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In their study, Shachar et al. assessed the association between sarcopenia, various body composition metrics, and the frequency of adverse events related to alpelisib in breast cancer patients [1]. Sarcopenia was diagnosed by measuring the skeletal muscle cross-sectional area using computed tomography images. It is important to note that the diagnosis of sarcopenia encompasses more than just muscle mass. Low muscle strength has been demonstrated to be a more reliable predictor of adverse outcome than muscle mass alone [2]. According to the criteria established by the European Working Group on Sarcopenia in Older People (EWGSOP) and other organizations [2, 3], low muscle strength is a prerequisite for the diagnosis of sarcopenia. Grip strength, a straightforward and practical test, is frequently used by clinicians to evaluate muscle strength. However, in oncology literature, “sarcopenia” is often misused to denote low muscle mass. Consequently, it would be prudent to adopt the term “myopenia” to identify low muscle mass and reserve the term “sarcopenia” for cases where muscle strength assessments have been performed.
Furthermore, the results indicated no association between body composition measures and overall grade 2 or higher adverse events. However, upon analyzing the frequencies of specific adverse events, statistically significant associations were observed. Specifically, skeletal muscle density was associated with the frequency of hyperglycemia, and visceral adipose tissue area was associated with the frequency of rash. Is there a biological explanation for this differential association between specific toxicities and specific body composition measures? One possible explanation for these significant associations is multiple testing. In the study, sixty p-values were reported in Table 3. At a significance level of 0.05, conducting 20 independent tests with true null hypotheses may result in one false positive due to randomness. Hence, given the degree of multiplicity, it seems plausible that these associations could be incidental, especially in the absence of a clear biological rationale.
References
Shachar E, Raphael A, Katz U, Kessner R, Shachar SS (2024) Body composition measures as a determinant of alpelisib related toxicity. Breast Cancer Res Treat. https://doi.org/10.1007/s10549-024-07315-9
Cruz-Jentoft AJ, Bahat G, Bauer J, Boirie Y, Bruyere O, Cederholm T et al (2019) Sarcopenia: revised European consensus on definition and diagnosis. Age Ageing 48(1):16–31
Bhasin S, Travison TG, Manini TM, Patel S, Pencina KM, Fielding RA et al (2020) Sarcopenia definition: the position statements of the sarcopenia definition and outcomes consortium. J Am Geriatr Soc 68(7):1410–1418
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Surmeli, Z. Letter to the editor: “Body composition measures as a determinant of alpelisib-related toxicity”. Breast Cancer Res Treat 206, 677 (2024). https://doi.org/10.1007/s10549-024-07394-8
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DOI: https://doi.org/10.1007/s10549-024-07394-8