Table 1.
Non-exhaustive overview of recent dose-response studies showing a large variety in all relevant parameters. This variety in outcome measures and reported dose thresholds complicate data pooling and the extraction of reliable clinical dose limits
| Study | Tumor type | Microsphere | Modality | Outcome | Dose model | Tumor dose | Liver dose | Remarks |
|---|---|---|---|---|---|---|---|---|
| Chiesa [61] | HCC | Glass | 99mTc-MAA SPECT | Choi 50% (CR and PR) [64] | EUD, BED, EUBED, D avg |
TCP(50%) 560 Gy (Davg) | NTCP(50%) 97 Gy (Davg) | No scatter correction; dose reported here based on SPECT-based delineation; large influence of tumor volume |
| Srinivas [58] | HCC | Glass | 90Y PET | mRECIST (CR, PR) | D avg | Davg responders = 215 Gy | – | Non-significant association |
| Garin [135, 136] | HCC | Glass | 99mTc-MAA SPECT | EASL (CR, PR and SD) | D avg | Threshold for response = 205 Gy | 84 Gy | Large, heterogeneous tumors probably require higher dose. |
| Chan [137] | HCC | Glass | 90Y PET | mRECIST | Dmedian, D70 | Dmedian responders = 225 Gy; Dmedian non-responders = 83 Gy; D70 responders = 140 Gy; D70 non-responders = 24 Gy | – | |
| Kappadath [134] | HCC | Glass | bSPECT | mRECIST | Davg, BEDavg | TCP (50%) Davg = 160 Gy (95% CI = 123 to 196 Gy)Dmedian responders: 209 Gy, non-responders: 138 Gy | No complication observed for normal liver Davg < 44 Gy | |
| Fowler [138] | HCC, NET, CRC | Resin and glass | 90Y PET/MR | (v)RECIST | D20, D70, Davg | Davg (29.8 Gy; sensitivity 76.9%; specificity 75.9%) and D70 (42.3 Gy; sensitivity 61.5%; specificity 96.6%) were predictive of response in CRC; No link found for other tumor types | – | |
| Strigari [68] | HCC | Resin | bSPECT | EASL/RECIST | BED | TCP(50%) 110–120 Gy | NTCP (50%) 52 Gy | |
| Kao [54] | HCC and cholangio | Resin | 90Y PET | mRECIST + ‘minor response’ | D 70 | D70 > 100 Gy (HCC); D70 > 90 Gy (cholangio) | – | Only patients with TN > =2 on MAA SPECT were selected for this study |
| Flamen [57, 139] | CRC | Resin | 99mTc-MAA SPECT | TLG change > 50% | D avg | Davg > = 66 Gy (c.i. 32–159 Gy) | – | Chang’s attenuation correction Patient-relative calibration; assuming no LSF |
| Van der Hoven [140] | CRC | Resin | 90Y PET | TLG change > 50% | Davg and LMER | Davg 40–60 Gy minimally | – | Higher baseline TLG leads to a higher reduction |
| Willowson [59] | CRC | Resin | 90Y PET | TLG change > 50% | D avg | 50 Gy | – | At lower doses, heterogeneity becomes more important |
| Eaton [55] | Metastatic melanoma | Resin | bSPECT | TLG change and SUVmax | Dmax, Davg, V50 | Sign. associations Dmax with decreased TLG; Davg and V50 with an absolute decrease in SUVmax. Stronger effect for D > 50 Gy | – | No scatter or attenuation correction. 12 mm post-filter; crystal effects neglected |
| Chansanti [141] | NET | Resin | 99mTc-MAA SPECT | mRECIST | D avg | Davg responders = 285.8 Gy; Davg non-responders = 128.1 Gy | Patients with moderate to severe toxicity received Davg > 50 Gy on the liver | Reported response at early (median 2.3 months) follow-up |
HCC hepatocellular carcinoma, NET neuroendocrine tumor, CRC colorectal cancer, Cholangio cholangiocarcinoma, LMER linear mixed-effects regression model, CR complete response, PR partial response, SD stable disease