Acute and Late Radiation-Related Toxicity After Treatment of Locally Advanced Rectal Cancer With Intensity Modulated Radiation Therapy Compared With 3-Dimensional Conformal Radiation Therapy in the RAPIDO Trial.

Purpose: Intensity modulated radiation therapy (IMRT) aims to lower radiation-related toxicity by delivering more conformal radiation therapy compared with 3-dimensional conformal radiation therapy (3D-CRT). This study investigated whether IMRT (including volumetric modulated arc therapy) resulted in less acute and late radiation-related toxicity and better treatment compliance compared with 3D-CRT in the phase 3 RAPIDO trial.

Methods And Materials: Patients with locally advanced rectal cancer (LARC), treated with short-course radiation therapy followed by consolidation therapy (total neoadjuvant treatment [TNT] arm) or chemoradiation therapy with optional postoperative chemotherapy (CRT arm) were included. IMRT was compared with 3D-CRT, stratified by treatment arm. Acute, late, and persistent toxicity endpoints included radiation-related gastrointestinal, general, genitourinary, hematologic, and sexual adverse events (CTCAEv4). Toxicity endpoints were analyzed as binary outcomes (grade ≥ 1 vs grade 0 and grade ≥ 3 vs grade 0-2) with univariable and multivariable logistic regression analyses.

Results: For acute and late toxicity analyses, 460 and 352 patients were eligible in the TNT arm, respectively, and 441 and 321 patients in the CRT arm. IMRT was delivered in 29% of the patients. After IMRT in the TNT arm, more acute fatigue grade ≥ 1 (OR, 2.71; 95% CI, 1.60-4.60; P < .001) and more acute nausea/vomiting grade ≥1 (OR, 1.79; 95% CI, 1.15-2.79; P = .010) was observed compared with 3D-CRT. After IMRT in the CRT arm, more any late radiation-related toxicity grade ≥ 1 (OR, 2.14; 95% CI, 1.28-3.57; P = .004) and more late sexual toxicity grade ≥ 1 (OR, 2.31; 95% CI, 1.24-4.29; P = .008) was observed compared with 3D-CRT. No differences were found for other grade ≥ 1 toxicity endpoints, grade ≥ 3 toxicity, or treatment compliance. Persistent toxicity was rare in both groups.

Conclusions: IMRT was not associated with less radiation-related toxicity compared with 3D-CRT after TNT or CRT. In contrast, some lower grade toxicities were more frequent after IMRT, in particular fatigue during TNT. Late persistent toxicity was uncommon in both groups.