Background: Vitamin D deficiency is a poor prognostic factor in metastatic colorectal cancer (mCRC); however, targeted supplementation trials have so far yielded limited results. We investigated clinical-laboratory parameters influencing vitamin D deficiency, with a particular focus on immune response, and the effect on survival. These parameters could help optimize targeted supplementation therapy. Methods: Association of plasma 25-hydroxyvitamin D (25(OH])D) with overall survival (OS) was assessed with the Hazard Ratio Smoothed Curve with Restricted Cubic Splines (HRSC-RCS) and maximally selected rank statistics (MSRS) in mCRC patients who underwent first-line chemotherapy. Several hematobiochemical variables were evaluated as predictors of vitamin D deficiency by means of Least Absolute Shrinkage and Selection Operator (LASSO) analysis. In a patient subset, peripheral lymphocyte subpopulations were also analyzed. Results: One hundred thirty-three mCRC patients were included. The median(m) baseline 25(OH)D was 10.8 ng/mL (range 3–53.4). HRSC-RCS revealed a linear association between 25(OH)D and OS. MSRS found 10 ng/mL as the optimal 25(OH)D cut-off. The median OS for 25(OH)D < 10 (n = 60) vs. > 10 ng/mL (n = 73) was 12.3 and 24.5 months, respectively (p = 0.002). The LASSO analysis identified high neutrophil-to-lymphocyte ratio (NLR > 3.5) as the strongest predictor of vitamin D deficiency (Odds Ratio 3.35, p 0.0009). Moreover, patients with low 25(OH)D levels (< 10 ng/mL) and high NLR (>3.5) had the shortest survival and patients with 25(OH)D >10 ng/mL and NLR <3.5 had the longest: mOS 8.1 and 28.1 months, respectively, HR 3.40 (1.76–6.59), p 0.0004. Besides the significant difference in NLR between 25(OH)D < and > 10 ng/mL patients (mNLR 3.6 vs. 2.9, p 0.03), the lymphocyte subpopulation analysis revealed that vitamin D deficiency was associated with high T- CD4+ (p = 0.04) and low B (p = 0.03) lymphocyte frequency. Conclusions: NLR is a powerful predictor of Vitamin D deficiency and can further help in stratifying prognosis. Vitamin D deficiency was associated with significant variations in peripheral immune cells. We hypothesize that integrated targeted interventions to both vitamin D and immune system would improve the prognosis of mCRC patients.

(1) Background: Sarcopenia lasting >1 year might be considered a chronic condition in many HNSCC patients. CT-scan-derived Skeletal Muscle Mass Index (SMI) is an established surrogate of sarcopenia; yet, the cut-off reported in the literature (literature-based, lb-SMI < 43.2) is mainly based on the risk of chemoradiotherapy-induced toxicity, and the optimal value to discriminate OS is under-investigated. (2) Methods: The effect on OS of the lb-SMI cutoff was compared with an untailored OS-oriented SMI cutoff obtained in a cohort of consecutive advanced HNSCC patients treated with primary chemoradiotherapy, bio-chemotherapy or chemo-immunotherapy (cohort-specific, cs-SMI cutoff). Gender- and BMI-tailored (gt-SMI and bt-SMI) cut-offs were also evaluated. Cutoff values were identified by using the maximally selected rank statistics for OS. (3) Results: In 115 HNSCC patients, the cs-SMI cutoff was 31.50, which was lower compared to the lb-SMI reported cut-off. The optimal cut-off separately determined in females, males, overweight and non-overweight patients were 46.02, 34.37, 27.32 and 34.73, respectively. gt-SMI categorization had the highest effect on survival (p < 0.0001); its prognostic value was independent of the treatment setting or the primary location and was retained in a multivariate cox-regression analysis for OS including other HNSCC-specific prognostic factors (p = 0.0004). (4) Conclusions: A tailored SMI assessment would improve clinical management of sarcopenia in chemoradiotherapy-, bio-chemotherapy- or chemo-immunotherapy-treated HNSCC patients. Gender-based SMI could be used for prognostication in HNSCC patients.