A Systematic Review and Meta-Analysis to Inform Cancer Screening Guidelines in Idiopathic Inflammatory Myopathies

Alexander G. S. Oldroyd; Andrew B. Allard; Jeffrey P. Callen; Hector Chinoy; Lorinda Chung; David Fiorentino; Michael D. George; Patrick Gordon; Kate Kolstad; Drew J. B. Kurtzman; Pedro M. Machado; Neil J. McHugh; Anna Postolova; Albert Selva-O'Callaghan; Jens Schmidt; Sarah Tansley; Ruth Ann Vleugels; Victoria P. Werth; Rohit Aggarwal

Disclosures

Rheumatology. 2021;60(6):2615-2628. 

In This Article

Abstract and Introduction

Abstract

Objectives: To identify clinical factors associated with cancer risk in the idiopathic inflammatory myopathies (IIMs) and to systematically review the existing evidence related to cancer screening.

Methods: A systematic literature search was carried out on Medline, Embase and Scopus. Cancer risk within the IIM population (i.e. not compared with the general population) was expressed as risk ratios (RR) for binary variables and weighted mean differences (WMD) for continuous variables. Evidence relating to cancer screening practices in the IIMs were synthesized via narrative review.

Results: Sixty-nine studies were included in the meta-analysis. DM subtype (RR 2.21), older age (WMD 11.19), male sex (RR 1.53), dysphagia (RR 2.09), cutaneous ulceration (RR 2.73) and anti-transcriptional intermediary factor-1 gamma positivity (RR 4.66) were identified as being associated with significantly increased risk of cancer. PM (RR 0.49) and clinically amyopathic DM (RR 0.44) subtypes, Raynaud's phenomenon (RR 0.61), interstitial lung disease (RR 0.49), very high serum creatine kinase (WMD −1189.96) or lactate dehydrogenase (WMD −336.52) levels, and anti-Jo1 (RR 0.45) or anti-EJ (RR 0.17) positivity were identified as being associated with significantly reduced risk of cancer. Nine studies relating to IIM-specific cancer screening were included. CT scanning of the thorax, abdomen and pelvis appeared to be effective in identifying underlying asymptomatic cancers.

Conclusion: Cancer risk factors should be evaluated in patients with IIM for risk stratification. Screening evidence is limited but CT scanning could be useful. Prospective studies and consensus guidelines are needed to establish cancer screening strategies in IIM patients.

Introduction

Idiopathic inflammatory myopathies (IIMs) are chronic multisystem autoimmune conditions that may cause muscle inflammation (myositis), skin manifestations and interstitial lung disease (ILD).[1,2] Adult-onset IIMs are associated with increased risk of cancer. A recent meta-analysis of such studies reported a standardized incidence ratio of 4.66 for DM and 1.75 for PM.[3] The generally accepted definition of cancer associated myositis (CAM) is malignancy within 3 years of IIM onset. Cancer remains the leading cause of death for adults with IIM.[4–6]

Around one in four patients are diagnosed with cancer within 3 years before or after IIM onset;[4] however, risk varies according to the presence/absence of certain factors.[7] Unfortunately, the data regarding risk factors are largely derived from retrospective studies with small populations, thus limiting the ability to form robust conclusions and extrapolate to the wider population.

Meta-analysis of existing evidence could synthesize results across studies and identify factors associated with cancer in IIM populations, thus potentially accounting for biases, such as publication bias and outlier studies. Further, assimilation of evidence relating to cancer screening specific to CAM could provide an evidence base informing clinical screening practices and facilitate the formulation of cancer screening guidelines.

The International Myositis Assessment and Clinical Studies Group (IMACS), the largest international group for scientific studies in myositis, began a special interest group to develop evidence-based cancer screening guidelines for newly diagnosed IIM patients. This meta-analysis forms an important component in guideline formation. Therefore, the overall aim of this study is to identify risk factors associated with CAM using meta-analysis, and to systematically review existing evidence relating to CAM screening approaches.

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