Predictors of grade ≥ 2 and grade ≥ 3 radiation pneumonitis in patients with locally advanced non-small cell lung cancer treated with three-dimensional conformal radiotherapy

Figures & data

Table I. Principal component analysis of DVH parameters.

LDVH parameters				HDVH parameters
Component	Total	Percentage of variance	Cumulative percentage	Component	Total	Percentage of variance	Cumulative percentage
1(LV30-LV50)	8.39	83.89	83.89	1(HV5-HV25)	7.46	74.60	74.60
2(LV5-LV25)	1.09	10.85	94.74	2(HV30-HV50)	1.77	17.72	92.32

HDVH and LDVH, dose-volume histogram of heart and lung, respectively; LVx and HVx, percentage of total normal heart or lung volume receiving at least x Gy of radiation.

Table II. Univariate analysis of patient demographic and tumor characteristics and dose-volume factors, by RP grade (N = 176).

Factors	RP0-1 (n = 107)	RP ≥ 2 (n = 69)	p-value	RP0-2 (n = 155)	RP ≥ 3 (n = 21)	p-value
Age (≥ 70/＜70)	36/71	29 (44.6%)/40 (36.0%)	0.261	53/102	12 (18.5%)/9 (8.1%)	0.041
Sex (Male/Female)	74/33	48 (39.3%)/21 (38.9%)	0.954	111/44	11 (9.0%)/10 (18.5%)	0.073
COPD history (Y/N)	17/90	5 (22.7%)/64 (41.6%)	0.091	20/135	2 (9.1%)/19 (12.3%)	0.660
Smoking history (Y/N)	66/41	39 (37.1%)/30 (42.3%)	0.496	94/61	11 (10.5%)/10 (14.1%)	0.469
Chemotherapy (Y/N)	73/34	52 (41.6%)/17 (33.3%)	0.922	107/48	18 (14.4%)/3 (5.9%)	0.308
Tumor position
Upper/Lower	69/38	38 (35.5%)/31 (44.9%)	0.212	97/58	10 (9.3%)/11 (15.9%)	0.188
Left/Right	50/57	41 (45.1%)/28 (32.9%)	0.100	77/78	14 (15.4%)/7 (8.2%)	0.144
LDVH-CV	2.47 ± 0.66	2.30 ± 0.74	< 0.001	2.68 ± 0.74	3.64 ± 0.73	< 0.001
HDVH-CV	2.59 ± 1.48	3.53 ± 1.41	< 0.001	2.81 ± 1.51	4.04 ± 1.06	< 0.001
MLD	14.36 ± 3.15	19.43 ± 4.02	< 0.001	15.64 ± 3.88	21.60 ± 3.59	< 0.001
MHD	16.00 ± 7.71	21.34 ± 6.68	< 0.001	17.38 ± 7.87	23.34 ± 4.09	< 0.001
PTV/Lung	0.09 ± 0.04	0.15 ± 0.05	< 0.001	0.11 ± 0.05	0.16 ± 0.05	< 0.001

COPD, chronic obstructive pulmonary disease; HDVH and LDVH, dose-volume histogram comprehensive value of heart and lung, respectively; MHD, mean heart dose; MLD, mean lung dose; PTV/Lung, ratio of planning target volume and total lung volume; RP, radiation pneumonitis.

Table III. Multivariate logistic regression analysis of factors associated with RP.

Variable	RP grade ≥ 2			RP grade ≥ 3
	OR	95% CI	p-value	OR	95% CI	p-value
Age (≥ 70/＜70 years)	2.99	1.25～7.17	0.014	11.46	2.86～45.88	0.001
Sex (Male/Female)	0.32	0.11～0.88	0.028
Chemotherapy (Yes/No)				5.38	1.18～24.55	0.030
MLD	1.32	1.13～1.52	< 0.001	1.55	1.31～1.85	< 0.001
PTV/Lung	3E + 011	426632.30～2E + 017	< 0.001

CI, confidence interval; MLD, mean lung dose; OR, odds ratio; PTV/Lung, ratio of planning target volume to total lung volume; RP, radiation pneumonitis.

Table IV. RP-related dose-volume variables in patients with grade ≥ 2 or grade ≥ 3 RP, corrected for age.

Variable	RP grade ≥ 2 (n = 69)			RP grade ≥ 3 (n = 21)
	Age ≥ 70 years (n = 29)	Age < 70 years (n = 40)	p-value	Age ≥ 70 years (n = 12)	Age < 70 years (n = 9)	p-value
LDVH-CV	3.35 ± 0.77	3.26 ± 0.73	0.622	3.58 ± 0.70	3.71 ± 0.80	0.702
HDVH-CV	3.90 ± 1.22	3.26 ± 1.48	0.059	4.16 ± 0.77	3.87 ± 1.40	0.540
MLD	18.24 ± 3.38	20.30 ± 4.27	0.035	19.35 ± 2.38	24.60 ± 2.60	< 0.001
MHD	21.28 ± 6.75	21.38 ± 6.71	0.950	22.34 ± 3.54	24.67 ± 4.60	0.204
PTV/Lung	0.13 ± 0.04	0.17 ± 0.05	0.007	0.14 ± 0.03	0.19 ± 0.07	0.021

HDVH-CV and LDVH-CV, dose-volume histogram comprehensive value of heart and lung, respectively; MHD, mean heart dose; MLD, mean lung dose; PTV/Lung, ratio of planning target volume to total lung volume; RP, radiation pneumonitis.

Table V. Comparison of RP rate by cut point of dose-volume variables (age ≥ 70) (n = 65).

Cut points	RP0-1	RP ≥ 2	p-value	Cut points	RP0-2	RP ≥ 3	p-value
MLD＞16.06	8	23 (35.4%)	< 0.001	MLD＞16.06	19	12 (18.5%)	< 0.001
MLD＜16.06	28	6 (9.2%)		MLD＜16.06	34	0 (0%)
PTV/Lung＞0.111	9	21 (32.3%)	< 0.001	PTV/Lung＞0.119	15	9 (13.8%)	0.002
PTV/Lung＜0.111	27	8 (12.3%)		PTV/Lung＜0.119	38	3 (4.6%)

Table VI. Comparison of RP rate by cut point of dose-volume variables (age＜70) (n = 111).

Cut points	RP0-1	RP ≥ 2	p-value	Cut points	RP0-2	RP ≥ 3	p-value
MLD＞15.71	20	36 (32.4%)	< 0.001	MLD＞22.71	4	8 (7.2%)	< 0.001
MLD＜15.71	51	4 (3.6%)		MLD＜22.71	98	1 (0.9%)
PTV/Lung＞0.109	16	37 (33.3%)	< 0.001	PTV/Lung＞0.157	17	9 (8.1%)	< 0.001
PTV/Lung＜0.109	55	3 (2.7%)		PTV/Lung＜0.157	85	0 (0%)

MLD, mean lung dose; PTV/Lung, ratio of planning target volume to total lung volume; RP, radiation pneumonitis.

Table VII. Study comparison of RP.

Reference	Scoring method	RP grade	Predictive factor
Barriger [4]	CTC v3.0	≥ 2	MLD, chemotherapy
Parashar [7]	RTOG	≥ 2	Age, chemotherapy
Dang [9]	CTC v3.0	≥ 2	Sex, chemotherapy
Jin [10]	CTC v3.0	≥ 2	Tobacco use, V20, V25, V35, V50
Fay [3]	CTC v2.0	≥ 2	MLD, V30
Shi [6]	CTC v3.0	≥ 3	NTCP, V10
Kimura [2]	CTC v3.0	≥ 3	V20, pulmonary emphysema
Wang [1]	CTC v3.0	≥ 3	V5
Kim [5]	RTOG	≥ 3	MLD
Robnett [8]	RTOG	≥ 3	Performance status, FEV1

CTC, Common Toxicity Criteria; FEV1, forced expiratory volume in 1 second; MLD, mean lung dose; NTCP, normal tissue complication probability; RTOG, Radiation Therapy Oncology Group; Vx, percentage of total normal lung volume.

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