Fig 1.
A CONsolidated Standards of Reporting Trials (CONSORT) flow diagram of the overall study patient population recruitment and disposition over the course of study.
Fig 2.
Intratibial PC3 tumor response to docetaxel (n = 6), radiation (IR, n = 6), or combination treatment (n = 6) shows an additive effect by anatomical and diffusion MRI compared to controls (n = 8).
(A) Tumor volumes plotted over time (p-values in legend show significance versus controls at day 7) show greater cell kill in the combination group (circles, solid line) than either docetaxel (triangles, long-dashed line) or IR (diamonds, short-dashed line) treatment alone, and all treatments resulted in significant cell kill over controls (squares, dotted line). (B) Comparison of mean ADC change to PRMADC+ at day 7 post-treatment-initialization resulted in no significant difference between measurements, but slightly elevated PRMADC+ over mean ADC in the combination treatment (significant difference from controls: * (p<0.05)). (C) ADC color over overlays are shown in the left two columns for pre-treatment and day 7, and corresponding PRMADC overlay and scatterplot are shown on the right.
Fig 3.
PC3 implantations treated with zoledronic acid (ZA, n = 4) show a bone-protective effect compared to controls (n = 8).
(A) MRI tumor volume and ADC determined at day 21 post-treatment-initiation shows a retardation of tumor growth and significantly lower ADC in the zoledronic acid treated animals. (B) PRMHU+ bar plot shows significantly higher volume of bone that increased in density after treatment compared to controls. (C) PRMHU- bar plot shows minimal loss of bone in the ZA-treated group, compared to progressively increasing bone loss in the controls. (D) Representative images for a control (top) and ZA-treated (bottom) mouse showing (from top to bottom) an isosurface, CT slice, PRM overlay, and PRM scatterplot from pre-treatment to 21 days post-treatment.
Fig 4.
LAPC-9 tumors show slower mixed PRMHU+/- response with docetaxel treatment compared to PC3.
(A) Time plots of tumor volume (solid line) and ADC (dashed line) show successful response to treatment (n = 3) as volume shrinkage and ADC increase. (B) PRMHU+ bar plot over time shows more bone density increase in the docetaxel-treated group compared to controls (n = 3), significant on days 14 and 21. (C) PRMHU- bar plot over time shows very little bone loss in the treated group compared to elevated bone mineral loss in the controls (though not significant in this study). (D) Representative images for a control (top) and docetaxel-treated (bottom) mouse showing (from top to bottom) an isosurface, CT slice, PRM overlay, and PRM scatterplot from pre-treatment to 21 days post-treatment.
Fig 5.
PRMHU plots over time post-implantation compare un-treated bone changes in PC3 (diamonds, solid line, n = 4) to LAPC-9 (squares, dashed line, n = 6) implants as quantified by (A) PRMHU+ and (B) PRMHU-.
Fig 6.
(A) Representative PRM overlays show stable disease (top) and progressive disease (bottom) for PRMHU (left) and PRMADC+ (right). Blue represents regions of decreased value, red increased value, and green statistically unchanged value. (B) The bar plot shows significant differences (marked with *) between stable disease (SD, gray, n = 8) and progressive disease (PD, black, n = 4) groups in volume fractions of bone PRM results (labeled PRMHU-, volume fraction of decreased attenuation at about 10 weeks post-treatment) and DW-MRI (volume fraction of increased ADC at about 2 weeks post-treatment).