MATERIALS AND METHODS

Patients and treatment

Six patients with germinoma treated in our institute from 2007 to 2018 were included in the study. All three hCG-related markers (hCGβ, intact hCG, and total hCG) were measured. The clinical characteristics of the six patients are summarized in Table 1. The median age of the patients was 15 years. The tumors were located at the pineal (n = 2), neurohypophyseal (n = 2), and basal ganglia regions (n = 2). For diagnosis, the patients underwent endoscopic biopsies, stereotactic needle biopsies, or craniotomies.
All patients were treated with platinum-based chemotherapy and radiotherapy. The irradiation fields were the whole ventricles in four patients and the whole brain in two patients with basal ganglia lesions. Chemotherapy consisted of carboplatin (450 mg/m2) on Day 1 and etoposide (150 mg/m2/day) on days 1–3. Patients received three cycles of chemotherapy at an interval of 28 days.11

Measurement of hCG

The blood samples of the patients were collected, and the three markers were measured before, during, and after treatment together with AFP to exclude nongerminomatous germ cell tumors. One patient was additionally measured with the hCGβ and total hCG during recurrence 2 years after the initial treatment (Case 2).
hCGβ, intact hCG, and total hCG were measured using the radioimmunoassay (Ball ELSA·F-βHCG kit, Cisbio Bioassays, France), electrochemiluminescent immunoassay (ECLusys HCG II STAT, Roche Diagnostics, Japan), and chemiluminescent immunoassay (Architect βhCG, Abbott Japan), respectively. The lower detection limits of hCGβ, intact hCG, and total hCG were 0.1 ng/mL, 0.5 mIU/mL, and 1.2 mIU/mL respectively, based on the manufacturers’ protocols. The lower limit of the normal range of AFP was 10.0 ng/mL.

Statistical analysis

For statistical analyses, group comparisons were performed using Friedman’s test with Bonferroni’s multiple comparisons test for the values of the samples and Cochran’s Q and McNemar tests for the positivity rates. All statistical analyses were calculated with EZR (Saitama Medical Center, Jichi Medical University, Saitama, Japan), which is a graphical user interface for R (The R Foundation for Statistical Computing, Vienna, Austria). More precisely, it is a modified version of R commander designed to add statistical functions frequently used in biostatistics.12 This investigation was approved by the ethical committee of the Saitama Medical University International Medical Center (Approval number: 19-032).