Page 828 - Read Online

Bhangui et al. Hepatoma Res 2020;6:71 I http://dx.doi.org/10.20517/2394-5079.2020.67 Page 7 of 15

Table 2. Characteristics of tumour recurrence and treatment modalities
Characteristics (n = 100) Values
Time to recurrence after LDLT 16 months
Median (range) (2-108 months)
AFP at the time of recurrence (ng/mL) Mean ± SD 80 ± 11,796
Site of tumour recurrence (number of patients)
Lungs 53
Liver 37
Bone 21
Lymph nodes 7
Brain 2
Scar site 2
More than one site of recurrence 36
Treatment for recurrence
Kinase inhibitors alone (Sorafenib, Regorafenib, Lenvatinib) 32 patients
Kinase inhibitors with mTORi’s (sirolimus, everolimus) only 36 patients
Medical (Kinase inhibitors with/without mTORi’s) plus other modalities (surgery, radiotherapy, ablation) 32 patients
Other modalities used in addition to kinase inhibitors and mTORi’s to treat metastases
Radiotherapy 15
TACE for liver metastases 5
VATS for lung metastases 5
Surgical resection of metastases (liver, scar site, mediastinal metastases, laminectomy, supra adrenal metastases) 9
Percutaneous ethanol injection in lymph node 3
Radiofrequency ablation and microwave ablation for liver, lung, or bone metastases 10
More than 1 modality used in one patient 11
LDLT: living donor liver transplantation; mTORi: mammalian target of rapamycin inhibitor; TACE: transarterial chemoembolization;
VATS: video assisted thoracoscopic surgery

When we compared the tumour characteristics at the time of recurrence between the three treatment
groups, we found that there was no statistically significant difference in AFP levels, occurrence of
metastases at single vs. multiple sites, single vs. multiple nodules at recurrence, or intrahepatic recurrence
only vs. intrahepatic and extrahepatic recurrence [Supplementary Table 2]. However, on post hoc analysis
we did find that more patients in the Kinase inhibitor + mToR inhibitor group had HCC recurrence within
1 year of LDLT (P = 0.05), and had multiple nodules at the time of recurrence (vs. single nodule, P = 0.04)
as compared to the combined therapy group.

Survival post recurrence
One-year, 2-year, and 3-year post recurrence survival were 57%, 31%, and 24%, respectively, with a median
survival of 12 months (IQR 4-24 months) [Figure 3]. The maximum post recurrence survival was 88 months
(7½ years), and the longest survivor still alive is 77 months post recurrence.

With regards to predictors of survival after recurrence, HCC recurrence within one year after LDLT (P
=0.004, HR = 2.38, 95%CI: 1.325-4.276), AFP > 200 ng/mL at the time of recurrence (P = 0.02, HR = 2.075,
95%CI: 1.121-3.841), and recurrence at multiple sites (P = 0.047, HR = 1.831, 95%CI: 1.009-3.321), were
poor prognostics factors for post recurrence survival [Table 3].

Post recurrence survival rates in the tyrosine kinase inhibitor only group (1-year, 3-year OS of 38%
and 15%), as well as the tyrosine kinase with mTORi group (1-year, 3-year OS of 56% and 19%) were
significantly inferior to those who received multimodality treatment using combined medical and surgical/
ablative/radiotherapy (1-year, 3-year OS of 77% and 39%); P = 0.017 [Figure 4].

DISCUSSION
Post- transplant HCC recurrence is seen in 10%-20% of the patients and this has remained stable over the
[6]
years, despite repeated efforts to refine the selection criteria for transplant to achieve best outcomes . This
is much higher when the selection criteria are expanded, especially in the LDLT setting. A 2015 systematic