Meta-analyses Is sarcopenia a predictor of prognosis for patients undergoing radiotherapy for head and neck cancer? A meta-analysis Merran Findlay a, b, c, * , Kathryn White c , Natalie Stapleton d , Judith Bauer e a Cancer Services, Royal Prince Alfred Hospital, Missenden Road, Camperdown, 2050, NSW, Australia b Chris O'Brien Lifehouse, Missenden Road, Camperdown, 2050, NSW, Australia c Cancer Nursing Research Unit, Susan Wakil School of Nursing and Midwifery, Faculty of Medicine and Health, University of Sydney, Sydney Local Health District, Level 6 e North, Chris O'Brien Lifehouse, Missenden Road, Camperdown, 2050, NSW, Australia d Cancer Council New South Wales, Sydney,153 Dowling Street, Woolloomooloo, 2011, NSW, Australia e School of Human Movement and Nutrition Sciences, Faculty of Health and Behavioural Sciences, University of Queensland, Brisbane, 4072, QLD, Australia article info Article history: Received 22 June 2020 Accepted 11 September 2020 Keywords: Head and neck neoplasms Sarcopenia Computed tomography Meta-analysis Radiotherapy Survival summary Introduction: Computed tomography (CT)-defined sarcopenia is a demonstrated poor prognostic factor for survival in patients with cancer, however, its impact in patients with head and neck cancer (HNC) has only recently been explored. This study aimed to determine the prognostic impact of CT-defined sar- copenia at the level of the third lumbar vertebra (L3) on overall survival in patients with HNC undergoing radiotherapy ± other treatment modality of curative intent. Methods: A systematic review of the literature published between January 2004 and May 2020 was conducted in Medline, Embase, CINAHL, AMED and PubMed. Empirical studies in adults (18 years) who had completed radiotherapy of curative intent ± other treatment modalities that evaluated sarcopenia using the gold standard method at L3 and applied sex-specific cut-offs were included. Outcome of in- terest was overall survival. Study quality was assessed using the Quality In Prognosis Studies (QUIPS) tool. Hazard ratios with 95% confidence intervals derived from multivariate analysis were extracted directly from studies. Random-effects meta-analysis was used to determine the pooled hazard ratio for overall survival in patients with sarcopenia versus those without using RevMan (Version 5.3). The cer- tainty of evidence was assessed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system. Results: A total of 6211 studies were identified and screened from which seven studies met the inclusion criteria with 1059 pooled patients. All studies defined sarcopenia as low muscle mass but varied in skeletal muscle index (SMI) threshold values applied and ethnicity. Sarcopenia prevalence ranged from 6.6 to 64.6% pre-treatment and 12.4 to 65.8% post-treatment. Pre-treatment sarcopenia was associated with reduced overall survival (HR 2.07; 95%CI, 1.47e2.92, p < 0.0001, I 2 ¼ 49%) with similar findings for post-treatment sarcopenia (HR 2.93; 95%CI, 2.00e4.29, p < 0.00001, I 2 ¼ 0%) with moderate to low heterogeneity exhibited amongst studies respectively. The certainty of evidence for overall survival ac- cording to GRADE was low for pre-treatment sarcopenia and moderate for post-treatment sarcopenia. Conclusions: CT-defined sarcopenia is independently associated with reduced overall survival in patients with HNC and holds a clinically meaningful prognostic value. Consensus regarding sarcopenia assess- ment and definitions is warranted in order to substantiate these findings and support implementation of body composition assessment as a clinically meaningful prognostic tool into practice. © 2020 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved. Abbreviations: BMI, Body Mass Index; CI, Confidence Interval; CT, Computed Tomography; GLIM, Global Leadership Initiative on Malnutrition; HR, Hazard Ratio; HNC, Head and Neck Cancer; L3, Third Lumbar Vertebra; MA, Muscle Attenuation; OS, Overall Survival; PET-CT, Positron Emission Tomography Computed Tomography; SMI, Skeletal Muscle Index. * Corresponding author. Royal Prince Alfred Hospital, Sydney Local Health District Cancer Services, Level 6, Gloucester House, Missenden Road, Camperdown, 2050, NSW, Australia. E-mail addresses: merran.findlay@health.nsw.gov.au (M. Findlay), kate.white@sydney.edu.au (K. White), nat.stapleton@outlook.com (N. Stapleton), j.bauer1@uq.edu.au (J. Bauer). Contents lists available at ScienceDirect Clinical Nutrition journal homepage: http://www.elsevier.com/locate/clnu https://doi.org/10.1016/j.clnu.2020.09.017 0261-5614/© 2020 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved. Clinical Nutrition xxx (xxxx) xxx Please cite this article as: M. Findlay, K. White, N. Stapleton et al., Is sarcopenia a predictor of prognosis for patients undergoing radiotherapy for head and neck cancer? A meta-analysis, Clinical Nutrition, https://doi.org/10.1016/j.clnu.2020.09.017