Factors Influencing Immunotherapy Outcomes in Cancer: Sarcopenia and Systemic Inflammation

Dear Editor,

We thank the authors for their valuable commentary on our study. Their discussion raises essential points regarding the definition of sarcopenia and the statistical considerations in assessing its impact on survival outcomes. We are pleased to address these concerns.

First, the authors emphasize the 2019 European Working Group on Sarcopenia in Older People-2 (EWGSOP-2) guidelines, which recommend incorporating measures such as dynapenia (muscle strength loss) and kratopenia (muscle power deficit) alongside myopenia (muscle mass loss) for a comprehensive sarcopenia diagnosis. While these criteria enhance the understanding of sarcopenia, it is important to note that assessing the skeletal muscle index (SMI) using lumbar computerized tomography (CT) imaging at the L3 vertebral level is a validated and one of the gold standard methods within the EWGSOP-2 framework. ¹ This approach is particularly relevant in oncological settings, where imaging data are readily available, providing a practical means to evaluate muscle mass in cancer patients. ² The assertion that the EWGSOP-2 guidelines reduce the significance of myopenia is challenging to support and requires caution. On the contrary, this guideline underscores the importance of CT and magnetic resonance imaging (MRI) in quantifying muscle and detecting sarcopenia in its early stages, especially in cancer patients. Furthermore, this guideline suggests a process that needs to confirm the diagnosis of sarcopenia by CT, MRI, or other methods. ¹ Due to this, myopenia remains a critical component of sarcopenia diagnosis, particularly in cancer research. ³

Second, we acknowledge the authors’ observation regarding the lack of a significant association between sarcopenia and overall survival (OS) in our study. As they rightly point out, this may be attributable to our study population’s limited sample size and heterogeneity. ⁴ In prospective studies, a more homogeneous and larger patient cohort will effectively uncover the proper relationship between sarcopenia and OS. These efforts will also facilitate comparisons across studies and enhance the reproducibility of findings.

In conclusion, while our study underscores the prognostic value of sarcopenia in immunotherapy, we agree that future research should aim to incorporate comprehensive diagnostic criteria and standardized methodologies to elucidate its clinical relevance better. We are grateful for the constructive feedback, highlighting the need for collaborative efforts to advance this field.