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e16127 Background: There are different views on the scope of indications for surgical treatment of HCC worldwide. Unlike the Barcelona Clinic Liver Cancer, the European Association for Study of the Liver, and the American Association for the Study of Liver Diseases which recommend surgical resection as the first choice only for early HCC, it is also recommended as the first treatment for selected patients with intermediate or advanced HCC in China. However, in any case, postoperative recurrence is an important issue affecting the long-term survival of HCC patients, and to date, there is no globally recognized treatment algorithm for adjuvant therapy. We performed a survey to understand the patient characteristics and clinical status of hepatobiliary surgeons’ decision aids for adjuvant treatment. Methods: This survey was conducted among senior hepatobiliary surgeons who work at high-volume hospitals in China. Surgeons were asked to fill out an online questionnaire by scanning the QR code. Results: From September to November 2021, 511 surgeons from 55 cities responded. Among them, 70.3% worked in general hospitals, 26.8% in cancer hospitals, and 2.9% in integrative medicine hospitals. The majority of the institutions were tertiary hospitals (91.2 %). When determining whether a patient was suitable or not for adjuvant therapy, surgeons mainly considered tumor factors (chosen by 92.8% and 81.6%) and patient factors (chosen by 80.8% and 75.3%). The analysis showed that the patients whom surgeons considered for adjuvant therapy had one or more of the following characteristics: Tumor factors including China liver cancer (CNLC) stage Ia-IIIb (preoperative), R1 resection, Child-Pugh A or B liver function, well recovery from surgery, presence of ≥1 high-risk recurrence factors (i.e. microvascular invasion, macrovascular tumor thrombus, and hilar lymph node metastasis); Patient factors which were hepatocarcinoma-related medical history (e.g., HBV/HCV) and affordability. Most surgeons used targeted therapy (83.8%, mainly anti-angiogenic multi-kinase inhibitors), TACE (72.8%), or combination therapy (60.3%, mainly targeted drugs combined with immunotherapy or TACE) as adjuvant therapy. When asked to choose the two most related factors impacting treatment compliance, 52.1% chose patients' financial status, and 51.7% considered adverse reactions. Less adverse reactions (71.0% of surgeons), better efficacy (66.7%), and a higher reimbursement ratio (53.3%) were the top 3 unmet need for future adjuvant therapy. Conclusions: This survey presented a patient portrait that Chinese hepatobiliary surgeons considered for adjuvant therapy and the practice patterns in adjuvant therapy for HCC. However, the patient group that can benefit from adjuvant therapy remains to be explored and validated in prospective clinical studies.

e16149 Background: Emerging data suggest that circulating tumor DNA (ctDNA) could detect minimal residual disease (MRD) and reflect tumor recurrence after radical resection in hepatocellular carcinoma (HCC). However, most reported ctDNA measurements are based on hotspot mutations and their predictive value in liver transplantation (LT) are still undetermined. We conducted a pilot study investigate ctDNA fingerprint as the detection marker of MRD in HCC patients undergoing LT. Methods: We enrolled 74 patients in HCC and monitored their ctDNA changes along the course of treatment at both pre- and post-operation by serial sampling of peripheral blood. All of the patents were treated by LT, and their ctDNA variations were used to assess the recurrence. We analyzed the correlation between ctDNA levels and recurrence-free survival (RFS) of the patients. Results: We monitored the ctDNA value of each patient before and after LT and found that the ctDNA-positive group was associated with higher recurrence rate (31.7% vs 11.5%), and has a shorter RFS than that of the ctDNA-negative group at baseline (preopreation) (HR, 3.25; CI 95% 1.18-8.97; p = 0.019). The conclusion also stands in patients at first timepoint follow-up after LT (postoperation) (recurrence rate, 46.2% vs 21.3%; HR, 4.26; CI 95% 1.62-11.2; p = 0.010). Moreover, changes of ctDNA were associated with RFS during the course after LT, both the ctDNA-decreased group and ctDNA-negative group have favorable clinical benefit than ctDNA-increased group. Conclusions: This study confirming the association between baseline levels of ctDNA and RFS in HCC undergoing LT. More importantly, it suggests the change of ctDNA level in plasma is a promising biomarker of MRD detection and patient prognosis in early HCC.

421 Background: Immune checkpoint inhibitors (ICI) targeting PD-1/L1 or in combination with CTLA-4 have shown therapeutic benefit in patients with advanced hepatocellular carcinoma (aHCC). This study aimed to evaluate the safety, tolerability, and preliminary efficacy of IBI310, an anti-CTLA-4 monoclonal antibody (mAb), combined with sintilimab, in patients with aHCC who failed or intolerant to previous systemic therapy. Methods: Three cohorts were pre-designed to explore recommended dose of IBI310 in de-escalation order: sintilimab 200 mg plus IBI310 3, 2 or 1 mg/kg every 3 week (q3w). Patients will receive the combined treatment up to 4 cycles, followed by sintilimab 200 mg q3w up to 24 months. Primary endpoint was safety. Key secondary endpoints included objective response rate (ORR), disease control rate (DCR), progress free survival (PFS) and overall survival (OS) by RECISTv1.1 per investigators. Results: 9 subjects were initially treated with sintilimab 200 mg plus IBI310 3 mg/kg q3w without predefined adverse event (AE) observed. 3 mg/kg was determined as recommended dose of IBI310 and no subject was assigned to other cohorts. As of the data cut-off of August 30, 29 subjects were enrolled (median age 51.4 years, 86.2% male, 96.6% BCLC C, 24.1% ICI treated). The average treatment cycles of IBI310 and sintilimab were 2.8 and 5.7. The most frequent treatment related adverse events (TRAEs) of any grade were alanine transaminase increases (34.5%), aspartate transaminase increases (34.5%), thrombopenia (24.1%), and lipase increases (24.1%). Grade ≥3 TRAEs occurred in 34.5% of subjects (including one grade 5 immune-mediated pneumonitis). Dose interruption and discontinuation rates due to AE were 55.2% and 6.9%. With a median follow-up of 9.89 months, investigator confirmed ORR and DCR were 17.2% (all partial response, including one anti-PD1 mAb failed) and 72.4%. The median PFS was 3.9 months (95% CI: 2.6, NR) and median OS not reached (95% CI: 11.4, NR). The 6-month PFS and OS rates were 45.8% (95%CI 25.2%, 64.2%) and 93.1% (95%CI 75.1%, 98.2%) respectively. 6 patients remain on treatment at cutoff date. Conclusions: The combination of sintilimab and IBI310 shows promising efficacy and managable safety profile in aHCC patients. Our results are comparable to that have been published in the same setting. This regimen is currently being evaluated in phase II study. Clinical trial information: NCT04401813.

4099 Background: Lenvatinib monotherapy and lenvatinib plus PD-1 antibody have shown some clinical benefit for advanced intrahepatic cholangiocarcinoma (ICC) in the second-line setting. Our study assesses the role of lenvatinib plus toripalimab (PD-1 antibody) for advanced ICC patients as the first line therapy. Methods: Patients (pts) with locally advanced or metastatic ICC received 12 mg/day (Body Weight ≥60 kg) or 8 mg/day (Body Weight

e16163 Background: The prognosis of advanced intrahepatic cholangiocarcinoma (ICC) remains dismal with gemcitabine-based first-line chemotherapy. This study is to evaluate the safety and efficacy of lenvatinib in combination with gemcitabine and oxaliplatin (Gemox) chemotherapy in the advanced ICC. Methods: Locally advanced or metastatic ICC patients (pts) were given lenvatinib 12 mg/day (body weight ≥60 kg) or 8 mg/day (body weight

514 Background: Adjuvant therapy for hepatocellular carcinoma (HCC) is an unmet need. Apatinib, a VEGFR2 inhibitor, showed antitumor activity and tolerable toxicity for advanced HCC in a phase 2 study. We were aiming to explore the safety and efficacy of apatinib in adjuvant settings after resection of HCC with portal vein tumor thrombosis (PVTT). Methods: This is a single-center single-arm phase 2 study. The key inclusion criteria were: (1) pathologically confirmed HCC; (2) underwent liver resection with curative intention within 4-6 wk before recruitment; (3) PVTT assessed by preoperative imaging or intraoperative findings. Eligible pts received apatinib at 500 mg/day for a maximum of 12 mo until unacceptable toxicity or tumor recurrence. The primary outcome was recurrence-free survival (RFS) defined as the interval between surgery and the diagnosis of tumor recurrence or death from any causes whichever comes first. The secondary outcome is overall survival (OS) and treatment safety. Results: From Aug 17, 2017 to Dec 18, 2018, 49 pts were screened, and 30 pts were recruited. PVTT were classified as Vp1 (n = 7), Vp2 (n = 11), and Vp3 (n = 12) according to the LCSGJ classification. As the data cutoff on Aug 22, 2019, 4 pts are still on treatment. The median follow-up was 14.3 mo (IQR 12.3-19.3). Median duration of treatment was 4.8 mo (IQR 2.0–8.8). 20 recurrence and 2 death occurred including one death without recurrence. The mRFS was 7.6 mo (95% CI, 3.7-11.5), and the 1-year RFS rate was 36.1%. The mOS was not reached, and 1-year OS rate was 93.3% (standard error, 4.6%). Treatment-related adverse events occurred in 29 pts (96.7%). Grade 3 or 4 adverse events were reported in 14 pts (46.7%) (Table). Dose modification due to adverse events was recorded in 23 pts (76.7%). Conclusions: Apatinib is tolerant in most pts after resection for HCC with PVTT. A controlled study is warranted to prove its efficacy on tumor recurrence. Clinical trial information: NCT03261791. [Table: see text]

e22093 Background: The epithermal growth factor receptor(EGFR) signaling pathways has been implicated in self-renewal of breast cancer stem cells. It has been proved that the EGFR tyrosine kinase inhibitor-gefitinib significantly decreased the mammosphere- forming efficiency(MFE) in ductal carcinoma in situ (DCIS) derived cancer cells. We investigated the response of breast cancer stem cells in breast cancer cell line MCF-7 to EGFR MAbs C225(cetuximab). Methods: Cells were used for nonadherent (i.e.,mammosphere) culture and were divided into four groups according to the different culture medium whether or not including exogenous EGF and MAbs C225. MFE was calculated as the number of mammospheres (≥60um) and was expressed as a percentage. We Compared the percentage of CD44+/CD24- cells from the four groups, and measured the levels of the Wnt and Notch-3 gene expression of the four groups. Results: There was no significant difference of MFE between groups. In the presence of exogenous EGF, MAbs C225 significantly decreased the MFE and the percentage of CD44+/CD24- cells of mammospheres compared with exogenous EGF alone(0.7% versus 1.5%, P < 0.001 and 4% versus 11%P < 0.001;respectively). In the absence of exogenous EGF, MAbs C225 aslo statistically decreased the MFE and the percentage of CD44+/CD24- cells of mammospheres compared with that of lacking exogenous EGF and MAbs C225(0.53% versus 1.3%,P = 0.003 and 9% versus 3%, P < 0.01;respectively). And we observed that the Notch-3 gene expression was compensativly increased in the two groups of addition of MAb C225. No significant differences of Wnt gene expression were observed between groups. Conclusions: EGFR MAbs C225 could disrupt mammoshpere formation and decrease the percentage of CD44+/CD24- cells of mammoshpere cells. The expression of Notch-3 is increased with the EGFR antagonistics in breast cancer stem cells. No significant financial relationships to disclose.

21521 Background: The biologic behavior spectrum of gastrointestinal stromal tumors (GISTs) exhibit from indolent to highly aggressive. Although risk stratification was proposed by the NIH criteria...