Dose-surface analysis for prediction of severe acute radio-induced skin toxicity in breast cancer patients

Figures & data

Figure 1. A pictorial representation of the Body dose-surface histogram extraction from the external body shell dose-volume histogram.

Table I. Clinical variables and correlation coefficient (Rs) with RIST incidence.

				Univariate analysis
Characteristics				Rs	p-Value
Continuous variables		Median (range)
Age (years)	N (%)	55 (32–84)		−0.044	0.606
32–45	27 (19.3)
45–55	41 (29.3)
55–65	30 (21.4)
65–75	26 (18.6)
75–85	16 (11.4)
Breast volume (cm^3)		736.8 (141.3–2494.1)		0.088	0.305
Breast skin surface (cm^2)		816.0 (319.0–1718.8)		−0.153	0.103
Categorical variables		N (%)
Smokers
No		96 (68.6)
Yes		44 (31.4)		−0.081	0.344
Chemotherapy
No		67 (47.9)
Yes		73 (52.1)		0.123	0.150
Hormonal therapy
No		20 (14.3)
Yes		120 (85.7)		−0.032	0.711
Supraclavicular beam
No		109 (77.9)
Yes		31 (22.1)		−0.024	0.777
HER-2
No		111 (79.3)
Yes		29 (20.7)		0.049	0.571
Phototype
1		43 (30.7)
2		81 (57.9)
3		16 (11.4)		−0.145	0.480
Psoriasis
No		122 (87.1)
Yes		18 (12.9)		0.363	<0.001
Atopic dermatitis
No		129 (92.1)
Yes		11 (7.9)		−0.087	0.312

Figure 2. (a) Mean cumulative patient DSHs. Red (gray, in black and white print version) lines: patients who developed severe radiation-induced skin toxicity ± SEM (Standard Error of the mean); black lines: patients who did not develop severe radiation-induced skin toxicity ± SEM. (b) Semi-logarithmic plot for the two-sample t-test between surface dose values for the two patient groups (with and without toxicity) at each dose point. The horizontal line represents the significance level of 0.05.

Figure 3. Likelihood estimation values plotted as a function of heart LKB parameters. (a) m and TD₅₀ for a fixed value of n=0.38; (b) TD₅₀ and n for a fixed value of m=0.14; (c) n and m for a fixed value of TD₅₀=39 Gy; (d) NTCP bundle of curves showing 95% confidence interval region for the model fit. The red point corresponds to the optimum LLH. LKB, Lyman-Kutcher-Burman; LLH, log-likelihood; NTCP, normal tissue complication probability; TD₅₀, uniform dose given to the entire organ volume that results in 50% complication probability.

Table II. NTCP models: parameters estimates and 95% confidence intervals of LKB model and best-fit coefficients for logistic model with odds ratios (OR). Performance measures for LKB and logistic NTCP models.

NTCP model						Rs	p-Value	AUC	95% CI
LKB						0.25	<0.001	0.77	0.62–0.92
	Parameter	Estimated value	95% CI
	TD50		39.0	37.1–41.4
	m	0.14	0.10–0.17
	n	0.38	0.31–0.44
Logistic						0.32	0.003	0.84	0.73–0.95
	Parameter	Estimated coefficient	SE	p-Value	OR
	Psoriasis					2.68	0.74	<0.001	14.54
	S30 (%)	0.18	0.08	0.026	1.20
	Constant	−15.54	5.75	0.007

AUC, the area under the receiver operator characteristic curve; LKB, Lyman-Kutcher-Burman; LLH, log-likelihood; NTCP, normal tissue complication probability; Rs, Spearman’s correlation coefficient; SE, standard error; TD₅₀, uniform dose given to the entire organ surface that results in 50% complication probability.

Figure 4. ROC curves for LKB and logistic NTCP models.

Figure 5. Comparison between the actuarial incidence of radiation-related skin toxicity (RIST) in the population and the predicted incidence by LKB and logistic NTCP models. Patients were binned according to the considered NTCP model with an equal number of patients in each bin.