Impact of target volume delineation accuracy on locoregional control and survival after postoperative radiotherapy for colorectal cancer

Table 1 Comparison of clinicopathological characteristics between the two groups, n (%)

Characteristic	Accurate target volume group (n = 126)	Inaccurate target volume group (n = 92)	χ2/Z value	P value
Gender			0.428	0.513
Male	78 (61.9)	54 (58.7)
Female	48 (38.1)	38 (41.3)
Age			0.195	0.659
≤ 60 years	68 (54.0)	52 (56.5)
> 60 years	58 (46.0)	40 (43.5)
Age [years, M (range)]	58 (32-78)	60 (35-77)	-0.864	0.388
ECOG score			1.203	0.548
Score 0	52 (41.3)	34 (37.0)
Score 1	62 (49.2)	48 (52.2)
Score 2	12 (9.5)	10 (10.9)
Primary tumor location			0.015	0.903
Rectum	76 (60.3)	56 (60.9)
Colon	50 (39.7)	36 (39.1)
Pathological type			0.003	0.958
Adenocarcinoma	118 (93.7)	86 (93.5)
Mucinous adenocarcinoma	8 (6.3)	6 (6.5)
Pathological differentiation			0.782	0.676
Well differentiated	18 (14.3)	10 (10.9)
Moderately differentiated	86 (68.3)	66 (71.7)
Poorly differentiated	22 (17.5)	16 (17.4)
pT stage			0.621	0.431
T3	94 (74.6)	65 (70.7)
T4	32 (25.4)	27 (29.3)
pN stage			1.847	0.397
N0	38 (30.2)	24 (26.1)
N1	58 (46.0)	38 (41.3)
N2	30 (23.8)	30 (32.6)
Vascular invasion			0.127	0.722
No	84 (66.7)	59 (64.1)
Yes	42 (33.3)	33 (35.9)
Neural invasion			0.009	0.924
No	98 (77.8)	71 (77.2)
Yes	28 (22.2)	21 (22.8)
Margin status			0.583	0.445
Negative	112 (88.9)	78 (84.8)
Positive or close	14 (11.1)	14 (15.2)
Preoperative CEA level			0.152	0.697
Normal	78 (61.9)	54 (58.7)
Elevated	48 (38.1)	38 (41.3)
Preoperative CA19-9 level			0.341	0.559
Normal	94 (74.6)	65 (70.7)
Elevated	32 (25.4)	27 (29.3)
Surgical approach			0.098	0.754
Open	46 (36.5)	32 (34.8)
Laparoscopic	80 (63.5)	60 (65.2)
Neoadjuvant therapy			0.218	0.641
No	98 (77.8)	74 (80.4)
Yes	28 (22.2)	18 (19.6)
Concurrent chemotherapy regimen			0.446	0.504
mFOLFOX6	88 (69.8)	61 (66.3)
Single-agent capecitabine	38 (30.2)	31 (33.7)
Number of chemotherapy cycles			0.528	0.768
≤ 4 cycles	26 (20.6)	21 (22.8)
4-6 cycles	82 (65.1)	58 (63.0)
> 6 cycles	18 (14.3)	13 (14.1)

CEA: Carcinoembryonic antigen; CA19-9: Carbohydrate antigen 19-9; ECOG: Eastern Cooperative Oncology Group.

Table 2 Comparison of survival outcomes between the two groups, n (%)

Survival indicator	Accurate target volume group (n = 126)	Inaccurate target volume group (n = 92)	χ2 value	P value
3-year local control rate (95%CI)	92.1 (87.2-97.0)	78.3 (69.8-86.8)	8.742	0.003
3-year regional control rate (95%CI)	94.4 (90.1-98.7)	81.5 (73.5-89.5)	9.328	0.002
3-year disease-free survival rate (95%CI)	83.6 (77.1-90.1)	66.8 (57.2-76.4)	10.156	0.001
3-year overall survival rate (95%CI)	89.2 (83.6-94.8)	72.5 (63.4-81.6)	11.483	< 0.001

CI: Confidence interval.

Table 3 Comparison of recurrence patterns between the two groups, n (%)

Recurrence pattern	Accurate target volume group (n = 23)	Inaccurate target volume group (n = 33)	χ2 value1	P value
In-field recurrence	15 (65.2)	8 (24.2)	10.236	0.006
Marginal recurrence	5 (21.7)	14 (42.4)
Out-of-field recurrence	3 (13.0)	11 (33.3)

¹χ² test was used for overall comparison (df = 2).

Table 4 Univariate analysis of factors affecting disease-free survival

Factor	HR	95%CI	P value
Gender (male vs female)	1.153	0.682-1.950	0.596
Age (> 60 years vs ≤ 60 years)	1.284	0.768-2.146	0.339
ECOG score (2 vs 0-1)	1.562	0.785-3.107	0.204
Tumor location (colon vs rectum)	0.894	0.524-1.524	0.681
Differentiation (poor vs moderate-well)	1.418	0.757-2.656	0.275
pT stage (T4 vs T3)a	1.856	1.126-3.059	0.015a
pN stage (N2 vs N0-1)a	1.924	1.187-3.118	0.008a
Lymph node metastasis (N+ vs N0)a	1.832	1.145-2.930	0.012a
Vascular invasion (yes vs no)	1.473	0.886-2.449	0.136
Neural invasion (yes vs no)a	1.726	1.041-2.863	0.034a
Margin status (positive vs negative)a	2.168	1.243-3.781	0.006a
Preoperative CEA (elevated vs normal)a	1.628	1.021-2.596	0.041a
Preoperative CA19-9 (elevated vs normal)	1.384	0.824-2.323	0.218
Surgical approach (laparoscopic vs open)	0.823	0.495-1.368	0.452
Neoadjuvant therapy (yes vs no)	0.765	0.413-1.418	0.398
Chemotherapy regimen (single vs combination)	1.245	0.735-2.109	0.415
Target delineation (inaccurate vs accurate)a	2.254	1.356-3.746	0.002a

^aP < 0.10, included in multivariate analysis.

HR: Hazard ratio; CI: Confidence interval; CEA: Carcinoembryonic antigen; CA19-9: Carbohydrate antigen 19-9; ECOG: Eastern Cooperative Oncology Group.

Table 5 Multivariate analysis of factors affecting disease-free survival

Factor	HR	95%CI	P value
Target delineation (inaccurate vs accurate)	2.186	1.304-3.665	0.003
pT stage (T4 vs T3)	1.524	0.914-2.541	0.105
pN stage (N2 vs N0-1)	1.782	1.089-2.915	0.021
Lymph node metastasis (N+ vs N0)	1.386	0.832-2.308	0.21
Neural invasion (yes vs no)	1.448	0.864-2.427	0.16
Margin status (positive vs negative)	1.928	1.095-3.396	0.023
Preoperative CEA (elevated vs normal)	1.396	0.871-2.238	0.166

HR: Hazard ratio; CI: Confidence interval; CEA: Carcinoembryonic antigen.

Table 6 Univariate analysis of factors affecting overall survival

Factor	HR	95%CI	P value
Gender (male vs female)	1.268	0.698-2.304	0.436
Age (> 60 years vs ≤ 60 years)	1.395	0.774-2.516	0.268
ECOG score (2 vs 0-1)	1.684	0.782-3.626	0.182
Tumor location (colon vs rectum)	0.856	0.465-1.576	0.619
Differentiation (poor vs moderate-well)	1.538	0.762-3.104	0.229
pT stage (T4 vs T3)a	1.982	1.096-3.584	0.023a
pN stage (N2 vs N0-1)a	2.156	1.268-3.666	0.004a
Lymph node metastasis (N+ vs N0)a	2.034	1.205-3.434	0.008a
Vascular invasion (yes vs no)a	1.658	0.928-2.964	0.089a
Neural invasion (yes vs no)a	1.812	1.022-3.213	0.042a
Margin status (positive vs negative)a	2.486	1.352-4.572	0.003a
Preoperative CEA (elevated vs normal)a	1.746	1.036-2.944	0.036a
Preoperative CA19-9 (elevated vs normal)	1.462	0.802-2.665	0.214
Surgical approach (laparoscopic vs open)	0.795	0.444-1.424	0.442
Neoadjuvant therapy (yes vs no)	0.728	0.362-1.465	0.374
Chemotherapy regimen (single vs combination)	1.318	0.725-2.397	0.364
Target delineation (inaccurate vs accurate)a	2.542	1.426-4.532	0.001a

^aP < 0.10, included in multivariate analysis.

HR: Hazard ratio; CI: Confidence interval; CEA: Carcinoembryonic antigen; CA19-9: Carbohydrate antigen 19-9; ECOG: Eastern Cooperative Oncology Group.

Table 7 Multivariate analysis of factors affecting overall survival

Factor	HR	95%CI	P value
Target delineation (inaccurate vs accurate)	2.398	1.334-4.311	0.004
pT stage (T4 vs T3)	1.586	0.872-2.885	0.132
pN stage (N2 vs N0-1)	1.946	1.132-3.345	0.016
Lymph node metastasis (N+ vs N0)	1.468	0.842-2.560	0.176
Vascular invasion (yes vs no)	1.324	0.736-2.382	0.348
Neural invasion (yes vs no)	1.512	0.846-2.702	0.162
Margin status (positive vs negative)	2.154	1.156-4.013	0.016
Preoperative CEA (elevated vs normal)	1.448	0.852-2.461	0.171

CEA: Carcinoembryonic antigen.

Table 8 Comparison of adverse events between two groups, n (%)

Adverse event	Accurate target volume group (n = 126)	Inaccurate target volume group (n = 92)	χ2 value	P value
Acute adverse events
Grade 1-2 gastrointestinal reactions	94 (74.6)	72 (78.3)	0.424	0.515
Grade 3-4 gastrointestinal reactions	12 (9.5)	10 (10.9)	0.118	0.731
Grade 1-2 hematologic toxicity	68 (54.0)	54 (58.7)	0.491	0.484
Grade 3-4 hematologic toxicity	7 (5.6)	6 (6.5)	0.083	0.773
Grade 1-2 urinary system reactions	32 (25.4)	26 (28.3)	0.23	0.632
Grade 3-4 urinary system reactions	2 (1.6)	3 (3.3)	0.678	0.41
Grade 1-2 skin reactions	28 (22.2)	24 (26.1)	0.449	0.503
Grade 3-4 skin reactions	1 (0.8)	2 (2.2)	0.799	0.371
Any grade 3-4 acute adverse events1	19 (15.1)	16 (17.4)	0.215	0.643
Late adverse events
Grade ≥ 2 intestinal adverse events	11 (8.7)	17 (18.5)	4.554	0.033
Grade ≥ 2 urinary system adverse events	6 (4.8)	8 (8.7)	1.464	0.226
Intestinal obstruction	3 (2.4)	6 (6.5)	2.245	0.134

¹Any grade 3-4 acute adverse events refer to the total number of patients experiencing any grade 3-4 toxic reaction. In the accurate target volume group, 3 patients experienced two types of grade 3-4 toxicities simultaneously; in the inaccurate target volume group, 5 patients experienced two types of grade 3-4 toxicities simultaneously.