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

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

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 ??

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.

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% - 110 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

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

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

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

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.

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