Radiobiological evaluation of simultaneously dose-escalated versus non-escalated intensity-modulated radiation therapy for patients with upper thoracic esophageal cancer

Figures & data

Table 1 Characteristics of 25 patients with UTEC

Patients	Gender	Age	Stage*	GTV (cc)	PTV64.8 (cc)	PTV50.4 (cc)
1	M	53	T3N1M0	25.4	75.0	191.6
2	M	64	T3N1M1	38.8	102.1	253.3
3	M	49	T3N1M0	16.9	47.8	196.4
4	M	64	T3N0M0	16.1	45.5	161.9
5	M	55	T3N1M0	22.5	70.3	180.0
6	M	73	T2N0M0	13.8	38.3	168.2
7	M	61	T3N1M0	11.3	34.1	158.9
8	M	59	T2N1M0	22.4	58.5	174.7
9	M	61	T4N0M1	61.9	126.5	325.2
10	M	59	T3N1M0	13.3	46.3	160.2
11	M	56	T4N1M0	21.7	62.1	199.4
12	F	53	T2N0M0	8.4	27.9	110.5
13	M	60	T4N1M0	23.5	70.7	178.4
14	M	64	T3N1M0	20.8	60.4	200.7
15	M	72	T3N0M0	21.8	56.2	162.8
16	M	66	T4N0M0	67.0	137.1	359.2
17	M	59	T4N0M0	38.3	85.9	233.7
18	M	59	T3N1M0	11.9	146.2	35.9
19	M	51	T3N1M0	32.4	222.7	174.6
20	M	67	T3N0M0	44.1	267.8	98.9
21	F	67	T2N1M1	14.3	224.4	98.4
22	F	65	T3N0M0	14.9	135.9	83.3
23	M	69	T2N1M0	7.0	104.5	32.8
24	M	61	T3N1M0	36.8	299.6	95.0
25	M	66	T2N1M0	22.4	216	57.8

Note:

* According to American Joint Committee on Cancer (AJCC), 6th edition.

Abbreviations: UTEC, upper thoracic esophageal cancer; GTV, gross tumor volume; PTV, planning target volume; M, male; F, female.

Figure 1 DVH of the GTV, lung, spinal cord, and esophagus.

Notes: (A) DVH of GTV; (B) DVH of lung; (C) DVH of spinal cord; (D) DVH of esophagus.
Abbreviations: DVH, dose volume histogram; GTV, gross tumor volume; DE-IMRT, dose-escalated intensity-modulated radiation therapy; NE-IMRT, non-escalated intensity-modulated radiation therapy.

Figure 2 Dose distributions in the transversal, coronal, and sagittal views from one representative case.

Notes: (A) NE-IMRT; (B) DE-IMRT. The dark green line represents PTV50.4, the red line represents PTV64.8, and the orange line represents GTV.
Abbreviations: PTV, planning target volume; GTV, gross tumor volume; DE-IMRT, dose-escalated intensity-modulated radiation therapy; NE-IMRT, non-escalated intensity-modulated radiation therapy.

Table 2 Physical dose difference between the DE-IMRT and NE-IMRT plans

Structures	Parameter	DE-IMRT	NE-IMRT	P-value
GTV	Dmean (Gy)	65.9±0.3	51.3±0.3	<0.001
	V10 (%)	23.4±7.0	22.4±6.8	<0.001
Lung	V20 (%)	11.4±4.3	10.1±4.1	0.002
	MLD (Gy)	6.5±1.8	6.1±1.7	<0.001
Spinal cord	Dmax (Gy)	39.2±3.2	37.2±3.2	<0.001
	V30 (%)	64.7±11.7	64.6±11.6	0.852
	V40 (%)	63.8±11.6	63.7±11.6	0.200
	V50 (%)	62.2±11.7	62.1±11.7	0.058
Esophagus	V60 (%)	48.1±13.5	0.0±0.0	<0.001
	Dmean (Gy)	41.2±7.9	33.8±5.9	<0.001
	Dmax (Gy)	66.8±0.4	52.6±0.7	<0.001

Notes: P-value was shown for the dosimetric differences between the DE-IMRT and NE-IMRT techniques. P<0.05 was identified as statistically significant.

Abbreviations: DE-IMRT, dose-escalated intensity-modulated radiation therapy; NE-IMRT, non-escalated intensity-modulated radiation therapy; GTV, gross tumor volume; MLD, mean lung dose; D_mean, mean dose; D_max, maximum dose; V_x, percentage of the target volume receiving ≥ x Gy.

Table 3 Prediction of tumor control and toxicities in the DE-IMRT and NE-IMRT plans

Structures	Model	DE-IMRT	NE-IMRT	P-value
Tumor	Geh (%)a	67.6±12.2	35.8±13.0	<0.001
	WN (%)a	91.6±1.6	52.5±5.5	<0.001
	EUD (%)a	95.1±0.2	54.2±1.4	<0.001
Lung	LKB (%)b	3.9±1.0	3.6±0.9	<0.001
Spinal cord	LKB (%)c	(7.2±5.5)×10^−2	(4.2±3.2)×10^−2	<0.001
	Kwint (%)d	75.6±5.8	73.1±6.1	<0.001
	Kwint (%)e	38.2±8.6	34.4±8.3	<0.001
Esophagus	Wijsman (%)f	64.7±13.9	49.8±11.1	<0.001
	Chen (%)g	(2.2±2.9)×10^−1	(1.7±1.8)×10^−23	<0.001

Notes:

a Indicates TCP models for predicting tumor local control;

b indicates LKB model for predicting grade ≥2 radiation pneumonitis;

c indicates LKB model for predicting radiation-induced myelitis/necrosis;

d indicates Kwint model for predicting grade ≥2 acute esophageal toxicity;

e indicates Kwint model for predicting grade ≥3 acute esophageal toxicity;

f indicates Wijsman model for predicting grade ≥2 acute esophageal toxicity;

g indicates Chen model for predicting late esophageal toxicity. P-value was shown for the tumor control and toxicity differences between the DE-IMRT and NE-IMRT techniques. P<0.05 was identified as statistically significant.

Abbreviations: DE-IMRT, dose-escalated intensity-modulated radiation therapy; NE-IMRT, non-escalated intensity-modulated radiation therapy; TCP, tumor control probability; Geh, Geh model; WN, Webb-Nahum model; EUD, equivalent uniform dose model; LKB, Lyman-Kutcher-Burman model; Kwint, Kwint model; Wijsman, Wijsman model; Chen, Chen model.