Key Points Question Is total neoadjuvant therapy (TNT) associated with improved outcomes when compared with standard concurrent chemoradiotherapy followed by surgery and adjuvant chemotherapy (CRT plus A) for locally advanced rectal cancer? Findings In this systematic review and meta-analysis of 7 unique studies including 2416 unique patients, TNT was found to be associated with a significantly higher rate of achieving a pathologic complete response and disease-free survival compared with the standard CRT plus A approach. No significant difference was found in rates of sphincter-preserving surgery or ileostomy requirements between the 2 approaches. Meaning Total neoadjuvant therapy was associated with improved pathologic complete response rates and has a potential disease-free survival advantage compared with the standard CRT plus A strategy in locally advanced rectal cancer.

Background and Aims: Atezolizumab plus bevacizumab (AtezoBev) is the standard of care for first-line treatment of unresectable HCC. No evidence exists as to its use in routine clinical practice in patients with impaired liver function.

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BackgroundNivolumab is Food and Drug Administration approved in sorafenib-experienced, advanced hepatocellular carcinoma (HCC). Post-registration data of treatment in a real-world setting is lacking.Patients and methodsWe performed an international, multicenter observational study to confirm safety and efficacy of nivolumab in 233 patients treated outside clinical trials from eight centers in North America, Europe and Asia.ResultsPatients received nivolumab for Barcelona Clinic Liver Cancer stage C (n=191, 92.0%) and Child-Pugh (CP) A (n=158, 67.8%) or B (n=75, 32.2%) HCC as first (n=85, 36.5%) or second to fourth systemic therapy line (n=148, 63.5%). Objective response rate (ORR) was 22.4% and disease control rate was 52.1%. Median overall survival (OS) was 12.2 months (95% CI 8.4 to 16.0) and median progression-free survival was 10.1 months (95% CI 6.1 to 14.2). Treatment-related adverse events of grade >2 occurred in 26 patients (11.2%). Efficacy and safety were similar across CP classes and therapy line. OS was shorter in CP-B than A (7.3 months vs 16.3 months, p<0.001) and in post-first line use (10.4 months vs 16.3 months, p=0.05). Achievement of an objective response predicted for improved OS (25.4 months vs 13.2 months, p<0.001).ConclusionsThis study confirms safety and efficacy of nivolumab in advanced HCC across various lines of therapy and degrees of liver dysfunction. Despite equal ORR and toxicity to nivolumab, patients with CP-B functional class have shorter survival than the patients with CP-A.