Evaluation of central non-enhancement in solid renal masses - without T1a

Author

Lu Mao

Published

February 10, 2026

Statistical analysis

Categorical variables are summarized by frequency and percentage; continuous variables are summarized by median and interquartile range (IQR). The agreement between two readers is assessed using the kappa coefficient for binary variables and the intraclass correlation coefficient (ICC) for continuous variables. The Wilcoxon rank sum test is used to compare histologic percent necrosis between groups with and without central non-enhancement (CNE). The correlation between volumetric non-enhancement to mass ratio and histologic percent necrosis is assessed using the Spearman correlation coefficient. Associations of histologic percent necrosis or volumetric non-enhancement to mass ratio with clinical outcomes are evaluated using the Spearman correlatione or Wilcoxon rank sum test as appropriate. P-values less than 0.05 are considered statistically significant. All statistical analyses are performed using R version 4.1.1 (R Foundation for Statistical Computing, Vienna, Austria).

Results

Patient characteristics

Patient characteristics are summarized by site and overall in Table 1 below.

Table 1: Patient characteristics

Characteristic	Overall, N = 282¹	UTSW, N = 51¹	MGB, N = 26¹	NYU, N = 43¹	Stanford, N = 53¹	Umich, N = 59¹	UW, N = 50¹
Age (years)	65 (56, 71)	67 (58, 74)	62 (55, 69)	64 (52, 71)	65 (56, 74)	63 (57, 70)	66 (54, 70)
Gender
Female	89 (32%)	13 (25%)	6 (23%)	13 (30%)	27 (51%)	20 (34%)	10 (20%)
Male	193 (68%)	38 (75%)	20 (77%)	30 (70%)	26 (49%)	39 (66%)	40 (80%)
Clinical T Stage
T1b	172 (64%)	32 (63%)	9 (56%)	25 (58%)	15 (31%)	50 (85%)	41 (82%)
T2	47 (18%)	19 (37%)	6 (38%)	0 (0%)	4 (8.3%)	9 (15%)	9 (18%)
T2a	13 (4.9%)	0 (0%)	0 (0%)	13 (30%)	0 (0%)	0 (0%)	0 (0%)
T2b	5 (1.9%)	0 (0%)	0 (0%)	5 (12%)	0 (0%)	0 (0%)	0 (0%)
T3	29 (11%)	0 (0%)	0 (0%)	0 (0%)	29 (60%)	0 (0%)	0 (0%)
T4	1 (0.4%)	0 (0%)	1 (6.3%)	0 (0%)	0 (0%)	0 (0%)	0 (0%)
Unknown	15	0	10	0	5	0	0
WHO/ISUP Grade
Grade 1	6 (2.6%)	1 (2.3%)	2 (8.3%)	2 (6.3%)	0 (0%)	0 (0%)	1 (2.2%)
Grade 2	95 (41%)	22 (50%)	7 (29%)	21 (66%)	16 (44%)	10 (20%)	19 (42%)
Grade 3	89 (38%)	14 (32%)	9 (38%)	7 (22%)	12 (33%)	33 (65%)	14 (31%)
Grade 4	42 (18%)	7 (16%)	6 (25%)	2 (6.3%)	8 (22%)	8 (16%)	11 (24%)
Unknown	50	7	2	11	17	8	5
AJCC TNM Stage
Stage I	129 (46%)	24 (47%)	9 (35%)	12 (28%)	15 (28%)	40 (68%)	29 (58%)
Stage II	28 (9.9%)	6 (12%)	6 (23%)	3 (7.0%)	7 (13%)	6 (10%)	0 (0%)
Stage III	112 (40%)	19 (37%)	8 (31%)	28 (65%)	24 (45%)	13 (22%)	20 (40%)
Stage IV	12 (4.3%)	2 (3.9%)	3 (12%)	0 (0%)	6 (11%)	0 (0%)	1 (2.0%)
Unknown	1 (0.4%)	0 (0%)	0 (0%)	0 (0%)	1 (1.9%)	0 (0%)	0 (0%)
Pathology Report Necrosis > 0%	116 (41%)	13 (25%)	25 (96%)	14 (33%)	24 (45%)	21 (36%)	19 (38%)
Rhabdoid Features
Present	20 (7.1%)	5 (9.8%)	2 (7.7%)	2 (4.7%)	3 (5.7%)	3 (5.1%)	5 (10%)
Not Present	234 (83%)	42 (82%)	24 (92%)	41 (95%)	26 (49%)	56 (95%)	45 (90%)
Unknown	28 (9.9%)	4 (7.8%)	0 (0%)	0 (0%)	24 (45%)	0 (0%)	0 (0%)
Sarcomatoid Features
Present	17 (6.0%)	3 (5.9%)	1 (3.8%)	1 (2.3%)	7 (13%)	3 (5.1%)	2 (4.0%)
Not Present	253 (90%)	46 (90%)	25 (96%)	42 (98%)	36 (68%)	56 (95%)	48 (96%)
Unknown	12 (4.3%)	2 (3.9%)	0 (0%)	0 (0%)	10 (19%)	0 (0%)	0 (0%)
Presence of CNE (Reader 1)	214 (76%)	38 (75%)	26 (100%)	26 (60%)	45 (85%)	46 (78%)	33 (66%)
Presence of CNE (Reader 2)	224 (79%)	44 (86%)	26 (100%)	22 (51%)	53 (100%)	37 (63%)	42 (84%)
Percentage of Central Non-Enhancement (Reader 1)	20 (10, 40)	20 (10, 40)	30 (10, 48)	30 (10, 48)	15 (10, 40)	30 (20, 40)	30 (20, 50)
Unknown	68	13	0	17	8	13	17
Percentage of Central Non-Enhancement (Reader 2)	30 (10, 40)	15 (10, 53)	30 (10, 50)	30 (10, 40)	30 (20, 40)	30 (20, 40)	20 (10, 38)
Unknown	58	7	0	21	0	22	8
¹ Median (IQR); n (%)

Reader agreement

For the presence of central non-enhancement, the two reader assessments are cross-tabulated in Table 2 below. The kappa coefficient is 0.592 (p<0.001), indicating a moderate agreement.

Table 2: Cross-tabulation of central non-enhancement presence by reader

	Presence of CNE (Reader 2)		Total	p-value¹
	No	Yes	Total	p-value¹
Presence of CNE (Reader 1)				<0.001
No	43 (15%)	25 (8.9%)	68 (24%)
Yes	15 (5.3%)	199 (71%)	214 (76%)
Total	58 (21%)	224 (79%)	282 (100%)
¹ Pearson’s Chi-squared test

For the quantitative volumetric non-enhancement to mass ratio and percentage of central non-enhancement, the scatter plot of the two reader assessments is shown in Figure 1 below. The ICC indicates a stronger agreement.

Figure 1: Scatter plot of non-enhancement to mass ratio and percentage of central non-enhancement by reader

CNE vs. histologic percent necrosis

Binary presence/absence of CNE

Consider Reader 1, Reader 2, and combinations of their assessments by AND and OR. The histologic percent necrosis is compared between groups with and without CNE for each definition of CNE presence. The results are summarized in Table 3 and Figure 2 below. Most of histologic percent necrosis is zero in the absence of CNE, and all comparisons are statistically significant.

Table 3: Wilcoxon rank sum test of histologic necrosis (%) vs. presence of CNE (N; median (IQR))

	No	Yes	P
Reader 1	N = 66; 0 (0, 0)	N = 204; 0 (0, 10)	<0.001
Reader 2	N = 58; 0 (0, 0)	N = 212; 0 (0, 10)	0.002
Both present	N = 81; 0 (0, 0)	N = 189; 0 (0, 10)	<0.001
Either present	N = 43; 0 (0, 0)	N = 227; 0 (0, 10)	0.001

Figure 2: Boxplot of histologic necrosis by reader-rated presence of CNE

Volumetric non-enhancement to mass ratio

The volumetric non-enhancement to mass ratio, by each reader and their average, is correlated with histologic percent necrosis in Figure 3. The correlations are moderately strong and statistically significant.

Figure 3: Correlation of reader-averaged non-enhancement to mass ratio and percentage of central non-enhancement with histologic necrosis (%)

Histologic percent necrosis vs. clinical outcomes

The histologic percent necrosis is compared between groups stratified by WHO/ISUP grade, AJCC TNM stage, rhabdoid features, and sarcomatoid features. The results are summarized in Table 4 (binary \(0\%\) vs. \(>0\%\)) and Figure 4 (quantitative) below.

Table 4: Association of histologic necrosis (%) vs. clinical outcomes

Characteristic	0%, N = 166¹	>0%, N = 116¹	p-value²
WHO/ISUP Grade			<0.001
Grade 1	3 (2.2%)	3 (3.2%)
Grade 2	71 (52%)	24 (25%)
Grade 3	52 (38%)	37 (39%)
Grade 4	11 (8.0%)	31 (33%)
Unknown	29	21
AJCC TNM Stage			<0.001
Stage I	88 (53%)	41 (35%)
Stage II	12 (7.2%)	16 (14%)
Stage III	63 (38%)	49 (42%)
Stage IV	2 (1.2%)	10 (8.6%)
Unknown	1 (0.6%)	0 (0%)
Rhabdoid Features			<0.001
Not Present	148 (98%)	86 (83%)
Present	3 (2.0%)	17 (17%)
Unknown	15	13
Sarcomatoid Features			0.002
Not Present	155 (97%)	98 (88%)
Present	4 (2.5%)	13 (12%)
Unknown	7	5
¹ n (%)
² Fisher’s exact test; Pearson’s Chi-squared test

Figure 4: Boxplot of histologic necrosis by clinical outcomes

CNE vs. clinical outcomes

Non-enhancement to mass ratio

The reader-averaged non-enhancement to mass ratio is compared between groups stratified by WHO/ISUP grade, AJCC TNM stage, rhabdoid features, and sarcomatoid features. The results are summarized in Figure 5 and Table 5 below.

Table 5: Association of non-enhancement to mass ratio (reader average) vs. clinical outcomes

Reader-Averaged Ratio by WHO ISUP Grade
Characteristic	Grade 1, N = 6¹	Grade 2, N = 95¹	Grade 3, N = 89¹	Grade 4, N = 42¹
Median (IQR)	0.04 (0.02, 0.10)	0.09 (0.02, 0.16)	0.15 (0.05, 0.24)	0.11 (0.04, 0.21)
Unknown	2	38	19	6
¹ Median (IQR)

Reader-Averaged Ratio by AJCC TNM Stage
Characteristic	Stage I , N = 129¹	Stage II , N = 28¹	Stage III , N = 112¹	Stage IV , N = 12¹	Unknown, N = 1¹
Median (IQR)	0.08 (0.03, 0.15)	0.16 (0.04, 0.31)	0.11 (0.03, 0.20)	0.20 (0.11, 0.38)	0.01 (0.01, 0.01)
Unknown	44	4	34	1	0
¹ Median (IQR)

Reader-Averaged Ratio by Rhabdoid Features
Characteristic	Not Present, N = 234¹	Present, N = 20¹
Median (IQR)	0.11 (0.03, 0.20)	0.10 (0.03, 0.17)
Unknown	76	2
¹ Median (IQR)

Reader-Averaged Ratio by Sarcomatoid Features
Characteristic	Not Present, N = 253¹	Present, N = 17¹
Median (IQR)	0.10 (0.03, 0.19)	0.14 (0.06, 0.26)
Unknown	78	2
¹ Median (IQR)

Moderate correlations with WHO/ISUP grade and AJCC TNM stage;
Weak to no correlation with rhabdoid and sarcomatoid features.

Percentage of central non-enhancement

The reader-averaged percentage of central non-enhancement is compared between groups stratified by WHO/ISUP grade, AJCC TNM stage, rhabdoid features, and sarcomatoid features. The results are summarized in Figure 6 and Table 6 below.

Table 6: Association of percentage of central non-enhancement (reader average) vs. clinical outcomes

Reader-Averaged Percentage by WHO ISUP Grade
Characteristic	Grade 1, N = 6¹	Grade 2, N = 95¹	Grade 3, N = 89¹	Grade 4, N = 42¹
Median (IQR)	33 (25, 38)	20 (10, 30)	35 (18, 48)	33 (17, 46)
Unknown	2	38	18	6
¹ Median (IQR)

Reader-Averaged Percentage by AJCC TNM Stage
Characteristic	Stage I , N = 129¹	Stage II , N = 28¹	Stage III , N = 112¹	Stage IV , N = 12¹	Unknown, N = 1¹
Median (IQR)	24 (15, 40)	38 (18, 43)	28 (15, 44)	45 (33, 50)	6 (6, 6)
Unknown	43	4	34	1	0
¹ Median (IQR)

Reader-Averaged Percentage by Rhabdoid Features
Characteristic	Not Present, N = 234¹	Present, N = 20¹
Median (IQR)	30 (15, 45)	25 (16, 44)
Unknown	75	2
¹ Median (IQR)

Reader-Averaged Percentage by Sarcomatoid Features
Characteristic	Not Present, N = 253¹	Present, N = 17¹
Median (IQR)	30 (15, 45)	35 (15, 43)
Unknown	77	2
¹ Median (IQR)