Thermal dose fractionation affects tumour physiological response

Figures & data

Table I.  Distribution of tumour grade, tumour site and tumour volume between treatment groups. Proportionally more high-grade tumours were present in tumours treated with three to four fractions per week.

Variable	Arm		P value
	1 per week	3–4 per week
Tumour grade
Low/intermediate	20 (95.2%)	7 (43.8%)	0.0007*
High	1 (4.8%)	9 (56.2)
Tumour site
Head	1 (4.8%)	2 (12.5.5)	0.23*
Trunk	2 (9.5.5)	4 (25.0%)
Extremity	18 (85.7%)	10 (62.5%)
Tumour volume (cm^3)
Mean	69.2	89.7	0.87
Median	72.3	60.1
Min	11.0	10.0
Max	142.6	360.3

Note: *Fisher's exact p value.

Table II.  Thermal parameters as a function of treatment group. Tumour temperatures were higher and duration of each hyperthermia treatment shorter in the one fraction per week group compared to the three to four fractions per week group. The total cumulative thermal dose, quantified as CEM43T₉₀ was slightly higher in the one fraction per week group but was within the target range of 20–50 CEM43T₉₀. It is doubtful that the small absolute difference in total CEM43T₉₀ values between groups is clinically significant.

	Arm		P value
Variable	1 per week (n = 21 dogs)	3–4 per week (n = 16 dogs)
T10 (°C) at first hyperthermia treatment
Mean	44.90	43.37	0.0013
Median	45.13	43.38
T50 (°C) at first hyperthermia treatment
Mean	42.91	41.47	<0.0001
Median	43.10	41.31
T90 (°C) at first hyperthermia treatment
Mean	41.15	40.08	<0.0001
Median	41.02	40.04
Total number of hyperthermia treatments
Mean	4.9	15.4	<0.0001
Median	5.0	16.0
Duration of first hyperthermia treatment (min)
Mean	55.8	82.6	0.009
Median	45.0	89.5
Total CEM43T10 (min)
Mean	1185.7	2109.1	0.044
Median	749.8	1814.0
Total CEM43T50 (min)
Mean	251.7	304.0	0.318
Median	200.5	291.1
Total CEM43T90 (min)
Mean	29.9	24.9	0.007
Median	32.1	24.2
Total duration of hyperthermia (min)
Mean	240	1459	<0.0001
Median	206	1506

Figure 1. Percentage tumour volume change at end of treatment as a function of treatment group. There was a statistically significant greater reduction in tumour volume at the end of treatment in tumours treated with one fraction per week compared to tumours treated with three to four fractions per week (p = 0.0022).

Figure 2. Median number of measured pO₂ points <2.5 mm Hg (24 h post treatment minus pretreatment) as a function of the percentage change in tumour volume at the end of treatment. Note the direction of the x-axis; decreasing tumour volume proceeds to the right. The pattern is a greater tumour volume reduction in tumours where the median number of measured points <2.5 mm Hg decreases compared to the pretreatment value, i.e. improving oxygenation (p = 0.0138, test for zero correlation; correlation coefficient 0.41).

Table III.  Median descriptors of tumour oxygenation prior to treatment versus 24 h after the first hyperthermia fraction. These data are for all tumours, in both fractionation groups combined. The change in median values is in a direction consistent with reduction in oxygenation, without respect to fractionation group.

Variable	Pretreatment	24 h after first HT treatment	P value
Median pO2	10.5	6.2	0.06
Median % measured pO2 points ≤2.5 mm Hg	22.5	34.2	0.44
Median % measured pO2 points ≤5 mm Hg	33.4	50.0	0.03
Median % measured pO2 points ≤10 mm Hg	48.9	61.8	0.02

Notes: HT, hyperthermia; SD, standard deviation. P value is from signed rank test to compare medians.

Figure 3. Difference in median percentile values for the apparent diffusion coefficient of water (ADC), post-treatment relative to pretreatment, as a function of the individual percentile as a function of treatment group. The greatest decrease occurred in the low end of the diffusion range in dogs receiving one fraction per week (0.0023 ≤ p ≤ 0.4322). 5HT, one hyperthermia fraction per week; 20 HT, three to four hyperthermia fractions per week.

Figure 4. Percentile distribution of apparent diffusion coefficient (ADC) values in an individual tumour before treatment and at the end of treatment. In this subject, treatment led to a generalised decrease in water diffusion but regions where water diffusion was more restricted prior to treatment (low ADC values) were characterised by greater decreases. Every 1000th point is shown. Fewer points are present after treatment because the tumour was smaller. Pre, before treatment.