Predicting Response to Total Neoadjuvant Treatment (TNT) in Locally Advanced Rectal Cancer Based on Multiparametric Magnetic Resonance Imaging: A Retrospective Study

Figures & data

Table 1 Patient Characteristics

Variable	Numbers
Cycles of chemotherapy
ICT	2 (0–5) cycles
CRT	1 (1–3) cycles
CCT	3 (0–5) cycles
Clinical T classification
T2	2 (2.82%)
T3	49 (69.01%)
T4a	14 (19.72%)
T4b	6 (8.45%)
Clinical N classification
N0	6 (8.45%)
N1	2 (2.82%)
N2	63 (88.73%)
Operation	64 (90.14%)
Wait & See	7 (9.86%)
ypT classification
T0	24 (37.50%)
T1	2 (3.13%)
T2	11 (17.19%)
T3	26 (40.63%)
T4	1 (1.56%)
ypN classification
N0	47 (73.44%)
N1	13 (20.31%)
N2	4 (6.25%)
MRI
MRIbaseline	71 (100%)
MRIbaseline + MRIICT	15 (21.13%)
MRIbaseline + MRICRT	55 (77.46%)
MRIbaseline + MRICCT	49 (69.02%)
Response
pCR	23 (32.39%)
cCR	1 (1.41%)
Non-pCR	41 (57.75%)
Non-cCR	6 (8.45%)
TRG
0	24 (37.50%)
1	14 (21.88%)
2	16 (25.00%)
3	10 (15.63%)
Sensitivity
H group	38 (59.38%)
M group	26 (40.62%)
L group	0 (0%)

Abbreviations: ICT, induction chemotherapy; CRT, concurrent chemoradiotherapy; CCT, consolidation chemotherapy; pCR, pathological complete response; cCR, clinical complete response; H group, the high sensitive group; M group, the moderate sensitive group; L group, the low sensitive group.

Figure 1 (A) Distribution of CR vs non-CR in the MRI_ICT, MRI_CRT and MRI_CCT. (B) Distribution of the high sensitive group (H group) vs the moderate sensitive group (M group) in the MRI_ICT, MRI_CRT and MRI_CCT.

Table 2 Logistic Regression Analysis of Post-ICT Predictive Factors of CR and High Sensitivity to TNT

Parameters	Univariate (CR)	Multivariate (CR)		Univariate (H Group)	Multivariate (H Group)
	P	95% CI	P	P	95% CI	P
Post-ICT ∆TL	0.008*	2.606–3.208	0.038*	0.01*	-	-
Post-ICT ∆LND	0.019*		0.988	0.300
Post-ICT ∆LNV	0.019*		0.988	0.188

Note: *P < 0.05.

Abbreviations: ICT, induction chemotherapy; TL, tumor length; LND, diameter of lymph node; LNV, volume of lymph node on T2 – weight.

Table 3 Logistic Regression Analysis of Post-CRT Predictive Factors of CR and High Sensitivity to TNT

Parameters	Univariate (CR)	Multivariate (CR)		Univariate (H Group)	Multivariate (H Group)
	P	95% CI	P	P	95% CI	P
Post-CRT EMVI	0.002*		0.709	0.013*	-	-
Post-CRT LNN	0.004*		0.978	0.125
Post-CRT LND	0.021*		0.896	0.272
Post-CRT ∆LNN	0.002*	1.209–80.258	0.033*	0.252
Post-CRT ∆LND	0.021*		0.896	0.242

Note: *P < 0.05.

Abbreviations: CRT, concurrent chemoradiotherapy; EMVI, extramural vascular invasion; LNN, the numbers of lymph node metastases; LND, diameter of lymph node.

Table 4 Logistic Regression Analysis of Post-CCT Predictive Factors of CR and High Sensitivity to TNT

Parameters	Univariate (CR)	Multivariate (CR)		Univariate (H Group)	Multivariate (H Group)
	P	95% CI	P	P	95% CI	P
Post-CCT ADCT	0.008*	27.517–52.047	0.003*	0.063		-
Post-CCT TTDWI	0.031*		0.205	0.037*		0.290
Post-CCT ∆TTDWI	0.029*		0.28	0.056		-
Post-CCT TTT2	0.08		-	0.009*		0.89
Post-CCT ∆TTT2	0.048*		0.705	0.009*		0.221
Post-CCT SDWI	0.064		-	0.036*		0.631
Post-CCT ∆SDWI	0.001*	6.374–40.883	0.01*	0.009*		0.993
Post-CCT ST2	0.104		-	0.008*		0.933
Post-CCT ∆ST2	0.006*		0.058	0.001*	0.004–0.392	0.006*
Post-CCT LNN	0.016*		0.998	0.103		-
Post-CCT ∆LNN	0.008*		0.127	0.016*		0.209
Post-CCT ∆LND	0.046*		0.067	0.056		-
Post-CCT LNV	0.003*		0.358	0.044*		0.607
Post-CCT ∆LNV	0.002*	35.108–61.120	0.017*	0.019*		0.439
Post-CCT ∆TV	0.069		-	0.007*		0.338
Post-CCT TL	0.053		-	0.005*		0.356
Post-CCT ∆TL	0.098		-	0.004*		0.371
Post-CCT DT stage	0.022*		0.421	0.022*		0.561

Note: *P < 0.05.

Abbreviations: CCT, consolidation chemotherapy; ADC_T, the mean apparent diffusion coefficient values of tumor; TT_DWI, tumor thickness on DWI; TT_T2, tumor thickness on T2 - weight; S_DWI, maximum cross - sectional area of tumor on diffusion-weighted imaging; S_T2, maximum cross - sectional area of tumor on T2 - weight; LNN, the numbers of lymph node metastases; LND, diameter of lymph node; LNV, volume of lymph node on T2 - weight; TV, tumor volume on T2 - weight; TL, tumor length; T stage, tumor stage.

Table 5 Multivariate Analysis Results About Magnetic Resonance Imaging (MRI) Findings for the Prediction of CR and High Sensitivity to TNT

Parameters	AUC (95% CI)	SEN	SPE	PPV	NPV	ACC	P value
MRI findings for the prediction of CR
Post-ICD ∆TL	0.92 (0.778–1.000)	100%	80%	71.4%	100%	86.7%	0.01*
Post-CRT ∆LNN	0.75 (0.603–0.891)	71.4%	79.4%	68.2%	81.8%	76.4%	0.002*
Post-CCT ∆SDWI	0.78 (0.646–0.92)	70.6%	81.2%	66.7%	83.9%	77.6%	0.001*
Post-CCT ADCT	0.72 (0.672–0.866)	64.7%	75%	57.9%	80%	71.4%	0.012*
Post-CCT ∆LNV	0.76 (0.629–0.899)	82.4%	71.9%	60.9%	88.5%	75.5%	0.003*
Post-CCT ∆SDWI + Post-CCT ADCT	0.86 (0.766–0.962)	94.1%	68.7%	61.5%	95.7%	77.6%	< 0.001*
Post-CCT ∆SDWI + Post-CCT ∆LNV	0.87 (0.766–0.97)	76.5%	81.2%	68.4%	86.7%	79.6%	< 0.001*
Post-CCT ADCT + Post-CCT ∆LNV	0.88 (0.786–0.972)	100%	62.5%	58.6%	100%	75.5%	< 0.001*
Post-CCT ∆SDWI + Post-CCT ADCT + Post-CCT ∆LNV	0.94 (0.873–1)	94.1%	90.6%	84.2%	96.7%	91.8%	< 0.001*
MRI findings for the prediction of high sensitivity to TNT
Post-CRT EMVI	0.69 (0.543–0.846)	100%	80%	76%	100%	68%	0.022*
Post-CCT ∆ST2	0.78 (0.645–0.917)	80%	76.2%	80%	76.2%	78.3%	0.001*
Post-ICD ∆TL	0.84 (0.610–1.000)	75%	100%	96%	70.4%	82.7%	0.048*

Note: *P < 0.05.

Abbreviations: AUC, area under curve; SEN, sensitivity; SPE, specificity; PPV, positive predictive value; NPV, negative predictive value; ACC, accuracy; MRI, magnetic resonance imaging; ICT, induction chemotherapy; CRT, concurrent chemoradiotherapy; CCT, consolidation chemotherapy; TL, tumor length; LNN, the numbers of lymph node metastases; S_DWI, maximum cross - sectional area of tumor on diffusion-weighted imaging; ADC_T, the mean apparent diffusion coefficient values of tumor; LNV, volume of lymph node on T2 - weight; EMVI, extramural vascular invasion; S_T2, maximum cross - sectional area of tumor on T2 - weight.

Figure 2 (A) ROC curves of predicting CR in the post-ICT MRI cohorts. (B) ROC curves of predicting CR in the post-CRT MRI cohorts. (C) ROC curves of predicting CR in the post-CCT MRI cohorts.

Figure 3 (A) ROC curves of predicting the high sensitive group (H group) in the post-ICT MRI cohorts.(B) ROC curves of predicting the high sensitive group (H group) in the post-CRT MRI cohorts. (C) ROC curves of predicting the high sensitive group (H group) in the post-CCT MRI cohorts.

Figure 4 (A) ROC curves of predicting CR (combination of post-CCT ∆S_DWI and post-CCT ∆LNV). (B) ROC curves of predicting CR (combination of post-CCT ∆S_DWI and post-CCT ADC_T). (C) ROC curves of predicting CR (combination of post-CCT ADC_T and post-CCT ∆LNV). (D) ROC curves of predicting CR (combination of post-CCT ∆S_DWI, post-CCT ADC_T and post-CCT ∆LNV).

Figure 5 (A) Post - ICT ∆TL of CR vs non – CR for each patient. (B) Post - ICT ∆TL of the high sensitive group (H group) vs the moderate sensitive group (M group) for each patient.