Systemic anti-tumour effects of local thermally sensitive liposome therapy

Figures & data

Table 1. Survival analysis for the different treatment groups.

Treatment	End point	Treated side	p Value	Hazard ratio (HR)	95% CI of HR
All groups	3×	Primary	<0.01	NA
All groups	3×	Secondary	0.02	NA
All groups	5×	Primary	0.04	NA
All groups	5×	Secondary	0.06	NA
DOXIL vs. control	3×	Primary	0.05	2.1	1.0–4.5
LTSL 3.8% vs. control	3×	Primary	0.02	2.5	1.2–5.4
LTSL 5.2% vs. control	3×	Primary	<0.01	3.6	1.6–8.1
DOXIL vs. control	3×	Secondary	0.17	1.6	0.8–3.3
LTSL 3.8% vs. control	3×	Secondary	<0.01	3.2	1.4–6.3
LTSL 5.2% vs. control	3×	Secondary	0.09	1.9	0.9–3.7
DOXIL vs. control	5×	Primary	0.04	2.2	1.1–5.0
LTSL 3.8% vs. control	5×	Primary	0.04	2.3	1.1–4.8
LTSL 5.2% vs. control	5×	Primary	0.006	3.1	1.4–7.1
DOXIL vs. control	5×	Secondary	0.43	1.34	0.6–2.8
LTSL 3.8% vs. control	5×	Secondary	0.17	1.7	0.8–3.5
LTSL 5.2% vs. control	5×	Secondary	0.02	2.6	1.2–5.8

Figure 1. Growth delay of the primary and secondary side as a function of relative intratumoural DOX measured with optical spectral imaging at 6 h (A), 12 h (B), and 24 h (C) after treatment. Data is given as mean and SEM for each group (n = 19, 20, 28, 26, 5, and 5 animals for control, DOXIL, LTSL1 with 3.8% PEG, LTSL2 with 5.2% PEG, LTSL1 (7.5 mg/kg) with 3.8% PEG, LTSL2 (7.5 mg/kg) with 5.2% PEG, respectively).

Figure 2. Primary treated side relative DOX level versus time (a). Secondary treated side relative DOX level versus time (b). Data is given as mean for each group (n = 19, 20, 28, 26, 5, and 5 animals for control, DOXIL, LTSL1 with 3.8% PEG, LTSL2 with 5.2% PEG, LTSL1 (7.5 mg/kg) with 3.8% PEG, LTSL2 (7.5 mg/kg) with 5.2% PEG, respectively).

Table 2. DOX accumulation results. Normalised area under the curve (AUC) and peak concentration for each treatment group and tumour side (Primary had local HT).

Treatment	AUC	Time of peak	Peak DOX concentration	Tumour side
DOXIL	1.81	24	0.113	Primary
DOXIL	0.98	24	0.063	Secondary
3.8% PEG	2.38	6	0.144	Primary
3.8% PEG	0.70	12	0.037	Secondary
5.2% PEG	2.73	6	0.194	Primary
5.2% PEG	0.74	6	0.044	Secondary
HD 3.8% PEG	4.14	6	0.238	Primary
HD 3.8% PEG	1.11	24	0.067	Secondary
HD 5.2% PEG	2.87	6	0.156	Primary
HD 5.2% PEG	0.92	24	0.049	Secondary

Figure 3. a and b demonstrate the mean temporal relationship for each treatment group of NAD(P)H after therapy for the primary side (a) and the secondary side (b). c and d demonstrate the mean percentage change of the NAD(P)H of each treatment group versus tumour growth delay of both the primary and secondary side at 6 h (c) and 12 h (d) with linear regression and 95% confidence bounds. At 6 h the results were statistically significant (n = 19, 20, 28, 26, 5, and 5 animals for control, DOXIL, LTSL1 with 3.8% PEG, LTSL2 with 5.2% PEG, LTSL1 (7.5 mg/kg) with 3.8% PEG, LTSL2 (7.5 mg/kg) with 5.2% PEG, respectively).

Figure 4. The mean NAD(P)H percentage change for each treatment group versus mean relative DOX concentration for each group at 6 and 12 h combining both treatment sides. Linear regression was then performed demonstrating a significant slope not equal to unity with 95% confidence intervals at 6 h. Note, linear regression overlay was not included, for clarity (n = 19, 20, 28, 26, 5, and 5 animals for control, DOXIL, LTSL1 with 3.8% PEG, LTSL2 with 5.2% PEG, LTSL1 (7.5 mg/kg) with 3.8% PEG, LTSL2 (7.5 mg/kg) with 5.2% PEG, respectively).