Background: Sorafenib remains an important treatment option for patients with radioiodine-refractory differentiated thyroid cancer (RAI-R DTC). This study evaluated real-world outcomes and prognostic factors in patients treated with sorafenib. Materials and Methods: This retrospective multicenter study included 176 patients with RAI-R DTC treated with sorafenib between 2000 and 2024 across sixteen centers. Clinical, pathological and treatment-related variables, including metastatic sites, radiotherapy, dose reduction, inflammatory markers (neutrophil-to-lymphocyte ratio [NLR] and platelet-to-lymphocyte ratio [PLR]) and pretreatment thyroglobulin (Tg), were analyzed. Progression-free survival (PFS) was evaluated using Kaplan–Meier analysis. Prognostic factors were assessed using univariate and multivariate Cox regression analyses. Results: The median follow-up duration was 24 months and the median PFS was 21 months (95% CI: 15.5–26.5). Partial response was observed in 82 patients (46.6%), stable disease in 55 (31.3%) and progressive disease in 35 (19.9%). Patients who underwent dose reduction had longer PFS than those without dose reduction (42 vs. 19 months, p = 0.030), and absence of dose reduction remained independently associated with progression risk. Patients who received radiotherapy had shorter PFS than those who did not receive radiotherapy (16 vs. 37 months, p = 0.002), and radiotherapy-related variables remained independent predictors of progression. Patients with PLR values >138.2 had shorter PFS than those with PLR values ≤ 138.2 (19 vs. 34 months, p = 0.047), although this association was not maintained in Cox regression analysis. Similarly, associations between NLR and Tg values and PFS did not reach statistical significance (p = 0.112 and p = 0.072, respectively). Hand–foot syndrome was the most common toxicity, occurring in 59 patients (33.5%), while Grade 3 hand–foot syndrome was observed in 7 patients (4.0%). Conclusions: Sorafenib provided meaningful disease control with a median PFS of 21 months in this real-world cohort. Dose reduction was associated with longer PFS, whereas radiotherapy requirement appeared to reflect a higher-risk subgroup. Toxicities were generally manageable.

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.

Background: Recent transcriptomic studies classify small-cell lung cancer (SCLC) into molecular subtypes driven by ASCL1, NEUROD1, POU2F3, and YAP1. This study evaluated an immunohistochemistry (IHC)-based subtyping framework using real-world data and assessed its ability to predict chemoimmunotherapy outcomes. Methods: Proteomic expression profiles were quantified by IHC in 100 patients with SCLC. Clinicopathological trajectories and overall survival (OS) were analyzed using a parsimonious multivariate Cox model designed to mitigate overfitting. Results: Significant subclonal heterogeneity was captured by co-dominant hybrid phenotypes, including SCLC-AN (9%) and SCLC-AP (5%). In the treatment-adjusted, parsimonious multivariate analysis, individual continuous biomarker expressions showed an independent association with ASCL1 percentage (HR = 1.011, p = 0.017). Traditional extensive-stage disease (HR = 3.801, 95% CI: 1.669–8.657, p = 0.001) and synchronous bone metastases (HR = 1.968, 95% CI: 1.074–3.604, p = 0.028) remained the only robust clinical predictors of poor OS. When adjusted for therapeutic interventions, first-line chemoimmunotherapy showed a strong protective numerical trend, reducing mortality risk by 49% (HR = 0.512, p = 0.060). Within the immunotherapy subgroup (n = 19), the NE-low group had a 100% response rate and a numerically longer median overall survival than the NE-high group (49.4 vs. 21.4 months; log-rank p = 0.080). Conclusions: Our pilot evaluation provides a clinically feasible routine IHC framework for characterizing subclonal mosaicism in SCLC.

Background: Lung cancer remains the leading cause of cancer-related mortality, with non-small cell lung cancer (NSCLC) accounting for approximately 85% of cases. Over the past decade, immune checkpoint inhibitors have become a core component of first-line treatment for advanced-stage NSCLC lacking driver mutations. Programmed death-ligand 1 (PD-L1) expression is currently used as the standard biomarker, yet its predictive value remains limited, and in most immunotherapy trials, treatment efficacy has been observed independently of PD-L1 expression status. Enhancer of zeste homolog 2 (EZH2), an epigenetic regulator, promotes immune escape by suppressing antigen presentation and impairing CD8+ T-cell function, thereby generating an immune-cold tumor microenvironment, positioning it as a promising candidate biomarker. Methods: We retrospectively analyzed 102 NSCLC patients treated with immunotherapy at a single center between 2018 and 2024. EZH2 expression was assessed by immunohistochemistry. A cohort-derived 25% threshold was used for the primary exploratory analysis, and the analyses were repeated using a 50% threshold as a sensitivity analysis. Patients were classified as EZH2-high (45.1%) and EZH2-low (54.9%) at the 25% threshold. Results: At the 25% threshold, objective response rate (ORR) was 53.6% in the EZH2-low group and 45.7% in the EZH2-high group (Fisher’s exact p = 0.551), while disease control rate (DCR) was 64.3% and 60.9%, respectively (p = 0.837). Median overall survival (OS) was 37 versus 27 months (log-rank p = 0.323), and median progression-free survival (PFS) was 15 versus 12 months (p = 0.387). No significant correlation was found between EZH2 and PD-L1 expression (r = 0.167, p = 0.138). In treatment-line-adjusted Cox models, EZH2 expression was not associated with OS (hazard ratio (HR) 0.953, 95% confidence interval (CI) 0.533–1.704; p = 0.870) or PFS (HR 0.996, 95% CI 0.573–1.733; p = 0.989), whereas squamous histology was an independent predictor of survival. Results remained non-significant at the 50% threshold. Early progression was uncommon and did not differ significantly by EZH2 status overall or within PD-L1 strata. Conclusions: In this real-world cohort, EZH2 expression was not independently associated with response, early progression, OS, or PFS, and showed no correlation with PD-L1. These exploratory findings do not support the clinical use of EZH2 as a biomarker at this stage; prospective, multicenter studies using predefined thresholds and standardized immunohistochemical methods are needed to clarify its potential role as a marker complementary to PD-L1.

Background/Objectives: Paragangliomas (PGLs) are rare neuroendocrine tumors, and data describing them from a medical oncology perspective are limited. We characterized clinicopathological features, tumor localization, and treatment outcomes. Methods: We retrospectively analyzed 43 patients with PGL at a single medical oncology department. The primary endpoint was recurrence-free survival (RFS), defined as time to first recurrence or death from any cause; overall survival (OS), objective response rate (ORR), disease control rate (DCR), and prognostic associations were secondary. Results: Median age was 44 years, 60.5% were female, and tumors were sympathetic (extra-adrenal) in 55.8% and parasympathetic (head and neck) in 39.5%. After a median follow-up of 116.8 months, 40 patients (93.0%) underwent resection, among whom 14 RFS events occurred (13 recurrences, 1 unrelated death). Median RFS and OS were not reached (60-month RFS, 67.1%; 120-month OS, 83.3%). Among nine patients receiving first-line systemic therapy (eight response-evaluable), ORR was 12.5% and DCR 37.5%. In exploratory univariable analysis, a Ki-67 index ≥ 3% correlated with recurrence (time-averaged hazard ratio, 4.53; 95% CI, 1.55–13.19; p = 0.006), alongside an R1 resection margin (not significant after Bonferroni correction). Conclusions: These findings may support further evaluation of Ki-67 within risk-adapted surveillance but do not replace germline testing.