Patient Population and Clinical Characteristics
As was mentioned above, the basic information of 19 pHGSG patients was shown in Table 1 and Table 2. Of the 19 patients, 11 were male and 8 were female, and the mean age at diagnosis was 12.7±4.7 years. The age distribution of the 19 pHGSG patients are shown in Fig. 1A. All patients underwent preoperative MRI scanning to identify lesions location and length. 8 (42.1%) lesions were located in the cervical spine, 1(5.3%) in the cervicothoracic spine, 7 (36.8%) in the thoracic spine, and 3 (15.8%) in the thoracolumbar spine. The mean length of lesions is 4.3±2.4 segments. Common symptoms include motor deficit (11, 57.9%), pain (8, 42.1%) and sensory deficit (6, 31.6%). There are 2 patients (10.5%) presented with Bowel/bladder dysfunction. Median duration of symptoms was 2 months (range: 0.3-18). Of preoperative neurological function, modified McCormick score (MMS) grade I-II was observed in 7 patients (36.8%) and MMS grade III-IV was observed in 12 patients (63.2%). Of postoperative neurological function, MMS grade I-II was observed in 10 patients (52.6%) and MMS grade III-IV was observed in 9 patients (47.4%). According to the 2021 WHO Classification of Tumors of the CNS, 12 patients of pHGSG belonged to H3 K27-altered group and 6 patients belonged to H3/IDH-wildtype group.
Thirteen patients of H3 K27-altered pHGSG with a mean age of 12.1±5.3 years old and comprising 53.8% male patients, and 6 patients of H3/IDH-wildtype pHGSG with a mean age of 14.0±3.0 years old and comprising 66.7% male patients. Of H3 K27-altered pHGSG, lesions located in the cervical spine were 53.8% and in the noncervical spine were 46.2%, with the mean length of 3.9±1.7 segments. Of H3/IDH-wildtype pHGSG, lesions located in the cervical spine were 33.3% and in the noncervical spine were 66.7%, with the mean length of 5.2±3.7 segments. The most common symptoms in both H3 K27-altered and H3/IDH-wildtype pHGSG patients were motor deficit, pain and sensory deficit. Median duration of symptoms were 2 (range: 0.3-14) months and 1.5 (range: 1-18) months in H3 K27-altered and H3/IDH-wildtype pHGSG, respectively. Preoperative MMS grade I-II and III-IV were observed in 4 and 9 patients with H3 K27-altered pHGSG, while postoperative MMS grade I-II and III-IV were observed in 7 and 6 patients. Three patients of H3/IDH-wildtype pHGSG have preoperative MMS grade I-II, whose postoperative MMS were still grade I-II; and 3 patients of H3/IDH-wildtype pHGSG have preoperative MMS grade III-IV, whose postoperative MMS were still grade III-IV. Thirteen H3 K27-altered pHGSG included 4 histological grade 3 gliomas and 9 histological grade 4 gliomas; 6 H3 K27-altered pHGSG included 4 histological grade 3 gliomas and 2 histological grade 4 gliomas
We compared the difference of age, sex, lesions location and length, symptoms, duration of symptom, MMS and histological grade between the two groups of pHGSG. There was no statistically significant difference between the two groups.
Treatment Modalities and Clinical Outcome
All patients received therapeutic surgical resection, 10 (55.6%) patients underwent GTR and 8 (33.3%) patients underwent STR. To assess the impact of surgical resection on neurological function of pHGSG, we firstly compare preoperative and postoperative MMS in all pHGSG patients. There was no significant difference between preoperative and postoperative MMS (p = 0.395) (Fig. 1B). In total, 14 (73.7%) of the patients received adjuvant radiation therapy after surgery, and 13 (68.4%) of the patients received adjuvant chemotherapy; adjuvant therapy status was unknown in 2 patients (10.5%). The median survival time of all patients was 14 months. Up to now, an 18-year-old male with a H3/IDH-wildtype tumor is alive for more than 5 years after GTR and adjuvant chemotherapy and radiation therapy.
The lesions located in the noncervical spine (HR 0.383, 95% CI 0.095-1.545, p = 0.048) were associated with a better prognosis, compared with the lesions located in the cervical spine. Histological grade and H3 K27M status are also the important prognostic factors. Histological grade 4 pHGSGs (HR 6.058, 95% CI 1.215-30.202, p = 0.015) have a worse prognosis compared to pHGSGs in histological grade 3. H3 K27-altered pHGSGs (HR 4.262, 95% CI 0.916-19.836, p = 0.044) exhibit a worse prognosis than H3/IDH-wildtype pHGSGs. For treatment modalities, pHGSG patients who underwent GTR (HR 0.218, 95% CI 0.060-0.790, p = 0.012) had better OS than patients who underwent STR. However, patients of pHGSG receiving adjuvant radiation therapy (p = 0.405) or chemotherapy (p = 0.118) did not show any beneficial effect on OS. Fig. 2 depicts the Kaplan-Meier curves of OS for all pHGSG patients in tumor location, histological grade, H3 K27 status and EOR. Table 3 summarizes the results of univariate analysis of all pHGSG patients.
Surgical Resection and Survival in H3 K27-altered and H3/IDH-wildtype pHGSG
We performed a subgroup analysis to further investigate the impact of the EOR on OS in H3 K27-altered and H3/IDH-wildtype pHGSG. Similarly, we separately compare preoperative and postoperative MMS in H3 K27-altered and H3/IDH-wildtype pHGSG patients. There was no significant difference between preoperative and postoperative MMS neither in H3 K27-altered (p = 0.350) (Fig. 1C) nor in H3/IDH-wildtype pHGSG patients (p = 0.881) (Fig. 1D). Interestingly, pHGSG patients with H3 K27-altered underwent GTR (HR 0.311, 95% CI 0.075-1.289, p = 0.091) had tended to increase OS. For patients of H3/IDH-wildtype pHGSG, there was no survival advantage associated with GTR (p = 0.157). The impact of the EOR on OS in two groups showed different results. Fig. 3 shows the Kaplan-Meier survival curves for H3 K27-altered and H3/IDH-wildtype groups.