The effect of modulated electro-hyperthermia on temperature and blood flow in human cervical carcinoma

Figures & data

Table 1. Baseline characteristics of patients (N = 20) assigned to treatment.

Characteristics	Number of patients (N = 20)
Age (years)
Range	30–81
Median	50.5
ECOG performance status
1	12 (60%)
2	8 (40%)
Presentation of tumour
Exophytic	14 (70%)
Endophytic	6 (30%)
Size of tumour (cm)
Horizontal x
Range	2.4–10.0
Median	5.05
Vertical y
Range	2.0–8.0
Median	4.15
Depth z
Range	2.9–8.0
Median	4.50
Stage
IIb	10 (50%)
IIIa	2 (10%)
IIIb	6 (30%)
IVa	1 (5%)
IVb	1 (5%)
Pathology
Adenocarcinoma	6 (30%)
Squamous cell carcinoma	13 (65%)
Carcinosarcoma	1 (5%)
Haemoglobin (g/dl)
Range	6.4–13.2
Median	10.41
Mild anaemia^a (11.0–12.9)	6 (30%)
Moderate anaemia^a (8.0–10.9)	10 (50%)
Severe anaemia^a (<8)	2 (10%)
Non-anaemia (≥13)	2 (10%)
Haematocrit (%)
Range	19.0–38.0
Median	31.35
CA 19-9 (U/ml)
Range	1.1–33.8
Median	7.89
CA 125 (U/ml)
Range	5.5–111.6
Median	45.45

^a WHO classification.

Table 2. The main values of starting characteristics divided into subgroups to show the cohort properties of the treated population.

A
	Mass size <5 cm (n = 11)	Mass size ≥5 cm (n = 9)	p value
RI index	0.38 ± 0.07	0.42 ± 0.015	0.65
S/D ratio	1.34 ± 0.17	1.65 ± 0.21	0.68
Peri-tumour temperature (°C)	36.58 ± 0.16	36.57 ± 0.24	0.21
SUVmax	10.36 ± 2.52	15.52 ± 5.32	0.27
Haemoglobin (g/dl)	11.4 ± 1.4	9.7 ± 1.3	0.0027
Haematocrit (%)	33.2 ± 3.9	27.6 ± 3.5	0.0021
CA 125 (U/ml)	37.7 ± 18.6	45.9 ± 31.5	0.88
CA 19-9 (U/ml)	7.3 ± 6.4	12.4 ± 8.1	0.04
B
	SUVmax <10 (n = 14)	SUVmax ≥10 (n = 6)	p value
RI index	0.35 ± 0.069	0.42 ± 0.13	0.12
S/D ratio	1.57 ± 0.201	1.68 ± 0.19	0.13
Peri-tumour temperature (°C)	36.57 ± 0.16	36.71 ± 0.89	0.2
SUVmax	8.33 ± 1.02	14.55 ± 4.72	–
Haemoglobin (g/dl)	9.9 ± 1.6	11.5 ± 1.7	0.047
Haematocrit (%)	29.8 ± 4.1	33.4 ± 5.6	0.07
CA 125 (U/ml)	45.0 ± 28.6	33.2 ± 19.4	0.45
CA 19-9 (U/ml)	10.1 ± 7.9	8.0 ± 8.5	0.11
C
	Tumour nature Endophytic (n = 6)	Tumour nature Exophytic (n = 14)	p value
RI index	0.39 ± 0.082	0.40 ± 0.13	0.91
S/D ratio	1.63 ± 0.21	1.66 ± 0.20	0.49
Peri-tumour temperature (°C)	36.6 ± 0.15	36.71 ± 0.24	0.071
SUVmax	10.81 ± 2.43	13.49 ± 0.53	0.015
Haemoglobin (g/dl)	11.0 ± 1.8	10.7 ± 1.8	0.32
Haematocrit (%)	32.6 ± 5.3	29.9 ± 4.5	0.19
CA 125 (U/ml)	42.9 ± 21.2	40.8 ± 28.9	0.62
CA 19-9 (U/ml)	9.4 ± 8.2	9.5 ± 8.1	0.93
D
	Squamous cell carcinoma (n = 13)	Non-squamous cell carcinoma (n = 7)	p value
RI index	0.37 ± 0.07	0.45 ± 0.017	0.32
S/D ratio	1.64 ± 0.20	1.67 ± 0.20	0.72
Peri-tumour temperature (°C)	36.7 ± 0.24	36.6 ± 0.97	0.87
SUVmax	12.18 ± 2.0	13.61 ± 7.5	0.94
Haemoglobin (g/dl)	10.7 ± 1.4	9.9 ± 1.4	0.32
Haematocrit (%)	31.2 ± 4.10	29.7 ± 4.8	0.45
CA 125 (U/ml)	37.2 ± 22.8	49.7 ± 32.3	0.58
CA 19-9 (U/ml)	6.9 ± 4.8	14.2 ± 10.6	0.13

Significant deviations were observed only in haemoglobin and haematocrit concentrations by mass and by SUVmax subdivisions.

Figure 1. Peri-tumour temperatures were measured at 30 min before hyperthermia (baseline), at 30 min and 60 min during the hyperthermia procedure, and at 30 min after hyperthermia. The peri-tumour temperatures of all patients are shown.

Table 3. Changes in the peri-tumour temperature, S/D ratio and RI index in cervical tumours.

	Baseline	30 min	60 min	+30 min	p value^a
Peri-tumour temperature (°C) (n = 20)	36.67 ± 0.22	37.47 ± 0.45*** (2.20 ± 1.10%)	38.46 ± 0.84*** (4.91 ± 2.01%)	37.13 ± 0.33* (1.26 ± 0.86%)	<0.0001
S/D ratio (n = 20)	1.65 ± 0.20	1.40 ± 0.13*** (–14.95 ± 5.21%)	1.22 ± 0.09*** (–25.09 ± 8.11%)	1.40 ± 0.16*** (–14.75 ± 8.32%)	<0.0001
RI index (n = 20)	0.40 ± 0.12	0.29 ± 0.11** (–27.67 ± 19.00%)	0.19 ± 0.06*** (–51.84 ± 13.14%)	0.30 ± 0.10* (–24.81 ± 10.58%)	<0.0001

All changes measured in the study were significant and the values are characteristic of the heating process.

Mean ± SD.

^aRepeated measures ANOVA.

Comparison with baseline: *p < 0.05, **p < 0.01 and ***p < 0.001 (Bonferroni-corrected p values).

Figure 2. High-resolution Doppler measurements of a representation patient at baseline (A), 30 min into the heating procedure (B), 60 min into the heating procedure (C), and at 30 min after the heating procedure (D).

Table 4. The peri-tumour temperatures, S/D ratios and RI indexes in squamous cell carcinoma (sqcc) and non-squamous cell carcinoma (non-sqcc).

	Pathology
Parameter/time point	Sqcc (n = 13)	Non-sqcc (n = 7)	p value^a
Peri-tumour temperature (°C)
Baseline	36.67 ± 0.24	36.66 ± 0.20	0.429
30	37.53 ± 0.44	37.36 ± 0.47
60	38.39 ± 0.79	38.60 ± 0.97
+30	37.15 ± 0.31	37.07 ± 0.38
S/D ratio
Baseline	1.64 ± 0.20	1.67 ± 0.20	0.5327
30	1.39 ± 0.13	1.41 ± 0.15
60	1.24 ± 0.08	1.20 ± 0.10
+30	1.38 ± 0.15	1.43 ± 0.19
RI index
Baseline	0.37 ± 0.07	0.45 ± 0.17	0.0439
30	0.29 ± 0.07	0.29 ± 0.17
60	0.19 ± 0.05	0.19 ± 0.08
+30	0.28 ± 0.06	0.33 ± 0.15

Mean ± SD.

^aRepeated measures ANOVA (pathology × parameter interaction p values).

Figure 3. The increase in peri-tumour temperature, excluding the cooling period, was negatively related to the RI and S/D by R² ≈ 0.999 (A) and R² ≈ 0.972 (B), respectively, and positively related to blood flow.