KEY POINTS
- This secondary analysis of the phase III RAPIDO trial combined prospectively collected toxicity data with retrospectively retrieved radiotherapy datasets from 35 centres. Acute-toxicity analyses included 309 patients receiving short-course total neoadjuvant treatment and 279 patients receiving conventional chemoradiation.
- The total neoadjuvant arm received 25 Gy in 5 fractions followed by six cycles of CAPOX or nine cycles of FOLFOX4 before surgery. The comparison arm received 50.0–50.4 Gy in 25–28 fractions with concurrent capecitabine, with postoperative chemotherapy optional.
- Grade ≥2 acute diarrhea occurred in 38% (117/309) after short-course total neoadjuvant treatment and 28% (77/279) after chemoradiation. In the short-course arm, RTOG bowel-bag V20Gy was independently associated with toxicity: each additional 100 cm³ irradiated increased the odds by 18% (OR 1.18, 95% CI 1.06–1.38; p=0.003).
- Associations were stronger after chemoradiation. For the EMBRACE bowel-loop contour, each additional 100 cm³ receiving ≥40 Gy was associated with 72% higher odds of acute diarrhea (OR 1.72, 95% CI 1.25–2.71; p<0.001); V15Gy and V30Gy were also significant.
- Model discrimination remained limited despite generally reasonable calibration. Cross-validated areas under the curve were only 0.48–0.61 in the short-course arm and 0.56–0.67 in the chemoradiation arm, limiting use for individual-patient toxicity prediction.
- EMBRACE bowel-loop and RTOG bowel-bag approaches performed similarly, and corresponding dose-volume measures were moderately to highly correlated (R² 0.67–0.92 after short-course treatment and 0.59–0.91 after chemoradiation). This suggests either contouring approach could reasonably support bowel-dose optimization.
- Late physician-graded diarrhea after chemoradiation showed dose associations only among patients with a stoma; RTOG V30Gy had OR 1.41 per 100 cm³ (95% CI 1.12–1.92; p<0.001). No bowel dose metric predicted patient-reported late diarrhea, and no metric predicted chemotherapy non-compliance.
CLINICAL TAKEAWAY
Reducing irradiated bowel volume remains a sensible optimization goal in both short-course total neoadjuvant treatment and conventional chemoradiation for rectal cancer, and either EMBRACE or RTOG bowel contours appears usable. The models are better viewed as planning guidance than individual toxicity calculators because discrimination was modest and external validation is still required.
SOURCE
International Journal of Radiation Oncology, Biology, Physics