Long-term results of induction chemotherapy for non-operable esophageal squamous cell carcinoma followed by concurrent chemoradiotherapy: a single-centre experience

Figure 1.

Figure 2.

Figure 3.

Figure 4.

Failure pattern [n (%)]

Variables	Before PSM			After PSM
	Without IC (n=199)	With IC (n=72)	p	Without IC (n=71)	With IC (n=71)	p
Local and/or regional
Local only	26 (13.1)	10 (13.9)	0.860	12 (16.9)	10 (14.1)	0.643
Local and regional	2 (1.0)	1 (1.4)	1.000	0 (0)	1 (1.4)	1.000
Regional only	0 (0)	0 (0)	—	0 (0)	0 (0)	—
Total locoregional failure	28 (14.1)	11 (15.3)	0.802	12 (16.9)	11 (15.5)	0.820
Distant
Bone only	3 (1.5)	1 (1.4)	1.000	1 (1.4)	1 (1.4)	1.000
Liver only	7 (3.5)	3 (4.2)	1.000	4 (5.6)	3 (4.2)	1.000
Lung only	17 (8.5)	5 (6.9)	0.670	6 (8.5)	5 (7.0)	0.754
Brain only	1 (0.5)	1 (1.4)	1.000	0 (0)	1 (1.4)	1.000
Multiple locationa	10 (5.0)	6 (8.3)	0.466	4 (5.6)	7 (9.9)	0.346
Other locationb	19 (9.5)	6 (8.3)	0.760	4 (5.6)	5 (7.0)	1.000
Total distant failure	57 (28.6)	22 (30.6)	0.760	19 (26.8)	22 (31.0)	0.579

Baseline characteristics for patients before and after propensity score matching (PSM) [M (QL, QU)/n(%)]

Variables	Before PSM (n = 271)				After PSM (n = 142)
	Total	Without IC (n = 199)	With IC (n = 72)	P	Total	Without IC (n = 71)	With IC (n = 71)	P
Age (year)	61.0 (56.0, 65.0)	61.0 (56.0, 66.0)	61.5 (55.0, 65.0)	0.739	61.5 (56.0, 65.0)	61.0 (57.0, 65.0)	62.0 (55.0, 65.0)	0.923
Total radiotherapy time (day)	43.0 (40.0, 47.0)	43.0 (40.0, 48.0)	42.0 (40.0, 45.8)	0.226	43.0 (40.0, 46.3)	43.0 (39.0, 48.0)	42.0 (40.0, 46.0)	0.361
Age (year)				0.820				0.865
< 60	116 (42.8)	86 (43.2)	30 (41.7)		59 (41.5)	30 (42.3)	29 (40.8)
≥ 60	155 (57.2)	113 (56.8)	42 (58.3)		83 (58.5)	41 (57.7)	42 (59.2)
Gender				0.073				0.285
Female	62 (22.9)	51 (25.6)	11 (15.3)		27 (19.0)	16 (22.5)	11 (15.5)
Male	209 (77.1)	148 (74.4)	61 (84.7)		115 (81.0)	55 (77.5)	60 (84.5)
ECOG PS				<0.001				1.000
0–1	183 (67.5)	148 (74.4)	35 (48.6)		70 (49.3)	35 (49.3)	35 (49.3)
2–3	88 (32.5)	51 (25.6)	37 (51.4)		72 (50.7)	36 (50.7)	36 (50.7)
Tumor Length(cm)				0.540				0.851
< 8	203 (74.9)	151 (75.9)	52 (72.2)		103 (72.5)	52 (73.2)	51 (71.8)
≥ 8	68 (25.1)	48 (24.1)	20 (27.8)		39 (27.5)	19 (26.8)	20 (28.2)
T stage				0.739				0.179
1–2	37 (13.7)	28 (14.1)	9 (12.5)		24 (16.9)	15 (21.1)	9 (12.7)
3–4	234 (86.3)	171 (85.9)	63 (87.5)		118 (83.1)	56 (78.9)	62 (87.3)
N stage				0.181				1.000
0–1	204 (75.3)	154 (77.4)	50 (69.4)		100 (70.4)	50 (70.4)	50 (70.4)
2–3	67 (24.7)	45 (22.6)	22 (30.6)		42 (29.6)	21 (29.6)	21 (29.6)
AJCC stage				0.291				0.411
I–II	61 (22.5)	48 (24.1)	13 (18.1)		30 (21.1)	17 (23.9)	13 (18.3)
III–IV	210 (77.5)	151 (75.9)	59 (81.9)		112 (78.9)	54 (76.1)	58 (81.7)
IC cycles (times)				<0.001				< 0.001
0	199 (73.4)	199 (100.0)	0 (0)		71 (50.0)	71 (100.0)	0 (0)
1/2	56 (20.7)	0 (0)	56 (77.8)		56 (39.4)	0 (0)	56 (78.9)
3/4	16 (5.9)	0 (0)	16 (22.2)		15 (10.6)	0 (0)	15 (21.1)
Response after IC
CR	—	—	0 (0)		—	—	0 (0)
PR	—	—	32 (44.4)		—	—	32 (45.1)
SD	—	—	33 (45.8)		—	—	32 (45.1)
PD	—	—	7 (9.7)		—	—	7 (9.9)

Cox multivariate analysis of overall survival (OS), recurrence-free survival (RFS), and distant metastasis-free survival (DMFS) after propensity score matching (PSM)

Variables	OS		RFS		DMFS
	HR (95% CI)	P	HR (95% CI)	P	HR (95% CI)	P
Total radiotherapy time (day)
< 49	1.000		1.000		1.000
≥ 49	1.762 (1.074–2.891)	0.025	1.920 (1.178–3.131)	0.009	1.827 (1.127–2.961)	0.014
AJCC stage
I–II	1.000		1.000		1.000
III–IV	2.533 (1.305–4.916)	0.006	2.738 (1.413–5.305)	0.003	2.951 (1.560–5.582)	0.001
Age (year)
< 60					1.000
≥ 60					0.592 (0.396–0.886)	0.011

Acute and late toxicities during treatment before and after propensity score matching (PSM) [n (%)]

Toxicities	Before PSM				p	After PSM				p
	Without IC (n=199)		With IC (n=72)			Without IC (n=71)		With IC (n=71)
	Grade 1-2	Grade 3-4	Grade 1-2	Grade 3-4		Grade 1-2	Grade 3-4	Grade 1-2	Grade 3-4
Acute adverse events
Esophagitis	183 (92.0)	6 (3.0)	67 (93.1)	2 (2.8)	0.951	63 (88.7)	3 (4.2)	66 (93.0)	2 (2.8)	0.678
Myelosuppression	109 (54.8)	58 (29.1)	40 (55.6)	19 (26.4)	0.873	37 (52.1)	20 (28.2)	39 (54.9)	19 (26.8)	0.944
Radiation pneumonitis	1 (0.5)	0 (0)	1 (1.4)	0 (0)	1.000	0 (0)	0 (0)	1 (1.4)	0 (0)	1.000
Esophageal fistula	3 (1.5)	0 (0)	0 (0)	0 (0)	0.696	0 (0)	0 (0)	0 (0)	0 (0)	—
Late adverse events
Esophageal stricture	92 (46.2)	3 (1.5)	29 (40.3)	3 (4.2)	0.364	29 (40.8)	1 (1.4)	28 (39.4)	3 (4.2)	0.584

Univariate Cox analysis of overall survival (OS), recurrence-free survival (RFS), and distant metastasis-free survival (DMFS) after propensity score matching (PSM)

Variables	OS		RFS		DMFS
	HR (95% CI)	P	HR (95% CI)	P	HR (95% CI)	P
Age (year)	0.986 (0.958–1.014)	0.324	0.985 (0.957–1.014)	0.306	0.981 (0.954–1.008)	0.161
Total radiotherapy time (day)	1.018(1.001–1.034)	0.032	1.015(1.000–1.031)	0.051	1.016(1.001–1.031)	0.039
Age (year)
< 60	1.000		1.000		1.000
≥ 60	0.749 (0.498–1.128)	0.167	0.794 (0.530–1.191)	0.265	0.682 (0.459–1.015)	0.059
Gender
Female	1.000		1.000		1.000
Male	1.566 (0.886–2.766)	0.122	1.511 (0.870–2.624)	0.143	1.808 (1.026–3.186)	0.040
ECOG PS
0–1	1.000		1.000		1.000
2–3	1.058 (0.701–1.596)	0.788	1.121 (0.747–1.682)	0.580	1.125 (0.755–1.675)	0.564
Tumor Length(cm)
< 8	1.000		1.000		1.000
≥ 8	1.481 (0.954–2.301)	0.080	1.651 (1.068–2.553)	0.024	1.510 (0.985–2.314)	0.059
Total radiotherapy time (day)
< 49	1.000		1.000		1.000
≥ 49	2.018 (1.234–3.300)	0.005	2.203 (1.354–3.583)	0.001	2.016 (1.249–3.255)	0.004
T stage
1–2	1.000		1.000		1.000
3–4	2.938 (1.421–6.075)	0.004	3.162 (1.530–6.536)	0.002	2.984 (1.501–5.932)	0.002
N stage
0–1	1.000		1.000		1.000
2–3	1.150 (0.744–1.779)	0.529	1.227 (0.798–1.886)	0.352	1.262 (0.827–1.926)	0.280
AJCC stage
I–II	1.000		1.000		1.000
III–IV	2.751 (1.426–5.307)	0.003	2.983 (1.548–5.752)	0.001	2.940 (1.568–5.511)	0.001
IC cycles (times)
0	1.000		1.000		1.000
1/2	0.935 (0.609–1.435)	0.759	0.835 (0.546–1.275)	0.403	0.921 (0.606–1.399)	0.699
3/4	0.509 (0.230–1.127)	0.096	0.458 (0.207–1.012)	0.054	0.725 (0.356–1.475)	0.374