Neoadjuvant sequential short-course radiotherapy and folfox versus neoadjuvant long-course chemo-radiation and evaluation of glascow scale sensitivity as a prognostic and predictive marker in locally advanced rectal cancer.

Background: The trial hypothesis was that short-course radiotherapy followed by near-total neoadjuvant chemotherapy would increase patient adherence to treatment compared to standard chemo-radiotherapy for locally advanced rectal cancer, without affecting oncological results. Methods: In this open-label RCT, patients with cT3, cT4, or node-positive non-metastatic rectal cancer were randomly assigned to receive complete mesorectal excision after receiving either 5*5 Gy of radiation and FOLFOX or concomitant chemo-radiotherapy and capecitabine. Adjuvant chemotherapy cycles were administered to patients using the FOLFOX regimen. The primary endpoint was to evaluate the response rate after the completion of treatment. The secondary goal was to assess the failure rate (local or distant) and treatment toxicity. Results: Of 100 patients, 50 were in arm 1 and 50 in arm 2. Patients’ characteristics differences between the two groups were not significant except for mutant BRAF and pre-treatment CEA levels p=0.043 and p<0.001. Tumour regression grade 1 was 18% in arm 1 and 2% in arm 2. The pathological response was statistically significant with BRAF mutation (p<0.001), pretreatment CEA level (p=0.006), treatment arms (p=0.031), and pre-treatment GPS (p<0.001). For Overall Survival (OS), the 3-year OS was 94% which was statistically insignificant between the two arms (p=0.564). Three years OS was higher in patients with GPS zero, normal pre-treatment CEA level, wild-type BRAF mutation, and TRG 1 and 2. For disease-free survival, the 3-year DFS was 90% that was statistically insignificant between the two arms (p=0.627). Three-year DFS was higher in TRG1 and 2 100% for both, normal pre-treatment CEA level and pre-treatment GPS zero. The chemotherapy adverse events were vomiting, anaemia, and neurotoxicity which were almost the same in both arms 1 and 2. As regard radiation therapy side effects, the main genitourinary toxicity in the form of dysuria and urinary tract infection46% in arm 1 and 66% in arm 2 (p=0.292), lower GIT toxicity proctitis occur in 40% in arm 1 and 30% of arm 2 (p=0.022) with no grade 3 or grade 4 toxicity in both arms. Conclusion: Short course radiotherapy followed by chemotherapy (near total neoadjuvant therapy) then TME offers comparable results *Watch and wait strategy may be the appropriate option in patients developing a complete pathological response. [ABSTRACT FROM AUTHOR]