Search Results (11,075)

Background: Platinum resistance remains a major therapeutic challenge in epithelial ovarian cancer (EOC). The tumour–stroma ratio (TSR) has emerged as a potential histopathological marker of tumour biology, but its clinical significance in different clinical settings remains unclear. We evaluated the association between stromal proportion, assessed using the TSR methodology, platinum resistance, and survival outcomes in patients undergoing primary debulking surgery (PDS) or neoadjuvant chemotherapy followed by interval debulking surgery (NACT+IDS). Methods: This retrospective study included 83 patients with epithelial ovarian cancer (EOC) who underwent either primary debulking surgery (PDS) or neoadjuvant chemotherapy followed by interval debulking surgery (NACT+IDS) between 2017 and 2024. Patients were analysed separately according to treatment strategy. Stromal proportion was assessed on primary surgical specimens in the PDS cohort and on pretreatment diagnostic biopsy specimens in the NACT+IDS cohort. For this retrospective analysis, platinum resistance was operationally defined as recurrence within six months after completion of first-line platinum-based chemotherapy. Survival outcomes were analysed using the Kaplan–Meier method, and univariable binary logistic regression was performed separately within the PDS and NACT+IDS cohorts to explore the association between stromal category and platinum resistance. Results: Platinum resistance occurred in 25.3% of patients. In the PDS cohort, stromal category was not associated with clinicopathological characteristics, platinum resistance, disease-free survival (DFS), or overall survival (OS). In the NACT+IDS cohort, patients in the stroma-high group had a numerically higher rate of platinum resistance than those in the stroma-low group (57.9% vs. 22.2%; Fisher’s exact p = 0.114). Based on univariable logistic regression analysis, the stroma-high group had higher estimated odds of platinum resistance (OR 4.81, 95% CI 0.78–29.40), although this finding did not reach statistical significance (p = 0.090). No significant association was observed between stromal category and survival outcomes in either cohort. Conclusions: In the NACT+IDS cohort, patients in the stroma-high group had a numerically higher rate of platinum resistance than those in the stroma-low group; however, this difference did not reach statistical significance. These results should be interpreted with caution due to the retrospective study design and limited sample size; however, they nonetheless support further investigation of pretreatment TSR as a simple and easily applicable histopathological parameter in EOC. Larger prospective multicentre studies are required to determine whether this exploratory signal is reproducible and clinically relevant. Full article

Background/Objectives: Axillary lymph node dissection (ALND) remains common in patients presenting with a high baseline axillary nodal burden despite substantial nodal downstaging after neoadjuvant chemotherapy (NAC). This study evaluated whether post-neoadjuvant radiologic axillary response could support selective axillary de-escalation in patients with clinically staged cN2 breast cancer and pathologically confirmed axillary metastasis. Methods: This retrospective single-center cohort included 166 cases treated between October 2020 and August 2024. All had pathologically confirmed axillary metastasis, completed neoadjuvant systemic therapy, underwent post-treatment axillary ultrasound, and received definitive surgery. Radiologic node-negative status (radN0) was defined by restoration of benign nodal morphology. Surgical management and pathological nodal outcomes were evaluated according to radiologic response. Results: Radiologic nodal clearance occurred in 61/166 cases (36.7%), while axillary pathological complete response [ypN0(i−)] was achieved in 59/166 (35.5%). ypN0(i−) was observed in 53/61 radN0 cases (86.9%) versus 6/105 radN+ cases (5.7%; p < 0.001). Among radN0 cases, 47/61 (77.0%) underwent limited sentinel lymph node biopsy/targeted axillary dissection (SLNB/TAD) without ALND, of whom 43/47 (91.5%) achieved ypN0(i−). Axillary pCR rates varied by molecular subtype, ranging from 20.5% in HR+/HER2− disease to 72.2% in triple-negative disease (p < 0.001). No ipsilateral axillary recurrence occurred in the limited SLNB/TAD group during a median follow-up of 36 months. Conclusions: Post-neoadjuvant radiologic nodal clearance was strongly associated with pathologically node-negative findings and may support consideration of carefully selected responders with cN2 breast cancer for SLNB/TAD-based staging. Radiologic response should complement, rather than replace, surgical staging and multidisciplinary decision-making. Full article

Background and Objectives: Treatment-emergent neuroendocrine prostate cancer (t-NEPC) is an aggressive resistance phenotype arising during metastatic castration-resistant prostate cancer (mCRPC). Because metastatic biopsy is not routinely feasible in advanced disease, real-world data on clinically defined t-NEPC/aggressive-variant prostate cancer (AVPC)-like disease remain limited. We aimed to characterize the clinical features, treatment patterns, survival outcomes, and prognostic factors of this clinically defined phenotype. Materials and Methods: We retrospectively reviewed 354 patients with prostate cancer treated at our institution between 2010 and 2020. Seventy-four patients with mCRPC who were clinically identified as having a t-NEPC/AVPC-like phenotype and had a treatment plan for platinum- and/or etoposide-based neuroendocrine-directed systemic therapy were included. Overall survival (OS) and radiographic progression-free survival (rPFS) were estimated using the Kaplan–Meier method, and prognostic factors were evaluated using Cox regression analyses. Results: At clinical identification of the phenotype, the median age was 66.4 years, and visceral metastases were present in 67.6% of patients, most commonly in the liver (55.4%). Median intervals from prostate cancer diagnosis and CRPC onset to clinical identification of the phenotype were 47.5 and 22.7 months, respectively. Neuroendocrine-directed therapy was initiated in 72 patients; platinum–etoposide was the most common first-line regimen (n = 41, 55.4%). Median OS was 4.4 months (95% confidence interval [CI], 2.9–5.8), and median rPFS was 3.5 months (95% CI, 2.7–4.2). In an exploratory, unadjusted analysis, median OS did not differ significantly between doublet chemotherapy and monotherapy (7.0 vs. 3.5 months; p = 0.167). Gleason score ≥9, hemoglobin <12 g/dL, and albumin <3.5 g/dL were independently associated with inferior OS. Conclusions: The clinically defined t-NEPC/AVPC-like phenotype was associated with an aggressive clinical course and poor survival. Earlier recognition, improved biomarker-based diagnostic strategies, and more effective therapeutic approaches are needed. Full article

Background/Objectives: Clinical outcomes with immune checkpoint inhibitors (ICIs), such as nivolumab, vary among patients with metastatic non-small cell lung cancer (NSCLC). The Lung Immune Prognostic Index (LIPI) may help stratify prognosis. This study evaluated the prognostic significance of LIPI in patients receiving second- or third-line nivolumab and developed a nomogram for individualized survival estimation. Methods: This single-center retrospective study included 142 patients with metastatic NSCLC who received second- or third-line nivolumab between February 2022 and December 2024, after progression on platinum-based chemotherapy. LIPI was calculated from baseline values obtained within 14 days before nivolumab initiation, based on a derived neutrophil-to-lymphocyte ratio (dNLR) > 3 and lactate dehydrogenase (LDH) > 225 U/L (institutional upper limit of normal), classifying patients as good-, intermediate-, or poor-risk (0, 1, or 2 factors, respectively). Overall survival (OS) and progression-free survival (PFS) were estimated by the Kaplan–Meier method; independent prognostic factors were assessed by multivariable Cox regression, and a prognostic nomogram combining ECOG performance status, serum albumin, and LIPI was developed and internally validated. Results: By LIPI, 34.5%, 45.1%, and 20.4% of patients were at good, intermediate, and poor risk, respectively. Objective response and disease control rates were 29.6% and 55.6%. Median OS and PFS were 19.3/8.0/3.1 and 8.6/3.1/2.5 months across good, intermediate, and poor LIPI groups (log-rank p < 0.001). In multivariable analysis, ECOG 2 (hazard ratio [HR], 4.94), albumin per 1 g/dL (HR 0.27), and poor versus good LIPI (HR 3.74) were independently associated with OS. A nomogram combining these three factors showed acceptable discrimination (optimism-corrected Harrell C-statistic 0.742). Conclusions: LIPI was independently associated with prognosis in this cohort. Combining LIPI with ECOG and albumin may aid individualized risk assessment, pending external validation. Full article

Background: Skeletal muscle depletion predicts poor outcomes in gastrointestinal cancers, but whether volumetric three-dimensional (3D) body composition adds anything over the standard two-dimensional (2D) single-slice approach in colorectal cancer (CRC) patients receiving chemoradiotherapy is unclear. We quantified CT-derived sarcopenia and directly compared 2D and 3D body composition metrics from a fully automated deep learning pipeline. Methods: We retrospectively analyzed 368 patients with CRC. Body composition was quantified automatically from CT using SMAT-BC, a pipeline combining TotalSegmentator-based vertebral localization with an nnU-Net Residual Encoder XL network incorporating a Transformer bottleneck for four-class tissue segmentation. Single-slice L3 (2D) and L1–L5 volumetric (3D) indices were derived. The primary endpoint was overall survival (OS); recurrence-free survival (RFS) was secondary. Cox proportional hazards models with bootstrap optimism correction were used. Measurement reproducibility was assessed in 25 external TCGA-COAD cases. Results: Sarcopenia was strongly associated with both overall and recurrence-free survival (unadjusted OS HR 2.16, 95% CI 1.55–3.00; unadjusted RFS HR 1.83, 95% CI 1.36–2.47; both raw p < 0.001; adjusted OS HR 1.89, 95% CI 1.57–2.28; adjusted RFS HR 1.44, 95% CI 1.22–1.70; FDR-adjusted p < 0.0001 for both). L3 single-slice indices were strongly correlated with volumetric indices (r = 0.91 for muscle index) and added discriminant value over the clinical model for overall survival (optimism-corrected C-index: clinical 0.602 (95% CI 0.578–0.626), clinical + 2D 0.631 (95% CI 0.609–0.654), clinical + 3D 0.599 (95% CI 0.574–0.624); DeLong p = 0.002 for clinical + 2D vs. clinical, FDR-adjusted p = 0.006). The 2D- and 3D-augmented models yielded overlapping bootstrap confidence intervals and were not clinically meaningfully different in this cohort (OS ΔC = +0.032, 95% CI +0.013 to +0.051; FDR-adjusted p = 0.006; RFS ΔC = +0.008, 95% CI −0.011 to +0.027; FDR-adjusted p = 0.612). Conclusions: Automated CT-derived sarcopenia is an independent predictor of survival in CRC patients receiving chemoradiotherapy. In our cohort, single-slice L3 measurement matched or exceeded volumetric discrimination, but the 2D- and 3D-augmented models yielded overlapping bootstrap confidence intervals for both endpoints: for overall survival, the DeLong FDR-adjusted p value for the 2D-versus-3D contrast was 0.006, and 0.612 for recurrence-free survival. Because no non-inferiority margin was pre-specified, the 2D–3D comparison is presented as exploratory, and we make no formal claim of non-inferiority or equivalence for either endpoint. The findings support single-slice L3 measurement as an efficient biomarker for risk stratification but warrant external validation in larger prospectively designed cohorts. Full article

Background: South Asian Americans (SAAs) represent the fastest-growing U.S. immigrant group but remain underrepresented in breast cancer research. This study utilizes the National Cancer Database (NCDB) to evaluate differences in tumor characteristics, treatment patterns, and survival outcomes between SAAs and non-Hispanic Whites (NHWs). Materials and Methods: A retrospective cohort analysis was conducted using NCDB data from 2004–2021. Women with breast cancer were stratified by race/ethnicity (SAA vs. NHW), and demographic, clinical, and treatment variables were compared. Outcomes assessed were overall survival (OS) and treatment delays, defined as initiation of surgery, chemotherapy, or radiation therapy > 60 days after diagnosis. Multivariable Cox proportional hazards models assessed OS. Results: Among 2,363,627 patients, 20,561 (0.9%) were SAAs and 2,343,066 (99.1%) NHWs. SAAs were younger at diagnosis, with 37.6% aged 20–49 vs. 20.6% of NHWs (p < 0.001). Insurance coverage differed, with SAAs more likely privately insured (63.0% vs. 54.2%, p < 0.001), less likely on Medicare (17.2% vs. 37.9%), and more often uninsured (4.5% vs. 1.2%). Time to first treatment was longer for SAAs (39.55 vs. 37.17 days, p < 0.001). Surgical delays >60 days increased mortality by 59%, while chemotherapy delays raised it by 44%. SAAs demonstrated higher survival at 5, 10, and 15 years (93%, 87%, 81%) vs. NHWs (87%, 76%, 64%). Median survival was 225.8 months but not estimable for SAAs. SAAs presented with aggressive subtypes: triple-negative and HER2-positive tumors. Conclusions: SAAs present younger with aggressive subtypes and treatment delays yet maintain survival advantages; reducing care barriers and clarifying tumor biology are vital to improving outcomes. Full article

Background and Clinical Significance: Local recurrence of extremity leiomyosarcoma after multiple operations and radiotherapy presents a major therapeutic challenge. Adequate oncologic clearance must be balanced against preservation of skeletal stability and reliable wound coverage within a scarred and poorly vascularized tissue bed; Case presentation: A 78-year-old woman presented with a painful recurrent leiomyosarcoma of the anterior proximal third of the right leg after three previous operations and adjuvant radiotherapy. Preoperative magnetic resonance imaging demonstrated a recurrent soft-tissue lesion extending to the anterior surface of the proximal tibia. Staging computed tomography of the chest, abdomen, and pelvis showed no distant metastatic disease before definitive surgery. A one-stage limb-sparing procedure was performed, including resection of the recurrent tumor bed and an approximately 7-cm anterior cortical lamella of the proximal tibia containing an area considered suspicious for neoplastic involvement. A locking tibial plate was applied prophylactically to reduce the risk of pathological fracture. The approximately 12 × 10-cm soft-tissue defect was covered with a muscle flap from the medial head of the gastrocnemius and a free skin graft harvested from the paraumbilical region. Gross pathological examination identified an 8-cm subcutaneous tumor formation. Histopathological examination demonstrated well-differentiated leiomyosarcoma; the spindle cells expressed vimentin, actin, and desmin. All examined resection lines were free of tumor infiltration. No pathogenic microorganism was isolated, and no early postoperative complication was documented. The patient mobilized with walking aids and protected weight bearing for 30 days. At approximately 16 months, the flap and skin graft provided stable coverage, no postoperative tibial fracture or clinically apparent implant-related complication had occurred, and the patient was independently ambulatory. Postoperative MRI demonstrated expected postoperative changes and a small indeterminate subcutaneous focus without diffusion restriction, requiring continued surveillance; Conclusions: This case illustrates the feasibility of combining oncologic resection, prophylactic tibial stabilization, and vascularized soft-tissue reconstruction in a previously irradiated extremity. The documented early functional and reconstructive outcome supports this individualized limb-sparing approach, although longer oncologic surveillance is required. Full article

Complete resection remains the only potentially curative treatment for localized intrahepatic cholangiocarcinoma (iCCA), yet postoperative recurrence is common, particularly in patients with high-risk disease. Neoadjuvant systemic therapy may permit earlier control of occult micrometastatic disease, optimize the delivery of systemic treatment, and provide an in vivo assessment of tumor biology prior to major hepatectomy. These potential benefits must be balanced against treatment-related toxicity, surgical delay, and the risk of disease progression precluding resection. Early evidence was primarily derived from retrospective studies, which yielded inconsistent survival outcomes and exhibited substantial vulnerability to confounding and treatment-selection bias. The single-arm NEO-GAP trial subsequently demonstrated the feasibility of administering neoadjuvant gemcitabine, cisplatin, and nab-paclitaxel followed by surgical resection. More recently, the randomized phase II–III ZSAB-neoGOLP trial showed that neoadjuvant gemcitabine–oxaliplatin, lenvatinib, and toripalimab followed by surgery prolonged median event-free survival compared with upfront surgery (median: 18.0 vs. 8.7 months) without substantially compromising surgical feasibility. However, the interim overall survival analysis was inconclusive, and the generalizability of these findings beyond selected, medically fit patients treated at Chinese centers remains uncertain. This narrative review critically appraises the evolving evidence, discusses patient selection and perioperative treatment, and identifies priorities for future research. Current evidence supports the selective consideration of neoadjuvant therapy in medically fit patients with technically resectable but oncologically high-risk iCCA, rather than its routine use in all resectable cases. Full article

The XII Forum on Translational Immunology and Cancer Immunotherapy (FIT Cancer 12), organized by the Spanish Group for Cancer Immuno-Biotherapies (GÉTICA), took place on 5–6 March 2026 in Málaga, Spain. This edition gathered clinicians, basic scientists, and translational researchers from Spain and international institutions to discuss the latest advances in cancer immunotherapy. Scientific contributions spanned a wide range of topics, including engineered T-cell therapies targeting solid tumors and hematological malignancies, neoantigen-based cancer vaccines in preventive and therapeutic settings, oncolytic virotherapy combined with immune cell recruitment strategies, metabolic reprogramming of the tumor microenvironment, epigenetic liquid biopsy biomarkers, and the management of immune-related adverse events in clinical practice. The abstracts presented here reflect the breadth and translational depth of immuno-oncology research currently underway within the GÉTICA network and its international collaborators. Full article

Background: Axillary lymph node (ALN) fine-needle aspirations (FNAs) can guide the next steps in the management of patients with invasive breast carcinoma (BC). The objective is to evaluate the diagnostic performance of ALN FNA in the detection of metastatic breast carcinoma. Methods: We evaluated ALN FNAs from 2020 to 2024 to determine the risk of malignancy (ROM) of different cytologic diagnostic categories using a general WHO cytology reporting system framework (insufficient, benign, atypical, suspicious, and malignant). Results: A total of 290 axillary lymph node FNAs from patients with newly diagnosed invasive breast carcinoma were identified, of which 226 (78%) had histologic and/or adequate clinical follow-up. Cytologic diagnoses included six (2.1%) non-diagnostic, 99 (34.1%) benign, two (0.7%) atypical, seven (2.4%) suspicious for malignancy, and 176 (60.7%) malignant cases. The risk of malignancy (ROM) was 50.0% for non-diagnostic, 17.0% for benign, 100% for atypical, 85.7% for suspicious, and 99.2% for malignant diagnoses. Most false-negative benign cases were attributed to sampling limitations rather than interpretive error, with five cases showing only a single sentinel lymph node metastasis measuring <5 mm. Indeterminate diagnoses were most commonly associated with scant cellularity, acellular cell blocks, obscuring blood or fibrin, and equivocal immunohistochemistry. Excluding cases without histologic follow-up, ALN FNA demonstrated a sensitivity of 86.5%, specificity of 97.4%, positive predictive value of 98.5%, negative predictive value of 79.2%, and overall accuracy of 90.3% for the detection of metastatic breast carcinoma (OR = 243.2, Fisher’s exact test, p < 0.0001). Conclusion: ALN FNA is a highly reliable method for confirming axillary lymph node metastasis in invasive breast carcinoma when malignant cells are identified, with a ROM of 99% for the malignant category. The suspicious category was also strongly associated with malignancy (ROM 86%). However, the 17% ROM observed in the benign category indicates that a negative FNA does not reliably exclude metastatic disease, and surgical nodal staging may still be warranted in clinically or radiologically suspicious cases. These findings support the clinical applicability of the WHO System for Reporting Lymph Node Cytopathology and provide breast carcinoma-specific ROM estimates for this clinical setting. Full article

Background: Neuroendocrine prostate cancer (NEPC) is a rare and aggressive malignancy with limited prognostic tools. The Lung Immune Prognostic Index (LIPI), derived from dNLR and lactate dehydrogenase, has demonstrated prognostic value in small-cell lung cancer but has not been evaluated in NEPC. This study assessed the prognostic role of LIPI in NEPC. Methods: This multicenter retrospective study included 34 patients with NEPC (21 secondary, 13 de novo) from four centers in Turkey. Laboratory data were collected at NEPC diagnosis (T3), initial prostate cancer diagnosis (T1), and castration-resistant prostate cancer diagnosis (T2). LIPI was scored using original fixed cut-offs. Survival analyses included Kaplan–Meier, Cox regression, and ROC methods. Results: At NEPC diagnosis, 18 patients (52.9%) had Good LIPI and 16 (47.1%) Intermediate + Poor LIPI. Intermediate + Poor LIPI was associated with significantly shorter overall survival (median 4 vs. 15 months; log-rank p = 0.001; HR 3.83, 95% CI 1.65–8.90). In multivariable analysis, albumin was an independent predictor (HR 0.37, p = 0.015), while LIPI showed a trend (HR 2.35, p = 0.091). LIPI demonstrated the highest discriminatory ability for 6-month overall survival (AUC 0.763, p = 0.009). LIPI at earlier disease stages did not predict time to transformation or castration resistance. Among secondary NEPC patients, worsening LIPI trajectory was associated with shorter survival (median 4 vs. 10 months; log-rank p = 0.031). Conclusions: LIPI at NEPC diagnosis was associated with overall survival and demonstrated the highest discriminatory ability among the inflammatory indices assessed. As a routine blood-based score, LIPI may support risk stratification at NEPC diagnosis. Prospective validation is warranted. Full article

Background and Objectives: In advanced high-grade serous tubo-ovarian carcinoma (HGSOC), the chemotherapy response score (CRS) assesses histopathologic response to neoadjuvant chemotherapy (NACT). CRS1 and CRS2 are commonly grouped for similar prognostic outcomes, but whether partial response carries prognostic value and which factors predict pathologic response remain unclear. This multicenter study evaluated predictors of pathologic response and the association of CRS with recurrence-free survival (RFS) and overall survival (OS) after NACT followed by interval debulking surgery (IDS). Materials and Methods: We retrospectively analyzed 157 patients with FIGO stage IIIC-IV HGSOC treated with NACT followed by IDS between 2015 and 2021. Pathologic response was defined as CRS2–3 versus CRS1; logistic regression identified predictors of response. Survival was assessed using Kaplan–Meier analysis, and Cox regression evaluated factors associated with RFS and OS. Secondary analyses evaluated the conventional CRS1–2 versus CRS3 classification, direct CRS3-versus-CRS2 contrasts, and ordinal trends for RFS and OS. Results: CRS1, CRS2, and CRS3 were observed in 33 (21.0%), 97 (61.8%), and 27 (17.2%) patients, respectively. Median RFS was 10.4, 16.4, and 24.1 months for CRS1, CRS2, and CRS3, respectively (p < 0.001). Median OS was 21.2, 39.1, and 47.0 months, respectively (p < 0.001). In multivariate Cox analysis, CRS2 and CRS3 were independently associated with better RFS (HR 0.36 and 0.24) and OS (HR 0.48 and 0.41) compared with CRS1. In the conventional CRS1–2 versus CRS3 model, CRS3 remained associated with lower recurrence risk after multivariate adjustment (HR 0.60; p = 0.042), but not OS (HR 0.74; p = 0.354). Direct CRS3-versus-CRS2 contrasts were nonsignificant for RFS and OS (p = 0.131 and p = 0.628), whereas ordinal trends toward lower hazards were significant for both endpoints (p = 0.001 and p = 0.041). A higher CA-125 decrease rate (OR 1.04) and more than three NACT cycles (OR 4.89) independently predicted pathologic response, whereas FIGO stage IV predicted a lower response (OR 0.15). Conclusions: Partial pathological response (CRS2) was independently associated with improved RFS and OS compared with no or minimal response (CRS1), suggesting that prognostic information is not confined to complete or near-complete pathological response. The conventional CRS1–2 versus CRS3 classification remained independently prognostic for RFS after multivariate adjustment but did not reach statistical significance for OS, while direct CRS3-versus-CRS2 contrasts were nonsignificant for both outcomes. Thus, separate evaluation of CRS2 may provide additional RFS stratification within CRS1–2. However, the incremental contribution of CRS3 beyond CRS2 could not be established in the present cohort and requires validation in larger cohorts. Full article

Background: Pleural effusion is a common clinical presentation in both benign and malignant conditions. The advent of liquid biopsy allowed new possibilities for non-invasive molecular profiling using body fluids. Pleural fluid, by virtue of its proximity to thoracic malignancies and its rich tumour-derived content, represents a particularly compelling matrix for liquid biopsy analysis. This review synthesises current evidence regarding the diagnostic, predictive, and prognostic utility of pleural liquid biopsy in clinical medicine. Methods: A narrative review was conducted using PubMed, MEDLINE, and EMBASE databases. Search terms included combinations of “pleural effusion”, “liquid biopsy”, “circulating tumour DNA”, “circulating tumour cells”, “exosomes”, “next-generation sequencing”, and “biomarkers”. Priority was given to original research articles, systematic reviews, and meta-analyses published between 2013 and 2026. Results: Pleural fluid contains a diverse repertoire of tumour-derived analytes, including cell-free and circulating tumour DNA (ctDNA), circulating tumour cells (CTCs), exosomes, and soluble proteins. These biomarkers enable molecular characterisation of underlying malignancies with sensitivity that often exceeds that of plasma-based liquid biopsy and complements histological tissue biopsy. Detection of actionable mutations, including EGFR, ALK, KRAS, and BRAF alterations, directly informs targeted therapy selection. Furthermore, serial sampling facilitates real-time monitoring of therapeutic resistance, disease progression, and clonal evolution. Conclusions: Pleural liquid biopsy offers a minimally invasive, reproducible, and clinically informative approach to molecular profiling in patients with pleural disease, particularly those with thoracic malignancies. Despite existing challenges in standardisation and analytical sensitivity, its integration into routine clinical pathways holds significant promise for advancing personalised oncological care. Multi-omics integration and artificial intelligence may further consolidate its role in therapeutic decision-making. Full article

Background/Objectives: Effective melanoma prevention depends on reliable instruments capable of assessing individual risk factors, knowledge, attitudes, risk perception, and preventive behaviors. However, no culturally adapted questionnaire has been available for Serbian melanoma patients. This study aimed to develop and evaluate the psychometric properties of a Serbian questionnaire designed to assess melanoma-related risk factors, knowledge, concern, attitudes, and sun-protective behavior in a clinical population. Methods: A cross-sectional study was conducted among 333 melanoma patients treated at the Oncology Institute of Vojvodina, Serbia. The questionnaire was developed using the conceptual framework of a previously published instrument as a methodological reference and was modified and expanded for the Serbian clinical setting. Internal consistency was evaluated using Cronbach’s alpha. Differences between participant groups were analyzed using independent-samples t-tests and one-way ANOVA. Correlations between questionnaire domains were assessed using Spearman’s correlation coefficients, while predictors of sun-protective behavior were identified using multivariable linear regression. Results: The developed questionnaire demonstrated satisfactory internal consistency, with Cronbach’s alpha coefficients ranging from 0.711 to 0.874. Participants demonstrated high levels of melanoma-related knowledge and attitudes, melanoma-related concern, and reported sun-protective behavior, whereas perceived personal melanoma risk was comparatively lower. Female participants reported significantly greater melanoma-related concern and more frequent sun-protective behavior than males (p < 0.05). Significant positive correlations were observed among all questionnaire domains, with the strongest associations identified between melanoma-related concern and sun-protective behavior and between knowledge and sun-protective behavior (both p < 0.001). Multivariable analysis demonstrated that melanoma-related concern and knowledge independently predicted adequate sun-protective behavior, explaining 61.2% of its variance. Conclusions: The developed Serbian questionnaire demonstrated satisfactory psychometric performance and represents a practical instrument for assessing melanoma-related knowledge, perceptions, and preventive behaviors in clinical settings. The findings emphasize the importance of combining knowledge with behavioral motivation and support the implementation of targeted educational interventions to improve melanoma prevention among high-risk individuals. Full article

Background: Immune checkpoint inhibitors have improved outcomes in metastatic clear-cell renal cell carcinoma (mRCC), yet clinically applicable tissue biomarkers remain limited. Growth differentiation factor-15 (GDF-15) promotes tumour immune evasion and has emerged as a potential therapeutic target in immuno-oncology. We evaluated the prognostic significance of tumour GDF-15 expression in patients with intermediate-risk clear-cell mRCC treated with second-line nivolumab. Methods: Forty-six patients with intermediate-risk clear-cell mRCC who received nivolumab after one line of tyrosine kinase inhibitor therapy were retrospectively evaluated. Tumour GDF-15 expression was assessed by immunohistochemistry and classified as low (0–1+) or high (2–3+). Objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and the development of cancer-associated cachexia were compared between expression groups. Results: High tumour GDF-15 expression was observed in 23 patients (50%). ORR was significantly higher in the low-expression group than in the high-expression group (57% vs. 26%, p = 0.036). Low tumour GDF-15 expression was associated with significantly longer PFS (24.5 vs. 7.5 months; HR 0.38, 95% CI 0.18–0.80; p = 0.009) and OS (28.6 vs. 12.6 months; HR 0.43, 95% CI 0.19–0.98; p = 0.041). The association with OS remained significant after adjustment for age. The frequency of cancer-associated cachexia did not differ according to tumour GDF-15 expression (43% vs. 35%, p = 0.546). Conclusions: Low tumour GDF-15 expression was associated with better objective response and longer progression-free and overall survival in patients with intermediate-risk metastatic clear-cell renal cell carcinoma treated with second-line nivolumab, with the association with overall survival remaining significant after adjustment for age. Tumour GDF-15 represents a promising tissue biomarker for prognostic risk stratification and warrants validation in larger prospective studies. Full article