Longitudinal Assessment of Hematologic and Immunonutritional Biomarkers from Treatment Initiation to Progression in...

Background: Systemic inflammatory indices such as the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII) have demonstrated prognostic relevance in metastatic colorectal cancer (mCRC). However, most available evidence relies on single baseline measurements, while the longitudinal dynamics of these biomarkers in relation to immunonutritional status remain insufficiently explored. Methods: This retrospective longitudinal study included 86 patients with previously untreated mCRC receiving first-line chemo-biological therapy. NLR, PLR, and SII were assessed at three predefined time points: before treatment initiation, after completion of induction therapy, and at radiologically confirmed disease progression. Nutritional and sarcopenia risk were evaluated using the NRS-2002 and SARC-F tools. Longitudinal differences were analyzed using the Friedman test with post hoc comparisons. Results: In nutritionally preserved patients, significant longitudinal changes were observed for NLR (χ²(2) = 16.72, p < 0.001), PLR (χ²(2) = 6.36, p = 0.003), and SII (χ²(2) = 24.57, p < 0.001), characterized by a marked decline following induction therapy and re-elevation at disease progression. In high nutritional risk patients, significant dynamics were observed only for SII (χ²(2) = 5.60, p = 0.007). Similarly, in the low SARC-F subgroup, all three indices demonstrated significant modulation over time, whereas no statistical analysis was feasible in the high SARC-F subgroup due to limited sample size. Among the evaluated parameters, SII showed the most consistent and pronounced longitudinal variation. Conclusions: The clinical value of inflammatory hematologic indices in mCRC appears to derive primarily from their longitudinal dynamics rather than single absolute measurements. SII, in particular, may serve as a marker of therapy-induced modulation of systemic inflammation, especially in patients with preserved immunonutritional reserve. Integration of dynamic inflammatory indices into routine clinical monitoring could enhance early identification of biological progression and improve risk stratification in mCRC.