1. Prognostic effect of complete pathologic response following TACE on HCC patients undergoing liver resection or transplantation
Prognostic effect of complete pathologic response following TACE on HCC patients undergoing liver resection or transplantation
Woo-Hyoung Kang, Shin Hwang, Young-Joo Lee, Ki-Hun Kim, Chul-Soo Ahn, Deok-Bog Moon, Gi-Won Song, Sung-Gyu Lee
Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea

2. Background Neoadjuvant TACE Definite treatment with curative intent
Palliative cytoreduction therapy
Downstaging treatment
Response test for suitability of LT
Combination
As you know,
The purposes of preoperative TACE were diverse
such as definite treatment with curative intent,
palliative cytoreduction therapy,
downstaging treatment For liver resection or transplantation
response test for suitability of LT,
or their combinations

3. Complete Pathologic Response(CPR)
Background
Study Group
Preop-TACE, HCC patients
Control Group
Minimal risk group of Tumor recurrence
: Solitary HCC ≤2 cm
: Absence of neoadjuvant treatment
: R0 resection
: BCLC stage A
Liver Resection or Liver transplantation
My study aimed to assess the prognostic effect of complete pathological response (CPR) after preoperative transcatheter arterial chemoembolization (TACE) for hepatocellular carcinoma (HCC) in patients undergone liver resection (LR) or liver transplantation (LT).
In this study, We compared long-term outcomes on TACE-induced CPR after both Liver resection and Liver transplantation, with those on minimal risk group of tumor recurrence
The inclusion criteria of minimal risk group were solitary HCC under 2 cm; absence of neoadjuvant treatment; and R0 resection, which are quite compatible to the early stage (A) of the original Barcelona Clinic Liver Cancer (BCLC) staging classification
Complete Pathologic Response(CPR)
Prognosis ??

4. Complete Pathologic Response(CPR) ??
Definition
Study Group
Complete Pathologic Response(CPR) ??
Area of necrosis ≥99% of the total tumor volume
Absence of viable tumor cells in any nodule.
We defined CPR as an area of necrosis over 99% of the total tumor volume, thus showing absence of viable tumor cells in any nodule. In our center, it is demonstrated like this.

5. Study design and patient selection
7783 HCC patients (January, 2000 ~ December, 2014)
n=6049
n=1334
Liver resection (LR) pathway
Liver transplantation (LT) pathway
TACE No
TACE No
Yes
Yes
n=997
n=5052
n=738
n=596 LR LR LT LT
We selected patients on this period for 15 years.
7783 patients of hepatocellular carcinoma underwent liver resection or liver transplantation were found.
In these, we devided two catergories, liver resection and transplantion.
Pre-resective TACE patients were 997, their 11% patients showed complete pathologic response on final biopsy.
And as Control group, minimal risk of recurrence group which had Single and miximal tumor size under 2cm, included 476 patients.
On the hand, in Liver transplantation pathway. Pretransplanted TACE patients were 738, their 31%-233 patients showed complete pathologic response. Another Control group included 184 patients. No
CPR
Single,
≤2 cm No No
One or two,
≤2 cm
CPR No
n=887
n=4576
n=505
n=412
Exclusion
Exclusion
Exclusion
Exclusion
Yes
Yes
Yes
Yes
n=110
n=476
n=233
n=184 LR
study group LR
Control group LT
study group LT
Control group

6. Minimal risk of tumor recurrence
Patietns demographics
CPR
Minimal risk of tumor recurrence
Group
Liver resection
Liver transplantation
Parameter
Study group
Control group
p-value
Patient number
110
476
233
184
Age (yrs)
54.9±8.5
55.6±9.1
0.864
53.7±7.4
53.0±6.7
1.000
Gender (Male / Female) (n)
93 / 17
341 / 135
0.005
191 / 42
147 / 37
0.589
TACE session
mean
1.4±1.2 NA
2.2±2.4
Once (n) 81 50
≥2 (n) 29
183
Type of liver resection (n)
0.125
Anatomical 95
434
Non-anatomical 15 42
Maximal tumor diameter (cm)
4.2±2.8
1.5±0.4
0.000
2.5±1.3
Tumor number (n)
0.193
Single
164
140
Two 11 37 44 ≥3 4 32
This is demographics
Tumor size 4 cm

7. Liver Transplantation
Recurrence rate
Liver resection
Liver Transplantation
Study group
Control group
Intrahepatic recurrence
40 (85.1%)
122 (94.6%)
4 (23.5%)
3 (60.0%)
Extrahepatic recurrence
Lung
3 (6.4%)
2 (1.6%)
6 (35.3%)
1 (20.0%)
Bone
3 (2.3%)
2 (11.8%)
Adrenal gland
1 (2.1%)
1 (5.9%)
Peritoneum
Combined intra- and extrahepatic recurrence
LR study
(p=0.000)
LR control
Proportions of Recurrence
(p=0.000)
This graph shows recurrence rate of each groups.
First, Transplanted patients had dramatically lower recurrence rate than resected patients.
In Resection study, follow up year tumor recurrence rates were higher than in LR control group its P-value is about 0.
It means that recurrence rate on tumor necrosis group is not better than minimal risk group
Similary, In transplanted study group, their recurrence rate are higher than in non-TACE, minimal risk control group. Its P-value is p=0.019.
Next, the Type of Tumor recurrence is shown.
Intrahepatic recurrence was the main type of initial tumor recurrence in both LR study and control groups.
But resection groups have more intrahepatic recurrence than transplantation groups. (85.1, 94.6% Vs 23.5,60.0%)
Probably. following LT, the risk of intrahepatic metastasis was decreased, because the diseased remnant liver was completely resected.
LT study
(p=0.019)
LT control
Postoperative months

8. Overall survival (p=0.112) Proportions of survival (p=0.000) (p=0.000)
LT control
LT study
Proportions of survival
(p=0.000)
LR control
LR study
(p=0.000)
This graph shows patient survival rate on each groups.
Overally, In comparing both resection & transplantation group, Transplanted group showed higher survival outcomes than resected patients. (p=0.000). Its P-value has statically significance.
In resection group, Survival rate of Study group was lower than in LR control group (p=0.000)
This means that overall survival rate of Study group after resection is not better than minimal risk group
In transplanted group, this graph shows like as lower survival in Study group. But it has not statically significance LT control group (p=0.112).
Postoperative months

9. Conclusion
* Incidence of Complete pathologic response : 11%(LR) Vs 31.6%(LT)
* Liver resection on CPR
surrogate pathologic predictor of improved post resection outcomes.
Not minimized the risk of tumor recurrence, as Control group
Resectable HCC : not recommended Preoperative TACE
Since TACE-induced CPR decrease only the active tumor load to the patients undergoing LR, CPR should not be interpreted as a reliable parameter permitting loose or less strict follow-up for HCC recurrence surveillance
* Liver Transplantation on CPR
Down-staging therapy, Reduction of post-transplant tumor recurrence
Compared Resection(CRR or not), Prognostic Advantage
Incidence of Complete pathologic response on both group are 11% Vs 31.6%. Its shows low incidence rate of CPR in the resected patients.
Maybe their back ground reasons are “preferred initial Tx of HCC is resection”, and “patients showing complete radiologic response might not undergo resection)
Liver resection on CPR
CPR could be used surrogate pathologic predictor of improved post resection outcomes
But it does not minimized the risk of tumor recurrence, as Control group
So, We suggested that, In patients with resectable HCC, preoperative TACE should be avoided.
And Since TACE-induced CPR decrease only the active tumor load to the patients undergoing LR, CPR should not be interpreted as a reliable parameter permitting loose or less strict follow-up for HCC recurrence surveillance
Liver Transplantation on CPR
After TACE as down-staging therapy, the active tumor load might be theoretically minimized
comparing with the LR study and control groups, the tumor recurrence rate in the LT study group appears to be much improved.
It has definitie prognostic advantage.

10. Thank You for your attention
Thank you for introduction.
I’m Woo-Hyoung Kang from Asan medical center
Todays,The title is Prognostic effect of complete pathologic response following TACE on HCC patients undergoing liver resection or transplantation