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22 pages, 1961 KB  
Article
Multimodal Fusion of Intraoperative FLIm and Preoperative PET/CT for Patient-Level Prediction of Lymph Node Metastasis in Head and Neck Cancer
by Lei Zhou, Nimu Yuan, Mohamed A. Hassan, Lisanne Kraft, Katjana Ehrlich, Brent W. Weyers, Vladimir Ivanovic, Osama A. A. Raslan, Dorina Gui, Marianne Abouyared, Arnaud F. Bewley, Andrew C. Birkeland, Donald Gregory Farwell, Laura Marcu and Jinyi Qi
Cancers 2026, 18(13), 2154; https://doi.org/10.3390/cancers18132154 (registering DOI) - 4 Jul 2026
Abstract
Background: Metastatic lymph node (MLN) detection remains a major clinical challenge in head and neck cancer, as nodal involvement is strongly associated with poor prognosis and directly affects treatment planning. Previous approaches typically rely on cropped lymph node (LN) regions or tumor contours [...] Read more.
Background: Metastatic lymph node (MLN) detection remains a major clinical challenge in head and neck cancer, as nodal involvement is strongly associated with poor prognosis and directly affects treatment planning. Previous approaches typically rely on cropped lymph node (LN) regions or tumor contours for MLN identification, requiring substantial expert annotation during preprocessing and relying solely on imaging information. As a result, small or low-contrast metastatic nodes may be missed, while benign lymph nodes may be incorrectly identified as metastatic due to overlapping imaging characteristics. To address these limitations, we propose a multimodal learning framework that integrates anatomical and metabolic features from head and neck PET/CT images with biochemical features derived from FLIm for patient-level MLN prediction, without requiring manual lymph node cropping or tumor contouring during inference. Methods: To enable robust imaging representation learning, a region-aware PET/CT network based on a merging-diverging architecture was first pretrained on the HECKTOR 2022 dataset and then fine-tuned on the institutional cohort. In parallel, FLIm point-wise measurements with clinical variables were encoded using a multilayer perceptron (MLP) and aggregated into subject-level representations. To effectively combine these modalities, two multimodal fusion strategies were evaluated at the decoder stage, including cube-based fusion and squeeze-and-excitation (SE)-based fusion. The proposed strategies were evaluated on a cohort of 53 patients. Results: Compared with the single-modality baselines, both multimodal fusion strategies achieved better patient-level MLN prediction. The PET/CT-only segmentation-driven model and FLIm-only model reached balanced accuracies of 0.815 and 0.665, with AUCs of 0.828 and 0.614, respectively. Cube-based fusion improved balanced accuracy and AUC to 0.827 and 0.850, respectively, while channel-wise SE-based fusion achieved the best overall performance, with a balanced accuracy of 0.839 and an AUC of 0.872. Conclusions: These results suggest that multimodal integration may improve patient-level MLN prediction compared with single-modality approaches. Given the limited sample size, these findings should be interpreted as hypothesis-generating and require validation in larger, independent patient cohorts. Full article
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9 pages, 3780 KB  
Case Report
Neoadjuvant Cemiplimab in Cutaneous Squamous Cell Carcinoma: Complete Primary Tumor Response with Regional Nodal Metastases Case Report
by Seung Hwan Chung, Hussein Ali-Ahmad, Andrew Zwyghuizen and Linda Qu
Reports 2026, 9(3), 210; https://doi.org/10.3390/reports9030210 (registering DOI) - 3 Jul 2026
Viewed by 129
Abstract
Background and Clinical Significance: Cutaneous squamous cell carcinoma (CSCC) is a common non-melanoma skin cancer, and while most cases are curable, a small proportion progresses to locally advanced or metastatic disease. As neoadjuvant immunotherapy with PD-1 inhibitors such as cemiplimab becomes more widely [...] Read more.
Background and Clinical Significance: Cutaneous squamous cell carcinoma (CSCC) is a common non-melanoma skin cancer, and while most cases are curable, a small proportion progresses to locally advanced or metastatic disease. As neoadjuvant immunotherapy with PD-1 inhibitors such as cemiplimab becomes more widely adopted, understanding real-world patterns of response remains essential. Case Presentation: We report a case of a man in his 50s with a large, locally advanced CSCC of the left hand in whom neoadjuvant cemiplimab was chosen to reduce tumor burden and preserve hand function when margin-negative resection was unlikely. The patient received four cycles of cemiplimab and demonstrated marked clinical improvement followed by complete pathological response at the primary site upon wide local excision. However, metastatic involvement of the epitrochlear and axillary lymph nodes was identified at surgery despite initial benign imaging. Postoperative PET/CT showed no additional disease, and the patient subsequently underwent axillary dissection and adjuvant cemiplimab with good functional recovery. Conclusions: This case highlights the potential for neoadjuvant cemiplimab to achieve substantial local tumor control and functional preservation while emphasizing the need for careful nodal assessment and ongoing surveillance in patients with very-high-risk CSCC. In cases where baseline cross-sectional staging is not performed, pre-existing occult nodal disease cannot be excluded. Full article
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24 pages, 950 KB  
Review
Reimagining Nodal Staging in Colorectal Cancer: Toward a Novel Non-Invasive Imaging Approach
by Perla Moreno, Michela Orsi, Karl-Philippe Beaudet, Rania Benyahya, Leonardo Sosa-Valencia, Stéphane Cotin, Alfonso Lapergola and Alain García Vázquez
Cancers 2026, 18(13), 2139; https://doi.org/10.3390/cancers18132139 - 2 Jul 2026
Viewed by 329
Abstract
Colorectal cancer (CRC) remains the third most common malignancy worldwide and a leading cause of cancer mortality, largely driven by metastatic dissemination. Among metastatic routes, lymphatic spread is crucial to determine the prognosis and establish an adequate therapeutic strategy. Lymph node metastasis (LNM) [...] Read more.
Colorectal cancer (CRC) remains the third most common malignancy worldwide and a leading cause of cancer mortality, largely driven by metastatic dissemination. Among metastatic routes, lymphatic spread is crucial to determine the prognosis and establish an adequate therapeutic strategy. Lymph node metastasis (LNM) defines stage III disease in the TNM classification, guiding adjuvant chemotherapy and surgical planning. However, nodal staging based on lymphadenectomy and histopathology is invasive, time-consuming, and may lead to overtreatment. Conventional imaging modalities, including computed tomography, magnetic resonance imaging, and endorectal ultrasound, show limited sensitivity and specificity for small or micro-metastatic nodes. Despite multimodal progress, no non-invasive technique reliably identifies malignant nodes in real time. PET–MRI, contrast-enhanced ultrasound, photoacoustic and fluorescence approaches, ICG mapping, and sentinel node biopsy improve detection but remain limited by specificity, cost, or availability. Extranodal extension (ENE) and tumor deposits (TDs) carry major prognostic value, reflecting aggressive biology and association with distant spread. Meanwhile, phylogenetic studies challenge linear dissemination models, indicating that some metastases arise directly from the primary tumor or TDs rather than LNMs. These data support refinement of staging and surgical strategies according to tumor biology rather than purely anatomical criteria. High-frequency quantitative ultrasound (HF-QUS) enables real-time, operator-independent, three-dimensional nodal assessment with reported sensitivity and specificity exceeding 85%. Combined with artificial intelligence and molecular profiling, it may support biologically informed staging, reduce unnecessary surgery, and foster precision oncology. Lymphatic dissemination in CRC offers a platform to merge tumor biology with technological innovation, where advanced imaging, molecular insight, and artificial intelligence may redefine nodal staging toward precision, non-invasive care. Full article
(This article belongs to the Special Issue Innovations in Colorectal Cancer)
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23 pages, 1506 KB  
Article
Sustainable Power-Quality Enhancement and Loss Reduction in Radial Distribution Networks Using a DCM Cuk-Based Power Factor Correction Scheme
by Luis Tipán, Carlos Barrera-Singaña, Diego Carrión and Manuel Jaramillo
Sustainability 2026, 18(13), 6699; https://doi.org/10.3390/su18136699 - 2 Jul 2026
Viewed by 185
Abstract
Power-quality degradation caused by nonlinear loads remains a critical challenge in sustainable low-voltage distribution systems, as it increases harmonic distortion, reactive power circulation, feeder losses, and thermal stress in network assets. This paper evaluates a discontinuous-conduction-mode (DCM) Cuk-based power factor correction (PFC) scheme [...] Read more.
Power-quality degradation caused by nonlinear loads remains a critical challenge in sustainable low-voltage distribution systems, as it increases harmonic distortion, reactive power circulation, feeder losses, and thermal stress in network assets. This paper evaluates a discontinuous-conduction-mode (DCM) Cuk-based power factor correction (PFC) scheme integrated with a silicon-controlled rectifier (SCR) stage to improve power quality in a radial distribution feeder. The IEEE 13-bus distribution test system is used as the benchmark network, with the nonlinear load connected at node 634, supplied through a 4.16/0.48 kV transformer. Two operating scenarios are compared, an uncompensated case and a compensated case, using the SCR–Cuk PFC structure. The assessment considers source-side voltage and current waveforms, power factor, total harmonic distortion (THD), voltage deviation, nodal harmonic propagation, active and reactive power flows, and line losses. The results show that the proposed scheme increases the source-side power factor from 0.431 to 0.99 and reduces the source current THD from 16.31% to 1.10%, meeting the source-side 5% harmonic reference level used in this study. At the network level, the THD at node 634 decreases from 17.12% to 6.23%, while the main affected feeders show relevant reductions in active and reactive losses. These findings indicate that localized active PFC can support more sustainable distribution system operation by improving power quality and reducing losses. However, feeder-wide harmonic compliance may require distributed compensation at additional harmonic-sensitive nodes. Full article
(This article belongs to the Special Issue Smart Electricity Grid and Sustainable Power Systems)
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11 pages, 6759 KB  
Article
PSMA PET/CT-Guided Multimodal Therapy for Pelvic Lymph Node Positive and De Novo Low-Volume Metastatic Prostate Cancer: A Gulf Region Single-Institution Experience
by Nadeem Pervez, Benazir Mir Khan, Sharjeel Usmani, Hasan Al-Sayegh, Iqbal Al Amri, Mahmoud Alfishawy, Sercan Yilmaz, Sulaiman Al Saadi, Munjid Al Harthy, Javeria Ahmed and Zahid Almandhari
Diseases 2026, 14(7), 232; https://doi.org/10.3390/diseases14070232 - 28 Jun 2026
Viewed by 264
Abstract
Background/Objectives: Metastatic prostate cancer is increasing in the Gulf Cooperation Council countries. This study presents a multimodal treatment protocol incorporating radiotherapy to primary and metastatic sites, guided by PSMA PET/CT, combined with systemic therapy for non-metastatic pelvic node-positive and de novo low-volume [...] Read more.
Background/Objectives: Metastatic prostate cancer is increasing in the Gulf Cooperation Council countries. This study presents a multimodal treatment protocol incorporating radiotherapy to primary and metastatic sites, guided by PSMA PET/CT, combined with systemic therapy for non-metastatic pelvic node-positive and de novo low-volume metastatic prostate cancer. Methods: We conducted a retrospective cohort study of patients treated with radical radiotherapy doses (68 Gy/25 Fr or 78 Gy/39 Fr) to the prostate gland and gross pelvic disease, and SBRT (35–40 Gy/5 Fr) to distant bone metastases. All patients received LHRH agonists ± abiraterone/prednisone or enzalutamide. Results: Twenty-four consecutive patients were analyzed. The median age was 70.1 years (IQR, 65.7–77.7), the median baseline PSA was 27.9 ng/mL (IQR = 19.7–53.8), and median follow up was 24 months (IQR = 20.4–31.2). Clinical staging was cT3b in (46%), cT2 in (25%), cT4 in (17%), cT3a in (13%) of patients. Pelvic nodal involvement (cN1) was present in 91.7% of patients, while 54.1% had metastatic disease. Treatment was well tolerated. Acute toxicity was predominantly grade 1 genitourinary (GU) toxicity, occurring in 87.5% of patients, with grade 2 GU toxicity observed in 8.2% and no acute gastrointestinal (GI) toxicity. Late toxicity remained minimal, with grade 1 and grade 2 GU toxicity reported in 45.8% and 4.2% of patients, respectively, and no late GI toxicity. Mild systemic treatment-related toxicities were reported in 25% of patients, including sexual dysfunction, hypokalemia, muscle weakness, osteoporosis and depression/anxiety. At the six-month follow-up PSMA PET/CT assessment, 85.7% achieved a complete metabolic response, and 14.2% achieved a partial response. Biochemically, 75% of patients achieved undetectable PSA levels (<0.01 ng/mL), with all patients achieving a PSA nadir < 0.2 ng/mL. Conclusions: This first, hypothesis-generating real-world experience from the GCC, suggests that an integrated approach combining systemic therapy with metastasis-directed therapy is feasible. Prospective randomized studies are required to validate these results. Full article
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15 pages, 3734 KB  
Article
Association of Pretreatment Immune-Inflammatory Biomarkers with Pathological Tumor Regression Following Neoadjuvant Chemoradiotherapy in Locally Advanced Rectal Cancer
by Ahmet Sencer Ergin, Burcin Cakan Demirel, Sahin Bedir, Nida Sünnetci Arıkan, Alparslan Saylar, Ali Karabulut, Nihat Bugdayci, Tevhide Bilgen Özcan and Hüsniye Esra Pasaoglu
J. Clin. Med. 2026, 15(13), 5039; https://doi.org/10.3390/jcm15135039 - 28 Jun 2026
Viewed by 180
Abstract
Background: Predicting tumor regression following neoadjuvant chemoradiotherapy (nCRT) remains a major challenge in the management of locally advanced rectal cancer (LARC). Readily available inflammatory biomarkers may provide useful information regarding treatment response. Methods: This retrospective single-center study included 88 patients with stage II–III [...] Read more.
Background: Predicting tumor regression following neoadjuvant chemoradiotherapy (nCRT) remains a major challenge in the management of locally advanced rectal cancer (LARC). Readily available inflammatory biomarkers may provide useful information regarding treatment response. Methods: This retrospective single-center study included 88 patients with stage II–III rectal adenocarcinoma who underwent neoadjuvant chemoradiotherapy followed by curative-intent surgery between 2017 and 2025. Patients were classified according to the College of American Pathologists tumor regression grading system as CAP 0 (pathological complete response, n = 22), CAP 2 (partial response, n = 50), or CAP 3 (poor/no response, n = 16). Pretreatment C-reactive protein, carcinoembryonic antigen (CEA), neutrophil, platelet, monocyte, and lymphocyte counts, together with NLR, PLR, and PIV, were compared across groups. Receiver operating characteristic and logistic regression analyses were performed for pathological complete response (pCR). Results: None of the evaluated biomarkers differed significantly across CAP groups. The smallest omnibus p-values were observed for neutrophil count (p = 0.052), monocyte count (p = 0.075), and CEA (p = 0.088). Monocyte count showed the highest discriminatory performance for pathological complete response (AUC = 0.663), followed by CEA (AUC = 0.640). In sensitivity analyses adjusted for baseline clinical T stage and receipt of total neoadjuvant therapy, CEA, neutrophil count, and monocyte count were not independently associated with pathological complete response. More favorable tumor regression was associated with lower residual tumor burden and reduced nodal involvement. Conclusions: Pretreatment inflammatory biomarkers showed biologically plausible numerical patterns across tumor regression groups, but their discriminatory and independent predictive performance was limited. These markers should not be considered stand-alone clinical prediction tools and should be validated within larger, multimodal prospective models. Full article
(This article belongs to the Section General Surgery)
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21 pages, 723 KB  
Review
PSMA PET in Lymph Node Staging of Prostate Cancer: From Diagnostic Accuracy to Clinical Decision-Making
by Francesco Esperto, Arianna Pischetola, Matteo Bauckneht, Jacopo Passoni, Antonio Testa, Stefania Ferretti, Stefano Puliatti, Sebastiano Buti, Roberto Mario Scarpa, Davide Campobasso and Rocco Papalia
Cancers 2026, 18(13), 2094; https://doi.org/10.3390/cancers18132094 - 27 Jun 2026
Viewed by 255
Abstract
Lymph node involvement in prostate cancer has major prognostic and therapeutic implications, yet conventional imaging based on size and morphology remains limited in detecting small-volume metastatic disease. Although extended pelvic lymph node dissection is considered the reference standard for nodal staging, it is [...] Read more.
Lymph node involvement in prostate cancer has major prognostic and therapeutic implications, yet conventional imaging based on size and morphology remains limited in detecting small-volume metastatic disease. Although extended pelvic lymph node dissection is considered the reference standard for nodal staging, it is invasive, associated with morbidity, and primarily diagnostic in intent. Prostate-specific membrane antigen positron emission tomography (PSMA PET) has reshaped staging by enabling molecular detection of nodal metastases, consistently demonstrating superior accuracy compared with conventional imaging. This narrative review critically evaluates the role of PSMA PET in lymph node staging, with a primary focus on primary diagnosis and selected considerations on biochemical recurrence, focusing not only on diagnostic accuracy but on clinical utility and decision-making. PSMA PET shows high specificity but moderate sensitivity for pelvic nodal metastases, with reduced performance for micrometastatic disease; therefore, a negative scan cannot reliably exclude nodal involvement in high-risk patients. Evidence indicates frequent stage migration and management changes, including refinement of surgical planning, radiotherapy target delineation, and treatment intensification strategies. However, most pivotal therapeutic trials were based on conventional imaging, and long-term outcome data validating PSMA PET-guided treatment adaptations remain limited. We discuss biological rationale, radiotracer characteristics, interpretation frameworks, guideline perspectives, real-world variability in adoption, and current limitations, including false-positive findings, PSMA heterogeneity, and lack of universal standardization. Rather than replacing established staging paradigms, PSMA PET should be integrated within a comprehensive, risk-adapted framework. Ongoing prospective trials will clarify whether molecularly defined nodal staging translates into improved oncologic outcomes and will determine its definitive role in contemporary prostate cancer management. Full article
(This article belongs to the Special Issue Advances in the Use of PET/CT and MRI in Prostate Cancer: 2nd Edition)
18 pages, 1104 KB  
Systematic Review
Artificial Intelligence-Based 18F-FDG PET/CT Radiomics for Mediastinal Lymph Node Staging in Non-Small Cell Lung Cancer: A Systematic Review
by Alessia-Stephania Rosian, Agneta-Maria Pusztai, Amalia Constantinescu, Gabriel-Aurel Rus, Cristian Oancea and Diana Manolescu
Diagnostics 2026, 16(13), 2014; https://doi.org/10.3390/diagnostics16132014 - 27 Jun 2026
Viewed by 268
Abstract
Background/Objectives: Accurate staging of mediastinal lymph nodes is essential for therapeutic decisions and prognostic assessment in non-small cell lung cancer (NSCLC). This systematic review evaluates diagnostic performance, validation strategies, and clinical significance of artificial intelligence (AI)-based 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET/CT) radiomics [...] Read more.
Background/Objectives: Accurate staging of mediastinal lymph nodes is essential for therapeutic decisions and prognostic assessment in non-small cell lung cancer (NSCLC). This systematic review evaluates diagnostic performance, validation strategies, and clinical significance of artificial intelligence (AI)-based 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET/CT) radiomics models for mediastinal nodal staging in NSCLC. Methods: Systematic literature searching was conducted in PubMed, ScienceDirect, and Scopus according to the PRISMA 2020 guidelines. Eligible studies used radiomic or AI-based approaches for mediastinal lymph node (LN) evaluation in NSCLC, with histopathology as a reference standard. Extracted data included study design, cohort characteristics, imaging method, validation strategy, and diagnostic performance metrics. Methodological quality was assessed by the QUADAS-2 tool. Results: Thirteen studies were included which are mainly retrospective in their designs with cohort sizes varying between 87 and 3265 patients. Models evaluated on external or prospective validation cohorts generally showed lower performance compared with training or internal datasets. However, clinically significant discriminative ability has been preserved across heterogeneous populations. In studies that directly compared methods, composite models integrating radiomic features with clinical factors and conventional PET metrics, sometimes including deep learning-derived features, consistently outperformed radiomics-only models. Additionally, selected approaches addressing FDG-related false-positive uptake improved distinction between benign and metastatic mediastinal lymph nodes; this is reflected by reduced false-positive classifications plus higher specificity compared with conventional PET/CT interpretation. Conclusions: AI-based 18F-FDG PET/CT radiomics show a promising discriminative capacity for mediastinal nodal staging in NSCLC, especially when it is integrated with clinical and conventional imaging variables. Although the model performance remains clinically significant within independent validation cohorts, attenuation compared with training datasets is commonly observed. Methodological heterogeneity, predominantly retrospective study designs, and the scarcity of prospective multicenter validation currently limit routine clinical implementation. Full article
(This article belongs to the Special Issue Recent Developments and Future Trends in Thoracic Imaging)
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19 pages, 866 KB  
Article
Profiles of FGF2, HGF, Fas/CD95, CASP9, ALDH1A1, and GLUT1 in GEP-NETs: A Comparative Tumor–Margin Study Based on Protein Concentration
by Agata Świętek, Joanna Katarzyna Strzelczyk, Dorota Hudy, Zenon P. Czuba, Karolina Snopek-Miśta, Mariusz Kryj, Katarzyna Kuśnierz, Marcin Zeman, Władysław Skałba, Agata Abramowicz and Janusz Strzelczyk
Int. J. Mol. Sci. 2026, 27(13), 5794; https://doi.org/10.3390/ijms27135794 - 26 Jun 2026
Viewed by 114
Abstract
Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are characterized by substantial biological heterogeneity and complex regulation of apoptosis, metabolism, and angiogenesis. The aim of this study was to evaluate the concentrations of selected proteins: FGF2, HGF, Fas/CD95, CASP9, ALDH1A1, and GLUT1 in tumor and margin samples [...] Read more.
Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are characterized by substantial biological heterogeneity and complex regulation of apoptosis, metabolism, and angiogenesis. The aim of this study was to evaluate the concentrations of selected proteins: FGF2, HGF, Fas/CD95, CASP9, ALDH1A1, and GLUT1 in tumor and margin samples and assess correlations with clinical and demographic parameters. A total of 59 samples from patients with GEP-NETs were analyzed using multiplex immunoassay and ELISA methods. Significant differences in protein expression between tumor and margin tissues were observed. Fas/CD95 levels were lower in tumor samples, whereas HGF concentration was higher. Elevated HGF, FGF2 and Fas/CD95 levels were associated with advanced tumor stage. HGF and GLUT1 concentrations varied depending on nodal status, while FGF2, Fas/CD95, and CASP9 levels were increased in metastatic cases. Additionally, differences related to tumor localization and the influence of smoking and alcohol consumption were identified. Dysregulation of apoptotic, metabolic, and angiogenic pathways plays a crucial role in GEP-NETs progression and highlights the importance of the tumor microenvironment. GEP-NET exhibit biological heterogeneity and complex progression driven by multiple interacting molecular pathways. The factors analyzed may have potential significance as biomarkers of disease progression; however, their exact role requires further investigation in larger, prospective cohorts. Full article
13 pages, 8280 KB  
Review
Contemporary Lung Cancer Nodal Staging and Therapeutic Decision-Making in the 9th TNM Era
by Takahiro Nakajima and George A. Eapen
Cancers 2026, 18(13), 2071; https://doi.org/10.3390/cancers18132071 - 25 Jun 2026
Viewed by 257
Abstract
In the era of precision medicine, managing non-small cell lung cancer (NSCLC) requires pathological confirmation, accurate nodal staging, and comprehensive biomarker profiling performed rapidly and concurrently. In the 9th edition of the TNM classification, the N2 category is subdivided into single-station (N2a) and [...] Read more.
In the era of precision medicine, managing non-small cell lung cancer (NSCLC) requires pathological confirmation, accurate nodal staging, and comprehensive biomarker profiling performed rapidly and concurrently. In the 9th edition of the TNM classification, the N2 category is subdivided into single-station (N2a) and multistation (N2b) subcategories, highlighting the clinical importance of precise mediastinal staging. This refinement necessitates systematic nodal evaluation using minimally invasive modalities such as endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) and endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) to appropriately stratify patients for surgery, neoadjuvant therapy, and definitive chemoradiotherapy. Concurrently, although N1 has not been formally subclassified because of the lack of standardized clinical diagnostic criteria, the increasing use of sublobar resection for early-stage NSCLC requires more precise hilar and intrapulmonary nodal assessments, which can potentially be facilitated by emerging technologies such as thin convex-probe EBUS. Concurrently, adequate tissue acquisition is essential for timely biomarker testing. Before administering neoadjuvant immune checkpoint inhibitors, actionable driver alterations, such as epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) rearrangements, must be identified to select appropriate treatment and prevent severe sequential toxicities associated with subsequent targeted therapies. This review highlights the indispensable role of endoscopic nodal staging and multidisciplinary collaboration in adapting to the updated TNM classification and optimizing personalized treatment strategies for patients with NSCLC. Full article
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12 pages, 2353 KB  
Article
Translational Validation of a Novel Multi-Locus ctDNA Methylation Assay for Early Detection and Stratification of Colorectal Cancer: An Exploratory Prospective, Case-Control Study
by Hayoung Lee, Jae Cheol Kang, In Ja Park, Gwang-un Kim, Hwi Hyun, Na Young Min, Sungwon Jeon and Byoung-Chul Kim
Int. J. Mol. Sci. 2026, 27(13), 5738; https://doi.org/10.3390/ijms27135738 - 25 Jun 2026
Viewed by 196
Abstract
To evaluate the diagnostic performance and clinicopathologic relevance of a multi-locus circulating tumor DNA methylation assay, in this prospective, single-center, case-control exploratory study, we enrolled 35 patients with colorectal cancer undergoing surgery and 57 healthy controls undergoing screening colonoscopy at the Asan Medical [...] Read more.
To evaluate the diagnostic performance and clinicopathologic relevance of a multi-locus circulating tumor DNA methylation assay, in this prospective, single-center, case-control exploratory study, we enrolled 35 patients with colorectal cancer undergoing surgery and 57 healthy controls undergoing screening colonoscopy at the Asan Medical Center, Seoul, Republic of Korea between July 2024 and January 2025. Peripheral blood was collected before surgery or colonoscopy, and circulating tumor DNA methylation was analyzed using a multi-locus panel targeting Septin9, IKZF1, BCAT1, Septin9-2, BCAN, and VAV3. The main outcomes were test accuracy (sensitivity, specificity, and area under the curve [AUC]) and associations between methylation marker positivity and clinicopathologic features. Circulating tumor DNA was positive in 74.3% of the patients and 12.3% of controls, yielding a sensitivity of 74.3%, specificity of 87.7%, and an AUC of 0.837, whereas serum carcinoembryonic antigen exhibited lower sensitivity (25.7%). Sensitivity in stage I disease was limited (36.4%). Circulating tumor DNA-positive tumors were larger (5.7 cm vs. 2.2 cm, p < 0.001) and had more advanced T and N stages. The number of positive markers increased with pathologic stage (p = 0.003). Individual marker analysis revealed that BCAT1, Septin9-2, and VAV3 were associated with higher T stage, whereas BCAN positivity was linked to nodal metastasis. The six-marker circulating tumor DNA methylation assay demonstrated acceptable diagnostic accuracy, with multi-locus patterns associated with tumor burden and invasive features. However, sensitivity for early-stage disease was limited. The assay may serve as a complementary tool for screening and risk stratification. Full article
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
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20 pages, 335 KB  
Review
Para-Aortic Lymph Node Staging and Oncologic Outcomes in Locally Advanced Cervical Cancer: A Narrative Review
by Juan Sebastián Obando-Rodríguez, Santiago Vieira-Serna, Jonathan Peralta, Juliana Rodríguez, Erick Estrada, Luisa López-Saldarriaga, Gabriel Levin and Rene Pareja
Cancers 2026, 18(13), 2058; https://doi.org/10.3390/cancers18132058 - 25 Jun 2026
Viewed by 438
Abstract
Background: Para-aortic lymph node involvement is present in approximately 17–24% of women with locally advanced cervical cancer (LACC) and is one of the strongest adverse prognostic factors in this population. Current international guidelines recommend two alternative staging techniques: the International Federation of [...] Read more.
Background: Para-aortic lymph node involvement is present in approximately 17–24% of women with locally advanced cervical cancer (LACC) and is one of the strongest adverse prognostic factors in this population. Current international guidelines recommend two alternative staging techniques: the International Federation of Gynecology and Obstetrics (FIGO) and European Society of Gynecologic Oncology (ESGO) endorse imaging-based staging as the primary method to define radiation fields, whereas the National Comprehensive Cancer Network (NCCN) lists pre-treatment minimally invasive para-aortic lymphadenectomy as a Category 2B recommendation. Objective: We aimed to review and critically appraise the available evidence on the oncologic impact (progression-free and overall survival) of pre-treatment surgical para-aortic staging compared with clinical imaging-based staging in women with LACC. Methods: We searched MEDLINE (Ovid), Embase, the Cochrane Central Register of Controlled Trials (CENTRAL), ClinicalTrials.gov, and Scopus from inception to January 2026, complemented by manually searching the reference lists for relevant articles and prior reviews. The review focused on comparative studies of women with LACC of squamous, adenocarcinoma, or adenosquamous histology—operationally defined as FIGO 2009 stages IB2–IVA with pelvic nodal involvement or FIGO 2018 stages IB3–IVA who received definitive-intent radiotherapy with or without concurrent chemotherapy and brachytherapy, and for whom comparative survival outcomes between a surgical-staging arm and an imaging-staging arm were reported. For this manuscript, a narrative review style was planned and reported in line with SANRA (Scale for the Assessment of Narrative Review Articles) quality criteria. Results: Twelve studies were included: two randomized controlled trials and ten observational studies (nine retrospective cohorts and one population-based analysis). Surgical staging consistently increased detection of occult para-aortic disease and led to more frequent use of extended-field radiotherapy (18–44%), but it did not yield a reproducible advantage in terms of progression-free or overall survival over imaging-guided chemoradiation. Conclusions: In LACC, pre-treatment surgical para-aortic staging improves anatomic and prognostic information but has not shown a consistent survival advantage over imaging-based staging combined with contemporary chemoradiation. Current comparative evidence does not support routine surgical staging, and its use still warrants further prospective evaluation in large clinical trials. Until results from ongoing phase III trials are available, surgical staging should be considered an individualized option in highly selected cases within multidisciplinary decision-making at experienced clinical centers. Full article
(This article belongs to the Special Issue Novel Approaches in the Management of Gynecological Cancers)
15 pages, 9888 KB  
Article
MRE11 Deficiency Occurs in a Small Group of Cancers from Various Different Tumor Entities
by Viktor Reiswich, Henry Recksiek, Katharina Möller, Florian Lutz, Florian Viehweger, Georgia Makrypidi-Fraune, Martina Kluth, Claudia Hube-Magg, Christian Bernreuther, Guido Sauter, Andreas H. Marx, Ronald Simon, Till Krech, Stefan Steurer, Christoph Fraune, Sarah Minner, Viktoria Chirico, Veit Bertram, Clara Lühr, Cosima Völkel, Morton Freytag, Natalia Gorbokon, Maximilian Lennartz, Eike Burandt, Anne Menz and Clara von Bargenadd Show full author list remove Hide full author list
Diagnostics 2026, 16(13), 1965; https://doi.org/10.3390/diagnostics16131965 - 24 Jun 2026
Viewed by 166
Abstract
Background/Objectives: The double-strand break repair protein MRE11 forms the core of the MRE11/RAD50/NBS1 (MRN) complex. Cancers with reduced MRE11 expression have been suggested to be more sensitive to radio-chemotherapy and may be subject to synthetic lethality. The aim of this study was [...] Read more.
Background/Objectives: The double-strand break repair protein MRE11 forms the core of the MRE11/RAD50/NBS1 (MRN) complex. Cancers with reduced MRE11 expression have been suggested to be more sensitive to radio-chemotherapy and may be subject to synthetic lethality. The aim of this study was to assess the prevalence of MRE11 deficiency and the potential role and clinical significance of elevated and/or reduced MRE11 expression in human cancer. Methods: A tissue microarray containing 14,966 samples from 134 different tumor entities was analyzed for MRE11 by immunohistochemistry. Results: In normal tissues, strong nuclear MRE11 staining occurred in almost all cell types. In cancers, nuclear MRE11 staining was strong in 11,797 (91.0%), moderate in 1018 (7.9%), weak in 86 (0.7%), and completely absent (MRE11 deficiency) in 55 (0.4%) of 12,956 informative tumor samples. Only six tumor entities had more than one MRE11-deficient cases including hepatocellular carcinoma (9 of 193), intestinal type gastric adenocarcinoma (4 of 208), endometrioid endometrial carcinoma (5 of 268), pulmonary adenocarcinoma (2 of 165), colorectal adenocarcinoma (CRC, 16 of 2183), and clear cell renal cell carcinoma (ccRCC, 7 of 1011). Reduced MRE11 staining was associated with mismatch repair deficiency (dMMR) in CRC and in gastric adenocarcinoma (p < 0.0001 each), advanced pT stage (p = 0.0003) and L1 status (p = 0.0019) in testicular seminoma, high grade (p < 0.05), advanced pT (p < 0.0001), and high UICC stage (p = 0.0014) in ccRCC, advanced pT stage in high-grade serous ovarian carcinoma (p = 0.0396), and nodal metastases in papillary thyroid cancer (p = 0.0332). Conclusions: MRE11 is highly expressed in most cancers. Reduced MRE11 expression is associated with aggressive phenotype in multiple cancer types. The potential to exploit MRE11 deficiency as a target for synthetic lethality deserves to be further explored. Full article
(This article belongs to the Section Pathology and Molecular Diagnostics)
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33 pages, 1560 KB  
Review
From Excision to Immunity: The Full Spectrum of Modern Melanoma Treatments
by Vimal Murugesan, Thusanth Thuraisingam and Danuta Radzioch
Cancers 2026, 18(13), 2043; https://doi.org/10.3390/cancers18132043 - 24 Jun 2026
Viewed by 213
Abstract
Cutaneous Melanoma is a biologically heterogeneous malignancy. Although recent therapeutic advances have improved survival, durable remissions remain elusive for many patients. Surgical excision with stage-appropriate margins and selective nodal staging remains the cornerstone of curative-intent management. In contrast, conventional cytotoxic chemotherapy now plays [...] Read more.
Cutaneous Melanoma is a biologically heterogeneous malignancy. Although recent therapeutic advances have improved survival, durable remissions remain elusive for many patients. Surgical excision with stage-appropriate margins and selective nodal staging remains the cornerstone of curative-intent management. In contrast, conventional cytotoxic chemotherapy now plays a limited, largely palliative role given its modest efficacy and substantial toxicity. Targeted therapy with BRAF/MEK inhibitors has improved outcomes in patients with BRAF V600-mutant melanoma, resulting in rapid tumor regression and meaningful survival benefits. However, long-term disease control is frequently compromised by adaptive resistance, commonly driven by MAPK pathway reactivation or compensatory PI3K/AKT signaling. In parallel, immune checkpoint inhibitors targeting PD-1, CTLA-4, and emerging pathways have reshaped treatment across disease stages, enabling deep and sometimes durable responses. Despite this progress, primary and acquired resistance, as well as acute and chronic immune-related toxicities, continue to pose significant clinical challenges. Current therapeutic strategies focus on rational combinations of targeted therapy, checkpoint blockade, IL-2-based approaches, oncolytic viruses, and adoptive cell therapies such as tumor-infiltrating lymphocytes to enhance response depth and durability. However, these intensified regimens carry increased toxicity risks, highlighting the need for improved patient selection and monitoring. Overall, emerging evidence supports a paradigm shift toward optimized treatment sequencing, response-adapted surgical strategies, and biomarker-guided personalization to maximize clinical benefit while minimizing toxicity. Full article
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28 pages, 53779 KB  
Article
TDGF1 Mediates the Oncogenic Effects of the OLMALINC/miR-3614-5p ceRNA Axis in Colon Cancer Through Nodal/Smad2 and Glypican-1/MAPK-AKT Signaling
by Feng Gao, Xiaoli Li, Jiawei Li, Shuo Yang, Boyu Zhang, Ying Sun, Lihua Zheng, Guannan Wang, Lei Liu, Yongli Bao and Xiaoguang Yang
Cells 2026, 15(13), 1141; https://doi.org/10.3390/cells15131141 - 23 Jun 2026
Viewed by 235
Abstract
The multifaceted oncogenic role of teratocarcinoma-derived growth factor 1 (TDGF1) in colon cancer remains incompletely understood. Through integrative bioinformatic and functional analyses, we identified a novel competing endogenous RNA (ceRNA) axis wherein the long non-coding RNA OLMALINC directly sponges hsa-miR-3614-5p, leading to the [...] Read more.
The multifaceted oncogenic role of teratocarcinoma-derived growth factor 1 (TDGF1) in colon cancer remains incompletely understood. Through integrative bioinformatic and functional analyses, we identified a novel competing endogenous RNA (ceRNA) axis wherein the long non-coding RNA OLMALINC directly sponges hsa-miR-3614-5p, leading to the derepression of TDGF1. This OLMALINC/miR-3614-5p/TDGF1 axis promoted colon cancer cell proliferation, migration, invasion, and anti-apoptosis in vitro, whereas TDGF1 knockdown significantly suppressed tumor growth in vivo. Mechanistically, TDGF1 co-activated oncogenic signaling via the Thr88-dependent Nodal/Smad2 cascade and the Glypican-1-mediated MAPK/AKT pathway. Beyond cell-autonomous effects, transcriptomic and single-cell analyses revealed that elevated TDGF1 correlates with an immunosuppressive microenvironment, characterized by reduced immune infiltration and altered LGALS9-CD44 malignant-T cell communication. Clinically, high TDGF1 expression in a tissue microarray cohort was significantly associated with advanced T stage, reduced expression of specific mismatch repair proteins (MLH1/PMS2), and poor overall survival. Collectively, this study delineates the OLMALINC/miR-3614-5p/TDGF1 regulatory circuit and establishes TDGF1 as a multifaceted driver of tumor progression, highlighting its potential as a prognostic biomarker and therapeutic target in colon cancer. Full article
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