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TPS445 Background: Pancreatic cancer is a major cause of cancer-related death. About 40% of patients with pancreatic cancer present with locally advanced disease and are not candidates for curative surgery. Most patients are treated with chemotherapy with a limited life expectancy. The role of local treatment such as radiation is not well defined. Other conventional ablative therapies, such as thermal or cryoablation have limited role due to the risk of collateral damage to the adjacent structures. Irreversible electroporation (IRE) is a novel non-thermal ablation technology that does not cause injury to nearby blood vessels, ducts, and bowel and has the potential to provide longer disease control and thereby better overall survival. We hypothesized that addition of IRE to combination chemotherapy in patients with locally advanced pancreatic cancer will improve their outcomes, and patients with undetectable 12-week post IRE circulating tumor cell DNA will have better prognoses. Methods: It is a prospective, multicenter, single-arm phase II study. The primary objective is to determine 12-month PFS rate of patients with locally advanced pancreatic cancer who are treated with combination chemotherapy and IRE. Secondary objectives include identification of prognostic and predictive biomarkers, 24-months survival rate, quality of life of subjects, as well as cost-effectiveness and complication rates of IRE. Based on the assumption that treatment with IRE and chemotherapy would result in doubling of PFS versus chemotherapy alone a sample of n = 27 of patients with locally advanced pancreatic adenocarcinoma is estimated. Eligible patients will be recruited at the two major cancer centers in Saskatchewan. All IRE-eligible patients will receive 12 weeks of induction combination chemotherapy and will undergo IRE if there is no disease progression. An additional 12 weeks of chemotherapy will be recommended. Patients who are not eligible for IRE will receive chemotherapy at the discretion of treating oncologist until disease progression or until they become eligible for IRE. Circulating tumor DNA and a panel of genes will be examined using next-generation sequencing for their correlation with prognosis. Quality of life will be assessed, and cost-effectiveness analysis of IRE will be performed.The results of this study will be used to develop a future multicenter, national phase III trial. Clinical trial information: NCT04276857.

TPS147 Background: Patients with mCRC generally have a limited life expectancy, however, a small number of patients with liver-only mCRC could be cured following metastasectomy. In highly selected patients with mCRC, FOLFOXIRI (5FU, oxaliplatin, and irinotecan) plus bev results in high response rates. However, very limited evidence is available about efficacy of this regimen in real-world patients with liver-only mCRC. Furthermore, there is paucity of biomarkers that predict liver metastasectomy in such patients. The current study aims a) to evaluate rate of conversion from unresectable to resectable liver metastases in real-world patients with liver-only mCRC following FOLFOXIRI-bev, b) to identify predictive markers including an early PET-FDG response that correlate with curative surgery, & c) to determine disease control rate, overall survival, quality of life, treatment toxicities, and cost-effectiveness of surgery. Methods: In this pragmatic phase 2 study, 37 patients with liver-only unresectable mCRC who are deemed eligible for FOLFOXIRI-bev by their oncologist will be recruited at the two major cancer centers in Saskatchewan. Patients will receive FOLFOXIRI-bev every two weeks for a total of 12 cycles and will undergo periodic imaging tests. The resectability of liver metastases will be determined by a multidisciplinary team. For those patients who are not able to undergo a curative surgery, a doublet chemotherapy regimen ±bev will be continued at the discretion of treating oncologist. . The prognostic and predictive value of mutations in specific genes involved in cell proliferation, cell death resistance, angiogenesis, and invasion in colorectal cancer along with the relationship between the abundance and characteristics of exRNA and conversion rate and survival will be assessed. Logistic regression and Cox proportional analyses will be performed to assess correlation between an eight-week FDG-PET/CT response to chemotherapy and other biomarkers and rate of removal of metastases and survival, respectively. This pragmatic study will help to determine conversion rate in real-world patients with FOLFOXIRI plus bev and role of early FDG-PET/CT scan response and other biomarkers in predicting metastasectomy along with cost-effectiveness of this approach. Clinical trial information: NCT03401294.

471 Background: Currently limited biomarkers are available to monitor disease status in cancer patients. Although host factors are critical in regulating cancer, the role of immune responses in aCRC is less clear. A predominant T helper 1 (Th1) response may be more effective to contain cancer than one with a substantial Th2 component. The Th1/Th2 phenotype can be inferred from relative prevalence of IgG isotypes among anti-cancer antibodies and may provide an innovative way to assess disease activity. The study aims to develop an ELISA assay to monitor IgG1:IgG2 and its utility in predicting disease status in aCRC. Methods: A validated ELISA assay (Bertech Pharma) utilizing CRC cell lines was developed to measure IgG1 (Th2) and IgG2 (Th1) levels. A sample size of 44 (24 CRC and 20 healthy control [HC]) was estimated to achieve 80% power and α error of 0.05 assuming that the assay correctly detect CRC specific antibody in > 80% cases. The IgG1:IgG2 was compared between/within groups with HC and aCRC. Results: Samples were collected from 62/66 individuals recruited at 2:1 over 1 yr. 43 CRC patients had median age of 65 yrs (39-86) and M:F 2.3:1. 25 had >1 metastatic site, 31 underwent primary tumor resection and 37 received chemotherapy. Using standard criteria, 14/43 (33%) CRC patients had elevated 1gG1 titer compared with 2/19 (10%) HCs (p = 0.06). Mean IgG1 of CRC group was 0.18±0.05 compared with 0.15±0.01 in HC (p = 0.01). Conversely, mean IgG2 level of CRC group was 0.26±0.11 compared with 0.38±0.15 in HC (p = 0.003). Mean IgG2:IgG1 of CRC group was 1.5±0.35 compared with 2.5±0.97 in HC (p < 0.001). Among 43 CRC patients, 7/12 (58%) with disease progression (DP) had elevated IgG1 compared 7/31 (23%) with stable disease (p = 0.03). Strikingly, 9/12 (75%) patients who died had elevated IgG1 compared with 5/31 (16%) who were alive during the follow up, p = 0.001. Logistic regression revealed positive association among elevated IgG1 and DP, HR:4.8 (95% CI:1.2-19.9) and mortality, HR:15 (95% CI:3.1-78.8). Conclusions: Our results revealed that patients with aCRC have abnormal IgG1:IgG2 compared with HC and elevated IgG1 (a predominant Th2 response) levels in aCRC correlate with DP and mortality.