Exploratory analyses have suggested associations between cytokine levels and symptom response in cancer patients receiving placebo; however, the inferential strength of these findings remains limited. This letter introduces the concept of "fragile results" to describe outcomes derived from underpowered models subject to extensive multiplicity and lacking internal validation. Key concerns include low events-per-predictor ratios, multiple hypothesis testing, and potential inflation of type I error in flexible modeling approaches. To guide future research, sample size requirements for confirmatory studies are estimated using contemporary prediction modeling frameworks, demonstrating the need for substantially larger cohorts. These considerations clarify the gap between exploratory observations and robust confirmatory evidence.

Cancer-related fatigue (CRF) is a multidimensional and highly prevalent symptom that severely impairs the quality of life in patients with cancer. Due to its complex etiology and the limited effectiveness of current therapeutic options, CRF remains a major clinical challenge. Moxibustion, a traditional thermal stimulation therapy characterized by its "warming and tonifying" effects in East Asian medicine, has shown potential in alleviating CRF, however, its underlying biological mechanisms remain insufficiently defined. This review aims to reconstruct the mechanistic basis of moxibustion in the management of CRF from an integrated psychoneuroimmunology (PNI) perspective and to reposition moxibustion as a systemic modulator of the PNI network capable of restoring neuro-endocrine-immune homeostasis rather than a unidimensional warming therapy. Current evidence indicates that moxibustion may exert coordinated regulatory effects on CRF across psychological-emotional, neuroendocrine, and immune-inflammatory dimensions. By reinterpreting the traditional concept of "warming and tonifying" within a modern PNI framework, this review proposes a novel integrative paradigm for moxibustion-based interventions in CRF. This framework supports a transition from symptom-oriented management toward network-level modulation, providing a theoretical foundation for non-pharmacological precision strategies in CRF.