Clinical management and survival outcomes of patients with different molecular subtypes of diffuse gliomas in China (2011–2017): a multicenter retrospective study from CGGA

Kenan Zhang; Xing Liu; Guanzhang Li; Xin Chang; Shouwei Li; Jing Chen; Zheng Zhao; Jiguang Wang; Tao Jiang; Ruichao Chai

doi:10.20892/j.issn.2095-3941.2022.0469

Article Figures & Data

Figures

Tables
Supplementary Materials

Download figure
Open in new tab
Download powerpoint
Figure 1
Flowchart of patients with eligible diffuse gliomas who were included in the study.
Download figure
Open in new tab
Download powerpoint
Download figure
Open in new tab
Download powerpoint
Figure 2
Survival outcomes of patients with different molecular subtypes. Kaplan-Meier estimates of overall survival (A) and progression-free survival (B) of patients with primary DG classified according to molecular subtypes. Kaplan-Meier estimation of the overall survival (C) and progression-free survival (D) of patients with recurrent DG classified according to molecular subtypes.
Download figure
Open in new tab
Download powerpoint
Figure 3
Survival outcomes of patients with primary GBM receiving different postsurgical treatments. (A–B) Kaplan-Meier curves estimating the overall survival of patients with primary GBM-IDHwt (A) and patients with primary GBM-IDHm (B). (C–D) Kaplan-Meier curves estimating the progression-free survival of patients with primary GBM-IDHwt (C) and patients with primary GBM-IDHm (D). *P < 0.05, ****P < 0.0001.
Download figure
Open in new tab
Download powerpoint
Figure 4
Survival outcomes of patients with recurrent GBM receiving different postsurgical treatments. (A–B) Kaplan-Meier curves estimating overall survival of patients with recurrent GBM-IDHwt patients (A) and patients with recurrent GBM-IDHm (B). (C–D) Kaplan-Meier curves estimating progression-free survival of patients with recurrent GBM-IDHwt (C) and patients with recurrent GBM-IDHm (D). *P < 0.05, **P < 0.01, ***P < 0.001.

View popup

Table 1

Distribution of 1418 cases of diffuse glioma according to clinicopathological information

Characteristics	Diffuse glioma	Primary diffuse glioma	Recurrent diffuse glioma	P
Sex
Male	839	541	298	0.0339
Female	579	405	174
Age
≥ 45	659	460	200	0.0276
< 45	755	486	272
Mean age, years (SD)	43.55 (12.33)	44.33 (12.95)	42.00 (10.67)
Symptom at onset (n = 1334)
Headache	555	445	110	< 0.0001
Seizure	457	331	126
Focal deficit	393	240	153
No clear symptoms	179	58	121
Karnofsky performance status (n = 1330)
≥ 80	1260	857	403	< 0.0001
< 80	70	30	40
Lateral involvement (n = 1390)
Right	656	450	206	0.6024
Left	659	439	220
Both sides	70	43	27
Midline	5	3	2
Cortex involvement (n = 1390)
Frontal lobe	931	607	324	0.0017
Temporal lobe	586	386	200
Insular lobe	309	237	72
Parietal lobe	298	183	115
Occipital lobe	120	77	43
Other lobes	72	50	22
Histological grade
II	376	309	67	< 0.0001
III	413	290	123
IV	629	347	282
Molecular subtype
LGG, IDH-mutant and 1p/19q-codeleted	167	130	37	< 0.0001
LGG, IDH-mutant	195	130	65
LGG, IDH-wildtype	141	103	38
LGG, NOS	286	236	50
GBM, IDH-wildtype	389	248	141
GBM, IDH-mutant	185	63	122
GBM, NOS	55	36	19
MGMT methylation (n = 1080)
Unmethylated	374	251	123	0.4077
Methylated	706	492	214
Types of surgery
Total resection	627	475	152	< 0.0001
Subtotal resection	511	333	178
Partial resection	278	138	140
Biopsy	2	0	2
Treatment (n = 1274)
Radio chemotherapy	643	520	123	< 0.0001
Radiotherapy	173	151	22
Chemotherapy	263	74	189
None	195	111	84

View popup

Table 2

Characteristics of primary diffuse gliomas

	n	LGG, IDH-mutant and 1p/19q-codeleted	LGG, IDH-mutant	LGG, IDH-wildtype	GBM, IDH-wildtype	GBM, IDH-mutant	P	LGG NOS	GBM NOS
Sex	946	130	130	103	248	63	0.7995	236	36
Male	541	72	75	59	150	40	0.7995	123	22
Female	405	58	55	44	98	23		113	14
Age
≥ 45	460	56	37	34	195	28	< 0.0001	83	27
< 45	486	74	93	69	53	35		153	9
Mean age, years	44.30	42.15	39.15	38.55	52.86	43.67		41.17	49.75
SD of age	12.73	9.89	8.57	16.04	12.57	11.79		9.98	11.57
Karnofsky performance status
≥ 80	857	126	123	100	233	58	0.3722	189	28
< 80	30	4	3	2	14	2		4	1
Diagnostic symptom	890	130	127	102	247	62	< 0.0001	193	29
Headache	445	49	56	48	156	43		77	16
Seizure	331	68	64	40	37	18		95	9
Neurofunction deficit	240	22	19	29	114	12		35	9
No clear symptom	58	15	6	8	5	1		22	1
Lateral involved	935	130	129	101	244	63	0.0408	233	35
Right	450	66	66	44	110	29		114	21
Left	439	57	57	46	123	32		113	11
Both sides	43	7	6	8	11	2		6	3
Midline	3	0	0	3	0	0		0	0
Cortex involved (n)	935	130	129	101	244	63	< 0.0001	233	35
Frontal lobe	607	103	93	51	114	43		181	22
Temporal lobe	386	40	50	40	118	32		92	14
Insular lobe	237	34	44	21	46	16		73	3
Parietal lobe	183	17	21	22	67	11		34	11
Occipital lobe	77	1	5	7	45	5		13	1
Other lobes	50	6	6	10	19	3		6	0

View popup

Table 3

Univariate and multivariate Cox proportional-hazards models for low grade gliomas

Variable	Hazard ratio (95% CI)
	LGG, IDH-mutant and 1p/19q-codeleted		LGG, IDH-mutant		LGG, IDH-wildtype
	Univariate	Multivariate	Univariate	Multivariate	Univariate	Multivariate
Age at diagnosis¹	1.069 (0.998–1.144)^†	1.378 (1.08–1.759)^*	0.984 (0.948–1.021)		1.026 (1.007–1.045)^†
Sex
Female	Reference		Reference		Reference
Male	0.702 (0.175–2.811)		1.331 (0.684–2.591)		1.598 (0.867–2.944)
Histological grade²	5.84 (0.713–47.86)^†	48.808 (1.193–1997.239)^*	3.902 (1.789–8.51)^†	2.659 (1.195–5.918)^*	3.776 (1.808–7.887)	6.024 (2.311–15.702)^*
MGMT
Unmethylated	Reference		Reference		Reference
Methylated	2.657 (0.318–22.229)		0.566 (0.284–1.125)		0.376 (0.194–0.729)^†
KPS_PRE³	0.991 (0.885–1.109)		0.98 (0.922–1.041)		0.971 (0.931–1.013)
KPS_POST⁴	0.925 (0.869–0.986)^†		0.933 (0.903–0.964)^†	0.956 (0.925–0.988)^*	0.944 (0.92–0.969)^†	0.949 (0.906–0.994)^*
Resection rate
Total resection	Reference	Reference	Reference	Reference	Reference	Reference
Subtotal resection	4.68 (0.424–51.663)	24.532 (0.522–1153.043)	2.083 (0.911–4.765)^†	1.707 (0.724–4.025)	6.022 (1.368–26.507)^†	11.326 (1.407–91.164)^*
Major partial resection	147.156 (13.035–1661.254)^†	4288.619 (17.419–1.056^10⁶)^*	21.3 (8.518–53.262)^†	13.381 (5.079–35.251)^*	28.795 (6.524–127.102)^†	46.648 (5.71–381.063)^*
Partial resection	251.105 (17.041–3700.168)^†	615281.86 (102.016–3.711^10⁹)^*	253.199 (43.115–1486.938)^†	120.991 (17.383–842.133)^*	42.932 (9.598–192.039)^†	100.392 (11.692–861.985)^*
Radiotherapy
Not received	Reference		Reference		Reference
Received	1.386 (0.279–6.894)		1.1 (0.459–2.636)		1.292 (0.616–2.708)
Chemotherapy
Not received	Reference		Reference		Reference
Received	1.585 (0.318–7.902)		0.748 (0.373–1.503)		2.011 (0.924–4.373)^†

¹The hazard ratio is for each 1-yr increase in age. ²The hazard ratio is for each 1 grade increase in WHO grade. ³The hazard ratio is for each 1 point increase in KPS score. ⁴The hazard ratio is for each 1 point increase in KPS score. ^†The P value of the hazard ratio was less than 0.1 for the univariate Cox models and included in the multivariate Cox model. ^*The hazard ratio was significant (P < 0.05).

View popup

Table 4

Univariate and multivariate cox proportional-hazards models for glioblastomas

Variable	Hazard ratio (95% CI)
	Glioblastoma, IDH-wildtype		Glioblastoma, IDH-mutant
	Univariate	Multivariate	Univariate	Multivariate
Age at diagnosis¹	1.018 (1.007–1.03)^†	1.012 (0.999–1.025)	1.012 (0.985–1.041)
Sex
Female	Reference		Reference
Male	1.052 (0.794–1.393)		1.208 (0.584–2.499)
MGMT
Unmethylated	Reference		Reference
Methylated	0.938 (0.706–1.246)		0.858 (0.424–1.739)
KPS_PRE²	0.987 (0.967–1.007)		0.96 (0.908–1.015)
KPS_POST³	0.962 (0.949–0.975)^†	0.975 (0.959–0.991)^*	0.965 (0.934–0.998)^†
Resection rate
Total resection	Reference	Reference	Reference	Reference
Subtotal resection	2.269 (1.646–3.127)^†	2.074 (1.468–2.929)^*	1.814 (0.804–4.093)	1.771 (0.726–4.319)
Major partial resection	7.259 (4.677–11.267)^†	5.598 (3.469–9.033)^*	30.002 (6.037–149.107)^†	66.577 (9.7–456.942)^*
Partial resection	84.175 (41.344–171.378)^†	76.094 (30.649–188.918)^*	99.335 (20.047–492.219)^†	361.066 (37.041–3519.607)^*
Radiotherapy
Not received	Reference		Reference
Received	0.582 (0.396–0.854)^†		0.771 (0.315–1.888)
Chemotherapy
Not received	Reference	Reference	Reference	Reference
Received	0.297 (0.198–0.447)^†	0.42 (0.271–0.652)^*	0.279 (0.113–0.691)^†	0.309 (0.115–0.829)^*

¹The hazard ratio is for each 1-yr increase in age. ²The hazard ratio is for each 1 point increase in KPS score. ³The hazard ratio is for each 1 point increase in KPS score. ^†The P value of the hazard ratio was less than 0.1 for the univariate Cox models and included in the multivariate Cox model.^*The hazard ratio was significant (P < 0.05).