Table I. Association of treatment characteristics with EFS.

Treatment characteristic	Subgroup	N studies	5-yr EFS of reference group (95% CI) and absolute rate differences of comparison subgroups (95% CI)	Omnibus p-value	Adjusteda 5-yr EFS of reference group (95% CI) and absolute rate differences of comparison subgroups (95% CI)	Omnibus p-value
CRT	CRT for all (reference)	43	63 (59, 68)	0.08	65 (61,69)	0.02
	Risk-directed CRT	21	-3 (-11, 5)		-9 (-15, -2)
	CNS + only	7	-6 (-18, 7)		-3 (-14, 7)
	No CRT	7	12 (1, 24)		5 (-4, 15)
IT chemotherapy	MTX (reference)	39	63 (58, 68)	0.89	65 (61, 69)	0.11
	TIT	38	0 (-1, 1)		-5(-11, 1)
Total doses of IT	0-9 (reference)	18	52 (45, 59)	<0.001	56 (49, 64)	0.16
	10-19	34	14 (6, 22)		8 (-1, 17)
	>=20	16	18 (8, 27)		10 (-1, 21)
HD Methotrexate	No HD MTX (reference)	24	58 (52,64)	0.045	61 (55, 66)	0.40
	HD MTX	45	8 (0, 15)		3 (-4, 10)
Asparaginase	<400,000 IU (reference)	52	60 (56, 65)	0.006	60 (57, 64)	0.007
	>=400,000 IU or PEG	15	12 (4, 20)		10 (3, 17)
Anthracycline	<300 mg/m2(reference)	46	64 (59, 68)	0.97	62 (58, 65)	0.14
	>=300 mg/m2	20	0 (-8, 8)		5 (-2, 12)
Induction steroid	prednisone (reference)	70	63 (59, 66)	0.54	63 (60, 66)	0.49
	dexamethasone	4	2 (-14, 19)		-9 (-24, 6)
	randomized	3	9 (-7, 25)		-2 (-16, 12)
EFS definition	includes induction failures (reference)	57	61 (57, 65)	0.06	61 (58, 65)	0.07
	excludes induction failures	7	14 (1, 26)		12 (2,23)
	definition not reported	14	5 (-3, 14)		1 (-6, 9)
Enrollment year	per 5 years		6 (4, 9)	<0.001	N/A	N/A
Asparaginase	per 100,000 IU/m2		3 (1, 5)	<0.001	2 (1, 4)	0.004
HD Methotrexate	per 5 grams/m2		1 (-1, 3)	0.20	1 (-1, 2)	0.33
Anthracycline	per 100 mg/m2		0 (-4, 3)	0.77	2 (-1, 4)	0.27

^aAdjusted for enrollment start year.

EFS= event-free survival;CRT=cranial irradiation therapy; IT = intrathecal; HD = high dose; PEG = polyethylene glycosylated asparaginase.