Background: Mucosal malignant melanoma (MMM) is a rare and aggressive malignancy with a dismal prognosis. While the Systemic Immune-Inflammation Index (SII) has emerged as a prognostic marker in various solid tumors, its specific value in MMM remains undefined. This study investigated the association between pretreatment SII and overall survival (OS) in patients with MMM. Methods: We retrospectively analyzed 106 adults with histologically confirmed MMM treated at six oncology centers in Turkey between 2005 and 2025. The baseline SII was calculated as platelet × neutrophil/lymphocyte counts obtained before definitive treatment. A receiver operating characteristic (ROC) analysis identified an optimal SII cutoff of 776 for overall survival (OS), defining low (<776) and high (≥776) SII groups. Results: Gastrointestinal and head and neck mucosa were the most frequent primary sites, and one-third of patients presented with metastatic disease. The median OS for the entire cohort was 23.3 months. Patients with a high versus low SII had a shorter OS (16.2 vs. 35.2 months; HR 2.71, 95% CI 1.67–4.40; p < 0.001). In multivariable analysis, a high SII (HR 1.88, 95% CI 1.12–3.14; p = 0.016), gastrointestinal primary site (HR 1.99, 95% CI 1.23–3.23; p = 0.005), and metastatic disease at diagnosis (HR 4.01, 95% CI 2.32–6.94; p < 0.001) independently predicted a worse OS. Conclusions: The SII is a novel, independent prognostic biomarker in MMM. Elevated pretreatment SII correlates with aggressive clinicopathologic features and inferior survival. As a readily accessible and cost-effective marker, SII may facilitate improved risk stratification in routine clinical practice for MMM patients.

Background/Objectives: The prognosis of metastatic rectal cancer remains poor, and few reliable prognostic biomarkers are available. DHX9 and CD47 have been implicated in colorectal cancer biology, but their prognostic value in metastatic disease remains unclear. We evaluated the associations of DHX9 and CD47 expression with clinical characteristics, molecular markers and overall survival. Methods: This retrospective, single-center cohort study included 65 patients with metastatic rectal cancer treated between 2010 and 2023. Expression of DHX9 and CD47 in primary tumor tissue was assessed by immunohistochemistry and classified as low or high. Clinical characteristics, metastatic presentation (de novo or recurrent), metastatic sites and molecular markers (KRAS, NRAS, BRAF and HER2) were recorded. Associations with marker expression were examined. Overall survival was analyzed using the Kaplan–Meier method, log-rank test and multivariable Cox proportional hazards regression adjusted for clinical and molecular factors. Results: High DHX9 expression was observed in 87.7% of tumors and high CD47 expression in 35.4%. During a median follow-up of 24 months, 53.1% of patients died. High CD47 expression was associated with shorter overall survival (log-rank p = 0.016) and this association persisted after adjustment for age, sex, metastatic presentation and DHX9 expression (HR = 2.71; 95% CI 1.34–5.48; p = 0.006). The association remained significant after further adjustment for RAS/RAF mutation status and HER2 positivity (HR = 2.78; 95% CI 1.02–7.59; p = 0.047). DHX9 expression was not associated with overall survival (log-rank p = 0.243). Expression of neither marker differed between de novo and recurrent metastatic disease or according to RAS, BRAF or HER2 status. Conclusions: In this exploratory, single-centre analysis, high CD47 expression was associated with shorter overall survival, whereas DHX9 expression was not. These hypothesis-generating findings require confirmation in larger, prospective, multicentre studies before any clinical application.

Background: Desmoid tumors (DT) are rare, locally aggressive neoplasms characterized by an unpredictable clinical course. Although anatomical localization has been associated with tumor behavior, its relationship with systemic inflammatory response remains insufficiently explored. This study aimed to evaluate the impact of tumor localization on systemic inflammatory markers and to investigate CD47 expression in DT. Methods: This retrospective cohort study included 127 patients diagnosed with DT between 2010 and 2023. Demographic, clinicopathological, and laboratory data were collected. Systemic inflammatory indices, including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), prognostic nutritional index (PNI), HALP score, and pan-immune-inflammation value (PIV), were calculated. Tumor localization was categorized as trunk, extremity, or head and neck. CD47 expression was evaluated by immunohistochemistry. Results: Tumors were most frequently located in the trunk (50.4%), followed by extremities (40.9%) and head and neck region (8.7%). Significant differences in inflammatory markers were observed according to tumor localization. The head and neck group demonstrated lower neutrophil counts (p = 0.020), NLR (p = 0.009), PLR (p < 0.001), and PIV (p = 0.003), while showing higher PNI (p = 0.043) and HALP scores (p = 0.001) compared to trunk-localized tumors. Additionally, smaller tumors (<49 mm) were associated with lower NLR (p = 0.041) and neutrophil counts (p = 0.015). No detectable CD47 expression was observed in any tumor samples. Conclusions: Anatomical localization is closely associated with distinct systemic inflammatory profiles in patients with DT. These findings suggest that tumor location may influence host immune–inflammatory interactions and contribute to the biological heterogeneity of DT. The absence of CD47 expression indicates that alternative immune-related mechanisms may play a role in DT biology. Easily accessible inflammatory markers may provide valuable insights for risk stratification in clinical practice.

Background/Objectives: Immune checkpoint inhibitors have become a standard treatment option for advanced/metastatic non-small cell lung cancer (NSCLC); however, considerable heterogeneity exists among patients regarding treatment response and survival. This study aimed to determine whether the pretreatment modified Glasgow Prognostic Score (mGPS), a marker of systemic inflammation and nutritional status, is prognostically associated with progression-free survival (PFS) and overall survival (OS) in patients with advanced/metastatic NSCLC treated with nivolumab at a single tertiary oncology center. Methods: This retrospective, single-center cohort study included 130 adult patients with histologically confirmed advanced/metastatic NSCLC who received nivolumab at the Department of Medical Oncology, Çukurova University Faculty of Medicine. The pretreatment mGPS (0, 1, or 2), derived from baseline serum C-reactive protein (CRP) and albumin levels, was analyzed in relation to PFS and OS using the Kaplan–Meier method, log-rank test, and Cox proportional hazards regression. The prognostic value of mGPS was tested in multivariable Cox models adjusted for age, sex, Eastern Cooperative Oncology Group (ECOG) performance status, histology, brain metastasis, liver metastasis, and neutrophil-to-lymphocyte ratio (NLR); the proportional hazards assumption was formally tested, and the incremental discriminative contribution of mGPS was assessed using bootstrap resampling. Results: Among 130 patients, 83.8% received nivolumab as second-line therapy. Pretreatment mGPS was 0, 1, and 2 in 40 (30.8%), 55 (42.3%), and 35 (26.9%) patients, respectively. Median OS was not reached, 9.7 months, and 3.0 months across mGPS 0, 1, and 2, respectively; corresponding median PFS values were 10.2, 4.8, and 3.0 months (log-rank p < 0.001 for both endpoints). After adjustment for age, sex, ECOG performance status, histology, brain metastasis, liver metastasis, and NLR, each one-point increase in mGPS remained associated with worse OS (adjusted HR 2.38; 95% CI 1.64–3.46; p < 0.001) and PFS (adjusted HR 1.81; 95% CI 1.32–2.48; p < 0.001), independent of the covariates included in the model. The proportional hazards assumption held for mGPS in both models. Addition of mGPS to the clinical-variables-only model was associated with higher model discrimination (Harrell’s C-index: 0.676 to 0.737 for OS and 0.620 to 0.666 for PFS), a difference confirmed as statistically significant by bootstrap resampling (2000 iterations; 95% CI for the difference excluding zero, p < 0.001 for both endpoints). Conclusions: Pretreatment mGPS is a simple, readily available marker that shows a robust prognostic—rather than treatment-predictive—association with both OS and PFS in patients with advanced/metastatic NSCLC treated predominantly as second-line nivolumab monotherapy. Its addition to established clinical variables was associated with a statistically significant, though modest, improvement in prognostic discrimination. These findings require prospective, multicenter validation, including in first-line immunotherapy settings, before mGPS can be recommended for routine clinical risk stratification.

Mucosal malignant melanoma (MMM) is a rare, aggressive malignancy with poor prognosis in the advanced setting. Although the Royal Marsden Hospital (RMH) sc

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.