Considered separately, either ERCC1 or TS mRNA levels in a primary gastric adenocarcinoma has a statistically significant relationship to response. ERCC1 mRNA levels have a statistically significant association with survival; in this cohort TS mRNA levels did not reach statistically significant association with survival as in our previous publication. Whether these molecular parameters are independent of each other as predictors of outcome remains to be determined.

For this cohort, the intratumoral TS/beta-actin ratio had a statistically significant association with response and survival. This relationship for other 5-FU schedules remains unknown. Confirmation of these data in a larger patient population could lead to determination of therapy for disseminated colorectal cancer based on a specific intratumoral molecular parameter.

The genetic expression of TS (TSmRNA level) influences response to 5FU-based chemotherapy and survival for a cohort of patients with primary gastric cancer. Confirmation of these data could lead to therapeutic decisions based on specific molecular properties within a tumor.

Key Points Question Is total neoadjuvant therapy (TNT) associated with improved outcomes when compared with standard concurrent chemoradiotherapy followed by surgery and adjuvant chemotherapy (CRT plus A) for locally advanced rectal cancer? Findings In this systematic review and meta-analysis of 7 unique studies including 2416 unique patients, TNT was found to be associated with a significantly higher rate of achieving a pathologic complete response and disease-free survival compared with the standard CRT plus A approach. No significant difference was found in rates of sphincter-preserving surgery or ileostomy requirements between the 2 approaches. Meaning Total neoadjuvant therapy was associated with improved pathologic complete response rates and has a potential disease-free survival advantage compared with the standard CRT plus A strategy in locally advanced rectal cancer.