Predictors of survival outcome following radical gastrectomy for gastric cancer.

BACKGROUND: Radical surgery with adjuvant therapy is now the standard treatment for locally advanced gastric cancer. However, the best regimen for adjuvant therapy remains controversial. We aim to determine the predictors of survival outcome of gastric cancer patients who underwent curative surgery with or without adjuvant therapy in our institution. METHODS: All patients who received surgery for gastric cancer from years 2000 to 2015 were studied using a prospective gastric cancer database at the National University Hospital, Singapore. RESULTS: A total of 405 patients underwent radical gastrectomy with curative intent. Seventy-eight percent received extended lymphadenectomy (≥D1). R0 resection was achieved in 377 patients (93%) with 30-day mortality rate of 1.7%. There was no significant difference in the complication rate between D1 and extended lymphadenectomy group. One hundred and forty-five patients (36%) received adjuvant therapy. With a median follow-up of 5.9 years, the 5-year disease-free survival for stage I to IV patients were 78%, 58%, 27% and 9%, respectively. Among the 141 patients with known recurrences, the first site of recurrence was 38% distant, 24% locoregional, 20% peritoneal and the rest were multiple sites. Stage of disease, adjuvant therapy, extent of lymphadenectomy, post-operative complication and approach of surgery were independent risk factors for long-term survival. CONCLUSIONS: Stage of disease, adjuvant therapy, extent of lymphadenectomy, post-operative complication and approach of surgery are significant predictors for long-term survival. Adequate and safe surgery to allow adjuvant therapy should be the goal of all surgeons for our gastric cancer patients.

Discovering novel SNPs that are correlated with patient outcome in a Singaporean cancer patient cohort treated with gemcitabine-based chemotherapy.

BACKGROUND: Single Nucleotide Polymorphisms (SNPs) can influence patient outcome such as drug response and toxicity after drug intervention. The purpose of this study is to develop a systematic pathway approach to accurately and efficiently predict novel non-synonymous SNPs (nsSNPs) that could be causative to gemcitabine-based chemotherapy treatment outcome in Singaporean non-small cell lung cancer (NSCLC) patients. METHODS: Using a pathway approach that incorporates comprehensive protein-protein interaction data to systematically extend the gemcitabine pharmacologic pathway, we identified 77 related nsSNPs, common in the Singaporean population. After that, we used five computational criteria to prioritize the SNPs based on their importance for protein function. We specifically selected and screened six candidate SNPs in a patient cohort with NSCLC treated with gemcitabine-based chemotherapy. RESULT: We performed survival analysis followed by hematologic toxicity analyses and found that three of six candidate SNPs are significantly correlated with the patient outcome (P < 0.05) i.e. ABCG2 Q141K (rs2231142), SLC29A3 S158F (rs780668) and POLR2A N764K (rs2228130). CONCLUSIONS: Our computational SNP candidate enrichment workflow approach was able to identify several high confidence biomarkers predictive for personalized drug treatment outcome while providing a rationale for a molecular mechanism of the SNP effect. TRIAL REGISTRATION: NCT00695994. Registered 10 June, 2008 'retrospectively registered'.