Early regression index-guided adaptive dose escalation in locally advanced rectal cancer: results of the…

StudyRadiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology· Aug 2026

Early regression index-guided adaptive dose escalation in locally advanced rectal cancer: results of the prospective THUNDER-2 trial.

G Chiloiro, A Romano, L Boldrini … M A Gambacorta

Colon & Rectal SurgeryStudyTreatmentQ1IF 5.0

Early Regression Index-guided adaptive dose escalation was associated with higher complete response rates in non-responders

Early regression index-guided adaptive dose escalation in locally advanced rectal cancer: results of the prospective THUNDER-2 trial.

G Chiloiro … M A Gambacorta

Radiotherapy and oncology · Aug 2026

Background

Complete response (complete response) after neoadjuvant chemoradiotherapy (nCRT) in locally advanced rectal cancer (locally advanced rectal cancer) is associated with improved outcomes and may enable organ-preserving strategies.

Methods

With Early Regression Index ≤ 13.1 continued standard radiotherapy, whereas those with Early Regression Index > 13.1 received an adaptive boost to 60.1 Gy using online adaptive radiotherapy.

Results

adaptive dose escalation raised complete responses far above the historical rate

HR 2.35 (95% CI 1.29 to 4.26)

null 1

1.29

4.26

CI excludes the null - significant

More results

Responders achieved significantly higher total mesorectal excision (total mesorectal excision)-free survival than non-responders (38.7% vs 8.3%; hazard ratio (HR) 2.35, 95% confidence interval (CI) 1.29-4.26; p = 0.004).

Two local regrowths occurred among non-responders and were successfully salvaged.

More results

Early Regression Index was the only variable significantly associated with complete response in both univariate and multivariable analyses (adjusted odds ratio (OR) 0.912, 95% CI 0.840-0.990; p = 0.028).

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Conclusion

Early Regression Index-guided magnetic resonance imaging-based adaptive dose escalation was feasible and associated with higher-than-expected complete response rates in predicted non-responders, supporting personalized treatment intensification and organ-preservation strategies in locally advanced rectal cancer (THUNDER-2; NCT04815694).

Early regression index-guided adaptive dose escalation in locally advanced rectal cancer: results of the prospective THUNDER-2 trial.

Early regression index-guided adaptive dose escalation in locally advanced rectal cancer: results of the prospective THUNDER-2 trial.

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