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Short-Course Versus Long-Course Neoadjuvant Chemoradiotherapy in Patients With Rectal Cancer: Long-Term Results of a Randomized Controlled Trial Publisher Pubmed



Aghili M1, 2 ; Aghaei MM1 ; Abyaneh R1 ; Babaei M1, 2 ; Farhan F1, 2 ; Lashkari M1, 2 ; Farazmand B1 ; Kolahdouzan K1, 2 ; Piozzi GN3 ; Counago F4, 5, 6, 7 ; Ghalehtaki R1, 2
Authors
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Authors Affiliations
  1. 1. Radiation Oncology Research Center, Cancer Research Institute, IKHC, Tehran University of Medical Sciences, Tehran, Iran
  2. 2. Department of Radiation Oncology, Cancer Institute, IKHC, Tehran University of Medical Sciences, Tehran, Iran
  3. 3. Department of Colorectal Surgery, Portsmouth Hospitals University NHS Trust, Portsmouth, United Kingdom
  4. 4. Department of Medicine, Faculty of Medicine, Health and Sport Sciences, Universidad Europea de Madrid, Madrid, Spain
  5. 5. GenesisCare, Madrid, Spain
  6. 6. Hospital Universitario San Francisco de Asis, Madrid, Spain
  7. 7. Hospital Universitario La Milagrosa, Madrid, Spain

Source: International Journal of Colorectal Disease Published:2025


Abstract

Background and purpose: Short-course radiotherapy (SCRT) and long-course radiotherapy (LCRT) are the primary neoadjuvant radiotherapy schedules for locally advanced rectal cancer. Recent research has questioned the efficacy of SCRT. This study presents an updated analysis of our previous research, extending the follow-up to evaluate 5-year outcomes by comparing the long-term results of these two strategies. Materials and methods: This randomized controlled trial compared SCRT and LCRT in locally advanced middle or high rectal adenocarcinoma. The SCRT group received 25 Gy/5 fractions over 1 week plus CAPOX, while the LCRT group received 50–50.4 Gy/25–28 fractions over 5–5.5 weeks plus capecitabine. All patients received consolidation chemotherapy and then underwent delayed surgery after 8 weeks or more post-radiotherapy. The endpoints of this updated analysis include overall survival (OS),disease-free survival (DFS), locoregional recurrence (LR) and distant metastasis (DM). Results: Ninety-nine cases (45 LCRT, 54 SCRT) were followed for a median of 4.7 years. Five-year OS rates were 77.3% for LCRT vs. 65.6% for SCRT group (P = 0.4). The 5-year DFS rates were 69.6% for LCRT vs. 54.9% for SCRT (P = 0.07). Cox regression indicated no prominent difference between the two groups regarding OS, LR, or DM. Subgroup analysis demonstrated a significantly better DFS with LCRT compared to SCRT in male patients ([HR] = 2.48, 95%CI: 1.04–5.93, P = 0.03), patients under the age of 60 (HR = 3.19, 95%CI: 1.03–9.92, P = 0.04), and cT4 patients (HR not calculated: no events in LCRT group, P = 0.004). Conclusion: DFS showed a trend in favor of the LCRT group, with LCRT being significantly superior among men, patients under 60, and cT4 stage. Despite being intensified, SCRT failed to achieve long-term outcomes comparable to LCRT. Further research is needed to compare these two approaches in the context of total neoadjuvant treatment. Trial registration data: IRCT2017110424266N3 (Registration date: 2017–11-12). https://irct.behdasht.gov.ir/trial/20526. © The Author(s) 2025.
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