Cancers

17 pages, 1046 KB

Open AccessArticle

Sleep Health and Quality of Life in Children and Adolescents with NF1: A Biopsychosocial Perspective

by Natalie A. Pride, Siobhan Banks, Dinberu Shebeshi, Shelley S. Arnold, Kristina Haebich, Jessica Habib, Crystal Yates, Hayley Darke, Kathryn N. North, Jack Nguyen and Jonathan M. Payne

Cancers 2026, 18(14), 2366; https://doi.org/10.3390/cancers18142366 - 22 Jul 2026

Viewed by 512

Abstract

Background: This study applies Buysse’s sleep health framework to examine sleep in children and adolescents with neurofibromatosis type 1 (NF1). By examining sleep timing, daytime sleepiness, sleep quality, sleep behavior, sleep duration, and sleep efficiency together, this framework captures the multidimensional nature of [...] Read more.

Background: This study applies Buysse’s sleep health framework to examine sleep in children and adolescents with neurofibromatosis type 1 (NF1). By examining sleep timing, daytime sleepiness, sleep quality, sleep behavior, sleep duration, and sleep efficiency together, this framework captures the multidimensional nature of sleep and its relationship with biopsychosocial factors and health-related quality of life (HR-QoL) in NF1. Methods: This multi-site, prospective, cross-sectional study included 131 children and adolescents with NF1 and 71 typically developing (TD) controls aged 6 to 16 years. A sleep health composite was derived from carer rating scales and 7 days of actigraphy. A biopsychosocial framework was used to examine factors associated with sleep health in NF1, including sociodemographic, cognitive, psychopathology, and biological variables. Independent predictors of QoL were examined to assess the unique contributions of sleep quality, sleep duration, and previously established predictors of HR-QoL in NF1. Results: Poorer sleep health was evident in children with NF1. Compared with TD controls, children with NF1 were five times as likely to have poor sleep quality, with almost 78% demonstrating impaired sleep efficiency and nearly half not obtaining sufficient sleep at night. The strongest risk factors were being male, elevated pain, and having greater levels of ADHD and autism spectrum disorder traits. Conclusions: Findings suggest sleep health in NF1 is interconnected with multiple biopsychosocial factors. A better understanding of these relationships will help identify early risk markers, improve prediction of clinical trajectories, and guide the development of targeted multimodal interventions for sleep disruption in NF1. Full article

(This article belongs to the Special Issue Advances in Neurofibromatosis in Children, Adolescents, and Young Adults)

► Show Figures

Graphical abstract

15 pages, 825 KB

Open AccessReview

Robotic Thoracic Surgery After Neoadjuvant Chemo-Immunotherapy for NSCLC: A Narrative Review

by Monica Casiraghi, Antonio Mazzella, Lara Girelli, Giorgio Lo Iacono, Luca Bertolaccini, Matteo Chiari, Giovanni Caffarena, Claudia Bardoni and Lorenzo Spaggiari

Cancers 2026, 18(14), 2365; https://doi.org/10.3390/cancers18142365 - 22 Jul 2026

Cited by 1 | Viewed by 362

Abstract

Background: The integration of neoadjuvant and perioperative chemo-immunotherapy (CT-IO) has significantly reshaped the treatment of resectable non-small-cell lung cancer (NSCLC), improving pathological response and survival outcomes. However, its impact on surgical management—particularly robotic-assisted thoracic surgery (RATS)—remains incompletely defined. This review provides a [...] Read more.

Background: The integration of neoadjuvant and perioperative chemo-immunotherapy (CT-IO) has significantly reshaped the treatment of resectable non-small-cell lung cancer (NSCLC), improving pathological response and survival outcomes. However, its impact on surgical management—particularly robotic-assisted thoracic surgery (RATS)—remains incompletely defined. This review provides a practical overview of current evidence and technical considerations for robotic lung resection following neoadjuvant chemo-immunotherapy. Methods: A narrative review of the literature was performed, focusing on phase III trials, meta-analyses, and surgical series reporting perioperative, oncological, and technical outcomes of minimally invasive—especially robotic—approaches after neoadjuvant or perioperative chemo-immunotherapy. Results: Randomized trials have established CT-IO as a standard treatment option for selected patients with resectable stage II–III NSCLC—although the specific standard varies according to stage, molecular and PD-L1 status, and regulatory approval—significantly improving pathological complete response and event-free survival. However, immune-related fibrosis, nodal scarring, and altered tissue planes increase surgical complexity and intra-postoperative complications. Available evidence, largely retrospective and derived from selected patient populations treated at experienced centers, suggest that RATS is feasible and safe, offering enhanced visualization and dexterity that may facilitate dissection in challenging post-induction settings. Vascular management and lymph node dissection remain critical technical aspects, and early conversion to open surgery, when required, should be regarded as an appropriate safety strategy rather than a complication. Conclusions: RATS after neoadjuvant chemo-immunotherapy appears feasible and promising in selected patients treated at experienced centers, but current evidence does not yet establish it as the preferred approach for all patients. Careful patient selection, adherence to oncological principles, and surgeon experience are essential. Prospective data are needed to define optimal surgical timing and standardize techniques. Full article

(This article belongs to the Special Issue Clinical Trials for Thoracic Cancers)

► Show Figures

Figure 1

28 pages, 1297 KB

Open AccessReview

Pharmacologic Resistance in Soft Tissue Sarcomas: Mechanisms, Biomarkers, and Translational Therapeutic Strategies

by Dorian Yarih García-Ortega, Gabriela Alamilla-García, Kevin Fernando Reyna-Pérez, Jessica Baldriche-Acosta, Luis Alonso Herrera-Montalvo and Carlo César Cortés-González

Cancers 2026, 18(14), 2364; https://doi.org/10.3390/cancers18142364 - 22 Jul 2026

Viewed by 554

Abstract

Soft tissue sarcomas are rare, biologically diverse mesenchymal malignancies in which pharmacologic resistance cannot be explained by a single unifying mechanism. In this narrative review, resistance is conceptualized as a dynamic, multilayered process shaped by histologic subtype, genomic architecture, transcriptional plasticity, the tumor [...] Read more.

Soft tissue sarcomas are rare, biologically diverse mesenchymal malignancies in which pharmacologic resistance cannot be explained by a single unifying mechanism. In this narrative review, resistance is conceptualized as a dynamic, multilayered process shaped by histologic subtype, genomic architecture, transcriptional plasticity, the tumor microenvironment, and treatment-driven selective pressure. Resistance to conventional chemotherapy arises through both intrinsic and acquired mechanisms, including altered drug transport and metabolism, enhanced DNA damage responses, impaired apoptotic signaling, clonal selection, and the emergence of therapy-persistent cellular states. By contrast, resistance to targeted and epigenetic therapies more often reflects adaptive bypass signaling, lineage reprogramming, and incomplete identification of subtype-specific dependencies than secondary on-target alterations alone. The tumor microenvironment further contributes to therapeutic failure through hypoxia, extracellular matrix-mediated barriers, abnormal vascularization, myeloid-dominant immunosuppression, and immune exclusion, thereby helping explain the modest and histology-dependent activity of immune checkpoint inhibitors in soft tissue sarcoma. This review also differentiates baseline predictive biomarkers from dynamic resistance-monitoring tools, underscoring the potential—despite still limited clinical maturity—of pharmacogenomic markers, immune signatures, tertiary lymphoid structures, circulating tumor DNA, and circulating methylation-based approaches. Finally, emerging strategies to overcome resistance are examined, including mechanism-based combinations, biomarker-guided treatment selection, synthetic lethality, functional precision platforms, and adaptive histology-specific trial designs. Collectively, these observations support a view of resistance in soft tissue sarcoma as a context-dependent biological process that demands integrated, subtype-aware, and translationally grounded therapeutic strategies. Full article

(This article belongs to the Special Issue Soft Tissue Sarcomas—New Diagnostic and Therapeutic Perspectives Through Clinical Genomic Profiling)

► Show Figures

Figure 1

11 pages, 1539 KB

Open AccessArticle

High Prevalence of Superficial Metastases Supports Percutaneous Ultrasound-Guided Biopsy for Diagnosis and Molecular Profiling of Advanced Lung Cancer: Results from a Prospective Cohort

by Marta Viscuso, Vanina Livi, Giovanni Sotgiu, Valeria Cetoretta, Alessandra Cancellieri, Mariangela Puci, Angelo Minucci, Emilio Bria, Federico Cappuzzo, Silvia Novello and Rocco Trisolini

Cancers 2026, 18(14), 2363; https://doi.org/10.3390/cancers18142363 - 22 Jul 2026

Viewed by 406

Abstract

Background: Despite therapeutic advances, many patients with metastatic lung cancer still lack access to comprehensive molecular profiling, often due to inadequate biopsy samples. Percutaneous ultrasound-guided needle aspiration biopsy (US-NAB) from both lung and metastatic sites has shown promise in improving diagnostic and molecular [...] Read more.

Background: Despite therapeutic advances, many patients with metastatic lung cancer still lack access to comprehensive molecular profiling, often due to inadequate biopsy samples. Percutaneous ultrasound-guided needle aspiration biopsy (US-NAB) from both lung and metastatic sites has shown promise in improving diagnostic and molecular profiling accuracy. However, data regarding its real-world utilization, diagnostic performance, and contribution to comprehensive molecular profiling in unselected patients with advanced lung cancer remain limited. Methods: We performed a secondary (post hoc) analysis of prospectively collected data from the Propheta Pro study, a prospective observational cohort of patients with advanced lung cancer. The aim of the present analysis was to assess patterns of invasive sampling procedures, with a particular focus on the prevalence of US-NAB utilization across histologic subtypes. We also assessed the diagnostic yield of US-NAB for cancer diagnosis, comprehensive genomic profiling, and PD-L1 expression. Results: Among the 348 patients enrolled, 123 (35.3%) underwent US-NAB, making it the most frequently utilized sampling technique overall and across individual histologic subtypes. Biopsy of metastatic sites was significantly more common than primary lung tumors (113, 91.9% versus 10, 8.1%; p < 0.001), with superficial metastases being the primary target (110, 89.4%). US-NAB demonstrated high diagnostic yields: 97% for histological diagnosis, 91.1% for comprehensive genomic profiling, and 95.8% for PD-L1 testing. Only two minor, self-limiting complications were observed. Conclusions: US-NAB is a highly effective yet underrecognized diagnostic option for advanced lung cancer, particularly given the high prevalence of accessible superficial metastases. Integrating US-NAB into interventional pulmonology services could enhance diagnostic and molecular profiling yields. Full article

(This article belongs to the Special Issue Molecular Advances in Lung Cancer: From Pathogenesis to Precision Therapy (2nd Edition))

► Show Figures

Figure 1

23 pages, 1376 KB

Open AccessSystematic Review

A Systematic Literature Review of the Effectiveness of CDK 4/6 Inhibitors for First-Line Treatment of HR+/HER2− Advanced/Metastatic Breast Cancer: A Comparison of Real-World Evidence

by Timothy Pluard, Thomas Grinda, Rodrigo Dienstmann, Marc Thill, Beata Korytowsky, Connie Chen, Sofiya Portuhay, Elizabeth M. Salvo-Halloran, Imtiaz A. Samjoo and Nadia Harbeck

Cancers 2026, 18(14), 2362; https://doi.org/10.3390/cancers18142362 - 22 Jul 2026

Viewed by 601

Abstract

Background/Objective: Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) combined with endocrine therapy are the standard first-line treatment for HR+/HER2− advanced/metastatic breast cancer (a/mBC), yet no head-to-head randomized trials have compared palbociclib, ribociclib, and abemaciclib. This systematic literature review (SLR) aimed to synthesize available real-world evidence [...] Read more.

Background/Objective: Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) combined with endocrine therapy are the standard first-line treatment for HR+/HER2− advanced/metastatic breast cancer (a/mBC), yet no head-to-head randomized trials have compared palbociclib, ribociclib, and abemaciclib. This systematic literature review (SLR) aimed to synthesize available real-world evidence (RWE) on the comparative effectiveness of these three CDK4/6i in the first-line setting. Methods: An SLR was conducted following PRISMA guidelines. Searches of MEDLINE, Embase, Cochrane, and gray literature (January 2015–September 2025) identified RWE studies reporting real-world progression-free survival (rwPFS) and/or overall survival (OS) for first-line CDK4/6i regimens. Eligible studies included adults with HR+/HER2− a/mBC receiving palbociclib, ribociclib, or abemaciclib, combined with endocrine-based therapy. Comparative outcomes were summarized qualitatively; study quality was assessed using the Newcastle–Ottawa Scale, ISPOR-AMCP-NPC questionnaire, and ESMO-GROW checklist. Results: From 13,345 records, 39 publications (32 unique studies) were identified, of which 21 were full-text studies meeting inclusion criteria. Most included studies used retrospective cohort designs, and approximately 50% evaluated all three CDK4/6is. Given the comparative nature of the included studies, quality issues were found to be related to study design and analytical approaches. Several analyses were unadjusted, and reporting of follow-up duration varied across studies, with some analyses providing incomplete follow-up information. Study sample sizes differed substantially across agents, with smaller populations generally reported for ribociclib and abemaciclib. Among the studies reporting rwPFS hazard ratios (HRs), 8/11 studies showed comparable rwPFS and 5/6 studies reported comparable OS outcomes between CDK4/6i regimens. Three full-text studies reported HRs favoring ribociclib or abemaciclib relative to palbociclib; these analyses primarily included populations receiving palbociclib, with smaller comparator cohorts for ribociclib and abemaciclib, as well as varied follow-up times. Conclusions: Most real-world studies included in the SLR suggested similar effectiveness of the three CDK4/6is in first-line HR+/HER2− a/mBC. Heterogeneity in patient characteristics, definitions of outcomes, follow-up time, sample size, and statistical approach may have important implications on study interpretability. Full article

(This article belongs to the Section Systematic Review or Meta-Analysis in Cancer Research)

► Show Figures

Figure 1

1 pages, 133 KB

Open AccessCorrection

Correction: Cruz et al. Drug Development in Non-Oncogene-Addicted Non-Small Cell Lung Cancer. Cancers 2026, 18, 880

by Pedro Cruz, Cristina Boixareu, Diogo J. Silva, Joshua Ting, Rayssa Sena, Steph A. Pang, Stephanie Mullings and Anna Minchom

Cancers 2026, 18(14), 2361; https://doi.org/10.3390/cancers18142361 - 22 Jul 2026

Viewed by 245

Abstract

During publication, the authors detected the following errors in this article [...] Full article

(This article belongs to the Section Clinical Research in Cancer)

3 pages, 589 KB

Open AccessCorrection

Correction: Oturkar et al. Estrogen Receptor-Beta2 (ERβ2)–Mutant p53–FOXM1 Axis: A Novel Driver of Proliferation, Chemoresistance, and Disease Progression in High Grade Serous Ovarian Cancer (HGSOC). Cancers 2022, 14, 1120

by Chetan C. Oturkar, Nishant Gandhi, Pramod Rao, Kevin H. Eng, Austin Miller, Prashant K. Singh, Emese Zsiros, Kunle O. Odunsi and Gokul M. Das

Cancers 2026, 18(14), 2360; https://doi.org/10.3390/cancers18142360 - 22 Jul 2026

Viewed by 235

Abstract

Update to Figure [...] Full article

(This article belongs to the Special Issue Ovarian Cancer: Recent Advances in Research and Clinical Therapy)

► Show Figures

Figure 2

13 pages, 1143 KB

Open AccessArticle

TROP2 Is Uniformly Expressed in Primary Prostate Cancer but Frequently Reduced in Recurrent Disease

by Jonathan Jeutner, Ronald Simon, Maximilian Lennartz, Sarah Minner, Eike Burandt, Fiete Gehrisch, Nina Schraps, Martina Kluth, Guido Sauter, Henning Plage, Jacob Schmidt, Natalia Gorbokon, Florian Viehweger, Hans Heinzer, Alexander Haese, Thorsten Schlomm, Markus Graefen, Stefan Steurer, Ria Schlichter, Christian Bernreuther, David Dum, Andreas Luebke, Bernhard Ralla and Neele Heckmann Show full author list Hide full author list

Cancers 2026, 18(14), 2359; https://doi.org/10.3390/cancers18142359 - 22 Jul 2026

Viewed by 363

Abstract

Background: TROP2 (TACSTD2) is a therapeutic target of antibody–drug conjugates and is broadly expressed in epithelial malignancies. Data on TROP2 protein expression in large, clinically annotated prostate cancer cohorts, particularly in recurrent disease, remain limited. Methods: TROP2 immunohistochemistry was performed on [...] Read more.

Background: TROP2 (TACSTD2) is a therapeutic target of antibody–drug conjugates and is broadly expressed in epithelial malignancies. Data on TROP2 protein expression in large, clinically annotated prostate cancer cohorts, particularly in recurrent disease, remain limited. Methods: TROP2 immunohistochemistry was performed on a prostate cancer tissue microarray comprising 17,747 primary radical prostatectomy specimens and 258 recurrent prostate cancer samples. TROP2 staining data were compared with clinicopathological parameters, biochemical recurrence and ERG status. Results: Among 12,807 interpretable primary prostate cancers, TROP2 staining was detectable in all cases and considered strong in 94.5%, moderate in 3.5%, and weak in 2.0%. Reduced TROP2 was statistically associated with high pT stage (p = 0.0011) and high Gleason grade (p < 0.0001), but absolute differences were small. Reduced TROP2 expression levels were unrelated to PSA recurrence in the entire cohort (p = 0.0787) but statistically linked to early PSA recurrence in ERG positive cancers (p = 0.0165). In four different scenarios of multivariate analyses, reduced TROP2 expression did not show an unequivocal independent prognostic role. As compared to primary tumors, TROP2 was markedly reduced among 250 evaluable recurrent cancers (strong 57.6%, moderate 31.6%, weak 8.4%, negative 2.4%; p < 0.0001 vs. primary cancers). Reduced TROP2 was also significantly more frequent in recurrent cancers than in the subgroup of high-grade primary tumors (Gleason ≥ 4+4; strong 57.6% vs. 90.2%; p < 0.0001). Conclusions: TROP2 is consistently expressed at high levels in primary prostate cancer but often reduced in recurrent disease. While uniform expression in primary tumors supports TROP2 as a therapeutic target in prostate cancer, reduced expression in many recurrent cancers highlights the potential need for TROP2 expression measurement as a predictive test in this subgroup. Full article

(This article belongs to the Special Issue Histopathology of Urological Cancers)

► Show Figures

Figure 1

32 pages, 2247 KB

Open AccessReview

Cancer-Associated Fibroblast Heterogeneity and Extracellular Matrix Remodeling as Orchestrators of Drug Resistance in Upper Gastrointestinal Cancers: Insights from Spatial Multi-Omics and Therapeutic Implications

by Yasamin Mirzabeigi, Joe Youssef, Jeffrey Gonzalez, Thais Martinez, Rima Avellan, Andres Wong, Miguel Perez, Luis Lorenzo Carvajal, Wassim Abou-Kheir and Hisham F. Bahmad

Cancers 2026, 18(14), 2358; https://doi.org/10.3390/cancers18142358 - 22 Jul 2026

Viewed by 914

Abstract

Upper gastrointestinal (GI) cancers, including esophageal, gastric, and pancreatic cancers, remain among the most lethal malignancies worldwide, mainly because they resist nearly every therapeutic modality, from platinum-based chemotherapy, and anti-HER2 and anti-VEGF agents, to immune checkpoint inhibitors. Although tumor cell-intrinsic resistance is well [...] Read more.

Upper gastrointestinal (GI) cancers, including esophageal, gastric, and pancreatic cancers, remain among the most lethal malignancies worldwide, mainly because they resist nearly every therapeutic modality, from platinum-based chemotherapy, and anti-HER2 and anti-VEGF agents, to immune checkpoint inhibitors. Although tumor cell-intrinsic resistance is well characterized, an increasing share of treatment failure traces to the tumor microenvironment (TME), where cancer-associated fibroblasts (CAFs) and the extracellular matrix (ECM) act not as passive stroma but as active orchestrators of resistance. Here we argue that the functional heterogeneity of CAFs, spanning myofibroblastic (myCAF), inflammatory (iCAF), and antigen-presenting (apCAF) subtypes, and the desmoplastic ECM they construct converge on a small number of shared resistance programs. Those include paracrine signaling, metabolic reprogramming, extracellular vesicle (EV) transfer, and biomechanical remodeling that together drive chemoresistance, targeted therapy evasion, and immune exclusion. Emerging spatial multi-omics now resolves these programs to define niches within upper GI tumors, reframing resistance as a spatially organized property of the tissue rather than the tumor cell alone. We bring this evidence together and evaluate strategies aimed at CAF reprogramming and ECM normalization, arguing that spatially resolved targeting of the stroma represents a tractable path to overcoming resistance in these refractory cancers. Full article

(This article belongs to the Special Issue Drug Resistance Mechanisms and Tumor Microenvironment in Upper Gastrointestinal Cancers)

► Show Figures

Figure 1

1 pages, 125 KB

Open AccessExpression of Concern

Expression of Concern: Park et al. Isorhamnetin Induces Cell Cycle Arrest and Apoptosis Via Reactive Oxygen Species-Mediated AMP-Activated Protein Kinase Signaling Pathway Activation in Human Bladder Cancer Cells. Cancers 2019, 11, 1494

by Cancers Editorial Office

Cancers 2026, 18(14), 2357; https://doi.org/10.3390/cancers18142357 - 22 Jul 2026

Viewed by 225

Abstract

With this notice, the Cancers Editorial Office alerts readers to concerns regarding this article [...] Full article

18 pages, 7881 KB

Open AccessArticle

Bridging Targeting Precision and Oncologic Safety: Localization Accuracy for Margin Adequacy in Cone-Beam Computed Tomography-Guided Pulmonary Nodule Resection

by Yu-Hsiang Wang, Hsu-Chih Huang, Chih-Yi Chen, Jiun-Yi Hsia, Guo-Zhi Wang, Ming-Chih Chou and Frank Cheau-Feng Lin

Cancers 2026, 18(14), 2356; https://doi.org/10.3390/cancers18142356 - 21 Jul 2026

Viewed by 353

Abstract

Background/Objectives: Ground-glass pulmonary nodules are often nonpalpable and not visible during thoracoscopic surgery, making accurate localization important for achieving adequate pathological margins. However, no clinically validated localization-error threshold has been established. We evaluated the association between Dmn and pathological margin adequacy after image-guided [...] Read more.

Background/Objectives: Ground-glass pulmonary nodules are often nonpalpable and not visible during thoracoscopic surgery, making accurate localization important for achieving adequate pathological margins. However, no clinically validated localization-error threshold has been established. We evaluated the association between Dmn and pathological margin adequacy after image-guided thoracoscopic pulmonary nodule resection and sought to identify a clinically relevant localization-accuracy threshold. Methods: We retrospectively reviewed 169 patients in a predefined peripheral-lesion cohort who underwent cone-beam computed tomography-guided pulmonary nodule localization using hook-wire placement or dye marking in a hybrid operating room, followed by thoracoscopic wedge resection. Dmn was defined as the shortest three-dimensional Euclidean distance from the localization needle tip to the tumor margin. Pathological margin adequacy was defined as a resection margin equal to or greater than the maximum tumor diameter. Logistic regression was used to identify predictors of pathological margin inadequacy, and receiver operating characteristic analysis was performed to determine the optimal Dmn cutoff. Results: Dmn was independently associated with pathological margin inadequacy (odds ratio, 1.617; 95% confidence interval, 1.356–1.928; p < 0.001). Receiver operating characteristic analysis yielded an area under the curve of 0.827 and an optimal Dmn cutoff of 4.90 mm, with a sensitivity of 71.0% and specificity of 94.2%. Pathological margin inadequacy occurred more frequently in patients with Dmn ≥ 4.9 mm than in those with Dmn < 4.9 mm (73.3% vs. 6.5%, p < 0.001). Conclusions: In this single-center cohort, a Dmn of approximately 4.9 mm was associated with pathological margin inadequacy after cone-beam computed tomography-guided pulmonary nodule localization and thoracoscopic wedge resection. This value may serve as a candidate intraoperative warning threshold for margin reassessment; however, prospective external validation is required before routine clinical implementation. Full article

(This article belongs to the Special Issue A New Era in the Treatment of Early-Stage Non-Small Cell Lung Cancer (2nd Edition))

► Show Figures

Figure 1

14 pages, 938 KB

Open AccessArticle

High-Concentration Capsaicin Patch and Oral Pregabalin as Second-Line Therapy for Intercostobrachial Neuralgia After Breast Cancer Surgery: Open-Label Follow-Up of a Multicenter Randomized Controlled Clinical Trial

by Denis Dupoiron, Florent Bienfait, Valérie Seegers and Sabrina Jubier-Hamon

Cancers 2026, 18(14), 2355; https://doi.org/10.3390/cancers18142355 - 21 Jul 2026

Viewed by 403

Abstract

Background: The CAPTRANE trial evaluated the efficacy of randomly assigned high-concentration capsaicin patch (HCCP) versus daily oral pregabalin (PGB) in adults with chronic neuropathic pain (DN4 ≥ 4) post-breast cancer surgery. The objective of its 4-month open-label extension following patient’s self-selection of their [...] Read more.

Background: The CAPTRANE trial evaluated the efficacy of randomly assigned high-concentration capsaicin patch (HCCP) versus daily oral pregabalin (PGB) in adults with chronic neuropathic pain (DN4 ≥ 4) post-breast cancer surgery. The objective of its 4-month open-label extension following patient’s self-selection of their second treatment (HCCP, PGB, or none) was to explore efficacy and safety of various strategies. Methods: The study was conducted in France between March 2019 and November 2022. At each clinic visit, we assessed pain intensity (NRS, 0–10), painful area (cm²), mood (HADS), and quality of life (EQ-5D-5L). Standard statistical tests were used. Results: Data from 116 patients (all females; 76% aged < 65 years) were collected. At Month 2, 71% (46/65) of HCCP-treated patients received a second HCCP application and none switched to PGB, whereas 27% (14/51) continued on PGB and 49% (25/51) of PGB-treated patients switched to HCCP. At Month 6, NRS scores had decreased in HCCP-treated patients, including PGB/HCCP-treated patients, with a reduction of −2.0 [−4.0; 0.0] and −3.0 [−4.0; −2.0] in the HCCP/HCCP and PGB/HCCP group, respectively (median[interquartile]). Adverse events aligned with those expected with HCCP and PGB; none were serious. Conclusions: This first study to examine switching between PGB and HCCP treatments for chronic intercostobrachial neuropathic pain after breast cancer surgery showed patients’ preference for HCCP, confirmed the benefit of repeated HCCP applications, and indicated that HCCP could be preceded by PGB without compromising efficacy or safety. These findings suggest that HCCP may be used early in this population, and PGB initiated before HCCP to relieve patients waiting for HCCP application. Full article

(This article belongs to the Section Cancer Survivorship and Quality of Life)

► Show Figures

Figure 1

18 pages, 345 KB

Open AccessReview

Palliative Systemic Therapy in Advanced Thymic Epithelial Tumors in 2026—A Narrative Review

by Felix C. Saalfeld and Tobias R. Overbeck

Cancers 2026, 18(14), 2354; https://doi.org/10.3390/cancers18142354 - 21 Jul 2026

Viewed by 675

Abstract

Palliative systemic therapy for advanced thymic epithelial tumors (TET) is challenging due to scarce evidence and biological heterogeneity. Scientific discussion, as in this review, is limited to cross-trial comparisons of small, non-randomized studies. Platinum-based combination chemotherapy is the standard first-line treatment. Here, we [...] Read more.

Palliative systemic therapy for advanced thymic epithelial tumors (TET) is challenging due to scarce evidence and biological heterogeneity. Scientific discussion, as in this review, is limited to cross-trial comparisons of small, non-randomized studies. Platinum-based combination chemotherapy is the standard first-line treatment. Here, we challenge the addition of anthracyclines to platinum in thymoma. We critically appraise new combinations with antiangiogenic drugs and immune checkpoint inhibitors (ICI) in thymic carcinoma and their implications for therapy sequences. We review the data on classic genomics-based targeted therapy that does not benefit most patients and explore established and upcoming biomarkers including KIT and HER2. Finally, we discuss investigational therapies like anti-TROP2 antibody–drug conjugates and proteasome inhibitors, as well as topics and design of future research. Full article

(This article belongs to the Special Issue New Insights into Thymic Tumors)

19 pages, 2467 KB

Open AccessArticle

Impact of COPD on Outcomes After Pulmonary Metastasectomy: A Propensity-Score Matched Analysis

by Konstantinos Grapatsas, Fabian Doerr, Roemer van Wijk, Thomas Bergmann, Ilias Arfanis, Viktor Grünwald, Sebastian Bauer, Stephan Lang, Stefan Kasper, Boris Hadaschik, Dirk Schadendorf, Ulf Neumann, Christian Taube, Martin Schuler, Servet Bölükbas and Natalie Baldes

Cancers 2026, 18(14), 2353; https://doi.org/10.3390/cancers18142353 - 21 Jul 2026

Viewed by 482

Abstract

Background: Pulmonary metastasectomy (PM) is an established component of multimodal oncological treatment, but its perioperative safety and long-term outcomes in patients with chronic obstructive pulmonary disease (COPD) remain insufficiently defined. We aimed to evaluate the impact of COPD on perioperative morbidity, mortality and [...] Read more.

Background: Pulmonary metastasectomy (PM) is an established component of multimodal oncological treatment, but its perioperative safety and long-term outcomes in patients with chronic obstructive pulmonary disease (COPD) remain insufficiently defined. We aimed to evaluate the impact of COPD on perioperative morbidity, mortality and long-term survival after PM. Methods: We retrospectively analysed 692 patients who underwent PM with curative intent. COPD severity was graded using the GOLD spirometric classification. Patients were classified according to their postbronchodilator FEV1/FVC ratio into a COPD group (<0.70) and a control group (≥0.70). Groups were compared regarding clinical and surgical characteristics, postoperative morbidity and mortality, and overall survival (Kaplan–Meier, log-rank). Independent predictors of morbidity and survival were identified via logistic and Cox regression, and a 1:1 propensity-score-matched analysis was performed to account for baseline imbalances. Results: Among 9684 patients, 692 (7.1%) patients underwent PM, of whom 171 (24.7%) had COPD. They were more frequently smokers and had a higher comorbidity burden and worse performance status and, as expected, significantly lower lung function. The main clinically relevant finding was a significantly higher rate of persistent air leak in patients with COPD (8.8% vs. 2.3%, p < 0.001). Overall morbidity and 30-day mortality, however, did not differ. With a median follow-up of 76.7 months, survival was similar between groups (3-year survival 76.5% vs. 78.4%, p = 0.495) and was unaffected by GOLD severity. Independent predictors of worse survival were preoperative systemic therapy (HR 2.18), repeat metastasectomy (HR 1.60) and increasing age (HR 1.02 per year). After propensity matching, survival remained comparable (HR 1.05, p = 0.835). Conclusions: Among carefully selected patients, COPD was not associated with increased mortality or reduced survival after PM, although persistent air leak was significantly more frequent. COPD alone should not, by itself, be considered a contraindication to curative-intent surgery in appropriately selected patients, and these findings should not be generalized to patients with severe or end-stage COPD. Full article

(This article belongs to the Special Issue Surgery in Metastatic Cancer (2nd Edition))

► Show Figures

Figure 1

13 pages, 796 KB

Open AccessArticle

Genomic Characterization of Urothelial Carcinoma and Sarcomatoid Carcinoma of the Upper Urinary Tract

by Salvador Jaime-Casas, Nicholas J. Salgia, Miguel Zugman, Vitor Goes, Ali Moradi, Koral Shah, Rahul Winayak, Regina Barragan-Carrillo, Jadon Fann, George Zhang, Benjamin Mercier, Daniela V. Castro, Nazli Dizman, JoAnn Hsu, Alexander Chehrazi-Raffle, Tanya Dorff, Wesley Yip, Sumanta K. Pal and Abhishek Tripathi

Cancers 2026, 18(14), 2352; https://doi.org/10.3390/cancers18142352 - 21 Jul 2026

Viewed by 470

Abstract

Background: Sarcomatoid carcinoma of the upper urinary tract (SCUT) is a rare and aggressive malignancy. Due to its rarity, the molecular landscape and the prevalence of potentially targetable alterations are poorly characterized. We aimed to compare the clinical, pathological, and genomic profiles of [...] Read more.

Background: Sarcomatoid carcinoma of the upper urinary tract (SCUT) is a rare and aggressive malignancy. Due to its rarity, the molecular landscape and the prevalence of potentially targetable alterations are poorly characterized. We aimed to compare the clinical, pathological, and genomic profiles of SCUT and upper tract urothelial carcinoma (UTUC). Methods: We leveraged the Tempus Lens clinically annotated genomic dataset to extract clinicopathologic and somatic genomic alteration data from patients with UTUC and SCUT. Patients with any-stage disease who underwent either blood- or tissue-based next-generation sequencing were included. Baseline clinical and demographic characteristics were summarized using descriptive statistics. Comparisons between groups were performed using Wilcoxon rank-sum test for continuous variables and the Chi-square test/Fisher’s exact test for categorical variables. Mutational frequencies and pairwise comparisons were performed to assess significant differences between groups. Results: In total, 1721 patients were included, of which 1600 (93%) had UTUC and 121 (7%) had SCUT. Patients with SCUT were younger at diagnosis, 61 years (interquartile range (IQR) 54, 70), compared to UTUC, 71 years (IQR 64, 77) (p < 0.001), and were more likely to have node-positive disease at presentation (all p < 0.001). SCUT patients were more likely to show visceral metastases to the lung (44% vs. 21%), bone (31% vs. 17%), and brain (7% vs. 1%), compared to UTUC (all p < 0.05). Among SCUT patients, the most common genomic alterations were TERT (30%), TP53 (29%), NF2 (19%), PTEN (13%), SETD2 (12%), PBRM1 (12%), and BAP1 (8%). Among UTUC patients, the most common were TERT (52%), TP53 (52%), KMT2D (30%), FGFR3 (25%), ARID1A (20%), and KDM6A (18%). Compared to UTUC, SCUT was significantly enriched with NF2, SETD2, PBRM1, PTEN, and BAP1 (all p < 0.05). SCUT was depleted in FGFR3 (0% vs. 25%) and FGF4 (0% vs. 8%) mutations compared to UTUC (both p < 0.05). Targetable alterations were observed in SCUT, including NF2, SETD2, and PTEN. Conclusion: Compared with UTUC, SCUT exhibits a more aggressive clinical and genomic phenotype, characterized by enrichment in NF2, SETD2, PBRM1, and PTEN. These findings underscore the divergent molecular landscape of SCUT and highlight potentially targetable genomic alterations. Full article

(This article belongs to the Special Issue Application of Large-Scale Genome Data in Identifying Clinically Actionable Targets in Cancer)

► Show Figures

Figure 1

2 pages, 417 KB

Open AccessCorrection

Correction: Raab et al. Truncated DAPK Variants Restore Tumor Suppressor Activity and Synergize with Standard Therapies in High-Grade Serous Ovarian Cancer. Cancers 2025, 17, 1910

by Monika Raab, Khayal Gasimli, Balázs Győrffy, Samuel Peña-Llopis, Sven Becker, Mourad Sanhaji and Klaus Strebhardt

Cancers 2026, 18(14), 2351; https://doi.org/10.3390/cancers18142351 - 21 Jul 2026

Viewed by 277

Abstract

In the original publication [...] Full article

► Show Figures

Figure 2

15 pages, 1195 KB

Open AccessArticle

D90 and D_2CC Dose in Vaginal CTV as Dosimetric Predictors of Late Vaginal Side Effects in Postoperative Vaginal Modern Brachytherapy (Interventional Radiotherapy) After External Beam Irradiation in Endometrial Cancer

by Yao Qiang, Faegheh Noorian, Rosa Abellana, Clara Baltrons, Valentina Lancellotta, Luca Tagliaferri, Jaume Ordi and Angeles Rovirosa

Cancers 2026, 18(14), 2350; https://doi.org/10.3390/cancers18142350 - 21 Jul 2026

Viewed by 387

Abstract

Background/Objectives: To evaluate clinical and dosimetric predictors of vaginal toxicity in patients treated with vaginal-cuff brachytherapy (VCB), with or without external beam radiotherapy (EBRT), and assess the impact of different prescription and optimization strategies on dose–volume parameters. Methods: We retrospectively analyzed [...] Read more.

Background/Objectives: To evaluate clinical and dosimetric predictors of vaginal toxicity in patients treated with vaginal-cuff brachytherapy (VCB), with or without external beam radiotherapy (EBRT), and assess the impact of different prescription and optimization strategies on dose–volume parameters. Methods: We retrospectively analyzed 217 patients treated with EBRT combined with VCB (n = 120) or VCB alone (n = 97). In VCB three prescription and optimization strategies (volume-based, graphical optimization, and 5 mm distance-based prescription) were compared to determine differences in dose–volume parameters. In patients who developed late vaginal side effects, the dosimetric parameters were evaluated using descriptive statistics and Cox regression modeling. Kaplan–Meier analysis was performed to assess time to toxicity. Results: In the EBRT+VCB cohort, 34/120 patients (28.3%) developed grade 1–2 vaginal toxicity compared to 35/97 (36%) in the VCB alone cohort. In the EBRT+VCB group, patients with toxicity received a higher D90 per fraction and higher vaginal D_2cc. In multivariable analysis, vaginal D_2cc (HR = 1.60, 95% CI = 1.01–2.54, p = 0.045) and CTV-DVH (HR = 0.77, 95% CI = 0.61–0.97, p = 0.027) were independently associated with toxicity. No significant dose–toxicity associations were observed in the VCB-alone cohort. Most events occurred within 48 months in both groups. Comparison of prescription strategies showed systematic differences in target and organ-at-risk dose–volume parameters, including vaginal D_2cc. The 5 mm distance-based prescription consistently resulted in higher D90, D100, EQD2, and vaginal D_2cc values. Conclusions: In patients receiving EBRT combined with VCB, both vaginal D_2cc and target dose distribution were associated with vaginal toxicity. The prescription and optimization strategy significantly influenced dose–volume parameters. Planning methodology and dosimetric aspects should be considered when interpreting dose–toxicity relationships in vaginal brachytherapy. Full article

(This article belongs to the Special Issue Endometrial Cancer Therapy: Foundations and Future Directions)

► Show Figures

Figure 1

13 pages, 1231 KB

Open AccessArticle

Incidence and Clinical Impact of Endocrinopathy Following First-Line Nivolumab-Plus-Relatlimab Therapy for Metastatic Melanoma

by Julia Reitkopp, Wolfram Samlowski and Mahir Hasan

Cancers 2026, 18(14), 2349; https://doi.org/10.3390/cancers18142349 - 21 Jul 2026

Viewed by 400

Abstract

Background: Dual immune checkpoint inhibitor therapy with nivolumab plus relatlimab has substantial clinical activity against metastatic melanoma. The incidence and timing of endocrine immune-related adverse events with this treatment remain poorly characterized. Methods: We conducted a retrospective record review of 52 sequential patients [...] Read more.

Background: Dual immune checkpoint inhibitor therapy with nivolumab plus relatlimab has substantial clinical activity against metastatic melanoma. The incidence and timing of endocrine immune-related adverse events with this treatment remain poorly characterized. Methods: We conducted a retrospective record review of 52 sequential patients who received nivolumab plus relatlimab as initial therapy for metastatic cutaneous melanoma. All patients underwent sequential endocrine screening (TSH, FT4, ACTH, cortisol) prior to each monthly treatment cycle. The incidence and onset of hypothyroidism and hypopituitarism were evaluated, as was cancer treatment outcome. Results: Biochemical evidence for endocrinopathy was identified in 25% of patients. This included a 13.5% incidence of hypothyroidism (median onset 79.0 ± 63.9 days) and 11.5% incidence of hypopituitarism (median onset 243.5 ± 75.6 days). Due to screening and early replacement therapy, there were no related hospitalizations. Patients who developed endocrinopathy showed a trend toward improved progression-free and overall survival. An exploratory analysis suggested that the incidence of endocrinopathy was significantly lower in patients treated with nivolumab plus relatlimab than in those treated with ipilimumab plus nivolumab. Conclusions: During treatment with nivolumab plus relatlimab, endocrinopathy developed in approximately 25% of metastatic melanoma patients, emphasizing a need for screening testing. In an exploratory analysis, endocrinopathy appeared less frequent than in ipilimumab-plus-nivolumab-treated patients. Recovery from endocrinopathy appeared uncommon. Development of delayed endocrinopathy following elective treatment discontinuation for patients in remission was rare (3.8%). Patients who developed endocrinopathy showed a trend toward improved clinical outcome. Full article

(This article belongs to the Special Issue Cancer Immunotherapy-Related Adverse Events and Therapy-Related Accelerated Aging)

► Show Figures

Figure 1

19 pages, 6007 KB

Open AccessArticle

Dissecting Immune Determinants in Lesional Skin of Cutaneous T-Cell Lymphoma During Mogamulizumab Therapy

by Xiao Ni, Wei Han, Niharika Kunta, Meghali Goswami, Jared K. Burks, Ye Zheng, Youn H. Kim and Madeleine Duvic

Cancers 2026, 18(14), 2348; https://doi.org/10.3390/cancers18142348 - 21 Jul 2026

Viewed by 428

Abstract

Background: Mycosis fungoides (MF) and Sézary syndrome (SS) are the predominant cutaneous T-cell lymphomas. Although malignant T cells in MF/SS overexpress CCR4 and respond to the anti-CCR4 antibody mogamulizumab, skin response rates vary. We hypothesized that immune components within the tumor microenvironment [...] Read more.

Background: Mycosis fungoides (MF) and Sézary syndrome (SS) are the predominant cutaneous T-cell lymphomas. Although malignant T cells in MF/SS overexpress CCR4 and respond to the anti-CCR4 antibody mogamulizumab, skin response rates vary. We hypothesized that immune components within the tumor microenvironment contribute to differential outcomes. Methods: Imaging mass cytometry with a 37-antibody panel was used to characterize immune and structural elements in FFPE tissues from sixteen MF/SS patients (6 MF, 10 SS) treated with Mogamulizumab, including seven skin responders and nine non-responders. Single-cell phenotyping and spatial analyses were performed using the Visiopharm^® Phenoplex™ platform, with supervision. Results: We identified 68,974 cells pre-treatment and 58,852 cells post-treatment. Malignant CD4⁺ T cells showed reduced baseline CD27, CD103, CD25, and ICOS expression compared with non-malignant CD4⁺ cells. Baseline MF lesions were enriched for IL-13⁺ and CD103⁺ malignant T cells, whereas SS lesions contained higher proportions of CD27⁺ and LAG3⁺ cells. IL 13⁺ malignant cells decreased after treatment, most prominently in MF. Myeloid profiles differed by disease and response: MF lesions exhibited baseline enrichment of M1-like macrophages (CD86⁺, HLA-DR⁺), while SS lesions were predominantly M2-polarized macrophages (CD163⁺, CD206⁺). Responders showed increased M1-like macrophages, whereas non-responders displayed reduced M1-features. An increase in DC3-like cells was observed in non-responders following treatment. Conclusions: This single-cell spatial atlas reveals shared and subtype-specific immune features in MF/SS. Th2-skewed malignant T-cell status and myeloid polarization correlate with clinical response, supporting their potential as spatial biomarkers for patient stratification in mogamulizumab therapy. Full article

(This article belongs to the Section Tumor Microenvironment)

► Show Figures

Figure 1

19 pages, 1876 KB

Open AccessArticle

Mismatch Between Cancer Burden and Clinical Trial Activity in the European Union: Analysis of Incidence, per Capita Indicators and Commercial Versus Non-Commercial Studies

by Klaudia Marciniak, Maja Janowczyk, Michał Brancewicz and Marlena Robakowska

Cancers 2026, 18(14), 2347; https://doi.org/10.3390/cancers18142347 - 21 Jul 2026

Viewed by 535

Abstract

Introduction: Cancer represents one of the greatest public health challenges in Europe. Clinical trials play a key role in the development of new diagnostic and treatment methods, but their geographic distribution may not reflect the true epidemiological burden. The aim of this study [...] Read more.

Introduction: Cancer represents one of the greatest public health challenges in Europe. Clinical trials play a key role in the development of new diagnostic and treatment methods, but their geographic distribution may not reflect the true epidemiological burden. The aim of this study was to assess the relationship between the incidence of selected cancers and clinical trial activity in European Union countries, with particular emphasis on commercial and non-commercial trials, as well as changes over time. Materials and Methods: Data on clinical trials conducted in European Union countries in 2012, 2014, 2017, and 2022 were analyzed. Epidemiological data were obtained from the GLOBOCAN and Global Burden of Disease databases, while clinical trial data were obtained from the EU Clinical Trials Register. Overall cancer incidence and selected cancer types, namely breast cancer, lung cancer, colorectal cancer, and prostate cancer, were analyzed. Clinical trial activity rates were calculated relative to incidence and population size (per capita). Pearson and Spearman correlation analyses were performed, and 95% confidence intervals and p-values were calculated for the principal correlations. Time trends were also assessed. The results are presented in the form of tables, figures, and maps. Results: Clinical trial activity in oncology varied considerably across European Union countries. Commercial trials were consistently more common than non-commercial trials and showed a more pronounced increase in activity during the analyzed period. Correlations between cancer incidence and the number of clinical trials varied depending on cancer type, year of analysis, and sponsor type. The strongest associations were observed in 2022 for commercial trials, particularly for colorectal cancer (Pearson’s r = 0.865, 95% CI: 0.723–0.937, p < 0.001) and lung cancer (Pearson’s r = 0.853, 95% CI: 0.701–0.931, p < 0.001). Spearman analysis confirmed strong rank-based associations in 2022, especially for lung cancer (ρ = 0.971, 95% CI: 0.937–0.987, p < 0.001). Analysis of trial activity indicators indicated a mismatch between disease burden and the intensity of research activity in some countries and oncology areas. Conclusions: Clinical trial activity in oncology in European Union countries does not always reflect the actual cancer burden. The observed differences between commercial and non-commercial trials and between individual cancer types may indicate a research gap and the need for more balanced clinical trial planning in the European Union. Full article

(This article belongs to the Special Issue Feature Paper in Section ‘Cancer Epidemiology and Prevention’ in 2025-2026)

► Show Figures

Figure 1

26 pages, 7969 KB

Open AccessReview

Vitamin D Status and Gastroenteropancreatic Neuroendocrine Neoplasms: Biological Rationale, Clinical Associations and Limitations of Current Evidence

by Bartosz Basiaga, Violetta Rosiek and Beata Kos-Kudła

Cancers 2026, 18(14), 2346; https://doi.org/10.3390/cancers18142346 - 20 Jul 2026

Viewed by 1222

Abstract

Background: Vitamin D deficiency is common in patients with gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs). Whether vitamin D status influences tumor aggressiveness and clinical outcomes remains uncertain. This review examines current evidence on the prevalence, determinants, clinical associations, and clinical relevance of vitamin D deficiency [...] Read more.

Background: Vitamin D deficiency is common in patients with gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs). Whether vitamin D status influences tumor aggressiveness and clinical outcomes remains uncertain. This review examines current evidence on the prevalence, determinants, clinical associations, and clinical relevance of vitamin D deficiency in GEP-NENs. Methods: A narrative and critical review of the literature was conducted using the PubMed/MEDLINE, Scopus, and Web of Science databases. Clinical studies, observational cohorts, translational research, selected mechanistic studies, and current clinical guidelines addressing vitamin D metabolism and neuroendocrine neoplasms were evaluated. Results: Vitamin D deficiency has been reported in approximately 60–80% of patients with GEP-NENs. Low serum 25-hydroxyvitamin D concentrations likely reflect multiple disease-related factors, including malabsorption, pancreatic exocrine insufficiency, chronic diarrhea, previous gastrointestinal surgery, and nutritional impairment. Several observational studies have linked lower vitamin D status with markers of more aggressive disease, including higher Ki-67 proliferation index values and shorter progression-free survival. Nevertheless, the available data are heterogeneous, predominantly observational, and do not support a causal relationship between vitamin D deficiency and tumor progression. At present, the main clinical rationale for assessing vitamin D status is to support metabolic care, preserve bone health, and prevent osteoporosis. Conclusions: Vitamin D deficiency is a frequent and clinically relevant comorbidity in patients with GEP-NENs. Although lower vitamin D status has been associated with markers of more aggressive disease, current findings do not support vitamin D supplementation as an anticancer treatment strategy. Prospective clinical and translational studies are needed to clarify the biological and clinical significance of vitamin D signaling in GEP-NENs. Full article

(This article belongs to the Section Cancer Pathophysiology)

► Show Figures

Figure 1

18 pages, 1671 KB

Open AccessSystematic Review

Metastasizing Pleomorphic Adenoma: A Systematic Review and Pooled Case-Report Analysis

by Stefan Janik, Blazen Marijic, Filip Tudor, Katharina B. Erovic and Boban M. Erovic

Cancers 2026, 18(14), 2345; https://doi.org/10.3390/cancers18142345 - 20 Jul 2026

Viewed by 1242

Abstract

Background/Objectives: Metastasizing pleomorphic adenoma (MPA) is a rare salivary gland tumor characterized by benign pleomorphic adenoma morphology despite regional or distant metastatic behavior. Because most evidence derives from case reports and small series, this systematic review and pooled case-report analysis aimed to summarize [...] Read more.

Background/Objectives: Metastasizing pleomorphic adenoma (MPA) is a rare salivary gland tumor characterized by benign pleomorphic adenoma morphology despite regional or distant metastatic behavior. Because most evidence derives from case reports and small series, this systematic review and pooled case-report analysis aimed to summarize published patient-level data and to explore clinicopathologic features, metastatic distribution, treatment, and survival without inferring causal treatment effects. Methods: PubMed, Scopus, Google Scholar, and reference lists were searched for English-language reports published up to 1 August 2025. Eligible reports described primary pleomorphic adenoma and metastatic disease reported as MPA with benign morphology; carcinoma ex pleomorphic adenoma and other malignant pleomorphic adenoma variants were excluded. The primary pooled analysis was restricted to 122 published case-report patients. Institutional cases are presented separately as illustrative cases and were not included in the primary pooled statistical analyses. Unknown, not reported, NA, and unclear values were treated as missing, and denominators are reported. Because only 16 deaths were available, survival analyses were exploratory and no multivariable Cox model was fitted. No formal risk-of-bias or certainty-of-evidence assessment was performed. Results: In the 122 published patients, sex was available for 121 patients and 71/121 (58.7%) were female. Primary tumors most frequently arose in the parotid gland (92/122, 75.4%), followed by the submandibular gland (15/122, 12.3%) and palate/soft palate (10/122, 8.2%). The median interval between primary pleomorphic adenoma and MPA was 12 years (IQR 7–21; range 0–69; n = 118). Metastatic site was reported in 120 patients and was non-mutually exclusive: bone/skeleton and lymph nodes/neck were each reported in 42/120 patients (35.0%), followed by lung/pulmonary metastases in 31/120 (25.8%). Treatment information was available for 98/122 patients. MPA-directed surgery was performed in 86/98 patients with available treatment information (87.75%). The non-surgical cohort received radiotherapy, chemotherapy, palliative treatment, treatment refusal, observation, or other non-surgical strategies. A total of 72 patients had complete covariate data for the reported Cox analyses, including 16 deaths. Estimated 1- and 5-year overall survival were 89.97% and 66.2%, respectively. Surgery was associated with improved overall survival in exploratory Kaplan–Meier comparison (log-rank p = 0.008) and univariable Cox analysis (HR 0.119, 95% CI 0.018–0.810, p = 0.030), but this association should not be interpreted as causal. Conclusions: MPA remains difficult to predict and the available evidence is limited by case-report design, missing data, publication bias, and heterogeneous follow-up. Surgical management may be considered in selected patients when technically feasible and clinically appropriate, but the observed survival association is exploratory and may be influenced by selection bias and disease characteristics. Multicenter registries, standardized reporting, centralized pathology review, molecular characterization, and longer follow-up are needed. Full article

(This article belongs to the Special Issue Advancements in Salivary Gland Tumors Management: From Diagnostic Imaging to Treatment Strategies)

► Show Figures

Figure 1

41 pages, 1535 KB

Open AccessReview

Non-Invasive Diagnosis of Early Breast Cancer: Current and Emerging Liquid Biopsy Biomarkers

by Amalia Kotsifaki, Charikleia-Rafaela Masoura, Georgia Limogianni, Georgia Kalouda, Martha Stathaki and Athanasios Armakolas

Cancers 2026, 18(14), 2344; https://doi.org/10.3390/cancers18142344 - 20 Jul 2026

Viewed by 765

Abstract

Background/Objectives: Breast cancer (BC) remains the most frequently diagnosed malignancy among women worldwide, and patient outcome is strongly influenced by disease stage at diagnosis. Although imaging-based screening has improved early detection, its performance may be reduced in dense breast tissue and is associated [...] Read more.

Background/Objectives: Breast cancer (BC) remains the most frequently diagnosed malignancy among women worldwide, and patient outcome is strongly influenced by disease stage at diagnosis. Although imaging-based screening has improved early detection, its performance may be reduced in dense breast tissue and is associated with false-positive findings. In addition, tissue biopsy is invasive and unsuitable for longitudinal disease monitoring. Liquid biopsy (LB) has emerged as a minimally invasive approach for detecting tumor-derived material in peripheral blood. However, early-stage tumors typically exhibit low tumor burden and limited biomarker shedding, generating weak systemic signals that challenge reliable detection. This review examines current and emerging LB biomarkers for early BC detection. Methods: A comprehensive review of recent literature was conducted focusing on circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), extracellular vesicles (EVs), circulating RNAs, proteins, and other blood-based biomarkers associated with early BC. Studies addressing biomarker biology, detection technologies, clinical applications, and methodological limitations were critically evaluated. Results: ctDNA, CTCs, EVs, circulating RNAs, proteins, and additional blood-based biomarkers capture distinct aspects of tumor biology and disease evolution. ctDNA enables the analysis of tumor-specific mutations, methylation patterns, and fragmentation profiles, whereas CTCs provide direct cellular and phenotypic information despite their rarity and marked epithelial–mesenchymal plasticity. EVs offer increased molecular stability and actively participate in tumor progression, immune modulation, and metastatic niche formation. Nevertheless, low biomarker abundance, biological heterogeneity, technical variability, and background biological noise continue to limit analytical performance, particularly in early-stage disease. Current evidence further suggests that no single biomarker consistently provides sufficient sensitivity and specificity for reliable early BC detection. Conclusions: LB represents a promising strategy for non-invasive early BC detection. Future clinical implementation will likely depend on integrated multi-analyte approaches that combine complementary genomic, transcriptomic, proteomic, and cellular information, supported by multi-omics technologies and artificial intelligence-based analytical frameworks. Full article

(This article belongs to the Special Issue Recent Advances in Liquid Biopsy Biomarkers of Cancer)

► Show Figures

Figure 1

39 pages, 612 KB

Open AccessReview

Muscle–Tumor Crosstalk in Exercise Oncology: Exercise-Induced Myokines and Cancer Cachexia

by Amirhossein Ahmadi Hekmatikar, Francesco Bettariga, Álvaro López Llorente, Diego Fernández-Lázaro, Katsuhiko Suzuki and D. Maryama Awang Daud

Cancers 2026, 18(14), 2343; https://doi.org/10.3390/cancers18142343 - 20 Jul 2026

Viewed by 703

Abstract

Exercise-induced myokines, such as IL-6, irisin, and myostatin, play crucial roles in mediating systemic adaptations and modulating tumor progression. This narrative review synthesizes evidence on how regular moderate-intensity exercise affects the myokine network within the tumor microenvironment (TME) of solid tumors. Results from [...] Read more.

Exercise-induced myokines, such as IL-6, irisin, and myostatin, play crucial roles in mediating systemic adaptations and modulating tumor progression. This narrative review synthesizes evidence on how regular moderate-intensity exercise affects the myokine network within the tumor microenvironment (TME) of solid tumors. Results from the 86 included studies indicate that structured training (aerobic: 45–65% VO₂ max; resistance: 45–70% 1RM) enhances the expression of beneficial myokines that support immune surveillance, reduce inflammation, and improve muscle–tumor cross-talk. IL-6 demonstrates a dual modulatory effect on inflammation and immunity; irisin contributes to tumor apoptosis, while myostatin downregulation supports muscle integrity and metabolic balance. Evidence suggests that exercise-induced alterations in these factors may influence tumor angiogenesis and immune infiltration, offering potential therapeutic implications. Overall, tailored exercise regimens represent a promising non-pharmacological strategy to optimize myokine signaling in cancer management. Further human studies are needed to confirm these mechanistic effects and define optimal exercise protocols. While existing data suggest that structured exercise may beneficially modulate myokine profiles and thereby influence tumor biology, these conclusions are based on limited qualitative evidence rather than quantitative synthesis. Further well-controlled clinical studies are required to confirm causality and define optimal exercise prescriptions for oncology settings. Full article

(This article belongs to the Special Issue Exercise and Cancer Treatment: The Clinical Application of Exercise Oncology)

28 pages, 1370 KB

Open AccessReview

Immunotherapy and Relevant Antibody–Drug Conjugates in Gynecologic Oncology: Recent Advances, Ongoing Challenges, and Future Directions

by Ting-Tai Yen, Tina Yi-Jin Hsieh and Eugene P. Toy

Cancers 2026, 18(14), 2342; https://doi.org/10.3390/cancers18142342 - 20 Jul 2026

Viewed by 709

Abstract

Immune checkpoint inhibitors and antibody–drug conjugates have rapidly expanded treatment options for gynecologic malignancies, although the magnitude of benefit varies substantially across tumor types and biomarker-defined populations. This narrative review summarizes the biologic rationale, predictive biomarkers, pivotal clinical trials, regulatory approvals, guideline-supported strategies, [...] Read more.

Immune checkpoint inhibitors and antibody–drug conjugates have rapidly expanded treatment options for gynecologic malignancies, although the magnitude of benefit varies substantially across tumor types and biomarker-defined populations. This narrative review summarizes the biologic rationale, predictive biomarkers, pivotal clinical trials, regulatory approvals, guideline-supported strategies, and emerging directions for immune checkpoint blockade and antibody–drug conjugates in endometrial, cervical, and ovarian cancers. In endometrial cancer, molecular classification and mismatch repair status have transformed treatment selection, with PD-1 or PD-L1 blockade now integrated into first-line chemoimmunotherapy and recurrent disease management. HER2-directed and TROP-2-directed antibody–drug conjugates are also emerging as biomarker-directed strategies. In cervical cancer, human papillomavirus-driven tumor biology, PD-L1 expression, and tissue factor expression support the use of checkpoint inhibitors, antibody–drug conjugates, and therapeutic vaccine approaches across locally advanced and recurrent or metastatic settings. In ovarian cancer, single-agent checkpoint blockade has shown limited activity in unselected populations, but recent advances include biomarker-selected chemoimmunotherapy in platinum-resistant disease and clinically meaningful activity of folate receptor alpha-directed and HER2-directed antibody–drug conjugates. Across gynecologic cancers, key challenges include refining predictive biomarkers, optimizing sequencing after prior immunotherapy exposure, managing overlapping toxicities, and designing trials that enrich for biologically responsive subgroups. Future progress will depend on integrating molecular classification, immune contexture, ADC target expression, and patient-specific clinical factors into treatment selection. Full article

(This article belongs to the Special Issue Immune Biomarkers and Checkpoint Inhibitors: Advancing Immunotherapy in Gynecologic Cancers)

► Show Figures

Figure 1

16 pages, 16266 KB

Open AccessArticle

Epidemiological Trends, Inter-Cancer Correlations, and Incidence Projections for 61 Cancer Types in Korea, 1999–2028: A Nationwide Population-Based Study

by Hyeran Jung and Minsun Jung

Cancers 2026, 18(14), 2341; https://doi.org/10.3390/cancers18142341 - 20 Jul 2026

Viewed by 412

Abstract

Background/Objectives: Korea has undergone rapid epidemiological transitions in cancer incidence over the past two decades. Using a 25-year nationwide dataset (1999–2023), we characterize long-term trends for 61 cancer types, examine inter-cancer correlations, and forecast incidence to 2028. Methods: Annual incidence counts, crude rates, [...] Read more.

Background/Objectives: Korea has undergone rapid epidemiological transitions in cancer incidence over the past two decades. Using a 25-year nationwide dataset (1999–2023), we characterize long-term trends for 61 cancer types, examine inter-cancer correlations, and forecast incidence to 2028. Methods: Annual incidence counts, crude rates, and age-standardized incidence rates (ASIRs) stratified by sex were obtained from the Korea Central Cancer Registry (KCCR) via the Korean Statistical Information Service (KOSIS). Annual percent change (APC) was estimated using log-linear regression. Pearson correlation coefficients were computed among cancer-specific ASIRs, with false-discovery-rate (FDR) correction for multiple comparisons. Multiple and hierarchical regression evaluated the statistical association of individual cancer types with the overall cancer rate, and variance inflation factors (VIFs) were used to quantify multicollinearity. Time series forecasting used damped Holt–Winters exponential smoothing; forecast accuracy was assessed with rolling-origin cross-validation (RMSE, MAE, MAPE) and benchmarked against ARIMA. A sensitivity analysis excluding the pandemic years (2020–2021) tested the robustness of trend estimates. Five-year prevalence data (2007–2023) were analyzed from the KCCR prevalence module. Results: Total cancer incidence increased from 101,854 in 1999 to 288,613 in 2023, a 183% increase. The overall ASIR rose from 402.7 to 522.9 per 100,000 (2020 standard population). The three fastest-growing cancers were thyroid (APC +7.56%, p < 0.001), prostate (+6.98%, p < 0.001), and breast (+5.03%, p < 0.001). Stomach (APC −2.20%) and liver (−2.90%) cancers showed significant declines. Hierarchical regression showed that adding thyroid, breast, and prostate to lung and stomach increased explained variance from R² = 0.449 to 0.997; however, high VIF values (up to ~263) indicate substantial multicollinearity and compositional dependence, so these coefficients should not be read as independent causal contributions. Holt–Winters and ARIMA produced comparable accuracy (mean MAPE 4.6% vs. 4.7%). The five-year cancer prevalence pool reached 1,035,107 in 2023. Forecasting projects a total incidence of approximately 319,000 by 2028. Conclusions: Korean cancer epidemiology is undergoing a transition from infection-related cancers toward hormone-sensitive and screening-detectable malignancies. These findings support strategic resource allocation for high-growth cancers while maintaining vigilance over rising pancreatic and other emerging cancers. Full article

(This article belongs to the Special Issue Advances in Cancer Data and Statistics: 2nd Edition)

► Show Figures

Figure 1

11 pages, 632 KB

Open AccessArticle

Evaluation of Longitudinal CD40 and CD40L Changes During Adjuvant Breast Cancer Therapy and Their Association with Left Ventricular Dysfunction

by Georgia Efthymiou, Maria Anastasiou, Evangelos Oikonomou, Panagiotis Theofilis, Hector Katifelis, Elias Giallafos, Maria Gazouli, Anastasia Kotanidou and Gerasimos Siasos

Cancers 2026, 18(14), 2340; https://doi.org/10.3390/cancers18142340 - 20 Jul 2026

Viewed by 420

Abstract

Background: Left ventricular (LV) dysfunction is a clinically important complication of anthracycline- and trastuzumab-based treatment in breast cancer. Inflammatory pathways may contribute to cancer therapy-related cardiac dysfunction, and the CD40/CD40 ligand (CD40L) axis has been implicated in vascular inflammation and myocardial injury. [...] Read more.

Background: Left ventricular (LV) dysfunction is a clinically important complication of anthracycline- and trastuzumab-based treatment in breast cancer. Inflammatory pathways may contribute to cancer therapy-related cardiac dysfunction, and the CD40/CD40 ligand (CD40L) axis has been implicated in vascular inflammation and myocardial injury. This study assessed longitudinal changes in CD40 and CD40L during adjuvant treatment and their association with LV dysfunction. Methods: Twenty-eight women with operable breast cancer receiving adjuvant anthracycline-based chemotherapy with or without trastuzumab were prospectively evaluated. Blood samples were collected at baseline, 6 months, and treatment completion at 15 months to measure CD40 and CD40L. Cardiac function was assessed by transthoracic echocardiography, including left ventricular ejection fraction and global longitudinal strain, at baseline and every 3 months. Repeated-measures analysis of variance examined temporal biomarker changes and interactions with LV dysfunction. Results: Participants had a mean age of 52.6 ± 10.7 years and a mean BMI of 25.8 ± 4.8 kg/m²; 64% were postmenopausal, 76% had HER2-positive disease, and 79.3% received radiotherapy and trastuzumab. During follow-up, 15 patients (53.6%) developed LV dysfunction. CD40 levels remained stable overall (p = 0.31), whereas CD40L increased significantly over time (p < 0.001). Baseline CD40 did not differ by LV dysfunction status (p = 0.79). However, CD40 showed a significant time-by-LV dysfunction interaction (p = 0.022), increasing late in patients with LV dysfunction and declining in those without it. CD40L showed no such interaction (p = 0.85). Conclusions: In this small exploratory cohort, CD40 demonstrated differential longitudinal patterns according to subsequent LV dysfunction, whereas CD40L increased over time without a clear association with LV dysfunction. These findings should be interpreted as hypothesis-generating and require validation in larger prospective cohorts. Full article

(This article belongs to the Special Issue Precision Prediction of Cardiotoxicity: Imaging, Biomarkers, Genetics, Risk Models, and Digital Innovation in Cardio-Oncology)

► Show Figures

Figure 1

20 pages, 3083 KB

Open AccessArticle

Identification of von Willebrand Factor-Enriched Small Extracellular Vesicles as a Blood-Based Biomarker for the Detection of Head and Neck Squamous Cell Carcinoma

by Yue Su, Kekoolani S. Visan, Sunyoung Ham, Xuanxuan Li, Su-Ho Park, Cherrie W. K. Ng, Judy Wai Ping Yam, Jason Y. K. Chan and Andreas Möller

Cancers 2026, 18(14), 2339; https://doi.org/10.3390/cancers18142339 - 20 Jul 2026

Viewed by 496

Abstract

Background: Head and neck squamous cell carcinoma (HNSCC) remains a major global health challenge due to the lack of effective and non-invasive diagnostic tools, often resulting in late-stage detection of cancer. Small extracellular vesicles (sEVs) have emerged as promising biomarkers for early [...] Read more.

Background: Head and neck squamous cell carcinoma (HNSCC) remains a major global health challenge due to the lack of effective and non-invasive diagnostic tools, often resulting in late-stage detection of cancer. Small extracellular vesicles (sEVs) have emerged as promising biomarkers for early cancer detection and disease monitoring due to their omnipresence and stability in bodily fluids, such as blood plasma. In addition, cancer-derived sEVs specifically carry cargo reflective of oncogene-derived molecular alterations. In summary, these characteristics position sEVs as a potential platform for non-invasive testing of HNSCC. Methods: Plasma-derived sEVs from HNSCC patients (n = 71) and benign subjects (n = 25) were isolated using size exclusion chromatography. Proteomic profiling via liquid chromatography-tandem mass spectrometry identified potential candidate biomarkers, followed by ELISA validation. Results: Proteomic analyses revealed a significant enrichment of multiple proteins in HNSCC-derived sEVs compared to sEVs derived from non-cancer individuals. The von Willebrand factor (vWF) was significantly higher in HNSCC patient-derived sEVs compared to those derived from benign individuals. A validation cohort confirmed that sEV-associated vWF (sEV-vWF) effectively distinguished HNSCC patients from benign subjects, demonstrating strong diagnostic performance, specifically in laryngeal HNSCC (AUC = 0.82) and oropharyngeal HNSCC (AUC = 0.96) patient cohorts. Moreover, postoperative reductions and recurrence-associated increases in sEV-vWF levels corresponded with clinical outcomes, indicating its potential as a dynamic disease indicator. Conclusions: These findings highlight sEV-vWF as a novel and non-invasive biomarker with potential applications in early detection and real-time monitoring of HNSCC, supporting advancement toward precision liquid biopsy strategies in head and neck oncology. Full article

(This article belongs to the Topic Biomarker Development and Application, 2nd Edition)

► Show Figures

Graphical abstract

3 pages, 151 KB

Open AccessCorrection

Correction: Piotrzkowska-Wróblewska, H. The Role of Quantitative Ultrasound in Monitoring Neoadjuvant Chemotherapy in Breast Cancer: A Narrative Review. Cancers 2025, 17, 3676

by Hanna Piotrzkowska-Wróblewska

Cancers 2026, 18(14), 2338; https://doi.org/10.3390/cancers18142338 - 20 Jul 2026

Viewed by 270

Abstract

Error in References [...] Full article

(This article belongs to the Section Cancer Therapy)

17 pages, 2270 KB

Open AccessArticle

Hippo–YAP Pathway Dysregulation and Prognostic Implications in HPV-Negative Oropharyngeal Carcinomas

by Ernesto Martín-Guillermo, Israel Rivera-García, Ana Álvarez-Alonso, Carlota Guizán-Alonso, Alejandra García-Torre, Daniela Corte-Torres, Corina Lorz, Juana M. García-Pedrero and Juan P. Rodrigo

Cancers 2026, 18(14), 2337; https://doi.org/10.3390/cancers18142337 - 20 Jul 2026

Viewed by 394

Abstract

Background: Human papillomavirus (HPV)-unrelated oropharyngeal squamous cell carcinoma (OPSCC) is a clinically aggressive disease characterized by poor outcomes and limited prognostic biomarkers. The Hippo–YAP pathway has emerged as a key regulator of tumorigenesis in epithelial cancers, although its role in OPSCC remains incompletely [...] Read more.

Background: Human papillomavirus (HPV)-unrelated oropharyngeal squamous cell carcinoma (OPSCC) is a clinically aggressive disease characterized by poor outcomes and limited prognostic biomarkers. The Hippo–YAP pathway has emerged as a key regulator of tumorigenesis in epithelial cancers, although its role in OPSCC remains incompletely defined. Methods: We conducted a retrospective study including 215 patients with HPV-negative OPSCC treated surgically with curative intent. Tissue microarrays were constructed, and immunohistochemical analysis of YAP1 and TAZ expression was performed. Associations with clinicopathological variables, disease-free survival (DFS) and disease-specific survival (DSS) were assessed using univariable and multivariable analyses. Results: Nuclear and cytoplasmic YAP1 expression were detected in 53% and 85.6% of tumors, respectively. Both nuclear and cytoplasmic YAP1 expression were significantly associated with reduced DFS (p = 0.019 and p = 0.004, respectively) and DSS (p = 0.01 and p = 0.006, respectively). Multivariable analysis identified nodal involvement (HR = 1.64, p = 0.023) and nuclear YAP1 expression (HR = 1.65, p = 0.004) as independent predictors of DFS, and advanced tumor stage (HR = 1.57, p = 0.038), nodal involvement (HR = 2.34, p < 0.001), and nuclear YAP1 expression (HR = 1.78, p = 0.002) as independent predictors of DSS. In contrast, nuclear TAZ expression was observed at a lower frequency (14.5%) and showed no significant association with clinical parameters or survival outcomes. Conclusions: YAP1 expression, particularly its nuclear activated form, emerges as an independent poor prognostic factor in HPV-negative OPSCC, whereas nuclear TAZ expression was rather infrequent and showed no clinical relevance. These findings highlight the importance of Hippo pathway dysregulation in this tumor subtype and suggest the potential of YAP1 as both a prognostic biomarker and a therapeutic target. Full article

(This article belongs to the Special Issue Molecular and Genetic Biomarkers in Oral Squamous Cell Carcinoma)

► Show Figures

Figure 1

Journal Menu

Journal Browser

Cancers, Volume 18, Issue 14 (July-2 2026) – 185 articles

Further Information

Guidelines

MDPI Initiatives

Follow MDPI