Neoadjuvant Modified Short-Course Radiotherapy Followed by Delayed Surgery for Locally Advanced Rectal Cancer

SIMPLE SUMMARY: Both short- and long-course neoadjuvant radiotherapy (NA-RT) followed by surgery have been adopted as standard treatments for locally advanced rectal cancer (LARC). We hypothesized that a modified short-course radiotherapy (mSC-RT) using an accelerated hyperfractionated regimen, with a dose of 2.5 Gy twice daily up to a total dose of 25 Gy in 10 fractions, can provide a favorable therapeutic ratio in comparison with the conventional regimens. Ninety-seven consecutive LARC patients undergoing mSC-RT followed by delayed surgery were analyzed in this retrospective study. Additionally, potential prognostic factors for overall survival (OS) were also assessed. The results showed that mSC-RT followed by delayed surgery achieved equivalent anti-tumor efficacy and acute toxicity that were comparable with long- and short-course NA-RT, respectively. A neutrophil-to-lymphocyte ratio (NLR) ≥ 1.83 was independently associated with poor OS in LARC patients receiving mSC-RT. Thus, mSC-RT can be a promising alternative to both standard long- and short-course NA-RT regimens. ABSTRACT: This study aimed to assess the clinical outcomes and predictive factors of neoadjuvant modified short-course radiotherapy (mSC-RT) for locally advanced rectal cancer (LARC). Data from 97 patients undergoing mSC-RT followed by radical surgery for LARC were retrospectively analyzed. A 2.5 Gy dose twice daily up to a total dose of 25 Gy in 10 fractions was administered through mSC-RT, and this was delivered with oral chemotherapy in 95 (97.9%) patients. Radical surgery was performed 6 (range, 3–13) weeks after mSC-RT. The median follow-up among surviving patients was 43 (8–86) months. All patients completed neoadjuvant radiotherapy with no acute toxicity grade ≥ 3. Three- and five-year local control rates were 96.3% and 96.3%, respectively. Three- and five-year overall survival (OS) rates were 92.7% and 79.8%, respectively. Univariate analyses revealed that poor OS was associated with no concurrent administration of capecitabine, C-reactive-protein-to-albumin ratio ≥ 0.053, carcinoembryonic antigen ≥ 3.4 ng/mL, and neutrophil-to-lymphocyte ratio (NLR) ≥ 1.83 (P = 0.045, 0.001, 0.041, and 0.001, respectively). Multivariate analyses indicated that NLR ≥ 1.83 was independently associated with poor OS (p = 0.018). mSC-RT followed by delayed surgery for LARC was deemed feasible and resulted in good clinical outcomes, whereas poor OS was associated with high NLR.