What is Trinitrotoluene (TNT) in the context of colon cancer?

From the Guidelines

TNT in the context of colon cancer refers to the Total Neoadjuvant Therapy approach, which includes neoadjuvant chemotherapy and either short-course radiation or long-course chemoradiation therapy, aiming to improve adherence, decrease distant metastases, and ultimately improve overall survival. This approach has been proposed as a way to enhance treatment outcomes for locally advanced rectal cancer, as noted in the 2024 ASCO guideline on the management of locally advanced rectal cancer 1. The guideline discusses the evolution of treatment paradigms for rectal cancer, including the shift from postoperative to preoperative chemoradiation therapy, and now the consideration of total neoadjuvant therapy as a potential standard of care.

Key aspects of TNT include:

• Neoadjuvant chemotherapy to address potential micrometastatic disease early
• The use of either short-course radiation or long-course chemoradiation therapy to enhance local control
• The potential for improved adherence to adjuvant therapy, as the entire neoadjuvant regimen is completed before surgery
• The possibility of omitting radiation therapy in certain scenarios or adopting a nonoperative strategy for patients with a clinical complete response to initial treatment, as discussed in the guideline 1

The benefits of TNT, as supported by recent developments in the treatment of locally advanced rectal cancer, include:

• Improved local control and reduced toxicity compared to traditional postoperative chemoradiation therapy
• Potential for better long-term outcomes, including overall survival, by addressing both local and systemic disease components early in the treatment sequence
• Enhanced sphincter preservation in low-lying tumors due to better tumor downstaging before surgery

Given the information provided in the 2024 ASCO guideline 1, the adoption of TNT as a treatment strategy for locally advanced rectal cancer is supported, especially for patients with high-risk features, as it offers a comprehensive approach to managing both local and systemic disease, potentially leading to improved morbidity, mortality, and quality of life outcomes.

From the Research

Definition of Trinitrotoluene (TNT) in the Context of Colon Cancer

• Trinitrotoluene (TNT) in the context of colon cancer refers to Total Neoadjuvant Therapy, a treatment approach that involves the administration of chemotherapeutic regimens and chemoradiation before surgery 2, 3, 4, 5, 6.
• This approach is used to treat locally advanced rectal cancer and aims to increase complete pathological and clinical responses, potentially allowing patients to avoid undergoing a proctectomy 2.

Key Components of TNT

• TNT typically involves the use of chemotherapeutic regimens such as FOLFOX or CAPEOX, in combination with chemoradiation 2.
• The goal of TNT is to deliver uninterrupted systemic therapy to eradicate micrometastases and improve treatment outcomes 4, 5.

Efficacy of TNT

• Studies have shown that TNT is associated with higher rates of pathologic complete response (pCR) compared to standard therapy 3, 5, 6.
• TNT has also been shown to improve disease-free survival (DFS) and overall survival (OS) outcomes in patients with locally advanced rectal cancer 5, 6.
• Additionally, TNT may reduce the risk of distant metastasis and improve local recurrence-free survival 6.

Safety and Tolerability of TNT

• TNT has been shown to be safe and efficient for patients with locally advanced rectal cancer, with no significant increase in toxic effects or perioperative complications 2, 3.
• However, further studies are needed to fully evaluate the long-term effects of TNT on disease recurrence and overall survival 5.