The Impacts of Active and Inactive Ghrelin on Cachexia and Immune Checkpoint Inhibitor Monotherapy in Patients with Non-Small Cell Lung Cancer.

Introduction: Identifying the underlying mechanisms of immune checkpoint inhibitor resistance in patients with cachexia is a current challenge. Ghrelin is a peptide hormone that plays an important role in the metabolism of patients with cancer cachexia. Despite the importance of ghrelin in cancer cachexia, most previous studies on the subject have not distinguished between the forms of ghrelin.

Methods: We retrospectively screened patients with advanced or recurrent non-small cell lung cancer receiving PD-1/PD-L1 inhibitor monotherapy. Active and inactive ghrelin levels were measured in 100 patients with available plasma samples at immune checkpoint inhibitor initiation. Cancer cachexia was defined as weight loss of at least 5% during the past 6 months or weight loss of at least 2% with a BMI <20. We analyzed the associations of the active and inactive ghrelin levels and active-to-inactive ghrelin ratio (AIR) with cancer cachexia. The prognostic impact of the active and inactive ghrelin levels and AIR were also analyzed.

Results: Among 100 patients, 35 were diagnosed with cancer cachexia. The active ghrelin level and AIR were significantly associated with cancer cachexia, whereas the inactive ghrelin level was not. The active and inactive ghrelin levels and AIR were not associated with patient prognosis.

Conclusion: The active ghrelin level and AIR were associated with cancer cachexia but not with patient prognosis. The function of the active and inactive forms of ghrelin may differ in cancer patients. The form of ghrelin should be clearly mentioned in relevant studies on cancer cachexia.