiliated Hospital of Zhengzhou University,to retrospectively review and analyze the clinical features,the radiological characteristics,and the treatment strategies.In addition,we analyzed the risk factors of outcome to provide references for the treatment of patients with ICGCTs.Methods:1.Patients and methods From January 2011 to May 2017,pediatric patients(age at presentation?14 years)with ICGCTs were treated at the First Affiliated Hospital of Zhengzhou University and were followed up.Some patients were histologically diagnosed with ICGCTs,while others were diagnosed as NGGCTs on the basis of clinical manifestations,radiologic features and the results of the serum AFP and/or?-HCG levels.The information about patient demographics,initial and presenting symptoms,tumor markers,histologic features,management,and outcomes during follow-up were analyzed retrospectively.2.Statistical Analysis Quantitative data were described as mean±standard deviation or median(ranges).Statistical significance of difference in 2?2 table was assessed by Pearson?~2 test,continuity correction?~2 test,or Fisher exact test.A Wilcoxon rank test,Kruskal-Wallis test,or Spearman rank correlation was used to evaluate the difference of R?C crosstabs.The Kaplan-Meier method and COX regression analysis was used to draw the survival distributions,and the log-rank test was used to assess difference in survival experience.All tests of hypotheses were two-sided and conducted at 0.05 level of significance.SPSS 22.0 and GraphPad Prism 5 were used in statistical analyses.Results:1.The peak age of onset in this group was 10 to 12 years old.There were 20males and 14 females,with a ratio of 1.43 to 1.The median age of onset was 9.7years(0.4~13.6 years),8.1 years(0.7~13.6 years)for males and 10.1 years(0.4~13.2years)for females.The median age of presentation was 10.1 years(4.5~14.7 years).2.The most common clinical manifestation is headache with nausea and vomiting,and polydipsia and polyuria is the second common manifestation.Headache without nausea and vomiting,vision loss,physical retardation and somnolence are also common clinical manifestations.3.Of the 34 patients,17 patients had symptom duration more than 1 month.11patients had symptom duration more than 6 months,and 8 patients had symptom duration more than 12 months.The duration of symptoms was related to the type of symptoms,tumor size,tumor location and so on.4.19 cases were single lesions(55.9%),11 cases(32.4%)were double lesions,and 4 cases(11.8%)were more than or equal to 3 lesions.Among the 19 patients with single lesion,pineal region was the most common disease site with 9 cases(47.4%)located in pineal region,4 cases(21.0%)were located in suprasellar region,3 cases(15.8%)were in the third ventricular area,and 3 cases(15.8%)were in basal ganglia.Males had a significantly higher tumor incidence in pineal region than females.5.29 cases were diagnosed pathologically,including 15 cases of germinoma,2cases of mature teratoma,2 cases of immature teratoma,2 cases of mature teratoma mixed with immature teratoma,1 case of yolk sac tumor,and 7 cases of malignant mixed germ cell tumors.6.Among the 34 patients,22 patients were performed with the detection of serum AFP and?-HCG before treatment.Among them,6 patients had both elevated AFP and?-HCG,2 patients only had elevated AFP and 4 patients had elevated?-HCG.The levels of?-HCG and AFP in 9 patients were within the normal range.There was no significant difference among different pathological types in these two tumor markers(p<0.05).7.Of the 28 patients who underwent craniotomy,8 patients underwent both radiotherapy and chemotherapy after the operation,12 patients received radiotherapy only,1 patient received chemotherapy only after operation,and 7 patients received neither chemotherapy nor radiotherapy.8.The 1-,3-and 5-year overall survival rates(OS)were 77.9%,74.5%,66.9%,respectively,and the 1-,3-and 5-year progression-free survival rates(PFS)were75.1%,61.5%,37.0%,respectively.The OS of females was significantly higher than that of males(p=0.032),and the OS of patients with yolk sac tumor in pathological components was significantly lower than that of patients without such pathological components(p=0.019).The OS in patients with maximum diameter of tumor greater than 30mm was significantly lower than that in patients with maximum diameter of tumor less than or equal to 30mm(p=0.021),and the PFS in patients with germinomas was significantly higher than that in patients with NGGCTs(p=0.003).The PFS of patients without neither postoperative radiotherapy nor chemotherapy was lower than that of other patients who received at least one postoperative treatment(p=0.043).Conclusion:1.The peak age of children with ICGCTs was 10~12 years old.The clinical manifestations of children with ICGCTs are atypical,which are mainly related to the location of tumor and tumor size.Headache with nausea and vomiting,and polydipsia and polyuria are common symptoms.2.The duration of symptoms in children with ICGCTs is long,which is related to the first symptom types,tumor size,tumor location and so on.3.The prognosis of male children with ICGCTs with maximal tumor diameter larger than 30 mm,with pathological type of NGGCTs and/or yolk sac tumor was poor.There is effect of postoperative radiotherapy or chemotherapy on progression-free survival rate(PFS)of the patients with ICGCTs after surgical resection.