Cancers

17 pages, 3526 KB

Open AccessArticle

Spectral Precision: The Added Value of Dual-Energy CT for Axillary Lymph Node Characterization in Breast Cancer

by Susanna Guerrini, Giulio Bagnacci, Paola Morrone, Cecilia Zampieri, Chiara Esposito, Iacopo Capitoni, Nunzia Di Meglio, Armando Perrella, Francesco Gentili, Alessandro Neri, Donato Casella and Maria Antonietta Mazzei

Cancers 2026, 18(3), 363; https://doi.org/10.3390/cancers18030363 - 23 Jan 2026

Abstract

Background/Objectives: To develop and validate a predictive model that combines morphological features and dual-energy CT (DECT) parameters to non-invasively distinguish metastatic from benign axillary lymph nodes in patients with breast cancer (BC). Methods: In this retrospective study, 117 patients (median age, [...] Read more.

Background/Objectives: To develop and validate a predictive model that combines morphological features and dual-energy CT (DECT) parameters to non-invasively distinguish metastatic from benign axillary lymph nodes in patients with breast cancer (BC). Methods: In this retrospective study, 117 patients (median age, 65 years; 111 women and 6 men) who underwent DECT followed by axillary lymphadenectomy between April 2015 and July 2023, were analyzed. A total of 375 lymph nodes (180 metastatic, 195 benign) were evaluated. Two radiologists recorded morphological criteria (adipose hilum status, cortical appearance, extranodal extension, and short-axis diameter) and placed regions of interest to measure dual-energy parameters: attenuation at 40 and 70 keV, iodine concentration, water concentration and spectral slope. Normalized iodine concentration was calculated using the aorta as reference. Univariate analysis identified variables associated with metastasis. Multivariate logistic regression with cross-validation was used to construct two models: one based solely on morphological features and one integrating water concentration. Results: On univariate testing, all DECT parameters and morphological criteria differed significantly between metastatic and benign nodes (p < 0.01). In multivariate analysis, water concentration emerged as the only independent DECT predictor (odds ratio = 0.97; p = 0.002) alongside cortical abnormality, absence of adipose hilum, extranodal extension and short-axis diameter. The morphologic model achieved an area under the receiver operating characteristic curve (AUC) of 0.871. Increasing water concentration increased the AUC to 0.883 (ΔAUC = 0.012; p = 0.63, not significant), with internal cross-validation confirming stable performance. Conclusions: A model combining standard morphologic criteria with water concentration quantification on DECT accurately differentiates metastatic from benign axillary nodes in BC patients. Although iodine-based metrics remain valuable indicators of perfusion, water concentration offers additional tissue composition information. Future multicenter prospective studies with standardized imaging protocols are warranted to refine parameter thresholds and validate this approach for routine clinical use. Full article

(This article belongs to the Special Issue Enhancing Precision in Cancer Treatment: AI-Driven Innovations in Imaging)

27 pages, 3209 KB

Open AccessArticle

Spanish Paediatric Haematology and Oncology Survival Results and Trends, 1999–2022

by Pau Alfonso-Comos, Álvaro Briz-Redón, José Luis Dapena Díaz, Susana Rives, José María Fernández Navarro, Jaime Verdú-Amorós, Adela Cañete and RETI-SEHOP Survival Working Group

Cancers 2026, 18(3), 362; https://doi.org/10.3390/cancers18030362 - 23 Jan 2026

Abstract

Background: Childhood cancer is the leading cause of natural death among children in high-income countries, despite treatment improvements. The Spanish Registry of Childhood Tumours (RETI-SEHOP) systematically records all cases treated within the network of SEHOP units. Using RETI-SEHOP data, we evaluated survival [...] Read more.

Background: Childhood cancer is the leading cause of natural death among children in high-income countries, despite treatment improvements. The Spanish Registry of Childhood Tumours (RETI-SEHOP) systematically records all cases treated within the network of SEHOP units. Using RETI-SEHOP data, we evaluated survival trends to assess progress in patient care, both overall and by tumour. Methods: A total of 20,534 childhood cancer cases (0–14 years) were recorded across the period 1999–2021. The 1-, 3-, and 5-year overall survival (OS) were estimated using the Kaplan–Meier method, applying the cohort approach for 1999–2018 and the period approach for 2019–2022. OS by age and sex was analysed in the recent 2009–2018 incidence cohort. Age-adjusted OS time trends were examined using joinpoint Cox models for 1999–2022. Results: For all tumours combined, 5-year OS increased from 75.4% to 84.6% between 1999–2003 and 2019–2022. While positive trends were identified for all haematological malignancies examined, a more varied scenario was evident for solid tumours, as ependymomas improved fastest (1.51 points annually), and sarcomas, except for rhabdomyosarcoma, remained stagnant. Conclusions: Our results reflect a period characterised by a combination of new therapeutic developments, improved diagnostics, and more refined risk stratification, which has ultimately led to a reduction in disease-related mortality. Full article

(This article belongs to the Special Issue Recent Advances in Epidemiology of Childhood Cancer)

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47 pages, 948 KB

Open AccessReview

A Decade of Innovation in Breast Cancer (2015–2025): A Comprehensive Review of Clinical Trials, Targeted Therapies and Molecular Perspectives

by Klaudia Dynarowicz, Dorota Bartusik-Aebisher, Sara Czech, Aleksandra Kawczyk-Krupka and David Aebisher

Cancers 2026, 18(3), 361; https://doi.org/10.3390/cancers18030361 - 23 Jan 2026

Abstract

The past decade has witnessed an unprecedented transformation in breast cancer management, driven by parallel advances in targeted therapies, immunomodulation, drug-delivery technologies, and molecular diagnostic tools. This review summarizes the key achievements of 2015–2025, encompassing all major biological subtypes of breast cancer as [...] Read more.

The past decade has witnessed an unprecedented transformation in breast cancer management, driven by parallel advances in targeted therapies, immunomodulation, drug-delivery technologies, and molecular diagnostic tools. This review summarizes the key achievements of 2015–2025, encompassing all major biological subtypes of breast cancer as well as technological innovations with substantial clinical relevance. In hormone receptor-positive (HR+)/HER2− disease, the integration of CDK4/6 inhibitors, modulators of the PI3K/AKT/mTOR pathway, oral Selective Estrogen Receptor Degraders (SERDs), and real-time monitoring of Estrogen Receptor 1 (ESR1) mutations has enabled clinicians to overcome endocrine resistance and dynamically tailor treatment based on evolving molecular alterations detected in circulating biomarkers. In HER2-positive breast cancer, treatment paradigms have been revolutionized by next-generation antibody–drug conjugates, advanced antibody formats, and technologies facilitating drug penetration across the blood–brain barrier, collectively improving systemic and central nervous system disease control. The most rapid progress has occurred in triple-negative breast cancer (TNBC), where synergistic strategies combining selective cytotoxicity via Antibody-Drug Conjugates (ADCs), DNA damage response inhibitors, immunotherapy, epigenetic modulation, and therapies targeting immunometabolic pathways have markedly expanded therapeutic opportunities for this historically challenging subtype. In parallel, photodynamic therapy has emerged as an investigational and predominantly local phototheranostic approach, incorporating nanocarriers, next-generation photosensitizers, and photoimmunotherapy capable of inducing immunogenic cell death and modulating antitumor immune responses. A defining feature of the past decade has been the surge in patent-driven innovation, encompassing multispecific antibodies, optimized ADC architectures, novel linker–payload designs, and advanced nanotechnological and photoactive delivery systems. By integrating data from clinical trials, molecular analyses, and patent landscapes, this review illustrates how multimechanistic, biomarker-guided therapies supported by advanced drug-delivery technologies are redefining contemporary precision oncology in breast cancer. The emerging therapeutic paradigm underscores the convergence of targeted therapy, immunomodulation, synthetic lethality, and localized immune-activating approaches, charting a path toward further personalization of treatment in the years ahead. Full article

(This article belongs to the Section Cancer Therapy)

2 pages, 503 KB

Open AccessCorrection

Correction: Jugel et al. Targeted Transposition of Minicircle DNA Using Single-Chain Antibody Conjugated Cyclodextrin-Modified Poly (Propylene Imine) Nanocarriers. Cancers 2022, 14, 1925

by Willi Jugel, Stefanie Tietze, Jennifer Daeg, Dietmar Appelhans, Felix Broghammer, Achim Aigner, Michael Karimov, Gabriele Schackert and Achim Temme

Cancers 2026, 18(3), 360; https://doi.org/10.3390/cancers18030360 - 23 Jan 2026

Abstract

In the original publication [...] Full article

(This article belongs to the Special Issue Cancer Smart Nanomedicine)

14 pages, 772 KB

Open AccessReview

TREM2 in Urological Malignancies and Benign Lesions: Mechanistic Convergence, Functional Heterogeneity, and Translational Perspectives: A Narrative Review

by Yu Dai, Yaqiang Feng, Cheng Wang, Helin Zhang and Panfeng Shang

Cancers 2026, 18(3), 359; https://doi.org/10.3390/cancers18030359 - 23 Jan 2026

Abstract

Triggering receptor expressed on myeloid cells-2 (TREM2) is a key myeloid immune checkpoint for macrophage plasticity. However, its functional landscape in urology is still incomplete. This review addresses this gap by providing the first systematic synthesis of TREM2 in urological malignancies (bladder, prostate, [...] Read more.

Triggering receptor expressed on myeloid cells-2 (TREM2) is a key myeloid immune checkpoint for macrophage plasticity. However, its functional landscape in urology is still incomplete. This review addresses this gap by providing the first systematic synthesis of TREM2 in urological malignancies (bladder, prostate, and renal cell carcinomas) and benign conditions. We find a strong correlation between TREM2 upregulation and adverse clinical outcomes in these cancers. Importantly, we highlight the phenomenon of “mechanistic convergence”: unlike the high context-dependency of other organ systems, TREM2 appears to drive progression in urological malignancies by a common convergent signaling hub, the PI3K/AKT pathway. This contrasts sharply with its metabolic role in benign prostatic hyperplasia and its protective role in non-malignant renal injury. We also consider the translational potential of TREM2 as a prognostic biomarker (specifically urine detection) and as a therapeutic target to reverse immunotherapy resistance. Full article

(This article belongs to the Section Cancer Pathophysiology)

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13 pages, 263 KB

Open AccessArticle

Neoadjuvant Pembrolizumab Associated with Chemotherapy in Early Triple-Negative Breast Cancer Patients: Real-World Data from a French Single-Center Experience

by Ichrak Ben Abdallah, Severine Guiu, Xavier Quantin, William Jacot and Philine Witkowski

Cancers 2026, 18(3), 358; https://doi.org/10.3390/cancers18030358 - 23 Jan 2026

Abstract

Introduction: The addition of immunotherapy to neoadjuvant treatment for early triple-negative breast cancer (TNBC) has been adopted in clinical practice in France since March 2022, with little real-world data published on the topic. The aim of this study was to evaluate real-world data [...] Read more.

Introduction: The addition of immunotherapy to neoadjuvant treatment for early triple-negative breast cancer (TNBC) has been adopted in clinical practice in France since March 2022, with little real-world data published on the topic. The aim of this study was to evaluate real-world data on treatment feasibility, efficacy, and related toxicities, with a specific focus on immune-related adverse events (irAEs). Methods: We conducted a retrospective analysis of patients who completed at least the neoadjuvant sequence of pembrolizumab combined with chemotherapy for early-stage TNBC at Montpellier Cancer Institute from April 2022 to July 2024. Adverse events were graded according to the Common Terminology Criteria for Adverse Events (CTCAE) v5.0. The pathological complete response (pCR) was defined as the absence of residual invasive disease in the breast and axillary lymph nodes (ypT0/Tis ypN0). Results: We reviewed data from 92 patient records. The median age at diagnosis was 50 years (range: 27–76). The history of autoimmune disease was noted in 3.2% of patients. Grade 3–4 irAEs were observed in 20% of patients and included hepatitis (8.6%), colitis (3.3%), skin toxicity (2.1%), myocarditis (2%), arthralgia (1%), autoimmune hemolytic anemia (1%), hypothyroidism (1%), and adrenal insufficiency (1%). No treatment-related deaths were reported. Immunotherapy was discontinued due to irAEs in 29.3% of patients in the study population. The pCR rate was 61,1%, with no significant association between the number of neoadjuvant pembrolizumab cycles and the pCR rate (p = 0.7). Patients experiencing grade 3–4 irAEs had a pCR rate of 80%, compared to 56.7% in those without such toxicities (p = 0.079). Initial positivity of antinuclear antibodies (ANA) was not associated with an increased incidence of irAEs. Conclusions: The immune-related adverse events and efficacy data observed in our cohort were broadly comparable to those reported in the KEYNOTE-522 trial, with no treatment-related deaths. Patients with grade 3–4 irAEs tended to have higher pCR rates. Full article

(This article belongs to the Special Issue Immune-Related Adverse Events in Cancer Immunotherapy)

17 pages, 10828 KB

Open AccessArticle

by Christina Yfanti, Georgia Levidou, Vicky Lampropoulou, Stefania Kokkali, Georgios Mandrakis, Stavros P. Papadakos, Dimitra Rontogianni and Stamatios Theocharis

Cancers 2026, 18(3), 357; https://doi.org/10.3390/cancers18030357 - 23 Jan 2026

Abstract

Background: Autophagy, a self-destructive cellular mechanism with a paradoxical nature, plays a part in both tumor suppression and induction by providing cancer cells with metabolic substrates, resulting in cell proliferation and survival. In this study, we aim to investigate the clinical significance of [...] Read more.

Background: Autophagy, a self-destructive cellular mechanism with a paradoxical nature, plays a part in both tumor suppression and induction by providing cancer cells with metabolic substrates, resulting in cell proliferation and survival. In this study, we aim to investigate the clinical significance of four autophagy pathway components (BECLIN, p62/, LC3b, ATG3) in pathogenetic mechanisms of thymic epithelial tumors (TETs) with possible prognostic importance. Methods: Immunohistochemistry was used to evaluate the cytoplasmic expression of BECLIN, p62, LC3b, and ATG3 in tumor cells of 99 TETs, and possible correlations with clinicopathological parameters were examined. Results: Higher BECLIN and p62 expression was associated with male gender (p = 0.027 and p = 0.014, respectively). B3 thymomas and thymic carcinomas (TCs) displayed higher p62 expression (p = 0.019), while LC3b expression was marginally higher in non-B3/TC TETs (p = 0.098). A positive correlation between higher BECLIN expression and advanced Masaoka–Koga stage was also observed (p = 0.009). ATG3 was not associated with any of the investigated clinicopathological parameters (p > 0.05). There was also no significant correlation between any of the four examined molecules and overall survival or relapse. Conclusions: Our findings indicate autophagy activation in B3/TC and advanced Masaoka–Koga stage cases. Further studies are needed to explore the role of these autophagy related proteins as potential biomarkers and therapeutic targets in TETs. Full article

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

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24 pages, 1970 KB

Open AccessReview

The Influence of Molecular Factors on the Effectiveness of New Therapies in Endometrial Cancer—Latest Evidence and Clinical Trials

by Wiktoria Mytych, Edyta Barnaś, Dorota Bartusik-Aebisher and David Aebisher

Cancers 2026, 18(3), 356; https://doi.org/10.3390/cancers18030356 - 23 Jan 2026

Abstract

Endometrial cancer (EC) is the most common gynecological cancer in developed countries, with approximately 417,000 new cases reported worldwide in 2020. Its incidence has been rising for the past 30 years, primarily due to population aging, obesity, and type 2 diabetes; obesity accounts [...] Read more.

Endometrial cancer (EC) is the most common gynecological cancer in developed countries, with approximately 417,000 new cases reported worldwide in 2020. Its incidence has been rising for the past 30 years, primarily due to population aging, obesity, and type 2 diabetes; obesity accounts for almost half of cases due to excessive estrogen production. The classic division into types I and II was replaced in 2013 by the molecular TCGA classification, which distinguishes four subtypes: POLE-ultramutated (best prognosis), MSI-hypermutated, copy-number low, and copy-number high (worst prognosis). This classification (refined in ProMisE and TransPORTEC) enables precise treatment: immunotherapy (pembrolizumab, dostarlimab) works excellently in dMMR/MSI-H tumors, PI3K/AKT/mTOR inhibitors and trastuzumab deruxtecan in selected molecular subtypes, and hormone therapy in ER-positive tumors. ctDNA monitoring supports therapeutic decisions. Integrating the molecular profile with FIGO allows for truly personalized treatment, although MMRp/MSS tumors remain a challenge. The future lies in multi-omics, new biomarkers, and combination therapies. Full article

(This article belongs to the Special Issue What’s Behind the Scenes? New Insights in Endometrial Cancer Management and Risk Stratification (2nd Edition))

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21 pages, 2805 KB

Open AccessArticle

Composition of Immune Cells in Sporadic Vestibular Schwannomas with Different Tumor Volumes

by Anna-Louisa Becker, Clara Helene Klause, Martin Sebastian Staege, Edith Willscher, Jonas Scheffler, Paola Schildhauer, Christian Ostalecki, Christian Strauss, Julian Prell, Christian Scheller, Stefan Rampp and Sandra Leisz

Cancers 2026, 18(3), 355; https://doi.org/10.3390/cancers18030355 - 23 Jan 2026

Abstract

Background/Objectives: Vestibular schwannoma (VS) is the most common benign tumor in the cerebellopontine angle. In preliminary studies, macrophage infiltration has been suggested to influence disease progression. However, the infiltration of other immune cells in VS remains largely unexplored. The aim of this study [...] Read more.

Background/Objectives: Vestibular schwannoma (VS) is the most common benign tumor in the cerebellopontine angle. In preliminary studies, macrophage infiltration has been suggested to influence disease progression. However, the infiltration of other immune cells in VS remains largely unexplored. The aim of this study was to comprehensively characterize the immune cells in sporadic VS. Methods: Cryosections of five tumor samples from VS patients with different tumor volumes were examined. The abundance of fourteen immune-cell markers, one vascular marker, and two tumor markers were detected using multi-epitope ligand cartography (MELC). This enabled the spatial distribution and colocalization of immune- and tumor cell markers to be examined. Furthermore, using qPCR and bulk RNAseq, the mRNA levels of the immune-cell markers were examined in 204 VS samples of different tumor sizes. Results: VSs with greater tumor volumes showed an increased number of immune cells, more precisely T-helper cells (T_H cells), cytotoxic T cells (T_c cells), CD68⁺, and CD163⁺ macrophages, as well as CD279⁺ (PD-1) and CTLA4⁺ cells (p < 0.05). In addition, an increased number of CD274⁺ (PD-L1) tumor cells were detected in VSs with higher tumor volume (p < 0.05). Conclusions: These results indicate that an increased diversity of immune-cell subtypes influences VS tumor size. Thus, novel diagnostic and therapeutic options could be developed by targeting the tumor-associated immune-cell populations in VSs. Full article

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

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23 pages, 497 KB

Open AccessSystematic Review

The Contribution of Genetic Modifiers to Ovarian Cancer Risk in BRCA1 and BRCA2 Pathogenic Variant Carriers

by Dagmara Cylwik, Roksana Dwornik and Katarzyna Białkowska

Cancers 2026, 18(3), 354; https://doi.org/10.3390/cancers18030354 - 23 Jan 2026

Abstract

The article presents the current state of knowledge on genetic modifiers of ovarian cancer risk in women carrying pathogenic variants (PVs) in the BRCA1 and BRCA2 genes, which are major contributors to hereditary susceptibility to this malignancy. Although PV carriers have high disease [...] Read more.

The article presents the current state of knowledge on genetic modifiers of ovarian cancer risk in women carrying pathogenic variants (PVs) in the BRCA1 and BRCA2 genes, which are major contributors to hereditary susceptibility to this malignancy. Although PV carriers have high disease penetrance (BRCA1: ~40% and BRCA2: 11–27%), substantial variability in individual risk is observed, suggesting the influence of additional genetic variants. Background: Ovarian cancer is characterized by late detection and high mortality, and a significant portion of risk among BRCA1/2 carriers is shaped by reproductive and environmental factors as well as genetic modifiers. The article emphasizes that carriers of the same BRCA PV can exhibit markedly different risk levels depending on additional variants that modulate key biological processes, such as DNA repair, cell cycle regulation, and apoptosis. Methods: A systematic literature search covering the years 1996–2025 was conducted in the PubMed database. Initially, 734 publications were identified; after removing duplicates, thematically irrelevant articles, non-full-text papers, and studies not meeting the inclusion criteria, 47 articles were included in the review. These studies covered candidate gene analyses, GWAS, and data from the CIMBA consortium, which enables the examination of large cohorts of PV carriers. Results: The review identified numerous variants associated with increased or decreased ovarian cancer risk in BRCA1 carriers, including the following: OGG1, DR4, MDM2, CYP2A7, CASP8, ITGB3, HRAS1, TRIM61, and MTHFR. The reviewed studies also identified both protective and risk-increasing variants among BRCA2 PV carriers: UNG, TDG, and PARP2, and haplotypes in ATM, BRIP1, BARD1, MRE11, RAD51, and 9p22.2. The analysis identified 11 variants affecting both BRCA1 and BRCA2 carriers, most of which increase risk, including the following: IRS1, RSPO1, SYNPO2, BABAM1, MRPL34, PLEKHM1, and TIPARP. Protective variants include BNC2 and LINC00824. The only SNP reaching genome-wide significance (p < 5 × 10⁻⁸) was in BNC2. Conclusions: The article summarizes the growing number of genetic modifiers of ovarian cancer risk among BRCA1/2 carriers and highlights their potential to improve individualized risk assessment, enhance patient stratification, support personalized prevention and surveillance strategies, deepen the understanding of disease biology, and identify potential therapeutic targets. Full article

(This article belongs to the Special Issue Genetics of Ovarian Cancer (2nd Edition))

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16 pages, 2048 KB

Open AccessTechnical Note

Clinical Workflow of Spine Stereotactic Radiotherapy and Radiosurgery: Insights from a Single-Institution Physics Perspective

by Dennis Mackin, Gizem Cifter, Yana Zlateva, Jihong Wang, Yao Ding, Muhammad Shafiq ul Hassan, Zhiheng Wang, Parmeswaran Diagaradjane, Fada Guan, Travis C. Salzillo, Shane Krafft, Jing Li, Martin C. Tom, Amol J. Ghia and Tina Marie Briere

Cancers 2026, 18(3), 353; https://doi.org/10.3390/cancers18030353 - 23 Jan 2026

Abstract

Spine stereotactic radiotherapy and radiosurgery (SSRS) techniques, encompassing both fractionated stereotactic treatments and single-fraction radiosurgery, are widely used for the management of spinal metastases due to their ability to deliver highly conformal radiation while limiting dose to adjacent critical structures. Clinical outcomes following [...] Read more.

Spine stereotactic radiotherapy and radiosurgery (SSRS) techniques, encompassing both fractionated stereotactic treatments and single-fraction radiosurgery, are widely used for the management of spinal metastases due to their ability to deliver highly conformal radiation while limiting dose to adjacent critical structures. Clinical outcomes following SSRS, including durable local control and acceptable toxicity, have been reported previously in multiple institutional series. In this manuscript, we describe the clinical workflow used to deliver SSRS at a high-volume academic center, with emphasis on the medical physics processes that support routine clinical practice. Key elements of the workflow include patient selection, treatment region-specific immobilization, CT and MRI-based simulation, treatment planning, patient-specific quality assurance, and image-guided treatment delivery. Rather than presenting new outcome data, this work provides a descriptive overview of how established SSRS techniques are integrated into day-to-day clinical care. Full article

(This article belongs to the Special Issue Stereotactic Body Radiation and Stereotactic Ablative Radiotherapy Therapy for Cancers 2nd edition)

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16 pages, 5092 KB

Open AccessArticle

Evaluating Adjuvant Radiation Therapy Survival Benefit in Early-Stage HER2-Positive Invasive Breast Cancer Following Breast-Conserving Surgery: A National Cohort Aligned with NRG-BR008 HERO Trial

by Jonathon S. Cummock, Ali J. Haider, Mohummad Kazmi, Waqar M. Haque, Andrew M. Farach, E. Brian Butler and Bin S. Teh

Cancers 2026, 18(3), 352; https://doi.org/10.3390/cancers18030352 - 23 Jan 2026

Abstract

Background and purpose: The role of adjuvant radiation therapy (RT) in early-stage HER2-positive breast cancer treated with breast-conserving surgery (BCS) and systemic therapy remains uncertain in the era of HER2-targeted regimens. This study evaluates the survival impact of RT in patients aligned with [...] Read more.

Background and purpose: The role of adjuvant radiation therapy (RT) in early-stage HER2-positive breast cancer treated with breast-conserving surgery (BCS) and systemic therapy remains uncertain in the era of HER2-targeted regimens. This study evaluates the survival impact of RT in patients aligned with the HERO RT de-escalation trial (NRG-BR008). Materials and methods: We queried the National Cancer Database for patients with early-stage HER2-positive invasive breast carcinoma treated with BCS and systemic therapy, stratified into HERO trial-aligned cohorts: Arm 1 (adjuvant systemic therapy) vs. Arm 2 (neoadjuvant systemic therapy, pathologic complete response). Within each cohort, patients receiving adjuvant RT were compared with those omitting RT. In the primary analysis, patients were propensity score matched (PSM) on demographics, diagnosis years, tumor characteristics, and trial stratification variables. Inverse probability of treatment weighting (IPTW) was additionally performed as a sensitivity analysis. Overall survival was evaluated using Kaplan–Meier, Cox regression, and restricted mean survival time (RMST). Results: In Arm 1 (818 patients, 94 deaths), 5-year OS was 96.9% with RT vs. 88.0% without RT, and 10-year OS was 94.3% vs. 68.5% (log-rank p < 0.001). RT omission was associated with higher mortality in the PSM Cox model (HR, 4.78; 95% CI, 2.84–8.02; p < 0.001), with an RMST advantage favoring RT of +2.86 months at 5 years and +12.55 months at 10 years (p < 0.001). In Arm 2 (176 patients, 10 deaths), 5-year OS was 97.6% with RT vs. 91.1% without RT, and OS at 107 months was 94.8% vs. 91.1% (log-rank p = 0.13). RT omission was not statistically significant in the PSM Cox model (HR, 3.40; 95% CI, 0.82–14.05; p = 0.09), though RMST favored RT (+1.83 months at 5 years, p = 0.004; +3.91 months at 107 months, p = 0.03). IPTW analyses were directionally consistent in Arm 1 (HR, 3.26; 95% CI, 2.52–4.21; p < 0.001) and inconclusive in Arm 2 (HR, 1.78; 95% CI, 0.80–3.95; p = 0.16). Conclusions: In this HERO-aligned national cohort, RT omission was associated with inferior OS in patients treated with adjuvant systemic therapy after BCS. Findings in the neoadjuvant pCR cohort were imprecise and hypothesis-generating. Given the retrospective registry design, lack of recurrence-specific endpoints, and potential residual confounding, results should not be interpreted as causal but support continued RT use outside prospective de-escalation trials. Full article

(This article belongs to the Special Issue Personalized Radiotherapy in Cancer Care (2nd Edition))

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14 pages, 2588 KB

Open AccessReview

GFR Evaluation Among Patients with Cancer: Insights and Clinical Implications

by Alok Arora, Parnika Shukla, Vinay Srinivasan, Leyre Zubiri Oteiza, Zachary LeMense, Ginseng Vang and Paul E. Hanna

Cancers 2026, 18(3), 351; https://doi.org/10.3390/cancers18030351 - 23 Jan 2026

Abstract

Accurately assessing the glomerular filtration rate (GFR) is critical in patients with cancer for acute kidney injury diagnosis, chemotherapy selection, drug dosing, and clinical trial eligibility. Yet, traditional equations such as Cockcroft–Gault and MDRD fail due to multiple physiological changes specific to this [...] Read more.

Accurately assessing the glomerular filtration rate (GFR) is critical in patients with cancer for acute kidney injury diagnosis, chemotherapy selection, drug dosing, and clinical trial eligibility. Yet, traditional equations such as Cockcroft–Gault and MDRD fail due to multiple physiological changes specific to this vulnerable population. Cancer-related sarcopenia, creatinine secretion blockade, and total body volume fluctuations may lead to inaccurate GFR estimations. This ultimately leads to undertreatment of underlying malignancy, overdosing of nephrotoxic therapies with adverse effects, and excluding patients from clinical trials unnecessarily. The 2024 KDIGO guidelines as well as the American Society of Onconephrology position statement recommend the use of combined GFR equation such as CKD-EPI 2021 that utilizes both cystatin C and creatinine to improve GFR estimation accuracy. Direct GFR measurement via exogenous filtration markers should be pursued in high-risk patients when precise values are warranted. This review highlights current challenges associated with GFR evaluation in patients with cancer and outlines clinical implications as well as recent recommendations for optimal clinical practice. Full article

(This article belongs to the Special Issue Treatment of Acute Kidney Injury in Cancer Patients: From Theory to Practice)

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17 pages, 747 KB

Open AccessArticle

Outcomes of Near-Infrared Photoimmunotherapy for Head and Neck Cancer: A Single-Center Retrospective Study

by Hiroaki Tahara, Tsutomu Ueda, Takayoshi Hattori, Minoru Hattori, Yuki Sato, Nobuyuki Chikuie, Takayuki Taruya, Takao Hamamoto, Takashi Ishino and Sachio Takeno

Cancers 2026, 18(3), 350; https://doi.org/10.3390/cancers18030350 - 23 Jan 2026

Abstract

Background/Objectives: Near-infrared photoimmunotherapy (NIR-PIT) represents a treatment approach for patients with locally advanced or recurrent head and neck cancers who are unsuitable for surgery post-standard therapy. Since its introduction in Japan in January 2021, NIR-PIT has been available exclusively under the national health [...] Read more.

Background/Objectives: Near-infrared photoimmunotherapy (NIR-PIT) represents a treatment approach for patients with locally advanced or recurrent head and neck cancers who are unsuitable for surgery post-standard therapy. Since its introduction in Japan in January 2021, NIR-PIT has been available exclusively under the national health insurance system, resulting in limited real-world clinical practice data. This study evaluated the association between NIR-PIT and overall survival (OS) in clinical practice. Methods: This single-center retrospective study included 45 patients with head and neck cancer who were not amenable to surgical resection owing to advanced local disease or regional recurrence without distant metastasis and who underwent NIR-PIT or systemic pharmacotherapy between January 2021 and April 2025. The primary endpoint was OS. Results: Twenty-two and 23 patients received NIR-PIT and pharmacotherapy, respectively. In the NIR-PIT group, irradiation was delivered to primary tumors in 20 patients, cervical lymph node lesions in one, and both primary and lymph node lesions in one. The median OS was 35 and 8 months, with median follow-up of 40 and 49 months in the NIR-PIT and pharmacotherapy groups, respectively. Among the NIR-PIT-eligible patients, 22 and 10 were treated with NIR-PIT and pharmacotherapy, respectively. The median OS was 35 and 8 months, with median follow-up of 40 and 24 months in the NIR-PIT and pharmacotherapy groups, respectively. Conclusions: NIR-PIT was independently associated with improved OS in patients with unresectable recurrent or metastatic head and neck cancer without distant metastasis. Prospective multicenter studies are warranted to validate these findings. Full article

(This article belongs to the Special Issue Near-Infrared Photoimmunotherapy for Cancer Treatment: 2nd Edition)

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82 pages, 2456 KB

Open AccessReview

Immune-Centered Cross-Talk Between Cancer Cells and the Tumor Microenvironment—Implications for Therapy

by Eliza Turlej, Aleksandra Domaradzka, Rostyslav Koksharov and Agnieszka Gizak

Cancers 2026, 18(3), 344; https://doi.org/10.3390/cancers18030344 - 23 Jan 2026

Abstract

The tumor microenvironment (TME), composed of various immune and non-immune cells, as well as cancer stem cells, plays a critical role not only in promoting cancer cell proliferation and metastasis but also in modulating therapeutic response. A wide range of therapeutic strategies targeting [...] Read more.

The tumor microenvironment (TME), composed of various immune and non-immune cells, as well as cancer stem cells, plays a critical role not only in promoting cancer cell proliferation and metastasis but also in modulating therapeutic response. A wide range of therapeutic strategies targeting the TME are currently employed in cancer treatment, including standard chemotherapy, radiotherapy, immunotherapy, anti-angiogenic therapies, agents targeting cancer-associated fibroblasts (CAFs), oncolytic viruses (OVs), cold atmospheric plasma therapy, and nanovaccines. This review provides a comprehensive overview of the influence of the TME on cancer sensitivity to these therapies across all types of solid tumors. Full article

(This article belongs to the Section Tumor Microenvironment)

20 pages, 7477 KB

Open AccessArticle

Fatty Acid Synthase as a Potential Metabolic Vulnerability in Ocular Adnexal Sebaceous Carcinoma

by Autumn Berlied, Isabella Boyack, Andre Vieira, Maria Gonzalez-Perez, Vikas Kumar and Cornelia Peterson

Cancers 2026, 18(2), 349; https://doi.org/10.3390/cancers18020349 - 22 Jan 2026

Abstract

Background: MYC dysregulation is frequent in ocular adnexal sebaceous carcinoma (SebCA), an aggressive malignancy without precision therapy. Fatty acid synthase (FASN) expression and lipid metabolism are commonly perturbed in high-MYC-expressing tumors; however, the role of MYC and FASN in the coregulation of [...] Read more.

Background: MYC dysregulation is frequent in ocular adnexal sebaceous carcinoma (SebCA), an aggressive malignancy without precision therapy. Fatty acid synthase (FASN) expression and lipid metabolism are commonly perturbed in high-MYC-expressing tumors; however, the role of MYC and FASN in the coregulation of lipid biosynthesis and tumorigenesis in SebCA is unknown. Methods: The aim of this study was to characterize the effects of FASN inhibition on MYC expression, oncogenic processes, and lipid profiles in vitro, using non-neoplastic human Meibomian gland epithelial cells (HMGECs) and three primary SebCA cell lines, and in vivo, utilizing a conditionally MYC-overexpressing mouse model. Results: FASN inhibition reduced cell viability, proliferation, and clonogenicity and altered the saturation profile of fatty acids across multiple lipid classes. The relative saturation of ceramides was the most variable between treatment conditions. MYC overexpression in the murine Meibomian gland promoted proliferation while suppressing sebaceous differentiation. Subsequent topical FASN inhibition further reduced sebaceous differentiation, attenuated PLIN2 expression, and induced apoptotic cell death. Conclusions: Collectively, these findings suggest that MYC expression in SebCA is responsive to FASN inhibition. Pharmacologic targeting of FASN reveals a metabolic vulnerability that may serve as a target for future therapeutic development. Full article

(This article belongs to the Special Issue Novel Treatments for Ocular and Periocular Cancers)

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13 pages, 322 KB

Open AccessReview

Achieving Pregnancy After Early Hormone Receptor-Positive Breast Cancer: Recent Evidence and Clinical Considerations

by Karine E. Ronan and Janice M. Walshe

Cancers 2026, 18(2), 348; https://doi.org/10.3390/cancers18020348 - 22 Jan 2026

Abstract

An increasing number of young women with hormone receptor-positive (HR+) early breast cancer desire pregnancy after treatment. Prolonged adjuvant endocrine therapy, concerns regarding recurrence risk, and treatment-related fertility decline have historically complicated reproductive decision-making in this population. This narrative review synthesizes current evidence [...] Read more.

An increasing number of young women with hormone receptor-positive (HR+) early breast cancer desire pregnancy after treatment. Prolonged adjuvant endocrine therapy, concerns regarding recurrence risk, and treatment-related fertility decline have historically complicated reproductive decision-making in this population. This narrative review synthesizes current evidence on pregnancy after early HR+ breast cancer, with particular emphasis on prospective data from the POSITIVE trial. We examine the safety of temporary endocrine therapy interruption, the impact of assisted reproductive technologies (ART) in achieving pregnancy, breastfeeding feasibility and impact, hormonal predictors of fertility, pregnancy outcomes and considerations for special populations, including BRCA mutation carriers. Retrospective studies have suggested no adverse survival impact associated with pregnancy after breast cancer. The POSITIVE trial provides prospective evidence that temporary interruption of endocrine therapy to attempt pregnancy does not increase short-term recurrence risk in selected patients. Approximately three-quarters of participants achieved pregnancy. Fertility preservation and ART were commonly used and were not associated with worse short-term oncologic outcomes. Biomarkers such as anti-Müllerian hormone offer supportive but imperfect prediction of fertility potential. Breastfeeding was feasible for many women and did not adversely affect breast cancer outcomes. Available data among BRCA mutation carriers are reassuring but largely observational. Current evidence supports the safety and feasibility of pregnancy after early HR+ breast cancer in carefully selected patients. However, longer follow-up, inclusion of higher-risk populations, and evaluation of newer therapies are needed. Individualized, multidisciplinary counselling remains central to informed decision-making. Full article

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

14 pages, 549 KB

Open AccessArticle

Combination of Metronomic Chemotherapy and Rituximab in Frail and Elderly Patients with Relapsed/Refractory Follicular Lymphoma and Ineligible for Lenalidomide Treatment: A Retrospective Analysis

by Sabrina Pelliccia, Marta Banchi, Lucrezia De Marchi, Emanuele Cencini, Claudia Seimonte, Alberto Fabbri, Andrea Nunzi, Susanna Destefano, Guido Bocci and Maria Christina Cox

Cancers 2026, 18(2), 347; https://doi.org/10.3390/cancers18020347 - 22 Jan 2026

Abstract

Background/Objectives: Relapsed or refractory follicular lymphoma (rrFL) remains difficult to treat in elderly or frail patients who cannot tolerate standard-dose immuno-chemotherapy as well as novel therapies. Metronomic chemotherapy (mCHEMO) may offer sustained antitumor activity with reduced toxicity. This study assessed the clinical activity [...] Read more.

Background/Objectives: Relapsed or refractory follicular lymphoma (rrFL) remains difficult to treat in elderly or frail patients who cannot tolerate standard-dose immuno-chemotherapy as well as novel therapies. Metronomic chemotherapy (mCHEMO) may offer sustained antitumor activity with reduced toxicity. This study assessed the clinical activity and safety of R-DEVEC or R-DEVEC-light in rrFL patients following lenalidomide discontinuation or ineligibility. Methods: Data from the ReLLi Lymphoma Registry (2013–2025) were retrospectively analyzed. Eligible patients had rrFL after ≥1 prior therapy and initiated mCHEMO at least six months before data cutoff. Thirteen patients received DEVEC or the etoposide-free DEVEC-light regimen; all but one also received rituximab. Responders received maintenance vinorelbine, low-dose prednisone, and rituximab, followed by vinorelbine-only maintenance until progression or intolerance. Responses were assessed by CT after cycle two and PET/CT at completion of six induction cycles. Results: median age was 77 years (range 58–92); most patients were frail and had advanced disease. At the end of induction, 84% achieved remission (46% CR, 38% PR), with three PR converting to CR during maintenance. After a median follow-up of 27 months, the PFS was 42% (95CI 15–69%) and the OS 73% (95CI 47–100%). A transformation occurred in one patient; the main toxicity was grade 3 neutropenia (31%). DEVEC-light showed improved tolerability versus full DEVEC, with manageable infections and rare discontinuations. Conclusions: Metronomic R-DEVEC-light is a feasible and effective disease-controlling strategy for frail, heavily pretreated rrFL patients who do not tolerate lenalidomide and are excluded from modern therapies. This schedule warrants further prospective evaluation and exploration in combination with targeted agents. Full article

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

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14 pages, 1167 KB

Open AccessArticle

Nationwide Survival Impact of Bevacizumab Under National Reimbursement for Advanced Cervical Cancer in South Korea

by Junhwan Kim, Jieun Jang, Krishnansu S. Tewari, Kyung Su Kim, Hyun-Cheol Kang and Sokbom Kang

Cancers 2026, 18(2), 346; https://doi.org/10.3390/cancers18020346 - 22 Jan 2026

Abstract

Background: The aim of this study was to evaluate the effectiveness of bevacizumab in advanced cervical cancer (CC) patients using nationwide data after its inclusion in South Korea’s National Health Insurance (NHI), considering various clinicopathologic factors. Methods: This retrospective study analyzed 3869 advanced [...] Read more.

Background: The aim of this study was to evaluate the effectiveness of bevacizumab in advanced cervical cancer (CC) patients using nationwide data after its inclusion in South Korea’s National Health Insurance (NHI), considering various clinicopathologic factors. Methods: This retrospective study analyzed 3869 advanced CC patients from South Korea’s cancer registry (2012–2019), alongside claims and death records (2012–2021). Among these 2792 patients diagnosed after bevacizumab’s NHI inclusion (August 2015), survival outcomes were compared between those receiving bevacizumab with platinum-based chemotherapy (n = 1787, 64.0%) versus chemotherapy alone (n = 1005, 36.0%). Overall survival (OS) was assessed using Cox proportional hazard regression with inverse probability of treatment weighting. Results: Following NHI coverage of bevacizumab, median OS increased from 1.5 to 2.5 years, and the 5-year OS rate increased from 25.6% to 41.4% (weighted hazard ratio [wHR], 0.63; 95% confidence interval [CI], 0.60–0.67). Among patients receiving bevacizumab, median OS was 2.6 years compared to 2.2 years for those not receiving bevacizumab, with 5-year OS rates of 42.0% and 40.2%, respectively (wHR, 0.84; 95% CI, 0.78–0.90). Subgroup analyses revealed that bevacizumab was associated with significantly better OS in patients with prior concurrent chemoradiation therapy (CCRT) history (wHR, 0.67; 95% CI, 0.61–0.75), regardless of histologic subtype (squamous cell carcinoma [SCC]: wHR, 0.69 [95% CI, 0.61–0.78] vs. non-SCC: wHR, 0.66 [95% CI, 0.55–0.79]). Conclusions: The national investment in the implementation of bevacizumab was associated with favorable survival outcomes in advanced CC patients. Particularly, bevacizumab showed pronounced survival benefit for patients with prior CCRT history, regardless of histologic subtype. Full article

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

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