Risk-Adapted Selective Elective Nodal Irradiation in the Total Neoadjuvant Therapy Era for Rectal Cancer.

Area of Science:

• Oncology
• Radiation Oncology
• Surgical Oncology

Background:

• Total neoadjuvant therapy (TNT) has expanded treatment options for locally advanced rectal cancer.
• Challenges persist in optimizing TNT protocols, particularly regarding neoadjuvant radiation therapy (RT).
• A recent study demonstrated non-inferiority of omitting RT in intermediate-risk rectal cancer when using full-dose neoadjuvant chemotherapy.

Purpose of the Study:

• To explore a risk-adapted approach for personalizing neoadjuvant radiation therapy within the TNT framework.
• To advocate for selective reduction of elective nodal irradiation, specifically lateral pelvic lymph nodes.
• To balance oncologic safety with reduced treatment toxicity and improved quality of life.

Main Methods:

• Reviewing findings from a randomized clinical study in intermediate-risk locally advanced rectal cancer.
• Drawing parallels between radiation therapy targeting and surgical practices like lateral pelvic lymph node dissection.
• Proposing a risk-adapted strategy focusing RT on mesorectal and presacral regions.
• Leveraging response assessment after induction chemotherapy for patient selection.

Main Results:

• Neoadjuvant full-dose systemic chemotherapy with response-adapted omission of RT is non-inferior to concurrent chemoradiotherapy.
• Selective omission of lateral pelvic lymph node irradiation may maintain oncologic safety.
• Reducing RT target volume with intensity-modulated RT enhances organs-at-risk sparing and mitigates toxicity.

Conclusions:

• A risk-adapted, personalized approach to neoadjuvant radiation therapy in TNT for rectal cancer is feasible.
• Selective omission of lateral nodal irradiation, guided by response assessment, can optimize treatment.
• This strategy holds promise for improving patient outcomes by balancing disease control and quality of life.