Impact of Center Volume on Cardiopulmonary and Mortality Outcomes after Immune-Checkpoint Inhibitors for Cancer: A Systematic Review and Meta-Analysis

TL;DR

High-volume hospitals have better outcomes for patients using immune-checkpoint inhibitors, with fewer severe side effects.

Contribution

Demonstrates a novel link between hospital case volume and reduced severe adverse events in immunotherapy treatment.

Findings

Centers with ≥33 annual cases had fewer cardiac-related adverse events.

Higher annual case volume was associated with reduced grade 5 adverse events.

Pooled event rates for grade 5 AEs were 2.75%.

Abstract

Immune-checkpoint inhibitors have been proven to aid in tumor regression. We performed a meta-analysis and systematic review to investigate the relationship between hospital volume and patient outcomes. We found that centers performing ≥ 33 annual cases had fewer cardiac-related adverse events (AEs). The pooled estimated rates of grade 5 AEs were 2.75% (95%CI: 2.18–3.47), with higher annual cases associated with reduced grade 5 AEs at meta-regression. Ultimately, patients should be referred to high-volume centers when severe immune-related AEs occur.

Immune-checkpoint inhibitors (ICIs) were proven effective in inducing tumor regression. However, its toxicity tends to be fatal. We sought to investigate the hospital volume/outcomes relationship. Databases were searched for studies reporting immune-checkpoint inhibitors adverse events (AEs) in patients with solid-organ malignancies. The outcomes were A) the pooled events rate (PER) of grade 5, grade 3–4, cardiac-related, and pulmonary-related AEs, and B) the assessment of the volume/outcomes relationship. One hundred and forty-seven studies met our inclusion criteria. The PER of grade 5, grade 3–4, and any-grade AEs was 2.75% (95%CI: 2.18–3.47), 26.69% (95%CI: 21.60–32.48), and 77.80% (95%CI: 70.91–83.44), respectively. The PER of pulmonary-related AEs was 4.56% (95%CI: 3.76–5.53). A higher number of annual cases per center was significantly associated with reduced grade 5 (p = 0.019), grade 3–4 (p = 0.004), and cardiac-related AEs (p = 0.035) in the meta-regression. In the current era of cancer immunotherapy, knowledge regarding the early diagnosis and management of immunotherapy-related AEs is essential. Our meta-analysis demonstrates the importance of center volume in improving outcomes and reducing the incidence of severe AEs.

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