Background/Objectives: The hemoglobin, albumin, lymphocyte, and platelet (HALP) score has been investigated as an immunonutritional biomarker in several solid tumors; however, data in metastatic renal cell carcinoma (mRCC) remain limited. This study aimed to evaluate the prognostic significance of the pretreatment HALP score in patients with mRCC receiving first-line tyrosine kinase inhibitor (TKI) therapy. Methods: A multicenter retrospective cohort study was conducted using data from the Turkish Oncology Group Kidney Cancer Consortium (TKCC) Database. HALP was calculated as hemoglobin (g/dL) × albumin (g/dL) × lymphocyte count (×10⁹/L)/platelet count (×10⁹/L). Patients were categorized into HALP-low and HALP-high groups according to the cohort median HALP value. Results: A total of 1001 patients were enrolled. The median time to treatment failure (TTF) was significantly shorter in the HALP-low group than in the HALP-high group (7.43 months [95% CI 6.4–8.5] vs. 14.26 months [95% CI 12.1–16.4], p < 0.001). The median overall survival (OS) was also significantly shorter in the HALP-low group (30.19 months [95% CI 25.2–35.1] vs. 46.06 months [95% CI 38.2–53.9], p < 0.001). In multivariable analysis, a high HALP score remained independently associated with longer TTF (HR 0.73, 95% CI 0.62–0.86; p < 0.001) and OS (HR 0.69, 95% CI 0.57–0.85; p < 0.001). Conclusions: The pretreatment HALP score was independently associated with TTF and OS in patients with mRCC treated with first-line TKI therapy. These findings support the prognostic relevance of HALP in this treatment setting and warrant further evaluation of its potential role alongside established clinical risk models.

Background/Objectives: Histologic regression in primary cutaneous melanoma has shown inconsistent prognostic associations, and its relevance to immune checkpoint inhibitor (ICI) outcomes in patients who later develop recurrent or metastatic disease remains unclear. Methods: This retrospective single-center cohort included 81 patients with resected stage I–III cutaneous melanoma who later developed recurrent or metastatic disease and received ICIs. Histologic regression was classified as present or absent based on primary pathology reports. Objective response rate (ORR) and disease control rate (DCR) were assessed according to RECIST v1.1. Progression-free survival (PFS) and overall survival (OS) from ICI initiation were estimated using Kaplan–Meier analysis and evaluated with prespecified multivariable Cox models. Results: Histologic regression was identified in 24 patients (29.6%). Baseline characteristics were largely comparable between groups, although regression was more frequent in male patients (83.3% vs 59.6%; p = 0.039). ORR was numerically higher in the regression-present group (58.3% vs 43.9%; p = 0.330), and DCR was also higher (87.5% vs 66.7%; p = 0.061). Median PFS was significantly longer in patients with regression (39.3 vs 17.8 months; log-rank p = 0.044). In multivariable analysis, regression remained independently associated with longer PFS (adjusted HR, 0.43; 95% CI, 0.19–0.94; p = 0.035), whereas no independent association with OS was observed (adjusted HR, 0.54; 95% CI, 0.28–1.06; p = 0.071). Conclusions: In patients with recurrent or metastatic melanoma treated with ICIs, primary tumor histologic regression was independently associated with prolonged PFS but not OS. These findings suggest a potential link between regression and early immune-mediated disease control, while its impact on long-term survival remains uncertain.

Background: Vandetanib and cabozantinib are the approved first-line antiangiogenic multikinase inhibitors (aaMKIs) for metastatic medullary thyroid carcinoma (MTC); however, real-world data on their comparative efficacy, optimal sequencing, and outcomes beyond the first-line setting remain limited. We report multicenter real-world outcomes from a large Turkish cohort. Methods: In this retrospective multicenter cohort study, we analyzed data from 24 oncology referral centers across Türkiye. Patients with histologically confirmed metastatic MTC who received systemic therapy between December 2011 and December 2024 were included. The primary endpoint was progression-free survival (PFS), assessed separately for first-line (PFS1) and second-line (PFS2) therapy. Overall survival (OS) and prognostic factors were evaluated using Kaplan–Meier and Cox proportional hazards analyses. Results: A total of 115 patients were included (median age 47.4 years; 63.5% male). In the first-line setting, vandetanib (47.8%) and cabozantinib (30.4%) were the most frequently used agents. Median PFS1 was 40.8 months with vandetanib and was not reached with cabozantinib; both were significantly superior to chemotherapy (median PFS1 4.9 months; log-rank p < 0.001). In the second-line setting, median PFS2 was not reached with cabozantinib and was 32.5 months with vandetanib. Sequential use of cabozantinib and vandetanib across the first two lines was associated with a median time to second progression of 114 months, compared with 39 months in patients receiving any other TKI combination (p = 0.003). Second-line use of cabozantinib or vandetanib was independently associated with improved OS (HR 0.40, 95% CI 0.16–0.98; p = 0.046). On multivariate analysis, younger age (HR 0.16, 95% CI 0.03–0.72; p = 0.017) and bone metastasis (HR 0.29, 95% CI 0.11–0.73; p = 0.009) were independent prognostic factors for OS. Conclusions: In this real-world cohort of patients with metastatic MTC, cabozantinib and vandetanib demonstrated durable efficacy across treatment lines, substantially outperforming alternative TKIs and chemotherapy. Sequential use of both approved aaMKIs was associated with prolonged disease control. These findings suggest a potential association between access to both agents and improved outcomes. They are consistent with their central role in treatment sequencing, particularly in settings with limited access to selective RET inhibitors. Given the retrospective design and small subgroup sizes, these results should be interpreted as exploratory and hypothesis-generating.