CD44, a stem cell-associated adhesion molecule, and CD47, an anti-phagocytic checkpoint, have been implicated in breast cancer chemoresistance, but their relationship to neoadjuvant response is poorly defined. We assessed both markers by immunohistochemistry in pre-treatment core biopsies from 43 women treated with neoadjuvant therapy at a single center. Total pathological complete response (pCR; ypT0/is ypN0), designated the primary endpoint during peer review, occurred in 12 patients (27.9%), and breast pCR (ypT0/is) in 14 (32.6%). Total pCR rates were 18.2% in CD44-positive and 38.1% in CD44-negative tumors (odds ratio, 0.36; 95% CI, 0.09–1.46; Fisher exact p = 0.185). CD44 positivity was concentrated in rarely responding hormone receptor-positive/HER2-negative tumors, and stratification by subtype moved the odds ratio toward the null (0.62; exact 95% CI, 0.07–5.25). For CD47, the odds ratio per one-point increase in immunoreactivity score was 0.80 (95% CI, 0.54–1.19; p = 0.264), but immunoreactivity was low (only two tumors reached the prespecified high-expression threshold) and possibly technically compromised, so these findings are inconclusive. No statistically detectable association was observed between either marker and total or breast pCR; treatment could not be adjusted for, and only very large effects were detectable. These exploratory data do not provide sufficient evidence to support CD44 or CD47 as response markers.

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.

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 and Objectives: Pulmonary neuroendocrine carcinomas (NECs) are characterized by aggressive clinical behavior and heterogeneous postoperative outcomes. Early recurrence, often reflecting occult micrometastatic disease, remains a key determinant of prognosis and is insufficiently captured by conventional staging systems. We hypothesized that the lactate dehydrogenase-to-albumin ratio (LAR), as an integrative tumor–host biomarker, may provide biologically informed risk stratification in this setting. Materials and Methods: We conducted a multicenter retrospective cohort study including 88 patients with resected small cell lung cancer (SCLC) or large cell neuroendocrine carcinoma (LCNEC). Preoperative LAR and comparator inflammatory indices were evaluated. The primary endpoints were disease-free survival (DFS) and overall survival (OS), with early recurrence (≤12 months) as a prespecified secondary endpoint. Time-dependent receiver operating characteristic analyses, Cox proportional hazards models, and logistic regression analyses were applied within a predefined analytical framework. Results: Using a cut-off derived from 12-month DFS (LAR = 45.58), elevated LAR was associated with significantly shorter DFS (median 12.3 vs. 26.1 months; p = 0.018) and OS (median 20.7 vs. 52.8 months; p = 0.010). In multivariable analyses, LAR remained independently associated with both DFS (HR 1.012, 95% CI 1.001–1.023; p = 0.037) and OS (HR 1.016, 95% CI 1.005–1.027; p = 0.003). Elevated LAR was also associated with an increased risk of early recurrence (adjusted OR 4.656, 95% CI 1.520–14.262; p = 0.007). In time-dependent receiver operating characteristic (ROC) analyses, LAR demonstrated the highest overall discriminatory performance across evaluated biomarkers and showed a statistically significant advantage over neutrophil-to-lymphocyte ratio (NLR) for 24-month OS. Conclusions: Preoperative LAR captures a clinically relevant tumor–host phenotype associated with early disease progression and adverse survival outcomes in resected pulmonary NECs. As a biologically integrative and readily accessible biomarker, LAR may complement existing risk stratification strategies in this heterogeneous disease context. Prospective validation and integration into multimodal risk models are warranted.

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.