Patients’ demographic characteristics
Comparison of patients’ demographic characteristics at baseline is outlined in Table 1. Among all 232 cases, there were 162 (69.8%) men and 70 (30.2%) women, and male-to-female ratio was 2.3:1. Patients who were diagnosed with pure germinoma and germinoma with STGC accounted for 88.4% (n=205) and 11.6% (n=27) of total number of cases, respectively. The majority of patients aged under 20 years old (range, 0-19 years old; n=181, 78.0%; Figure 1A). Patients’ mean age in the groups of pure germinoma and germinoma with STGC was 15.3±6.2 and 16.9±6.1 (range, 4-44 and 6-27) years old, respectively (P=0.195). Patients with basal ganglia lesions (median age, 10.5±3.0 years old) experienced a younger age of disease onset than other patients (Figure 1B).
In the pure germinoma group, tumors were located in sellar/suprasellar region in 69 (33.7%), in pineal region in 53 (25.9%), in basal ganglia in 28 (13.7%), in bifocal region in 31 (15.1%), in multifocal region in 20 (9.8%), and in other regions in 4 (1.8%) cases. In the germinoma with STGC group, tumors were located in sellar/suprasellar region in 8 (29.6%), in pineal region in 5 (18.5%), in basal ganglia in 7 (25.9%), in bifocal region in 2 (7.4%), in multifocal region in 3 (11.2%), and in other regions in 2 (7.4%) cases. No significant difference was found in tumor location between the two groups (P=0.222).
In addition, female patients with lesions located in the sellar/suprasellar region accounted for 74.3% (n=52) (Figure 1C). The male-to-female ratio in the sellar/suprasellar region was 1:2.1, 57:1 in the pineal region, 7.8:1 in basal ganglia, 4.5:1 in bifocal region, and 2.3:1 in multifocal region.
Polyuria and/or polydipsia was the most common symptom (n=99, 42.7%), followed by headache (n=94, 40.5%), visual disturbance (n=87, 37.5%), motor impairment (n=66, 28.4%), nausea/vomiting (n=57, 24.6%), and dizziness/vertigo (n=40, 17.2%). Several patients presented with menstruation disorders (n=19), growth retardation (n=15), hearing impairment (n=10), slurred speech (n=7), memory defection (n=6), incontinence (n=5), and precocious puberty (n=2).
Polyuria/polydipsia was predominantly observed in patients with tumors located in sellar/suprasellar region (60/77, 77.9%) and bifocal region (24/33, 72.7%). Headache and nausea/vomiting are the symptoms of increased intracranial pressure and are strongly correlated to hydrocephalus (P<0.001 and P<0.001, respectively). The majority of patients (32 of 35, 91.4%) with tumors in basal ganglia suffered from motor impairment. In multifocal region, 12 cases experienced motor impairment, of whom 8 (66.7%) cases had tumors in the basal ganglia.
Besides, 6 of 162 (3.7%) male patients had growth retardation and 9 of 70 (12.9%) were women (P=0.017). Moreover, 12 (80.0%) patients with growth retardation were identified before puberty (age, ≤ 14 years old), and the preference of patients before puberty presented with growth retardation was observed (P=0.043). Menstruation disorders, such as irregular menstruation and amenorrhea, were observed in 19 cases, which were related to the sellar/suprasellar region (n=15), bifocal region (n=2), and multifocal region (n=2)). Two patients had precocious puberty and they all were male with tumors located in the basal ganglia. The elevation of serum β-HCG level was observed in all patients (21.39 IU/L and 21.63 IU/L).
Among the 232 cases, a mild elevation of serum β-HCG level (>5.0 IU/L) was found in 9 of 27 (33.3%) patients in the germinoma with STGC group and 28 of 205 (13.7%) in the pure germinoma group. As illustrated in Figure 2A, the median serum level of β-HCG was 2.50 IU/L and 0.86 IU/L in the two groups, respectively. There was a statistically significant difference between the two groups (P=0.001).
Of the 5 cases with an elevated serum level of AFP (>7 ng/ml), 1 case in the germinoma with STGC group and 4 cases in the pure germinoma group were detected. Figure 2B shows the profile of the serum AFP level in two groups. The median serum level of AFP was 2.71 ng/ml and 2.28 ng/ml in the two groups, respectively, and no significant difference was noted between the two groups (P=0.540).
Intracranial dissemination and spinal seeding
Cranial imaging data of all patients were assessed, in which 61 (26.3%) patients had intracranial dissemination, including intracranial ventricular seeding and extraventricular seeding, and 10 and 51 patients were diagnosed with germinoma with STGC and pure germinoma, respectively. No statistically significant difference was identified between the two groups (P=0.177). Tumors’ locations were strongly associated with intracranial dissemination (P<0.001), in which tumors that were located in bifocal or multifocal regions were easily spread (21/33, 63.6% and 13/23, 56.5%, respectively) compared with tumors in the sellar/suprasellar region (10/77, 13.0%), pineal region (14/58, 24.1%), and tumors in basal ganglia showed a significant reluctance to cerebrospinal fluid (CSF) dissemination (2/35, 5.7%). Furthermore, when patients with primary tumors located in the sellar/suprasellar region, pineal region, basal ganglia, and other regions were assigned to localized group, the difference in intracranial dissemination among different locations was statistically significant compared with tumors in bifocal or multifocal lesions (15.3% vs. 60.7%, P<0.001).
Among 121 cases with available spinal MRI data, 30 (24.8%) cases had spinal seeding, in which 2 and 28 cases were in germinoma + STGCs and pure germinoma groups, respectively (P=0.514). In patients with tumors located at sellar/suprasellar region, 6 of 36 (16.7%) had spinal seeding, and 4 of 29 (13.8%) and 3 of 19 (15.8%) had tumors in in the pineal region and basal ganglia, respectively. In contrast, 13 of 21 (61.9%) cases had tumors located in bifocal region and 4 of 12 (33.3%) had tumors located in multifocal region, which indicated spinal seeding. There was a noticeable association for sites according to spinal MRI findings (P=0.002). When localized cases were compared with those with bifocal or multifocal lesions, the trend of spinal seeding appeared statistically significant (14.8% vs. 51.5%, P<0.001).
A total of 115 patients underwent open craniotomy (partial resection (n=43), subtotal resection (n=19), and gross total resection (n=53)) and 117 patients received stereotactic biopsy. The mean operation time of open craniotomy was 268.8 min with an average volume of blood loss of 316.9 ml, compared with 27.0 min and 6.2 ml for stereotactic biopsy (P<0.001 and P<0.001, respectively; Table 3). Significant differences were also observed in length of hospital stay and inpatient expenses between these two surgical approaches (P<0.001 and P<0.001, respectively). As shown in Table 4, a total of 66 patients developed postoperative complications and the most common complication was postoperative hemorrhage. Other complications included postoperative effusion (n=16, 6.9%), infections (n=14, 6.0%), new-onset seizure (n=7, 3.0%), postoperative hydrocephalus (n=7, 3.0%), and cerebral infarction (n=2, 0.9%). Moreover, the perioperative mortality was 0.4%. One patient died on the 8th day after receiving gross total resection because of suspected pulmonary embolism.
The KPS scores are summarized in Table 5. As displayed in Figure 3, the open craniotomy significantly decreased KPS scores after surgery compared with the biopsy (P<0.001). Patients who received biopsy had higher KPS scores at hospital discharge than on admission in contrast to open craniotomy (P=0.047). Figure 4A illustrates that patients in the stereotactic biopsy group had a lower reduction of postoperative KPS scores (-2.3) than partial resection (-24.0), subtotal resection (-26.3), and gross total resection groups (-29.0; P<0.001, P<0.001, and P<0.001, respectively). However, stereotactic biopsy showed a lower reduction of KPS scores at hospital discharge (0.9) compared with partial resection (-0.2), subtotal resection (-1.1), and gross total resection (-3.2), while no significant differences were found (P=0.467, 0.302, and 0.328, respectively, Figure 4B).
Deterioration of KPS at hospital discharge compared with on admission was observed in 30 patients, of whom 4, 7, 18, and 1 patients received partial resection, subtotal resection, gross total resection, and biopsy, respectively (P<0.001).