高雄醫學大學附設醫院外傷及重症外科胃腸及一般外科

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高雄醫學大學附設醫院外傷及重症外科胃腸及一般外科 2017台灣外科醫學會 The relationship of ERCC1, ERCC2, XRCC1 expression and clinical outcome of advanced gastric cancer patients treated with neoadjuvant FOLFOX4 chemotherapy 葉永松王照元高雄醫學大學附設醫院外傷及重症外科胃腸及一般外科

Aim Gastric cancer is one of the most common cancers worldwide and remains a major public health problem. Mortality rate remains high because of local recurrences or distant metastases occurring in up to 60% of the patients. Clinical results in patients with unresectable advanced or recurrent gastric cancer highlight the need for effective systemic chemotherapy.

How to identify patients who could benefit most !!?

Pharmacogenetics and Genomics 2011, 21:18–25

Journal of Surgical Oncology, 2013 Dec;108(7):457-64

Nucleotide excision repair(NER) excision repair cross complementing group 1 (ERCC1), excision repair cross‐complementing 2 (ERCC2), X‐ray cross‐complementing 1 (XRCC1) Tissue resistance to oxaliplatin multifactorial, NER is reported to be associated with resistance to platinum-based chemotherapy. Resistance to oxaliplatin has been attributed to enhance tolerance and repair of DNA damage through the NER pathway.

Aim evaluate the correlation between expression of these three DNA repair genes and clinical outcome of patients with locally advanced/metastatic gastric cancer administrated with FOLFOX-4 regimen

Materials and Methods From January 2009 to January 2017, 44 patients with histologically confirmed unresectable advanced or recurrent gastric cancer were enrolled in this study. All patients were treated with an FOLFOX-4 regimen of 85 mg/m2 of oxaliplatin and 200 mg/m2 of leucovorin on the first day, followed by a 24-hour continuous infusion of 1,000 mg/m2 of 5-fluorouracil in 2 days with a 2-week interval. Treatment continued until disease progression or intolerable adverse events occurred.

Materials and Methods KMUH, 44 patients with unresectable advanced or recurrent gastric cancer  13 patients: response group (partial response in 13 patients)  31 patients: non-response group (stable disease in 18 patients and progressive disease in 13 patients)

Immunohistochemical staining of ERCC1,ERCC2,and XRCC1 Immunohistochemical staining of ERCC1, XRCC1, and XPD in colorectal cancer tissue. ERCC1 and XRCC1 protein were stained in the nuclear and ERCC2 protein was stained in the cytoplasm of tumor cells (brown color). The proportion and intensity of cells with ERCC1, ERCC2, and XRCC1 expression was rated as follows: score 0: no staining; score 1: less than 50% positive cells with staining; score 2: more than 50% positive cells with staining. Original magnification, 100×. © IF THIS IMAGE HAS BEEN PROVIDED BY OR IS OWNED BY A THIRD PARTY, AS INDICATED IN THE CAPTION LINE, THEN FURTHER PERMISSION MAY BE NEEDED BEFORE ANY FURTHER USE. PLEASE CONTACT WILEY'S PERMISSIONS DEPARTMENT ON PERMISSIONS@WILEY.COM OR USE THE RIGHTSLINK SERVICE BY CLICKING ON THE 'REQUEST PERMISSION' LINK ACCOMPANYING THIS ARTICLE. WILEY OR AUTHOR OWNED IMAGES MAY BE USED FOR NON-COMMERCIAL PURPOSES, SUBJECT TO PROPER CITATION OF THE ARTICLE, AUTHOR, AND PUBLISHER.

Crosstables

Crosstables

Grade 3/4 toxicities

Efficacy

Overall Survival

Progression-Free Survival

Results A multivariate analysis showed that ERCC1 overexpression (P=0.001), ERCC2 overexpression (P=0.012), any one of ERCC1 or ERCC2 overexpression (P=0.001) and both of ERCC1 and ERCC2 overexpression (P=0.008) were significantly correlated to non-response group.

Results Additionally, ERCC1 and ERCC2 overexpression were not only predictors of response but also for overall survival (both P<0.01) and progression-free survival (both P<0.01).

Conclusion ERCC1 and ERCC2 overexpression are promising predictive markers in locally advanced/metastatic gastric cancer patients receiving neoadjuvant FOLFOX‐4 chemotherapy These two biomarkers may help identify patients who would benefit from this therapeutic strategies

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