Beyond the tumor region: Peritumoral radiomics enhances prognostic accuracy in locally advanced rectal cancer

doi:10.3748/wjg.v31.i8.99036

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World Journal of Gastroenterology

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World J Gastroenterol. Feb 28, 2025; 31(8): 99036
Published online Feb 28, 2025. doi: 10.3748/wjg.v31.i8.99036

Table 1 Clinicoradiological characteristics of patients, n (%)

Variable	Total (n = 409)	Training (n = 273)	Validation (n = 136)	¹P value
Age (years), median (IQR)	56 (49-64)	58 (49-64)	56 (47-64)	0.219
Sex				> 0.999
Male	276 (67.5)	184 (67.4)	92 (67.6)
Female	133 (32.5)	89 (32.6)	44 (32.4)
BMI				0.351
< 18.5	45 (11.0)	31 (11.4)	14 (10.3)
18.5-24	178 (43.5)	112 (41.0)	66 (48.5)
> 24	186 (45.5)	130 (47.6)	56 (41.2)
CEA level (ng/mL)				0.625
< 5	222 (54.3)	151 (55.3)	71 (52.2)
≥ 5	187 (45.7)	122 (44.7)	65 (47.8)
CA199 level (U/mL)				0.695
< 35	282 (68.9)	186 (68.1)	96 (70.6)
≥ 35	127 (31.1)	87 (31.9)	40 (29.4)
NCRT regimen				0.952
Capecitabine + RT	173 (42.3)	114 (41.8)	59 (43.4)
CapeOx + RT	230 (56.2)	155 (56.8)	75 (55.1)
Other	6 (1.5)	4 (1.5)	2 (1.5)
Adjuvant chemotherapy				> 0.999
No	104 (25.4)	69 (25.3)	35 (25.7)
Yes	305 (74.6)	204 (74.7)	101 (74.3)
Clinical T stage				0.914
cT2	29 (7.1)	20 (7.3)	9 (6.6)
cT3	253 (61.9)	167 (61.2)	86 (63.2)
cT4	127 (31.1)	86 (31.5)	41 (30.1)
Clinical N stage				0.446
cN0	65 (15.9)	45 (16.5)	20 (14.7)
cN1	192 (46.9)	125 (45.8)	67 (49.3)
cN2	99 (24.2)	63 (23.1)	36 (26.5)
cNx	53 (13.0)	40 (14.7)	13 (9.6)
Overall clinical stage				0.643
II	65 (15.9)	45 (16.5)	20 (14.7)
III	344 (84.1)	228 (83.5)	116 (85.3)
Tumor location (cm)				0.950
≤ 5	166 (40.6)	111 (40.7)	55 (40.4)
5.1-10	221 (54.0)	148 (54.2)	73 (53.7)
> 10	22 (5.4)	14 (5.1)	8 (5.9)
Circumferential tumor extent				0.062
1/4-2/4	45 (11.0)	37 (13.6)	8 (5.9)
3/4	103 (25.2)	68 (24.9)	35 (25.7)
4/4	261 (63.8)	168 (61.5)	93 (68.4)
MRF status				0.781
Negative	187 (45.7)	123 (45.1)	64 (47.1)
Positive	222 (54.3)	150 (54.9)	72 (52.9)
EMVI				0.070
Negative	274 (67.0)	191 (70.0)	83 (61.0)
Positive	135 (33.0)	82 (30.0)	53 (39.0)
ypT stage				0.644
ypT 0-2	228 (55.7)	150 (54.9)	78 (57.4)
ypT 3-4	181 (44.3)	123 (45.1)	58 (42.6)
ypN stage				0.027^a
ypN0	331 (80.9)	231 (84.6)	100 (73.5)
ypN1	67 (16.4)	36 (13.2)	31 (22.8)
ypN2	11 (2.7)	6 (2.2)	5 (3.7)
TRG				0.246
1-2	218 (53.3)	140 (51.3)	78 (57.4)
3-5	191 (46.7)	133 (48.7)	58 (42.6)

¹P value for the comparison of training and validation sets using the χ² test for categorical variables or the Mann-Whitney U test for continuous variables.

^aP < 0.05.

BMI: Body mass index; CA199: Carbohydrate antigen 199; CapeOx: Capecitabine plus oxaliplatin; CEA: Carcinoembryonic antigen; EMVI: Extramural vascular invasion; IQR: interquartile range; MRF: Mesorectal fascia; NCRT: Neoadjuvant chemoradiotherapy; RT: Radiotherapy; TRG: Tumor regression grade; ypT stage: Pathological T stage after neoadjuvant chemoradiotherapy; ypN stage: Pathological N stage after neoadjuvant chemoradiotherapy.

Table 2 Univariate and multivariate analyses of clinicoradiological characteristics in the training set

Variable	Training	Univariate analysis		Multivariate analysis
Variable	Training	3-year PFS (%)	¹P value	HR (95%CI)²	²P value
Age (years)	273		0.518
Sex			0.424
Male	184	86.23
Female	89	83.09
BMI			0.013^a
< 18.5	31	67.59		1 (Ref.)
18.5-24	112	86.39		0.44 (0.20-0.98)	0.045^a
> 24	130	88.40		0.40 (0.18-0.91)	0.029^a
CEA level (ng/mL)			0.312
< 5	151	87.38
≥ 5	122	82.51
CA199 level (U/mL)			0.112
< 35	186	87.54
≥ 35	87	80.19
NCRT regimen
Capecitabine + RT	114	83.32	0.667
CapeOx + RT	155	86.89
Other	4	75.00
Adjuvant chemotherapy			0.936
No	69	85.31
Yes	204	85.19
Clinical T stage			0.698
cT2	20	90.00
cT3	167	83.10
cT4	86	88.24
Clinical N stage			0.776
cN0	45	88.72
cN1	125	84.66
cN2	63	84.04
cNx	40	84.71
Overall clinical stage			0.323
II	45	88.72
III	228	84.52
Tumor location (cm)			0.535
≤ 5	111	85.40
5.1-10	148	84.36
> 10	14	92.86
Circumferential tumor extent			0.810
1/4-2/4	37	86.15
3/4	68	86.74
4/4	168	84.37
MRF status			0.011^a
Negative	123	90.12		1 (Ref.)
Positive	150	81.19		1.71 (0.86-3.42)	0.129^a
EMVI			0.667
Negative	191	85.75
Positive	82	84.00
ypT stage			0.005^a
ypT0-2	150	89.88		1 (Ref.)
ypT3-4	123	79.53		1.25 (0.59-2.63)	0.561
ypN stage			< 0.001^a
ypN0	231	88.62		1 (Ref.)
ypN1	36	69.44		2.45 (1.18-5.07)	0.016^a
ypN2	6	50.00		3.88 (1.28-11.79)	0.017^a
TRG			0.006^a
1-2	140	89.87		1 (Ref.)
3-5	133	80.30		1.71 (0.83–3.53)	0.145

¹P prediction of OS calculated according to the log-rank test.

²P HR and P value calculated using multivariate Cox regression analysis.

^aP < 0.05.

BMI: Body mass index; CA199: Carbohydrate antigen 199; CapeOx: Capecitabine plus oxaliplatin; CEA: Carcinoembryonic antigen; EMVI: Extramural vascular invasion; MRF: Mesorectal fascia; NCRT: Neoadjuvant chemoradiotherapy; RT: Radiotherapy; TRG: Tumor regression grade; ypT stage: Pathological T stage after neoadjuvant chemoradiotherapy; ypN stage: Pathological N stage after neoadjuvant chemoradiotherapy; PFS: Progression-free survival; HR: Hazard ratio; CI: Confidence interval.

Table 3 C-indices of prognostic models for progression free survival prediction in locally advanced rectal cancer

Model	Training set			Validation set
Model	C-index (95%CI)	¹P value	²P value	C-index (95%CI)	¹P value	²P value
Clinicoradiological model
YpTN	0.670 (0.593-0.748)	Ref.	0.003	0.670 (0.558-0.781)	Ref.	0.009
Clin	0.718 (0.639-0.797)	0.003	Ref.	0.733 (0.634-0.833)	0.009	Ref.
Radiomics model
Intra	0.670 (0.603-0.736)	Ref.	0.297	0.669 (0.574-0.764)	Ref.	0.310
Peri	0.754 (0.680-0.827)	0.015	0.194	0.703 (0.597-0.809)	0.316	0.839
Omics	0.797 (0.741-0.853)	< 0.001	< 0.001	0.758 (0.670-0.847)	< 0.001	0.101
Clinicoradiological-omics model
Clin + intra	0.764 (0.697-0.832)	Ref.	< 0.001	0.765 (0.677-0.853)	Ref.	0.030
Clin + peri	0.804 (0.740-0.868)	0.044	< 0.001	0.778 (0.685-0.871)	0.432	0.010
ICRO	0.836 (0.787-0.886)	< 0.001	< 0.001	0.801 (0.722-0.879)	0.001	< 0.001

¹P represents the comparison between models within the same group.

²P represents the comparison across all models.

P value of C-indices between models calculated using the DeLong test. Eight prognostic models were constructed, integrating different types of features as follows: (1) Model pathological T and N stages after neoadjuvant chemoradiotherapy (NCRT) based on pathological T stage after NCRT and pathological N (ypN) stages; (2) Model based on clinicoradiological features, including body mass index, mesorectal fascia status, ypN stage, and tumor regression grade; (3) Model based on intratumoral radiomic features; (4) Model based on peritumoral radiomic features; (5) Model based on intratumoral-peritumoral radiomic features; (6) Model based on clinicoradiological-intratumoral features; (7) Model based on clinicoradiological-peritumoral features; and (8) Model based on clinicoradiological-intratumoral–peritumoral features. CI: Confidence interval; C-index: Concordance index; Clin: Clinicoradiological; Intra: Intratumoral; Peri: Peritumoral; ypT stage: Pathological T stage after neoadjuvant chemoradiotherapy; ypN stage: Pathological N stage after neoadjuvant chemoradiotherapy; YpTN: Pathological T and N stages after neoadjuvant chemoradiotherapy; ICRO: Integrated clinical-radiological-omics.

Table 4 Variable parameters and permutation feature importance of Model based on integrated clinical-radiological-omics

Variable	β	HR (95%CI)	P value	Relative importance weight 1	Relative importance weight 2
Intratumoral radiomic score¹	0.936	2.55 (1.43-4.54)	0.001	0.3510
Log.sigma50.mm.3D GLDM DependenceVariance	1.267	0.28 (0.10-0.79)	0.016		0.6047
Wavelet.HHL_firstorder_RootMeanSquared	0.621	1.86 (0.95-3.64)	0.069		0.0388
Wavelet.LHL_GLSZM_LargeAreaLowGrayLevelEmphasis	1.024	0.36 (0.12-1.04)	0.059		0.9806
Peritumoral radiomic score¹	0.948	2.58 (1.90-3.51)	< 0.001	1.0000
Wavelet.LLH_GLCM_ClusterShade	0.007	1.01 (1.00-1.01)	0.008		0.5858
Wavelet.LLL_GLSZM_LargeAreaLowGrayLevelEmphasis	0.016	1.02 (1.01-1.03)	0.002		0.1473
Log.sigma30.mm.3D_firstorder_90Percentile	0.654	1.92 (0.93-3.99)	0.080		0.5038
Wavelet.LHL_GLCM_Correlation	0.878	0.42 (0.22-0.78)	0.007		0.0226
Wavelet.HLH_firstorder_Kurtosis	0.889	0.41 (0.22-0.77)	0.005		0.3817
Wavelet.HHH_NGTDM_Contrast	0.774	2.17 (1.02-4.62)	0.045		0.0430
Square_GLDM_DependenceVariance	0.865	2.37 (1.21-4.65)	0.012		1.0000
BMI				0.0943	0.5510
< 18.5		1 (Ref.)
18.5-24	0.337	0.71 (0.32-1.62)	0.418
> 24	0.673	0.51 (0.22-1.17)	0.111
MRF status				-0.0867	-0.3670
Negative		1 (Ref.)
Positive	0.332	1.39 (0.69-2.82)	0.355
ypN stage				-0.0510	-0.0208
ypN0		1 (Ref.)
ypN1	0.857	2.36 (1.14-4.87)	0.021
ypN2	0.958	2.61 (0.85-7.97)	0.093
TRG				0.1019	0.8614
1-2		1 (Ref.)
3-5	0.691	2.00 (1.03-3.87)	0.040

¹Intratumoral and peritumoral radiomic scores calculated by combining radiomic feature values weighted by their coefficient β values (radiomic features are listed in the present table).

The β, hazard ratio, and P value were calculated using multivariable Cox regression analysis. The relative importance weight of a variable was calculated using permutation feature importance, measuring the change in the model’s concordance index after random shuffling of each feature’s value, with the importance scaled relative to the maximum observed change. HR: Hazard ratio; BMI: Body mass index; CI: Confidence interval; GLCM: Grey level co-occurrence matrix; GLDM: Grey level dependence matrix; GLSZM: Grey level size zone matrix; HHH: High-high-high; HHL: High-high-low; HLH: High-low-high; LHL: Low-high-low; LLH: Low-low-high; LLL: Low-low-low; MRF: Mesorectal fascia; NGTDM: Neighboring grey tone difference matrix; TRG: Tumor regression grade; ypN stage: Pathological N stage after neoadjuvant chemoradiotherapy.

Citation: Liang ZY, Yu ML, Yang H, Li HJ, Xie H, Cui CY, Zhang WJ, Luo C, Cai PQ, Lin XF, Liu KF, Xiong L, Liu LZ, Chen BY. Beyond the tumor region: Peritumoral radiomics enhances prognostic accuracy in locally advanced rectal cancer. World J Gastroenterol 2025; 31(8): 99036
URL: https://www.wjgnet.com/1007-9327/full/v31/i8/99036.htm
DOI: https://dx.doi.org/10.3748/wjg.v31.i8.99036