Analysis Of Liver Metastases Research Articles

Abstract CT507: ATP128 vaccine with ezabenlimab promotes antigen-specific immune responses in stage IV colorectal cancer in the KISIMA-01 phase 1b trial

Abstract Background: KISIMA࣪ is a vaccine platform based on a single chimeric fusion protein, containing a proprietary cell-penetrating peptide (CPP) for antigen delivery, a proprietary Toll-like receptor (TLR)-peptide agonist with self-adjuvant properties and a modulable multi-antigenic domain (Mad). ATP128 vaccine targets 3 antigens: carcinoembryonic antigen (CEA), Survivin and Achaete-scute complex homolog 2 (ASCL2); it is used in combination with a PD-1 inhibitor in the treatment of MSS/MMR proficient stage IV colorectal cancer (CRC) patients, after first line of standard of care therapy or as perioperative administration in patients with resectable liver metastases. Method: KISIMA-01 (NCT04046445) is an open-label, multi-center Phase 1b trial to investigate the safety, tolerability and immunogenicity of AT128 alone or in combination with the anti-PD-1 antibody ezabenlimab in patients with stage IV CRC. ATP128 is given SC q2w for the first 3 immunizations (prime) and q4w for the last 3 immunizations (boost). Ezabenlimab is administered q3w starting with the first ATP128 administration. Blood and tissue samples are collected before, during and after ATP128 treatment to monitor the induction of a tumor associated antigen-specific immune response (ELISpot) and immune-related changes in the peripheral blood and in the tumor microenvironment by immunohistochemistry (IHC) and flow cytometry. Results: In more than 50% of evaluated patients treated with ATP128 alone or with ezabenlimab, a cellular immune response against at least one out of three antigens was observed as determined by IFN-γ ELISpot analyses of patient PBMCs after the 3rd vaccination. Analysis of liver metastases by IHC indicated that evaluated patients were positive for all 3 antigens in ATP128. Furthermore, for the patients with paired biopsies, a significant increase in CD8 T cells infiltration into the tumor parenchyma was observed after 3 vaccine administrations, along with a significantly higher proportion of CD45RO expressing memory cells within the CD4 population as compared to baseline. Tumor infiltrating lymphocytes (TILs) flow cytometry analysis comparing untreated (historical controls) and ATP128/ezabenlimab-treated patients showed a similar quantity of the different infiltrated subsets but an improved quality of infiltrated T cells, indicated by an increase (more than 2-fold) in proportion of central memory T cells and an impressive decrease of the proportion of cells positive for exhaustion markers expression in KISIMA-01 patients. Conclusions: Analyses indicate induction of ATP128-specific immune response in the peripheral circulation and increased infiltration of TILs into liver metastases with an improved quality of T cells. Citation Format: Heinz-Josef Lenz, Hanz Prenen, Eric Van Cutsem, Thibaud Kössler, Jean-François Mayol, Francesca Trapani, Matthieu Tihy, Laura Rubbia-Brandt, Christian Toso, Thomas Bogenrieder, Elodie Belnoue, Madiha Derouazi, Scott Kopetz. ATP128 vaccine with ezabenlimab promotes antigen-specific immune responses in stage IV colorectal cancer in the KISIMA-01 phase 1b trial [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr CT507.

Analysis of liver metastasis after resection for pancreatic ductal adenocarcinoma

To investigate the risk factors affecting the liver metastasis (LM) of pancreatic ductal adenocarcinoma (PDAC) after resection. We retrospectively analyzed 101 PDAC patients who underwent surgical resection at the Samsung Medical Center between January 2000 and December 2004. Forty one patients with LM were analyzed for the time of metastasis, prognostic factors affecting LM, and survival. LM was found in 40.6%. The median time of the LM (n = 41) was 6.0 ± 4.6 mo and most LM occurred within 1 year. In univariate analysis, tumor size, preoperative carbohydrate antigen 19-9, and perineural invasion were factors affecting LM after resection. In multivariate analysis, tumor size was the most important factor for LM. In univariate analysis, tumor cell differentiation was significant to LM in low-risk groups. LM after resection of PDAC occurs early and shows poor survival. Tumor size is the key indicator for LM after resection.

Prognostic analysis of liver metastasis in gastric cancer patients with radical gastrectomy

To elucidate the prognostic factors of liver metastasis in gastric cancer patients with radical gastrectomy. Clinicopathological data of 87 liver metastasis patients, undergone radical gastrectomy for gastric cancer from 1996 to 2001, were retrospectively analyzed. Of these 87 patients, the 1-, 3- and 5-year survival rates were 28.8%, 3.6% and 0 respectively and the average survival time after gastrectomy was (11.3+/-1.1) months. By univariate analysis, tumor location, tumor size, histologic differentiation, invasive depth, Lauren classification, metastasis of lymph nodes from lymphadenectomy, vascular invasion, nervous invasion, peritoneal metastasis, number of liver metastasis, liver metastatic distribution and resection of liver metastasis were found to be significant factors associated with the prognosis of liver metastatic patients after radical gastrectomy. By multivariate analysis, location, the Lauren classification, liver metastatic distribution and resection of liver metastasis were found to be independent factors associated with hepatic metastasis after radical gastrectomy. Location of gastric cancer, Lauren classification, liver metastatic distribution and resection of liver metastasis are important factors to evaluate the prognosis of liver metastasis in gastric cancer patients with radical gastrectomy.

Five-year survival analysis of liver metastasis of colorectal cancer after hepatic resection

14571 Background: To evaluate the relation between hepatic resecion and survival rate of liver metastasis of colorectal cancer ( LMCC). Methods: Use retrograde case analysis method, 133 cases of LMCC received hepatic resection from 1/1/2000 to 31/12/2005 were included,with attention to the relation between hepatic resection and survival rate. Results: There were 133 cases underwent curative hepatic resection in all 470 LMCC cases, of which 30 cases (30/196,15.3%) in synchronous liver metastasis (SLM) group and 103 cases (103/274,37.6%) in metachronous liver metastasis (MLM) group, P<0.01. Mortality rate related to operation was 3.3%(1/30) in SLM and 1.9%(2/103) in MLM(P<0.05). Until 31/6/2006, all 133 cases were followed-up, 1,3,5 years survival rate and median survival time of SLM (81.0%, 40.3%, 16.5%, 22 months) is similar to that of MLM (88.2%, 49.1%, 31.7%, 25 months, P > 0.05), but the recurrence rate is higher(36.7% vs 20.4%,P=0.03). Compared to 49 cases whose liver metastases focus can be resected but chosen non- operative therapy, 1, 3, 5 years survival rate of 133 resected cases is higher (55.6%, 11.0%, 0 vs 86.2%, 39.2%, 29.4%, P=0.0034). In SLM, 22 cases received I stage resection of the primary colorectal tumor and liver metastasis and 8 cases received liver metastasis resection after the primary surgery (II stage operation). 1, 2, 3 years survival are 90.0% vs 87.5%(P > 0.05),61.4% vs 55.3%(P > 0.05)and 35.4% vs 30.0%(P > 0.05) and the median survival time is 28 months vs 26months(P > 0.05).COX multivariate analysis was used to analyze the prognositic factors. Incision margin =1cm(β=-0.8351,P=0.0363)and reoperation after recurrence(β=- 0.9428,P=0.0411)were protective survival factors, and postoperation recurrence (β=0.6471,P=0.0226) was survival risk factor. Conclusions: Curative hepatic resection is the first choice of liver metastasis of colorectal cancer and can improve survival. No significant financial relationships to disclose.

大腸癌肝転移症例の検討

大腸癌肝転移症例の検討