DW-MRI and DCE-MRI are of complementary value in predicting pathologic response to neoadjuvant chemoradiotherapy for esophageal cancer

Figures & data

Table 1. Patient and treatment-related characteristics for both institutes.

	Study population UMCU (n = 31)	Study population NKI (n = 14)	Combined analysis DWI/DCE UMCU + NKI (n = 34)
Gender
Male	27	11	29
Female	4	3	5
Age, years (at start nCRT)*	64.5 ± 7.6	58.6 ± 13.0	62.4 ± 10.1
Clinical T-stage
T2	6 (19%)	2 (14%)	5 (15%)
T3	25 (81%)	12 (86%)	29 (85%)
Clinical N-stage
N0	9 (29%)	6 (43%)	10 (29%)
N1	8 (26%)	5 (36%)	12 (35%)
N2	12 (39%)	3 (21%)	9 (26%)
N3	2 (6%)	0 (0%)	3 (9%)
Type
SCC	3 (10%)	2 (14%)	4 (12%)
AC	26 (84%)	12 (86%)	28 (82%)
ASC	2 (6%)	0 (0%)	2 (6%)
Location
Proximal third of esophagus	1 (3%)	0 (0%)	1 (3%)
Middle third of esophagus	3 (10%)	1 (7%)	3 (9%)
Distal third of esophagus	23 (74%)	6 (43%)	21 (62%)
Gastroesophageal junction	4 (13%)	7 (50%)	9 (26%)
Acquisition, no. of days
Pre (before start nCRT)†	6 (2–14)	5 (–1–11)	6 (–1–14)
Per (after start nCRT)†	10 (8–17)	15 (9–16)	10 (8–17)
Post (after completion nCRT)†	41 (17–62)	39 (31–65)	40.5 (17–57)
Post scan – surgery interval†	10 (5–48)	11.5 (4–19)	11.5 (4–48)

The patient characteristics from the combined analysis are summarized in the third column. SCC: squamous cell carcinoma; AC: adenocarcinoma; ASC: adenosquamous carcinoma.

Data presented as counts with percentages in the parentheses unless stated otherwise.

* Data presented as mean ± SD.

† Data presented as median (range).

Table 2. Scan parameters of the used MRI protocol.

	DWI EPI (STIR)	DCE (3D – FFE T1W)	T2W (MS-TSE)	B0 (Dual acquisition)
Scan plane	Transverse	Coronal	Transverse	Transverse
Slice thickness (mm)	4.00	3.00	4.00 (gap: 2.48)	4.00
Voxel size (mm)	3.25	1.18 or 1.98*	0.67	4.06
TR (ms)	7241	3.43	1604	630.4
TE (ms) (TE2)	76.2	1.53	100	4.6 (9.2)
Flip angle (˚)	90	20	90	30
Temporal resolution (s)	N.A.	3	N.A.	N.A.
Number of time frames	N.A.	62	N.A.	N.A.
b-values (s/mm^2)	0, 200, 800	N.A.	N.A.	N.A.

N.A.: not applicable ; *second parameter applicable for scans acquired with Ingenia scanner.

Figure 1. An example of acquired MRI scans for one patient for one time point (pre scan). In (a) a T₂W scan is shown with in (d) the coronal view of the same scan. (b) A b800 DW-MRI scan and its corresponding ADC-map in (c). In (e) the 24th scan of a DCE-MRI series is shown, during inflow of contrast in the tumor. The corresponding calculated AUC-map is found in (f).

Figure 2. In (a) and (b) 90th percentile (P90) ΔAUC_per-pre is presented as a function of response and in (c) and (d) 75th percentile (P75) ΔADC_post-pre. In (a, c) pathologic complete response (pCR) and no-pCR are differentiated while in (b, d) good response (GR) versus poor response is shown. Each dot represents a patient and the two institutes are indicated separately (UMCU in black/NKI in grey). The solid black line for each group represents the median. Threshold lines are indicated for which predictive values are calculated for separation based on response.

Table 3. Predictive values for both DW-MRI and DCE-MRI discriminating pCR versus no-pCR and GR versus noGR.

	n	Threshold	Sensitivity (%)	Specificity (%)	PPV (%)	NPV (%)	c-index	p-value
GR vs. noGR
P90 ΔAUCper-pre	45	33.7%	68.2	56.5	60	65	0.64	.261
P75 ΔADCpost-pre	34	22.4%	86.7	57.9	61.9	84.6	0.75	.031
pCR vs. no-pCR
P90 ΔAUCper-pre	45	27.7%	90	62.9	40.9	95.7	0.79	.028
P75 ΔADCpost-pre	34	29.5%	83.3	53.6	27.8	93.8	0.76	.050
Combined	34	0.138*	100	75	46	100	0.89	.086/.052**

Only the most predictive parameters are shown. Also a combined analysis using multivariable logistic regression, which was found to be complementary, is presented. GR: good response; pCR: pathologic complete response; P90/P75: 90th and 75th percentiles, respectively.

*Probability value following Equation 1 with model values: α = −2.244, β_AUC = −0.034 and β_ADC = 0.044

** for P90 ΔAUC_per-pre and P75 ΔADC_post-pre, respectively.

Figure 3. 90th percentile (P90) ΔAUC_per-pre is plotted as function of 75th percentile (P75) ΔADC_post-pre. Each dot represents a patient and TRG scores are differentiated using different symbols, with pathologic complete response (pCR) highlighted in red. Equal thresholds from Figure 2 predicting pCR are indicated in dotted lines. The solid line represents the threshold line (separating pCR from no-pCR) from the multivariable logistic regression model, for which the probability equals 0.138.