Eddy Maurice Paul Brugman

SIRT of liver metastases: physiological and pathophysiological considerations

Available literature on the differences in circulation and microcirculation of normal liver and liver metastases as well as in rheology of the different radiolabelled microspheres [99mTc-labelled macroaggregates of albumin (MAA), 90Y-TheraSpheres and 90Y-SIR-spheres] used in selective internal radiation therapy (SIRT) are reviewed and implications thereof on the practice of SIRT discussed. As a result of axial accumulation and skimming, large microspheres are preferentially deposited in regions of high flow, whereas smaller microspheres are preferentially diverted to regions of low flow. As flow to normal liver tissue is considerably variable between segments and also within one segment, microspheres will be delivered heterogeneously within the microvasculature of normal liver tissue. This non-uniformity in microsphere distribution in normal liver tissue has a significant “liver-sparing” effect on the dose distribution of 90Y-labelled microspheres. Arterial flow to liver metastases is most pronounced in the hypervascular rim of metastases, followed by the smaller metastases and finally by the central hypoperfused region of the larger metastases. Because of the wide variability in size of labelled MAAs and because of the skimming effect, existing differences in flow between metastatic lesions of variable size are likely exaggerated on 99mTc-MAA scintigraphy when compared to 90Y-TheraSpheres and 90Y-SIR-spheres (smaller variability in size and probably also in specific activity). Ideally, labelled MAAs would contain a size range similar to that of 90Y-SIR-spheres or 90Y-TheraSpheres. Furthermore, the optimal number of MAA particles to inject for the pretreatment planning scintigraphy warrants further exploration as it was shown that concentrated suspensions of microspheres produce more optimal tumour to normal liver distribution ratios. Finally, available data suggest that the flow-based heterogeneous distribution of microspheres to metastatic lesions of variable size might be optimized, that is rendered more homogeneous, through the combined use of angiotensin II and degradable starch microspheres.

Prätherapeutische quantitative VOI-Analyse von Lebermetastasen

UNLABELLED Using quantitive VOI analysis, the percentage (99m)Tc-MAA uptake and SUVmax and mean values of liver metastases obtained prior to SIRT were related to treatment response using both a lesion-based and clinical dichotomous approach. Based on the VOI % of (99m)Tc-MAA activity, the estimated (90)Y-microspheres activity/cc (MBq/cc) was calculated from the effective dose injected. Baseline VOI FDG PET SUVmean and max values and estimated MBq/cc values were related to treatment response using a lesion-based approach (% change in SUVmean ≥  50%) and a clinical dichotomous approach. Fifteen treatment sessions were analyzed (13 patients). Using the lesion-based approach (12 treatment sessions) 40 lesions responded and 37 did not. SUVmax and mean values proved significantly different between non-responding and responding lesions; 18.6 (SD 10.8) versus 13.5 (SD 8.4 ) for SUVmax (p = 0.02) and 11.4 (SD 3.8) versus 6.3 (SD 4.5) for SUVmean (p = 0.002). Using the clinical dichotomous approach (15 treatment sessions / 11 responding), 91 lesions were analyzed; 57 responded. VOI volumes and estimated (90)Y-loaded glass microspheres activity (MBq/cc) did not differ between responders and non responders; 24 cc (SD 27) versus 21 cc (SD 21 cc) (p = 0.4) and 1.95 MBq/cc (SD 1.1 MBq/cc) versus 1.90 MB/cc (SD 2.7 MBq/cc) (p = 0.92). On the contrary, SUVmax and mean values proved significantly different between responders and non-responders; 23.7 (SD 9.8) versus 9.4 (SD 3.8 ) for SUVmax (p = 0.0001) and 13.1 (SD 8.1) versus 4.9 (SD 1.4) for SUVmean. CONCLUSION These findings suggest that in patients presenting with high baseline SUVmax and mean values, the administration of higher activities or alternatively, other potentially more useful treatment options might be considered.

Quantitative p retreatment VOI analysis of liver metastases

UNLABELLED Using quantitive VOI analysis, the percentage (99m)Tc-MAA uptake and SUVmax and mean values of liver metastases obtained prior to SIRT were related to treatment response using both a lesion-based and clinical dichotomous approach. Based on the VOI % of (99m)Tc-MAA activity, the estimated (90)Y-microspheres activity/cc (MBq/cc) was calculated from the effective dose injected. Baseline VOI FDG PET SUVmean and max values and estimated MBq/cc values were related to treatment response using a lesion-based approach (% change in SUVmean ≥  50%) and a clinical dichotomous approach. Fifteen treatment sessions were analyzed (13 patients). Using the lesion-based approach (12 treatment sessions) 40 lesions responded and 37 did not. SUVmax and mean values proved significantly different between non-responding and responding lesions; 18.6 (SD 10.8) versus 13.5 (SD 8.4 ) for SUVmax (p = 0.02) and 11.4 (SD 3.8) versus 6.3 (SD 4.5) for SUVmean (p = 0.002). Using the clinical dichotomous approach (15 treatment sessions / 11 responding), 91 lesions were analyzed; 57 responded. VOI volumes and estimated (90)Y-loaded glass microspheres activity (MBq/cc) did not differ between responders and non responders; 24 cc (SD 27) versus 21 cc (SD 21 cc) (p = 0.4) and 1.95 MBq/cc (SD 1.1 MBq/cc) versus 1.90 MB/cc (SD 2.7 MBq/cc) (p = 0.92). On the contrary, SUVmax and mean values proved significantly different between responders and non-responders; 23.7 (SD 9.8) versus 9.4 (SD 3.8 ) for SUVmax (p = 0.0001) and 13.1 (SD 8.1) versus 4.9 (SD 1.4) for SUVmean. CONCLUSION These findings suggest that in patients presenting with high baseline SUVmax and mean values, the administration of higher activities or alternatively, other potentially more useful treatment options might be considered.

Quantitative p retreatment VOI analysis of liver metastases. (99m)Tc-MAA SPECT/CT and FDG PET/CT in relation with treatment response to SIRT.

UNLABELLED Using quantitive VOI analysis, the percentage (99m)Tc-MAA uptake and SUVmax and mean values of liver metastases obtained prior to SIRT were related to treatment response using both a lesion-based and clinical dichotomous approach. Based on the VOI % of (99m)Tc-MAA activity, the estimated (90)Y-microspheres activity/cc (MBq/cc) was calculated from the effective dose injected. Baseline VOI FDG PET SUVmean and max values and estimated MBq/cc values were related to treatment response using a lesion-based approach (% change in SUVmean ≥  50%) and a clinical dichotomous approach. Fifteen treatment sessions were analyzed (13 patients). Using the lesion-based approach (12 treatment sessions) 40 lesions responded and 37 did not. SUVmax and mean values proved significantly different between non-responding and responding lesions; 18.6 (SD 10.8) versus 13.5 (SD 8.4 ) for SUVmax (p = 0.02) and 11.4 (SD 3.8) versus 6.3 (SD 4.5) for SUVmean (p = 0.002). Using the clinical dichotomous approach (15 treatment sessions / 11 responding), 91 lesions were analyzed; 57 responded. VOI volumes and estimated (90)Y-loaded glass microspheres activity (MBq/cc) did not differ between responders and non responders; 24 cc (SD 27) versus 21 cc (SD 21 cc) (p = 0.4) and 1.95 MBq/cc (SD 1.1 MBq/cc) versus 1.90 MB/cc (SD 2.7 MBq/cc) (p = 0.92). On the contrary, SUVmax and mean values proved significantly different between responders and non-responders; 23.7 (SD 9.8) versus 9.4 (SD 3.8 ) for SUVmax (p = 0.0001) and 13.1 (SD 8.1) versus 4.9 (SD 1.4) for SUVmean. CONCLUSION These findings suggest that in patients presenting with high baseline SUVmax and mean values, the administration of higher activities or alternatively, other potentially more useful treatment options might be considered.