Post-treatment three-dimensional voxel-based dosimetry after Yttrium-90 resin microsphere radioembolization in HCC

Abstract

Background: Post-therapy [⁹⁰Y] PET/CT-based dosimetry is currently recommended to validate treatment planning as [^99mTc] MAA SPECT/CT is often a poor predictor of subsequent actual [⁹⁰Y] absorbed dose. Treatment planning software became available allowing 3D voxel dosimetry offering tumour-absorbed dose distributions and dose-volume histograms (DVH). We aim to assess dose-response effects in post-therapy [⁹⁰Y] PET/CT dosimetry in SIRT-treated HCC patients for predicting overall and progression-free survival (OS and PFS) and four-month follow-up tumour response (mRECIST). Tumour-absorbed dose and mean percentage of the tumour volume (V) receiving ≥ 100, 150, 200, or 250 Gy and mean minimum absorbed dose (D) delivered to 30%, 50%, 70%, and 90% of tumour volume were calculated from DVH's. Depending on the mean tumour -absorbed dose, treated lesions were assigned to a < 120 Gy or ≥ 120 Gy group.

Results: Thirty patients received 36 SIRT treatments, totalling 43 lesions. Median tumour-absorbed dose was significantly different between the ≥ 120 Gy (n = 28, 207 Gy, IQR 154-311 Gy) and < 120 Gy group (n = 15, 62 Gy, IQR 49-97 Gy, p <0 .01). Disease control (DC) was found more frequently in the ≥ 120 Gy group (79%) compared to < 120 Gy (53%). Mean tumour-absorbed dose optimal cut-off predicting DC was 131 Gy. Tumour control probability was 54% (95% CI 52-54%) for a mean tumour-absorbed dose of 120 Gy and 90% (95% CI 87-92%) for 284 Gy. Only D30 was significantly different between DC and progressive disease (p = 0.04). For the ≥ 120 Gy group, median OS and PFS were longer (median OS 33 months, [range 8-33 months] and median PFS 23 months [range 4-33 months]) than the < 120 Gy group (median OS 17 months, [range 5-33 months] and median PFS 13 months [range 1-33 months]) (p < 0.01 and p = 0.03, respectively).

Conclusions: Higher 3D voxel-based tumour-absorbed dose in patients with HCC is associated with four-month DC and longer OS and PFS. DVHs in [⁹⁰Y] SIRT could play a role in evaluative dosimetry.

Keywords: Dose-volume histogram; Dose–response effects; Dosimetry; Hepatocellular carcinoma; Selective internal radiation therapy; Tumour-absorbed dose.

Fig. 1

Flowchart for the selection of patients. CRC colorectal cancer, CCC cholangiocellular carcinoma, MBC metastatic breast cancer, NET neuroendocrine tumour

Fig. 2

Mean tumour dose for observed responses (mRECIST). Group comparisons showed no significant differences. CR complete response, PR partial response, SD stable disease, PD progressive disease, DC disease control

Fig. 3

a AUDVH of lesions showing DC (n = 30) and PD (n = 13), where AUDVH represents tumour-absorbed dose (p = 0.05). b ROC analysis for AUDVH to predict DC. Optimal cut-off noted with asterisk at 131 Gy, with 61.54% sensitivity and 73.33% specificity). The area under the ROC curve of AUDVH for predicting DC was 0.692 (95% CI 0.515–0.869). AUDVH area under dose-volume histogram, DC disease control, PD progressive disease

Fig. 4

Tumour control probability (TCP) plotted in relation to tumour-absorbed dose. Black curve is a fit of linear quadratic model (95% confidence intervals dotted in grey). Binned data with 20 Gy intervals are shown with diamond shapes. Individual cases are represented by black lines in the bottom. CI confidence interval

Fig. 5

a Mean tumour volume percentage (V) at V100, V150, V200, and V250. b Mean minimum absorbed dose (D) delivered for D30 (p = 0.04), D50, D70, and D90. DC disease control, PD progressive disease

Fig. 6

a Kaplan–Meier overall survival (OS) estimates (p < 0.01), b Kaplan Meier progression-free survival (PFS) estimates (p = 0.03)