High Presurgical Levels of Angiogenic and Growth Factors Are Associated With Poorer Survival After Gastric Resection
In patients undergoing gastric resection for gastric/gastroesophageal junction cancers, high levels of angiogenic and growth factors are associated with poorer overall survival, according to the results of a retrospective study presented by Park et al in the Annals of Surgical Oncology. Thus, these factors may delineate tumor biology and help to stratify patient prognosis.
Study Details
Numerous clinical pathways exist that may serve as biomarkers for determining therapy for patients with gastric cancer. To determine the predictive value of these biomarkers, the investigators analyzed the medical records of 147 patients with gastric and gastroesophageal junction type II or III cancers undergoing surgical resection. Serum samples were analyzed for vascular endothelial growth factor A (VEGF-A), epidermal growth factor (EGF), fibroblast growth factor 2 (FGF2), and hepatocyte growth factor (HGF). A preoperative adjusted total value was assigned for all four factors for each patient. Most patients were white and male, with a mean age of 67 years. The median follow-up was 35.3 months.
Most of the tumors occurred at the lower and middle thirds of the stomach (59.2%). Additional tumor sites included the proximal stomach (19%) and the gastroesophageal junction (19%). Distal gastrectomy was performed in 44.9% of patients, total gastrectomy was performed in 35.4% of patients, esophagogastrectomies were performed in 17% of patients, and proximal gastrectomy was performed in 2.7% of patients.
The mean level of HGF (1,353.9 pg/mL) was the highest of the four factors, and VEGF-A was found to have a wider range of levels than EGF or FGF2. The correlation among all four factors was greatest with VEGF-A, FGF2, and HGF.
There was a significant association between factor levels and pathologic characteristics. For instance, higher VEGF-A levels were found in patients having an R1 resection compared with patients having an R0 resection (P = .037). In addition, higher FGF2 levels were associated with poorly or undifferentiated tumors, Lauren diffuse-type tumors, and tumors with extensive nodal disease.
Lower VEGF-A and HGF Levels Associated With Improved Survival
Patients with lower levels of VEGF-A and HGF had significantly higher survival rates than did patients with higher levels of VEGF-A and HGF. The 5-year overall survival rate for patients with high VEGF-A levels was 49.6%, compared with 76% for patients with low VEGF-A levels (P = .009). As for HGF levels, patients with high levels had a survival rate of 49.6%, compared with 71.7% for those with lower levels (P = .005).
Higher EGF or FGF2 levels were associated with poorer overall survival, but there was no significant difference between the two factors. As for the previously mentioned preoperative adjusted total values, patients with high values had a lower survival rate (53.9%) than patients with low values (84.1%; P = .005).
Neoadjuvant treatment, given to 36 patients in the study, did not appear to be associated with improved overall survival. However, in patients who did not receive neoadjuvant therapy therapy, the adjusted total values of all four factors were significantly associated with overall survival.
Clinical Implications
Almost all of the factors studied (margin status, tumor grade, tumor size, vascular invasion, as well as levels of VEGF-A, HGF, and adjusted total values) were prognostic for overall survival, according to the investigators. Thus, the results from their study confirmed the benefit of measuring circulating angiogenic and growth factors before performing resection of gastric tumors. The results also supported the utility of measuring circulating factors in directing the choice of targeted therapies.
The investigators remarked, “This study demonstrates that circulating angiogenic and growth factors may be helpful in determining the prognosis of gastric cancer patients undergoing surgical resection.”
Sam S. Yoon, MD, of the Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, is the corresponding author of the article in the Annals of Surgical Oncology.
The authors disclosed no potential conflicts of interest.
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