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A Systematic Review of Clinical Practice Guidelines for Managing Pulmonary Toxicities Caused by Immune Checkpoint
Kofi N Donkor1, Hyeree Jang1, Reena Sail2
1Department of Hematology/Oncology, Loma Linda University Health, Loma Linda, CA, USA.
Background:
Pulmonary toxicities caused by immune checkpoint inhibitors are a prominent concern for clinicians. Clinical Practice Guidelines (CPGs) are critical for managing these toxicities.
Methods:
A systematic search of CPGs on checkpoint-associated pulmonary toxicities (ca-PT) was conducted in October 2022. PubMed, Embase, Cochrane Library, CINAHL, and Web of Science were searched. AGREE II and AGREE-REX were used to appraise CPGs and recommendations quality, respectively. Descriptive statistics, intraclass correlation coefficient, Kruskal-Wallis (H) test, and Spearman's correlation were used for analyses. P-values < .05 were considered statistically significant. Matrices were used to determine recommendation differences between CPGs. The study's design was based on the PRISMA 2020 checklist for systematic reviews. Protocol registration number: CRD42022358435.
Results:
Eight CPGs (two high-quality, three moderate-quality, and three low-quality) were identified. All CPGs covered pneumonitis. One CPG covered pleural effusions and pneumonitis/SARs-CoV-2-infection. Three CPGs covered sarcoidosis-like-reactions. CPGs for pulmonary fibrosis, airway disease, bronchiolitis, and diffuse alveolar damage, were unavailable. No CPG recommendation was based on a prospective study, and none were appraised as high-quality. Also, recommendations were not specific to histopathologic subtypes. AGREE II's "rigor of development," the domain that evaluates a guideline's methodological approach and strategies in gathering scientific evidence, correlated strongly with AGREE-REX's "overall quality" pneumonitis recommendations, r = .952; P < .01. Approximately 73% of recommendations on pneumonitis were similar between high-quality CPGs. About 16% to 74% of low-quality CPGs were similar to those recommended by high-quality CPGs.
Conclusion:
Prospectively designed research projects focusing on all types of ca-PT and their histopathologic subtypes are urgently needed. Due to the lack of high-quality recommendations in available CPGs, the disparities in treatment recommendations between high-quality CPGs, and the similarities in recommendations that exists between high-quality and low-quality CPGs, clinicians should thoroughly assess and responsibly appraise all available CPG recommendations in formulating treatment strategies for ca-PT.
Insights
Clinical Practice Guidelines (CPGs) for immune checkpoint inhibitor-associated pulmonary toxicities (ca-PT) often lack high-quality evidence and specificity. Clinicians must critically evaluate existing CPGs due to variability in recommendations.
Area of Science:
- Oncology
- Pulmonology
- Clinical Practice Guidelines
Background:
- Immune checkpoint inhibitors (ICIs) can cause significant pulmonary toxicities.
- Clinical Practice Guidelines (CPGs) are essential for managing these toxicities effectively.
- Checkpoint-associated pulmonary toxicities (ca-PT) require clear management strategies.
Purpose of the Study:
- To systematically review and appraise existing CPGs for ca-PT.
- To assess the quality and consistency of recommendations within these CPGs.
- To identify gaps in the current guidelines for managing ca-PT.
Main Methods:
- Systematic literature search for CPGs on ca-PT (October 2022).
- Appraisal of CPGs using AGREE II and recommendations using AGREE-REX.
- Statistical analyses including correlation and Kruskal-Wallis test; PRISMA 2020 guidelines followed.
Main Results:
- Eight CPGs were identified; only two were high-quality.
- All CPGs addressed pneumonitis, but few covered other ca-PT like pleural effusions or sarcoidosis-like reactions.
- No recommendations were based on prospective studies, and quality varied significantly; high-quality CPGs showed moderate agreement on pneumonitis recommendations.
Conclusions:
- There is an urgent need for prospectively designed research on all ca-PT types and their histopathologic subtypes.
- Current CPGs have limitations in quality, specificity, and evidence base.
- Clinicians must carefully appraise all CPG recommendations when developing treatment strategies for ca-PT.
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