Compliance and Toxicity of Total Neoadjuvant Therapy in Locally Advanced Rectal Cancer: A Systematic Review and Network Meta-analysis.

Abstract

The individual chemotherapy- and radiotherapy-related toxicities between induction (iTNT) and consolidation total neoadjuvant therapy (cTNT) remain unclear. This network meta-analysis (NMA) comparing iTNT, cTNT, and traditional neoadjuvant chemoradiation (nCRT) evaluated the comparative treatment-related toxicities and compliance of the TNT schemas. A systematic review of randomized clinical trials and nonrandomized studies of interventions was performed as per Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)-NMA guidelines. A Bayesian NMA was conducted, and odds ratios (OR) with 95% credible intervals (CrI) are reported for all outcomes. Eighteen studies including 5730 patients were identified. iTNT ranked highest on rate of rectal bleeding (cTNT: OR 0.23 95% CrI 0.05-0.93; nCRT: OR 0.33, 95% CrI 0.09-0.96), proctitis (cTNT: OR 0.2, 95% CrI 0.06-0.55; nCRT: OR 0.2, 95% CrI 0.06-0.51), and postoperative diarrhea (cTNT: OR 0.37, 95% CrI 0.18-0.73; nCRT: OR 0.33, 95% CrI 0.15-0.71); cTNT ranked highest on rate of vomiting (iTNT: OR 0.24, 95% CrI 0.05-0.96; nCRT: OR 0.29, 95% CrI 0.06-0.89) and a higher rate of lymphopenia than iTNT (iTNT: OR 0.56, 95% CrI 0.34-0.99). Radiotherapy compliance was highest in cTNT (iTNT: OR 0.23, 95% CrI 0.05-0.72; nCRT: OR 0.18, 95% CrI 0.04-0.58). There was no difference in overall toxicity and mortality, chemotherapy compliance, and remaining individual system-based toxicities and postoperative complications. Across all treatment strategies, iTNT had higher radiation-related gastrointestinal toxicities and postoperative diarrhea; cTNT had higher vomiting and lymphopenia rates. While no treatment strategy was superior in chemotherapy compliance, radiotherapy compliance was ranked highest in cTNT.