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Multimodality treatment is a standard of care for LARC, but the optimal sequencing of the treatment modalities remains unclear. Several randomized clinical trials (RCTs) compared total neoadjuvant treatment (TNT) vs. standard neoadjuvant chemoradiotherapy (CRT) with inconsistent results. A systematic review and meta-analysis was performed to evaluate the efficacy of TNT in terms of complete pathological response (pCR) rate, disease-free and overall survival vs. standard CRT in LARC. A systematic search was performed through MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials and meeting abstracts up to May 2020. RCTs comparing CRT vs. TNT followed by surgery in LARC were eligible for the study. Study selection and data extraction were done following PRISMA guidelines by two independent reviewers. The Mantel–Haenzel method was used to obtain a fixed-effects model of pooled odds or hazard ratios for the main outcomes. Eight RCTs, including 2301 patients, met the eligibility criteria. TNT significantly improved pCR rate (OR = 1.99, 95% confidence interval (CI) 1.59–2.49; p < 0.001), 3-year disease-free-survival (DFS) (HR = 0.82, 95%CI 0.71–0.95; p = 0.01) and 3-year overall survival (OS) (hazard ratio (HR) = 0.81, p = 0.04). Grade 3–4 adverse events were not significantly different in both strategies (OR = 1.58; p = 0.14). An improved pCR rate was documented regardless of the type of radiotherapy administered (long vs. short fractionation schedules). No significant heterogeneity was found. The results of this meta-analysis show that TNT improves pCR and survival rates vs. standard preoperative CRT in patients with LARC. TNT may become a new standard of care in LARC, although longer follow-up is needed to properly assess its long-term impact on survival.

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Background:Combination of capecitabine and irinotecan (XELIRI regimen) is an active and well tolerated treatment for metastatic colorectal cancer (mCRC). The aim of this study was to evaluate the efficacy and safety of this regimen in combination with bevacizumab (BV), as first-line treatment for mCRC.Patients and methods:A total of 46 consecutive patients received a combination of BV (5 mg kg−1, day 1), irinotecan (175 mg m−2, day 1) and capecitabine (1000 mg m−2 twice daily on day 2–8), every 2 weeks. Patients were treated until disease progression or unacceptable toxicity. The primary objective was to determine the progression-free survival (PFS) and safety profile.Results:The overall response rate (ORR) was 67.4%, with a disease control rate (ORR+stable disease) of 93.5%. Median PFS and overall survival (OS) were 12.3 months (95% confidence interval (CI): 6.5–18.1 months) and 23.7 months (95% CI: 16.7–30.6 months), respectively. The most frequent grade 3/4 treatment-related adverse events were asthenia (7%), diarrhoea (7%), nausea (9%) and vomiting (7%).Conclusion:Bevacizumab combined with biweekly XELIRI is a highly active first-line regimen for mCRC treatment, showing encouraging PFS, ORR and OS with a good tolerability.