Cancers

15 pages, 1323 KB

Open AccessArticle

Association of a CD44s-v5-v6 Null Phenotype with Advanced Stage Cholangiocarcinoma: A Preliminary Study

by Kyaw Zwar Myint, Thanakrit Mongkonsiri, Artit Jinawath and Rutaiwan Tohtong

Cancers 2026, 18(1), 21; https://doi.org/10.3390/cancers18010021 (registering DOI) - 20 Dec 2025

Background/Objectives: Cholangiocarcinoma (CCA) is an aggressive malignancy with a poor prognosis, creating an urgent need for novel biomarkers to improve risk stratification. The prognostic significance of the transmembrane glycoprotein CD44 and its isoforms (CD44s, v5, v6) in CCA remains controversial. This preliminary [...] Read more.

Background/Objectives: Cholangiocarcinoma (CCA) is an aggressive malignancy with a poor prognosis, creating an urgent need for novel biomarkers to improve risk stratification. The prognostic significance of the transmembrane glycoprotein CD44 and its isoforms (CD44s, v5, v6) in CCA remains controversial. This preliminary study aimed to investigate whether the combined loss of these isoforms could serve as a distinct prognostic indicator. Methods: We evaluated the expression of CD44s, CD44v5, and CD44v6 via immunohistochemistry on a retrospective cohort of 61 paraffin-embedded CCA patient tissue blocks from Ramathibodi Hospital, Bangkok, Thailand. Expression levels were correlated with clinicopathological parameters. Survival analyses, including Kaplan–Meier and Cox proportional hazards models, were used to determine the prognostic value of individual isoforms and the complete absence of all three. Results: Expression of CD44s, CD44v5, and CD44v6 was found in 52.5%, 47.5%, and 82.0% of tumors, respectively. In univariate and multivariate analyses, the expression of any single isoform was not a significant predictor of overall survival. However, a subgroup of 8 patients (13.1%) was identified whose tumors were negative for all three isoforms, a phenotype we termed “CD44s-v5-v6 Null”. This status was significantly associated with advanced TNM stages (p = 0.022). Patients with these Null tumors also showed a clinically relevant, though not statistically significant, trend towards poorer survival (median 7.0 vs. 12.0 months, p = 0.336). Conclusions: Individual CD44 isoforms did not serve as reliable independent prognostic markers in this cohort. Instead, the complete loss of the CD44 expression program characterizes a potential “CD44s-v5-v6 Null” phenotype associated with advanced-stage disease. Full article

(This article belongs to the Special Issue Advancements in “Cancer Biomarkers” for 2025–2026)

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16 pages, 3523 KB

Open AccessArticle

The Role of Computed Tomography-Determined Total Tumor Volume at Baseline in Predicting Outcomes of Patients with Locally Advanced Unresectable or Metastatic Pancreatic Ductal Adenocarcinoma

by Elissar Moujaes, Jules Dupont, Littisha Lawrance, Fiona Frau, Ghina Jardali, Lama Dawi, Michèle Kind, Caroline Su, Samy Ammari, Nohad Masri, Anamaria Bianca Mihele, Valérie Boige, Thomas Pudlarz, Cristina Smolenschi, Marine Valéry, Geraldine M. Camilleri, Alice Boilève, Michel Ducreux, Nathalie Lassau and Antoine Hollebecque

Cancers 2026, 18(1), 20; https://doi.org/10.3390/cancers18010020 (registering DOI) - 20 Dec 2025

Abstract

Background: Total tumor volume (TTV), derived from imaging data, has emerged as a potential prognostic biomarker in various cancers. This study aimed to evaluate the impact of TTV on outcomes in advanced pancreatic ductal adenocarcinoma (PDAC) and to validate a survival prediction model [...] Read more.

Background: Total tumor volume (TTV), derived from imaging data, has emerged as a potential prognostic biomarker in various cancers. This study aimed to evaluate the impact of TTV on outcomes in advanced pancreatic ductal adenocarcinoma (PDAC) and to validate a survival prediction model combining TTV with baseline clinico-biological markers. Materials and Methods: We conducted a retrospective analysis of 150 patients with locally advanced or metastatic PDAC treated with first-line FOLFIRINOX from 2010 to 2021. TTV was calculated by manually segmenting all visible lesions on baseline CT scans. Progression-free survival (PFS) and overall survival (OS) were the primary endpoints. A cut-off value for TTV predicting 6-month PFS was determined in 140 patients using AUC and Youden’s Index and then applied to OS analysis. A multivariate Cox regression model incorporating TTV, CA 19-9, and neutrophil-to-lymphocyte ratio (NLR) was developed in 94 patients to establish a survival risk score. Results: 12,028 lesions were annotated. OS was slightly but significantly different between TTV above and below the median value of 69.60 cm³ (12.4 vs. 13.5 months, p = 0.0269). A cut-off of 400 cm³ distinguished two groups: patients with TTV > 400 cm³ had significantly shorter OS (9.4 months) compared to those with TTV ≤ 400 cm³ (13.0 months, p = 0.0056). A similar trend was observed for PFS, though not statistically significant (7.4 months for TTV > 400 cm³ vs. 8.2 months for TTV ≤ 400 cm³, p = 0.0735). The combined model achieved a mean c-index of 0.62 for PFS and 0.64 for OS. Based on the risk score, high-risk patients had significantly worse median PFS (5.5 vs. 9.2 months, p = 0.0008) and median OS (7.2 vs. 13.5 months, p < 0.0001). Conclusions: TTV is a valuable prognostic marker in advanced PDAC. A model integrating TTV with biological markers enhances survival prediction and supports risk stratification in clinical practice. Full article

(This article belongs to the Special Issue Advances in Pancreatic Ductal Adenocarcinoma Diagnosis and Treatment 2nd Edition)

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15 pages, 996 KB

Open AccessArticle

Pleuro-Pulmonary Extramedullary Plasmacytomas in Multiple Myeloma: A 15-Year Experience from a Tertiary Center

by Sorina Badelita, Sinziana Barbu, Camelia Dobrea, Cerasela Jardan, Monica Popescu, Codruta Delia Popa, Claudia Toma, Larisa Zidaru, Mihai Emanuel Himcinschi, Horia Mihail Sandu, Didona Vasilache, Adelina Vlad and Daniel Coriu

Cancers 2026, 18(1), 19; https://doi.org/10.3390/cancers18010019 (registering DOI) - 20 Dec 2025

Abstract

Background/Objectives: Extramedullary involvement in multiple myeloma represents an aggressive disease phenotype, associated with reduced survival and an unfavorable prognosis. Thoracic manifestations are rare and remain poorly characterized in the literature. Methods: We conducted a retrospective, single-center study at the Fundeni Clinical [...] Read more.

Background/Objectives: Extramedullary involvement in multiple myeloma represents an aggressive disease phenotype, associated with reduced survival and an unfavorable prognosis. Thoracic manifestations are rare and remain poorly characterized in the literature. Methods: We conducted a retrospective, single-center study at the Fundeni Clinical Institute, including patients diagnosed with multiple myeloma between February 2010 and February 2025. The study cohort consisted of 34 patients with infiltration of the pulmonary parenchyma, pleura, or the presence of myelomatous pleural effusion. Diagnosis was confirmed using a combination of imaging modalities (computed tomography or magnetic resonance imaging), cytological examination, immunophenotyping, and histopathological confirmation whenever feasible. Results: Out of a total of 2012 patients with multiple myeloma, the incidence of pleuro-pulmonary extramedullary involvement was 1.6%. The median age at diagnosis was 58 years. Pleuro-pulmonary disease was present at initial diagnosis in 26.5% of cases, while 73.5% developed it at relapse. The most common presentation involved combined pleural involvement and myelomatous effusion (70.6%). Adverse prognostic markers included elevated β2-microglobulin levels (in over 80% of cases) and increased lactate dehydrogenase (LDH) in approximately 50%. Cytogenetic abnormalities such as del(17p), t(4;14), t(14;16), t(11;14), and 1q gain were identified. The median overall survival (OS) from the diagnosis of pleuro-pulmonary extramedullary disease was 16 months, with a 2-year survival rate of 25%. No patient survived beyond 5 years. The median progression-free survival (PFS) was 9 months. Conclusions: Our findings confirm the aggressive clinical course and poor prognosis of these disease manifestations, mainly when they occur at relapse. In the absence of standardized treatment guidelines, individualizing therapy and accessing novel strategies may be essential for improving patient survival. Full article

(This article belongs to the Special Issue Diagnosis of Hematologic Malignancies: 2nd Edition)

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21 pages, 2736 KB

Open AccessArticle

Finding the True Responders: Stratifying dMMR/MSI-H Tumors for ICI Response

by Nari Kim, Seongwon Na, Jisung Jang, Mihyun Kim, Jun Hee Pyo and Kyung Won Kim

Cancers 2026, 18(1), 18; https://doi.org/10.3390/cancers18010018 (registering DOI) - 19 Dec 2025

Abstract

Background/Objectives: Immune checkpoint inhibitors (ICIs) show durable efficacy in tumors with deficient mismatch repair (dMMR) or high microsatellite instability (MSI-H), yet clinical responses remain heterogeneous. This study aimed to define immune subgroups within dMMR/MSI-H tumors and develop a reproducible transcriptomic signature predictive [...] Read more.

Background/Objectives: Immune checkpoint inhibitors (ICIs) show durable efficacy in tumors with deficient mismatch repair (dMMR) or high microsatellite instability (MSI-H), yet clinical responses remain heterogeneous. This study aimed to define immune subgroups within dMMR/MSI-H tumors and develop a reproducible transcriptomic signature predictive of ICI response. Methods: Four MSI-H-enriched cancer types (UCEC, COAD, READ, STAD) from The Cancer Genome Atlas were analyzed. Tumors were stratified by immune cell infiltration (MCP-counter immune composite score) and T-cell-inflamed gene expression profiles (GEP score). Integrating these two axes defined four immune subgroups. Differential expression, random forest feature selection, and pathway enrichment were performed to identify immune programs. A 20-gene immune signature representing the most immune-active subgroup was developed and validated across TCGA, GEO (GSE39582), and IMvigor210 cohorts. Results: Among the four subgroups, the most immune-active group showed strong activation of interferon signaling, antigen presentation, and T-cell-mediated pathways. The 20-gene signature—including CD74, STAT1, TAP1, and HLA-class genes—achieved high reproducibility (mean AUC = 0.95 ± 0.02; accuracy ≈ 89%). In the IMvigor210 cohort, this signature identified tumors with higher PD-L1 blockade response (55.6% vs. 32.8%, p = 0.034) and improved survival trends in the TMB-high subset. Conclusions: The proposed 20-gene signature quantitatively captures immune heterogeneity in dMMR/MSI-H tumors and serves as a practical, interpretable biomarker to identify true ICI responders and guide precision immunotherapy. Full article

(This article belongs to the Section Cancer Immunology and Immunotherapy)

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13 pages, 649 KB

Open AccessReview

Oral Squamous Cell Carcinoma Associated with Dental Implants: A Literature Review with Focus on Field-Cancerized Mucosa

by Maria Cuevas-Nunez, Cosimo Galletti, Gianluca Tenore, Umberto Romeo, Rosa Ballester Victoria, María José Biosca Gómez de Tejada, Javier Bara-Casaus and Maria Teresa Fernández Figueras

Cancers 2026, 18(1), 17; https://doi.org/10.3390/cancers18010017 - 19 Dec 2025

Abstract

Background: The oncologic safety of dental implants (DIs) in patients with oral field cancerization (OFC) remains uncertain. Increasing reports of oral squamous cell carcinoma (OSCC) developing adjacent to DIs have raised concerns regarding the interaction between implants, chronic inflammation, and genetically altered mucosa. [...] Read more.

Background: The oncologic safety of dental implants (DIs) in patients with oral field cancerization (OFC) remains uncertain. Increasing reports of oral squamous cell carcinoma (OSCC) developing adjacent to DIs have raised concerns regarding the interaction between implants, chronic inflammation, and genetically altered mucosa. Methods: A comprehensive PubMed/MEDLINE search was performed through June 2025 to identify English- or Spanish-language publications reporting primary OSCC occurring in proximity to DIs. Extracted variables included patient demographics, tumor site, clinical presentation, presence of oral potentially malignant disorders (OPMD) or prior OSCC, peri-implant inflammation, management, and outcomes. Cases describing clinical features compatible with field-altered mucosa (e.g., OPMD or prior OSCC) were evaluated descriptively, recognizing that formal histopathologic or molecular evidence of OFC was rarely reported. Results: A total of 105 implant-associated OSCC cases were identified. The mean patient age was 66.8 years (range: 40–90), with a female predominance (1.3:1). The mandible was the most frequently involved site (86.7%). A prior history of OPMD or OSCC was reported in 53 patients (50.5%), and peri-implantitis preceding diagnosis in 21 cases (19.0%). The most common clinical presentations were exophytic (59.0%) and ulcerated (37.1%) lesions, frequently mimicking peri-implantitis and contributing to diagnostic delay. Reported outcomes included recurrence in 11 cases (10.5%) and death in 13 cases (12.4%). Conclusions: Current evidence suggests that implant-associated OSCC frequently occurs in patients with pre-existing mucosal alterations and may be influenced by the interaction of field cancerization with local inflammatory and mechanical factors. Implant rehabilitation in individuals with OPMD, prior OSCC, or epithelial dysplasia should be undertaken cautiously, with rigorous long-term surveillance to ensure oncologic safety. Full article

(This article belongs to the Special Issue Oral Potentially Malignant Disorders and Oral Cavity Cancer)

14 pages, 590 KB

Open AccessReview

Depression as a Prodromal Symptom of Pancreatic Cancer: A Narrative Review

by Chiara Deori, Federica Andreis, Valentina Giubileo, Silvia Noventa, Ester Oneda, Fausto Meriggi and Alberto Zaniboni

Cancers 2026, 18(1), 16; https://doi.org/10.3390/cancers18010016 - 19 Dec 2025

Abstract

Background: Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies, typically diagnosed at an advanced stage. The identification of prodromal symptoms could support earlier detection. Among these, depression is frequently reported, raising the question of whether it may represent not only [...] Read more.

Background: Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies, typically diagnosed at an advanced stage. The identification of prodromal symptoms could support earlier detection. Among these, depression is frequently reported, raising the question of whether it may represent not only a reactive response but also a paraneoplastic manifestation. Methods: We conducted a narrative review of clinical, epidemiological and biological literature published between 1988 and 2025. Searches were performed in PubMed/MEDLINE, Scopus, and Web of Science using predefined keywords related to pancreatic cancer, depression, prodromal symptoms, cytokines, and the kynurenine pathway. Eligible studies included clinical cohorts, population-based analyses, biological investigations, and case reports exploring the temporal or mechanistic link between depression and PDAC. Results: A substantial proportion of patients (10–20%) exhibit depressive symptoms in the months preceding the clinical diagnosis of pancreatic cancer. In several cases, depression occurs independent of weight loss and new-onset diabetes. Biological evidence highlights the involvement of pro-inflammatory cytokines (IL-6, IL-1β, TNF-α), NF-κB signaling, and activation of the tryptophan–kynurenine pathway (IDO), suggesting a link between tumor-related processes and mood alterations. These mechanistic findings are actually hypothesis-generating, deriving mainly from small clinical cohorts and preclinical models. Clinically, depression is associated with reduced adherence to treatment, poorer quality of life, and shorter survival. However, no specific depressive phenotype has been identified. Conclusions: Depression may represent a potential prodromal symptom of pancreatic cancer, reflecting systemic biological processes as well as psychological reactions. Its utility as a standalone marker remains limited; future studies should integrate psychiatric, clinical and biological biomarker assessments to enhance early clinical diagnosis. Full article

(This article belongs to the Section Cancer Causes, Screening and Diagnosis)

15 pages, 2659 KB

Open AccessArticle

Targeting Glutamine Transporters as a Novel Drug Therapy for Synovial Sarcoma

by Tran Duc Thanh, Naoki Takada, Hana Yao, Yoshitaka Ban, Naoto Oebisu, Manabu Hoshi, Nguyen Tran Quang Sang, Nguyen Van Khanh, Dang Minh Quang, Le Thi Thanh Thuy, Tran Trung Dung and Hidetomi Terai

Cancers 2026, 18(1), 15; https://doi.org/10.3390/cancers18010015 - 19 Dec 2025

Abstract

Background/Objectives: Synovial sarcoma (SS) is a malignant soft tissue neoplasm with good outcomes in adolescents with localized tumors, but poor outcomes in older adults and in advanced or metastatic cases. Targeting cancer metabolism, such as glutamine metabolism, is a promising therapeutic [...] Read more.

Background/Objectives: Synovial sarcoma (SS) is a malignant soft tissue neoplasm with good outcomes in adolescents with localized tumors, but poor outcomes in older adults and in advanced or metastatic cases. Targeting cancer metabolism, such as glutamine metabolism, is a promising therapeutic strategy. In this study, we investigated glutamine dependency in SS and assessed the therapeutic potential of inhibiting the glutamine transporter ASCT2 using V9302. Methods: Immunohistochemistry (IHC) was used to evaluate ASCT2 expression in SS and liposarcoma (LPS) specimen. The effects of glutamine deprivation and V9302 were examined in a SS cell line (HS-SY-II), patient-derived SS cells (SSH1), and a normal cell line (HEK293). Cell viability, apoptosis, and protein expression were assessed using the CCK-8 assay, flow cytometry, and Western blotting, respectively. The therapeutic efficacy of V9302 was evaluated in a xenograft model using IHC. Results: ASCT2 expression was elevated in SS tumor tissues compared with adjacent normal tissues and LPS specimens. Both the HS-SY-II cell line and SSH1 cells exhibited strong glutamine dependency for proliferation. V9302 selectively reduced HS-SY-II cell viability by suppressing the AKT/mTOR signaling pathway and inducing apoptosis via caspase-3 activation, with minimal effects on control cells. In vivo, V9302 administration significantly inhibited tumor growth without inducing systemic toxicity, and IHC of the treated tumors confirmed the suppression of the mTOR pathway and induction of apoptosis. Conclusions: Our findings suggest that SS is a glutamine-dependent malignancy and validate ASCT2 as a promising therapeutic target. The ASCT2 inhibitor V9302 demonstrated therapeutic efficacy both in vitro and in vivo, supporting its potential as a therapeutic agent for SS. Full article

(This article belongs to the Section Cancer Drug Development)

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18 pages, 836 KB

Open AccessArticle

Human Papillomavirus Self-Sampling Attitudes Amongst Women Living with HIV Prior to a Self-Sampling Intervention

by Sofia Nicolls, Emma Karlsen, Isabelle Boucoiran, Shariq Haider, Valérie Martel-Laferrière, Vanessa Poliquin, Marie-Louise Vachon, Sharon Walmsley, Alexander Wong, Sean Yaphe, Mark H. Yudin, Gina Ogilvie, Deborah Money and Elisabeth McClymont

Cancers 2026, 18(1), 14; https://doi.org/10.3390/cancers18010014 - 19 Dec 2025

Abstract

Background/Objectives: Our objective was to determine the acceptability of and attitudes towards HPV self-sampling among women with HIV and investigate any associations between self-sampling attitudes and participant demographic and clinical characteristics. Methods: Women with HIV aged 18–45 were given a description of [...] Read more.

Background/Objectives: Our objective was to determine the acceptability of and attitudes towards HPV self-sampling among women with HIV and investigate any associations between self-sampling attitudes and participant demographic and clinical characteristics. Methods: Women with HIV aged 18–45 were given a description of HPV self-sampling and instructions on how to self-collect the sample. Participants completed a questionnaire assessing their perceptions of the acceptability and comfort of HPV self-sampling before using the self-sampling methodology. Responses were based on a 5-point Likert scale (strongly agree to strongly disagree) for each statement. Participants’ characteristics were included in bivariate analysis. Chi-square and Fisher’s exact tests were used to assess associations between questionnaire results and participant characteristics. Results: Of the 117 completed questionnaires, 79.6% of participants had a CD4+ T cell count ≥ 500 cells/mm³. Participants’ median age was 39 (IQR 34–43). One hundred participants (85.5%) felt confident they could collect their samples correctly, and 77.8% did not think they would experience difficulties with self-collection. Most participants (68.4%) preferred to self-collect their sample instead of provider-collected sampling. Ninety-six participants (82.1%) agreed they would likely use self-collection methods for future cervical screening. Many participants were concerned about receiving a positive HPV result (68.4%), passing HPV on to their partner(s) (75.7%), and disclosing their HPV status to friends/family (49.6%). Conclusions: Women with HIV seem to be accepting of HPV self-sampling as a cervical cancer screening methodology; however, many participants were concerned about the implications associated with a positive HPV test result. Full article

(This article belongs to the Special Issue Cervical Cancer Screening: Current Practices and Future Perspectives)

12 pages, 1468 KB

Open AccessArticle

Prognostic Impact of Pulmonary Metastasectomy for Uterine Malignancies: A Retrospective Analysis of 38 Cases

by Hiroyuki Adachi, Hiroyuki Ito, Takuya Nagashima, Tetsuya Isaka, Kotaro Murakami, Noritake Kikunishi, Naoko Shigeta and Aya Saito

Cancers 2026, 18(1), 13; https://doi.org/10.3390/cancers18010013 - 19 Dec 2025

Abstract

Background: Uterine malignancies frequently metastasize to the lungs. Pulmonary metastasectomy has demonstrated survival benefits in some malignancies; however, its efficacy for uterine malignancies remains unclear. Methods: We retrospectively analyzed 38 patients who underwent pulmonary metastasectomy for uterine malignancies at the Kanagawa Cancer Center [...] Read more.

Background: Uterine malignancies frequently metastasize to the lungs. Pulmonary metastasectomy has demonstrated survival benefits in some malignancies; however, its efficacy for uterine malignancies remains unclear. Methods: We retrospectively analyzed 38 patients who underwent pulmonary metastasectomy for uterine malignancies at the Kanagawa Cancer Center between 2010 and 2020. The primary endpoint was recurrence-free survival (RFS) after pulmonary resection. Results: The median patient age was 63 years. The primary sites were the cervical uteri (n = 22) and corpus uteri (n = 16). The FIGO stages at the time of treatment for the primary tumor were I, II, III, IV, and unknown in 20, 7, 9, 1, and 1 patient, respectively. The median disease-free interval (DFI), defined as the interval between primary treatment and first recurrence, was 26.5 months. Most patients had single metastasis (n = 32). The procedures for metastasectomy included lobectomy, segmentectomy, and wedge resection (n = 15, 8, and 15, respectively), and two cases resulted in microscopically incomplete resection. The median follow-up period after pulmonary metastasectomy was 57 months, with 16 patients experiencing recurrence after pulmonary metastasectomy (5-year RFS rate: 55.6%). Univariate analysis identified FIGO stage ≥ III, DFI < 12 months, presence of synchronous extrapulmonary recurrence, and uterine sarcoma as poor prognostic factors. No prognostic differences were found between cervical and corpus uteri cancers. Conclusions: Pulmonary metastasectomy may confer prognostic benefits in patients with uterine malignancies. Careful consideration is warranted for patients with advanced-stage primary tumors, early recurrence after primary treatment, synchronous extrapulmonary recurrence, and uterine sarcoma. Full article

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

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18 pages, 3861 KB

Open AccessArticle

Cardiovascular Risk Factors Among Younger and Older C-AYA Cancer Survivors Treated with Anthracyclines: A Single-Center Analysis

by Matthew Dean, Ben Bane, OreOluwa Aluko, Yiwei Hang, Ericka Miller, Sherin Menachery, David Chuquin, Adam Aston, Xiaoyan Deng, Dipankar Bandyopadhyay, Jennifer Jordan, Uyen Truong, Madhu Gowda and Wendy Bottinor

Cancers 2026, 18(1), 12; https://doi.org/10.3390/cancers18010012 - 19 Dec 2025

Abstract

Background/Objectives: Among survivors of cancer diagnosed in childhood, adolescence, or young adulthood (C-AYAs), cardiotoxic therapies combined with acquired cardiovascular risk factors (CVRFs) increase the risk for cardiovascular events. To our knowledge, no prior analysis has examined CVRFs among C-AYAs < 20 years [...] Read more.

Background/Objectives: Among survivors of cancer diagnosed in childhood, adolescence, or young adulthood (C-AYAs), cardiotoxic therapies combined with acquired cardiovascular risk factors (CVRFs) increase the risk for cardiovascular events. To our knowledge, no prior analysis has examined CVRFs among C-AYAs < 20 years old or compared CVRFs among younger and older C-AYAs. Methods: In this single-center study, individuals diagnosed with cancer at ≤39 years, treated with anthracycline-based chemotherapy (2010–2023), and with a post-treatment lipid panel and ≥2 post-treatment ambulatory blood pressure measurements were included. The CVRF prevalence was assessed among C-AYAs < 20 and ≥20 years old, using age-appropriate AAP and ACC/AHA guidelines. These prevalences were compared with the ICD-9/10 code prevalence. The prescription of medications with antihypertensive effects (MAHEs) and lipid-lowering therapy was assessed. Results: Among 276 C-AYAs, the median age was 28.1 years (IQR 18.1–38.3) at dyslipidemia screening and 29.3 (IQR 20.0–38.7) at hypertension screening. Dyslipidemia was present in 52.9% (146/276) and hypertension in 56.2% (155/276) of C-AYAs. C-AYAs < 20 years old had a high prevalence of dyslipidemia, 51.7% (45/87), and hypertension, 31.9% (29/91). CVRFs were frequently underdiagnosed, particularly dyslipidemia, among C-AYAs < 20 years old, with only 12.6% (11/87) having a diagnosis via the ICD code. C-AYAs < 20 years old with diagnoses of dyslipidemia and hypertension were significantly less likely to receive lipid-lowering therapy (2.2% vs. 14.9%) and trended toward less MAHEs (13.8% vs. 31.0%) compared to C-AYAs ≥ 20. Conclusions: Among C-AYAs treated with anthracyclines, dyslipidemia and hypertension were highly prevalent even at a young age (<20 years). Younger survivors with dyslipidemia and hypertension were less frequently prescribed lipid-lowering therapy or MAHEs. Full article

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

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13 pages, 991 KB

Open AccessSystematic Review

Liver Transplantation Versus Resection for Hepatocellular Carcinoma: An Umbrella and Meta-Meta-Analysis of Published Evidence, 2000–2025

by Seoung Hoon Kim, Byeong Ho An, Jin A Lee and Go Woon Jeong

Cancers 2026, 18(1), 11; https://doi.org/10.3390/cancers18010011 - 19 Dec 2025

Abstract

Background: Multiple meta-analyses have compared liver resection (LR) with liver transplantation (LT) for hepatocellular carcinoma (HCC), but overlapping primary studies and heterogeneous outcome definitions have complicated interpretation. Methods: A PRISMA/PRIOR-compliant umbrella review (PROSPERO CRD420251069248) was conducted. PubMed, Embase, and CENTRAL were searched for [...] Read more.

Background: Multiple meta-analyses have compared liver resection (LR) with liver transplantation (LT) for hepatocellular carcinoma (HCC), but overlapping primary studies and heterogeneous outcome definitions have complicated interpretation. Methods: A PRISMA/PRIOR-compliant umbrella review (PROSPERO CRD420251069248) was conducted. PubMed, Embase, and CENTRAL were searched for meta-analyses published between 1 January 2000 and 30 September 2025. Quantitative meta-analyses comparing LT and LR were included, while one systematic review of meta-analyses was synthesised narratively. Effect directions were standardised; hazard ratio (HR)-based summaries (LR:LT; values > 1 favour LT) were pooled using random-effects models, whereas odds ratio (OR)-based summaries were described qualitatively because of heterogeneity in endpoint definitions. Results: Four quantitative meta-analyses and one systematic review of meta-analyses met the inclusion criteria. Pooled HRs confirmed LT superiority: overall survival (OS) HR 1.35 (95% CI 1.17–1.55) and disease-free survival (DFS) HR 2.58 (95% CI 2.25–2.96). OR-based summaries from recent meta-analyses were directionally consistent but were not pooled. Conclusions: This umbrella synthesis demonstrates that LT provides superior long-term OS and DFS compared with LR for HCC, with consistent robustness across both Milan and extended selection criteria. Methodological safeguards against study overlap and subgroup insights—including intention-to-treat analyses, viral etiology (hepatitis B virus/hepatitis C virus), era, and geographic region—reinforce LT as the preferred strategy for eligible patients, while LR remains a critical option where graft availability is limited. Full article

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

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14 pages, 527 KB

Open AccessReview

Circulating Tumor Cells in Glioblastoma

by Robert H. Eibl and Markus Schneemann

Cancers 2026, 18(1), 10; https://doi.org/10.3390/cancers18010010 - 19 Dec 2025

Abstract

Glioblastoma multiforme (GBM) remains a devastating brain tumor with poor prognosis, traditionally viewed as non-metastatic. The recent detection of circulating tumor cells (CTCs) in glioblastoma challenges this long-held view and opens new opportunities for liquid biopsy in neuro-oncology. This review summarizes current understanding [...] Read more.

Glioblastoma multiforme (GBM) remains a devastating brain tumor with poor prognosis, traditionally viewed as non-metastatic. The recent detection of circulating tumor cells (CTCs) in glioblastoma challenges this long-held view and opens new opportunities for liquid biopsy in neuro-oncology. This review summarizes current understanding of glioblastoma CTCs, emphasizing their unique properties, detection technologies, and differences compared to CTCs in extracranial cancers. Key challenges include their rarity, the absence of epithelial markers, and the presence of the blood–brain barrier. Despite the need for specialized enrichment approaches, CTC analysis in glioblastoma can offer helpful information regarding tumor heterogeneity, treatment response, and minimal residual disease. We discuss emerging clinical studies leveraging CTCs for early relapse detection and therapy monitoring. Integrating CTC phenotyping with molecular and functional characterization may enhance future personalized treatment strategies in glioblastoma. Refined CTC methodologies combined with other liquid biopsy modalities may transform glioblastoma management, improving patient outcomes through less invasive, dynamic tumor surveillance. Full article

(This article belongs to the Special Issue Circulating Tumor Cells (CTCs) and the Implementation of Liquid Biopsy (2nd Edition))

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25 pages, 1653 KB

Open AccessReview

AI-Powered Histology for Molecular Profiling in Brain Tumors: Toward Smart Diagnostics from Tissue

by Maki Sakaguchi, Akihiko Yoshizawa, Kenta Masui, Tomoya Sakai and Takashi Komori

Cancers 2026, 18(1), 9; https://doi.org/10.3390/cancers18010009 - 19 Dec 2025

Abstract

The integration of molecular features into histopathological diagnoses has become central to the World Health Organization (WHO) classification of central nervous system (CNS) tumors, improving prognostic accuracy and supporting precision medicine. However, unequal access to molecular testing limits the universal application of integrated [...] Read more.

The integration of molecular features into histopathological diagnoses has become central to the World Health Organization (WHO) classification of central nervous system (CNS) tumors, improving prognostic accuracy and supporting precision medicine. However, unequal access to molecular testing limits the universal application of integrated diagnosis. To address this, artificial intelligence (AI) models are being developed to predict molecular alterations directly from histological data. In gliomas, deep learning applied to whole-slide images (WSIs) of permanent sections achieves neuropathologist-level accuracy in predicting biomarkers such as IDH mutation and 1p/19q co-deletion, as well as in molecular subtype classification and outcome prediction. Recent advances extend these approaches to intraoperative cryosections, enabling real-time glioma grading, molecular prediction, and label-free tissue analysis using modalities such as stimulated Raman histology and domain-adaptive image translation. Beyond gliomas, AI-powered histology is being explored in other brain tumors, including morphology-based molecular classification of spinal cord ependymomas and intraoperative discrimination of gliomas from primary CNS lymphomas. This review summarizes current progress in AI-assisted molecular profiling prediction of brain tumors from tissue, highlighting opportunities for rapid, accurate, and globally accessible diagnostics. The integration of histology and computational methods holds promise for the development of smart AI-assisted neuro-oncology. Full article

(This article belongs to the Special Issue Molecular Pathology of Brain Tumors)

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25 pages, 10991 KB

Open AccessArticle

Histogenesis of Atypical Teratoid Rhabdoid Tumors: Anatomical and Embryological Perspectives

by Tadanori Tomita

Cancers 2026, 18(1), 8; https://doi.org/10.3390/cancers18010008 - 19 Dec 2025

Abstract

Objectives: Atypical teratoid/rhabdoid tumors (ATRTs) are rare, malignant central nervous system (CNS) neoplasms that predominantly affect infants and young children. While ATRT arises throughout the CNS, its extracranial counterpart, malignant rhabdoid tumor, occurs in other organs. A single-institutional cohort is reviewed to map [...] Read more.

Objectives: Atypical teratoid/rhabdoid tumors (ATRTs) are rare, malignant central nervous system (CNS) neoplasms that predominantly affect infants and young children. While ATRT arises throughout the CNS, its extracranial counterpart, malignant rhabdoid tumor, occurs in other organs. A single-institutional cohort is reviewed to map anatomic distribution of pediatric ATRTs and to integrate a literature review to contextualize ATRT histogenesis from anatomical and embryological perspectives. Methods: A retrospective review was conducted on a cohort of 50 pediatric patients with ATRT treated over 20 years. Demographic, surgical, and neuroimaging data were correlated to define tumor location, extent, and compartmental involvement. A focused literature review synthesized molecular subclassifications and proposed cells of origin/cytogenesis. Results: Of the 50 ATRTs, 18 (36%) were infratentorial, 15 (30%) supratentorial, 11 (22%) in the pineal region, and 6 (12%) in the spinal compartment. Among infratentorial tumors, 10 were centered in the fourth ventricle, with or without extension into the cerebellopontine angle (CPA) cistern; the remainder arose in the CPA. Among ATRTs of the cerebral hemispheres, 3 showed bi-hemispheric involvement crossing the falx cerebri. ATRTs of the pineal region predominantly originated from the superior medullary velum. These topographic data were corelated with embryological and molecular information available in the literature. Conclusions: ATRTs arise across diverse neuroanatomical compartments—including intraparenchymal, intraventricular, extra-axial, and extradural sites—underscoring biological heterogeneity. Inactivation of SMARCB1 is the defining molecular event and principal oncogenic driver, although the upstream mechanisms precipitating these alterations remain incompletely resolved. Molecular subgroups—ATRT-TYR, ATRT-SHH, and ATRT-MYC—display distinct age distributions and anatomic predilections, implicating developmental context in tumor initiation. The characteristic cellular admixture of rhabdoid cells with mesenchymal and/or epithelial differentiation, together with intra- and extra-axial and occasional extradural presentations, supports a model in which at least a subset of ATRTs may originate from neural crest-derived lineages, despite little or no neural crest contribution to brain parenchyma development. Neural plate border progenitors with bipotent features represent a plausible intraparenchymal cell of origin. Definitive resolution of these origins and the mechanisms of SMARCB1 disruption will require integrated approaches. Further investigations are warranted to clarify these mechanisms. Full article

(This article belongs to the Special Issue Current Concept and Management of Pediatric ATRTs—2nd Edition)

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23 pages, 1797 KB

Open AccessReview

Beyond Precision: Ambiomic Survivorship in Childhood and AYA Cancer

by Juan Antonio Ortega-García, Omar Shakeel, Nicole M. Wood, Antonio Pérez-Martínez, Jose Luís Fuster-Soler and Mark D. Miller

Cancers 2026, 18(1), 7; https://doi.org/10.3390/cancers18010007 - 19 Dec 2025

Abstract

Background: Survival among children and adolescents and young adults (AYA) with cancer has improved substantially over recent decades; however, dominant survivorship models remain reactive—activated post-treatment and anchored to static exposure- and organ-based screening. This design underuses the anticipatory window at diagnosis and overlooks [...] Read more.

Background: Survival among children and adolescents and young adults (AYA) with cancer has improved substantially over recent decades; however, dominant survivorship models remain reactive—activated post-treatment and anchored to static exposure- and organ-based screening. This design underuses the anticipatory window at diagnosis and overlooks environmental and social determinants that modulate outcomes across the life course. Methods: We narratively reviewed international frameworks including the Children’s Oncology Group (COG), the International Late Effects of Childhood Cancer Guideline Harmonization Group (IGHG), the Pan-European Network for Care of Survivors after Childhood and Adolescent Cancer (PanCare) and the National Comprehensive Cancer Network (NCCN), and synthesized evidence on environmental determinants, exposomics, toxicogenomics, and implementation. Building on two decades of real-world practice, we describe the evolution from the Pediatric Environmental History (PEHis) to the Ambiomic Health Compass (AHC), integrating genomic, exposomic, geospatial, clinical, and biomonitoring layers into routine care. In this framework, survivorship is conceptualized as beginning at the time of cancer diagnosis (“day 0”). Results: PEHis operationalizes guideline-based care with structured environmental and social assessment, personalized plans, and community integration, contributing to improved survival, healthier behaviors, reduced treatment-related mortality and stronger oncology–primary-care coordination. AHC extends PEHis with dynamic risk recalibration, contextual alerts, targeted biomonitoring, and toxicogenomic interpretation, enabling anticipatory decisions from day 0. The manuscript summarizes the paradigm shift (current vs. Ambiomic models), the domain-specific expansion over existing guidelines, the core clinical/system tools, and time-bound metrics (12, 24, 60 months) to support implementation and evaluation. Conclusions: Survivorship should move upstream—from late surveillance to ambiomic, exposure-aware care beginning at diagnosis. Integrating advanced exposomics, mutational epidemiology, and explainable analytics can reduce preventable events and chronicity, enhance equity, and align pediatric oncology with planetary health. The PEHis–AHC continuum offers a scalable blueprint for next-generation survivorship programs in Europe and beyond. Ambiomic medicine does not replace precision medicine—it completes and extends it by integrating exposomics, social context, and anticipatory analytics from day 0. Full article

(This article belongs to the Special Issue Advancements in Child, Adolescent, and Young Adult Cancer Survivorship)

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12 pages, 371 KB

Open AccessArticle

Associations of Obesity with Function and Patient-Reported Outcomes Among Rural Advanced Cancer Patients: A Cross-Sectional Analysis of the Nurse AMIE Randomized Controlled Trial

by Samantha J. Werts-Pelter, Clair Smith, Stephen Baker, Charity G. Patterson, Nicole Stout, Jennifer Moss, William A. Calo, Shawna E. Doerksen and Kathryn H. Schmitz

Cancers 2026, 18(1), 6; https://doi.org/10.3390/cancers18010006 - 19 Dec 2025

Abstract

Background/Objectives: Obesity is a common comorbidity but there remains limited understanding on how higher obesity rates in rural areas may impact physical function decline and other health domains among cancer patients. This study addresses this gap by examining the association between body mass [...] Read more.

Background/Objectives: Obesity is a common comorbidity but there remains limited understanding on how higher obesity rates in rural areas may impact physical function decline and other health domains among cancer patients. This study addresses this gap by examining the association between body mass index (BMI) and physical function among a cohort of rural advanced cancer patients. Methods: This cross-sectional analysis uses baseline data from the Nurse AMIE trial (NCT04673019). Individuals were categorized as ‘normal weight’ (BMI ≤ 25 kg/m²), ‘overweight’ (BMI > 25 to 30 kg/m²), and ‘obese’ (BMI > 30 kg/m²). Objective physical function was measured by the Short Physical Performance Battery (SPPB) and subjective physical function and health domains were measured using surveys (PROMIS; SF-36). Results: Of 348 patients included, 88 (25.3%) were classified as ‘normal weight’, 107 (30.7%) as ‘overweight’, and 153 (44.0%) as ‘obese’. Average age was 64.8 years (SD = 12.2), 46% (n = 160) were female, 95% were white (n = 331), and 52% (n = 182) were Stage 4. Total SPPB scores revealed poorer functioning with higher BMI (M ± SD: BMI ≤ 25 kg/m²: 9.1 ± 2.3; BMI > 25–30 kg/m²: 8.3 ± 3.1; BMI > 30 kg/m²: 8.1 ± 2.8; p = 0.04). Similarly, scores from the SF-36 revealed subjective physical function was lower with higher BMI (BMI ≤ 25 kg/m²: 57.9 ± 29.1; BMI > 25–30 kg/m²: 53.7 ± 28.0; BMI > 30 kg/m²: 47.6 ± 27.6; p = 0.004). Participants reported lower levels of energy and greater fatigue with higher BMI (BMI ≤ 25 kg/m²: 49.8 ± 26.1; BMI > 25–30 kg/m²: 45.1 ± 24.6; BMI > 30 kg/m²: 40.7 ± 22.6; p = 0.01). Conclusions: Higher BMI is associated with poorer physical function and increased fatigue among rural advanced cancer patients, highlighting the need for supportive care related to physical function in this at-risk group. Full article

(This article belongs to the Special Issue Obesity and Cancers)

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17 pages, 2036 KB

Open AccessReview

Pharmacokinetic and Pharmacodynamic Modeling of Antibody-Drug Conjugates

by Patrick M. Glassman

Cancers 2026, 18(1), 5; https://doi.org/10.3390/cancers18010005 - 19 Dec 2025

Abstract

Antibody-drug conjugates (ADCs) have risen in prominence over the past 15 years, with numerous regulatory approvals in oncology. A complicating factor in the development of ADCs is the presence of numerous analytes with unique pharmacologic properties. Following administration, ADCs are present in the [...] Read more.

Antibody-drug conjugates (ADCs) have risen in prominence over the past 15 years, with numerous regulatory approvals in oncology. A complicating factor in the development of ADCs is the presence of numerous analytes with unique pharmacologic properties. Following administration, ADCs are present in the body as the intact ADC, unconjugated antibody, and liberated payload. Due to heterogeneity in conjugation and in vivo deconjugation rates, the drug-to-antibody ratio (DAR) changes with time. Each of these molecular species has unique pharmacokinetic (PK) and pharmacodynamic (PD) properties that should be understood and characterized. One approach that is frequently applied is the development of in silico mathematical models to characterize and predict the PK/PD of ADCs. In this review, we summarize key mechanisms controlling the PK/PD of ADCs. This provides context for a detailed discussion of the array of PK/PD models that have been applied for ADCs, ranging from empirical compartmental models all the way through system-level models, such as physiologically based pharmacokinetics (PBPK) and cell-level PK/PD models. We provide a critical discussion of the strengths, weaknesses, and utility of each of these model structures. Full article

(This article belongs to the Special Issue Advances in Antibody–Drug Conjugates (ADCs) in Cancers)

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26 pages, 538 KB

Open AccessArticle

Surgical Treatment Options for Renal Cell Carcinoma Metastases to the Pancreas—25 Years of Single-Center Experience

by Magdalena Gajda, Ewa Grudzińska, Paweł Szmigiel, Paweł Sasiński and Sławomir Mrowiec

Cancers 2026, 18(1), 4; https://doi.org/10.3390/cancers18010004 - 19 Dec 2025

Abstract

Background: Clear cell renal cell carcinoma (RCC) is the most common primary tumor that metastasizes to the pancreas, and surgery is the established treatment option. The aim of this study was to compare surgical treatment options for RCC metastases to the pancreas [...] Read more.

Background: Clear cell renal cell carcinoma (RCC) is the most common primary tumor that metastasizes to the pancreas, and surgery is the established treatment option. The aim of this study was to compare surgical treatment options for RCC metastases to the pancreas and to assess long-term outcomes, identifying risk factors for recurrence and death. Methods: We retrospectively analyzed data from 62 patients with RCC metastases to the pancreas who underwent pancreatic surgery at the Department of Gastrointestinal Surgery, Medical University of Silesia, Katowice. Patients were divided into two groups: those who underwent local tumor removal (group A, N = 10) and those who underwent classical pancreatic resection (group B, N = 52). Demographic data, postoperative course, histological findings, and clinical outcomes—recurrence-free survival (PFS) and overall survival (OS)—were analyzed. Results: In group A, tumors were smaller (p < 0.001) and exclusively single (p = 0.100), and Clavien–Dindo complications were milder, with a predominance of grade 0 (90% vs. 28.8%; p = 0.042). In group B, blood loss was greater (p < 0.001), and hospitalization was longer (median 12.5 days vs. 10.5 days; p = 0.022) compared with group A. Group A had a longer PFS (144 months vs. 61 months; p = 0.007) and longer OS (144 months vs. 70 months; p = 0.006) compared with group B. In the entire cohort, independent factors associated with worse OS in multivariate analysis were larger tumor size (p = 0.003), lymphatic invasion (p < 0.001), vascular invasion (p < 0.001), perineural invasion (p < 0.001), R1 resection (p < 0.001), and symptoms of the metastases (p < 0.001). Conclusions: The prognosis following surgical resection of pancreatic RCC metastases is excellent: median OS is 77 months, and 5-year survival reaches 71.4%. In multivariate analysis, the type of surgical treatment is not significantly associated with OS or PFS. The choice of surgical procedure should depend on the preoperative CT results and the intraoperative assessment of the surrounding tissues. Full article

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

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12 pages, 603 KB

Open AccessArticle

Patient-Reported Financial Burden in Head and Neck Cancer Undergoing Radiotherapy

by Renata Zahu, Monica Emilia Chirila, Otilia Ciobanu, Daniela Elena Sturzu, Andrei Ciobanu, Gabriela Ciobanu, Noemi Besenyodi, Madalina Vesel-Pop, Flavius Coșer, Roxana Costache and Gabriel Kacso

Cancers 2026, 18(1), 3; https://doi.org/10.3390/cancers18010003 - 19 Dec 2025

Abstract

Background/Objectives: Financial toxicity (FT) refers to the financial burden directly or indirectly caused by a patient’s medical care. Patients with head and neck cancer (HNC) are particularly vulnerable to FT due to lower rates of return to work and higher out-of-pocket payments [...] Read more.

Background/Objectives: Financial toxicity (FT) refers to the financial burden directly or indirectly caused by a patient’s medical care. Patients with head and neck cancer (HNC) are particularly vulnerable to FT due to lower rates of return to work and higher out-of-pocket payments (OOPP). In this cross-sectional study, we assessed the amount and types of OOPP, as well as the prevalence of FT, in HNC patients who had completed curative radiotherapy. Methods: We included HNC patients who underwent curative-intent radiotherapy at four private clinics in Romania, within 12 months of completing treatment. Participants completed a 25-item questionnaire capturing sociodemographic information, insurance status, income, and OOPP. To assess subjective FT, we used the validated nine-item Financial Index of Toxicity (FIT), which measures three FT domains: financial stress, financial strain, and lost productivity. Each domain and the total score range from 0 to 100, with higher scores indicating greater financial toxicity. Descriptive statistics were used to summarize patient characteristics. Pearson’s chi-square, t-tests, and one-way ANOVA were used to assess statistical associations, with a significance threshold of p < 0.05. Results: Among 113 patients (mean age: 59), the majority were male (74.3%) and married (74.3%), with 40% having completed university or higher education. The most frequent tumor sites were the oropharynx (29 cases), larynx (22), and oral cavity (21). Concurrent chemoradiation was the most common treatment modality (47%). The mean total FT score was 18.8. Overall, 39.8% of patients experienced financial toxicity, and 29.2% scored above the mean in financial stress. Moderate financial strain (score > 21) was reported by 39.8% of participants, and approximately one-third reported loss of productivity. Transportation and nutritional supplements were the most common OOPP categories. Notably, 42% of patients spent at least 400 euros—equivalent to Romania’s monthly minimum income—on transportation during radiotherapy. FT was significantly associated with employment and marital status, but not with tumor site or treatment type. Conclusions: Among Romanian HNC patients treated with curative radiotherapy, we found substantial OOPP, particularly for transportation and nutritional supplements. While overall FT levels were moderate, divorced patients and those retired due to other chronic conditions were the most vulnerable to financial distress. Financial toxicity can directly affect treatment adherence, survival, and quality of life. By integrating financial counseling, social support, and broader coverage of treatment-related expenses, healthcare systems can mitigate FT for these patients. Full article

(This article belongs to the Special Issue Advances in Radiation Therapy for Head and Neck Cancer)

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