. 2022 Jan 28;4(1):vdac007. doi: 10.1093/noajnl/vdac007

Table 2.

Clinical Trials and Retrospective Studies Underlying the Current Standard of Oncological Treatment of Elderly Glioblastoma Patients

Age (Years)	PS	Radiation Dose (Gy)/Fractions	Number of Patients	Chemotherapy	MGMT Methylation	Median Survival (Months)	Study	Note
≤70	0–2	60/30	286	TMZ	All	14.6	Stupp et al., 2005^4,13 and Hegi et al., 2005⁵ (Phase 3 trial)	Established adjuvant RT60/30 with concurrent and adjuvant TMZ as standard of care. Established the survival benefit of TMZ in MGMT positive patients. 170 of the 573 patients were aged 61–70 years. In this older subset of patients, mOS using the combined-modality approach compared to radiation therapy alone was similar (mOS 10.9 vs 11.8 months)¹³.
					Positive	21.7
					Negative	12.7
			287	No TMZ	All	12.1
					Positive	15.3
					Negative	11.1
≥60	0–3	60/30	51	No TMZ		5.1	Roa et al., 2004²⁷ (Phase 3 trial)	RT40/15 was noninferior to RT60/30, P = 0.57.
		40/15	49			5.6
All	0–3^a	60/30	100	No TMZ		6.0	Nordic Phase 3 trial²²	In patients > 70 years RT60/30 was inferior to RT34/10, P = 0.02.
		34/10	98	No TMZ		7.5
		No RT	93	TMZ		8.3
60–70	0–3^a	60/30	59	No TMZ		7.6
		34/10	58	No TMZ		8.8
		No RT	51	TMZ		7.9
≥70	0–3^a	60/30	41	No TMZ		5.2
		34/10	40	No TMZ		7.0
		No RT	42	TMZ		9.0
≥65	0–3	60/30	178	No TMZ	All	9.6	NOA-08 Phase 3 trial²³	Dose-dense TMZ alone was noninferior to standard radiotherapy in elderly patients with malignant astrocytoma, P = 0.028.
					Positive	9.6
					Negative	10.4
		No RT	195	TMZ	All	8.6
					Positive	Not reached
					Negative	7.0
≥65	0–2	40/15	281	TMZ	All	9.3	Perry et al., 2017 Phase 3 trial¹⁴	The addition of TMZ to RT40/15 is associated with longer survival than RT40/15 alone P < .001). The survival benefit of TMZ was greater in MGMT-methylated compared to unmethylated patients (P < .001) but a clinically meaningful survival benefit of TMZ was also detected in MGMT-unmethylated patients albeit it did not reach statistical significance(P = .055).
					Positive	13.5
					Negative	10.0
			281	No TMZ	All	7.6
					Positive	7.7
					Negative	7.9
≥70	<3	60/30	92	No TMZ		7.5-9.5	McAleese et al., 2003 (retrospective case-control study)²⁸	Despite providing a lesser survival benefit than radical RT, hypofractionated RT is better tolerated in patients with low PS.
		30/6	92	No TMZ		5.1
≥65	<3	50/30	29	No TMZ		10	Bauman et al., 1994 (prospective case-control study)²⁹	Short course palliative RT is associated with improved survival compared to best supportive care.
		30/10	29	No TMZ		6
		No RT	29	No TMZ		1

^aChemoradiation regimes not stratified for PS. 33 patients had PS 0–1 and 9 patients PS 2–3 (of these, 7 patients were PS = 3 due to neurological impairments only.