Effects of dexrazoxane on doxorubicin-related cardiotoxicity and second malignant neoplasms in children with osteosarcoma: a report from the Children’s Oncology Group

Kopp, Lisa M.; Womer, Richard B.; Schwartz, Cindy L.; Ebb, David H.; Franco, Vivian I.; Hall, David; Barkauskas, Donald A.; Krailo, Mark D.; Grier, Holcombe E.; Meyers, Paul A.; Wexler, Leonard H.; Marina, Neyssa M.; Janeway, Katherine A.; Gorlick, Richard; Bernstein, Mark L.; Lipshultz, Steven E.

doi:10.1186/s40959-019-0050-9

Table 7 Echocardiographic and NT-proBNP of Patients After METT^a (28 weeks)^b

From: Effects of dexrazoxane on doxorubicin-related cardiotoxicity and second malignant neoplasms in children with osteosarcoma: a report from the Children’s Oncology Group

Variable	LV Fractional Shortening Z-scores	LV End-Diastolic Dimension Z-scores	LV End-Diastolic Posterior Wall Thickness Z-scores	LV Thickness to Dimension Ratio Z-scores	End-Diastolic Septal Thickness Z-scores	LV Mass Z-scores	NT-proBNP^c
Overall	n = 81	n = 78	n = 78	n = 82	n = 70	n = 74	n = 59
	\( \overline{x} \) = − 0.19	\( \overline{x} \) = − 0.49	\( \overline{x} \) = − 0.29	\( \overline{x} \) = − 0.23	\( \overline{x} \) = − 0.84	\( \overline{x} \) = − 0.74	GM = 47.3
	(− 0.54, 0.17)	(− 0.76, − 0.21)	(− 0.60, 0.02)	(− 0.53, 0.07)	(− 1.2, − 0.48)	(− 1.06, − 0.42)	(36.3, 61.6)
	P = 0.30	P < 0.01	P = 0.06	P = 0.13	P < 0.01	P < 0.01	P < 0.01
Sex
Female	n = 32	n = 30	n = 30	n = 33	n = 27	n = 29	n = 28
	\( \overline{x} \) = − 0.46	\( \overline{x} \) = − 0.82	\( \overline{x} \) = − 0.57	\( \overline{x} \) = − 0.29	\( \overline{x} \) = − 1.20	\( \overline{x} \) = − 1.23	GM = 63.2
	(− 1.02, 0.10)	(−1.24, − 0.40)	(− 1.04, − 0.09)	(− 0.75, 0.16)	(−1.76, − 0.64)	(− 1.71, − 0.75)	(43.8, 91.4)
	P = 0.10	P < 0.01	P = 0.02	P = 0.20	P < 0.01	P < 0.01	P = 0.02
Male	n = 49	n = 48	n = 48	n = 49	n = 43	n = 45	n = 31
	\( \overline{x} \) = 0.00	\( \overline{x} \) = − 0.26	\( \overline{x} \) = − 0.10	\( \overline{x} \) = − 0.18	\( \overline{x} \) = − 0.60	\( \overline{x} \) = − 0.39	GM = 36.1
	(− 0.46, 0.47)	(− 0.60, 0.08)	(− 0.50, 0.30)	(− 0.57, 0.21)	(− 1.06, − 0.15)	(−0.80, 0.01)	(25.3, 51.6)
	P = 0.99	P = 0.14	P = 0.63	P = 0.36	P = 0.01	P = 0.06	P < 0.01
Study
AOST0121	n = 8	n = 5	n = 5	n = 9	n = 5	n = 5	n = 15
	\( \overline{x} \) = − 0.70	\( \overline{x} \) = − 0.61	\( \overline{x} \) = − 0.64	\( \overline{x} \) = 0.10	\( \overline{x} \) = −3.82	\( \overline{x} \) = − 0.86	GM = 60.5
	(−2.06, 0.67)	(−1.82, 0.59)	(− 2.06, 0.78)	(−0.97, 1.17)	(−5.05, − 2.59)	(−2.23, 0.50)	(35.0, 104.6)
	P = 0.31	P = 0.31	P = 0.37	P = 0.85	P < 0.01	P = 0.21	P = 0.07
P9754	n = 73	n = 73	n = 73	n = 73	n = 65	n = 69	n = 44
	\( \overline{x} \) = −0.15	\( \overline{x} \) = − 0.48	\( \overline{x} \) = − 0.27	\( \overline{x} \) = − 0.26	\( \overline{x} \) = − 0.63	\( \overline{x} \) = − 0.73	GM = 43.9
	(−0.52, 0.22)	(−0.76, − 0.20)	(−0.59, 0.04)	(− 0.57, 0.05)	(− 0.96, − 0.31)	(− 1.07, − 0.40)	(32.4, 59.3)
	P = 0.43	P < 0.01	P = 0.09	P = 0.10	P < 0.01	P < 0.01	P < 0.01
Assessment Point^d
0 to 37 days	n = 48	n = 48	n = 45	n = 45	n = 40	n = 38	n = 30
	\( \overline{x} \) = −0.18	\( \overline{x} \) = −0.38	\( \overline{x} \) = − 0.40	\( \overline{x} \) = − 0.43	\( \overline{x} \) = − 0.39	\( \overline{x} \) = − 0.67	GM = 32.6
	(−0.72, 0.35)	(−0.75, − 0.01)	(−0.85, 0.05)	(− 0.90, 0.03)	(− 0.80, 0.03)	(− 1.13, − 0.20)	(18.4, 57.7)
	P = 0.49	P = 0.05	P = 0.08	P = 0.06	P = 0.07	P < 0.01	P = 0.01
38 to 81 days	n = 42	n = 40	n = 38	n = 41	n = 36	n = 32	n = 32
	\( \overline{x} \) = −0.13	\( \overline{x} \) = −0.60	\( \overline{x} \) = 0.15	\( \overline{x} \) = 0.15	\( \overline{x} \) = −0.82	\( \overline{x} \) = −0.43	GM = 45.2
	(−0.70, 0.43)	(−1.00, − 0.21)	(−0.33, 0.64)	(− 0.33, 0.63)	(− 1.24, − 0.40)	(−0.93, 0.07)	(26.4, 77.3)
	P = 0.64	P < 0.01	P = 0.53	P = 0.53	P < 0.01	P = 0.09	P = 0.01
> 81 days	n = 39	n = 37	n = 37	n = 40	n = 29	n = 36	n = 34
	\( \overline{x} \) = −0.24	\( \overline{x} \) = −0.51	\( \overline{x} \) = − 0.57	\( \overline{x} \) = − 0.35	\( \overline{x} \) = − 1.46	\( \overline{x} \) = − 1.06	GM = 67.6
	(−0.82, 0.34)	(−0.91, − 0.10)	(− 1.05, − 0.09)	(−0.83, 0.12)	(− 1.91, − 1.02)	(−1.53, − 0.60)	(39.9, 114.5)
	P = 0.41	P = 0.01	P = 0.02	P = 0.14	P < 0.01	P < 0.01	P = 0.11

^aMETT minimal expected treatment time
^bIn the Z-score columns, a Z-score of 0 represents the average value for a healthy child of the same age
^cNT-proBNP is a raw score. Analysis for the NT-proBNP was done using a natural log transformation to better adhere to the normality assumption for regression. The back-transformed NT-proBNP numbers are presented here for ease of interpretability. Due to the back transformations, these represent geometric means (GM). The P-value is from the two-sided hypothesis test with null hypothesis H₀: the population GM is 100
^dAssessment Point is the measure in days after the minimum expected treatment (28 weeks/196 days) and broken up into tertiles based on the 33.3rd and 66.7th percentiles of the assessment points of all measurements. Due to multiple measurements per patient, it is possible for patients to be in multiple tertiles

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