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Volume 17
Issue 5
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Cancers, Volume 17, Issue 5 (March-1 2025) – 197 articles

Cover Story (view full-size image): Immune checkpoint inhibitors have revolutionized the treatment of solid cancers. However, only a minority of patients respond to therapy, even if they are selected on the basis of FDA-approved biomarkers. In this study, we developed a machine learning model that integrates genomic and transcriptomic biomarkers to more accurately predict the outcome of anti-PD1 treatment in melanoma. We employed LASSO regression with 49 features derived from both tumor–normal WES and bulk RNA-Seq data. Our model achieved an ROC AUC of 0.7 and 0.64 in the training and test datasets, respectively, outperforming the current gold-standard TMB. A subsequent SHAP analysis revealed the most predictive biomarkers, which included activated response pathways, tumor mutational burden, and immune cell infiltration. View this paper
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13 pages, 1581 KiB  
Article
Endoscopic Ultrasound-Guided Anastomoses of the Gastrointestinal Tract: A Multicentric Experience
by Giacomo Emanuele Maria Rizzo, Chiara Coluccio, Edoardo Forti, Alessandro Fugazza, Cecilia Binda, Giuseppe Vanella, Francesco Maria Di Matteo, Stefano Francesco Crinò, Andrea Lisotti, Marcello Fabio Maida, Giovanni Aragona, Aurelio Mauro, Alessandro Repici, Andrea Anderloni, Carlo Fabbri, Ilaria Tarantino and on behalf of the I-EUS Group
Cancers 2025, 17(5), 910; https://doi.org/10.3390/cancers17050910 - 6 Mar 2025
Cited by 1 | Viewed by 703
Abstract
This multicenter retrospective study included patients undergoing EUS-guided GI anastomoses from 2016 to 2023. Indications for EUS-guided anastomosis were GOO, ALS or patients with altered anatomy needing endoscopic interventions. The primary outcome was technical success, while secondary outcomes included clinical success, safety, lumen-apposing [...] Read more.
This multicenter retrospective study included patients undergoing EUS-guided GI anastomoses from 2016 to 2023. Indications for EUS-guided anastomosis were GOO, ALS or patients with altered anatomy needing endoscopic interventions. The primary outcome was technical success, while secondary outcomes included clinical success, safety, lumen-apposing metal stent (LAMS) patency, and the need for reinterventions. A total of 216 patients (mean age 64.5 [±13.94] years; 49.1% males) were included. In total, 149 cases (69%) were GOO, 44 (20.4%) cases were bilioenteric anastomotic strictures or lithiasis in altered anatomy, 14 cases (6.5%) were ALS, and 9 patients (4.2%) were for ERCP in altered anatomy after EUS-GG. Overall, EUS-GE was performed in 181 patients (83.8%), EUS-JJ in 44 cases (20.4%), and EUS-GG in 10 (4.6%). Technical success was 94.91%, and clinical success was 93.66%. The adverse event (AE) rate was 11.1%. The reintervention rate was 7.69%. The median follow-up was 85 days. In conclusions, EUS-guided GI anastomoses are technically feasible and safe in both malignant and benign diseases. Full article
(This article belongs to the Special Issue Gastrointestinal and Its Associated Malignancies: Diagnosis, Targets and Therapies)
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11 pages, 1143 KiB  
Review
Bioactive Compounds Targeting Dihydroceramide and Their Therapeutic Potential in Cancer Treatment
by Yumi Jang
Cancers 2025, 17(5), 909; https://doi.org/10.3390/cancers17050909 - 6 Mar 2025
Viewed by 509
Abstract
Dihydroceramide (dhCer) was previously considered an inactive precursor of ceramide, a well-known sphingoid base involved in regulating apoptosis and cell death. However, recent studies have shown that dhCer plays a crucial role in various important cellular responses. In this review, we summarize the [...] Read more.
Dihydroceramide (dhCer) was previously considered an inactive precursor of ceramide, a well-known sphingoid base involved in regulating apoptosis and cell death. However, recent studies have shown that dhCer plays a crucial role in various important cellular responses. In this review, we summarize the latest findings on the biological functions of dhCer and the enzymes involved in its biosynthesis. We specifically focus on the emerging evidence implicating dhCer in cancer, as well as its role in regulating key processes such as cell cycle arrest, autophagy, apoptosis, ER stress, and oxidative stress. Furthermore, we discuss bioactive compounds that can modulate dhCer levels in cancer cells, highlighting their potential therapeutic applications in counteracting cancer progression. This review emphasizes the growing recognition of dhCer as a bioactive sphingolipid metabolite with significant potential for cancer therapy. Full article
(This article belongs to the Section Cancer Therapy)
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16 pages, 1061 KiB  
Article
Harnessing Baseline Radiomic Features in Early-Stage NSCLC: What Role in Clinical Outcome Modeling for SBRT Candidates?
by Stefania Volpe, Maria Giulia Vincini, Mattia Zaffaroni, Aurora Gaeta, Sara Raimondi, Gaia Piperno, Jessica Franzetti, Francesca Colombo, Anna Maria Camarda, Federico Mastroleo, Francesca Botta, Lorenzo Spaggiari, Sara Gandini, Matthias Guckenberger, Roberto Orecchia, Monica Casiraghi and Barbara Alicja Jereczek-Fossa
Cancers 2025, 17(5), 908; https://doi.org/10.3390/cancers17050908 - 6 Mar 2025
Viewed by 621
Abstract
Aim: An Early-Stage Non-Small Cell Lung Cancer (ES-NSCLC) patient candidate for stereotactic body radiotherapy (SBRT) may start their treatment without a histopathological assessment, due to relevant comorbidities. The aim of this study is twofold: (i) build prognostic models to test the association between [...] Read more.
Aim: An Early-Stage Non-Small Cell Lung Cancer (ES-NSCLC) patient candidate for stereotactic body radiotherapy (SBRT) may start their treatment without a histopathological assessment, due to relevant comorbidities. The aim of this study is twofold: (i) build prognostic models to test the association between CT-derived radiomic features (RFs) and the outcomes of interest (overall survival (OS), progression-free survival (PFS) and loco-regional progression-free survival (LRPFS)); (ii) quantify whether the combination of clinical and radiomic descriptors yields better prediction than clinical descriptors alone in prognostic modeling for ES-NSCLC patients treated with SBRT. Methods: Simulation CT scans of ES-NSCLC patients treated with curative-intent SBRT at the European Institute of Oncology (IEO), Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Milan, Italy between 2013 and 2023 were retrospectively retrieved. PyRadiomics v3.0.1 was used for image preprocessing and subsequent RFs extraction and selection. A radiomic score was calculated for each patient, and three prognostic models (clinical model, radiomic model, clinical-radiomic model) for each survival endpoint were built. Relative performances were compared using the C-index. All analyses were considered statistically significant if p < 0.05. The statistical analyses were performed using R Software version 4.1. Results: A total of 100 patients met the inclusion criteria. Median age at diagnosis was 76 (IQR: 70–82) years, with a median Charlson Comorbidity Index (CCI) of 7 (IQR: 6–8). At the last available follow-up, 76 patients were free of disease, 17 were alive with disease, and 7 were deceased. Considering relapses, progression of any kind was diagnosed in 31 cases. Regarding model performances, the radiomic score allowed for excellent prognostic discrimination for all the considered endpoints. Of note, the use of RFs alone proved to be more informative than clinical characteristics alone for the prediction of both OS and LRPFS, but not for PFS, for which the individual predictive performances slightly favored the clinical model. Conclusion: The use of RFs for outcome prediction in this clinical setting is promising, and results seem to be rather consistent across studies, despite some methodological differences that should be acknowledged. Further studies are being planned in our group to externally validate these findings, and to better determine the potential of RFs as non-invasive and reproducible biomarkers in ES-NSCLC. Full article
(This article belongs to the Special Issue Advances in Thoracic Oncology: A Multi-disciplinary Approach to Lung Cancer)
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25 pages, 1453 KiB  
Review
Molecular Mechanisms in the Transformation from Indolent to Aggressive B Cell Malignancies
by Nawar Maher, Samir Mouhssine, Bassam Francis Matti, Alaa Fadhil Alwan and Gianluca Gaidano
Cancers 2025, 17(5), 907; https://doi.org/10.3390/cancers17050907 - 6 Mar 2025
Viewed by 664
Abstract
Histological transformation (HT) into aggressive lymphoma is a turning point in a significant fraction of patients affected by indolent lymphoproliferative neoplasms, namely, chronic lymphocytic leukemia (CLL), follicular lymphoma (FL), marginal zone lymphomas (MZLs), and lymphoplasmacytic lymphoma (LPL) [...] Full article
(This article belongs to the Special Issue Oncogenesis of Lymphoma)
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43 pages, 2417 KiB  
Review
Targeting Immune Checkpoint Inhibitors for Non-Small-Cell Lung Cancer: Beyond PD-1/PD-L1 Monoclonal Antibodies
by Nicolas Roussot, Courèche Kaderbhai and François Ghiringhelli
Cancers 2025, 17(5), 906; https://doi.org/10.3390/cancers17050906 - 6 Mar 2025
Cited by 1 | Viewed by 1221
Abstract
Non-small-cell lung cancer (NSCLC) remains a leading cause of cancer-related mortality worldwide. Immunotherapy targeting the PD-1/PD-L1 axis has revolutionized treatment, providing durable responses in a subset of patients. However, with fewer than 50% of patients achieving significant benefits, there is a critical need [...] Read more.
Non-small-cell lung cancer (NSCLC) remains a leading cause of cancer-related mortality worldwide. Immunotherapy targeting the PD-1/PD-L1 axis has revolutionized treatment, providing durable responses in a subset of patients. However, with fewer than 50% of patients achieving significant benefits, there is a critical need to expand therapeutic strategies. This review explores emerging targets in immune checkpoint inhibition beyond PD-1/PD-L1, including CTLA-4, TIGIT, LAG-3, TIM-3, NKG2A, and CD39/CD73. We highlight the biological basis of CD8 T cell exhaustion in shaping the antitumor immune response. Novel therapeutic approaches targeting additional inhibitory receptors (IR) are discussed, with a focus on their distinct mechanisms of action and combinatory potential with existing therapies. Despite significant advancements, challenges remain in overcoming resistance mechanisms and optimizing patient selection. This review underscores the importance of dual checkpoint blockade and innovative bispecific antibody engineering to maximize therapeutic outcomes for NSCLC patients. Full article
(This article belongs to the Special Issue Lung Cancer: From Mechanisms of Action and Risk Factors in Disease Onset to Management)
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13 pages, 4445 KiB  
Article
Granulocyte-Macrophage Colony Stimulating Factor Receptor Contributes to Plexiform Neurofibroma Initiation
by Jay Pundavela, Ashley Hall, Samantha Anne Dinglasan, Kwangmin Choi, Tilat A. Rizvi, Bruce C. Trapnell, Jianqiang Wu and Nancy Ratner
Cancers 2025, 17(5), 905; https://doi.org/10.3390/cancers17050905 - 6 Mar 2025
Viewed by 500
Abstract
Plexiform neurofibroma (PNF) is an immune cell-rich peripheral nerve sheath tumor that develops primarily in individuals with Neurofibromatosis Type 1 (NF1). Granulocyte-macrophage colony stimulating factor receptor-β (GM-CSFR-βc) is a shared component of receptors for the cytokines GM-CSF, IL-3, and IL-5, ligands [...] Read more.
Plexiform neurofibroma (PNF) is an immune cell-rich peripheral nerve sheath tumor that develops primarily in individuals with Neurofibromatosis Type 1 (NF1). Granulocyte-macrophage colony stimulating factor receptor-β (GM-CSFR-βc) is a shared component of receptors for the cytokines GM-CSF, IL-3, and IL-5, ligands with immunomodulatory and tumor promoting roles. In the present study, we use genetically engineered mouse model of neurofibroma. We identified the expression of GM-CSFR-βc and GM-CSFR-α on PNF cells and on macrophages and dendritic cells in the PNF, using the Nf1f/f; DhhCre mouse model of neurofibroma formation. Genetic deletion of GM-CSFR-βc in this model reduced the number of PNFs, which was associated with decreased numbers of tumor-associated Iba1+ macrophages and CD11c+ dendritic cells (DC), while loss of GM-CSFR-α had no effect. Deletion of GM-CSFR-α or GM-CSFR-βc did not improve mouse survival or the structure of Remak bundles in peripheral nerves. Proteome analysis of tumor lysates showed altered levels of numerous cytokines after receptor loss, suggesting that the compensatory effects of other cyto/chemokines maintain a proinflammatory environment promoting neurofibroma. Thus, GM-CSFR-βc signaling contributes modestly to neurofibroma formation, apparently independently of its ligand GM-CSF. Full article
(This article belongs to the Special Issue Neurofibromatosis Type 1 (NF1) Related Tumors)
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19 pages, 2552 KiB  
Systematic Review
Evaluating the Impact of Hyperthermic Intraperitoneal Chemotherapy (HIPEC) on Interval and Secondary Debulking in Ovarian Cancer: A Systematic Review
by Dimitrios Tsolakidis, Dimitrios Kyziridis, Theodoros Panoskaltsis, Apostolos Kalakonas, Vasileios Theodoulidis, Kimon Chatzistamatiou, Dimitrios Zouzoulas and Antonios-Apostolos Tentes
Cancers 2025, 17(5), 904; https://doi.org/10.3390/cancers17050904 - 6 Mar 2025
Viewed by 572
Abstract
Background/Objectives: Hyperthermic intraperitoneal chemotherapy (HIPEC) was revealed as a promising adjunct to cytoreductive surgery (CRS) in the treatment of advanced epithelial ovarian cancer (EOC). This review evaluated the impact HIPEC had on survival outcomes, recurrence patterns and safety in patients that underwent HIPEC [...] Read more.
Background/Objectives: Hyperthermic intraperitoneal chemotherapy (HIPEC) was revealed as a promising adjunct to cytoreductive surgery (CRS) in the treatment of advanced epithelial ovarian cancer (EOC). This review evaluated the impact HIPEC had on survival outcomes, recurrence patterns and safety in patients that underwent HIPEC in conjunction with interval and secondary CRS for advanced and recurrent ovarian cancer. Methods: A thorough search was conducted using PubMed, Scopus, Cochrane Library, and Google Scholar to identify relevant studies published until 1 January 2025. The studies were assessed for survival outcomes, recurrence patterns, safety, and quality of life. The risk of bias was evaluated using the ROB 2 tool for randomized and ROBINS-I for non-randomized articles. The results are presented narratively, highlighting key findings, comparing results and assessing inconsistencies and limitations. Results: HIPEC demonstrated significant improvements in progression-free survival (PFS) and overall survival (OS), particularly in cases with optimal cytoreduction (CC-0/CC-1). The recurrence patterns showed a reduction in peritoneal dissemination with HIPEC, although extraperitoneal recurrences were reported in some cases. Most studies reported comparable morbidity rates between HIPEC and non-HIPEC groups, with acceptable safety profiles. The variability in the HIPEC protocols and the limited quality-of-life and cost-effectiveness data were noteworthy limitations. Conclusions: HIPEC, when performed during interval or secondary CRS, offers survival benefits and can modify recurrence patterns in advanced EOC, although challenges related to protocol standardization, patient selection, and long-term outcomes persist. Future research should focus on multicenter trials with uniform protocols, long follow-up periods and patient-centered outcomes to further validate the role of HIPEC in clinical practice. Full article
(This article belongs to the Special Issue Advances in Ovarian Cancer Research and Treatment: 2nd Edition)
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27 pages, 10658 KiB  
Article
QSAR-Based Drug Repurposing and RNA-Seq Metabolic Networks Highlight Treatment Opportunities for Hepatocellular Carcinoma Through Pyrimidine Starvation
by Nicholas Dale D. Talubo, Emery Wayne B. Dela Cruz, Peter Matthew Paul T. Fowler, Po-Wei Tsai and Lemmuel L. Tayo
Cancers 2025, 17(5), 903; https://doi.org/10.3390/cancers17050903 - 6 Mar 2025
Viewed by 627
Abstract
Background/Objectives: The molecular heterogeneity and metabolic flexibility of Hepatocellular Carcinoma (HCC) pose significant challenges to the efficacy of systemic therapy for advanced cases. Early screening difficulties often delay diagnosis, leading to more advanced stages at presentation. Combined with the inconsistent responses to [...] Read more.
Background/Objectives: The molecular heterogeneity and metabolic flexibility of Hepatocellular Carcinoma (HCC) pose significant challenges to the efficacy of systemic therapy for advanced cases. Early screening difficulties often delay diagnosis, leading to more advanced stages at presentation. Combined with the inconsistent responses to current systemic therapies, HCC continues to have one of the highest mortality rates among cancers. Thus, this paper seeks to contribute to the development of systemic therapy options through the consideration of HCC’s metabolic vulnerabilities and lay the groundwork for future in vitro studies. Methods: Transcriptomic data were used to calculate single and double knockout options for HCC using genetic Minimal Cut Sets. Furthermore, using QSAR modeling, drug repositioning opportunities were assessed to inhibit the selected genes. Results: Two single knockout options that were also annotated as essential pairs were found within the pyrimidine metabolism pathway of HCC, wherein the knockout of either DHODH or TYMS is potentially disruptive to proliferation. The result of the flux balance analysis and gene knockout simulation indicated a significant decrease in biomass production. Three machine learning algorithms were assessed for their performance in predicting the pIC50 of a given compound for the selected genes. SVM-rbf performed the best on unseen data achieving an R2 of 0.82 for DHODH and 0.81 for TYMS. For DHODH, the drugs Oteseconazole, Tipranavir, and Lusutrombopag were identified as potential inhibitors. For TYMS, the drugs Tadalafil, Dabigatran, Baloxavir Marboxil, and Candesartan Cilexetil showed promise as inhibitors. Conclusions: Overall, this study suggests in vitro testing of the identified drugs to assess their capabilities in inducing pyrimidine starvation on HCC. Full article
(This article belongs to the Section Cancer Drug Development)
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13 pages, 1925 KiB  
Review
Recent Advances in Radical Prostatectomy: A Narrative Review of Surgical Innovations and Outcomes
by Seon Beom Jo and Jong Wook Kim
Cancers 2025, 17(5), 902; https://doi.org/10.3390/cancers17050902 - 6 Mar 2025
Viewed by 820
Abstract
Prostate cancer is one of the most commonly diagnosed malignancies worldwide and is a major cause of cancer-associated morbidity in men. Radical prostatectomy (RP) is a cornerstone of intervention for organ-confined diseases and offers a potentially curative outcome. In recent decades, RP has [...] Read more.
Prostate cancer is one of the most commonly diagnosed malignancies worldwide and is a major cause of cancer-associated morbidity in men. Radical prostatectomy (RP) is a cornerstone of intervention for organ-confined diseases and offers a potentially curative outcome. In recent decades, RP has undergone transformative changes, moving from open surgery, with significant morbidity, to minimally invasive and robot-assisted techniques. These advances have improved surgical precision, reduced blood loss, and accelerated functional recovery. Key enhancements, such as the “Veil of Aphrodite”, hood-sparing, and Retzius-sparing approaches, aim to preserve neurovascular structures vital for continence and sexual function, addressing the persistent challenge of balancing oncological control with quality-of-life outcomes. Single-port (SP) robotic platforms represent the latest frontier, offering various access routes, including extraperitoneal, transvesical, transperitoneal, and transperineal routes, to further reduce incisional morbidity. Early experiences with SP robot-assisted radical prostatectomy(RARP) suggest favorable continence rates and short hospital stays, although concerns remain regarding the technical complexity and potential margin status of the advanced disease. Comparisons across these techniques revealed broadly similar long-term oncological outcomes, underscoring the importance of patient selection, tumor staging, and surgeon expertise. Ongoing innovations in robotic systems, augmented imaging modalities, and personalized surgical planning are likely to refine prostate cancer care and enhance both survival and post-treatment quality of life. Full article
(This article belongs to the Special Issue Novel Advances in Surgery for Prostate Cancer)
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19 pages, 5897 KiB  
Article
A Peptide Derived from Nectin-4 Increases Cisplatin Cytotoxicity in Cell Lines and Cells from Ovarian Cancer Patients’ Ascites
by Kristin L. M. Boylan, Caitlin Walz, Alexandra M. Schefter and Amy P. N. Skubitz
Cancers 2025, 17(5), 901; https://doi.org/10.3390/cancers17050901 - 6 Mar 2025
Viewed by 583
Abstract
Background/Objectives: New approaches to the treatment of women with ovarian cancer are desperately needed, since most women develop resistance to chemotherapy and the 5-year survival rate remains low. The hypothesis guiding this study was that the inhibition of cell adhesion could be used [...] Read more.
Background/Objectives: New approaches to the treatment of women with ovarian cancer are desperately needed, since most women develop resistance to chemotherapy and the 5-year survival rate remains low. The hypothesis guiding this study was that the inhibition of cell adhesion could be used as a novel strategy to increase the chemosensitivity of ovarian cancer cells. Methods: The Nectin-4 peptide N4-P10 was used to inhibit the formation of cell–cell aggregates (spheroids) using cell lines and cells isolated from ovarian cancer patients’ ascites. Cell lines were pre-treated with peptide N4-P10 or control scrambled peptides and monitored for spheroid formation with live-cell imaging by digital time-lapse photography. Cells were then tested for the cytotoxicity of the chemotherapeutic agent, cisplatin. Results: Peptide N4-P10 blocked aggregation in cell lines with different levels of Nectin-4 expression and different spheroid morphologies. The cytotoxicity of cisplatin increased in cells pre-treated with peptide N4-P10. Similarly, when single cells were isolated from the ascites of ovarian cancer patients, peptide N4-P10 blocked cell aggregation and increased the cytotoxicity of cisplatin. Conclusions: These results suggest that targeting the cell–cell adhesive property of cancer cells could serve as a new approach to augment the cytotoxic effect of chemotherapy and potentially reduce disease recurrence in ovarian cancer patients. Full article
(This article belongs to the Section Molecular Cancer Biology)
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13 pages, 234 KiB  
Review
Revisiting the Role of Day 14 Bone Marrow Biopsy in Acute Myeloid Leukemia
by Omer Jamy, Garrett Bourne, Todd William Mudd, Haley Thigpen and Ravi Bhatia
Cancers 2025, 17(5), 900; https://doi.org/10.3390/cancers17050900 - 6 Mar 2025
Viewed by 610
Abstract
In recent years, the practice of routinely obtaining day 14 bone marrow biopsies during AML intensive induction therapy has been scrutinized. While current guidelines recommend obtaining mid-induction biopsies to gauge early response to treatment and guide potential changes in future management, concerns have [...] Read more.
In recent years, the practice of routinely obtaining day 14 bone marrow biopsies during AML intensive induction therapy has been scrutinized. While current guidelines recommend obtaining mid-induction biopsies to gauge early response to treatment and guide potential changes in future management, concerns have been raised that these biopsies may not be as prognostically accurate as hoped and subsequently may result in additional and unwarranted chemotherapy toxicity in select patients. In this review, our goal is to summarize the most recent evidence surrounding day 14 bone marrow biopsies that have been published and clarify the utility of this currently recommended practice. Here, we review major developments in mid-induction biopsy in AML, along with ongoing and future planned studies in this area, outlining the limitations of available data and our future goals. Full article
(This article belongs to the Special Issue New Insights of Hematology in Cancer)
20 pages, 1062 KiB  
Review
The Emerging Role of Nanoparticles Combined with Either Radiotherapy or Hyperthermia in Head and Neck Cancer: A Current Review
by Elena Vlastou, Andromachi Kougioumtzopoulou, Kalliopi Platoni, Ioannis Georgakopoulos, Nefeli Lagopati, Vasileios Kouloulias and Anna Zygogianni
Cancers 2025, 17(5), 899; https://doi.org/10.3390/cancers17050899 - 6 Mar 2025
Viewed by 715
Abstract
Head and neck cancer (HNC) includes various malignancies and represents the seventh most common cancer worldwide. The early diagnosis of HNC results in a 70–90% five-year survival rate, which declines with locally advanced stages of disease. Current care employs a multimodal strategy encompassing [...] Read more.
Head and neck cancer (HNC) includes various malignancies and represents the seventh most common cancer worldwide. The early diagnosis of HNC results in a 70–90% five-year survival rate, which declines with locally advanced stages of disease. Current care employs a multimodal strategy encompassing surgery, radiation therapy (RT), chemotherapy, and immunotherapy, while treatment options vary according to the stage, tumor features, and patient characteristics. About 75% of patients with HNC will benefit from RT, either as a primary treatment or as adjuvant therapy following surgical resection. Technological improvements in RT, such as intensity-modulated RT (IMRT) and image-guided RT (IGRT), have enhanced tumor targeting and minimized adjacent healthy tissue irradiation while also expanding RT to the recurrent or metastatic setting. Innovative therapeutic strategies for HNC integrate RT with immunotherapy, gene therapy, molecular targeted therapy, photodynamic therapy, photothermal therapy, and nanoparticles (NPs), with the objective of optimizing tumor control while reducing damage to normal tissues. NPs are emerging as possible radiosensitizers in HNC treatment, enhancing the efficacy of RT, chemotherapy, and immunotherapy. In vivo and in vitro studies on the irradiation of tumors containing gold (Au), gadolinium (Gd), and hafnium oxide (HfO2) NPs show promising results in enhancing tumor destruction and survival rates, indicating their potential for clinical application. Hyperthermia, investigated as an adjunct treatment, potentially improves outcomes when combined with RT or chemotherapy, with advancements in nanotechnology renewing interest in this approach in HNC. At present, NBTXR3 is the sole NP that is being investigated in clinical trials for the enhancement of HNC RT. Full article
(This article belongs to the Special Issue Advances in Radiation Therapy for Head and Neck Cancer)
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14 pages, 1802 KiB  
Article
Avelumab Maintenance Therapy in Advanced Urothelial Carcinoma: Implications of Timing and Treatment Sequencing
by Lisa Gonçalves, Helena Guedes, Ana Raquel Fortuna, Tânia Lemos, João Gramaça, Natacha Mourão, Gonçalo Cunha, Rita Pichel, Pedro Simões, Joana Alves Luís, Rita Freitas, Inês Dunões, Ana Sofia Spencer, Joana Marinho and Luís Costa
Cancers 2025, 17(5), 898; https://doi.org/10.3390/cancers17050898 - 6 Mar 2025
Viewed by 1046
Abstract
Background: Platinum-based chemotherapy (PBC) followed by avelumab maintenance is a treatment option for patients with advanced urothelial carcinoma (aUC) patients. However, the optimal treatment sequencing in the era of antibody–drug conjugates (ADCs) is yet to be determined. Recent studies suggest that the timing [...] Read more.
Background: Platinum-based chemotherapy (PBC) followed by avelumab maintenance is a treatment option for patients with advanced urothelial carcinoma (aUC) patients. However, the optimal treatment sequencing in the era of antibody–drug conjugates (ADCs) is yet to be determined. Recent studies suggest that the timing of immune checkpoint inhibitor (ICI) administration may impact patient outcomes, with a potential benefit from morning infusions. Methods: This retrospective study included 105 patients with aUC treated with avelumab in Portugal and intended to assess the safety and clinical outcomes (progression-free survival (PFS), overall survival (OS), and overall response rate (ORR)) and evaluate the impact of treatment timing (morning vs. afternoon) on patient outcomes. Results: The median follow-up from the start of avelumab was 17.7 months, the median PFS (mPFS) was 9.8 months (95% CI 4.9–14.7), and the median OS (mOS) was 39.5 months (95% CI 13.2–65.7). Immune-related adverse events (irAEs) were reported in 65.8% of patients, with 6.7% experiencing G3 irAEs. Among those who received a subsequent-line ADC upon disease progression (43%), the mOS from the start of avelumab was 23.1 months (95% CI 9.2–37.0). Multivariate analysis showed significant improvement in mOS with morning avelumab infusions (HR 0.35, 95% CI: 0.12–0.97, p = 0.042) and a trend towards improved mPFS (HR 0.43, 95% CI: 0.179–1.02, p = 0.055). Conclusions: This study confirms the clinical efficacy and safety of avelumab, showing improved outcomes over JAVELIN Bladder 100 and suggesting that morning infusions may offer a survival benefit in this context. Further research is needed to optimize treatment sequencing and explore the impact of infusion timing in ICI strategies. Full article
(This article belongs to the Section Cancer Therapy)
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18 pages, 4098 KiB  
Review
Human Papillomavirus-Related Cutaneous Squamous Cell Carcinoma
by Alejandra Sandoval-Clavijo, Ignasí Martí-Martí, Carla Ferrándiz-Pulido, Júlia Verdaguer-Faja, Ane Jaka and Agustí Toll
Cancers 2025, 17(5), 897; https://doi.org/10.3390/cancers17050897 - 5 Mar 2025
Viewed by 605
Abstract
The human papillomavirus (HPV) has been associated with the carcinogenesis of cutaneous squamous cell carcinoma (cSCC), especially in immunosuppressed patients. This article reviews the microbiology of HPV and its role in tissue tropism, invasion, and oncogenesis. It also describes possible HPV oncogenic ability [...] Read more.
The human papillomavirus (HPV) has been associated with the carcinogenesis of cutaneous squamous cell carcinoma (cSCC), especially in immunosuppressed patients. This article reviews the microbiology of HPV and its role in tissue tropism, invasion, and oncogenesis. It also describes possible HPV oncogenic ability due to the inactivation of the host p53 and retinoblastoma protein (pRb) by HPV oncoproteins E6 and E7, producing a suppression of cell cycle checkpoints and uncontrolled cell proliferation that may eventually result in invasive carcinoma. We will focus on β-HPV types and their role in epidermodysplasia verruciformis (EV), as well as α types and their ability to cause cutaneous and mucosal pathology. We also intend to examine the clinical characteristics of cSCC related to HPV and host immunosuppression conditions such as solid organ transplant in order to provide management guidelines for patients with cSCC associated with HPV based on available data. Other topics addressed in this article include particular locations of cSCC, such as nails; the prognosis; the recurrence; therapeutic modalities; and the role of HPV vaccines. Full article
(This article belongs to the Special Issue Human Papillomavirus (HPV) and Related Cancer)
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13 pages, 5590 KiB  
Article
Mutant KRAS and GATA6 Stratify Survival in Patients Treated with Chemotherapy for Pancreatic Adenocarcinoma: A Prospective Cohort Study
by Jung Won Chun, Dong-eun Lee, Nayoung Han, SooBeen Heo, Hyeji Kim, Mi Rim Lee, Hyeong Min Park, Sung-Sik Han, Sang-Jae Park, Tae Hyun Kim, Woo Jin Lee, Yun-Hee Kim, Sun-Young Kong and Sang Myung Woo
Cancers 2025, 17(5), 896; https://doi.org/10.3390/cancers17050896 - 5 Mar 2025
Viewed by 759
Abstract
Background: Several pancreatic adenocarcinoma (PA) biomarkers beyond the traditional carbohydrate antigen (CA)19-9 have been identified but are lacking large-scale prospective validation. This prospective cohort study evaluated the prognostic impact of potential PA biomarkers. Methods: We enrolled 238 of 288 patients with histologically proven [...] Read more.
Background: Several pancreatic adenocarcinoma (PA) biomarkers beyond the traditional carbohydrate antigen (CA)19-9 have been identified but are lacking large-scale prospective validation. This prospective cohort study evaluated the prognostic impact of potential PA biomarkers. Methods: We enrolled 238 of 288 patients with histologically proven PA. We assessed candidate biomarkers, including CA19-9, germline BRCA1/2, and ATM mutations, as well as mutant KRAS circulating tumor DNA (ctDNA) in blood samples. Additionally, we evaluated the expression of SLC29A1 (hENT1), DCK, CES2, and GATA6. We examined the association of candidate biomarkers with progression-free survival (PFS) and overall survival (OS). Results: We analyzed biomarker efficacy in 200 (median age 65 years; 55% male) of the enrolled patients who received chemotherapy. A high mutant KRAS ctDNA concentration (hazard ratio [HR]: 1.508 and 95% confidence interval [CI]: 1.052–2.161 for PFS; HR: 1.796 and 95% CI: 1.203–2.681 for OS) and high CA19-9 level (HR: 1.647 and 95% CI: 1.177–2.306 for PFS; HR: 1.803 and 95% CI: 1.248–2.605 for OS) were associated with poor prognosis. High GATA6 RNA expression was linked to longer PFS (HR: 0.336 and 95% CI: 0.195–0.582) and OS (HR: 0.304 and 95% CI: 0.165–0.560). Conclusions: Plasma mutant KRAS ctDNA concentrations and GATA6 expression could serve as significant prognostic biomarkers in patients with PA, potentially guiding therapeutic decisions and prognostication. Full article
(This article belongs to the Section Cancer Biomarkers)
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11 pages, 1888 KiB  
Article
Frozen Section Analysis in Submandibular Gland Tumors: Optimizing Intraoperative Decision-Making
by Amir Bolooki, Felix Johnson, Anna Stenzl, Zhaojun Zhu and Benedikt Gabriel Hofauer
Cancers 2025, 17(5), 895; https://doi.org/10.3390/cancers17050895 - 5 Mar 2025
Viewed by 452
Abstract
Introduction: With around 25 different salivary gland tumor entities described by the World Health Organization, the correct preoperative identification of masses as benign or malignant remains a challenge. If preoperative needle biopsy is inconclusive, frozen section analysis is a possible alternative for [...] Read more.
Introduction: With around 25 different salivary gland tumor entities described by the World Health Organization, the correct preoperative identification of masses as benign or malignant remains a challenge. If preoperative needle biopsy is inconclusive, frozen section analysis is a possible alternative for accurate histological identification. The purpose of our study was to evaluate the diagnostic effectiveness of frozen section performed for primary submandibular gland masses. Methods: In addition to acquiring epidemiological data from patients who underwent submandibular gland excision over a 20-year period, we analyzed the diagnostic effectiveness of frozen section performed for submandibular gland masses. We also examined the impact of frozen section on overall survival. Furthermore, we investigated whether there was an impact on the surgical revision rate for malignant submandibular gland masses that required additional neck dissection within the submandibular triangle. Results: Frozen section was performed for 54 submandibular gland tumors, with a specificity of 100% and a sensitivity of 81.3%. Frozen section was conducted in 12 cases of primary salivary gland malignancies, of which 9 cases were identified correctly. In three cases, the frozen section results were inconclusive. We calculated a relative risk reduction of 27% for revision surgery by performing frozen section. There was no significant association between frozen section results and overall survival. Conclusions: Frozen section demonstrates a significant reduction in the need for revision surgery. With a specificity of 100%, frozen section is especially suited to identifying benign masses. It is a valid diagnostic tool when preoperative sampling is not possible or is inconclusive. Full article
(This article belongs to the Special Issue Advances in Salivary Gland Carcinoma: 2nd Edition)
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12 pages, 5418 KiB  
Article
Model Predicting Survival in Intermediate-Stage HCC Patients Reclassified for TACE Based on the 2022 BCLC Criteria
by Jihoon Kim, Jin-Hyoung Kim, Eunbyul Ko, Jeong-Yeon Kim, Byung Soo Im, Gun Ha Kim, Hee Ho Chu, Heung-Kyu Ko, Dong Il Gwon, Ji Hoon Shin and Ibrahim Alrashidi
Cancers 2025, 17(5), 894; https://doi.org/10.3390/cancers17050894 - 5 Mar 2025
Viewed by 496
Abstract
Background/Objectives: The Barcelona Clinic Liver Cancer (BCLC) staging system for hepatocellular carcinoma (HCC) was updated in 2022 to refine patient stratification, particularly in patients with intermediate-stage (BCLC B) HCC. Although transarterial chemoembolization (TACE) remains a key treatment for these patients, there is [...] Read more.
Background/Objectives: The Barcelona Clinic Liver Cancer (BCLC) staging system for hepatocellular carcinoma (HCC) was updated in 2022 to refine patient stratification, particularly in patients with intermediate-stage (BCLC B) HCC. Although transarterial chemoembolization (TACE) remains a key treatment for these patients, there is no prognostic model for survival outcomes based on the pretreatment factors of patients who meet the updated 2022 BCLC indications for TACE. The aim of this study was to develop a pretreatment risk model predicting overall survival (OS) in patients with intermediate-stage HCC and reclassified as candidates for TACE according to the updated 2022 BCLC criteria. Methods: This retrospective study included 658 HCC patients treated with first-line TACE according to the updated BCLC 2022 guidelines. Pretreatment factors such as the Child–Pugh score, tumor burden (up-to-11 criteria), bilobar tumor involvement, and serum alpha-fetoprotein (AFP) levels were analyzed. Cox proportional hazards models were used to identify significant predictors of OS, with these factors subsequently incorporated into a risk prediction model. Results: Significant predictors of OS included Child–Pugh score ≥ 7, bilobar tumor involvement, beyond up-to-11 criteria, and AFP ≥ 400 ng/mL. A risk model was developed using these factors, stratifying patients into low-, intermediate-, and high-risk groups. The median OS in the low-, intermediate-, and high-risk groups was 53, 35, and 21 months, respectively. Conclusions: The proposed pretreatment risk prediction model may be useful for predicting OS and guiding TACE candidacy in intermediate-stage HCC patients based on the updated 2022 BCLC guidelines. Full article
(This article belongs to the Special Issue Developments in the Management of Gastrointestinal Malignancies)
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16 pages, 1799 KiB  
Article
Integrating CT Radiomics and Clinical Features to Optimize TACE Technique Decision-Making in Hepatocellular Carcinoma
by Max Masthoff, Maximilian Irle, Daniel Kaldewey, Florian Rennebaum, Haluk Morgül, Gesa Helen Pöhler, Jonel Trebicka, Moritz Wildgruber, Michael Köhler and Philipp Schindler
Cancers 2025, 17(5), 893; https://doi.org/10.3390/cancers17050893 - 5 Mar 2025
Viewed by 576
Abstract
Background/Objectives: To develop a decision framework integrating computed tomography (CT) radiomics and clinical factors to guide the selection of transarterial chemoembolization (TACE) technique for optimizing treatment response in non-resectable hepatocellular carcinoma (HCC). Methods: A retrospective analysis was performed on 151 patients [33 conventional [...] Read more.
Background/Objectives: To develop a decision framework integrating computed tomography (CT) radiomics and clinical factors to guide the selection of transarterial chemoembolization (TACE) technique for optimizing treatment response in non-resectable hepatocellular carcinoma (HCC). Methods: A retrospective analysis was performed on 151 patients [33 conventional TACE (cTACE), 69 drug-eluting bead TACE (DEB-TACE), 49 degradable starch microsphere TACE (DSM-TACE)] who underwent TACE for HCC at a single tertiary center. Pre-TACE contrast-enhanced CT images were used to extract radiomic features of the TACE-treated liver tumor volume. Patient clinical and laboratory data were combined with radiomics-derived predictors in an elastic net regularized logistic regression model to identify independent factors associated with early response at 4–6 weeks post-TACE. Predicted response probabilities under each TACE technique were compared with the actual techniques performed. Results: Elastic net modeling identified three independent predictors of response: radiomic feature “Contrast” (OR = 5.80), BCLC stage B (OR = 0.92), and viral hepatitis etiology (OR = 0.74). Interaction models indicated that the relative benefit of each TACE technique depended on the identified patient-specific predictors. Model-based recommendations differed from the actual treatment selected in 66.2% of cases, suggesting potential for improved patient–technique matching. Conclusions: Integrating CT radiomics with clinical variables may help identify the optimal TACE technique for individual HCC patients. This approach holds promise for a more personalized therapy selection and improved response rates beyond standard clinical decision-making. Full article
(This article belongs to the Special Issue Novel Approaches and Advances in Interventional Oncology)
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17 pages, 13208 KiB  
Article
Global Burden of Thyroid Cancer in Children and Adolescents, 1990–2021: Trends, Disparities, and Future Projections
by Tianyu Li, Zhen Cao, Chen Lin and Weibin Wang
Cancers 2025, 17(5), 892; https://doi.org/10.3390/cancers17050892 - 5 Mar 2025
Viewed by 780
Abstract
Background: Thyroid cancer is a rising concern in children and adolescents, with unique biological behaviors compared to adults. This study aimed to explore the epidemiological trends, pathological features, and regional disparities of thyroid cancer in this population using data from the Global Burden [...] Read more.
Background: Thyroid cancer is a rising concern in children and adolescents, with unique biological behaviors compared to adults. This study aimed to explore the epidemiological trends, pathological features, and regional disparities of thyroid cancer in this population using data from the Global Burden of Disease (GBD) 2021. Methods: Data on thyroid cancer incidence and mortality from 1990 to 2021 were extracted for individuals under 20 years old. The estimated annual percentage change (EAPC) was calculated to evaluate temporal trends. The Sociodemographic Index (SDI) was applied to assess regional variations. Future trends were projected using a Bayesian age–period–cohort model. Results: From 1990 to 2021, the global incidence of thyroid cancer in children and adolescents increased significantly, with an EAPC of 1.17%. Low-SDI regions exhibited the highest rise in incidence (EAPC: 2.19%), while high-SDI regions experienced a slight decline (EAPC: −0.69%). Mortality decreased globally (EAPC: −0.27%), with notable reductions in high- and middle-SDI regions but stable or increasing rates in low-SDI regions. Females consistently exhibited higher incidence rates across all SDI levels, while males in high-SDI regions showed higher mortality rates. Future projections suggest a steady decline in incidence and mortality rates through 2050. Conclusions: The increasing incidence and persistent mortality disparities of thyroid cancer in children and adolescents highlight the need for targeted public health interventions. Regions with low socioeconomic development require prioritized strategies to address this growing burden. These findings provide crucial insights for early diagnosis, treatment optimization, and global health policy formulation. Full article
(This article belongs to the Special Issue Evolving Understanding of the Epidemiology of Thyroid Cancer)
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12 pages, 242 KiB  
Article
Metabolomic Profiling of Disease Progression Following Radiotherapy for Breast Cancer
by Alexandra N. McMahon, Isildinha M. Reis, Cristiane Takita, Jean L. Wright and Jennifer J. Hu
Cancers 2025, 17(5), 891; https://doi.org/10.3390/cancers17050891 - 5 Mar 2025
Viewed by 599
Abstract
Background: This study aims to explore metabolic biomarkers and pathways in breast cancer prognosis. Methods: We performed a global post-radiotherapy (RT) urinary metabolomic analysis of 120 breast cancer patients: 60 progression-free (PF) patients as the reference and 60 with progressive disease (PD: recurrence, [...] Read more.
Background: This study aims to explore metabolic biomarkers and pathways in breast cancer prognosis. Methods: We performed a global post-radiotherapy (RT) urinary metabolomic analysis of 120 breast cancer patients: 60 progression-free (PF) patients as the reference and 60 with progressive disease (PD: recurrence, second primary, metastasis, or death). UPLC-MS/MS (Metabolon Inc.) identified 1742 biochemicals (1258 known and 484 unknown structures). Following normalization to osmolality, log transformation, and imputation of missing values, a Welch’s two-sample t-test was used to identify biochemicals and metabolic pathways that differed between PF and PD groups. Data analysis and visualization were performed with MetaboAnalyst. Results: Metabolic biomarkers and pathways that significantly differed between the PD and PF groups were the following: amino acid metabolism, including phenylalanine, tyrosine, and tryptophan biosynthesis (impact value (IV) = 1.00; p = 0.0007); histidine metabolism (IV = 0.60; p < 0.0001); and arginine and proline metabolism (IV = 0.70; p = 0.0035). Metabolites of carbohydrate metabolism, including glucose (p = 0.0197), sedoheptulose (p = 0.0115), and carboxymethyl lysine (p = 0.0098), were elevated in patients with PD. Gamma-glutamyl amino acids, myo-inositol, and oxidative stress biomarkers, including 7-Hydroxyindole Sulfate and sulfate, were elevated in patients who died (p ≤ 0.05). Conclusions: Amino acid metabolism emerged as a key pathway in breast cancer progression, while carbohydrate and oxidative stress metabolites also showed potential utility as biomarkers for breast cancer progression. These findings demonstrate applications of metabolomics in identifying metabolic biomarkers and pathways as potential targets for predicting breast cancer progression. Full article
(This article belongs to the Section Cancer Therapy)
11 pages, 9159 KiB  
Article
LiverSCA 2.0: An Enhanced Comprehensive Cell Atlas for Human Hepatocellular Carcinoma and Intrahepatic Cholangiocarcinoma
by Tina Suoangbaji, Renwen Long, Irene Oi-Lin Ng, Loey Lung-Yi Mak and Daniel Wai-Hung Ho
Cancers 2025, 17(5), 890; https://doi.org/10.3390/cancers17050890 - 5 Mar 2025
Viewed by 602
Abstract
Background: Hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) are two distinct types of primary liver cancer (PLC) characterized by considerable extents of cellular and molecular heterogeneities. We recently developed a web-based cell atlas called LiverSCA that possesses a user-friendly interface and comprehensive functionalities. [...] Read more.
Background: Hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) are two distinct types of primary liver cancer (PLC) characterized by considerable extents of cellular and molecular heterogeneities. We recently developed a web-based cell atlas called LiverSCA that possesses a user-friendly interface and comprehensive functionalities. It facilitates the exploration of gene expression patterns, cellular compositions, and intercellular communication within the microenvironments of liver and PLC tumors. Methods: To further enhance the documentation of data pinpointing different phenotypes/subtypes of liver and PLC, we extended the catalog of LiverSCA with additional datasets, e.g., ICC and metabolic dysfunction-associated steatotic liver disease/steatosis (MASLD/MASH). Results: The current enhanced version of the LiverSCA cell atlas encompasses six phenotypes (normal, HBV-HCC, HCV-HCC, non-viral HCC, ICC, and MASH), 63 patients, and over 248,000 cells. Furthermore, we have incorporated comparative visualization methods that allow users to simultaneously examine and compare gene expression levels between two different phenotypes. Conclusions: We are committed to the continuous development of LiverSCA and envision that it will serve as a valuable resource to support researchers in convenient investigations into the cellular and molecular landscapes of liver and PLC. Full article
(This article belongs to the Special Issue Molecular Genetics, Signaling Pathways, and Therapeutic Strategies for Liver Cancer)
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19 pages, 331 KiB  
Review
Systemic Treatment in Soft Tissue Sarcomas: Are We Making a Difference?
by Amrit Paudel, Priya Chattopadhyay, Brandon Rose, Aleksandra Watson, Gina D’Amato, Jonathan Trent, Steven Bialick and Emily Jonczak
Cancers 2025, 17(5), 889; https://doi.org/10.3390/cancers17050889 - 5 Mar 2025
Viewed by 626
Abstract
Soft tissue sarcomas [STSs] are rare tumors of mesodermal origin that arise in diverse tissues such as muscles, fat, and nerves. There are over 100 subtypes of STS, each with distinct clinical behaviors and responses to treatment. Recent advances in treatment have moved [...] Read more.
Soft tissue sarcomas [STSs] are rare tumors of mesodermal origin that arise in diverse tissues such as muscles, fat, and nerves. There are over 100 subtypes of STS, each with distinct clinical behaviors and responses to treatment. Recent advances in treatment have moved towards histology-specific approaches, emphasizing the integration of pathological, immunohistochemical, and molecular features to guide treatment. Localized STS is primarily treated with surgery, often supplemented by neoadjuvant or adjuvant radiation and/or chemotherapy. However, about half of patients with localized disease will progress to an advanced stage, which is typically managed with systemic therapies including anthracycline-based chemotherapy such as doxorubicin or epirubicin. Despite these treatments, the survival rates for most subtypes of advanced metastatic STS remain relatively low. While anthracycline-based chemotherapy remains the mainstay of treatment, ongoing research into the biology of STSs is enhancing our understanding and approach to these complex tumors with an expansion beyond chemotherapy to include targeted therapy and immunotherapy to improve response rates and survival outcomes. This review focuses on STS other than gastrointestinal stromal tumors [GISTs], examines the current systemic treatment strategies, highlights recent advances, and explores future directions in the systemic therapy of sarcoma patients. Full article
(This article belongs to the Special Issue Interdisciplinary Approach to Soft Tissue Sarcoma Care: Bridging Gaps for Better Outcomes)
13 pages, 809 KiB  
Article
The Impact of Paratracheal Lymphadenectomy on Survival After Esophagectomy: A Nationwide Propensity Score Matched Analysis
by Eliza R. C. Hagens, B. Feike Kingma, Mark I. van Berge Henegouwen, Alicia S. Borggreve, Jelle P. Ruurda, Richard van Hillegersberg and Suzanne S. Gisbertz
Cancers 2025, 17(5), 888; https://doi.org/10.3390/cancers17050888 - 5 Mar 2025
Viewed by 453
Abstract
Purpose: To investigate the impact of paratracheal lymphadenectomy on survival in patients undergoing an esophagectomy for cancer. The secondary objective was to assess the effect on short-term outcomes. Methods: Between 2011–2017, patients with an esophageal or gastroesophageal junction carcinoma treated with elective transthoracic [...] Read more.
Purpose: To investigate the impact of paratracheal lymphadenectomy on survival in patients undergoing an esophagectomy for cancer. The secondary objective was to assess the effect on short-term outcomes. Methods: Between 2011–2017, patients with an esophageal or gastroesophageal junction carcinoma treated with elective transthoracic esophagectomy with two-field lymphadenectomy were included from the Dutch Upper Gastro-intestinal Cancer Audit registry. After 1:1 propensity score matching of patients with and without paratracheal lymphadenectomy within histologic subgroups, short-term outcomes and overall survival were compared between the two groups. Results: A total of 1154 patients with adenocarcinoma and 294 patients with squamous cell carcinoma were matched. Lymph node yield was significantly higher (22 versus 19 nodes, p < 0.001) in patients with paratracheal lymphadenectomy for both tumor types. Paratracheal lymphadenectomy was associated with more recurrent laryngeal nerve injury (10% versus 5%, p = 0.002) and chylothorax in patients with adenocarcinoma (10% versus 5%, p = 0.010) and with more anastomotic leakage in patients with squamous cell carcinoma (42% versus 27%, p = 0.014). The 3- and 5-year survival in patients with and without a paratracheal lymphadenectomy were for adenocarcinoma, respectively, 58% versus 56% and 48% in both groups (log rank: p = 0.578) and for patients with a squamous cell carcinoma, 62% in both groups and 57% versus 54% (log rank: p = 0.668). Conclusions: The addition of paratracheal lymphadenectomy significantly increases lymph node yield in transthoracic esophagectomy but did not result in improved survival for esophageal cancer patients in the current dataset. However, there was an increase in postoperative morbidity in patients who underwent a paratracheal lymphadenectomy. Full article
(This article belongs to the Section Cancer Survivorship and Quality of Life)
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19 pages, 5074 KiB  
Article
Spectroscopic Nuclear Magnetic Resonance and Fourier Transform–Infrared Approach Used for the Evaluation of Healing After Surgical Interventions for Patients with Colorectal Cancer: A Pilot Study
by Lavinia Raluca Șaitiș, David Andras, Ioana-Alina Pop, Cătălin Șaitiș, Ramona Crainic and Radu Fechete
Cancers 2025, 17(5), 887; https://doi.org/10.3390/cancers17050887 - 5 Mar 2025
Viewed by 571
Abstract
Background/Objectives: Colorectal cancer (CRC) is one of the most common and deadly types of cancer. Compared with the classical histopathological approach, this study discusses the application of 1H NMR and FT-IR techniques for the fast evaluation degree of healing of patients with [...] Read more.
Background/Objectives: Colorectal cancer (CRC) is one of the most common and deadly types of cancer. Compared with the classical histopathological approach, this study discusses the application of 1H NMR and FT-IR techniques for the fast evaluation degree of healing of patients with CRC after surgical intervention. Methods: Native and deproteinized blood plasma collected from 10 patients with confirmed CRC and 20 healthy volunteers were analyzed using 1H NMR T2 distributions and FT-IR spectra measured for samples collected before and 7 days after surgery. The average FT-IR spectrum from 20 healthy volunteers is also presented. Principal component analysis (PCA) was performed on the FT-IR spectra. The results were used for further statistical analysis using receiver operating characteristic (ROC) and area under the curve (AUC) and to produce a series of prediction maps using a machine learning library. Results: Both experimental methods combined with analysis methods demonstrated that the native blood plasma samples can be better used to predict the CRC patients’ evolution 7 days after surgery. Three patients showed a significant evolution by 1H NMR T2 distribution, correlated to the observation of FT-IR–PCA analysis. Maps of medical state probability were generated using a trained machine learning-based ANN. Conclusions: The experimental measurements combined with an advanced statistical analysis and machine learning were successfully used and show that the healing process of patients with CRC is not linear, from the preoperative state to the state associated with healthy volunteers, but passes through a distinct healing state Full article
(This article belongs to the Section Clinical Research of Cancer)
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14 pages, 1779 KiB  
Article
Role of Bioimpedance Phase Angle and Hand Grip Strength in Predicting 12-Month Mortality in Patients Admitted with Haematologic Cancer
by Lara Dalla Rovere, Rocio Fernández-Jiménez, Alessandro Guerrini, María García-Olivares, Cristina Herola-Cobos, Carmen Hardy-Añón, Rahinatu Awol-Tanko, Agustín Hernandez-Sanchez and José Manuel García-Almeida
Cancers 2025, 17(5), 886; https://doi.org/10.3390/cancers17050886 - 5 Mar 2025
Viewed by 582
Abstract
Background/Objectives: Haematologic cancers, such acute leukaemia, lymphoma, and multiple myeloma, are associated with high morbidity and mortality rates, often exacerbated by malnutrition and functional decline. This study aims to evaluate the prognostic value of bioimpedance phase angle (PhA) and hand grip strength [...] Read more.
Background/Objectives: Haematologic cancers, such acute leukaemia, lymphoma, and multiple myeloma, are associated with high morbidity and mortality rates, often exacerbated by malnutrition and functional decline. This study aims to evaluate the prognostic value of bioimpedance phase angle (PhA) and hand grip strength (HGS) as nutritional and clinical markers for predicting 12-month mortality in hospitalized patients with haematologic cancers. Methods: A retrospective observational study was conducted on 121 patients admitted to Hospital Quironsalud Málaga between January 2019 and June 2021. PhA was measured using bioelectrical impedance analysis (BIA) and HGS was assessed using a dynamometer. Nutritional status was evaluated through Subjective Global Assessment (SGA) and the Global Leadership Initiative on Malnutrition (GLIM) criteria. The primary outcome was 12-month mortality, analysed using ROC curves, Kaplan–Meier survival estimates, and multivariate logistic regression models. Results: Lower PhA (<3.8° for females, <5.4° for males) and reduced HGS (<17 kg for females, <28 kg for males) were significantly associated with higher 12-month mortality (p < 0.001). The optimal PhA cut-off showed high sensitivity (85.5%) and specificity (62.2%). Multivariate analysis confirmed PhA as an independent predictor of mortality (OR = 0.417, p = 0.023). Patients with lower PhA and HGS values exhibited reduced survival rates, emphasizing the importance of these markers in clinical practice. Conclusions: PhA and HGS are reliable, non-invasive tools for assessing prognosis in haematologic cancer patients. Incorporating these markers into routine care could improve risk stratification, guide nutritional interventions, and enhance patient outcomes. Full article
(This article belongs to the Section Cancer Epidemiology and Prevention)
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12 pages, 415 KiB  
Review
Diffuse Large B-Cell Lymphoma in the Older and Frail Patient
by Emily C. Ayers and Sonali M. Smith
Cancers 2025, 17(5), 885; https://doi.org/10.3390/cancers17050885 - 5 Mar 2025
Viewed by 680
Abstract
Outcomes in older, unfit, and frail patients with diffuse large B-cell lymphoma (DLBCL) are inferior compared to younger and fit patients. Despite tremendous progress in the treatment landscape of DLBCL, few clinical trials have focused specifically on this high-risk patient population. This review [...] Read more.
Outcomes in older, unfit, and frail patients with diffuse large B-cell lymphoma (DLBCL) are inferior compared to younger and fit patients. Despite tremendous progress in the treatment landscape of DLBCL, few clinical trials have focused specifically on this high-risk patient population. This review focuses on the pathophysiology unique to the older patient with DLBCL, as well as the evidence behind current treatment approaches. This article also aims to highlight emerging prognostic tools and novel treatment strategies that may improve the outcomes in this patient cohort in the future. Full article
(This article belongs to the Special Issue Evolution of B-Cell Malignancy Therapy and Treatment Resistance: Where Are We Headed? (2nd Edition))
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13 pages, 798 KiB  
Review
Efficiency of Fulvestrant Monotherapy After CDK4/6 Inhibitor Exposure: Is This a Viable Choice?
by Nanae Ogata, Brian G Barnett, Nicholas J. H. Sharp, Takeo Fujii, Toshiaki Iwase, Sandra E. Dunn and Naoto T. Ueno
Cancers 2025, 17(5), 884; https://doi.org/10.3390/cancers17050884 - 4 Mar 2025
Viewed by 1746
Abstract
Guidelines for the first-line treatment of Hormone Receptor-positive, HER2-negative advanced or recurrent breast cancer have shifted to combination therapies of a CDK4/6 inhibitor and endocrine therapy. However, determining an optimal subsequent therapy following CDK4/6 inhibitor progression remains challenging, especially for tumors lacking actionable [...] Read more.
Guidelines for the first-line treatment of Hormone Receptor-positive, HER2-negative advanced or recurrent breast cancer have shifted to combination therapies of a CDK4/6 inhibitor and endocrine therapy. However, determining an optimal subsequent therapy following CDK4/6 inhibitor progression remains challenging, especially for tumors lacking actionable mutations. Real-world data suggest that fulvestrant monotherapy is frequently selected in this post-CDK4/6 inhibitor setting. This review examines its therapeutic potential in this evolving landscape. A systematic literature search using PubMed and ClinicalTrials.gov identified 153 clinical trials published between 2017 and November 2024, from which ten studies met our strict inclusion criteria, focusing solely on fulvestrant monotherapy. These trials encompassed 1038 patients who had prior exposure to CDK4/6 inhibitors. The selected studies were categorized into three groups: monotherapy trials (EMERALD, SERENA-2, AMEERA-3, and ELAINE-1), combination therapy trials (CAPItello-291 and VERONICA), and CDK4/6 inhibitor rechallenge trials (post-MONARCH, PACE, PALMIRA, and MAINTAIN). The median progression-free survival for fulvestrant monotherapy was 3.18 months (range 1.9–5.3 months). Factors affecting the efficacy of fulvestrant monotherapy in second-line therapy include prior treatments, treatment duration, and genetic mutations. Given that the efficacy of fulvestrant was short-lived in the second or subsequent lines, participating in clinical trials is a vital option until a novel alternative treatment choice becomes available. Full article
(This article belongs to the Section Clinical Research of Cancer)
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15 pages, 774 KiB  
Systematic Review
Immunotherapy in the Management of Penile Cancer—A Systematic Review
by Hossein Taghizadeh and Harun Fajkovic
Cancers 2025, 17(5), 883; https://doi.org/10.3390/cancers17050883 - 4 Mar 2025
Viewed by 688
Abstract
Penile cancer, though a rare malignancy, presents a significant challenge in the domain of male genitourinary oncology, particularly due to its limited treatment options and due to the profound physical and psychological impact on patients [...] Full article
(This article belongs to the Special Issue Research on Current Progress in Penile Cancer)
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127 pages, 2092 KiB  
Review
A Thorough Review of the Clinical Applications of Artificial Intelligence in Lung Cancer
by Serafeim-Chrysovalantis Kotoulas, Dionysios Spyratos, Konstantinos Porpodis, Kalliopi Domvri, Afroditi Boutou, Evangelos Kaimakamis, Christina Mouratidou, Ioannis Alevroudis, Vasiliki Dourliou, Kalliopi Tsakiri, Agni Sakkou, Alexandra Marneri, Elena Angeloudi, Ioanna Papagiouvanni, Anastasia Michailidou, Konstantinos Malandris, Constantinos Mourelatos, Alexandros Tsantos and Athanasia Pataka
Cancers 2025, 17(5), 882; https://doi.org/10.3390/cancers17050882 - 4 Mar 2025
Viewed by 1366
Abstract
According to data from the World Health Organization (WHO), lung cancer is becoming a global epidemic. It is particularly high in the list of the leading causes of death not only in developed countries, but also worldwide; furthermore, it holds the leading place [...] Read more.
According to data from the World Health Organization (WHO), lung cancer is becoming a global epidemic. It is particularly high in the list of the leading causes of death not only in developed countries, but also worldwide; furthermore, it holds the leading place in terms of cancer-related mortality. Nevertheless, many breakthroughs have been made the last two decades regarding its management, with one of the most prominent being the implementation of artificial intelligence (AI) in various aspects of disease management. We included 473 papers in this thorough review, most of which have been published during the last 5–10 years, in order to describe these breakthroughs. In screening programs, AI is capable of not only detecting suspicious lung nodules in different imaging modalities—such as chest X-rays, computed tomography (CT), and positron emission tomography (PET) scans—but also discriminating between benign and malignant nodules as well, with success rates comparable to or even better than those of experienced radiologists. Furthermore, AI seems to be able to recognize biomarkers that appear in patients who may develop lung cancer, even years before this event. Moreover, it can also assist pathologists and cytologists in recognizing the type of lung tumor, as well as specific histologic or genetic markers that play a key role in treating the disease. Finally, in the treatment field, AI can guide in the development of personalized options for lung cancer patients, possibly improving their prognosis. Full article
(This article belongs to the Special Issue Recent Advances in Trachea, Bronchus and Lung Cancer Management)
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24 pages, 2256 KiB  
Article
Targeted Treatment of Sarcomas by Single Protein Encapsulated Doxorubicin with Undetectable Cardiotoxicity and Superior Efficacy
by Changjun Yu, Faqing Huang, Leslie Wang, Mengmeng Liu, Warren A. Chow, Xiang Ling, Fengzhi Li, Galen Cook-Wiens, Linrong Li and Xiaojiang Cui
Cancers 2025, 17(5), 881; https://doi.org/10.3390/cancers17050881 - 4 Mar 2025
Viewed by 656
Abstract
As rare tumors, sarcomas represent ~0 [...] Full article
(This article belongs to the Section Cancer Drug Development)
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