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Volume 17
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Cancers, Volume 17, Issue 1 (January-1 2025) – 150 articles

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17 pages, 3052 KiB  
Systematic Review
Robotic Versus Laparoscopic Adrenalectomy for Adrenal Tumors: An Up-to-Date Meta-Analysis on Perioperative Outcomes
by Giuseppe Esposito, Barbara Mullineris, Giovanni Colli, Serena Curia and Micaela Piccoli
Cancers 2025, 17(1), 150; https://doi.org/10.3390/cancers17010150 (registering DOI) - 5 Jan 2025
Abstract
Background: Minimally invasive surgery (MIS) for adrenal glands is becoming increasingly developed worldwide and robotic surgery has advanced significantly. Although there are still concerns about the generalization of outcomes and the cost burden, the robotic platform shows several advantages in overcoming some laparoscopic [...] Read more.
Background: Minimally invasive surgery (MIS) for adrenal glands is becoming increasingly developed worldwide and robotic surgery has advanced significantly. Although there are still concerns about the generalization of outcomes and the cost burden, the robotic platform shows several advantages in overcoming some laparoscopic shortcomings. Materials and Methods: A systematic review and meta-analysis were conducted using the PubMed, MEDLINE and Cochrane library databases of published articles comparing RA and LA up to January 2024. The evaluated endpoints were technical and post-operative outcomes. Dichotomous data were calculated using the odds ratio (OR), while continuous data were analyzed usingmean difference (MD) with a 95% confidence interval (95% CI). A random-effects model (REM) was applied. Results: By the inclusion of 28 studies, the meta-analysis revealed no statistically significant difference in the rates of intraoperative RBC transfusion, 30-day mortality, intraoperative and overall postoperative complications, re-admission, R1 resection margin and operating time in the RA group compared with the LA. However, the overall cost of hospitalization was significantly higher in the RA group than in the LA group, [MD USD 4101.32, (95% CI 3894.85, 4307.79) p < 0.00001]. With respect to the mean intraoperative blood loss, conversion to open surgery rate, time to first flatus and length of hospital stay, the RA group showed slightly statistically significant lower rates than the laparoscopic approach. Conclusions: To our knowledge, this is the largest and most recent meta-analysis that makes these comparisons. RA can be considered safe, feasible and comparable to LA in terms of the intraoperative and post-operative outcomes. In the near future, RA could represent a promising complementary approachto LA for benign and small malignant adrenal masses, particularly in high-volume referral centers specializing in robotic surgery. However, further studies are needed to confirm these findings. Full article
(This article belongs to the Section Systematic Review or Meta-Analysis in Cancer Research)
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14 pages, 570 KiB  
Article
Long-Term Outcomes and Quality of Life of High-Risk Neuroblastoma Patients Treated with a Multimodal Treatment Including Anti-GD2 Immunotherapy: A Retrospective Cohort Study
by Tim Flaadt, Jonas Rehm, Thorsten Simon, Barbara Hero, Ruth L. Ladenstein, Holger N. Lode, Desiree Grabow, Sandra Nolte, Roman Crazzolara, Johann Greil, Martin Ebinger, Michael Abele, Ursula Holzer, Michaela Döring, Johannes H. Schulte, Peter Bader, Paul-Gerhardt Schlegel, Matthias Eyrich, Peter Lang, Thomas Klingebiel and Rupert Handgretingeradd Show full author list remove Hide full author list
Cancers 2025, 17(1), 149; https://doi.org/10.3390/cancers17010149 (registering DOI) - 5 Jan 2025
Abstract
Background: The incorporation of anti-GD2 antibodies such as ch14.18/SP2/0 into the multimodal treatment of high-risk neuroblastoma (HR-NB) patients has improved their outcomes. As studies assessing the long-term outcomes, long-term sequelae, and health-related quality of life (HRQoL) of this treatment are limited, this retrospective [...] Read more.
Background: The incorporation of anti-GD2 antibodies such as ch14.18/SP2/0 into the multimodal treatment of high-risk neuroblastoma (HR-NB) patients has improved their outcomes. As studies assessing the long-term outcomes, long-term sequelae, and health-related quality of life (HRQoL) of this treatment are limited, this retrospective analysis aimed to explore these. Patients and Methods: Between 1991 and 2002, 65 children received a multimodal treatment, including ch14.18/SP2/0, for primary HR-NB. All received chemotherapy according to the NB90/NB97 trial, 51 received high-dose chemotherapy, and all received ch14.18/SP2/0 treatment. We analyzed the long-term sequelae and HRQoL (EORTC QLQ-C30), and evaluated overall and event-free survival (OS/EFS). Results: Twenty-five survivors were evaluated for HRQoL and long-term effects. All reported long-term sequelae, including ototoxicity in 16/25 (64%), cardiac toxicity in 6/25 (24%), and endocrine toxicity in 19/25 (76%) patients. Chronic diarrhea was reported in 20% of female patients. Seven patients developed autoimmune diseases. HRQoL scores were better across multiple scales than those of the matched German general population. Twenty-five-year OS and EFS were 50.8% (95% confidence interval: 31–55) and 43% (30.1–55.3), with 33 (50.8%) long-term survivors. Thirty-two patients died: 28 (43.1%) because of progression/relapse and 4 (6.2%) because of secondary neoplasms. Conclusions: Multimodal treatment, including ch14.18/SP2/0, can achieve long-term survival in HR-NB patients, with a substantial proportion of survivors reporting better HRQoL compared to the general population. All patients reported long-term side effects mostly attributable to chemotherapy and radiotherapy. The relatively high prevalence of autoimmune diseases and persistent diarrhea warrants additional longitudinal research on individuals treated with anti-GD2 antibodies. Full article
(This article belongs to the Special Issue Challenges and Opportunities for Novel Therapeutic Strategies in Pediatric Oncology)
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19 pages, 8234 KiB  
Article
Integrated Analysis of Single-Cell and Bulk RNA Data Reveals Complexity and Significance of the Melanoma Interactome
by Michael J. Diaz, Jasmine T. Tran, Arthur M. Samia, Mahtab Forouzandeh, Jane M. Grant-Kels and Marjorie E. Montanez-Wiscovich
Cancers 2025, 17(1), 148; https://doi.org/10.3390/cancers17010148 (registering DOI) - 5 Jan 2025
Abstract
Background: Despite significant strides in anti-melanoma therapies, resistance and recurrence remain major challenges. A deeper understanding of the underlying biology of these challenges is necessary for developing more effective treatment paradigms. Methods: Melanoma single-cell data were retrieved from the Broad Single Cell Portal [...] Read more.
Background: Despite significant strides in anti-melanoma therapies, resistance and recurrence remain major challenges. A deeper understanding of the underlying biology of these challenges is necessary for developing more effective treatment paradigms. Methods: Melanoma single-cell data were retrieved from the Broad Single Cell Portal (SCP11). High-dimensional weighted gene co-expression network analysis (hdWGCNA), CellChat, and ligand-receptor relative crosstalk (RC) scoring were employed to evaluate intercellular and intracellular signaling. The prognostic value of key regulatory genes was assessed via Kaplan-Meier (KM) survival analysis using the ‘SKCM-TCGA’ dataset. Results: Twenty-seven (27) gene co-expression modules were identified via hdWGCNA. Notable findings include NRAS Q61L melanomas being enriched for modules involving C19orf10 and ARF4, while BRAF V600E melanomas were enriched for modules involving ALAS1 and MYO1B. Additionally, CellChat analysis highlighted several dominant signaling pathways, namely MHC-II, CD99, and Collagen-receptor signaling, with numerous significant ligand-receptor interactions from melanocytes, including CD99-CD99 communications with cancer-associated fibroblasts, endothelial cells, NK cells, and T-cells. KM analysis revealed that higher expression of SELL, BTLA, IL2RG, PDGFA, CLDN11, ITGB3, and SPN improved overall survival, while higher FGF5 expression correlated with worse survival. Protein-protein interaction network analysis further indicated significant interconnectivity among the identified prognostic genes. Conclusion: Overall, these insights underscore critical immune interactions and potential therapeutic _targets to combat melanoma resistance, paving the way for more personalized and effective treatment strategies. Full article
(This article belongs to the Collection Emerging Therapeutics in Advanced Melanoma)
21 pages, 966 KiB  
Review
A Personalized Approach for Oligometastatic Prostate Cancer: Current Understanding and Future Directions
by Parissa Alerasool, Susu Zhou, Eric Miller, Jonathan Anker, Brandon Tsao, Natasha Kyprianou and Che-Kai Tsao
Cancers 2025, 17(1), 147; https://doi.org/10.3390/cancers17010147 (registering DOI) - 5 Jan 2025
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Abstract
Oligometastatic prostate cancer (OMPC) represents an intermediate state in the progression from localized disease to widespread metastasis when the radiographically significant sites are limited in number and location. With no clear consensus on a definition, its diagnostic significance and associated optimal therapeutic approach [...] Read more.
Oligometastatic prostate cancer (OMPC) represents an intermediate state in the progression from localized disease to widespread metastasis when the radiographically significant sites are limited in number and location. With no clear consensus on a definition, its diagnostic significance and associated optimal therapeutic approach remain controversial, posing a significant challenge for clinicians. The current standard of care for metastatic disease is to start systemic therapy; however, active surveillance and _targeted radiotherapy have become attractive options to mitigate the long-term effects of androgen deprivation therapy (ADT). Furthermore, evolving biomarker methodologies may further define optimal treatment selection. In this review, we summarize the current understanding that guides the treatment of OMPC, with a focus on how host response can be an important contributing factor. Evolving scientific understanding and clinical development will continue to shape the landscape of treatment strategies for this distinct disease state. Full article
(This article belongs to the Special Issue Updates on Urologic Oncology: From Diagnosis to Localized and Systemic Therapy Options (2nd Edition))
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17 pages, 303 KiB  
Review
Glioblastoma: Clinical Presentation, Multidisciplinary Management, and Long-Term Outcomes
by David Sipos, Bence L. Raposa, Omar Freihat, Mihály Simon, Nejc Mekis, Patrizia Cornacchione and Árpád Kovács
Cancers 2025, 17(1), 146; https://doi.org/10.3390/cancers17010146 (registering DOI) - 5 Jan 2025
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Abstract
Glioblastoma, the most common and aggressive primary brain tumor in adults, presents a formidable challenge due to its rapid progression, treatment resistance, and poor survival outcomes. Standard care typically involves maximal safe surgical resection, followed by fractionated external beam radiation therapy and concurrent [...] Read more.
Glioblastoma, the most common and aggressive primary brain tumor in adults, presents a formidable challenge due to its rapid progression, treatment resistance, and poor survival outcomes. Standard care typically involves maximal safe surgical resection, followed by fractionated external beam radiation therapy and concurrent temozolomide chemotherapy. Despite these interventions, median survival remains approximately 12–15 months, with a five-year survival rate below 10%. Prognosis is influenced by factors such as patient age, molecular characteristics, and the extent of resection. Patients with IDH-mutant tumors or methylated MGMT promoters generally have improved survival, while recurrent glioblastoma is associated with a median survival of only six months, as therapies in these cases are often palliative. Innovative treatments, including TTFields, add incremental survival benefits, extending median survival to around 20.9 months for eligible patients. Symptom management—addressing seizures, headaches, and neurological deficits—alongside psychological support for patients and caregivers is essential to enhance quality of life. Emerging _targeted therapies and immunotherapies, though still limited in efficacy, show promise as part of an evolving treatment landscape. Continued research and clinical trials remain crucial to developing more effective treatments. This multidisciplinary approach, incorporating diagnostics, personalized therapy, and supportive care, aims to improve outcomes and provides a hopeful foundation for advancing glioblastoma management. Full article
(This article belongs to the Special Issue Outcomes in Glioblastoma Patients: From Diagnosis to Palliation)
13 pages, 1558 KiB  
Article
Oral Maintenance Therapy in Early Breast Cancer—How Many Patients Are Potential Candidates?
by Nikolas Tauber, Lisbeth Hilmer, Dominik Dannehl, Franziska Fick, Franziska Hemptenmacher, Natalia Krawczyk, Thomas Meyer-Lehnert, Kay Milewski, Henriette Princk, Andreas Hartkopf, Achim Rody and Maggie Banys-Paluchowski
Cancers 2025, 17(1), 145; https://doi.org/10.3390/cancers17010145 (registering DOI) - 5 Jan 2025
Viewed by 117
Abstract
Background/Objectives: This single-center analysis evaluated the number of potential candidates for endocrine-based oral maintenance therapy in a real-world setting, focusing on three therapeutic agents, namely, olaparib, abemaciclib, and ribociclib, for patients with hormone receptor-positive HER2-negative early breast cancer. Methods: All breast cancer cases [...] Read more.
Background/Objectives: This single-center analysis evaluated the number of potential candidates for endocrine-based oral maintenance therapy in a real-world setting, focusing on three therapeutic agents, namely, olaparib, abemaciclib, and ribociclib, for patients with hormone receptor-positive HER2-negative early breast cancer. Methods: All breast cancer cases from the past 10 years (n = 3230) that underwent treatment at the certified Breast Cancer Center of the Department of Gynecology and Obstetrics, University Hospital Schleswig-Holstein, Lübeck Campus, were analyzed. Results: Of a total of 2038 patients with HR+ HER2− eBC, 685 patients (33.6%) qualified for one or more of the three agents—olaparib, abemaciclib, and ribociclib. Of these 685 patients, 523 patients (76.4%) had node-positive and 162 (23.6%) node-negative disease. Moreover, 368 patients (18.1% of a total of 2038 patients with HR+ HER2− eBC) were eligible exclusively for ribociclib, including all node-negative patients. A total of 141 patients (6.9%) met the criteria for all three agents. In contrast, 1353 patients (66.4%) had no indication for combined endocrine therapy. Conclusions: To our knowledge, this is the largest analysis addressing all three therapeutic strategies for combined endocrine therapy. The broad indication criteria of the NATALEE study may increase clinic workloads due to more frequent physician/patient interactions. It also remains unclear how therapy recommendations will influence actual treatment, as increased visits and potential side effects could affect patient compliance and adherence. Full article
(This article belongs to the Special Issue Advances in Invasive Breast Cancer: Treatment and Prognosis)
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19 pages, 792 KiB  
Review
Recurrent and Metastatic Head and Neck Cancer: Mechanisms of Treatment Failure, Treatment Paradigms, and New Horizons
by William T. Barham, Marshall Patrick Stagg, Rula Mualla, Michael DiLeo and Sagar Kansara
Cancers 2025, 17(1), 144; https://doi.org/10.3390/cancers17010144 (registering DOI) - 5 Jan 2025
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Abstract
Background: Head and neck cancer is a deadly disease with over 500,000 cases annually worldwide. Metastatic head and neck cancer accounts for a large proportion of the mortality associated with this disease. Many advances have been made in our understanding of the mechanisms [...] Read more.
Background: Head and neck cancer is a deadly disease with over 500,000 cases annually worldwide. Metastatic head and neck cancer accounts for a large proportion of the mortality associated with this disease. Many advances have been made in our understanding of the mechanisms of metastasis. The application of immunotherapy to locally recurrent or metastatic head and neck cancer has not only improved oncologic outcomes but has also provided valuable insights into the mechanisms of immune evasion and ultimately treatment failure. Objectives: This review paper will review our current understanding of biological mechanisms of treatment failure and metastasis. Published and ongoing clinical trials in the management of metastatic head and neck cancer will also be summarized. Methods: A narrative review was conducted to address the current understanding of the mechanisms of treatment failure and current treatment paradigms in recurrent and metastatic head and neck carcinoma. Conclusions: Our understanding of treatment failure in this disease is rapidly evolving. Immunotherapy represents a valuable new tool in the fight against recurrent and metastatic head and neck squamous cell carcinoma. Integrating patient and tumor specific data via artificial intelligence and deep learning will allow for a precision oncology approach, thereby achieving better prognostication and management of patients with this deadly disease. Full article
(This article belongs to the Collection Advances in Diagnostics and Treatment of Head and Neck Cancer)
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14 pages, 1438 KiB  
Article
Adjuvant Immunotherapy After Resected Melanoma: Survival Outcomes, Prognostic Factors and Patterns of Relapse
by Sergio Martinez-Recio, Maria Alejandra Molina-Pérez, Eva Muñoz-Couselo, Alberto R. Sevillano-Tripero, Francisco Aya, Ana Arance, Mayra Orrillo, Juan Martin-Liberal, Luis Fernandez-Morales, Rocio Lesta, María Quindós-Varela, Maria Nieva, Joana Vidal, Daniel Martinez-Perez, Andrés Barba and Margarita Majem
Cancers 2025, 17(1), 143; https://doi.org/10.3390/cancers17010143 (registering DOI) - 5 Jan 2025
Viewed by 121
Abstract
Background: Anti-PD-1-based immunotherapy has improved outcomes in stage IIB to IV resected melanoma patients in clinical trials. However, little is known about real-world outcomes, prognostic factors and patterns of relapse. Methods: This is a retrospective multicenter observational study including patients with resected melanoma [...] Read more.
Background: Anti-PD-1-based immunotherapy has improved outcomes in stage IIB to IV resected melanoma patients in clinical trials. However, little is known about real-world outcomes, prognostic factors and patterns of relapse. Methods: This is a retrospective multicenter observational study including patients with resected melanoma treated with subsequent anti-PD-1-based adjuvant immunotherapy. Data on clinical and demographic characteristics, delivered treatment, prognostic factors, time and pattern of relapse were collected. Results: We included 245 patients from eight centers; 4% of patients were at stage IIB-C, 80% at stage IIIA-D and 16% at stage IV. Recurrence-free survival (RFS) rates at 18 and 36 months were 60% and 48%, respectively, with a median RFS of 33.7 months. Prognostic factors associated with recurrence were melanoma primary site (HR 2.64, 95% CI 1.15–6.01) and starting adjuvant therapy more than 12 weeks after the last resection (HR 1.68, 95% CI 1.13–2.5); presence of serious immune-related adverse events was associated with better RFS (HR 0.4, 95% CI 0.19–0.87). Early relapses accounted for 63% of the total recurrences, with a higher number of metastatic sites (18%); in contrast, late relapses presented more frequently with brain metastases (20%). Conclusions: In our patients with resected melanoma who underwent anti-PD-1-based adjuvant immunotherapy, survival outcomes were worse than those reported in clinical trials. Primary melanoma site and time interval between the last resection and the start of adjuvant therapy were associated with survival. Full article
(This article belongs to the Special Issue Diagnosis and Treatment of Cutaneous Melanoma)
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19 pages, 708 KiB  
Review
Menin Inhibitors: New _targeted Therapies for Specific Genetic Subtypes of Difficult-to-Treat Acute Leukemias
by Pasquale Niscola, Valentina Gianfelici, Marco Giovannini, Daniela Piccioni, Carla Mazzone and Paolo de Fabritiis
Cancers 2025, 17(1), 142; https://doi.org/10.3390/cancers17010142 (registering DOI) - 4 Jan 2025
Viewed by 283
Abstract
Menin (MEN1) is a well-recognized powerful tumor promoter in acute leukemias (AL) with KMT2A rearrangements (KMT2Ar, also known as MLL) and mutant nucleophosmin 1 (NPM1m) acute myeloid leukemia (AML). MEN1 is essential for sustaining leukemic transformation due to its interaction with wild-type KMT2A [...] Read more.
Menin (MEN1) is a well-recognized powerful tumor promoter in acute leukemias (AL) with KMT2A rearrangements (KMT2Ar, also known as MLL) and mutant nucleophosmin 1 (NPM1m) acute myeloid leukemia (AML). MEN1 is essential for sustaining leukemic transformation due to its interaction with wild-type KMT2A and KMT2A fusion proteins, leading to the dysregulation of KMT2A _target genes. MEN1 inhibitors (MIs), such as revumenib, ziftomenib, and other active small molecules, represent a promising new class of therapies currently under clinical development. By disrupting the MEN1-KMT2Ar complex, a group of proteins involved in chromatin remodeling, MIs induce apoptosis and differentiation AL expressing KMT2Ar or NPM1m AML. Phase I and II clinical trials have evaluated MIs as standalone treatments and combined them with other synergistic drugs, yielding promising results. These trials have demonstrated notable response rates with manageable toxicities. Among MIs, ziftomenib received orphan drug and breakthrough therapy designations from the European Medicines Agency in January 2024 and the Food and Drug Administration (FDA) in April 2024, respectively, for treating R/R patients with NPM1m AML. Additionally, in November 2024, the FDA approved revumenib for treating R/R patients with KMT2Ar-AL. This review focuses on the pathophysiology of MI-sensitive AL, primarily AML. It illustrates data from clinical trials and discusses the emergence of resistance mechanisms. In addition, we outline future directions for the use of MIs and emphasize the need for further research to fully realize the potential of these novel compounds, especially in the context of specific genetic subtypes of challenging AL. Full article
(This article belongs to the Section Cancer Therapy)
19 pages, 6330 KiB  
Article
Characterisation of Castration-Resistant Cell-Derived Exosomes and Their Effect on the Metastatic Phenotype
by Jorge Recio-Aldavero, Lorena Parra-Gutiérrez, Laura Muñoz-Moreno, Irene D. Román, María Isabel Arenas and Ana M. Bajo
Cancers 2025, 17(1), 141; https://doi.org/10.3390/cancers17010141 (registering DOI) - 4 Jan 2025
Viewed by 236
Abstract
Background/Objectives: Prostate cancer (PCa) is characterised by its progression to a metastatic and castration-resistant phase. Prostate tumour cells release small extracellular vesicles or exosomes which are taken up by _target cells and can potentially facilitate tumour growth and metastasis. The present work studies [...] Read more.
Background/Objectives: Prostate cancer (PCa) is characterised by its progression to a metastatic and castration-resistant phase. Prostate tumour cells release small extracellular vesicles or exosomes which are taken up by _target cells and can potentially facilitate tumour growth and metastasis. The present work studies the effect of exosomes from cell lines that are representative of the different stages of the disease on the tumoral phenotype of PC3 cells. Methods: Exosomes were isolated by ultracentrifugation from human prostate epithelial cells (RWPE-1) and androgen-dependent PCa cells (LNCaP) and castration-resistant PCa cells (CRPC) with moderate (DU145) or high (PC3) metastatic capacity. The biophysical and biochemical properties of the exosomes were characterised as well as their effects on PC3 cell viability and migration. Results: The study of the exosomes of prostate cell lines shows heterogeneity in their size, presenting in some of them two types of populations; in both populations, a larger size in those derived from PC3 cells and a smaller size in those derived from non-tumourigenic prostate cells were detected. Differences were found in the physical properties of those derived from healthy and PCa cells, as well as between cells representative of the most aggressive stages of the disease. The highest gamma-glutamyl transferase (GGT) activity was observed in androgen-dependent cells and differences in the pro-metalloproteinases (MMP) activity were detected in healthy cells and in castration-resistant cells with moderate metastatic capacity with respect to PC3 cells. The treatment of PC3 cells with their own exosomes increased PC3 cell viability and migration. Conclusion: Exosomes represent a promising field of research in the diagnosis, prognosis, and treatment of prostate cancer. Full article
(This article belongs to the Special Issue Exosomes in Cancer Metastasis)
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13 pages, 3107 KiB  
Article
Maxillectomy Guided by 3D Printing Versus Conventional Surgery for Patients with Head and Neck Cancer
by Sung Yool Park, Sung Ha Jung, Anna Seo, Hakjong Noh, Hwansun Lee, Hyo Jun Kim, Younghac Kim, Man Ki Chung, Han-Sin Jeong, Chung-Hwan Baek, Young-Ik Son and Nayeon Choi
Cancers 2025, 17(1), 140; https://doi.org/10.3390/cancers17010140 (registering DOI) - 4 Jan 2025
Viewed by 226
Abstract
Background: This study evaluates the impact of three-dimensional (3D) printing-guided maxillectomy compared with conventional maxillectomy on surgical precision and oncological outcomes in patients with head and neck cancer. Materials and Methods: A retrospective analysis was conducted on 42 patients undergoing maxillectomy (16 in [...] Read more.
Background: This study evaluates the impact of three-dimensional (3D) printing-guided maxillectomy compared with conventional maxillectomy on surgical precision and oncological outcomes in patients with head and neck cancer. Materials and Methods: A retrospective analysis was conducted on 42 patients undergoing maxillectomy (16 in a 3D printing-guided group and 26 in a conventional group). Patient demographics, tumor characteristics, and outcomes were compared. Survival outcomes were analyzed using the Kaplan–Meier method. Results: The 3D printing group showed higher rates of negative resection margins (81.3% vs. 76.9%) compared with the conventional group and a trend toward improved 5-year local recurrence-free survival (87.5% vs. 58.7%, respectively) and overall survival (84.4% vs. 70.1%, respectively). However, the differences were not statistically significant. Conclusions: Maxillectomy guided by 3D printing may offer enhanced surgical precision and improved local control in patients undergoing head and neck cancer surgeries. Further research with larger cohorts is necessary to confirm these findings. Full article
(This article belongs to the Special Issue Advancements in Head and Neck Cancer Surgery)
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13 pages, 2767 KiB  
Article
A Digital Phenotypic Assessment in Neuro-Oncology (DANO): A Pilot Study on Sociability Changes in Patients Undergoing Treatment for Brain Malignancies
by Francesca Siddi, Patrick Emedom-Nnamdi, Michael P. Catalino, Aakanksha Rana, Alessandro Boaro, Hassan Y. Dawood, Francesco Sala, Jukka-Pekka Onnela and Timothy R. Smith
Cancers 2025, 17(1), 139; https://doi.org/10.3390/cancers17010139 (registering DOI) - 4 Jan 2025
Viewed by 226
Abstract
Background: The digital phenotyping tool has great potential for the deep characterization of neurological and quality-of-life assessments in brain tumor patients. Phone communication activities (details on call and text use) can provide insight into the patients’ sociability. Methods: We prospectively collected digital-phenotyping data [...] Read more.
Background: The digital phenotyping tool has great potential for the deep characterization of neurological and quality-of-life assessments in brain tumor patients. Phone communication activities (details on call and text use) can provide insight into the patients’ sociability. Methods: We prospectively collected digital-phenotyping data from six brain tumor patients. The data were collected using the Beiwe application installed on their personal smartphones. We constructed several daily sociability features from phone communication logs, including the number of incoming and outgoing text messages and calls, the length of messages and duration of calls, message reciprocity, the number of communication partners, and number of missed calls. We compared variability in these sociability features against those obtained from a control group, matched for age and sex, selected among patients with a herniated disc. Results: In brain tumor patients, phone-based communication appears to deteriorate with time, as evident in the trend for total outgoing minutes, total outgoing calls, and call out-degree. Conclusions: These measures indicate a possible decrease in sociability over time in brain tumor patients that may correlate with survival. This exploratory analysis suggests that a quantifiable digital sociability phenotype exists and is comparable for patients with different survival outcomes. Overall, assessing neurocognitive function using digital phenotyping appears promising. Full article
(This article belongs to the Special Issue Novel Diagnostic and Therapeutic Approaches in Diffuse Gliomas)
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10 pages, 233 KiB  
Review
Exploring the Role of Symptom Diversity in Facial Basal Cell Carcinoma: Key Insights into Preoperative Quality of Life and Disease Progression
by Domantas Stundys, Alvija Kučinskaitė, Simona Gervickaitė, Jūratė Grigaitienė, Janina Tutkuvienė and Ligita Jančorienė
Cancers 2025, 17(1), 138; https://doi.org/10.3390/cancers17010138 (registering DOI) - 4 Jan 2025
Viewed by 219
Abstract
Facial basal cell carcinoma (BCC) is the most common skin cancer, yet delays in diagnosis and treatment persist. These delays affect quality of life (QoL), advance disease progression, and increase healthcare burden. This study explores the relationship between symptom diversity, QoL, and care-seeking [...] Read more.
Facial basal cell carcinoma (BCC) is the most common skin cancer, yet delays in diagnosis and treatment persist. These delays affect quality of life (QoL), advance disease progression, and increase healthcare burden. This study explores the relationship between symptom diversity, QoL, and care-seeking behaviors, focusing on the impact of symptoms on clinical outcomes and consultation timing. A total of 278 adults with histologically confirmed facial BCC underwent surgical treatment at Vilnius University Hospital from November 2022 to April 2024. The data collected included demographics, tumor characteristics, and self-reported symptoms (pain, bleeding, itching, tumor presence, discomfort, and erosion). Disease-specific QoL was assessed using the Skin Cancer Index. ANCOVA compared QoL across symptom groups, multiple regression analyzed symptom effects on QoL, and logistic regression evaluated care-seeking behavior over time. Cox regression assessed symptom associations with time to medical consultation. The mean time from symptom onset to consultation was 21 months. Tumor presence (27%), erosion (18%), and discomfort (17%) were the most reported symptoms. Discomfort significantly reduced QoL in emotional, social, and appearance domains (p < 0.05). Logistic regression showed tumor presence and pain were associated with earlier care-seeking within 12 months (p < 0.05). Other symptoms, such as bleeding, itching, and erosion, did not significantly influence consultation timing. The findings highlight the need for public education and proactive patient counseling to promote timely intervention and reduce the disease progression. Full article
(This article belongs to the Special Issue Advances in Skin Cancer: Diagnosis, Treatment and Prognosis)
15 pages, 4485 KiB  
Article
AI-Driven Enhancement of Skin Cancer Diagnosis: A Two-Stage Voting Ensemble Approach Using Dermoscopic Data
by Tsu-Man Chiu, Yun-Chang Li, I-Chun Chi and Ming-Hseng Tseng
Cancers 2025, 17(1), 137; https://doi.org/10.3390/cancers17010137 - 3 Jan 2025
Viewed by 363
Abstract
Background: Skin cancer is the most common cancer worldwide, with melanoma being the deadliest type, though it accounts for less than 5% of cases. Traditional skin cancer detection methods are effective but are often costly and time-consuming. Recent advances in artificial intelligence have [...] Read more.
Background: Skin cancer is the most common cancer worldwide, with melanoma being the deadliest type, though it accounts for less than 5% of cases. Traditional skin cancer detection methods are effective but are often costly and time-consuming. Recent advances in artificial intelligence have improved skin cancer diagnosis by helping dermatologists identify suspicious lesions. Methods: The study used datasets from two ethnic groups, sourced from the ISIC platform and CSMU Hospital, to develop an AI diagnostic model. Eight pre-trained models, including convolutional neural networks and vision transformers, were fine-tuned. The three best-performing models were combined into an ensemble model, which underwent multiple random experiments to ensure stability. To improve diagnostic accuracy and reduce false negatives, a two-stage classification strategy was employed: a three-class model for initial classification, followed by a binary model for secondary prediction of benign cases. Results: In the ISIC dataset, the false negative rate for malignant lesions was significantly reduced, and the number of malignant cases misclassified as benign dropped from 124 to 45. In the CSMUH dataset, false negatives for malignant cases were completely eliminated, reducing the number of misclassified malignant cases to zero, resulting in a notable improvement in diagnostic precision and a reduction in the false negative rate. Conclusions: Through the proposed method, the study demonstrated clear success in both datasets. First, a three-class AI model can assist doctors in distinguishing between melanoma patients who require urgent treatment, non-melanoma skin cancer patients who can be treated later, and benign cases that do not require intervention. Subsequently, a two-stage classification strategy effectively reduces false negatives in malignant lesions. These findings highlight the potential of AI technology in skin cancer diagnosis, particularly in resource-limited medical settings, where it could become a valuable clinical tool to improve diagnostic accuracy, reduce skin cancer mortality, and reduce healthcare costs. Full article
(This article belongs to the Special Issue Recent Advances in Skin Cancers)
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19 pages, 2749 KiB  
Review
Prioritizing Context-Dependent Cancer Gene Signatures in Networks
by Enrico Capobianco, Thomas S. Lisse and Sandra Rieger
Cancers 2025, 17(1), 136; https://doi.org/10.3390/cancers17010136 - 3 Jan 2025
Viewed by 249
Abstract
There are numerous ways of portraying cancer complexity based on combining multiple types of data. A common approach involves developing signatures from gene expression profiles to highlight a few key reproducible features that provide insight into cancer risk, progression, or recurrence. Normally, a [...] Read more.
There are numerous ways of portraying cancer complexity based on combining multiple types of data. A common approach involves developing signatures from gene expression profiles to highlight a few key reproducible features that provide insight into cancer risk, progression, or recurrence. Normally, a selection of such features is made through relevance or significance, given a reference context. In the case of highly metastatic cancers, numerous gene signatures have been published with varying levels of validation. Then, integrating the signatures could potentially lead to a more comprehensive view of the connection between cancer and its phenotypes by covering annotations not fully explored in individual studies. This broader understanding of disease phenotypes would improve the predictive accuracy of statistical models used to identify meaningful associations. We present an example of this approach by reconciling a great number of published signatures into meta-signatures relevant to Osteosarcoma (OS) metastasis. We generate a well-annotated and interpretable interactome network from integrated OS gene expression signatures and identify key nodes that regulate essential aspects of metastasis. While the connected signatures link diverse prognostic measurements for OS, the proposed approach is applicable to any type of cancer. Full article
(This article belongs to the Special Issue Technological Development for Advances in Cancer Research and Precision Oncology)
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18 pages, 5480 KiB  
Article
A Novel In Vitro Model of the Bone Marrow Microenvironment in Acute Myeloid Leukemia Identifies CD44 and Focal Adhesion Kinase as Therapeutic _targets to Reverse Cell Adhesion-Mediated Drug Resistance
by Eleni E. Ladikou, Kim Sharp, Fabio A. Simoes, John R. Jones, Thomas Burley, Lauren Stott, Aimilia Vareli, Emma Kennedy, Sophie Vause, Timothy Chevassut, Amarpreet Devi, Iona Ashworth, David M. Ross, Tanja Nicole Hartmann, Simon A. Mitchell, Chris J. Pepper, Giles Best and Andrea G. S. Pepper
Cancers 2025, 17(1), 135; https://doi.org/10.3390/cancers17010135 - 3 Jan 2025
Viewed by 288
Abstract
Background/Objectives: Acute myeloid leukemia (AML) is an aggressive neoplasm. Although most patients respond to induction therapy, they commonly relapse due to recurrent disease in the bone marrow microenvironment (BMME). So, the disruption of the BMME, releasing tumor cells into the peripheral circulation, has [...] Read more.
Background/Objectives: Acute myeloid leukemia (AML) is an aggressive neoplasm. Although most patients respond to induction therapy, they commonly relapse due to recurrent disease in the bone marrow microenvironment (BMME). So, the disruption of the BMME, releasing tumor cells into the peripheral circulation, has therapeutic potential. Methods: Using both primary donor AML cells and cell lines, we developed an in vitro co-culture model of the AML BMME. We used this model to identify the most effective agent(s) to block AML cell adherence and reverse adhesion-mediated treatment resistance. Results: We identified that anti-CD44 treatment significantly increased the efficacy of cytarabine. However, some AML cells remained adhered, and transcriptional analysis identified focal adhesion kinase (FAK) signaling as a contributing factor; the adhered cells showed elevated FAK phosphorylation that was reduced by the FAK inhibitor, defactinib. Importantly, we demonstrated that anti-CD44 and defactinib were highly synergistic at diminishing the adhesion of the most primitive CD34high AML cells in primary autologous co-cultures. Conclusions: Taken together, we identified anti-CD44 and defactinib as a promising therapeutic combination to release AML cells from the chemoprotective AML BMME. As anti-CD44 is already available as a recombinant humanized monoclonal antibody, the combination of this agent with defactinib could be rapidly tested in AML clinical trials. Full article
(This article belongs to the Special Issue _targeting the Tumor Microenvironment (Volume II))
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14 pages, 1383 KiB  
Article
Impact of the COVID-19 Pandemic on Histopathological Cancer Diagnostics in Lower Silesia: A Comparative Analysis of Prostate, Breast, and Colorectal Cancer from 2018 to 2022
by Danuta Szkudlarek, Katarzyna Kalinowska and Benita Wiatrak
Cancers 2025, 17(1), 134; https://doi.org/10.3390/cancers17010134 - 3 Jan 2025
Viewed by 273
Abstract
Background/Objective: The COVID-19 pandemic significantly disrupted healthcare systems worldwide including cancer diagnostics. This study aimed to assess the impact of the pandemic on histopathological cancer diagnostics in Lower Silesia, Poland, specifically focusing on prostate, breast, and colorectal cancer cases from 2018 to 2022. [...] Read more.
Background/Objective: The COVID-19 pandemic significantly disrupted healthcare systems worldwide including cancer diagnostics. This study aimed to assess the impact of the pandemic on histopathological cancer diagnostics in Lower Silesia, Poland, specifically focusing on prostate, breast, and colorectal cancer cases from 2018 to 2022. The objective was to evaluate diagnostic volumes and trends before, during, and after the pandemic and to understand the effect of healthcare disruptions on cancer detection. Methods: Histopathological and cytological data were collected from multiple laboratories across Lower Silesia. Samples were categorized into three periods: pre-pandemic (January 2018–February 2020), pandemic (March 2020–May 2022), and post-pandemic (June–December 2022). Statistical analyses included comparisons of diagnostic volumes and positive diagnoses across these periods. Results: A significant reduction in the number of histopathological examinations occurred during the pandemic, particularly during its early phase. This decline was accompanied by a higher frequency of positive cancer diagnoses, suggesting the prioritization of high-risk cases. Post-pandemic, diagnostic activity showed partial recovery, though it remained below the pre-pandemic levels, with notable differences across cancer types. Conclusions: The COVID-19 pandemic significantly disrupted cancer diagnostics in Lower Silesia, delaying detection and highlighting healthcare system vulnerabilities. These findings underscore the importance of resilient healthcare systems that can ensure the continuity of essential diagnostic services and address inequalities in access to care during crises. Full article
(This article belongs to the Special Issue How COVID-19 Affects Cancer Patients)
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32 pages, 3337 KiB  
Review
Exploring the Metabolic Impact of FLASH Radiotherapy
by Febe Geirnaert, Lisa Kerkhove, Pierre Montay-Gruel, Thierry Gevaert, Inès Dufait and Mark De Ridder
Cancers 2025, 17(1), 133; https://doi.org/10.3390/cancers17010133 - 3 Jan 2025
Viewed by 286
Abstract
FLASH radiotherapy (FLASH RT) is an innovative modality in cancer treatment that delivers ultrahigh dose rates (UHDRs), distinguishing it from conventional radiotherapy (CRT). FLASH RT has demonstrated the potential to enhance the therapeutic window by reducing radiation-induced damage to normal tissues while maintaining [...] Read more.
FLASH radiotherapy (FLASH RT) is an innovative modality in cancer treatment that delivers ultrahigh dose rates (UHDRs), distinguishing it from conventional radiotherapy (CRT). FLASH RT has demonstrated the potential to enhance the therapeutic window by reducing radiation-induced damage to normal tissues while maintaining tumor control, a phenomenon termed the FLASH effect. Despite promising outcomes, the precise mechanisms underlying the FLASH effect remain elusive and are a focal point of current research. This review explores the metabolic and cellular responses to FLASH RT compared to CRT, with particular focus on the differential impacts on normal and tumor tissues. Key findings suggest that FLASH RT may mitigate damage in healthy tissues via altered reactive oxygen species (ROS) dynamics, which attenuate downstream oxidative damage. Studies indicate the FLASH RT influences iron metabolism and lipid peroxidation pathways differently than CRT. Additionally, various studies indicate that FLASH RT promotes the preservation of mitochondrial integrity and function, which helps maintain apoptotic pathways in normal tissues, attenuating damage. Current knowledge of the metabolic influences following FLASH RT highlights its potential to minimize toxicity in normal tissues, while also emphasizing the need for further studies in biologically relevant, complex systems to better understand its clinical potential. By _targeting distinct metabolic pathways, FLASH RT could represent a transformative advance in RT, ultimately improving the therapeutic window for cancer treatment. Full article
(This article belongs to the Special Issue Feature Paper in Section “Cancer Therapy” in 2024)
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11 pages, 2882 KiB  
Article
Doxycycline Restores Gemcitabine Sensitivity in Preclinical Models of Multidrug-Resistant Intrahepatic Cholangiocarcinoma
by Annamaria Massa, Francesca Vita, Caterina Peraldo-Neia, Chiara Varamo, Marco Basiricò, Chiara Raggi, Paola Bernabei, Jessica Erriquez, Francesco Leone, Massimo Aglietta, Giuliana Cavalloni and Serena Marchiò
Cancers 2025, 17(1), 132; https://doi.org/10.3390/cancers17010132 - 3 Jan 2025
Viewed by 248
Abstract
Background/Objectives: Intrahepatic cholangiocarcinoma (iCCA) is a malignant liver tumor with a rising global incidence and poor prognosis, largely due to late-stage diagnosis and limited effective treatment options. Standard chemotherapy regimens, including cisplatin and gemcitabine, often fail because of the development of multidrug resistance [...] Read more.
Background/Objectives: Intrahepatic cholangiocarcinoma (iCCA) is a malignant liver tumor with a rising global incidence and poor prognosis, largely due to late-stage diagnosis and limited effective treatment options. Standard chemotherapy regimens, including cisplatin and gemcitabine, often fail because of the development of multidrug resistance (MDR), leaving patients with few alternative therapies. Doxycycline, a tetracycline antibiotic, has demonstrated antitumor effects across various cancers, influencing cancer cell viability, apoptosis, and stemness. Based on these properties, we investigated the potential of doxycycline to overcome gemcitabine resistance in iCCA. Methods: We evaluated the efficacy of doxycycline in two MDR iCCA cell lines, MT-CHC01R1.5 and 82.3, assessing cell cycle perturbation, apoptosis induction, and stem cell compartment impairment. We assessed the in vivo efficacy of combining doxycycline and gemcitabine in mouse xenograft models. Results: Treatment with doxycycline in both cell lines resulted in a significant reduction in cell viability (IC50 ~15 µg/mL) and induction of apoptosis. Doxycycline also diminished the cancer stem cell population, as indicated by reduced cholangiosphere formation. In vivo studies showed that while neither doxycycline nor gemcitabine alone significantly reduced tumor growth, their combination led to marked decreases in tumor volume and weight at the study endpoint. Additionally, metabolic analysis revealed that doxycycline reduced glucose uptake in tumors, both as a monotherapy and more effectively in combination with gemcitabine. Conclusions: These findings suggest that doxycycline, especially in combination with gemcitabine, can restore chemotherapy sensitivity in MDR iCCA, providing a promising new strategy for improving outcomes in this challenging disease. Full article
(This article belongs to the Collection Primary Liver Cancer)
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15 pages, 1134 KiB  
Article
Does Personality Influence the Quality of Life of Patients with Brain Tumors Treated with Radiotherapy?
by Agnieszka Pilarska, Anna Pieczyńska, Krystyna Adamska and Katarzyna Hojan
Cancers 2025, 17(1), 131; https://doi.org/10.3390/cancers17010131 - 3 Jan 2025
Viewed by 213
Abstract
Background: Understanding the role of personality traits in shaping treatment outcomes is crucial given the multifaceted challenges posed by brain tumors and the significant adverse impact of radiotherapy (RT) on patients’ well-being. Purpose: This study aimed to provide insights into how personality traits [...] Read more.
Background: Understanding the role of personality traits in shaping treatment outcomes is crucial given the multifaceted challenges posed by brain tumors and the significant adverse impact of radiotherapy (RT) on patients’ well-being. Purpose: This study aimed to provide insights into how personality traits affect psychosocial well-being and quality of life during RT in patients with high-grade malignant brain tumors. Methods: Personality traits in patients with high-grade glioma were assessed using the Eysenck Personality Questionnaire-Revised (EPQ-R). Quality of life was analyzed using EORTC questionnaires: the Questionnaire-Core 30 (QLQ-C30) and the Brain Cancer Module (QLQ-BN20). Patients were evaluated before RT, immediately after 6 weeks of RT, and 3 months post-RT. Results: Neuroticism predicted emotional function only three months post-RT. Extraversion decreased quality of life in global health status (third assessment), role function (second assessment), and emotional function (second and third assessments) but improved cognitive (first assessment) and social function (second assessment). The trait associated with lying was linked to a better quality of life in all domains except physical and cognitive function. Anxiety predicted a lower quality of life in brain tumor patients across all domains at various stages of RT treatment. Conclusions: This study advances our understanding of the psychosocial aspects of brain tumor care by highlighting the influence of personality traits on quality-of-life outcomes during RT. Identifying high-grade glioma patients at greater risk of a diminished quality of life based on personality profiles allows healthcare professionals to tailor interventions to address specific psychosocial needs, ultimately enhancing patient outcomes and holistic care during oncological treatment. Full article
(This article belongs to the Section Cancer Survivorship and Quality of Life)
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18 pages, 4377 KiB  
Article
Deep Convolutional Framelets for Dose Reconstruction in Boron Neutron Capture Therapy with Compton Camera Detector
by Angelo Didonna, Dayron Ramos Lopez, Giuseppe Iaselli, Nicola Amoroso, Nicola Ferrara and Gabriella Maria Incoronata Pugliese
Cancers 2025, 17(1), 130; https://doi.org/10.3390/cancers17010130 - 3 Jan 2025
Viewed by 232
Abstract
Background: Boron neutron capture therapy (BNCT) is an innovative binary form of radiation therapy with high selectivity towards cancer tissue based on the neutron capture reaction 10B(n,α)7Li, consisting in the exposition of patients to neutron beams after administration [...] Read more.
Background: Boron neutron capture therapy (BNCT) is an innovative binary form of radiation therapy with high selectivity towards cancer tissue based on the neutron capture reaction 10B(n,α)7Li, consisting in the exposition of patients to neutron beams after administration of a boron compound with preferential accumulation in cancer cells. The high linear energy transfer products of the ensuing reaction deposit their energy at the cell level, sparing normal tissue. Although progress in accelerator-based BNCT has led to renewed interest in this cancer treatment modality, in vivo dose monitoring during treatment still remains not feasible and several approaches are under investigation. While Compton imaging presents various advantages over other imaging methods, it typically requires long reconstruction times, comparable with BNCT treatment duration. Methods: This study aims to develop deep neural network models to estimate the dose distribution by using a simulated dataset of BNCT Compton camera images. The models pursue the avoidance of the iteration time associated with the maximum-likelihood expectation-maximization algorithm (MLEM), enabling a prompt dose reconstruction during the treatment. The U-Net architecture and two variants based on the deep convolutional framelets framework have been used for noise and artifact reduction in few-iteration reconstructed images. Results: This approach has led to promising results in terms of reconstruction accuracy and processing time, with a reduction by a factor of about 6 with respect to classical iterative algorithms. Conclusions: This can be considered a good reconstruction time performance, considering typical BNCT treatment times. Further enhancements may be achieved by optimizing the reconstruction of input images with different deep learning techniques. Full article
(This article belongs to the Section Methods and Technologies Development)
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18 pages, 1606 KiB  
Review
Insulin-like Growth Factor 1 (IGF1) and Its Isoforms: Insights into the Mechanisms of Endometrial Cancer
by Abdul Muzhill Hannaan Abdul Hafizz, Norfilza Mohd Mokthar, Reena Rahayu Md Zin, Nigel P. Mongan, Mohd Nazzary Mamat @ Yusof, Nirmala Chandralega Kampan, Kah Teik Chew and Mohamad Nasir Shafiee
Cancers 2025, 17(1), 129; https://doi.org/10.3390/cancers17010129 - 3 Jan 2025
Viewed by 368
Abstract
Endometrial cancer (EC) is a common gynaecological malignancy associated with metabolic dysfunctions such as obesity, diabetes and insulin resistance, as well as hormonal imbalances, particularly involving oestrogen and progesterone. These factors disrupt normal cellular metabolism, heightening the risk of developing endometrioid EC (EEC), [...] Read more.
Endometrial cancer (EC) is a common gynaecological malignancy associated with metabolic dysfunctions such as obesity, diabetes and insulin resistance, as well as hormonal imbalances, particularly involving oestrogen and progesterone. These factors disrupt normal cellular metabolism, heightening the risk of developing endometrioid EC (EEC), the most prevalent subtype of EC. The insulin-like growth factor-1 (IGF1) pathway, a key regulator of growth, metabolism, and organ function, is implicated in EC progression. Recent research highlights the distinct roles of IGF1 isoforms, including IGF1-Ea, IGF1-Eb, and IGF1-Ec, in promoting tumour growth, metastasis, and hormone signalling interactions, particularly with oestrogen. This review examines the function and clinical significance of IGF-1 isoforms, emphasising their mechanisms in gynaecological physiology and their contributions to EC pathogenesis. Evidence from other cancers further underscores the relevance of IGF1 isoforms in driving tumour behaviours, offering valuable insights into their potential as biomarkers and therapeutic _targets. Understanding these mechanisms provides opportunities for novel approaches to the prevention, diagnosis, and treatment of EC, improving patient outcomes and advancing the broader field of hormone-driven cancers. Full article
(This article belongs to the Special Issue Biomarkers for Treatment Prediction, Prognosis and Early Detection of Gynecologic Cancer)
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11 pages, 1089 KiB  
Article
Gastric Intestinal Metaplasia in Children and Adolescents Is Reversible upon Reaching Adulthood—Results from a Long-Term Cohort Study
by Jan Drnovšek, Nina Zidar, Jera Jeruc, Lojze M. Šmid, Gaj Vidmar, Borut Štabuc and Matjaž Homan
Cancers 2025, 17(1), 128; https://doi.org/10.3390/cancers17010128 - 3 Jan 2025
Viewed by 257
Abstract
Background/Objectives: Gastric intestinal metaplasia (GIM) is considered an irreversible preneoplastic precursor for gastric adenocarcinoma in adults. However, its significance in children and the long-term outcome remain poorly understood. Methods: All children diagnosed with GIM between 2000 and 2020 were identified at a large [...] Read more.
Background/Objectives: Gastric intestinal metaplasia (GIM) is considered an irreversible preneoplastic precursor for gastric adenocarcinoma in adults. However, its significance in children and the long-term outcome remain poorly understood. Methods: All children diagnosed with GIM between 2000 and 2020 were identified at a large tertiary referral centre. Upon reaching adulthood (≥18 years), the patients were invited to undergo follow-up esophagogastroduodenoscopy (using narrow-band imaging additionally to high-definition white light endoscopy), with gastric biopsies obtained according to the updated Sydney protocol. Childhood and adulthood gastric biopsies were re-evaluated by two experienced gastrointestinal pathologists using Kreyberg staining. Results: Paediatric GIM was diagnosed in 178/14,409 (1.2%) esophagogastroduodenoscopies performed during the study period. Fifty adult patients with childhood GIM agreed to participate in the study. The mean age at childhood and adulthood endoscopies were 14.3 years (median 15) and 25.2 years (median 24), respectively. The mean follow-up interval was 10.5 years. All childhood GIM cases were classified as complete-type. Notably, GIM completely resolved in 41/50 of patients (82%) by the time of adulthood follow-up. No dysplasia or carcinoma was detected in any patient. Childhood Helicobacter pylori infection, similar to other evaluated host-related factors, was not significantly associated with the persistence of GIM into adulthood (11.2% vs. 29.3%, p = 0.41). Conclusions: Childhood GIM was a rare finding but demonstrated a high rate of reversibility by adulthood regardless of Helicobacter pylori status, with no cases of dysplasia or carcinoma observed during long-term follow-up. Full article
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10 pages, 464 KiB  
Article
Challenging the Binary Classification of Endometrioid Endometrial Adenocarcinoma: The Evaluation of Grade 2 as an Independent Entity Based on Prognostic Characteristics and Recurrence Patterns
by Andreas Zouridis, Ammara Kashif, Ahmed Darwish, Christina Pappa, Federico Ferrari, Sarah Louise Smyth, Negin Sadeghi, Alisha Sattar, Stephen Damato, Mostafa Abdalla, Sean Kehoe, Susan Addley and Hooman Soleymani Majd
Cancers 2025, 17(1), 127; https://doi.org/10.3390/cancers17010127 - 3 Jan 2025
Viewed by 209
Abstract
Background: Although grade is a well-recognised prognostic factor for endometrioid endometrial cancer (EEC), in more studies grade 1 (G1) and grade 2 (G2) EEC are combined and compared together with grade 3 (G3) tumours. The aim of our study is to separately investigate [...] Read more.
Background: Although grade is a well-recognised prognostic factor for endometrioid endometrial cancer (EEC), in more studies grade 1 (G1) and grade 2 (G2) EEC are combined and compared together with grade 3 (G3) tumours. The aim of our study is to separately investigate the outcomes, prognostic factors and recurrence patterns of G2 EEC and whether the differentiation between G1 and G2 EEC is clinically useful. Methods: we retrospectively reviewed 523 patients with EEC treated with primary surgery over a decade (March 2010–January 2020) at Oxford University Hospitals NHS Trust, focusing on those with G2 disease. Results: Patients with G2 EEC had worse 5-year cancer-specific survival (93.3% vs. 98.5%, p < 0.01) compared to patients with G1 EEC, but a favourable prognosis compared to G3 EEG, both in terms of disease-free survival (91.6 vs. 83.8%, p = 0.04) and cancer-specific survival (93.3% vs. 78.5%, p < 0.01). Both stage and grade are independent risk factors for cancer-specific mortality in EEC. Cervical stromal involvement, parametrial involvement and distant metastatic disease are all independent risk factors for cancer-related mortality in G2 ECC. Only 12.5% of recurrences of G2 EEC were diagnosed with examination in routine follow up in asymptomatic patients. Conclusions: our results suggest that the grading system should continue to differentiate G1 EEC and G2 EEC for better prognosis interpretation. Full article
(This article belongs to the Special Issue Gynecologic Oncology: Clinical and Translational Research)
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14 pages, 1789 KiB  
Article
Multi-Centered Pre-Treatment CT-Based Radiomics Features to Predict Locoregional Recurrence of Locally Advanced Esophageal Cancer After Definitive Chemoradiotherapy
by Nuo Yu, Xiaolin Ge, Lijing Zuo, Ying Cao, Peipei Wang, Wenyang Liu, Lei Deng, Tao Zhang, Wenqing Wang, Jianyang Wang, Jima Lv, Zefen Xiao, Qinfu Feng, Zongmei Zhou, Nan Bi, Wencheng Zhang and Xin Wang
Cancers 2025, 17(1), 126; https://doi.org/10.3390/cancers17010126 - 3 Jan 2025
Viewed by 275
Abstract
Purpose: We constructed a prediction model to predict a 2-year locoregional recurrence based on the clinical features and radiomic features extracted from the machine learning method using computed tomography (CT) before definite chemoradiotherapy (dCRT) in locally advanced esophageal cancer. Patients and methods [...] Read more.
Purpose: We constructed a prediction model to predict a 2-year locoregional recurrence based on the clinical features and radiomic features extracted from the machine learning method using computed tomography (CT) before definite chemoradiotherapy (dCRT) in locally advanced esophageal cancer. Patients and methods: A total of 264 patients (156 in Beijing, 87 in Tianjin, and 21 in Jiangsu) were included in this study. All those locally advanced esophageal cancer patients received definite radiotherapy and were randomly divided into five subgroups with a similar number and divided into training groups and validation groups by five cross-validations. The esophageal tumor and extratumoral esophagus were segmented to extract radiomic features from the gross tumor volume (GTV) drawn by radiation therapists before radiotherapy, and six clinical features associated with prognosis were added. T stage, N stage, M stage, total TNM stage, GTV, and GTVnd volume were included to construct a prediction model to predict the 2-year locoregional recurrence of patients after definitive radiotherapy. Results: A total of 264 patients were enrolled from August 2012 to April 2018, with a median age of 62 years and 81% were males. The 2-year locoregional recurrence rate was 52.6%, and the 2-year overall survival rate was 45.6%. About 66% of patients received concurrent chemotherapy. In total, we extracted 786 radiomic features from CT images and the Principal Component Analysis (PCA) method was used to screen out the maximum 30 features. Finally, the Support Vector Machine (SVM) method was used to construct the integrated prediction model combining radiomics and clinical features. In the five training groups for predicting locoregional recurrence, the mean value of C-index was 0.9841 (95%CI, 0.9809–0.9873), and in the five validation groups, the mean value was 0.744 (95%CI, 0.7437–0.7443). Conclusions: The integrated radiomics model could predict the 2-year locoregional recurrence after dCRT. The model showed promising results and could help guide treatment decisions by identifying high-risk patients and enabling strategies to prevent early recurrence. Full article
(This article belongs to the Section Cancer Therapy)
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11 pages, 520 KiB  
Article
Usefulness of Serum Biomarkers in Predicting Anastomotic Leakage After Gastrectomy
by Diego Ramos, Enrique Gallego-Colón, Javier Mínguez, Ignacio Bodega, Pablo Priego and Francisca García-Moreno
Cancers 2025, 17(1), 125; https://doi.org/10.3390/cancers17010125 - 3 Jan 2025
Viewed by 322
Abstract
Background/Objectives: Anastomotic leakage (AL) is one of the most concerning complications following gastrectomy. The aim of this study was to assess and compare the predictive accuracy of C-reactive protein (CRP), procalcitonin (PCT), the neutrophil-to-lymphocyte ratio (NLR), the platelet-to-lymphocyte ratio (PLR), fibrinogen, and the [...] Read more.
Background/Objectives: Anastomotic leakage (AL) is one of the most concerning complications following gastrectomy. The aim of this study was to assess and compare the predictive accuracy of C-reactive protein (CRP), procalcitonin (PCT), the neutrophil-to-lymphocyte ratio (NLR), the platelet-to-lymphocyte ratio (PLR), fibrinogen, and the mean platelet volume (MPV) in the early diagnosis of post-gastrectomy AL. Methods: A prospective bicentric observational study was conducted including all patients undergoing elective gastrectomy between August 2018 and December 2022. The performance of the selected biomarkers in predicting the existence of AL within the first 7 postoperative days (PODs) was assessed. Results: A total of 107 patients were included for analysis. The incidence of AL was 20.56%, and the median day of diagnosis was on POD5 (interquartile range 4–6). CRP, PCT, the NLR, the PLR, and fibrinogen showed significant associations with the presence of AL (from POD2 for CRP and fibrinogen and from POD3 for PCT, NLR, and PLR). CRP demonstrated a superior predictive accuracy on POD4, with a threshold value of 181.4 mg/L (NPV 99%; AUC 0.87, p < 0.001); PCT demonstrated a superior predictive accuracy on POD7, with a threshold value of 0.13 μg/L (NPV 98%; AUC 0.84, p < 0.001); the NLR showed a superior predictive accuracy on POD6, with a threshold ratio of 6.77 (NPV 95%; AUC 0.86, p < 0.001); the PLR achieved a superior predictive accuracy on POD7, with a ratio of 234 (NPV 98%; AUC 0.71; p = 0.002); and fibrinogen demonstrated a superior predictive accuracy on POD5, with a threshold of 7.344 g/L (NPV 98%; AUC 0.74; p = 0.003). In the comparison of predictive accuracy, CPR, PCT, and the NLR were found to be superior to all other biomarkers. Conclusions: CRP, PCT, and the NLR are biomarkers with a sufficient predictive ability to clinically discard the presence of AL within the first postoperative week. Full article
(This article belongs to the Special Issue Advances in Abdominal Surgical Oncology and Intraperitoneal Therapies)
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24 pages, 377 KiB  
Review
Advances in Glioblastoma Diagnosis: Integrating Genetics, Noninvasive Sampling, and Advanced Imaging
by Ryan Gough, Randall W. Treffy, Max O. Krucoff and Rupen Desai
Cancers 2025, 17(1), 124; https://doi.org/10.3390/cancers17010124 - 2 Jan 2025
Viewed by 291
Abstract
Glioblastoma is the most common primary brain tumor in adult patients, and despite standard-of-care treatment, median survival has remained less than two years. Advances in our understanding of molecular mutations have led to changes in the diagnostic criteria of glioblastoma, with the WHO [...] Read more.
Glioblastoma is the most common primary brain tumor in adult patients, and despite standard-of-care treatment, median survival has remained less than two years. Advances in our understanding of molecular mutations have led to changes in the diagnostic criteria of glioblastoma, with the WHO classification integrating important mutations into the grading system in 2021. We sought to review the basics of the important genetic mutations associated with glioblastoma, including known mechanisms and roles in disease pathogenesis/treatment. We also examined new advances in image processing as well as less invasive and noninvasive diagnostic tools that can aid in the diagnosis and surveillance of those undergoing treatment for glioblastoma. Our review is intended to serve as an overview of the current state-of-the-art in the diagnosis and management of glioblastoma. Full article
(This article belongs to the Special Issue Outcomes in Glioblastoma Patients: From Diagnosis to Palliation)
10 pages, 242 KiB  
Article
Identification of the Determinants of Plexiform Neurofibroma Morbidity in Pediatric and Young Adult Neurofibromatosis Type 1 Patients: A Pilot Multivariate Approach
by Biagio de Brons, Britt Dhaenens, Rick van Minkelen and Rianne Oostenbrink
Cancers 2025, 17(1), 123; https://doi.org/10.3390/cancers17010123 - 2 Jan 2025
Viewed by 314
Abstract
Background: Plexiform neurofibromas (PNs) are histologically benign peripheral nerve sheath tumors associated with neurofibromatosis type 1 (NF1) and often lead to significant morbidity due to growth. Management includes watchful waiting, surgery for partial debulking, and, since recently, systemic treatment with MEK inhibitors. However, [...] Read more.
Background: Plexiform neurofibromas (PNs) are histologically benign peripheral nerve sheath tumors associated with neurofibromatosis type 1 (NF1) and often lead to significant morbidity due to growth. Management includes watchful waiting, surgery for partial debulking, and, since recently, systemic treatment with MEK inhibitors. However, due to the scarcity of natural history studies, our understanding of the natural progression of PNs to guide clinicians in deciding in whom and when to intervene is scarce. This study aims to describe the characteristics of NF1 patients with PNs and compare those at high risk for PN progression or experiencing significant morbidity from PN (complex PN) with NF1 patients with PNs of lower complexity. Methods: In this retrospective cohort study using clinical data from hospital records of NF1 patients with PNs seen at the Sophia Children’s Hospital in the Netherlands between 2012 and 2023, we assessed determinants of clinical phenotypes and PN characteristics predictive of outcomes, including PN complexity and the timing of intervention for PN. We assessed the outcomes using logistic regression analysis and Cox regression. Results: Ninety patients with a median age at last evaluation of 15.7 years and a median follow-up duration of 9.8 years were included. Out of 90 individuals with a benign PN, 37 developed plexiform neurofibroma morbidity during follow-up. Older age was (corrected for pathogenic NF1 variant and PN location) significantly associated with plexiform neurofibroma morbidity. Cox regression revealed that craniofacial and trunk PNs were associated with a higher intervention hazard compared to limb PNs. Conclusion: Our pilot multivariate approach identified older age and the location of the PN to be mostly associated with a higher chance of plexiform neurofibroma morbidity and higher intervention hazard. This may contribute to decisions regarding in whom and when to initiate treatment in NF1 patients with PNs. Full article
(This article belongs to the Special Issue Neurofibromatosis)
13 pages, 1497 KiB  
Systematic Review
Pancreaticobiliary Maljunction and Its Relationship with Biliary Cancer: An Updated and Comprehensive Systematic Review and Meta-Analysis on Behalf of TROGSS—The Robotic Global Surgical Society
by Yeisson Rivero-Moreno, Aman Goyal, Victor Bolívar, Nnenna Osagwu, Sophia Echevarria, José Gasca-Insuasti, Freddy Pereira-Graterol, Dagny von Ahrens, Omar Felipe Gaytán Fuentes, Luis Osvaldo Suárez-Carreón, Miljana Vladimirov, Beniamino Pascotto, Juan Santiago Azagra, Natale Calomino, Adel Abou-Mrad, Luigi Marano and Rodolfo J. Oviedo
Cancers 2025, 17(1), 122; https://doi.org/10.3390/cancers17010122 - 2 Jan 2025
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Abstract
Objective: This systematic review and meta-analysis aimed to determine the degree to which pancreaticobiliary maljunction (PBM) increases the risk of different types of biliary cancer (BC). Methods: A systematic review and meta-analysis were carried out using the following databases: PubMed, Embase, Cochrane Library, [...] Read more.
Objective: This systematic review and meta-analysis aimed to determine the degree to which pancreaticobiliary maljunction (PBM) increases the risk of different types of biliary cancer (BC). Methods: A systematic review and meta-analysis were carried out using the following databases: PubMed, Embase, Cochrane Library, Scopus, Web of Science, and Science Direct. We systematically searched from inception to April 2024. The search terms included were derived from the keywords “Pancreaticobiliary Maljunction” OR “Anomalous Pancreaticobiliary Junction” AND “Cancer” OR “Malignancy”. Studies that provided data comparing BC rates in relation to PBM presence or vice versa were included. The Newcastle–Ottawa Scale (NOS) was used for quality assessment. The random-effects model was used. Results: Fifteen studies were included with a total sample of 8604 patients, of whom 5015 (58.29%) were female with a mean age of 54.58 years. Patients with PBM had 8.42 (95% CI = 3.57–19.87) more risk of developing any type of BC, with a higher risk of GBC than BDC (OR = 16.91 vs. OR = 3.36, p-value = 0.003). There was a higher risk of having PBM in patients with GBC than BDC only when considering the Asian population (OR = 3.12, 95% CI = 1.09–8.94). Meta-regression analysis revealed that neither mean age (p = 0.087) nor percentage of female patients in the study population (p = 0.197) were statistically associated with the variations in OR for the risk of BC based on the presence of PBM. Conclusions: There is a significant association between PBM and the risk of having BC, mainly GBC when compared to BDC. Most of the studies published reported data from Japanese patients, which limits the generalization of the results. The age of patients and sex were not significantly associated with the relation between PBM and BC. Further prospective studies in broader populations will provide additional details to take measures for screening and early management of PBM and BC. Full article
(This article belongs to the Section Systematic Review or Meta-Analysis in Cancer Research)
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21 pages, 1013 KiB  
Article
Advanced Brain Tumor Classification in MR Images Using Transfer Learning and Pre-Trained Deep CNN Models
by Rukiye Disci, Fatih Gurcan and Ahmet Soylu
Cancers 2025, 17(1), 121; https://doi.org/10.3390/cancers17010121 - 2 Jan 2025
Viewed by 363
Abstract
Background/Objectives: Brain tumor classification is a crucial task in medical diagnostics, as early and accurate detection can significantly improve patient outcomes. This study investigates the effectiveness of pre-trained deep learning models in classifying brain MRI images into four categories: Glioma, Meningioma, Pituitary, and [...] Read more.
Background/Objectives: Brain tumor classification is a crucial task in medical diagnostics, as early and accurate detection can significantly improve patient outcomes. This study investigates the effectiveness of pre-trained deep learning models in classifying brain MRI images into four categories: Glioma, Meningioma, Pituitary, and No Tumor, aiming to enhance the diagnostic process through automation. Methods: A publicly available Brain Tumor MRI dataset containing 7023 images was used in this research. The study employs state-of-the-art pre-trained models, including Xception, MobileNetV2, InceptionV3, ResNet50, VGG16, and DenseNet121, which are fine-tuned using transfer learning, in combination with advanced preprocessing and data augmentation techniques. Transfer learning was applied to fine-tune the models and optimize classification accuracy while minimizing computational requirements, ensuring efficiency in real-world applications. Results: Among the tested models, Xception emerged as the top performer, achieving a weighted accuracy of 98.73% and a weighted F1 score of 95.29%, demonstrating exceptional generalization capabilities. These models proved particularly effective in addressing class imbalances and delivering consistent performance across various evaluation metrics, thus demonstrating their suitability for clinical adoption. However, challenges persist in improving recall for the Glioma and Meningioma categories, and the black-box nature of deep learning models requires further attention to enhance interpretability and trust in medical settings. Conclusions: The findings underscore the transformative potential of deep learning in medical imaging, offering a pathway toward more reliable, scalable, and efficient diagnostic tools. Future research will focus on expanding dataset diversity, improving model explainability, and validating model performance in real-world clinical settings to support the widespread adoption of AI-driven systems in healthcare and ensure their integration into clinical workflows. Full article
(This article belongs to the Special Issue Novel Approaches to Machine Learning and Artificial Intelligence in Cancer Research and Care)
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