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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

From: The physics of radioembolization

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

  1. 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