Gastric cancer is a very heterogeneous tumor, meaning that the growth rate, aggressiveness, sensitivity to drugs, and outcome vary greatly among gastric cancers. Therefore, the individualized treatment model of “different treatment for the same disease” is particularly important in gastric cancer.
So what factors do clinicians take into account when developing individualized treatment plans, in addition to stage?
Pathologic staging and choice of chemotherapeutic agents
Pathologists will look at the morphology of gastric cancer cells under a microscope and perform tissue staging, according to which gastric cancer can be classified as intestinal or diffuse.
Intestinal gastric cancer usually develops at a later age, often infiltrates lymphatic vessels and/or blood vessels, and often metastasizes in scattered distant metastases, with liver metastases being more common. Bax expression is significantly higher in intestinal gastric cancer than in other gastric cancers, and this group of patients may be more sensitive to oxaliplatin-containing regimens.
Diffuse gastric cancer is more common in young women and rarely forms disseminated metastases, but is prone to peritoneal dissemination of implants. The presence of peritoneal dissemination can lead to cancerous bowel obstruction, ascites formation, and ovarian metastases, which have a greater impact on quality of life and poorer patient outcomes. Therefore, for patients with diffuse gastric cancer, physicians usually select the appropriate chemotherapeutic agent according to their biological characteristics at the early stage of treatment, and their sensitivity to paclitaxel-based first-line chemotherapy regimens is usually better.
Molecular typing and selection of targeted drugs
Doctors also test for molecular expression on the tumor surface by immunohistochemical means, such as HER2, or human epidermal growth factor receptor 2, calcium adhesion protein E (E-cadherin), the cellular value-added index Ki-67, and vascular endothelial growth factor (VEGF). Based on the expression of these molecules in tumor tissue, physicians can determine molecular staging, which is an important basis for physicians to choose treatment options.
For example, HER2 expression is a test that patients with gastric cancer typically receive. If a patient is positive for HER2 expression, the tumor is more sensitive to targeted therapy against HER2, so doctors usually choose the targeted drug trastuzumab (Trastuzumab) in combination with standard chemotherapy as the treatment of choice.
Selection of metastatic site and treatment
Gastric cancers with metastases are all stage IV, but the choice of drugs, the significance of palliative surgery, and the timing of local therapeutic interventions can vary, even to the extent that the aim of treatment is somewhat different. For example, when peritoneal metastases occur, physicians generally use peritoneal infusion chemotherapy combined with systemic systemic chemotherapy; when liver metastases occur, physicians may use radiofrequency ablation or hepatic artery embolization chemotherapy, etc.
These differences are genetically determined, for example, patients with liver metastases from gastric cancer are predominantly intestinal, with higher expression of genes such as EGFR, HER2, and catenin, and those with peritoneal metastases from gastric cancer are predominantly diffuse, with mutations in the p53 gene, which can provide some basis for rough screening of therapeutic agents among clinicians. The results of this study are summarized below.
In fact, in the individualized treatment of gastric cancer, physicians have to consider much more than the above, as patient differences include age, co-morbidities, concomitant medications, risk of tumor-related complications, and even socioeconomic reasons such as family background, economic conditions, literacy, and treatment compliance, all of which are important influencing factors for physicians to choose individualized treatment plans. (Coauthored by Songcheng Yin, Department of Gastrointestinal Oncology, The First Hospital of China Medical University)