Aim To evaluate the prognostic value of tumor markers in a European cohort of patients with resectable gastric cancer. Methods We performed a post hoc analysis of the CRITICS trial, in which 788... Show moreAim To evaluate the prognostic value of tumor markers in a European cohort of patients with resectable gastric cancer. Methods We performed a post hoc analysis of the CRITICS trial, in which 788 patients received perioperative therapy. Association between survival and pretreatment CEA, CA 19-9, alkaline phosphatase, neutrophils, hemoglobin and lactate dehydrogenase were explored in uni- and multivariable Cox regression analyses. Likelihoods to receive potentially curative surgery were investigated for patients without elevated tumor markers versus one of the tumor markers elevated versus both tumor markers elevated. The association between tumor markers and the presence of circulating tumor DNA (ctDNA) was explored in 50 patients with available ctDNA data. Results In multivariable analysis, in which we corrected for allocated treatment and other baseline characteristics, elevated pretreatment CEA (HR 1.43; 95% CI 1.11-1.85, p < 0.001) and CA 19-9 (HR 1.79; 95% CI 1.42-2.25, p < 0.001) were associated with worse OS. Likelihoods to receive potentially curative surgery were 86%, 77% and 60% for patients without elevated tumor marker versus either elevated CEA or CA 19-9 versus both elevated, respectively (p < 0.001). Although both preoperative presence of ctDNA and tumor markers were prognostic for survival, no association was found between these two parameters. Conclusion CEA and CA 19-9 were independent prognostic factors for survival in a large cohort of European patients with resectable gastric cancer. No relationship was found between tumor markers and ctDNA. These factors could potentially guide treatment choices and should be included in future trials to determine their definitive position. Show less
Linders, D.; Deken, M.; Valk, M. van der; Tummers, W.; Bhairosingh, S.; Schaap, D.; ... ; Hilling, D. 2021
Rectal cancer patients with a complete response after neoadjuvant therapy can be monitored with a watch-and-wait strategy. However, regrowth rates indicate that identification of patients with a... Show moreRectal cancer patients with a complete response after neoadjuvant therapy can be monitored with a watch-and-wait strategy. However, regrowth rates indicate that identification of patients with a pathological complete response (pCR) remains challenging. Targeted near-infrared fluorescence endoscopy is a potential tool to improve response evaluation. Promising tumor targets include carcinoembryonic antigen (CEA), epithelial cell adhesion molecule (EpCAM), integrin alpha v beta 6, and urokinase-type plasminogen activator receptor (uPAR). To investigate the applicability of these targets, we analyzed protein expression by immunohistochemistry and quantified these by a total immunostaining score (TIS) in tissue of rectal cancer patients with a pCR. CEA, EpCAM, alpha v beta 6, and uPAR expression in the diagnostic biopsy was high (TIS > 6) in, respectively, 100%, 100%, 33%, and 46% of cases. CEA and EpCAM expressions were significantly higher in the diagnostic biopsy compared with the corresponding tumor bed (p < 0.01). CEA, EpCAM, alpha v beta 6, and uPAR expressions were low (TIS < 6) in the tumor bed in, respectively, 93%, 95%, 85%, and 62.5% of cases. Immunohistochemical evaluation shows that CEA and EpCAM could be suitable targets for response evaluation after neoadjuvant treatment, since expression of these targets in the primary tumor bed is low compared with the diagnostic biopsy and adjacent pre-existent rectal mucosa in more than 90% of patients with a pCR. Show less
Purpose: It is suggested that tumour markers carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) could be used to predict the stage of pancreatic cancer. However, optimal cut-off... Show morePurpose: It is suggested that tumour markers carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) could be used to predict the stage of pancreatic cancer. However, optimal cut-off values for CEA and CA19-9 are disputable. This study aimed to assess the value of CEA and CA19-9 serum levels at diagnosis of pancreatic ductal adenocarcinoma (PDAC) as predictors for the advanced stage of PDAC in patients discussed at pancreatic multidisciplinary team (MDT) meetings. Methods: Patients with suspected PDAC discussed at MDT meetings from 2013 to 2017 were reviewed, in order to determine optimal cut-off values of both CEA and CA19-9. Results: In total, 375 patients were included. Optimal cut-off values for predicting advanced PDAC were 7.0 ng/ml for CEA and 305.0 U/ml for CA19-9, resulting in positive predictive values of 83.3%, 73.6%, and 91.4% for CEA, CA19-9 and combined, respectively. Both tumour markers were independent predictors of advanced PDAC, demonstrated by an odds ratio of 4.21 (95% CI:1.85-9.56; p = 0.001) for CEA and 2.58 for CA19-9 (95% CI:1.30-5.14; p = 0.007). Conclusions: CEA appears to be a more robust predictor of advanced PDAC than CA19-9. Implementing CEA and CA19-9 serum levels during MDT meetings as an additional tool for establishing tumour resectability is worthwhile for tailored diagnostics. Show less
