Top Line: Total neoadjuvant therapy is now well established as the preferred treatment for patients with high risk, locally advanced rectal cancer.
The Study: Within the TNT paradigm, though, there are multiple architectures of how to integrate chemotherapy and radiation. Compared with other landmark TNT trials, TNTCRT took the unique approach of interdigitating long course radiation with a continuous regimen of capecitabine and oxaliplatin. The trial included 458 patients with locally advanced rectal cancer and at least one high risk feature (cT4a-b, cN2, mesorectal fascia involvement, or cT3c-d with extramural vascular invasion). Those in the TNT arm received a total of 6 cycles of capecitabine and oxaliplatin including one induction cycle, two during chemoradiation (50-50.4 Gy in 25-28 fractions), and three consolidation. Oxaliplatin dosing and frequency was stable throughout, but capecitabine was given at a lower dose and on every treatment day during radiation versus 2 out of every 3 weeks during induction and consolidation. The standard arm received neoadjuvant long course chemoradiation and 6 cycles of adjuvant capecitabine and oxaliplatin. At 3 years, the TNT regimen significantly improved DFS (74.8% v 66%) and also increased the pCR rate (26.4% v 9.8%). The rate of locoregional failure was similar between arms (6% v 6.2%). There was no difference in OS at 3 years (90.2% v 87.5%). Grade 3+ adverse events were higher with TNT during the neoadjuvant phase of therapy (27.6% v 8.6%), however, rates were similar when looked at across the entire course of treatment (28% v 24.3%).
TBL: TNTCRT reinforces the total neoadjuvant therapy paradigm, which improves DFS in high risk patients, while offering a different twist on chemo and radiation sequencing. | Wang, J Clin Oncol 2026
The Study: Within the TNT paradigm, though, there are multiple architectures of how to integrate chemotherapy and radiation. Compared with other landmark TNT trials, TNTCRT took the unique approach of interdigitating long course radiation with a continuous regimen of capecitabine and oxaliplatin. The trial included 458 patients with locally advanced rectal cancer and at least one high risk feature (cT4a-b, cN2, mesorectal fascia involvement, or cT3c-d with extramural vascular invasion). Those in the TNT arm received a total of 6 cycles of capecitabine and oxaliplatin including one induction cycle, two during chemoradiation (50-50.4 Gy in 25-28 fractions), and three consolidation. Oxaliplatin dosing and frequency was stable throughout, but capecitabine was given at a lower dose and on every treatment day during radiation versus 2 out of every 3 weeks during induction and consolidation. The standard arm received neoadjuvant long course chemoradiation and 6 cycles of adjuvant capecitabine and oxaliplatin. At 3 years, the TNT regimen significantly improved DFS (74.8% v 66%) and also increased the pCR rate (26.4% v 9.8%). The rate of locoregional failure was similar between arms (6% v 6.2%). There was no difference in OS at 3 years (90.2% v 87.5%). Grade 3+ adverse events were higher with TNT during the neoadjuvant phase of therapy (27.6% v 8.6%), however, rates were similar when looked at across the entire course of treatment (28% v 24.3%).
TBL: TNTCRT reinforces the total neoadjuvant therapy paradigm, which improves DFS in high risk patients, while offering a different twist on chemo and radiation sequencing. | Wang, J Clin Oncol 2026