SHORT VS LONG COURSE RADIOTHERAPY IN RECTAL CANCER: ACUTE TOXICITY AND OUTCOMES FROM A SINGLE-CENTRE COHORT"
Main Article Content
Keywords
Locally Advanced Rectal Cancer, Short-Course Radiotherapy (SCRT), Total neoadjuvant therapy (TNT), Acute Toxicities, Outcomes
Abstract
Background: Short-course radiotherapy (SCRT) and long-course chemoradiation (LCRT) are accepted neoadjuvant options in locally advanced rectal cancer (LARC), yet real-world comparative data on acute toxicity and early surgical quality are limited.
Methods: This single-centre randomized two-arm cohort compared SCRT (25 Gy/5 fractions with delayed surgery) versus LCRT (45 Gy/25 fractions with concurrent capecitabine plus 5.4 Gy boost). Acute toxicities were graded by RTOG/WHO criteria. The primary endpoint was clinically relevant acute toxicity; secondary endpoints included sphincter preservation, margin status, postoperative complications, pathological response, and early distant metastasis. Analyses were intention-to-treat using Fisher’s exact tests with 95% CIs.
Results: Thirty-nine patients were enrolled (SCRT = 16; LCRT = 23). Clinically relevant acute toxicities were markedly lower with SCRT: no ≥G2 skin events (0% vs 69.6%), fewer GI/proctitis ≥G2 (31.3% vs 87.0%), and no hematologic ≥G2 (0% vs 13.0%). Sphincter preservation (46.7% vs 40.9%), R0 resection rates (87.5% vs 87.0%), margins, and 30-day complications were comparable. Pathologic CR occurred in 10.3% overall. Early distant metastasis was 0% after SCRT vs 13.0% after LCRT.
Conclusions: Compared with LCRT, SCRT with consolidation chemotherapy and delayed surgery produced substantially lower acute skin, gastrointestinal, and hematologic toxicity with comparable surgical quality metrics, supporting SCRT as a tolerable, resource-efficient neoadjuvant strategy warranting confirmation in larger prospective cohorts with longer follow-up and patient-reported outcomes.
References
2. van Gijn W, Marijnen CA, Nagtegaal ID, Kranenbarg EM, Putter H, Wiggers T et.al.Preoperative radiotherapy combined with TME: 10-year follow-up of the Dutch TME trial. Lancet Oncol. 2011;12(6):575–82.
3. Sebag-Montefiore D, Stephens RJ, Steele R, Monson J, Grieve R, Khanna S et.al. Preoperative radiotherapy vs selective postoperative chemoradiotherapy (MRC CR07/NCIC-CTG C016). Lancet. 2009;373(9666):811–20.
4. Sauer R, Becker H, Hohenberger W, Rödel C, Wittekind C, Fietkau R et.al. Preoperative vs postoperative chemoradiotherapy (CAO/ARO/AIO-94). N Engl J Med. 2004;351(17):1731–40.
5. Sauer R, Liersch T, Merkel S, Fietkau R, Hohenberger W, Hess C et.al. Preoperative versus postoperative chemoradiotherapy for locally advanced rectal cancer: results of the German CAO/ARO/AIO-94 randomized phase III trial after a median follow-up of 11 years. J Clin Oncol. 2012;30(16):1926–33.
6. Bujko K, Nowacki MP, Nasierowska-Guttmejer A, Michalski W, Bebenek M, Kryj M. Long-term results of randomized trial: preop short-course RT vs conventionally fractionated preop chemoradiation. Br J Surg. 2006;93(10):1215–23.
7. Ciseł B, Pietrzak L, Michalski W, Wyrwicz L, Rutkowski A, Kosakowska E et.al. Polish Colorectal Study Group. LCRT vs 5×5 Gy + consolidation chemotherapy for cT4/fixed cT3: long-term Polish II results. Ann Oncol. 2019;30(8):1298–303.
8. Erlandsson J, Holm T, Pettersson D, Berglund Å, Cedermark B, Radu C. Stockholm III: timing to surgery and fractionation of preop RT. Lancet Oncol. 2017;18(3):336–46.
9. Pettersson D, Lörinc E, Holm T, Iversen H, Cedermark B, Glimelius B et.al. Tumour regression in Stockholm III. Br J Surg. 2015;102(8):972–8.
10. Patel A, Spychalski P, Corrao G, Jereczek-Fossa BA, Glynne-Jones R, Garcia-Aguilar J et.al. Neoadjuvant short-course radiotherapy with consolidation chemotherapy for locally advanced rectal cancer: a systematic review and meta-analysis. Acta Oncologica. 2021;60(10):1308-16.
11. Wang X, Zheng B, Lu X, Bai R, Feng L, Wang Q, et.al. Preoperative short-course radiotherapy and long-course radiochemotherapy for locally advanced rectal cancer: Meta-analysis with trial sequential analysis of long-term survival data. PLoS One. 2018;13(7):e0200142.
12. Pu JJ, Drabick JJ, Prockop SE. Checkpoint inhibition in hematologic malignancies. Front Oncol. 2024;14:1429854.
13. Bahadoer RR, Dijkstra EA, van Etten B, Marijnen CA, Putter H, Kranenbarg EM et. Al. RAPIDO investigators. Short-course RT followed by chemo vs standard CRT (RAPIDO). Lancet Oncol. 2021;22(1):29–42.
14. Dijkstra EA, Hospers GA, Kranenbarg EM, Fleer J, Roodvoets AG, Bahadoer RR et.al. Quality of life and late toxicity after short-course radiotherapy followed by chemotherapy or chemoradiotherapy for locally advanced rectal cancer–The RAPIDO trial. Radiother Oncol. 2022;171:69-76.
15. Conroy T, Bosset JF, Etienne PL, Rio E, François É, Mesgouez-Nebout N et.al. PRODIGE-23 investigators. Neoadjuvant mFOLFIRINOX then CRT vs standard preop CRT. Lancet Oncol. 2021;22(5):702–15.
16. Conroy T, Lamfichekh N, Etienne PL. PRODIGE-23. Long-term outcomes update. Ann Oncol. 2024;35(10).
17. Garcia-Aguilar J, Patil S, Gollub MJ, Kim JK, Yuval JB, Thompson HM, et.al. Organ preservation in patients with rectal adenocarcinoma treated with total neoadjuvant therapy. J Clin Oncol. 2022;40(23):2546–56.
18. Verheij FS, Thompson HM, Lee M. OPRA long-term results: durability of organ preservation. J Clin Oncol. 2024;42(32).
19. Jin J, Tang Y, Hu C, Jiang LM, Jiang J, Li N et.al. STELLAR: short-term RT + preop chemotherapy vs long-course CRT in LARC (phase III). J Clin Oncol. 2022;40(16):1681–92.
20. Lee CH, Lin CH, Hsu YJ. Network meta-analysis of neoadjuvant strategies in LARC. EClinicalMedicine. 2023;59:101949
21. Hofheinz RD, Fokas E, Benhaim L, Price TJ, Arnold D, Beets-Tan R et.al. ESMO Guidelines Committee. Localised rectal cancer: ESMO Clinical Practice Guideline (2025 update). Ann Oncol. 2025;36(9):1007–24.
22. Benson AB, Venook AP, Adam M, Chang G, Chen YJ, Ciombor KK et.al. NCCN Guidelines® Insights: Rectal Cancer, Version 3.2024. J Natl Compr Canc Netw. 2024;22(6):366–75.
23. Wo JY, Ashman JB, Bhadkamkar NA, Bradfield L, Chang DT, Hanna N et.al. ASTRO Clinical Practice Guideline Focused Update: Radiation Therapy for Rectal Cancer. Pract Radiat Oncol. 2025;15(2):124–43.
24. Cox JD, Stetz J, Pajak TF. Toxicity criteria of the RTOG and EORTC (acute/late scoring). Int J Radiat Oncol Biol Phys. 1995;31(5):1341–6.