Intensity-modulated radiation therapy can reduce acute toxicities in long-course neoadjuvant radiation therapy combined with S-1 for locally advanced rectal cancer.

Background: The purpose of this study was to compare outcomes and adverse events between three-dimensional conformal radiation therapy (3D-CRT) and intensity-modulated radiation therapy (IMRT) in patients undergoing long-course neoadjuvant radiation therapy (NA-RT) for locally advanced rectal adenocarcinoma (LARC).

Methods: We retrospectively analyzed a total of 47 consecutive patients who received NA-RT for LARC between January 2011 and September 2022. Seven and 40 patients were diagnosed with clinical stages II and III, respectively. The prescribed dose per fraction was 1.8 Gy for total doses of 45 or 50.4 Gy. Seventeen and 30 patients received 3D-CRT and IMRT, respectively. NA-RT was delivered with concurrent chemotherapy of oral administration of S-1.

Results: Planned NA-RT was completed without any treatment interruption in 43 of the 47 patients. Two patients experienced treatment interruption, and two patients discontinued due to grade ≥ 3 toxicities. No significant differences were observed between patients receiving 3D-CRT and IMRT in local control, progression-free survival, and overall survival (P = 0.488, 0.259, and 0.636, respectively). Patients receiving IMRT showed significantly fewer non-hematological grade ≥ 2 acute toxicities than those receiving 3D-CRT (33.3% vs. 70.6%, P = 0.018). In addition, patients who received IMRT tended to have less intestinal toxicity of grade ≥ 2 than those who received 3D-CRT (P = 0.057).

Conclusion: IMRT significantly reduced grade ≥ 2 acute toxicities without compromising oncologic outcomes compared to 3D-CRT. Therefore, IMRT may be considered as a current standard treatment in the total neoadjuvant therapy era.