S695
Clinical – Lower GI
ESTRO 2026
Purpose/Objective: To compare standard versus escalated doses in neoadjuvant chemoradiotherapy for locally advanced rectal cancer. To describe the ypCR rates, toxicity, postoperative complications, and 5-year disease-free and overall survival in our series. Material/Methods: From 2012 to 2019, 99 patients were analyzed retrospectively: standard arm (mean of 47.5 Gy) vs. dose-escalated arm (mean of 54.3 Gy). All patients were treated with 3DRT in 25 fractions, with concomitant capecitabine and surgery performed according to the total mesorectal excision principles in both arms.
transformed values were used for clustering (K-means and hierarchical). Mann–Whitney U tests assessed differences in ctDNA kinetics between patients receiving a boost at T2 and those treated without. Results: Median baseline ctDNA was 0.74% (IQR 0.62–1.30), decreasing to 0.42% (IQR 0.36–0.62) at T2 and 0.61% (IQR 0.34–1.26) at T3. One patient exhibited a pronounced ctDNA rise (15.9%) at T3 and was treated as an outlier. Overall, 8/10 patients (80%) showed ctDNA reduction between T1 and T3, mean Δ = –0.49% (range –4.54 to +2.66). Among patients receiving a radiotherapy boost (n=5), mean Δ was –0.21% vs. – 0.64% in non-boost cases (p=0.54). Although not statistically significant, non-boost patients tended to have greater ctDNA clearance, while boosted cases showed greater variability and occasional rebound.Three patients (30%) achieved pathological complete response: two where addressed to watch- and-wait (W&W) and one with ypT0N0, all without boost. No clear association between baseline cTNM and ctDNA kinetics was observed. From the qualitative point of view, the most frequent mutations involved were DNMT3A, TP53 and APC, involving loss-of- function or inactivating variants. Conclusion: Serial ctDNA monitoring during MRIgRT nCRT is feasible and sensitive to early molecular changes in LARC. Most patients showed overall decreasing of ctDNA levels, while persistent or rising ctDNA predicted incomplete pathological regression. The radiotherapy boost did not significantly modify ctDNA kinetics in this preliminary cohort, suggesting its benefit may be linked to intrinsic tumor biology rather than to dose intensification. These early findings suggest that integrating ctDNA dynamics within multi- omics predictive models may support in defining response-adapted treatment strategies in LARC. The study is totally funded by AIRC - Next Generation Clinician Scientist Call grant (ID 28614). Keywords: ctDNA; rectal cancer; MRIgRT; multi-omics; Impact of dose-escalated chemoradiation on pathological complete response in patients with locally advanced rectal cancer. Carolina Domingo-Boluda 1 , Diego Dualde 2 , Teresa Taberner-Bonastre 1 , Fernando López-Campos 3,4 1 Radiation Oncology, Hospital Universitario de La Ribera, Alzira, Spain. 2 Radiation Oncology, Hospital Clínico Universitario de Valencia, Valencia, Spain. 3 Radiation Oncology, Hospital Universitario Ramón y Cajal, Madrid, Spain. 4 Radiation Oncology, Genesis Care Hospital Vithas La Milagrosa, Madrid, Spain Digital Poster 1258
Results: From 2012 to 2019, 99 patients were retrospectively analyzed (standard group: 49 and dose-escalation group: 50), with a median follow-up of 5.93 years (IQR: 0.03–11.33). The ypCR was reported using the “College of American Pathologist grades”; the gastrointestinal (GI) and genitourinary (GU) toxicity was reported using the “Common Terminology Criteria for Adverse Events” (CTCAE 4.0). The ypCR rates were higher in the dose- escalated group (25% vs. 10.64%; p = 0.07), with a lower rate of non-treatment response (61.36% vs. 38.64%; p = 0.11). No statistical differences between the arms were found in terms of the oncological outcomes, postoperative complications (p = 0.15), second surgeries (p = 0.62), or deaths (p = 0.62). The CTCAE acute GI and GU toxicity were grade I or II in both arms.
Conclusion: In our study, we found a trend towards higher ypCR rates with neoadjuvant 3DRT intensification compared to the standard scheme. Although no statistical differences were shown, intensification is useful for specimen sterilization and should be offered to selected patients (tumors without deep invasion in our cohorts). Well-designed randomized and controlled
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