A typical 3D-RD tumor dosimetric analysis is shown in . 153Sm-EDTMP uptake in tumors was clearly identifiable in both the low- and high-dose posttherapy SPECT images. Heterogeneous tumor densities were observed at the voxel level in all tumors that were studied. In the tumors analyzed, the mean tumor density ranged between 0.8 and 1.3 g-cm−3. The tumor density and absorbed dose volume histograms shown in represent a typical example of the variability observed in all tumors. In the 6-wk interval between the low-dose () and high-dose () therapy, new tumor growth was also observed in some patients on 153Sm-EDTMP SPECT and was confirmed using CT.
FIGURE 1 Example of 3D-RD analysis. Four hours after low-dose 153Sm-EDTMP SPECT for patient 2, 2 tumors were identified (T1 and T2) for dosimetry analysis (A). Density and dose–volume histograms for tumors are also shown. Four hours after high-dose 153 (more ...)
summarizes the 3D-RD tumor dosimetric analysis. Six patients (19 tumors) had datasets complete enough for the 3D-RD analysis. The tumor mass ranged between 11 and 633 g. In the 7 tumors (5 patients) that were analyzed at low-dose therapy, the mean and SD of the tumor-absorbed dose, BED, and EUD were 4.5 ± 4.7, 4.6 ± 4.8, and 2.3 ± 1.2 Gy, respectively. In the 12 tumors (4 patients) that were analyzed at high-dose therapy, the mean and SD of tumor-absorbed dose, BED, and EUD were 17.2 ± 17.0, 22.6 ± 25.4, and 5.4 ± 3.6 Gy, respectively. The 5-fold increase in administered activity from low- to high-dose therapy resulted in an approximately 4-fold (3.8) increase in mean tumor-absorbed dose averaged over the treated patients. However, the equivalent uniform dose on average increased only about 2-fold (2.4). In 5 tumors (3 patients) that were treated at both low- and high-dose therapy, the average ratio of mean tumor-absorbed dose in the same tumors that were treated at both low and high dose was 6.6 and ranged from 2.7 to 14.8. In 2 patients (1 and 6), the percentage reduction in tumor volume could not be measured after high-dose therapy, because the patients had disease progression and did not return for follow-up radiographic evaluation.
Summary of Patient-Specific (3D-RD) Tumor Dosimetry
show the tumor mass and mean density dependence of mean tumor-absorbed dose. A large variation was observed in the mean tumor-absorbed dose across individual tumors in the 6 patients studied. No relationship between mean tumor-absorbed dose and tumor mass or tumor density could be discerned. Likewise, show no corresponding relationship for EUD.
FIGURE 2 Patient-specific 3D-RD tumor dosimetry analyses. Plots of tumor mass and mean tumor density against mean tumor-absorbed dose per unit administered activity (A and B, respectively) and tumor mass and mean tumor density dependence of equivalent uniform (more ...)
shows the curve fit for the OLINDA/EXM dose coefficients for the unit-density spheres of various masses for 153Sm. The fit parameters were a = 149.9 and b = −0.9886. shows the percentage difference in dose coefficients for individual sphere mass between 3D-RD and OLINDA/EXM (percentage difference, mean ± SD, −1.3% ± 0.01%; range, −0.4% to −3.9%). The percentage difference in the mean tumor-absorbed dose between the patient-specific 3D-RD and the OLINDA/EXM unit-density sphere model ranged between −0.5% and 4%. compare 3D-RD–calculated patient tumor-absorbed doses (obtained from the whole-tumor VOI) with OLINDA-derived estimates. The results show that 3D-RD values were greater by no more than 4%, compared with the OLINDA estimates. This is because the 3D-RD calculation accounts for dose contributions from other source volumes in the body. The effect of tumor mass, density, and sphericity is examined to see if any trends may be discerned in the already small differences found. shows that the percentage difference in mean tumor-absorbed dose was (marginally) larger for tumor masses less than 60 g. To some extent, this difference depends on the tumor location relative to normal organ activity distribution and on the cross-organ contribution to the mean tumor-absorbed dose. In general, however, the mean tumor-absorbed dose to smaller tumors was influenced by external dose contributions to a greater extent than the mean absorbed dose to larger tumors. There was no clear trend observed for the mean tumor-absorbed dose comparison with mean tumor density. The sphericity of the tumors ranged between 0.63 and 0.99. shows the percentage difference in mean tumor-absorbed dose between 3D-RD and OLINDA/EXM as a function of sphericity of the tumors. Smaller tumors formed a cluster on the sphericity plot around 1.0 (equivalent to a sphere). Larger tumors formed a cluster around 0.6 (equivalent to a tetrahedron), exhibiting nonspheric shape.
FIGURE 3 Mean absorbed dose calculation based on unit-density sphere model. (A) Power-law fit (dotted line) to OLINDA/EXM dose coefficients against 153Sm-filled homogeneous unit-density spheres of various masses (1–600 g) is demonstrated. 3D-RD–generated (more ...)
Comparison of percentage difference in mean absorbed dose estimates between 3D-RD and OLINDA/EXM unit-density sphere model as function of individual patient tumor mass (A), density (B), and sphericity (C). Tumor mass is in logarithmic scale in A.
Radiographic response of disease was evaluated after recovery from the first, low-dose therapy and again after recovery from the higher-dose therapy. All 6 patients experienced disease progression after low-dose therapy. Two patients (2 and 5) had stable disease after the high-dose treatment. As noted in a previous publication (2
), the median time to progression was 79 d for the entire cohort of patients. Two patients achieved prolonged survival (990 and 1,432 d), despite eventual disease progression. shows the mean tumor-absorbed dose and EUD for individual tumors, categorized by overall patient response. The plot indicates that the tumors identified in patients who had disease stabilization had received at least a 21-Gy mean absorbed dose and correspondingly a tumor EUD of 6 Gy. Because the absorbed dose was not calculated for all tumors used in the overall response evaluation, the significance of the observed 21-Gy mean tumor-absorbed dose threshold for progressive disease versus stable disease and corresponding 6-Gy threshold for EUD depends on the degree to which the collection of individual calculated mean tumor-absorbed doses reflects the mean absorbed dose to all of the tumors in each patient. As shown in , this depends on the patient and on the dosimetry parameter. For example, the average absorbed dose per administered activity for any one of the tumors in patients 5, 6, and possibly 1 is likely to reflect the average absorbed dose to all tumors, whereas this is not the case for patient 2. Because the EUD also accounts for spatial nonuniformity, the EUD for any 1 patient tumor is less likely to reflect the EUD for the collection of patient tumors, and we see approximately the same EUD in each of the 5 analyzed tumors for patient 6.
Mean tumor-absorbed dose (left y-axis) and EUD (right y-axis) for individual tumors, plotted against overall radiographic response criteria. PD = progressive disease; SD = stable disease.
Individual tumor response versus dose data is shown in . Tumors grew when the mean absorbed dose or EUD was below 21 or 6 Gy, respectively. Statistical analysis of these data suggests that both mean tumor-absorbed dose and EUD are positively related to percent tumor volume reduction (P = 0.031 and 0.023, respectively).
Plot of percentage volume reduction against mean tumor-absorbed dose (A) or EUD (B).