Using Normalized Carcinoembryonic Antigen and Carbohydrate Antigen 19 to Predict and Monitor the Efficacy of Neoadjuvant Chemotherapy in Locally Advanced Gastric Cancer

Carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) are established prognostic biomarkers for patients with gastric cancer. However, their potential as predictive markers for neoadjuvant chemotherapy (NACT) efficacy has not been fully elucidated. Methods: We conducted a retrospective analysis to determine values of CEA and CA19-9 prior to NACT (pre-NACT) and after NACT (post-NACT) in 399 patients with locally advanced gastric cancer (LAGC) who received intended NACT and surgery. Results: Among the 399 patients who underwent NACT plus surgery, 132 patients (33.1%) had elevated pre-NACT CEA/CA19-9 values. Furthermore, either pre-NACT or post-NACT CEA /CA19-9 levels were significantly associated with prognosis (p = 0.0023) compared to patients with non-elevated levels. Moreover, among the patients, a significant proportion (73/132, 55.3%) achieved normalized CEA/CA19-9 following NACT, which is a strong marker of a favorable treatment response and survival benefits. In addition, the patients with normalized CEA/CA19-9 also had a prolonged survival compared to those who underwent surgery first (p = 0.0140), which may be attributed to the clearance of micro-metastatic foci. Additionally, the magnitude of CEA/CA19-9 changes did not exhibit a statistically significant prognostic value. Conclusions: Normalization of CEA/CA19-9 is a strong biomarker for the effectiveness of treatment, and can thus be exploited to prolong the long-term survival of patients with LAGC.

[1]  D. Cunningham,et al.  Gastric cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. , 2022, Annals of oncology : official journal of the European Society for Medical Oncology.

[2]  [Chinese expert consensus on perioperative treatment of locally advanced gastric cancer (2021 version)]. , 2021, Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery.

[3]  J. Ji,et al.  Perioperative or postoperative adjuvant oxaliplatin with S-1 versus adjuvant oxaliplatin with capecitabine in patients with locally advanced gastric or gastro-oesophageal junction adenocarcinoma undergoing D2 gastrectomy (RESOLVE): an open-label, superiority and non-inferiority, phase 3 randomised c , 2021, The Lancet. Oncology.

[4]  Jae Hyun Kim,et al.  PRODIGY: A Phase III Study of Neoadjuvant Docetaxel, Oxaliplatin, and S-1 Plus Surgery and Adjuvant S-1 Versus Surgery and Adjuvant S-1 for Resectable Advanced Gastric Cancer , 2021, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[5]  Wentao Liu,et al.  Prediction Model of Tumor Regression Grade for Advanced Gastric Cancer After Preoperative Chemotherapy , 2021, Frontiers in Oncology.

[6]  H. Shimada,et al.  Prognostic impact of CEA/CA19-9 at the time of recurrence in patients with gastric cancer , 2021, Surgery Today.

[7]  S. Luo,et al.  Long noncoding RNA FER1L4 suppresses proliferation, invasion, migration and lymphatic metastasis of gastric cancer cells through inhibiting the Hippo-YAP signaling pathway. , 2020, American journal of translational research.

[8]  Ling Xu,et al.  Wnt/β-Catenin Signaling Axis Is Required for TFEB-Mediated Gastric Cancer Metastasis and Epithelial–Mesenchymal Transition , 2020, Molecular Cancer Research.

[9]  H. Grabsch,et al.  Gastric cancer , 2020, The Lancet.

[10]  R. Perona,et al.  Targeting MAD2 modulates stemness and tumorigenesis in human Gastric Cancer cell lines , 2020, Theranostics.

[11]  Hua-she Wang,et al.  Nomogram for predicting pathological complete response to neoadjuvant chemotherapy in patients with advanced gastric cancer , 2020, World journal of gastroenterology.

[12]  H. Nagai,et al.  CA19-9 is a significant prognostic marker of patients with stage III gastric cancer. , 2020, European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology.

[13]  B. Erickson,et al.  Importance of Normalization of CA19-9 Levels Following Neoadjuvant Therapy in Patients With Localized Pancreatic Cancer. , 2020, Annals of surgery.

[14]  J. Ji,et al.  The clinical value and usage of inflammatory and nutritional markers in survival prediction for gastric cancer patients with neoadjuvant chemotherapy and D2 lymphadenectomy , 2020, Gastric Cancer.

[15]  Han Liang,et al.  Multi-omics characterization of molecular features of gastric cancer correlated with response to neoadjuvant chemotherapy , 2020, Science Advances.

[16]  J. Kinoshita,et al.  Peripheral Blood Platelet–Lymphocyte Ratio Is Good Predictor of Chemosensitivity and Prognosis in Gastric Cancer Patients , 2020, Cancer management and research.

[17]  B. Zilberstein,et al.  Lymph node regression after neoadjuvant chemotherapy: A predictor of survival in gastric cancer , 2019, Journal of surgical oncology.

[18]  M. Egger,et al.  Perioperative chemotherapy with fluorouracil plus leucovorin, oxaliplatin, and docetaxel versus fluorouracil or capecitabine plus cisplatin and epirubicin for locally advanced, resectable gastric or gastro-oesophageal junction adenocarcinoma (FLOT4): a randomised, phase 2/3 trial , 2019, The Lancet.

[19]  Yingwei Xue,et al.  Peripheral Venous Blood Platelet-to-Lymphocyte Ratio (PLR) for Predicting the Survival of Patients With Gastric Cancer Treated With SOX or XELOX Regimen Neoadjuvant Chemotherapy , 2019, Technology in cancer research & treatment.

[20]  Yao Wei,et al.  Clinicopathological and prognostic significance of high circulating lymphocyte ratio in patients receiving neoadjuvant chemotherapy for advanced gastric cancer , 2018, Scientific Reports.

[21]  Lianhai Zhang,et al.  Correlation of pathological complete response with survival after neoadjuvant chemotherapy in gastric or gastroesophageal junction cancer treated with radical surgery: A meta-analysis , 2018, PloS one.

[22]  D. Coit,et al.  Proposal of a new stage grouping of gastric cancer for TNM classification: International Gastric Cancer Association staging project , 2017, Gastric Cancer.

[23]  A. Viale,et al.  Phase I Study of Epigenetic Priming with Azacitidine Prior to Standard Neoadjuvant Chemotherapy for Patients with Resectable Gastric and Esophageal Adenocarcinoma: Evidence of Tumor Hypomethylation as an Indicator of Major Histopathologic Response , 2016, Clinical Cancer Research.

[24]  Quan P. Ly,et al.  Gastric Cancer, Version 3.2016; Clinical Practice Guidelines in Oncology , 2016 .

[25]  G. Colloca,et al.  CA125-related tumor cell kinetics variables after chemotherapy in advanced ovarian cancer: a systematic review , 2016, Clinical and Translational Oncology.

[26]  Japanese Gastric Cancer Association Japanese gastric cancer treatment guidelines 2014 (ver. 4) , 2016, Gastric Cancer.

[27]  S. H. Lee,et al.  Prognostic value of CA 19‐9 kinetics during gemcitabine‐based chemotherapy in patients with advanced cholangiocarcinoma , 2016, Journal of gastroenterology and hepatology.

[28]  Y. Toiyama,et al.  Preoperative prediction of peritoneal metastasis in gastric cancer as an indicator for neoadjuvant treatment. , 2016 .

[29]  Y. Sakamoto,et al.  Post-chemotherapeutic CEA and CA19-9 are prognostic factors in patients with colorectal liver metastases treated with hepatic resection after oxaliplatin-based chemotherapy. , 2015, Anticancer research.

[30]  Zhipeng Sun,et al.  Clinical evaluation of CEA, CA19-9, CA72-4 and CA125 in gastric cancer patients with neoadjuvant chemotherapy , 2014, World Journal of Surgical Oncology.

[31]  J. Ji,et al.  PP242 suppresses cell proliferation, metastasis, and angiogenesis of gastric cancer through inhibition of the PI3K/AKT/mTOR pathway , 2014, Anti-Cancer Drugs.

[32]  P. Lambin,et al.  Blood biomarkers are helpful in the prediction of response to chemoradiation in rectal cancer: a prospective, hypothesis driven study on patients with locally advanced rectal cancer. , 2014, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[33]  Shu-juan Yang,et al.  Serum carbohydrate antigen 19-9 and prognosis of patients with gastric cancer , 2014, Tumor Biology.

[34]  Jia-Hong Wang,et al.  [Predicting value of serum CEA and CA19-9 in neoadjuvant chemotherapy for advanced gastric carcinoma]. , 2012, Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery.

[35]  J. Pignon,et al.  Perioperative chemotherapy compared with surgery alone for resectable gastroesophageal adenocarcinoma: an FNCLCC and FFCD multicenter phase III trial. , 2011, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[36]  P. Schlag,et al.  Neoadjuvant chemotherapy compared with surgery alone for locally advanced cancer of the stomach and cardia: European Organisation for Research and Treatment of Cancer randomized trial 40954. , 2010, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[37]  C. V. D. van de Velde,et al.  Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. , 2006, The New England journal of medicine.

[38]  Tao Cai,et al.  Automated genome annotation and pathway identification using the KEGG Orthology (KO) as a controlled vocabulary , 2005, Bioinform..

[39]  H. Putter,et al.  Neo-adjuvant chemotherapy for operable gastric cancer: long term results of the Dutch randomised FAMTX trial. , 2004, European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology.

[40]  W. Hohenberger,et al.  CEA and CA 19-9 measurement as a monitoring parameter in metastatic colorectal cancer (CRC) under palliative first-line chemotherapy with weekly 24-hour infusion of high-dose 5-fluorouracil (5-FU) and folinic acid (FA). , 2001, Annals of oncology : official journal of the European Society for Medical Oncology.

[41]  Kazuhiko Yoshida,et al.  Clinicopathological features of CA19-9-producing gastric cancer. , 2014, Hepato-gastroenterology.

[42]  L. Schwartz,et al.  New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). , 2009, European journal of cancer.

[43]  R. Coleman,et al.  Early changes in CA125 after treatment with pegylated liposomal doxorubicin or topotecan do not always reflect best response in recurrent ovarian cancer patients. , 2007, The oncologist.

[44]  Susumu Goto,et al.  The KEGG resource for deciphering the genome , 2004, Nucleic Acids Res..